The abstract states that gallstone disease is a prevalent hepatobiliary disorder involving interactions among metabolic imbalance, biliary dysfunction and chronic inflammation. Although cholesterol supersaturation and impaired gallbladder motility are described as well established, the review examines how immune and metabolic processes may contribute to gallstone formation. It focuses specifically on the relationship between biliary bacterial colonization, inflammatory signalling, NET formation and MMP activity.

According to the abstract, bacterial colonization of the biliary tract can trigger inflammatory signalling pathways, cytokine release and oxidative stress. These processes are associated with activation of MMPs, which the review says may disrupt extracellular-matrix integrity and the protective mucin barrier. Such changes are presented as promoting cholesterol-crystal nucleation and retention in the gallbladder. In parallel, NETs are described as structural scaffolds that may enhance crystal aggregation and help stabilize gallstone growth.

The review further argues that bile-acid toxicity and altered lipid metabolism can intensify epithelial injury and inflammatory responses, reinforcing a pro-lithogenic environment. By connecting infection-associated inflammation, extracellular-matrix changes, NET scaffolds, bile-acid effects and lipid metabolism, the proposed framework links biliary and immune processes to gallstone development. The abstract identifies NET formation, MMP activity and bile-acid-mediated toxicity as potential molecular targets and possible avenues for therapeutic investigation, but it does not report tested treatments, clinical outcomes or evidence that targeting these pathways prevents gallstones. Because the source provided is an abstract, the review’s detailed methods, extent of literature coverage and limitations cannot be assessed from the available material.

Subject of Research: Immunometabolic mechanisms implicated in gallstone formation

Article Title: Immunometabolic crosstalk in gallstone disease: driving roles of bacterial infection, NETs and MMP activation

Article References: Murali, S., Krishna, R. B. D., Krishnamurthy, N., Balu, J., Ram, P. N., Vijayaraghavan, S., Shanmugam, R. K., P, H. K., & Francis, A. M. (2026). Immunometabolic crosstalk in gallstone disease: driving roles of bacterial infection, NETs and MMP activation. Molecular Biology Reports, 53(1), Article 1564. https://doi.org/10.1007/s11033-026-12741-7

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12741-7

Keywords: gallstone disease, bacterial infection, neutrophil extracellular traps, matrix metalloproteinases, bile acids, cholesterol crystallization, inflammation, gallbladder biology, Immunometabolic, crosstalk, gallstone, disease

The clinical problem is especially important in emergency and acute-care settings, where respiratory symptoms can arise from several causes. A patient may have a viral infection, a bacterial infection, or both, yet symptoms such as fever, cough, shortness of breath and abnormal vital signs may overlap. Misidentifying a viral illness as bacterial can expose patients to unnecessary antibiotics, contribute to adverse reactions and accelerate antimicrobial resistance. Conversely, overlooking bacterial infection can delay appropriate treatment. Laboratory evidence is therefore central to the initial assessment, but the available markers do not always produce an unambiguous classification.

MxA is an antiviral protein that is produced in response to type I interferon signaling. This signaling pathway is activated by viral infections, making MxA biologically different from many general markers of illness. C-reactive protein, for example, is a broad indicator of inflammation and can rise in response to both viral and bacterial disease. Procalcitonin tends to increase more strongly in bacterial infection and is used in some clinical settings, but its performance depends on the population, the infection site and the timing of measurement. MxA offers another route to viral identification because it reflects a host response specifically associated with viral replication rather than inflammation alone.

For the study, 869 consecutive adult patients were allocated to groups according to whether they had an infection and what caused it. The researchers evaluated the diagnostic performance of MxA and MxA-based ratios, then compared their results with an optimal statistical model produced through multiple linear regression. They also examined factors that might influence MxA production and developed an algorithm intended to guide antibiotic prescribing in a subgroup of patients with respiratory tract infections. The design reflects a practical question: whether a measurable biological signal can improve classification in routine adult acute care, not merely whether MxA differs between laboratory-defined groups.

MxA was significantly elevated in patients with viral infection and in those with mixed viral and bacterial infections. At an optimal cutoff of 21 micrograms per liter, the study reported a sensitivity of 79.8% and a specificity of 87.1%. The area under the receiver operating characteristic curve was 0.87, indicating that MxA separated viral from bacterial cases with substantial diagnostic accuracy across possible decision thresholds. These findings mean that many patients with viral disease could be identified by a relatively simple concentration measurement, while most patients without the marker had a condition other than a viral infection.

Sensitivity and specificity describe different sides of the same diagnostic problem. A test with high sensitivity is more likely to detect most cases of the target condition, while high specificity means that a positive result is less likely to occur in people without it. The reported values therefore support MxA as a potentially useful rule-out aid for viral infection, although they do not mean that every value can be interpreted independently of the clinical presentation. A false-negative result could occur in a patient with viral infection whose MxA concentration remains below the selected threshold, while a false-positive result could arise when another condition raises MxA. The optimal cutoff is therefore best understood as a value derived from this study population rather than a universal threshold.

The strongest performance emerged when MxA was combined with C-reactive protein and procalcitonin. In this analysis, the combined approach performed comparably to the optimal statistical model, indicating that MxA contributed information that was not fully captured by the more familiar inflammatory markers. Combining tests can be especially useful in ambiguous cases: MxA supplies evidence for viral activity, while CRP and PCT provide complementary information about the host response and the likelihood of bacterial involvement. Rather than replacing clinical assessment, the result supports an integrated interpretation in which viral biology and systemic inflammation are considered together.

The amount of MxA also differed according to viral etiology, showing that the host response is not identical across viral infections. That variability has implications for interpretation. A highly detectable marker may be especially useful for some pathogens and less informative for others, and clinicians should therefore avoid assuming that a single concentration represents every type of viral disease. The study did not report a consistent change in MxA expression associated with comorbidities, suggesting that common accompanying illnesses did not systematically distort the signal in the cohort. Nevertheless, the observational design and the composition of the enrolled population mean that broader studies would be needed to establish how the marker performs in other hospitals, age groups and disease settings.

The respiratory subgroup was especially relevant to the question of antibiotic stewardship. The researchers developed an algorithm to guide prescribing in patients with respiratory tract infections, where the presence of a bacterial pathogen can be difficult to determine from symptoms alone. The findings do not show that MxA alone can replace cultures, molecular testing or clinical judgment, nor do they establish a universal rule for withholding antibiotics. Instead, the proposed algorithm indicates how biomarker results might be integrated into a structured decision process. In that context, a viral MxA signal could contribute to the evidence used to reconsider unnecessary antibiotic therapy, while bacterial indicators could support continued assessment and treatment when warranted.

Antibiotic stewardship is not simply a matter of reducing antibiotic use. It requires ensuring that patients who need treatment receive it at the appropriate time and that unnecessary exposure is minimized. A biomarker that adds specific information about viral infection could help make that balance more precise, particularly when standard markers are discordant or the clinical picture is uncertain. MxA would not settle every diagnostic question, because the reported sensitivity leaves a meaningful proportion of viral infections below the selected cutoff and because bacterial and viral infections can coexist. Its strongest role may therefore be as one component of a broader strategy that combines laboratory findings, pathogen detection, examination, imaging when appropriate and repeated clinical assessment.

