The retrospective study reviewed four consecutive children aged between 13 and 26 months who were admitted to Vietnam National Children’s Hospital between June and December 2022. To be included, each child had to show acute neurological dysfunction together with adenovirus detected by real-time polymerase chain reaction, or PCR, in both the cerebrospinal fluid and a nasopharyngeal specimen. This dual requirement is important: it demonstrates that the virus was circulating systemically and that viral DNA had also reached the compartment surrounding the brain and spinal cord. All four children were previously healthy, with no known immunodeficiency that would predispose them to overwhelming viral infection, which makes the severity of their presentations all the more unusual and clinically significant.

The cerebrospinal fluid findings are the technical heart of the paper. In classical viral encephalitis or meningitis, clinicians expect a pleocytosis, an elevated number of white blood cells in the spinal fluid, typically accompanied by raised protein. In these four toddlers, leukocyte counts ranged from just 1 to 3 cells per microliter, values that would generally be considered within or barely above the normal range, and protein concentrations ranged from 0.38 to 0.62 grams per liter, likewise unremarkable. Yet real-time PCR returned positive results for adenovirus in every sample. The authors argue that such near-normal indices do not exclude clinically important adenovirus-associated central nervous system disease, and that clinicians should not be falsely reassured by a clean-looking spinal tap when a child is neurologically deteriorating in the context of systemic adenoviral illness.

Neuroimaging added further complexity. Brain magnetic resonance imaging was performed in two of the four children. One scan showed bilateral frontoparietal cortical lesions compatible with encephalitic involvement, providing objective evidence that the brain parenchyma itself was affected. The other showed nonspecific widening of the frontoparietal subarachnoid spaces, a finding that could reflect cerebral volume loss or atrophy but is not diagnostic of any single process. The limited imaging data reflect the realities of retrospective case series in an intensive care setting, where the sickest children may be too unstable for transport to the scanner. Even so, the images underscore that adenovirus can produce structural brain injury in immunocompetent toddlers, not merely self-limited meningitic symptoms.

The systemic component of the illness was equally severe. All four children required invasive mechanical ventilation, and one additionally needed extracorporeal membrane oxygenation, a heart-lung bypass technique reserved for patients whose respiratory or circulatory failure cannot be managed by a ventilator alone, as well as renal replacement therapy for kidney failure. The combination of respiratory failure, circulatory collapse, renal injury, and neurological dysfunction in previously healthy toddlers illustrates the fulminant, multisystem character of the syndrome. Adenovirus is capable of infecting respiratory epithelium, gastrointestinal tract, liver, and other organs, and in these cases the infection appears to have triggered a cascade of organ dysfunction that outpaced the children’s physiological reserves.

A particularly notable laboratory feature was marked hyperferritinemia, an extremely elevated blood level of ferritin, the iron-storage protein. Very high ferritin values are a hallmark of systemic hyperinflammation and are seen in conditions such as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, disorders in which the immune system’s scavenger cells become pathologically activated and release a storm of inflammatory cytokines. In this series, two children received a clinical diagnosis of macrophage activation syndrome during their admission, although the authors note that a complete evaluation according to the HLH-2004 criteria was not performed. This raises the possibility that at least part of the tissue damage in these children was driven not by direct viral cytopathic effect but by a runaway inflammatory response to the infection, a mechanism with important implications for treatment.

The therapeutic implications are considerable. If hyperinflammation contributes substantially to the deterioration of these patients, then immunomodulatory strategies, such as those used in macrophage activation syndrome or hemophagocytic lymphohistiocytosis, might theoretically be considered alongside antiviral therapy and organ support. At the same time, the authors are careful to draw a boundary around what their data can support. They conclude that escalation of respiratory, circulatory, renal, or extracorporeal support should be guided by the child’s physiological deterioration and objective measures of organ dysfunction, rather than by cerebrospinal fluid PCR positivity alone. In other words, finding adenoviral DNA in the spinal fluid is a diagnostic clue, not a treatment algorithm, and clinical judgment anchored in the patient’s trajectory remains paramount.

Why adenovirus reached the central nervous system in these children, and why the spinal fluid showed so little inflammation, remains unresolved. Several mechanisms are plausible: direct viral invasion of neural tissue, infection of the meninges, or a post-infectious inflammatory process. The paucity of pleocytosis could reflect very early sampling in the disease course, before the inflammatory cascade had spilled into the cerebrospinal fluid, or a pattern of parenchymal rather than meningeal involvement. It is also possible that the profound systemic hyperinflammation altered the usual immunology of the central nervous system compartment. The authors of the series do not claim to have settled these questions; their contribution is to document that the dissociation between positive PCR results and normal routine indices can occur, and that it matters for clinical practice.

The study’s design imposes limits that readers should keep in view. It is a retrospective case series of four children at a single hospital over a six-month period, without a comparison group, and the authors did not perform a complete HLH-2004 workup, so the diagnoses of macrophage activation syndrome rest on clinical assessment. Case series cannot establish incidence, cannot prove causation between adenovirus and the neurological syndrome, and cannot determine whether the outcomes would have differed under alternative management strategies. Nevertheless, the consistency of the pattern, four previously healthy toddlers, all with dual respiratory and cerebrospinal fluid PCR positivity, all requiring mechanical ventilation, and three deaths, is difficult to dismiss as coincidence, and the ethical review board of Vietnam National Children’s Hospital approved the study under the Declaration of Helsinki with consent requirements waived for its retrospective design.

For clinicians caring for young children, the practical message is one of heightened vigilance rather than alarm. Adenovirus remains a common and usually benign pathogen of early childhood. But when a toddler with confirmed or suspected adenoviral infection develops new neurological dysfunction, whether seizures, altered consciousness, or focal signs, the new data suggest that cerebrospinal fluid PCR testing for adenovirus deserves a place in the etiological assessment, even when cell counts and protein are normal or nearly so. Equally, the presence of marked hyperferritinemia and other signs of systemic hyperinflammation should prompt consideration of macrophage activation syndrome in the differential diagnosis. As molecular diagnostics become faster and more widely available, the challenge will be to integrate these sensitive tools with sound physiological reasoning, so that detection of viral genetic material informs, rather than dictates, the care of the sickest children.

Subject of Research: Severe multisystem adenovirus infection with central nervous system involvement in immunocompetent toddlers

Article Title: Fulminant multisystem adenovirus-associated illness with cerebrospinal fluid PCR positivity and minimal pleocytosis in previously healthy toddlers: a case series

Article References: Do, T. H., Van, A. V., Trong, H. D., Thi, H. T. N., & Nguyen, S. D. (2026). Fulminant multisystem adenovirus-associated illness with cerebrospinal fluid PCR positivity and minimal pleocytosis in previously healthy toddlers: a case series. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07691-9

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07691-9

Keywords: adenovirus, cerebrospinal fluid, PCR, encephalitis, hyperinflammation, macrophage activation syndrome, pediatric critical care, toddlers, central nervous system, mechanical ventilation, ECMO, BMC Pediatrics

The technology behind ECPR is borrowed from extracorporeal membrane oxygenation, or ECMO, the machine that made headlines during the COVID-19 pandemic as a last-resort lung support. In venoarterial ECMO, blood is drained from large veins, passed through a membrane oxygenator that adds oxygen and removes carbon dioxide, and pumped back into the arterial system. Applied during cardiac arrest, this circuit can push roughly 2.0 liters per minute through the body—more than three times what compressions achieve—sustaining the brain, heart, and other organs while clinicians treat the underlying cause of the arrest. The catch is time. Studies reviewed by the authors show that for every ten-minute delay between collapse and the start of ECPR, the likelihood of favorable neurological recovery falls significantly, which is precisely why researchers have begun moving the machines out of the hospital and into ambulances.

The randomized trial evidence is striking but nuanced. In the American ARREST trial, patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation who received early ECPR were discharged from the hospital at a rate of 43 percent, compared with just 7 percent among those receiving conventional resuscitation. Yet two European trials, INCEPTION in the Netherlands and PRAGUE-OHCA in the Czech Republic, found no such advantage—and the review’s authors point to a telling detail: in those studies, the average time to ECPR initiation stretched to roughly 61 to 74 minutes. The emerging consensus is that ECPR delivers meaningful benefit only when the so-called low-flow duration, the interval without effective circulation, stays under about 60 minutes, and only in carefully selected patients. Even then, the sub-60-minute mark is a benchmark rather than an absolute cutoff, since good outcomes have occasionally been achieved beyond it when compressions remain high quality.

