The controversy stems from the Bucharest consensus conference, which established standards for controlled donation after circulatory determination of death, known as cDCDD, in adults and issued specific recommendations on the use of normothermic regional perfusion, or NRP. In this technique, blood flow is restored to the abdominal organs, and in some protocols to the thorax as well, after death has been declared, allowing organs to be rewarmed and oxygenated in situ before retrieval. Jorda-Aragón and colleagues argued that the lung has been relegated to a secondary role in these consensus documents and that early lung ventilation, resumed immediately after the mandatory hands-off period and declaration of death, is essential to optimize lung graft preservation. The reply authors do not agree with that assertion, clarifying that the consensus processes were never intended to provide detailed, organ-specific technical guidance except where such guidance was directly relevant to the application of NRP itself.

According to the reply, the management of lungs for transplantation in the context of both abdominal NRP, abbreviated A-NRP, and thoracoabdominal NRP, known as TA-NRP, is appropriately addressed in the dedicated NRP consensus document. The authors fully support measures aimed at achieving early optimal lung preservation, pointing out that there is international experience with combined lung recovery and A-NRP, including published protocols in which mechanical ventilation is resumed soon after death has been formally declared in combination with the initiation of A-NRP. Studies from Spain, including work from the Santander group, have demonstrated that lungs recovered simultaneously with abdominal NRP can achieve outcomes comparable to those from donors after brain death, while French protocols combining in situ abdominal NRP with ex vivo lung perfusion have similarly expanded the pool of viable lung grafts from circulatory death donors.

Yet the picture is far from uniform across jurisdictions. Concerns exist in some countries that the immediate resumption of cyclical ventilation could potentially be associated with restoration of effective cardiac activity, a scenario that would breach the dead donor rule, the ethical cornerstone requiring that organ retrieval must not cause or hasten the donor’s death. In response, safety measures are required in certain protocols to delay the resumption of mechanical ventilation beyond the completion of the hands-off period. These protocols allow for immediate reintubation but require delay of lung insufflation until ten minutes after the onset of mechanical asystole, with cyclical ventilation only during the pulmonary flush at surgical retrieval. National standards in the United Kingdom and best practice guidelines in Australia reflect this cautious approach, prioritizing legal certainty over the theoretical benefits of earlier re-oxygenation of the lung graft.

The technical solution adopted in Spain and other A-NRP centers involves monitoring of the left radial artery during cDCDD as a simple means of detecting any restoration of effective cardiac activity and systemic circulation, or the possibility of restoring cerebral perfusion due to inadequate occlusion of the thoracic aorta. Such an event would be readily identified by the appearance of a pulsatile arterial pressure waveform in the left radial artery in the event of restoration of effective cardiac activity, or by the appearance of non-pulsatile pressure in the left radial artery in the event of inadequate occlusion of the thoracic aorta. This real-time hemodynamic surveillance allows clinicians to proceed with abdominal perfusion while remaining confident that the brain is not being re-perfused, a critical safeguard that has been validated in published research on avoiding donor resuscitation in controlled donation after circulatory death with NRP.

The reply authors emphasize that these differences highlight the importance of ongoing evaluation of post-mortem interventions and the publication of case series or incident sharing. As international clinical experience continues to accumulate, greater harmonization of practices across countries may become possible. However, the specific timing of the resumption of mechanical ventilation following the determination of death was not addressed during the Bucharest consensus deliberations, and consequently no specific recommendation on this issue was made. This gap in the consensus reflects the genuine uncertainty that persists in the field, where the physiological benefits of early ventilation must be weighed against jurisdiction-specific legal interpretations of what constitutes permissible post-mortem intervention.

On the question of thoracoabdominal NRP, which allows simultaneous recovery of the heart and lungs, the reply acknowledges a lack of standardization in combined recovery protocols. As the letter authors point out, the ESOT Bucharest Consensus explicitly acknowledges the potential risks of lung congestion and cardiac distension during TA-NRP, complications that arise because blood returning through the pulmonary circulation cannot be effectively ejected without cardiac function, leading to hydrostatic pressure buildup and pulmonary edema. Left atrial venting, through the insertion of a venting catheter via the interatrial groove at the initiation of TA-NRP, has been proposed as a preventive maneuver. However, although this issue was discussed during the Consensus Conference, no consensus was reached among the panelists, and the reply authors therefore cannot recommend this maneuver based on the findings of the Delphi process that underpinned the consensus.