The study was supported through the Cooperatio Program for intensive care medicine, infection and immunity at Charles University, with financial support for biochemical and statistical analyses provided by Biovendor. The sponsor was reported to have had no role in study design, data acquisition, analysis, interpretation, manuscript preparation or the decision to submit the paper, and the authors declared no competing interests. The findings are now reported in BMC Infectious Diseases as a prospective observational evaluation of MxA in adult acute care. The 869-patient cohort, the reported area under the curve of 0.87 and the improvement achieved with CRP and PCT together point toward a promising addition to viral diagnostics, while the need for prospective validation and clinical implementation studies keeps the conclusions appropriately bounded.

Subject of Research: Evaluation of MxA as a diagnostic biomarker for distinguishing viral from bacterial infection in acutely ill adults

Article Title: Clinical utility of Myxovirus resistance protein A (MxA) for differentiation between viral and bacterial infection in adult acute care: a prospective observational study

Article References: Muller, J., Rajdl, D., Vimmerova, H., & Matejovic, M. (2026). Clinical utility of Myxovirus resistance protein A (MxA) for differentiation between viral and bacterial infection in adult acute care: a prospective observational study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14385-1

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14385-1

Keywords: MxA, viral infection, bacterial infection, diagnostic biomarker, procalcitonin, C-reactive protein, acute care, antibiotic stewardship, respiratory infection, interferon response, Clinical, utility

The clinical story began with what seemed, at first, to be a routine neonatal complaint. According to the case report, the infant had shown skin jaundice for two days before admission, and in the three hours before she was brought to the hospital she had decreased her milk intake and cried persistently. These are among the most common reasons newborns are evaluated by pediatricians, and none of them points specifically toward sepsis. That ambiguity is precisely what makes the case instructive, the authors argue: neonatal Edwardsiella tarda septicemia presents with non-specific clinical manifestations, which makes early diagnosis exceptionally challenging. A delayed or missed diagnosis of bacterial sepsis in a newborn can be fatal, so the stakes of recognizing unusual pathogens are high.

Blood culture provided the decisive answer. Culturing the infant’s blood allowed the laboratory to identify Edwardsiella tarda as the organism circulating in her bloodstream, confirming the diagnosis of neonatal septicemia. Blood culture remains the diagnostic gold standard for neonatal sepsis, because the clinical signs of infection in newborns, from temperature instability to poor feeding and lethargy, overlap so heavily with other neonatal illnesses that laboratory confirmation is essential before targeted therapy can be chosen. In this case, the identification of an organism that most pediatricians will never encounter in a newborn blood culture immediately placed the infant’s care in uncommon territory.

Edwardsiella tarda is a Gram-negative bacterium in the family Enterobacteriaceae, and its natural history is dominated by aquatic environments and cold-blooded animals. It is a well-documented pathogen of fish, causing disease in farmed and wild species, and it can also colonize reptiles and amphibians. Human infections are uncommon and typically occur through exposure to contaminated water or aquatic food sources, most often producing gastrointestinal illness. When the bacterium does invade the bloodstream, the consequences can be severe; the authors note that Edwardsiella tarda bacteremia can be a fatal disease in humans. Its appearance in the blood of a five-day-old infant is an event rare enough that the Jiangyou team combined their case with a review of the published literature to map what is known about this infection in newborns.

One of the most striking elements of the case involved a finding that extended beyond the bloodstream infection itself. During hospitalization, the infant was found to have a subgaleal hematoma over the left parietal region of her skull, a collection of blood between the scalp and the skull covering that had been present on imaging. That hematoma progressed to abscess rupture during her hospital stay, meaning the blood collection became infected and broke down. A subgaleal abscess in a newborn represents a serious complication, because the potential space between the galea aponeurotica and the skull can allow blood and pus to spread widely across the scalp, and infection in this compartment can seed the underlying structures. The progression of a sterile hematoma into an abscess in the setting of bacteremia illustrates how a circulating infection and a local collection of blood can reinforce one another, with bacteria seeding the hematoma and the hematoma providing a protected environment in which the bacteria can proliferate beyond the reach of circulating antibiotics.

Treatment combined two complementary strategies. The infant received meropenem, a broad-spectrum carbapenem antibiotic active against many Gram-negative organisms, including Enterobacteriaceae such as Edwardsiella tarda. Carbapenems are typically reserved for severe infections or for situations in which resistance to narrower agents is a concern, and their use here reflects the gravity of neonatal septicemia and the need to achieve rapid, reliable bacterial killing. Alongside the antibiotic, the clinicians administered adjunctive intravenous immunoglobulin, or IVIG, a blood-derived product concentrated with antibodies that can support the immature immune system of a newborn. Neonates have limited capacity to produce their own antibodies and to opsonize encapsulated and Gram-negative bacteria effectively, and IVIG is sometimes used as adjunctive therapy in severe neonatal sepsis to supplement the infant’s antibody repertoire while antibiotics address the underlying infection.

Supportive care completed the therapeutic picture. Newborns with septicemia require meticulous management of fluid balance, nutrition, temperature, and organ function, because the physiological reserves of a five-day-old are minimal and the systemic inflammatory response to bacterial sepsis can rapidly destabilize multiple organ systems. In this infant, the combination of meropenem, IVIG, and supportive measures succeeded in clearing the infection and resolving the local complication. The subgaleal abscess, despite its rupture during hospitalization, did not prevent a full recovery, and the authors report that the infant was discharged without long-term complications, an outcome that stands in welcome contrast to the potentially fatal trajectory of untreated Edwardsiella tarda bacteremia.

The rarity of this infection in newborns is what gives the case report its scientific value. By pairing their single case with a literature review, the authors have assembled a reference point for clinicians who may encounter similar presentations. The published record of Edwardsiella tarda infections in neonates is sparse, and each documented case contributes to a collective understanding of how the infection is acquired, how it manifests, and how it responds to treatment. The authors emphasize that awareness of potential environmental or aquatic exposures may be helpful when considering Edwardsiella tarda infection in neonates, a recommendation that reflects the bacterium’s ecology. In practice, this means that when a newborn presents with sepsis and cultures yield an unexpected aquatic-associated organism, clinicians should think to ask about the environments the mother and infant have contacted, from household water sources to contact with fish or aquatic animals.

The case also highlights the role of maternal exposure in the chain of transmission. The article’s keywords include maternal exposure, underscoring the authors’ interest in how a newborn so young, with no independent contact with the outside world beyond the delivery environment, could acquire a bacterium associated with water and aquatic animals. Possible routes in such cases include contamination during labor and delivery, contact in the home environment after discharge, or transmission from a colonized mother. The report does not resolve this question definitively for this infant, but by flagging maternal and environmental exposure as a consideration, it gives pediatricians a concrete line of inquiry when the unusual diagnosis arises.