Prehospital ECPR aims to attack the clock directly. Instead of resuscitating at the scene and then transporting, specialized teams reach the patient quickly and establish ECMO support either on-site or inside a mobile intensive care unit, working in parallel with compressions and airway management. Observational data suggest the approach is feasible: favorable neurological outcomes have been reported in roughly 20 to 25 percent of prehospital ECPR patients. A French analysis by Leroux and colleagues found no survival difference between prehospital and in-hospital initiation, but the low-flow duration was a full 30 minutes shorter when ECMO was started in the field. In Germany, Walter and colleagues achieved survival with good neurological function in 24.6 percent of 69 prehospital ECPR patients, while a French helicopter-borne team described by Hutin and colleagues still recorded 15 percent favorable survival despite low-flow times exceeding 110 minutes.

A handful of systems worldwide have made this a reality. Paris pioneered mobile ECPR in 2011, dispatching 24/7 teams—an anesthesiologist or emergency physician, an anesthesia nurse, and a paramedic—alongside standard mobile intensive care units, with a goal of establishing ECMO within 60 minutes of collapse. The first reported Paris case involved a marathon runner who received 4.5 liters per minute of extracorporeal flow about an hour after the emergency call and began recovering organ function within two days. In Albuquerque, New Mexico, the University of New Mexico partnered with the local fire department in 2019 to field a specially equipped ambulance crewed by an ECPR-trained intensivist and two paramedics, targeting witnessed arrests where hospital transport would exceed 35 minutes. The Netherlands equips all of its air ambulance units with ECPR capability, and in Regensburg, Germany, ambulance crews and the ECPR team are dispatched simultaneously, with exclusion criteria such as trauma, terminal illness, and unwitnessed arrest filtering candidates before cannulation begins.

The procedure itself relies on peripheral cannulation rather than open-chest surgery. Central access, which requires a sternotomy and placement of catheters in the right atrium and aorta, is considered infeasible in the field. Instead, teams use the percutaneous Seldinger or semi-Seldinger technique, typically accessing the femoral artery and vein, sometimes with ultrasound guidance. Recent studies support both approaches in prehospital protocols, and the review’s authors argue that restricting field programs to these percutaneous methods shortens intervention time and reduces complications. The technique is not without hazards: femoral cannulation carries a real risk of distal limb ischemia, particularly when a distal perfusion catheter cannot be placed, and achieving hemostasis in anticoagulated patients is difficult in uncontrolled environments. Maintaining aseptic technique at a roadside scene presents yet another challenge that early enthusiasm sometimes understates.

Training is the other formidable barrier. International teams typically comprise at least one physician, a nurse, a paramedic, and intensive care expertise, all credentialed in ECMO circuit setup, management, and troubleshooting. An Australian program described in the review trained 11 physicians and 6 critical care paramedics with no prior ECMO experience through a multiphase curriculum combining animal models, cadaver-based cannulation practice, simulation scenarios, and formal examinations; every participant ultimately met the learning objectives. The Extracorporeal Life Support Organization recommends certified basic and advanced ECMO training for anyone involved in ECPR. Patient selection is equally strict: candidates generally must have a witnessed arrest, immediate bystander CPR, a shockable initial rhythm such as ventricular fibrillation, and a low-flow duration under 60 minutes, while terminal illness, traumatic arrest, and advanced age—often capped at 65 to 70 years in French and Dutch protocols—exclude patients. Even so, only an estimated 2 to 10 percent of out-of-hospital cardiac arrest patients are potential candidates.

For Turkey, the review paints a sobering baseline. The national TROHCA study of 1,003 out-of-hospital arrests found that only 4.4 percent of patients reaching the hospital survived to discharge and just 2.7 percent achieved favorable neurological outcomes—figures below the global average, driven in part by bystander CPR rates of only about 2 to 5 percent. Turkish ECMO experience is limited to in-hospital cases: a Koşuyolu hospital series reported 36.4 percent neurologically intact survival among 22 in-hospital arrest patients, a Başkent University series weaned only 30.4 percent of 46 cardiac patients from VA-ECMO, and only a small number of Turkish centers are registered with ELSO. No prehospital ECPR case has ever been reported in the country, and no formal ECMO transport teams exist. The authors propose a phased pilot built on a centralized hub-and-spoke model with a Targeted-Dispatch strategy: local 112 teams begin high-quality resuscitation immediately, and if a witnessed arrest meets strict criteria without return of spontaneous circulation within ten minutes of advanced life support, a dedicated ECPR team deploys from a hub hospital to perform ultrasound-guided percutaneous cannulation in the field or a mobile intensive care unit.

Cost looms over any such plan. An Australian analysis by Zmudzki and colleagues estimated the average prehospital ECPR cost per patient at 12,741 Australian dollars, with a cost-effectiveness ratio near 44,000 dollars per quality-adjusted life year—falling to roughly 22,000 dollars when secondary benefits such as increased organ donation were included. The review’s authors stress that ECPR should be framed not as a replacement for basic life support but as an apex intervention layered on top of a strengthened chain of survival, and they call for ethical and legal governance covering clinical liability, consent, and withdrawal criteria, alongside formal cost-utility analysis before any rollout. Their proposed framework, they caution, is an expert-informed pilot concept rather than a validated protocol, limited initially to metropolitan regions with short transport distances and ECPR-capable referral hospitals. If prospective studies confirm feasibility, the idea of a heart-lung machine humming beside a roadside could move from medical science fiction to standard emergency care—one carefully selected patient at a time.

Subject of Research: Prehospital extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest

Article Title: Prehospital extracorporeal cardiopulmonary resuscitation: global trends and the Turkish perspective

Article References: Denizli, F., Kınış, Z., & Hızaler, E. (2026). Prehospital extracorporeal cardiopulmonary resuscitation: global trends and the Turkish perspective. Journal of Emergency and Disaster Medicine, 2(1), Article 20. https://doi.org/10.1007/s44467-026-00023-y

Image Credits: AI Generated

DOI: 10.1007/s44467-026-00023-y

Keywords: ECPR, ECMO, cardiac arrest, prehospital care, resuscitation, out-of-hospital cardiac arrest, emergency medicine, patient selection, cannulation, cost-effectiveness, Turkey, emergency medical services

The clinical story began weeks before the arrest. The patient had previously undergone a transcatheter aortic valve replacement for severe aortic stenosis, a narrowing of the heart’s outflow valve that forces the heart to pump against crushing resistance. When that bioprosthetic valve began failing again, he developed the classic signs of congestive heart failure: worsening shortness of breath, an inability to lie flat, and chest pain. His medical history compounded the danger. He had coronary artery disease treated with a drug-eluting stent in the left anterior descending artery, and he was on long-term hemodialysis for end-stage renal disease. An echocardiogram revealed a mean gradient of 43 mmHg across the valve with a peak velocity of 3.98 meters per second, both indicating severe obstruction, while his left ventricular ejection fraction had collapsed from 35 to 40 percent a year earlier to just 5 to 10 percent. Cardiac catheterization pinpointed the likely culprit: in-stent restenosis, a re-narrowing inside the previously placed coronary stent.

Interventional cardiologists opened the blocked stent with angioplasty and deployed a second drug-eluting stent, loading the patient with aspirin and clopidogrel, two antiplatelet drugs that further raise bleeding risk. Despite the revascularization, his requirement for inotropic drugs, medications that force the weakened heart to contract harder, kept climbing over the next 24 hours. The team planned an urgent TAVR-in-TAVR, meaning a new valve delivered by catheter inside the failing one, to relieve the persistent shock. Before that could happen, the patient deteriorated into pulseless electrical activity, a rhythm in which the heart’s electrical system fires but no mechanical pumping follows. Advanced cardiovascular life support protocols were initiated, and the ECMO team was mobilized for extracorporeal cardiopulmonary resuscitation, in which a machine takes over circulation while the underlying cause is treated.

The cannulation itself was engineered to waste as little blood as possible. Over a no-flow period of just one minute followed by a low-flow period of 44 minutes, for a total of 45 minutes of CPR, the team percutaneously inserted a 25 French drainage cannula into the right common femoral vein and a 17 French return cannula into the left common femoral artery. Manual pressure was applied continuously whenever dilators were exchanged, a simple but critical maneuver to prevent ooze from the access site. A 6 French distal perfusion cannula, placed with a micropuncture needle, protected the leg from ischemia. Before anything else proceeded, the team confirmed with the family exactly which interventions the patient’s faith permitted: cardiopulmonary bypass, ECMO, and cell saver technology, which recovers and returns the patient’s own blood, were all acceptable, while allogeneic transfusions were not.