The exchange underscores a broader challenge in transplantation medicine: the tension between rapid innovation and the need for standardized, evidence-based protocols. The lung, with its distinctive physiological characteristics, including its ability to be oxygenated directly through the airway rather than relying solely on vascular perfusion, presents unique opportunities and challenges in the post-mortem setting. Protocols should incorporate measures to optimize lung oxygenation and preservation while taking advantage of these characteristics, the reply authors argue, but at the same time the acceptability and implementation of specific interventions may remain context-dependent and influenced by the regulatory framework of each country. What is permissible in Spain may be restricted in the United Kingdom or Australia, and vice versa, creating a patchwork of practices that complicates international collaboration and data comparison.

As international experience with the simultaneous recovery of the heart and lungs using TA-NRP continues to grow, the technique may become increasingly standardized, allowing optimal preservation of all organs. The reply authors completely agree with the letter authors that the lung should not be regarded as the forgotten organ in regional perfusion strategies or cDCDD consensus guidelines. The dialogue between these two groups of experts, published as part of the ongoing discussion surrounding the Bucharest consensus, illustrates how the field is evolving through constructive disagreement, with each exchange refining the technical and ethical boundaries of what is possible in donation after circulatory death.

For transplant professionals and the public alike, the debate serves as a reminder that the expansion of organ donation after circulatory death depends not only on surgical innovation but also on careful attention to the legal, ethical, and physiological details that govern every step of the retrieval process. The lungs, far from being forgotten, are now at the forefront of efforts to maximize the number of organs that can be safely and effectively transplanted from this growing donor population, with early in situ oxygenated preservation emerging as a critical factor in determining whether these vital organs ultimately reach the patients who need them.

Subject of Research: Reply to Don’t forget to safeguard the lungs during DCD multi-organ retrieval! Early in situ oxygenated preservation matters

Article Title: Reply to Don’t forget to safeguard the lungs during DCD multi-organ retrieval! Early in situ oxygenated preservation matters

Article References: Miñambres, E., Gardiner, D., & Opdam, H. (2026). Reply to Don’t forget to safeguard the lungs during DCD multi-organ retrieval! Early in situ oxygenated preservation matters. Transplant International, 39, Article 17755. https://doi.org/10.3389/ti.2026.17755

Image Credits: AI Generated

DOI: 10.3389/ti.2026.17755

Keywords: Reply, forget, safeguard, lungs, during, multi-organ, retrieval, Early, situ, oxygenated, preservation, matters

The core technical issue is deceptively simple. Mechanical ventilators measure pressure at the airway opening, a value that sums two unknowns: the pressure required to inflate the lung and the pressure required to expand the chest wall surrounding it. In most patients the chest wall contributes a modest share, so airway pressure serves as a reasonable proxy for lung stress. But in patients with severe obesity, the chest wall becomes a dominant factor. The authors of the reply agree with the commentary of Barrau and colleagues that the primary influence of massive obesity on chest wall mechanics arises from mass loading and a rightward shift of the chest wall’s pressure-volume relationship. In plain terms, the heavy abdominal contents and chest wall tissue press inward throughout the tidal range, raising the pleural pressure needed for expansion at every breath.

This distinction matters because the stiffness of the chest wall itself may not be dramatically altered in obese patients, even though the pressure needed to move it is substantially raised. The authors emphasize that the pleural pressure required for chest wall expansion, and therefore for calculating chest wall elastance at the bedside, is elevated by mass loading across the entire tidal range. Elastance, the reciprocal of compliance, describes how much pressure change is needed to produce a given volume change. When the chest wall’s elastance is inflated by mass loading rather than by inherent tissue stiffness, the interpretation of bedside measurements changes in important ways, with implications for lung recruitment, effective lung protection, and the value of esophageal pressure measurement for managing ARDS.