For the wider medical community, the takeaways are practical. First, neonatal sepsis remains a diagnosis in which the clinical picture can deceive: jaundice and poor feeding, two of the most ordinary findings in a newborn, were the opening signs of a life-threatening bloodstream infection. Second, blood cultures must be obtained promptly whenever sepsis is suspected, because identifying the organism is the only way to move from empiric coverage to targeted therapy, particularly when the pathogen involved is as unusual as Edwardsiella tarda. Third, unusual organisms demand unusual histories, and asking about aquatic and environmental exposures can illuminate infections that would otherwise remain unexplained. Finally, the case demonstrates that even a rare and potentially fatal neonatal infection can have a good outcome when it is diagnosed by culture, treated with appropriate broad-spectrum antibiotics and adjunctive immunotherapy, and monitored closely for local complications such as the infected subgaleal hematoma that complicated this infant’s course. The authors, Qinnan Shao, Haixia Xie, Haixia Liu, and Hong Lin, all of the Department of Pediatrics at Jiangyou People’s Hospital, published the case as an open-access report so that clinicians elsewhere can draw on the experience when the same rare pathogen next appears in a newborn’s blood culture.

Subject of Research: Neonatal septicemia caused by Edwardsiella tarda

Article Title: Neonatal septicemia caused by Edwardsiella tarda: a case report and literature review

Article References: Shao, Q., Xie, H., Liu, H., & Lin, H. (2026). Neonatal septicemia caused by Edwardsiella tarda: a case report and literature review. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07819-x

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07819-x

Keywords: Edwardsiella tarda, neonatal sepsis, bloodstream infection, blood culture, meropenem, intravenous immunoglobulin, subgaleal hematoma, abscess, aquatic exposure, maternal exposure, neonatology, bacterial infection

The study’s primary objective was to evaluate how well admission procalcitonin levels could distinguish patients with confirmed bacterial infections from those without. The results were sobering. The area under the receiver operating characteristic curve, a standard measure of diagnostic discrimination where 1.0 represents perfect accuracy and 0.5 represents no better than chance, was just 0.56 with a 95 percent confidence interval of 0.45 to 0.68. At the optimal cutoff of 0.465 nanograms per milliliter, the test achieved a sensitivity of only 57 percent and a specificity of 60 percent. In practical terms, this means that procalcitonin measured at admission missed more than four in ten true bacterial infections while simultaneously misclassifying a substantial proportion of patients without bacterial infection as positive.

This poor diagnostic performance stands in stark contrast to the biomarker’s prognostic capabilities. When the researchers assessed procalcitonin’s ability to identify patients meeting the study-defined quick Sequential Organ Failure Assessment, or qSOFA, criteria for sepsis, the results were markedly different. The area under the curve rose to 0.83 with a confidence interval of 0.738 to 0.928, indicating good discrimination. The optimal cutoff for identifying sepsis was 2.65 nanograms per milliliter, yielding a sensitivity of 82 percent and a specificity of 85 percent. These figures suggest that while procalcitonin may struggle to confirm the presence of bacterial infection itself, it performs considerably better at flagging patients whose infections have progressed to a more dangerous systemic state.

Procalcitonin is a peptide precursor of the hormone calcitonin, produced primarily by thyroid C cells under normal conditions. However, during systemic bacterial infections, its expression is upregulated in extra-thyroidal tissues, particularly the liver, in response to pro-inflammatory cytokines such as interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6. Blood levels typically begin rising within two to four hours of a bacterial insult and peak at six to twelve hours, making it theoretically attractive as an early marker of bacterial rather than viral or non-infectious inflammation. Clinical guidelines in Europe and North America have increasingly incorporated procalcitonin into antibiotic stewardship protocols, using falling levels to justify discontinuing antimicrobial therapy in patients whose condition is improving.

The Ethiopian study also examined whether serial procalcitonin measurements could guide antibiotic discontinuation decisions. Among the 50 participants who underwent repeat procalcitonin testing on day three of hospitalization, a decline in the biomarker was significantly associated with clinician-directed antibiotic discontinuation. Day-three procalcitonin demonstrated excellent discriminatory performance for this outcome, with an area under the curve of 0.926 and both sensitivity and specificity of 90 percent. This finding, while promising, comes with important caveats. The researchers emphasize that the serial procalcitonin analysis was exploratory in nature and limited to a selected subgroup of patients, meaning the results should be interpreted cautiously and require validation in larger, more diverse cohorts.

The overall in-hospital mortality rate among the study participants was 6.7 percent, with 14 of the 210 enrolled patients dying during their hospital stay. In an exploratory multivariable analysis that controlled for potential confounding variables, meeting the qSOFA-based sepsis classification was associated with higher odds of mortality, although the researchers note that this estimate was imprecise due to the small number of deaths in the cohort. This limitation underscores the challenges of conducting prognostic research in settings where patient volumes and follow-up capacity may constrain statistical power.

The study employed a hospital-based longitudinal design, enrolling admitted patients at Jimma Medical Center between May and November 2025. Participants were selected consecutively until the expected sample size was achieved, a method that reduces selection bias compared to convenience sampling. Data collection used structured questionnaires covering sociodemographic characteristics, clinical information, and laboratory parameters. The mean admission procalcitonin level across the cohort was 1.65 nanograms per milliliter with a standard deviation of 2.1, indicating considerable variability in baseline biomarker levels among patients presenting with suspected bacterial infection. Statistical analysis was performed using SPSS version 27, with receiver operating characteristic curves used to determine optimal cutoff values and multivariate regression models employed to adjust for confounders.

The findings carry significant implications for clinical practice in low- and middle-income countries, where bacterial infections remain a leading cause of hospitalization and death. Ethiopia, like many sub-Saharan African nations, faces a high burden of infectious diseases alongside rising rates of antimicrobial resistance. If procalcitonin cannot reliably distinguish bacterial from non-bacterial illness in this population, clinicians may need to rely on other diagnostic strategies, including microbiological cultures, clinical scoring systems, and imaging, to guide initial antibiotic decisions. At the same time, the strong performance of procalcitonin for sepsis identification and antibiotic stewardship suggests the biomarker retains value as a prognostic and monitoring tool rather than a standalone diagnostic test.

The disconnect between diagnostic and prognostic performance observed in this study aligns with a growing body of international literature suggesting that procalcitonin’s utility depends heavily on the clinical question being asked. Previous meta-analyses have reported variable diagnostic accuracy for procalcitonin across different patient populations, infection types, and healthcare settings, with performance generally declining in patients with localized infections, early disease, or conditions that elevate procalcitonin through non-bacterial mechanisms such as trauma, surgery, or severe inflammation. The Ethiopian data add an important geographic dimension to this literature, as most existing evidence derives from European and North American cohorts with different epidemiological profiles, comorbidity burdens, and access to pre-hospital care.