With mechanical support running, the bloodless medicine protocol swung into action. The patient received daily infusions of epoetin alfa, a synthetic version of the hormone that drives red blood cell production in the bone marrow, at 20,000 units per day with a boost of 40,000 units on the day of cannulation and valve replacement. Intravenous ferric gluconate supplied the iron raw material for hemoglobin synthesis, while daily cobalamin and folic acid supported the cellular machinery of hematopoiesis. Blood draws, a notorious cause of hospital-acquired anemia in the critically ill, were minimized, clustered together, and performed with pediatric collection tubes that require only tiny volumes. Nutrition was carefully maintained, because malnutrition worsens both anemia and coagulopathy. All of this had to coexist with therapeutic heparin anticoagulation and dual antiplatelet therapy, a pharmacological tightrope walk between clotting in the circuit and bleeding from every puncture site.

Three days after ECMO cannulation, the patient underwent the transfemoral TAVR-in-TAVR procedure. Every vascular access was obtained under combined ultrasound and fluoroscopic guidance using micropuncture needles in a single pass, a technique that maximizes the chance of first-stick success and minimizes hematoma formation. Ten days after cannulation, the team successfully weaned him from V-A ECMO and decannulated him, returning the blood remaining in the circuit to his body and repairing both cannulation sites primarily. The numbers tell the story of how close the margins were. His hemoglobin stood at 11.7 grams per deciliter on the day of cannulation, fell to 7.5 by decannulation, and touched a nadir of 6.3 during the admission. Platelets dropped from 180,000 per cubic millimeter at ECMO initiation to 92,000 at decannulation, with a low of 73,000 on the circuit. He remained therapeutically anticoagulated throughout the entire support period.

The outcome, measured over a full year, was remarkable. At discharge, his ejection fraction had recovered to 15 to 20 percent and the valve gradient had fallen from 43 to 12.7 mmHg. At one year, the ejection fraction reached 30 to 35 percent with a gradient of 9 mmHg and only trace aortic insufficiency. Neurologically, he was intact, oriented to person, place, time, and situation, with no deficits despite 45 minutes of resuscitation. He spent 46 days in the hospital and was discharged to a long-term acute care facility, initially requiring maximum assistance with daily activities alongside occupational and physical therapy. The only ECMO-related complication was a polymicrobial infection at the surgical cutdown site, involving E. coli, S. marcescens, and E. faecium, which required antibiotics, surgical re-exploration, and a vacuum-assisted closure device. Notably, he received no transfusions at any point despite multiple cardiovascular interventions.

The case matters because the statistics for bleeding during extracorporeal resuscitation are sobering. Depending on how bleeding is defined, between 9 and 40 percent of ECPR patients experience hemorrhage requiring transfusion, and the SAVE-J II trial demonstrated that as many as 64 percent of ECPR patients need blood, sometimes up to ten units of packed red cells on top of fresh frozen plasma and platelets. Known risk factors include thrombocytopenia at presentation, older age, elevated D-dimer, surgical or central cannulation, and renal replacement therapy, and this patient carried several of them. Jehovah’s Witnesses, whose faith prohibits blood product transfusion, have therefore often been considered poor candidates for ECMO, and published reports of successful bloodless ECPR remain scarce. The Temple team argues that being a Witness is not an absolute contraindication, provided an algorithmic approach is followed and decisions are made jointly with the patient and family.

The protocol they describe extends well beyond this single case. Ultrasound-guided vascular puncture avoids repeated needle sticks that cause hematomas and limb ischemia, and a two-person cannulation team allows continuous manual pressure during equipment exchanges. Retrograde autologous priming, in which the patient’s own blood displaces the crystalloid fluid that fills the circuit, can prevent hemodilution when time permits. Once on support, the authors suggest considering anticoagulation targets below the standard ELSO recommendation of an aPTT 1.5 to 2.5 times baseline or an anti-Xa level of 0.3 to 0.7 IU/mL, balancing thrombotic risk against bleeding, guided by institutional protocols. Should hemorrhage occur, they recommend a predetermined multidisciplinary plan: stop systemic anticoagulation immediately, administer acceptable hemostatic alternatives, and intervene early for mechanical control. Shortening the duration of support matters too, since rapid liberation from V-A ECMO is independently associated with fewer bleeding complications, and weaning should proceed only once hemodynamics are unequivocal to avoid re-cannulation.

What elevates this report from a curious anecdote to a reference point is its demonstration that bloodless medicine, usually planned weeks in advance for elective surgery, can be executed in the chaos of an emergency resuscitation. The key elements, careful cannulation technique, hematopoietic support, minimized phlebotomy, nutritional optimization, and meticulous circuit management, are all deployable once a patient is stabilized on the machine. With well-defined goals of care agreed upon in advance and a disciplined, algorithmic approach, the authors conclude that extracorporeal cardiopulmonary resuscitation can be a viable option for Jehovah’s Witness patients in cardiac arrest. Given how few such cases have been reported with successful outcomes, this experience offers clinicians a practical roadmap for one of the most challenging scenarios in critical care, and a reminder that respecting a patient’s religious convictions and delivering aggressive, life-saving technology need not be mutually exclusive.

Subject of Research: Bloodless extracorporeal cardiopulmonary resuscitation with ECMO in a Jehovah's Witness patient

Article Title: Extracorporeal cardiopulmonary resuscitation for cardiogenic shock in a Jehovah’s witness

Article References: Afflu, D. K., F. Chai, L., Kehara, H., Baskin, S. M., Toyoda, Y., & Yanagida, R. (2026). Extracorporeal cardiopulmonary resuscitation for cardiogenic shock in a Jehovah’s witness. Journal of Artificial Organs, 29(4), Article 65. https://doi.org/10.1007/s10047-026-01591-6

Image Credits: AI Generated

DOI: 10.1007/s10047-026-01591-6

Keywords: ECMO, ECPR, cardiogenic shock, Jehovah's Witness, bloodless medicine, mechanical circulatory support, TAVR, cardiac arrest, blood conservation, anticoagulation, epoetin, cardiac surgery

The Impella family of devices works by drawing blood from the left ventricle through an inlet area near the pump’s tip and expelling it into the ascending aorta, providing up to several liters per minute of forward flow while simultaneously unloading the failing ventricle. The pump motor and bearing assembly sit within the blood stream, and heat and mechanical stress make that region a nidus for thrombus formation. To prevent clot from accumulating around the motor, the device continuously flushes a sterile purge solution through the narrow clearance space between the rotor and the housing; the solution then exits into the circulation. Because this purge fluid is delivered directly into the patient’s blood, whatever is dissolved in it becomes part of the patient’s systemic drug exposure. Historically, the manufacturer’s instructions have called for heparin to be added to the purge solution, so the purge line acts as a continuous low-dose heparin infusion on top of whatever systemic anticoagulation the patient is already receiving.

That arrangement is straightforward when Impella is used alone, but it becomes genuinely complicated when ECMO is added. Patients on ECPELLA support are typically managed with systemic anticoagulation to protect the oxygenator and tubing of the extracorporeal circuit, guided by protocols such as those issued by the Extracorporeal Life Support Organization, whose 2021 adult and pediatric anticoagulation guidelines consolidated contemporary practice. Layering a heparin-containing purge on top of systemic heparin, or on top of an alternative agent such as bivalirudin, creates a second, parallel route of anticoagulant delivery whose contribution to the total dose is not independently measured by standard monitoring. Clinicians therefore face a balancing act: enough anticoagulation to protect two devices and a circuit, but not so much that bleeding, the most common complication of mechanical circulatory support, becomes life-threatening. Some centers have responded by removing heparin from the purge bag entirely, running the purge with anticoagulant-free solutions such as 5% dextrose in water or sodium bicarbonate, and relying on systemic anticoagulation to protect the pump.

The question is whether an anticoagulant-free purge actually protects the device. The purge flow rate is titrated to maintain a specified pressure gradient across the purge circuit, which serves as a proxy for patency of the tiny channels that bathe the motor; if those channels clot, purge pressure rises, the purge rate climbs to compensate, and in the worst case the pump malfunctions. Prior single-center experiences, including analyses of heparin 25 units per milliliter purge solutions and separate evaluations of bicarbonate-based purge solutions in patients with cardiogenic shock supported by Impella, have suggested that non-standard purge strategies can be workable, but the data remain limited and the patients most likely to receive ECPELLA, those in profound cardiogenic shock, have been underrepresented. The new study by Nathaniel J. Martin, Christoph G. S. Nabzdyk, Scott D. Nei, Andrew N. Rosenbaum, Troy G. Seelhammer, and Patrick M. Wieruszewski was designed to examine exactly this gap: Impella device function in patients receiving combined ECMO and Impella support, stratified by whether their purge solution contained heparin or not.