Esophageal pressure measurement, typically abbreviated Pes, works because the esophagus runs through the chest between the lungs and the spine, surrounded by pleural space. A balloon catheter positioned in the mid-esophagus senses the pressure of the pleural compartment around it, offering the closest available surrogate for the pressure acting on the outside of the lung. Subtracting Pes from airway pressure yields the transpulmonary pressure, the true distending stress applied to lung tissue. With that number, clinicians can titrate positive end-expiratory pressure, the PEEP that holds lung units open between breaths, so that the lung is neither overdistended at end-inspiration nor collapsed at end-expiration. Without it, PEEP is chosen from population averages that may badly misrepresent the individual patient.

The senior author of the reply, Daniel Talmor, conducted the landmark PEEP-titration study published in the New England Journal of Medicine in 2008, which demonstrated that mechanical ventilation guided by esophageal pressure could improve oxygenation and compliance in patients with acute lung injury. That trial, led by Talmor with Sarge, Malhotra and colleagues, remains the reference point for the argument that transpulmonary pressures, not airway pressures, should anchor ventilator strategy. The new correspondence places that evidence in the specific context of severe obesity, where the gap between airway pressure and transpulmonary pressure is widest and where conventional PEEP selection is most likely to fail. In an obese patient, a PEEP that looks protective on the ventilator may leave large regions of dependent lung collapsed, while the airway pressure needed to reach a protective transpulmonary target may exceed population norms.

The authors note that their reply was shaped by the theme and word-restricted format required of the brief invited article they were answering about. They focused on specific management aspects, especially since their original discussion of Pes was not confined solely to massive obesity or to controlled ventilation. That scope is significant. Esophageal pressure monitoring has potential value across the spectrum of ARDS, not only in the obese subgroup. It can inform spontaneous breathing as well as fully controlled mechanical ventilation, helping clinicians detect excessive inspiratory effort, assess whether the patient’s own breathing is generating dangerous negative pleural pressures, and adjust support accordingly. The reply’s emphasis on management aspects signals that the authors see the catheter as a practical bedside tool rather than a research curiosity.

The exchange also highlights a persistent technical controversy in the field: whether the elevated chest wall elastance observed in obese patients reflects inherent tissue stiffness or simply the mass loading that shifts the pressure-volume curve rightward. The authors’ position is that while the inherent stiffness of the chest wall may not be dramatically altered, the pleural pressure needed for its expansion is raised throughout the tidal range. This framing has direct consequences for how clinicians should interpret esophageal measurements in obese patients. If the chest wall’s pressure-volume relationship is shifted rightward by mass loading, then the esophageal pressure at any given lung volume will be higher than in a lean patient, and the transpulmonary pressure calculated from it will be lower. A clinician who ignores this shift may under-titrate PEEP, leaving lung units collapsed, or may misjudge the lung’s own elastance when partitioning respiratory mechanics.

The practical question facing the field is whether esophageal balloon catheters should be deployed routinely to personalize ventilation of ARDS. The authors’ reply, written with Ferguson and Talmor, argues implicitly that the answer is yes for patients in whom chest wall mechanics dominate, with massive obesity as the clearest example. The catheter offers the only bedside method for separating lung from chest wall mechanics, and the alternative, guessing from airway pressures alone, has been shown to misclassify individual patients. The 2008 trial’s demonstration that esophageal pressure guidance could improve physiology, combined with the growing recognition that obesity reshapes respiratory mechanics in ways that defeat population-based protocols, strengthens the case for wider deployment. The authors declare no competing interests, and the correspondence was received in September 2026 and published on 15 October 2026.

For the broader critical care community, the exchange represents a step toward precision ventilation, the idea that ventilator settings should be tailored to the measured mechanics of each patient rather than to averages derived from trials. The technical tools exist: balloon catheters are inexpensive, insertion is feasible at the bedside, and the calculations of transpulmonary pressure and chest wall elastance are straightforward once the measurement is obtained. What remains contested is the evidence threshold for routine use, the reliability of the measurement across patient positions and breathing patterns, and the training required to interpret the numbers correctly. The reply from Marini, Ferguson and Talmor addresses the obesity question directly and concedes the commentators’ point about mass loading while defending the broader value of Pes measurement. As the debate continues in Intensive Care Medicine, the esophageal balloon catheter is moving from the research laboratory toward the bedside, and patients with the most mechanically hostile chest walls stand to benefit first.