The researchers acknowledge several limitations of their work. The single-center design at Jimma Medical Center may limit generalizability to other healthcare settings in Ethiopia and beyond. The modest sample size of 210 patients, while adequate for the primary diagnostic analysis, constrained the precision of mortality-related estimates and limited the serial procalcitonin subgroup to 50 participants. The study also relied on clinician-directed antibiotic discontinuation as an outcome, which reflects real-world practice patterns but may be influenced by factors beyond biomarker values, including clinical judgment, radiological findings, and microbiological results. Despite these constraints, the study represents one of the most detailed prospective evaluations of procalcitonin performance in a sub-Saharan African hospital population and provides a foundation for larger multi-center validation studies that could inform evidence-based antimicrobial stewardship guidelines tailored to resource-limited settings.

Subject of Research: Diagnostic and prognostic performance of the biomarker procalcitonin in hospitalized adults with suspected bacterial infection in Ethiopia

Article Title: Diagnostic and prognostic performance of procalcitonin among hospitalized adults with suspected bacterial infection in Southwest Ethiopia: a prospective observational study

Article References: Abadiko, E. A., Ashine, A. H., Ahimed, M. D., Herego, N. S., Shifa, A. B., Mengistu, F. G., Woyimo, T. G., & Gudina, E. K. (2026). Diagnostic and prognostic performance of procalcitonin among hospitalized adults with suspected bacterial infection in Southwest Ethiopia: a prospective observational study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14655-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14655-y

Keywords: procalcitonin, bacterial infection, sepsis, biomarker, antimicrobial stewardship, diagnostic accuracy, Ethiopia, qSOFA, antibiotic discontinuation, hospitalized patients, ROC analysis, infectious diseases

The research team, led by investigators at Rutgers School of Public Health and Columbia University, focused on four of the most serious bacterial infections associated with injection drug use: skin and soft tissue infections, osteomyelitis, infective endocarditis, and central nervous system abscesses. These conditions represent a spectrum of severity, from painful tissue infections that may require surgical drainage to life-threatening heart valve infections and brain abscesses that demand weeks of intravenous antibiotics. All of them share a common thread in the context of the ongoing drug overdose crisis, in which contaminated injection practices introduce bacteria into the bloodstream and deep tissues, creating infections that frequently require prolonged hospitalization.

Methodologically, the study is a retrospective cohort analysis designed to produce nationally representative estimates. The researchers applied survey weights to the Nationwide Readmission Database, a federal dataset that captures readmissions across state lines and allows analysts to track patients who move between hospitals, a critical feature given that many patients with substance use disorders receive care at multiple institutions. After weighting, the analysis encompassed 392,984 index admissions of adults hospitalized with a primary diagnosis of one of the four target infections. Each admission was classified into one of four exposure groups based on ICD-10-CM diagnostic codes: neither disorder, opioid use disorder only, stimulant use disorder only, or co-occurring opioid and stimulant use disorders.

The demographic profile of the cohort underscores how deeply these infections intersect with an aging population of people who inject drugs. The mean age of hospitalized patients was 58.8 years, 57.1 percent were male, and 46.9 percent carried Medicare coverage, a striking figure for a population often assumed to be younger and uninsured. Within the cohort, 4.5 percent of admissions involved opioid use disorder alone, 3.9 percent involved stimulant use disorder alone, and 2.4 percent involved both disorders simultaneously. The overall unplanned readmission rates were 4.3 percent within seven days of discharge and 12.48 percent within thirty days, meaning roughly one in eight patients returned to the hospital within a month of being sent home.

After statistical adjustment for patient and hospital characteristics, the central finding emerged clearly: having opioid use disorder, stimulant use disorder, or both was associated with higher odds of both seven-day and thirty-day unplanned all-cause readmission compared with patients who had neither disorder. This pattern held across the short and slightly longer follow-up windows, suggesting that the elevated risk is not confined to the immediate post-discharge period but persists through the first month, when patients are typically transitioning from intravenous antibiotics in the hospital to oral regimens or outpatient infusion therapy.

Perhaps the most clinically provocative result concerns the co-occurring group. Patients diagnosed with both opioid and stimulant use disorders showed higher odds of readmission than those with opioid use disorder alone, although the authors note that this particular comparison did not reach statistical significance in their models. The direction of the effect is nonetheless consistent with a growing body of literature on polysubstance use, which suggests that people who use multiple drug classes experience compounded medical and social vulnerabilities. Stimulants such as methamphetamine and cocaine can drive frequent injection episodes, cardiovascular strain, and erratic engagement with care, while opioids contribute to overdose risk and withdrawal-related treatment disruption. When both disorders are present, the pathways back to the hospital may multiply.

The mechanisms behind these associations are likely multifactorial, and the study’s design cannot fully disentangle them. Patients with untreated opioid use disorder may leave the hospital against medical advice to avoid withdrawal, cutting short antibiotic courses for infections like endocarditis that require weeks of therapy. Others may be discharged without linkage to medications for opioid use disorder such as buprenorphine or methadone, returning to injection practices that seed new infections at old or new sites. Social factors, including housing instability, lack of transportation to follow-up appointments, and stigma within healthcare settings, can compound the pharmacological challenges. Readmissions in this population may also reflect non-infectious causes, including withdrawal, overdose, and complications of untreated chronic disease, since the study measured all-cause readmission rather than infection-specific recurrence.

For the authors, the implications point squarely toward integrating addiction treatment into inpatient infection care. Hospitalization for a serious bacterial infection represents a rare moment of sustained contact between this population and the healthcare system, often the longest period of stability a patient experiences in months. Evidence from other fields suggests that initiating medications for opioid use disorder during hospital admission, combined with warm handoffs to community-based treatment, can reduce subsequent opioid use and improve retention in care. The new findings extend the logic to infectious diseases practice, where hospitals have historically treated the infection and discharged the patient without addressing the underlying substance use disorder that produced it.

The study carries important caveats that shape how its results should be interpreted. Diagnostic codes for substance use disorders depend on clinician documentation, and undercoding is common, particularly for stimulant use disorder, which may mean some exposed patients were misclassified as unexposed and the true associations could be stronger than estimated. The all-cause readmission outcome cannot distinguish between returns driven by infection relapse and those driven by other acute events. As with any database study, residual confounding by severity of illness, social determinants of health, and treatment intensity remains possible. The authors also relied on the 2022 database year, and patterns of drug use and hospital practice continue to evolve rapidly, meaning the estimates represent a snapshot of a dynamic epidemic.

Even with those limitations, the scale of the analysis gives its central message considerable weight. Nearly 400,000 weighted hospitalizations for injection-related bacterial infections in a single year, with one in eight patients readmitted within thirty days, describes an enormous and largely preventable burden on patients, families, and the healthcare system. The finding that opioid and stimulant use disorders independently elevate short-term readmission risk reframes these disorders not as peripheral social issues but as central clinical drivers of infectious disease outcomes. As the authors conclude, embedding addiction medicine within inpatient infectious disease care, from bedside initiation of treatment to structured post-discharge linkage, could transform the hospital stay from a revolving door into a genuine turning point for one of the most vulnerable populations in American medicine.