The design was observational and modest in scale, and the authors are explicit about its limits. The team identified 25 patients supported with ECPELLA at their institution. Fourteen of these patients received an anticoagulant-free purge solution, either 5% dextrose or sodium bicarbonate, while the remaining 11 received a heparin-containing purge solution. The median duration of ECPELLA support was five days, a duration long enough for purge-related thrombosis to become clinically apparent if it were going to occur. The primary observation of interest was Impella device malfunction attributable to purge failure, the outcome that would most directly signal that an anticoagulant-free purge was inadequate to keep the motor housing clear. Ethical approval for the study came from the Mayo Clinic Institutional Review Board, with a waiver of informed consent, consistent with the retrospective review of clinical care.

The headline finding is stark in its simplicity. Across the entire cohort, the only episode of Impella device malfunction occurred in a patient in the heparin-containing group. No patient in the anticoagulant-free group experienced a purge-related device failure during their course of support, and device longevity appeared acceptable in both groups. Read at face value, the result suggests that dextrose- or bicarbonate-based purge solutions, paired with systemic anticoagulation, did not compromise the mechanical integrity of the Impella during a median of five days of combined support. In an environment where every additional unit of heparin delivered through the purge line potentially shifts a critically ill patient’s hemostatic balance, a strategy that removes that infusion without evident device harm is clinically meaningful, even if the evidence behind it is still thin.

The authors themselves are careful not to overstate the case, and their caution is warranted for reasons that go to the heart of how small clinical studies work. With only 25 patients and a low overall event rate, the study cannot exclude a modest increase in device malfunction risk associated with anticoagulant-free purge solutions; the single malfunction in the heparin group, far from indicting heparin, illustrates precisely how noisy such comparisons are at this scale. Bleeding outcomes, thromboembolic events, and hemolysis, all of which matter enormously in this population, are not the focus of the abstract-level reporting, and confounding by indication is a live concern: the choice of purge solution likely reflected evolving institutional practice and individual patient characteristics rather than random assignment. The conclusion the authors draw is correspondingly measured. Given the low event rate and the apparent maintenance of acceptable device longevity, they write, use of anticoagulant-free purge solutions alongside systemic anticoagulation in ECPELLA patients may be reasonable, but the strategy requires validation in an appropriately powered study.

Even so, the study contributes to a broader and increasingly visible conversation about how anticoagulation should be managed across the growing arsenal of temporary circulatory support devices. Pharmacotherapy reviews have called for optimization of anticoagulation in Impella-supported patients, noting the tension between manufacturer recommendations, center-specific protocols, and the absence of definitive trial evidence. Comparisons of bivalirudin versus heparin for systemic anticoagulation during ECMO, published in Critical Care Medicine by members of the same Mayo group, reflect the same underlying effort to rationalize hemostatic management in extracorporeal support. The purge solution sits at an unusual intersection within this landscape: it is simultaneously a device-maintenance fluid and a systemic drug delivery route, and it is frequently overlooked in discussions that focus on the more visible systemic anticoagulants. Recognizing the purge line as a pharmacologic exposure, and studying it as one, is a conceptual step forward for the field.

For the bedside intensivist, pharmacist, and perfusionist managing an ECPELLA patient tonight, the practical takeaway is not a new protocol but a new data point in an evolving conversation. Anticoagulant-free purge solutions, whether 5% dextrose or sodium bicarbonate, have now been used in a consecutive series of ECPELLA patients at a high-volume center without evident compromise of device function over a median of five days of support. That observation will not end the debate, and no one should abandon heparinized purge on the strength of 25 patients, but it legitimizes the strategy as a subject for the large, prospectively designed comparative study it deserves. Until such a study exists, the choice of purge solution will remain a matter of institutional protocol and clinical judgment, exercised within the same delicate balance that defines all of extracorporeal support: keeping the blood fluid enough to survive the machine, and the patient solid enough to survive the bleeding. This small study suggests the balance can be struck without heparin in the purge bag, and that alone makes it worth the field’s attention.

Subject of Research: Impella purge solution strategy and device function in patients receiving combined ECMO and Impella (ECPELLA) support

Article Title: Impella purge solutions in patients receiving extracorporeal membrane oxygenation

Article References: Martin, N. J., Nabzdyk, C. G. S., Nei, S. D., Rosenbaum, A. N., Seelhammer, T. G., & Wieruszewski, P. M. (2026). Impella purge solutions in patients receiving extracorporeal membrane oxygenation. Journal of Artificial Organs, 29(4), Article 64. https://doi.org/10.1007/s10047-026-01595-2

Image Credits: AI Generated

DOI: 10.1007/s10047-026-01595-2

Keywords: Impella, ECMO, ECPELLA, purge solution, anticoagulation, heparin, mechanical circulatory support, cardiogenic shock, left ventricular unloading, device malfunction, critical care, ventricular assist device

The outbreak first came to the attention of the World Health Organization on May 2, 2026, when passengers aboard the MV Hondius, which carried 147 crew members and passengers from 23 countries, presented with fever and gastrointestinal symptoms that rapidly progressed to pneumonia, shock, and acute respiratory distress syndrome. Laboratory confirmation of Andes virus infection by polymerase chain reaction followed between May 4 and May 6. By July 2, 2026, 13 cases had been identified on the vessel, 12 confirmed and one probable, and three patients had died, yielding a case fatality ratio of 23 percent. Epidemiologists hypothesize that an initial case acquired the infection from a rodent before boarding, with subsequent human-to-human transmission occurring during the prolonged, close contact that confined shipboard conditions inevitably produce.

Andes virus, formally Orthohantavirus andesense, occupies a unique position among hantaviruses. While hantaviruses are typically transmitted from rodents to humans through contact with urine, feces, or saliva, and humans are generally considered dead-end hosts, Andes virus is the only hantavirus documented to spread efficiently between people. First identified in Argentina in 1995, the virus has an incubation period ranging from 7 to 42 days, with a median of 18 days, and viral RNA has been detected in blood, respiratory secretions, urine, and semen. Transmission can occur through mucosal or respiratory exposure to infectious respiratory particles, although the virus is not classified as highly airborne. Case fatality ratios have reached 50 percent in some settings, and the virus has a documented history of super-spreading events, most dramatically during Argentina’s 2018 to 2019 outbreak, when transmission at a large social gathering linked to three super-spreaders produced the largest Andes virus outbreak recorded to date, with a case fatality ratio of approximately 32 percent.

Genomic sequencing of viruses isolated from the MV Hondius passengers detected no new lineages, and the circulating strain closely resembled Andes virus lineages previously identified in Argentina and Chile. The outbreak’s reproductive number was estimated at 0.7, considerably lower than the median reproductive numbers of 2.12 and 0.96 observed before and after infection control measures during the Argentine outbreak. Because the incubation period can extend to six weeks, disembarked passengers were asked to quarantine for 42 days, a duration that health authorities calculate provides a 96 percent probability of safe release. The episode has nonetheless highlighted the vulnerability of international transportation systems, where restricted spaces, overcrowding, inadequate ventilation, and limited access to intensive care can amplify transmission. Experts now recommend screening passengers boarding from hantavirus-endemic regions, controlling rodents on ships and in harbors, and establishing approved protocols for managing infectious diseases in international waters.

The pathogenesis of Andes virus infection centers on endothelial dysfunction. Hantaviruses target endothelial cells, producing enhanced microvascular permeability in the principal target organs: the lungs in hantavirus cardiopulmonary syndrome, which predominates in the Americas, and the kidneys in hemorrhagic fever with renal syndrome, which prevails in Europe and Asia. Immune-mediated mechanisms play a pivotal role. CD8-positive T cell activation has been documented during acute phases of both syndromes, immunoblasts circulate in patients experiencing shock or pulmonary edema, and fatal cases show high densities of cytokine-releasing cells in lung tissue. Elevated levels of tumor necrosis factor alpha can drive capillary leakage, pulmonary edema, and shock, while high interleukin 2 levels increase vascular permeability. Hantavirus cardiopulmonary syndrome unfolds in three phases: a prodromal phase of non-specific flu-like symptoms, a cardiopulmonary phase marked by pulmonary capillary leak and hemodynamic compromise that can culminate in cardiogenic shock, and a convalescent recovery phase.