Subject of Research: Esophageal pressure-guided personalized ventilation in ARDS

Article Title: Should the esophageal balloon catheter be deployed to personalize ventilation of ARDS? Authors’ reply

Article References: Marini, J. J., Ferguson, N. D., & Talmor, D. (2026). Should the esophageal balloon catheter be deployed to personalize ventilation of ARDS? Authors’ reply. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08644-7

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08644-7

Keywords: Should, esophageal, balloon, catheter, deployed, personalize, ventilation, ARDS, Authors, reply, scientific research

At the heart of the debate is metaiodobenzylguanidine, known almost universally in the field as MIBG. For roughly four decades, radiolabeled MIBG has been the workhorse of neuroblastoma imaging. The molecule is a norepinephrine analog that is taken up by cells expressing the norepinephrine transporter, a protein abundantly displayed on neuroblastoma cells. When labeled with iodine-123, a gamma-emitting radionuclide, MIBG allows physicians to map tumor deposits across the body using single-photon emission computed tomography, or SPECT. The same biology underpins a second use: when labeled with iodine-131, a beta-emitting isotope, MIBG becomes both a diagnostic probe and a therapeutic agent, delivering targeted radiation to tumor cells that absorb it. This dual identity makes MIBG unusually important, because the tracer used to find the disease is also the tracer used to treat it.

The challenger in this story is a fluorinated cousin of MIBG called 18F-metafluorobenzylguanidine, abbreviated mFBG. Chemically, the two molecules are close relatives: both are guanidine derivatives that hijack the norepinephrine transporter to accumulate inside neuroendocrine and neuroblastoma cells. The critical difference lies in the radioactive label. Fluorine-18 is a positron emitter, which means it enables imaging with positron emission tomography rather than SPECT. PET detectors register the annihilation photons produced when positrons meet electrons, yielding images with substantially higher spatial resolution, better contrast, and more accurate quantification than conventional gamma-camera imaging. Fluorine-18 also has a physical half-life of about 110 minutes, compared with roughly 13 hours for iodine-123, which affects logistics, radiation dosimetry, and the practicalities of distribution to hospitals without an on-site cyclotron.

The case for mFBG gained momentum through a series of clinical studies. A first-in-human biodistribution and dosimetry study published in the Journal of Nuclear Medicine in 2018 by Nadia Pandit-Taskar and colleagues evaluated 18F-meta-fluorobenzylguanidine in patients with neuroendocrine malignancies and established its safety profile and radiation dose characteristics. More recently, in 2025, the same group published a lesion-based analysis of mFBG PET imaging specifically in neuroblastoma, examining how the tracer performs at the level of individual tumor deposits. These investigations suggested that the fluorinated agent could detect disease with a sensitivity and image quality that might rival or exceed the established iodine-123 compound, while offering the quantification advantages inherent to PET.

Against this backdrop, Albano, Bertagna, Piccardo, Fiz, and Treglia published a systematic review and meta-analysis in Pediatric Radiology in 2026 that directly compared 18F-mFBG with 123I-MIBG in neuroblastoma. Meta-analysis is a statistical technique that pools the results of multiple independent studies to extract a more precise estimate of a diagnostic test’s performance than any single trial can provide. Their head-to-head synthesis, drawing on the accumulated published evidence, represented one of the first attempts to formally quantify whether the new fluorinated tracer truly outperforms the old guard. The work quickly became a reference point in the field, and, as is often the case when a new technology threatens to displace an entrenched standard, it did not go unchallenged.

The challenge came from Yadgarov, Antonevskaya, and Likar, whose reply, published on 17 August 2026, took issue with aspects of the meta-analysis and with the broader inference that mFBG PET/CT is ready to supplant MIBG scintigraphy in routine clinical practice. Their critique, and the response from Albano and Treglia published two weeks later, exemplifies a familiar pattern in diagnostic imaging research. When a new tracer with superior physics arrives, enthusiasm can outrun the evidence. Questions that matter in this transition include whether the studies being compared enrolled comparable patient populations, whether the reference standards used to confirm true disease status were equivalent, whether lesion detection rates were analyzed per patient or per lesion, and whether the dosimetric implications of switching tracers have been fully characterized in children rather than extrapolated from adult neuroendocrine tumor cohorts.