Subject of Research: The association between opioid and stimulant use disorders and unplanned hospital readmission after injection drug use-related bacterial infections

Article Title: The impact of co-occurring opioid and stimulant use disorders on unplanned readmissions among patients hospitalized with bacterial infections

Article References: Hu, J., Blair, N., Mauro, P. M., Samples, H., Bushnell, G., Yin, M. T., & Shiau, S. (2026). The impact of co-occurring opioid and stimulant use disorders on unplanned readmissions among patients hospitalized with bacterial infections. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14321-3

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14321-3

Keywords: opioid use disorder, stimulant use disorder, bacterial infection, hospital readmission, injection drug use, infective endocarditis, osteomyelitis, polysubstance use, addiction treatment, Nationwide Readmission Database, infectious diseases, public health

The test in question, known as the MeMed BV or MMBV score, measures the relative concentrations of three proteins that the human immune system produces in response to infection: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), IP-10 (interferon gamma-induced protein 10), and CRP. The underlying biology is elegant. TRAIL and IP-10 are part of the antiviral arm of innate immunity, induced through interferon signaling pathways when the body detects a virus, whereas CRP rises robustly during bacterial challenge as part of the acute-phase response. By integrating the three measurements into a single algorithmic score, the test exploits the distinct immunological fingerprints that bacterial and viral pathogens leave on the host, rather than searching for the pathogens themselves. This host-response approach has a practical advantage over cultures and PCR panels: it does not depend on detecting an organism that may be present in low quantities, may be localized to a difficult-to-sample site, or may take days to grow in the laboratory.

The meta-analysis, conducted by a research team led by Azizah Hendi Aljohany and Muayad Albadrani of Taibah University in Saudi Arabia together with Shyamkumar Sriram of the University of North Texas, is, according to the authors, the first pediatric-focused evaluation of the diagnostic test accuracy of the MMBV score. The team searched PubMed, Scopus, the Cochrane Library, and Web of Science for relevant studies published up to October 2025. After removing 252 duplicates from an initial haul of 407 records and screening the remainder against predefined criteria, the researchers identified 17 entries eligible for inclusion in their review. Two independent reviewers extracted data covering baseline study characteristics, diagnostic accuracy estimates, and antibiotic prescription rates, and all analyses were performed in R version 4.3.3, following the PRISMA reporting framework and the QUADAS-2 quality assessment tool for diagnostic accuracy studies.

The pooled diagnostic performance figures are striking. Across 12 studies that could be combined in a bivariate model, the host-protein signature achieved a summary sensitivity of 89.3 percent, with a 95 percent confidence interval of 82.5 to 93.6 percent, and a summary specificity of 91 percent, with a 95 percent confidence interval of 89.1 to 92.5 percent. In practical terms, the test correctly identified roughly nine out of ten bacterial infections while simultaneously correctly classifying more than nine out of ten viral infections as non-bacterial. The area under the summary receiver operating characteristic curve, a single number that captures the overall discriminative power of a diagnostic test across all possible thresholds, was 0.943, with a confidence interval of 0.88 to 0.96. Values above 0.9 are conventionally regarded as indicating high diagnostic accuracy, and few biomarker-based tests for infection etiology reach this level in pooled pediatric analyses.

For clinicians, the asymmetry between rule-in and rule-out performance matters enormously. A test with excellent sensitivity and a very low negative likelihood ratio can be used to confidently exclude bacterial infection, which is precisely the decision that drives antibiotic prescribing in febrile children. When a clinician can rule out a bacterial cause with high confidence, the rationale for empirical antibiotics largely disappears, and the child can be managed with observation and supportive care instead. The meta-analysis authors emphasize this rule-out capability as the signature’s most clinically valuable property, noting that it is the ability to safely withhold antibiotics, rather than to confirm bacterial disease, that stands to deliver the greatest public health benefit.

The implications for antibiotic stewardship are where the analysis becomes most consequential. Multiple studies included in the review indicate that the signature has significant potential to reduce inappropriate antibiotic use. Modeling estimates cited in the analysis suggest that the test could lower antibiotic overuse in patients with viral infections by as much as 88 percent, with relative reductions ranging from 78 percent to 97 percent across different clinical settings. In one specific model, antibiotic overuse among children ultimately diagnosed with viral infections could fall from 29.6 percent to 9.1 percent, a relative reduction of 69.4 percent. Additional analyses set in emergency departments and inpatient hospital environments support the test’s utility, showing potential reductions in both antibiotic prescriptions and diagnostic errors when the score is incorporated into clinical decision-making.

These numbers should be understood against the backdrop of global antimicrobial resistance. A substantial proportion of antibiotics prescribed to children are given for viral respiratory and febrile illnesses against which they have no effect. Every unnecessary course contributes to the selection pressure that drives resistant bacteria, exposes children to side effects ranging from diarrhea to more serious adverse events, and disrupts the developing microbiome. A diagnostic tool that reliably separates bacterial from viral disease at the point of care therefore functions not merely as a laboratory convenience but as an antimicrobial stewardship intervention. If the pooled accuracy estimates translate into routine practice, the MMBV score could give clinicians the confidence to de-escalate or withhold antibiotics in the majority of febrile children who present without an obvious bacterial focus.

The authors are careful about the limitations inherent in any meta-analysis of diagnostic accuracy studies. The included studies varied in setting, patient age distribution, reference standards used to classify infections, and prevalence of bacterial disease, all of which can introduce heterogeneity into pooled estimates. Diagnostic accuracy studies also tend to be conducted under more controlled conditions than routine clinical care, and real-world performance can degrade when the test is applied to ambiguous cases, mixed infections, or children with underlying conditions. The bivariate modeling approach used by the team accounts for the trade-off between sensitivity and specificity, but the confidence intervals around the summary estimates, particularly for sensitivity, indicate some variability across the evidence base. The review nonetheless provides the strongest synthesis available of how the three-protein signature performs specifically in pediatric populations, a group in which adult-derived accuracy data cannot simply be assumed to apply.

The broader significance of the study lies in the maturation of host-response diagnostics as a field. Rather than chasing pathogens with increasingly sensitive molecular assays, researchers have increasingly turned to measuring the host’s own transcriptional and proteomic response to infection, an approach that captures the physiological consequences of disease regardless of which organism triggered it. The TRAIL/IP-10/CRP signature is among the most advanced examples of this strategy to reach clinical evaluation, and the new meta-analysis consolidates the evidence that it performs at a level that could justify wider deployment. The authors conclude that the analysis confirms the high accuracy of the MMBV host-protein signature for differentiating between viral and bacterial febrile illness in children, and that its excellent rule-out capability can reduce unnecessary antibiotic prescriptions. Whether that potential is realized at scale will depend on implementation studies, cost-effectiveness analyses, and the willingness of health systems to embed a rapid host-protein assay into the first hour of a febrile child’s evaluation, but the evidence assembled here makes a compelling case that the technology is ready for that next step.