Early diagnosis is critical because no specific antiviral agent exists. Reverse transcription polymerase chain reaction can detect viral RNA in whole blood during the asymptomatic and prodromal phases, and serological confirmation relies on IgM and IgG assays performed with chemiluminescence immunoassay technology. IgM antibodies appear at symptom onset, rise within a week, and clear after one to three months, whereas IgG antibodies emerge three to seven days after symptoms begin and persist for years, making them unsuitable for early diagnosis. Notably, some polymerase chain reaction-positive cases have been entirely asymptomatic, and viremia can precede symptoms. Differential diagnoses during the prodromal phase include influenza, COVID-19, viral and atypical pneumonias, yellow fever, dengue, leptospirosis, endocarditis with pulmonary edema, sepsis with acute respiratory distress syndrome, and arenavirus infections, underscoring the diagnostic challenge clinicians face.

Clinically, initial symptoms of hantavirus cardiopulmonary syndrome typically emerge one to eight weeks after exposure and include chills, fever, gastrointestinal upset, nausea, vomiting, diarrhea, headache, dizziness, and myalgia, before sudden progression to respiratory distress, hypotension, and shock. A recent systematic review and meta-analysis identified prognostic factors for severe outcomes, including female sex, age over 18, rural residence, pulmonary infiltrates on chest radiographs, underlying disease with elevated serum creatinine and hematocrit, and signs of bleeding. For patients with severe disease, extracorporeal membrane oxygenation can be life-saving; in experienced centers in the United States, Argentina, and Chile, ECMO-supported survival has ranged from approximately 60 to 75 percent. Timely administration of antipyretics, vasopressors, fluid therapy, mechanical ventilation, and renal replacement therapy, tailored to infection severity and organ involvement, remains the foundation of care.

On the pharmacological front, favipiravir is the most studied antiviral under consideration for Andes virus, though most safety and efficacy data derive from its use against other viral infections. A recently published case report described a 69-year-old man, diagnosed through screening after repatriation from the cruise ship, who received a combination of oral favipiravir, subcutaneous icatibant, intravenous then oral ribavirin, and oral baricitinib over a proposed 10-day course. The patient developed hypoxemia, hyponatremia, thrombocytopenia, and bilateral interstitial infiltrates roughly 24 hours after diagnosis, but recovered clinically, radiologically, and laboratory-wise from day two without progressing to shock or requiring vasopressors or invasive ventilation. Ribavirin and favipiravir were discontinued on days five and nine, respectively, after recurrent diarrhea and hyponatremia. The authors caution that a single favorable outcome cannot establish efficacy, and larger studies are required. Icatibant, a selective bradykinin B2 receptor antagonist, is hypothesized to alleviate bradykinin-driven vascular leakage, while the interleukin 6 receptor antagonist tocilizumab showed striking signals in a MEURI case series: five of five untreated ICU patients with Andes virus cardiopulmonary syndrome died, compared with four of five survivors among those receiving a single 8 mg/kg intravenous dose within 24 hours of admission. By contrast, a double-blind randomized trial in Chile found that high-dose intravenous methylprednisolone provided no significant clinical benefit in hantavirus cardiopulmonary syndrome, and monoclonal antibodies, molnupiravir, and baloxavir remain at earlier stages of investigation.

Vaccine development remains an empty pipeline in Western nations, with no approved hantavirus vaccine in the United States or Europe, although the inactivated Hantavax vaccine is used in Korea and China. A DNA vaccine targeting the Andes virus glycoprotein has completed Phase I testing: in a randomized controlled trial of 48 healthy adults, needle-free administration of 2 mg or 4 mg doses in three- or four-dose schedules was generally well tolerated, induced neutralizing antibodies, and achieved seropositivity rates of 67 to 90 percent by day 337, with only mild to moderate adverse events. Viral vector vaccines based on vesicular stomatitis virus and mRNA vaccines using both uridine and N1-methylpseudouridine platforms are in preclinical development, and recombinant human monoclonal antibodies JL16 and MIB22 have provided high levels of post-exposure protection in animal models by neutralizing viral glycoproteins. The review’s authors conclude that while the public health risk from the current outbreak remains low, the MV Hondius episode demonstrates that Andes virus could become a broader global concern, and they urge accelerated development of specific antivirals and vaccines, particularly mRNA platforms, alongside sustained vigilance in isolation, physical distancing, rodent control, and global cooperation to manage unpredictable outbreaks in the years ahead.

Subject of Research: Epidemiology, pathogenesis, and pharmacological management of the 2026 Andes virus outbreak linked to a cruise ship

Article Title: Incidence, pathogenesis, clinical manifestations, and pharmacological management of the 2026 Andes virus outbreak

Article References: Ghasemiyeh, P., & Mohammadi-Samani, S. (2026). Incidence, pathogenesis, clinical manifestations, and pharmacological management of the 2026 Andes virus outbreak. Virology Journal, 23(1), Article 208. https://doi.org/10.1186/s12985-026-03298-9

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03298-9

Keywords: Andes virus, hantavirus, hantavirus cardiopulmonary syndrome, MV Hondius, cruise ship outbreak, human-to-human transmission, favipiravir, tocilizumab, ECMO, DNA vaccine, mRNA vaccine, public health

The work, published in Biomedical Microdevices, extends a long-running effort to build what the group calls an artificial placenta: a lung assist device assembled from arrays of single oxygenator units, each a microfluidic chip fabricated from polydimethylsiloxane, the transparent silicone elastomer beloved by microfluidics engineers. PDMS is easy to mold, gas-permeable and optically clear, but in contact with blood it is profoundly thrombogenic. When plasma proteins adsorb onto its hydrophobic surface, they undergo conformational changes that activate the coagulation factors, platelets and complement proteins that normally patrol the vasculature. In a device whose channels are measured in tens or hundreds of micrometers, even a small clot can occlude flow, degrade gas exchange and shed emboli into the patient’s circulation.

The McMaster strategy centers on a molecule with an unusual pedigree. Antithrombin is the body’s natural brake on coagulation, a serine protease inhibitor that neutralizes thrombin and factor Xa. Heparin accelerates this inhibition dramatically, but heparin immobilized on biomaterial surfaces has historically underperformed, because the pentasaccharide sequence that activates antithrombin must be presented in a specific orientation and because bound heparin alone cannot catalyze inhibition without recruiting antithrombin from plasma. To sidestep these limitations, Anthony Chan, John Brash and colleagues developed a covalent antithrombin-heparin complex in which the two molecules are permanently linked, preserving the catalytic machinery in a single, surface-tethered unit. Earlier studies showed that such complexes, when coated onto flat PDMS using polydopamine as an adhesive layer, could render the material blood-compatible.

Polydopamine itself is a piece of bioinspired chemistry borrowed from marine mussels, which anchor themselves to rocks in churning surf using adhesive proteins rich in the amino acid DOPA. When dopamine is oxidized under mildly alkaline conditions, it polymerizes into a thin, conformal film that adheres tenaciously to virtually any surface, from metals to polymers, through a combination of covalent and noncovalent interactions. In the new study, the team flowed a polydopamine solution through the microchannels of the oxygenator units, then introduced the antithrombin-heparin complex under flow as well, allowing the coating to build up uniformly inside the tortuous three-dimensional geometry that flat-surface experiments cannot fully replicate.

Quantifying what sticks to the inside of a sealed microfluidic device is a technical challenge in its own right. The researchers solved it by radiolabelling the antithrombin-heparin complex, which allowed them to measure surface density directly: the coated units carried 0.21 plus or minus 0.05 micrograms of the complex per square centimeter. More importantly, the coating proved durable. When the modified devices were perfused with flowing blood for two days, 76 percent of the bound complex remained on the surface, a stability figure that matters enormously for any device intended to support a neonate for days or weeks. A coating that leaches away within hours would offer only fleeting protection and might itself become a source of embolic debris.

Surface density alone does not guarantee function, so the team also measured whether the immobilized heparin retained its biological activity. Their assay exploited the fact that active heparin binds antithrombin from plasma with high affinity. Devices coated with the antithrombin-heparin complex captured 47.78 plus or minus 10.63 nanograms of antithrombin per square centimeter from plasma, roughly four times the 11.56 plus or minus 4.58 nanograms per square centimeter measured on devices coated with polydopamine alone. That fourfold difference demonstrates that the covalent complex presents heparin in a catalytically competent configuration, effectively turning the entire blood-contacting surface of the device into an anticoagulant reactor that continuously neutralizes thrombin as blood passes through.