These methodological points are not pedantic. In pediatric neuroblastoma, imaging findings directly determine risk stratification and therapy. The International Neuroblastoma Risk Group staging system and the treatment protocols built upon it rely on MIBG avidity as a defining biological feature of the disease. A child whose tumor takes up MIBG is eligible for 131I-MIBG targeted radiotherapy if standard treatment fails; a tumor that is MIBG-negative generally is not. If mFBG were to replace MIBG for diagnostic imaging, the field would need to confirm that the new tracer identifies the same transporter-expressing cell population, so that diagnostic avidity continues to predict therapeutic avidity. A tracer that lights up more lesions on a prettier image is not automatically a better tracer if it changes the relationship between what is seen and what can be treated.

The dosimetry question adds another layer of complexity, particularly acute in pediatrics. Children are more radiosensitive than adults, and every imaging examination must be justified against the radiation burden it imposes. Fluorine-18’s short half-life means the administered activity clears quickly, which can reduce the effective dose compared with longer-lived isotopes, but the full-body biodistribution of mFBG in children, including uptake in organs such as the myocardium, liver, and salivary glands, must be mapped carefully. The 2018 first-in-human study provided adult dosimetry data, and the 2025 lesion analysis extended the clinical picture, but pediatric-specific dosimetry remains an area where reviewers and regulators rightly demand rigor. Any claim that one tracer is safer than another must rest on measured dose coefficients in the population actually being imaged, not on assumptions carried across age groups and disease types.

There is also a practical economics dimension that the scientific exchange implicitly raises. Iodine-123 MIBG is available through established radiopharmacy supply chains in many countries, whereas 18F-mFBG requires either a local cyclotron and radiochemistry capability or a regional distribution network, infrastructure that many pediatric oncology centers, particularly in lower-resource settings, do not possess. Conversely, the higher spatial resolution of PET can change management by revealing lesions that SPECT misses, potentially altering surgical planning and response assessment. Whether that incremental diagnostic yield justifies the infrastructure investment is precisely the kind of question that meta-analyses, correspondence, and rebuttals are meant to adjudicate in public, with the reasoning visible to clinicians who must make decisions for individual children.

What the Albano and Treglia reply ultimately illustrates is that the transition from 123I-MIBG to 18F-mFBG in neuroblastoma will be decided not by any single study but by the cumulative weight of carefully scrutinized evidence. The authors of both the original meta-analysis and the critique agree on the fundamentals: mFBG is a promising tracer with genuine physical advantages, and the emerging literature supports its diagnostic potential. Where they differ is in how strongly the current evidence licenses a change in practice. That disagreement, aired transparently in the correspondence columns of Pediatric Radiology, is how the field protects itself against both premature adoption and unwarranted delay. For the children whose scans will guide their treatment in the coming years, the outcome of this technical argument is anything but academic; it will help determine which images their doctors trust, which therapies they become eligible for, and how precisely their disease can be measured from diagnosis through remission.

Subject of Research: Comparison of 18F-metafluorobenzylguanidine PET/CT and 123I-MIBG scintigraphy for neuroblastoma imaging

Article Title: Reply to:18F-Metafluorobenzylguanidine positron emission tomography/computed tomography in neuroblastoma

Article References: Albano, D., & Treglia, G. (2026). Reply to:18F-Metafluorobenzylguanidine positron emission tomography/computed tomography in neuroblastoma. Pediatric Radiology. https://doi.org/10.1007/s00247-026-06769-x

Image Credits: AI Generated

DOI: 10.1007/s00247-026-06769-x

Keywords: neuroblastoma, 18F-mFBG, 123I-MIBG, PET/CT, SPECT, pediatric radiology, nuclear medicine, meta-analysis, norepinephrine transporter, dosimetry, molecular imaging, Reply