Subject of Research: Diagnostic accuracy of the TRAIL/IP-10/CRP host-protein signature for differentiating bacterial from viral infections in children

Article Title: The TRAIL/IP-10/CRP host-protein signature (MMBV Test) in differentiating bacterial vs. viral infection in pediatric populations: a systematic review and meta-analysis of diagnostic test accuracy studies

Article References: Aljohany, A. H., Abualfaraj, T., Sriram, S., & Albadrani, M. (2026). The TRAIL/IP-10/CRP host-protein signature (MMBV Test) in differentiating bacterial vs. viral infection in pediatric populations: a systematic review and meta-analysis of diagnostic test accuracy studies. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07725-2

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07725-2

Keywords: host-protein signature, MMBV test, TRAIL, IP-10, C-reactive protein, pediatric fever, diagnostic test accuracy, meta-analysis, antibiotic stewardship, bacterial infection, viral infection, BMC Pediatrics

The review first lays out the molecular machinery. In the canonical pathway, loss of mitochondrial membrane potential stabilizes the serine/threonine kinase PINK1 on the outer mitochondrial membrane, where it phosphorylates and activates the E3 ubiquitin ligase Parkin. Parkin then decorates outer membrane proteins such as mitofusin-2 and VDAC1 with ubiquitin chains, which are recognized by cargo receptors including p62/SQSTM1, NDP52, optineurin, NBR1 and Tax1-binding protein 1. These receptors carry both ubiquitin-binding domains and LC3-interacting regions, physically bridging ubiquitinated mitochondria to LC3-positive autophagosomal membranes. Alongside this ubiquitin-driven route, noncanonical receptor-mediated mitophagy relies on mitochondrial proteins such as FUNDC1, BNIP3, BNIP3L/NIX, BCL2L13, AMBRA1, FKBP8, PHB2 and NLRX1, which bind LC3 and GABARAP family proteins directly through their own LIR motifs. Even mitochondrial lipids can act as eat-me signals: cardiolipin is externalized from the inner membrane by NDPK-D, and C18-ceramide generated by CerS1 binds LC3-II to trigger clearance.

The authors also describe mitochondria-derived vesicles, or MDVs, as a first-line quality-control system sometimes termed micromitophagy. Under basal conditions, single-membrane vesicles enriched in TOMM20 are formed in a DRP1- and MIRO-dependent manner, while stress induces PINK1/Parkin-dependent double-membrane vesicles containing matrix cargo such as pyruvate dehydrogenase, generated through OPA1, syntaxin 17 and sorting nexin 9. These vesicles ferry selected mitochondrial components to lysosomes, peroxisomes or multivesicular bodies, and can even be released as extracellular vesicles. Dysregulated MDV trafficking has been implicated in diseases including cancer metastasis, underscoring that mitochondrial quality control operates on several tiers before whole-organelle mitophagy is engaged.

Why does this matter for immunity? Because when mitophagy fails, mitochondria spill their contents. Mitochondrial DNA is rich in hypomethylated CpG motifs, making it a potent danger signal once it escapes into the cytosol or endosomes. Cytosolic mtDNA is sensed by cyclic GMP-AMP synthase, absent in melanoma 2 and Z-DNA binding protein 1, while endosomal mtDNA activates Toll-like receptor 9, and both native and oxidized mtDNA can fire the NLRP3 inflammasome. The cGAS-STING axis in particular drives interferon regulatory factor 3 activation, robust type I interferon production and NF-κB, STAT6 and MAPK signaling. Cells lacking PINK1 or Parkin accumulate cytosolic mtDNA and mount exaggerated cGAS-STING-dependent interferon responses, and impaired BNIP3L-dependent mitophagy promotes aggregation of the antiviral adaptor MAVS with heightened inflammatory cytokine output. Excessive type I interferon signaling, notably, is associated with worse outcomes in active pulmonary tuberculosis, illustrating that more immune activation is not always better.

Against this backdrop, the review catalogs how bacterial pathogens manipulate mitophagy to their advantage. Staphylococcus aureus induces mitophagy in macrophages through an HDAC11-suppression/IL-10 axis that dampens mTOR signaling, scavenging mitochondrial reactive oxygen species and promoting intracellular survival; the bacterium also hyperactivates the MEK1-ERK1/2 axis to suppress CHEK2, driving excessive mitophagy that impairs bactericidal activity. Burkholderia pseudomallei uses its type III secretion needle tip protein BipD to hijack a Kelch-like 9-kelch-like 13-cullin3 ubiquitin ligase complex, K63-ubiquitinating the inner membrane protein mitofilin and triggering p62-mediated mitophagy that suppresses mtROS. Neisseria gonorrhoeae delivers the porin PorB via outer membrane vesicles, dissipating membrane potential to activate PINK1- and OPTN/NDP52-dependent mitophagy while also recruiting RNF213 for K63-linked ubiquitination. Salmonella Typhimurium’s effector SseJ activates PINK1/Parkin mitophagy through the receptor PHB2, promoting bacterial persistence, and Listeria monocytogenes uses its virulence factor listeriolysin O to oligomerize NLRX1 and induce host mitophagy that keeps the bacterium alive.

Not all bacteria push mitophagy in the same direction, however, and the review is careful to note the exceptions. Helicobacter pylori’s CagA protein binds redistributed CYP11A1 and accelerates mitochondrial cholesterol accumulation, blocking mitophagy and thereby NLRP3 inflammasome activation and apoptosis of infected cells. Porphyromonas gingivalis disrupts mitophagic flux and lysosomal acidification in endothelial cells, preventing autophagic clearance and enabling persistent intracellular infection, even though PINK1/Parkin-mediated mitophagy can attenuate inflammation in periodontitis. In Mycobacterium tuberculosis infection, BNIP3-dependent mitophagy in macrophages lowers mtROS and favors bacterial survival, whereas Brucella abortus requires BNIP3L-mediated mitophagy for its egress from cells and cell-to-cell spread. Strikingly, in a model of bleomycin-induced lung injury, overgrowth of tissue-resident Klebsiella quasipneumoniae drove macrophage mitophagy and TGF-β1 production, linking mitophagy activation to pulmonary fibrosis through microbiota dysregulation.

Viruses, if anything, are even more inventive. Protective mitophagy is documented in coxsackievirus B3 myocarditis, where Parkin- and BNIP3-mediated clearance maintains cardiac function, and in Zika virus infection, where PINK1 activation suppresses replication and the uncoupling agent niclosamide inhibits the virus by promoting PINK1/Parkin mitophagy. But many viral effectors subvert the pathway. Herpes simplex virus 1 proteins ICP34.5 and US11 repress Parkin transcription through the EIF2S1-ATF axis, promoting infection and NF-κB-mediated neuroinflammation, while ICP0 depletes the autophagy adaptors p62 and optineurin. SARS-CoV-2 deploys multiple tools: ORF9b co-localizes with MAVS to suppress RIG-I-like receptor signaling, ORF10 translocates to mitochondria and degrades MAVS through mitophagy, and Spike 1 protein inhibits mitophagy while enhancing mtROS, NLRP3 activation and IL-18 maturation that drive cardiopulmonary inflammation. The influenza A virus proteins PB1-F2 and the nucleoprotein both induce TUFM- or toll-interacting protein-dependent mitophagy that blunts MAVS signaling, and respiratory syncytial virus NS1 acts as a bona fide mitophagy receptor by binding LC3B and TUFM.