The functional consequences were visible at the macroscopic scale. When plasma was perfused through the modified units for one hour, the devices resisted clotting, whereas unmodified or polydopamine-only controls showed the fibrin deposition and flow obstruction characteristic of biomaterial-triggered coagulation. Just as critically, the researchers verified that the coating did not compromise the device’s primary job. Oxygen permeability, the property that allows the thin PDMS membranes to transfer gas between an oxygen supply and the blood, was unchanged by the surface treatment. That dual requirement, anticoagulant function without degraded gas exchange, has been the stumbling block for many previous hemocompatibility strategies, including polyethylene glycol layers and zwitterionic coatings, which can delaminate or alter transport properties over time.

The clinical context gives the work its urgency. Neonatal extracorporeal membrane oxygenation, or ECMO, remains an anticoagulation enigma, as pediatric intensivists have described it, because the systemic heparin required to keep circuits patent exposes infants, whose hemostatic systems are immature, to serious bleeding risks including intracranial hemorrhage. Ventilator-induced lung injury adds another layer of harm for preterm babies, whose alveoli can be damaged by the very pressures meant to keep them alive. A lung assist device whose internal surfaces actively inhibit clot formation could reduce the systemic anticoagulation burden, and the artificial placenta concept envisions pumpless microfluidic oxygenator arrays that could support preterm neonates with far less trauma than conventional extracorporeal circuits.

What distinguishes the new study is the translation from flat substrates to functional devices under realistic flow conditions. Coating chemistry that works on a flat coupon frequently fails inside a microchannel, where flow profiles, channel aspect ratios and surface-to-volume ratios conspire to produce uneven films. By performing both the polydopamine deposition and the complex immobilization under flow, the team showed that the strategy scales to the device level, a prerequisite for assembling the single oxygenator units into the integrated arrays that would constitute a clinical lung assist device. The authors note that the results demonstrate a previously developed modification strategy can be translated from flat PDMS substrates to microfluidic units, providing device-level anticoagulant function without measurably compromising membrane oxygen permeability under the conditions tested.

Challenges remain before the technology reaches the neonatal intensive care unit. The one-hour plasma clotting resistance and two-day stability experiments, while encouraging, must be extended to longer durations, whole blood and ultimately animal models, and the group has already explored pairing the antithrombin-heparin coating with immobilized tissue plasminogen activator to add fibrinolytic activity to the anticoagulant function. Regulatory pathways for combination products that blend a device with a pharmacologically active surface will also demand careful scrutiny. Still, the study offers a compelling proof of concept: by borrowing the adhesive tenacity of a mussel and the catalytic elegance of a natural anticoagulant complex, the researchers have shown that the surfaces of life-supporting microdevices can be engineered to fight the clotting response they provoke, bringing the artificial placenta one step closer to the bedside of the tiniest patients.

Subject of Research: Covalent antithrombin-heparin surface modification of PDMS microfluidic oxygenator units for anticoagulant function in neonatal lung assist devices

Article Title: Surface modification of microfluidic oxygenator units with an antithrombin-heparin (ATH) covalent complex for enhanced anticoagulant function

Article References: Li, S., Sandejas, D., Saraei, N., Dabaghi, M., Atkinson, H. M., Fusch, G., Rochow, N., Fusch, C., Selvaganapathy, P. R., Chan, A. K. C., Brash, J. L., & Sask, K. N. (2026). Surface modification of microfluidic oxygenator units with an antithrombin-heparin (ATH) covalent complex for enhanced anticoagulant function. Biomedical Microdevices, 28(3), Article 60. https://doi.org/10.1007/s10544-026-00842-w

Image Credits: AI Generated

DOI: 10.1007/s10544-026-00842-w

Keywords: antithrombin-heparin complex, microfluidic oxygenator, polydopamine, PDMS surface modification, blood compatibility, neonatal respiratory distress, artificial placenta, lung assist device, anticoagulant coating, hemocompatibility, Biomedical Microdevices, ECMO

The letter, authored by Barina Khan of Karachi Medical and Dental College and published on 3 September 2026 as Volume 29, article number 59 of the journal, is written in direct response to a pilot study by Tran and colleagues that documented dynamic platelet dysfunction in patients undergoing extracorporeal membrane oxygenation. That pilot work, which appeared in the same journal earlier in 2026, used platelet function testing to follow how platelet performance changed over the course of ECMO support and explored whether those changes tracked with clinically significant bleeding. The new letter does not dispute that platelet dysfunction is real and important in ECMO patients. Instead, it questions whether the specific instrument and protocol used can reliably detect it in this population.

The core of the concern lies in what laboratory scientists call a ceiling effect. The PFA-200 measures the time it takes for platelets, under controlled high shear conditions, to form a plug that occludes a microscopic aperture in a cartridge coated with platelet agonists such as collagen and epinephrine or collagen and adenosine diphosphate. When platelet function is severely impaired, the plug simply never forms, and the instrument reports a result at or above the maximum assay limit, typically a value greater than 300 seconds. In profoundly thrombocytopenic or platelet-exhausted patients, which many ECMO patients quickly become, large numbers of test results pile up at this artificial ceiling. Once a value has been censored at the upper limit, the assay can no longer distinguish between moderately severe and catastrophic platelet failure, compressing exactly the range of dysfunction that matters most for predicting bleeding.

Khan’s letter argues that this censoring problem is particularly acute during ECMO, where platelet counts fall progressively, platelets become activated and exhausted through continuous contact with the oxygenator membrane and circuit tubing, and acquired platelet defects accumulate over days of support. If a study correlates closure times with bleeding episodes in such a cohort, the relationship may be flattened or distorted by the many results that read simply as greater than 300 seconds. Statistical associations computed on censored data risk either underestimating the true strength of the link between platelet failure and hemorrhage or, depending on how the ceiling values are handled in the analysis, producing misleading conclusions about when platelet dysfunction begins to matter clinically.

The second confounder the letter highlights is hematocrit, the proportion of blood volume occupied by red blood cells. It is a long-standing observation in hematology that the PFA-100 and PFA-200 are exquisitely sensitive to the hematocrit of the sample. Red cells are not passive bystanders in primary hemostasis; they physically push platelets toward the vessel wall in flowing blood and contribute chemical signals, including adenosine diphosphate released from erythrocytes, that amplify platelet activation. When the hematocrit drops below roughly 30 percent, closure times lengthen even if platelets themselves are functioning normally, and severe anemia can push closure times beyond the assay limit on its own. Conversely, elevating the hematocrit can shorten closure times and mask genuine platelet defects, an effect documented decades ago in studies of uremic and cirrhotic patients evaluated on the platelet function analyzer.

This sensitivity is a serious problem in the ECMO population specifically. Patients on extracorporeal support are frequently anemic, whether from hemodilution caused by circuit priming, hemolysis within the circuit, repeated blood sampling, gastrointestinal bleeding, or the suppressed red cell production that accompanies critical illness. In such patients, a prolonged closure time may reflect the red cell deficit rather than intrinsic platelet failure, and the degree of prolongation may bear little relationship to the true functional capacity of the platelets. Khan’s letter suggests that unless hematocrit is either matched across study groups or formally adjusted for in the statistical model, the association reported between PFA-200 closure times and bleeding in ECMO patients may be confounded from the outset, with anemia masquerading as platelet dysfunction.

The letter places these concerns in a broader and somewhat sobering context. The clinical utility of closure times on the platelet function analyzer has been debated for more than two decades. Studies in cardiac surgery patients have repeatedly questioned whether the device predicts blood loss after cardiopulmonary bypass, another setting in which acquired platelet defects, hemodilution and anemia coexist. A comprehensive review in the American Journal of Hematology catalogued the assay’s utility across bleeding disorders while also documenting its susceptibility to hematologic variables, and a worldwide survey of platelet function testing practices conducted under the auspices of the International Society on Thrombosis and Haemostasis underscored how much variability exists in how platelet function is assessed even among expert laboratories. Against that backdrop, applying the PFA-200 to the uniquely harsh environment of extracorporeal circulation demands particular caution about the assay’s known limitations.

None of this means the assay should be abandoned in the ECMO setting, the letter’s argument implies, but rather that its results must be interpreted with an awareness of when the instrument can and cannot see. Practical strategies exist. Researchers can report the proportion of censored results explicitly and use statistical methods designed for data with detection limits rather than treating the ceiling value as a genuine number. Studies can stratify closure times by hematocrit, exclude samples with severe anemia from platelet-focused analyses, or measure closure times only after red cell transfusion has stabilized the hematocrit. Complementary tests that are less dependent on shear, hematocrit and sample handling, such as light transmission aggregometry, flow cytometric markers of platelet activation, or other point-of-care viscoelastic and platelet-mapping devices, can help triangulate the true state of platelet function. The pilot study’s central observation, that platelet dysfunction evolves dynamically during ECMO, remains valuable; the question is whether the PFA-200, as deployed, is measuring that dysfunction or partly measuring the anemia around it.