The viral catalog extends across the animal and human pathogen spectrum. Varicella zoster virus glycoprotein E promotes DRP1-dependent fission and PINK1/Parkin mitophagy to block MAVS oligomerization and STING translocation. The severe fever with thrombocytopenia syndrome virus nucleoprotein recruits TUFM to degrade MAVS. Hepatitis C virus NS5A recruits NDP52 and optineurin to mitochondria; Senecavirus A protein 2C binds K27-ubiquitinated TUFM; African swine fever virus p17 links p62 to TOMM70; and classical swine fever virus nonstructural proteins co-opt the ESCRT machinery to close phagophores and accelerate mitophagy. Even the oncolytic Newcastle disease virus reprograms metabolism, degrading SIRT3 via PINK1/Parkin mitophagy to support replication, while enterovirus 71 uses PINK1/Parkin mitophagy to degrade MAVS and release virion-containing mitochondria into the extracellular space, aiding dissemination.

In sepsis, the picture becomes genuinely double-edged. Restoring mitophagy is generally beneficial: PINK1 protects dendritic cell function in cecal ligation puncture models; TMBIM1 and TMBIM6 preserve cardiac mitochondrial quality control; FUNDC1 ameliorates septic cardiomyopathy by suppressing ferroptosis; and bioinformatic clustering of 348 sepsis samples showed that the cluster with the highest mitophagy activity had the lowest disease severity, with prohibitin 1 negatively correlated with severity. Sirtuins are central players, with SIRT1-Rab7 and SIRT3-Parkin axes suppressing STING, NLRP3 and pyroptosis in lung injury, and melatonin attenuating septic kidney injury through SIRT3-mediated deacetylation of mitochondrial transcription factor A. Yet in polymicrobial sepsis, PINK1/Parkin-mediated mitophagy suppresses macrophage activation and impairs bacterial clearance, reducing mouse survival, a reminder that context determines whether mitophagy helps the host or the pathogen.

Therapeutically, the review highlights a growing pharmacopeia. The mitophagy activator ALT001 promotes ULK1/Rab9-dependent mitophagy and interferon-mediated antiviral defense against HSV-1; gut microbial metabolites nicotinamide N-oxide and taurine restore mitophagy in herpes simplex encephalitis; verbenalin, emodin, bergapten, dendrobine, puerarin, olaparib and even high-concentration hydrogen show protective effects in sepsis models through pathway-specific mitophagy activation. Conversely, mitochondrial division inhibitor-1 enhances SARS-CoV-2-specific CD8+ T cell responses by blocking excessive mitophagy-linked metabolic remodeling, and protopine and Liang-Ge-San alleviate lung injury by downregulating mitophagy in specific compartments. The authors conclude that selectively inducing or inhibiting mitophagy, tailored to pathogen and disease stage, represents a promising but still immature strategy, with key questions remaining about which mitophagy modes matter for which infections and how microbial effectors precisely co-opt the machinery. As the field matures, mitophagy modulation may become an adjunctive weapon against intractable infections and the inflammatory storm of sepsis.

Subject of Research: The role of mitophagy in bacterial and viral infection pathogenesis and sepsis, and its therapeutic modulation

Article Title: Mitophagy in pathogenesis and therapeutic implications for infection

Article References: Jung, B., Lee, B., Sapkota, A., Roh, T., Seo, W., Kim, J. K., & Jo, E.-K. (2026). Mitophagy in pathogenesis and therapeutic implications for infection. Experimental & Molecular Medicine. https://doi.org/10.1038/s12276-026-01852-7

Image Credits: AI Generated

DOI: 10.1038/s12276-026-01852-7

Keywords: mitophagy, autophagy, PINK1, Parkin, bacterial infection, viral infection, sepsis, mtDNA, cGAS-STING, NLRP3 inflammasome, MAVS, innate immunity

The tracer, named β-Me-2-[18F]FDG, is described in a study published in Nature Biomedical Engineering. It is derived from [18F]FDG, the glucose analogue that has anchored clinical PET for decades, but with a crucial chemical modification: a methyl group attached at the anomeric C-1 position through a β-glycosidic linkage. That small structural change transforms the molecule from a probe of host metabolism into a probe of bacterial metabolism. Human cells import glucose through GLUT and SGLT transporters, which depend on hydroxyl groups at the C-1 and C-2 positions of the sugar. By replacing the C-1 hydroxyl with a methyl group and lacking the C-2 hydroxyl entirely, β-Me-2-[18F]FDG is no longer recognized by mammalian transporters. Bacteria, however, possess an entirely different carbohydrate import machinery, the phosphoenolpyruvate-dependent phosphotransferase system, or PTS, which simultaneously transports and phosphorylates sugars using phosphoenolpyruvate as the phosphoryl donor. Because this system exists only in prokaryotes, it offers a metabolic doorway that is invisible to human tissue.

The discovery began with a remarkably simple synthetic strategy. Rather than building each candidate tracer from scratch, the researchers took clinical-grade [18F]FDG, dried it by azeotropic distillation, and subjected it to Fischer glycosidation with a series of alcohols under acidic conditions. In a single step, and with isolated radiochemical yields ranging from roughly 33 to 92 percent, they generated a library of nine 18F-labelled alkyl glucosides. Screening these compounds against Staphylococcus aureus in vitro revealed that the methyl glucoside, an anomeric mixture of α and β forms, accumulated in the bacteria far more readily than any of its longer-chain counterparts. Because glucosides do not undergo mutarotation under physiological conditions, the team could separate the two anomers by high-performance liquid chromatography and test them independently. The result was unambiguous: the β-anomer drove essentially all of the bacterial uptake, while the α-anomer was nearly inert.

Crucially, the active β-anomer can be manufactured without any new equipment. The researchers synthesized a β-methyl mannose triflate precursor and showed that it could be radiofluorinated and hydrolyzed using the same workflow, and even the same commercially available cassettes, used for routine [18F]FDG production. Manual synthesis delivered the tracer in 74.6 percent radiochemical yield with purity above 99 percent within 40 minutes, and an automated run on a GE FASTlab module produced it in 31.3 percent yield starting from 37 GBq of fluoride in about 34 minutes. In an era when most experimental PET tracers require bespoke radiochemistry, a compound that can be swapped into existing FDG infrastructure is a significant translational advantage. The team also demonstrated that direct glycosidation of clinical [18F]FDG could serve as an alternative route for imaging centers that receive FDG from commercial vendors but lack their own cyclotrons.

In laboratory assays, β-Me-2-[18F]FDG was taken up robustly and consistently by every clinical isolate of methicillin-resistant and methicillin-susceptible S. aureus tested, spanning the USA100 through USA800 pulsed-field types, as well as by methicillin-susceptible and vancomycin-intermediate Staphylococcus epidermidis. Streptococcus agalactiae and Streptococcus pyogenes also accumulated the tracer, though with somewhat more variability. By contrast, uptake in Escherichia coli, Mycobacterium smegmatis and mammalian cell lines was negligible. Heat-killed bacteria did not take up the compound, and uptake was blocked by excess non-radioactive competitor, confirming that accumulation requires live, metabolically active organisms. The tracer was also stable in both mouse and human serum for at least four hours at 37 degrees Celsius, a prerequisite for clinical use.