The stakes are far from academic. Bleeding remains one of the most feared complications of ECMO, occurring in a substantial fraction of patients and driving decisions about anticoagulation intensity, transfusion thresholds and circuit management. If closure times on the PFA-200 are adopted as a bedside guide without accounting for ceiling effects and hematocrit, clinicians risk both false reassurance, when an apparently normal result is actually capped by the assay limit in a patient with profound platelet exhaustion, and false alarm, when a prolonged result in an anemic patient triggers unnecessary platelet transfusion. Given that platelet transfusions carry their own risks, including allergic reactions, transfusion-associated circulatory overload and the theoretical promotion of thrombosis in a patient group already prone to circuit clotting, refining which patients truly need platelet support is a matter of real clinical consequence.

Khan’s letter is a compact methodological intervention, but it lands at a moment when interest in platelet function testing during extracorporeal support is growing rapidly. As devices for measuring closure times, aggregometry and platelet activation migrate from hematology laboratories to the intensive care unit bedside, the letter serves as a reminder that the validity of any such measurement depends on the biology of the sample as much as the precision of the instrument. In ECMO patients, where thrombocytopenia, platelet exhaustion and anemia march together, closure times must be read with both eyes open. Whether future studies can confirm a robust, hematocrit-independent association between PFA-200 results and bleeding in this population will determine whether the assay earns a genuine place in the ECMO management toolkit, or remains a test whose ceiling it cannot see above and whose red cell context it cannot escape.

Subject of Research: The reliability of PFA-200 platelet function closure times for assessing bleeding risk during extracorporeal membrane oxygenation

Article Title: PFA-200 closure times in ECMO: Are ceiling effects and hematocrit confounding the bleeding association?

Article References: Khan, B. (2026). PFA-200 closure times in ECMO: Are ceiling effects and hematocrit confounding the bleeding association?. Journal of Artificial Organs, 29(4), Article 59. https://doi.org/10.1007/s10047-026-01589-0

Image Credits: AI Generated

DOI: 10.1007/s10047-026-01589-0

Keywords: ECMO, PFA-200, platelet function, closure time, bleeding risk, hematocrit, coagulation, extracorporeal membrane oxygenation, platelet dysfunction, anemia, point-of-care testing, Journal of Artificial Organs

Andes virus is a New World orthohantavirus carried primarily by the long-tailed pygmy rice rat, and it is unusual among hantaviruses in its capacity for person-to-person transmission, a feature documented in household clusters in Chile and in so-called super-spreading events in Argentina. Infection produces hantavirus cardiopulmonary syndrome, a biphasic illness that begins with a prodrome of fever, myalgia and gastrointestinal symptoms before progressing abruptly to cardiopulmonary compromise. The hallmark pathophysiology is a dramatic increase in microvascular permeability driven by infection of endothelial cells, leading to non-cardiogenic pulmonary edema, hypoxemia and myocardial depression. Unlike many viral hemorrhagic fevers, the dominant clinical problem is the lung and heart rather than bleeding, and the window from first respiratory symptoms to critical illness can be a matter of hours.

The new study was motivated in part by renewed international attention to the disease after a reported case-outbreak of hantavirus cardiopulmonary syndrome on a cruise ship, an event that highlighted how rarely appreciated zoonoses can surface in unexpected settings and how gaps remain in global preparedness. The research team, led by Gabriela Meza-Fuentes and René López of Universidad del Desarrollo and Clínica Alemana in Santiago, used Chile’s Diagnosis-Related Groups database to identify patients admitted with the syndrome over a six-year window, a period spanning the pre-pandemic baseline, the COVID-19 pandemic itself and the post-pandemic recovery.

The cohort comprised 215 patients with laboratory-confirmed hantavirus cardiopulmonary syndrome, of whom 69.3 percent were male and 87 percent were adults. Respiratory support was required by 148 patients. Within this group, the escalation of organ support was striking: 14.2 percent received non-invasive ventilation, 36.5 percent were managed with invasive mechanical ventilation, and 49.3 percent ultimately needed extracorporeal membrane oxygenation. In other words, among patients who could not maintain oxygenation on their own, half progressed to the most invasive form of life support available, reflecting the fulminant nature of the cardiopulmonary phase and the limited ability of conventional ventilation to compensate for a lung flooded with protein-rich edema fluid.

Outcomes tracked this intensity of care. The median hospital length of stay was eight days, with an interquartile range of three to fifteen days, and overall in-hospital mortality was 20.5 percent. Case fatality rose steeply with the level of organ support, reaching 29.6 percent among patients on invasive mechanical ventilation and 32.9 percent among those supported with ECMO. These figures are consistent with the historical literature, in which venoarterial or venovenous extracorporeal support has been credited with rescuing a substantial fraction of patients who would otherwise have died of refractory hypoxemia and shock. Early reports from the late 1990s in North America, and subsequent Chilean and Argentine series, established ECMO as the single most effective rescue therapy for the syndrome, and the current cohort confirms that this dependence has not diminished in contemporary practice.

Perhaps the most consequential finding of the temporal analysis concerns the pandemic period. After adjusting for covariates, the COVID-19 pandemic years were independently associated with higher in-hospital mortality from hantavirus cardiopulmonary syndrome, with an adjusted odds ratio of 2.73 and a p-value of 0.045. This echoes observations from other settings in which critically ill patients without COVID-19 fared worse during pandemic surges, a phenomenon attributed to strained intensive care capacity, deferred admissions, exhausted staff and reduced availability of highly specialized resources such as ECMO referral. For a disease in which survival hinges on timely transfer to a center capable of extracorporeal support, pandemic-era system stress could plausibly have delayed the escalation of care precisely when patients were deteriorating fastest.

The pathophysiological substrate of the disease helps explain why it remains so refractory to treatment. Hantaviruses enter host cells through protocadherin-1 and related receptors, infecting pulmonary endothelium and, as recent biomarker work suggests, the alveolar epithelium as well. The resulting vascular leak is amplified by sensitization to vascular endothelial growth factor, while the myocardium fails in a manner resembling a viral cardiomyopathy. Because the injury is primarily immune-mediated and permeability-driven rather than cytopathic destruction, antiviral drugs and corticosteroids have both failed to show clear benefit in randomized trials, including a double-blind Chilean trial of high-dose methylprednisolone and a multicenter trial of human immune plasma. Supportive critical care, fluid-restricted hemodynamic management and extracorporeal rescue therefore remain the pillars of therapy, and mortality has changed little over two decades.

The authors note that their dataset, derived from a national administrative database, captures the real-world distribution of organ support across both public and private hospitals, rather than the referral-biased case series that have dominated the literature. This matters for planning: hantavirus cardiopulmonary syndrome is seasonal, tied to rodent population dynamics and human exposure in rural central and southern Chile, and clusters of severe cases can rapidly consume regional ECMO capacity. With person-to-person transmission documented and the virus endemic across a broad swathe of Patagonia on both sides of the Andes, the study provides a contemporary benchmark against which emerging interventions can be judged. Several candidate therapeutics, including monoclonal antibodies directed at the viral envelope, are in preclinical development, and any future trial will need outcome data of exactly this kind to size studies and define endpoints.

For clinicians, the message is sobering but practical. Hantavirus cardiopulmonary syndrome in the modern era still kills one in five hospitalized patients, and among those who need respiratory support, the majority will require invasive ventilation and nearly half will need extracorporeal life support. Early recognition of the cardiopulmonary phase, immediate referral to centers with ECMO capability and vigilant preservation of critical care capacity during health system crises are the interventions most likely to move these numbers. The finding that pandemic-era mortality nearly tripled serves as a warning that even a well-organized national response can be vulnerable when intensive care resources are diverted, and it underscores the preparedness gap that recent commentaries on rare zoonoses have emphasized for Andes virus and its relatives.

The study was supported by Chile’s National Agency for Research and Development, and its dataset is publicly available through the Chilean National Health Fund’s open data platform. As climate change, land-use change and human encroachment on rodent habitats continue to reshape the ecology of zoonotic spillover in South America, national cohorts of this kind will remain essential for tracking whether the critical care burden of Andes virus infection is shifting, and whether decades of experience with extracorporeal support are finally being translated into falling mortality.

Subject of Research: Critical care burden, organ support use and outcomes of Andes virus-associated hantavirus cardiopulmonary syndrome in Chile.

Article Title: Temporal trends in critical care burden and outcomes of Andes virus-associated hantavirus cardiopulmonary syndrome: a national Chilean cohort

Article References: Meza-Fuentes, G., Delgado, I., Vial, P. A., Godoy-Faúndez, A., Rivera, D., Bernal, Y., Graf, J., & López, R. (2026). Temporal trends in critical care burden and outcomes of Andes virus-associated hantavirus cardiopulmonary syndrome: a national Chilean cohort. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08599-9

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08599-9

Keywords: Andes virus, hantavirus cardiopulmonary syndrome, critical care, ECMO, mechanical ventilation, in-hospital mortality, Chile, zoonosis, COVID-19 pandemic, intensive care, respiratory support, epidemiology

ARDS entered medical history in 1967, when Ashbaugh and colleagues described adults with severe hypoxemia, diffuse pulmonary infiltrates, reduced lung compliance and a clinical picture resembling the “shock lung” previously recognized after trauma. The syndrome is now understood as a form of acute inflammatory lung injury in which the alveolar-capillary barrier becomes abnormally permeable. Fluid floods the air spaces, surfactant function deteriorates, areas of lung collapse, and blood continues to pass through poorly ventilated regions. The result is profound impairment of oxygen transfer. Mechanical ventilation can sustain gas exchange, but excessive pressures and volumes may stretch vulnerable lung tissue, producing ventilator-induced lung injury. Extracorporeal support emerged as a way to interrupt that cycle by transferring part of the work of gas exchange from the damaged lungs to an external circuit.

The earliest systems were technically demanding and associated with substantial complications. In the 1970s, investigators used membrane lungs to oxygenate blood outside the body for patients with severe post-traumatic respiratory failure. A landmark randomized study published in 1979, however, failed to demonstrate a clear survival advantage for extracorporeal membrane oxygenation in severe adult respiratory failure. At the time, equipment limitations, high anticoagulation requirements and inadequate ventilation strategies constrained the therapy. ECMO subsequently declined in adult practice for several decades, even as it became an important treatment for selected newborns and children. The field began to change when improved pumps, polymethylpentene oxygenators, safer vascular cannulation and more protective ventilator strategies made prolonged support more feasible.

The modern revival of adult ECMO was strongly influenced by the CESAR trial, published in 2009, which compared conventional treatment with referral to an ECMO-capable specialist center. The study showed a higher probability of survival without severe disability among patients managed through the specialist pathway, although the trial evaluated referral to a comprehensive center rather than ECMO alone. The 2009 H1N1 influenza pandemic then provided an unexpected global test of the technology. Hospitals in Australia, the United Kingdom, Italy and elsewhere reported that selected patients with otherwise fatal viral pneumonia could survive with ECMO. During the COVID-19 pandemic, international registry studies further demonstrated that VV-ECMO could support patients with severe viral ARDS, although outcomes worsened when systems became overwhelmed and patients were referred after prolonged mechanical ventilation or extensive secondary organ injury.

Venovenous ECMO is designed primarily for respiratory failure. Blood is drained from the venous circulation, propelled through an artificial lung where carbon dioxide diffuses out and oxygen enters, and returned to the right side of the heart. The patient’s own heart then circulates the oxygenated blood through the body. Unlike venoarterial ECMO, which can provide both cardiac and respiratory support, VV-ECMO does not directly replace the pumping function of the heart. Its principal value in ARDS is that it can maintain oxygen delivery while allowing clinicians to reduce ventilator intensity. Lower tidal volumes, lower driving pressures and reduced respiratory rates can limit mechanical stress on the remaining functional lung. In some patients, ECMO also permits prone positioning, spontaneous breathing strategies or carefully controlled near-apneic ventilation, although each approach requires specialized monitoring.

The review emphasizes that ECMO is not a universal treatment for every patient with hypoxemia. Candidates generally have severe, potentially reversible respiratory failure despite optimized conventional care, including lung-protective ventilation, prone positioning and appropriate treatment of the underlying cause. Clinicians must also consider the duration of mechanical ventilation, age, frailty, neurological status and the presence of irreversible disease affecting other organs. Registry analyses and prognostic models such as RESP, PRESERVE and ECMOnet can help structure assessment, but they cannot determine an individual patient’s outcome with certainty. Obesity alone should not automatically exclude a patient, and selected people with cancer or other complex conditions may benefit. Conversely, advanced multisystem organ failure, devastating brain injury or an inability to recover from the underlying disease may make ECMO medically inappropriate.

Once support begins, management extends far beyond the circuit itself. Ventilator settings must be adjusted to avoid continuing injury while ensuring sufficient gas exchange and preventing dangerous derecruitment. Blood flow, sweep gas, oxygen transfer, carbon dioxide removal and recirculation must be assessed together rather than treated as isolated variables. Anticoagulation is usually required because blood contacts artificial surfaces, yet anticoagulation increases the risk of bleeding. Large international studies have documented frequent hemorrhagic and thrombotic events, including cannula-site bleeding, gastrointestinal hemorrhage, intracranial bleeding, oxygenator clotting and circuit thrombosis. Neurological complications are particularly serious; rapid changes in carbon dioxide after ECMO initiation may alter cerebral blood flow and have been associated with brain injury. Infection, limb ischemia, hemolysis, kidney failure, pressure injuries and profound muscle weakness add to the burden of prolonged support.

Liberation from ECMO is another area in which practice is evolving. As the lungs recover, clinicians gradually reduce sweep gas and test whether the patient can maintain acceptable oxygenation and carbon dioxide levels with less extracorporeal assistance. Successful weaning depends on improving pulmonary compliance, gas exchange, respiratory muscle function and the condition of other organs. There is no single universally accepted weaning protocol, and an international survey published in 2026 highlighted continued variation between centers. The review also notes that prone positioning during VV-ECMO remains an active subject of research. The PRONECMO randomized trial found that prone positioning could be performed safely in experienced centers, but broader questions remain about which patients benefit most and whether the strategy improves survival rather than simply oxygenation.

ECCO₂R represents a different concept. Instead of providing enough blood flow to replace most pulmonary gas exchange, ECCO₂R uses a lower-flow extracorporeal circuit primarily to remove carbon dioxide. Because carbon dioxide is more easily removed than oxygen is added, the technology can operate through smaller vascular catheters and may be less invasive than full ECMO. The proposed benefit is “ultra-lung-protective” ventilation: clinicians could reduce tidal volume or airway pressure beyond conventional protective targets while using the circuit to prevent carbon dioxide accumulation. Early studies, including Xtravent and SUPERNOVA, demonstrated technical feasibility and the ability to lower ventilator intensity in selected patients. Yet physiological improvement has not consistently translated into better outcomes. In the REST randomized trial, ECCO₂R-facilitated lower tidal-volume ventilation did not reduce 90-day mortality in patients with acute hypoxemic respiratory failure, and bleeding and other device-related risks remained important concerns.

The future of extracorporeal lung support will therefore depend less on simply building more powerful machines than on identifying the right patient at the right moment. Newer ECCO₂R platforms are being evaluated in mild-to-moderate ARDS, while studies are exploring support before invasive mechanical ventilation, advanced imaging, biological phenotyping and artificial-intelligence-assisted prediction. Researchers are also examining right-ventricular injury, a complication of severe pulmonary vascular stress that may improve when VV-ECMO reduces hypoxemia and unloads the heart. At the same time, long-term follow-up is revealing that survival is only the beginning of recovery. Survivors may experience persistent weakness, impaired cognition, post-traumatic stress, depression, anxiety and new mental-health diagnoses. The central lesson of six decades is therefore both promising and cautionary: ECMO can create time for injured lungs to heal, but it cannot replace careful critical care, and its success must ultimately be measured by meaningful recovery after the circuit is removed.

Subject of Research: Extracorporeal lung support for acute respiratory distress syndrome, including venovenous ECMO and ECCO₂R

Article Title: 60 years of ARDS and the evolution of extracorporeal lung support – from ECMO to ECCO₂R

Article References: Fernando SM, Brodie D, Slutsky AS, et al. “60 years of ARDS and the evolution of extracorporeal lung support – from ECMO to ECCO₂R.” Intensive Care Medicine (2026).

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08533-z

Keywords: Acute respiratory distress syndrome; extracorporeal life support; venovenous ECMO; extracorporeal membrane oxygenation; ECCO₂R; respiratory failure; lung-protective ventilation