Genetic experiments pinpointed the transporter responsible. S. aureus encodes four glucose uptake systems: the PTS components GlcA, GlcB and GlcC, and a non-PTS transporter called GlcU. Using a panel of transposon mutants, the researchers showed that deletion of glcA, which encodes the glucose-specific PTS component EIICBAGlc1, dramatically reduced tracer uptake, whereas deletion of glcB, glcC, glcU or manA had no effect. HPLC analysis of bacterial lysates revealed that most intracellular radioactivity corresponded to a phosphorylated metabolite, consistent with the PTS mechanism of import-coupled phosphorylation, which traps the sugar inside the cell and prevents efflux. Notably, β-Me-2-[18F]FDG was not phosphorylated by mammalian hexokinase, reinforcing its selectivity for bacterial biochemistry. Protein sequence analysis showed that EIICBAGlc1 is highly conserved across Staphylococcus species, explaining why the tracer performed well against multiple staphylococcal pathogens.

In healthy mice, the tracer behaved exactly as a bacteria-specific agent should. Dynamic PET/CT imaging showed rapid distribution to lung, liver and kidneys followed by predominantly renal excretion into the bladder, with low retention in brain, heart and other background tissues. Pharmacokinetic modeling yielded a distribution half-life of 0.48 minutes and an elimination half-life of 44.34 minutes, and extrapolated human dosimetry estimated effective doses of 0.020 to 0.041 mSv/MBq depending on sex and the ICRP model applied, with the urinary bladder receiving the highest absorbed dose. Urine analysis confirmed high in vivo metabolic stability, with no detectable degradation to [18F]FDG, an advantage attributed to the stability of β-glycosidic linkages over their α counterparts.

The imaging performance in disease models was striking. In a murine myositis model, sites inoculated with live S. aureus showed a target-to-non-target ratio of 6.1, rising to 14.6 when imaging was delayed to four hours after injection, while sites inoculated with heat-killed bacteria and tissues of mice with lipopolysaccharide-induced sterile inflammation showed no significant uptake. Conventional [18F]FDG, by comparison, lit up brain, spinal cord and brown adipose tissue in inflamed animals, illustrating precisely the background problem the new tracer is designed to solve. In a wound infection model, signal at infected tissue was nearly seventeenfold higher than in uninfected tissue, and in a pulmonary model, infected lungs accumulated 11.3 percent of the injected dose per cubic centimeter versus 0.6 in uninfected lungs. In a rat model of vertebral discitis-osteomyelitis, tracer signal at the inoculated spinal level rose progressively over six days, reaching sixteenfold above baseline, and expanded to adjacent vertebrae in a pattern that mirrors multifocal spondylodiscitis in patients.

Perhaps the most clinically consequential experiments involved treatment monitoring and disseminated infection. In mice dually infected with oxacillin-susceptible and oxacillin-resistant S. aureus, serial PET scans before and after a three-day course of oxacillin showed a significant drop in signal at the susceptible site, from 5.1 to 2.9 percent injected dose per cubic centimeter, while the resistant site showed persistent uptake and visible spread of infection. Ex vivo bacterial counts correlated with the imaging findings. In a bacteremia model, the tracer revealed secondary foci of infection in the brain, heart, liver, shoulder joint and ilium by day three, sites that the gram-negative-targeting comparator tracer [18F]FDS failed to highlight. The researchers note that interpreting PET signals during bloodstream infection requires caution, since circulating bacteria and sepsis-altered tracer kinetics can confound quantification, but the pattern of focal uptake still mapped plausibly onto hematogenous dissemination.

The team, led by David M. Wilson and Sang Hee Lee at UCSF, is now preparing an investigational new drug application, including toxicity testing of the non-radioactive 19F standard, to support first-in-human studies. Because β-Me-2-[18F]FDG targets gram-positive organisms, it is envisioned as a clinical complement to [18F]FDS, which images gram-negative bacteria, allowing tracer selection based on the likely pathogen. If human trials confirm the preclinical profile, the tracer could enable physicians to distinguish infection from sterile inflammation, localize disseminated disease, and judge antibiotic success within days rather than weeks, potentially shortening therapy, sparing patients unnecessary drugs, and offering a new tool in the fight against resistant pathogens such as MRSA.

Subject of Research: Development of a bacteria-specific PET radiotracer targeting the glucose phosphotransferase system for imaging gram-positive infections

Article Title: Selective PET imaging of bacterial infection using a glycosylated 18F-fluorodeoxyglucose-derived tracer

Article References: Lee, S. H., Kim, J. M., López-Álvarez, M., Wadhwa, A., Bidkar, A. P., Ur Rahim, J., Blecha, J., Flavell, R. R., Ordonez, A. A., Seo, Y., Engel, J., Ohliger, M. A., & Wilson, D. M. (2026). Selective PET imaging of bacterial infection using a glycosylated 18F-fluorodeoxyglucose-derived tracer. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-026-01798-1

Image Credits: AI Generated

DOI: 10.1038/s41551-026-01798-1

Keywords: PET imaging, bacterial infection, Staphylococcus aureus, radiotracer, phosphotransferase system, 18F-FDG, MRSA, antimicrobial resistance, molecular imaging, gram-positive bacteria, antibiotic response monitoring, infection diagnostics

The research, led by Panyu Chen, Bingyuan Huang, Wentao Chen and Xiao Lin, with corresponding authors including Cheng Luo, Min Shi, Yuanyuan Zhang, Yugang Wang and Xiong Ma, brings together teams from Shanghai Jiao Tong University School of Medicine, the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences and collaborating institutions across China. Their central discovery is that a subset of macrophages known as scar-associated macrophages proliferates as acute-on-chronic liver failure progresses, and that these cells lose a critical antibacterial function precisely when patients need it most. That functional collapse, the authors report, is linked to poor prognosis in the disease.

Macrophages are the tissue-resident sentinels of the innate immune system, and in the liver they include Kupffer cells that patrol the sinusoids, engulfing bacteria, cellular debris and other threats. Scar-associated macrophages are a distinct population that accumulates within fibrotic, scarred regions of chronically injured liver. In cirrhotic tissue they are often viewed as accomplices of fibrosis, promoting the deposition of extracellular matrix that stiffens the organ. The new work reframes them as pivotal players in the acute decompensation that defines liver failure, not merely as passive markers of scarring but as cells whose behavior can determine whether a patient survives a bacterial challenge.

The team’s mechanistic focus landed on EP300, a histone acetyltransferase that decorates histone proteins with acetyl groups and thereby helps open chromatin and activate gene transcription programs. Because EP300 sits at the interface of signaling pathways and gene expression, pharmacologically blocking it can broadly reshape the transcriptional identity of a cell. Using an inhibitor approach, the researchers found that EP300 inhibition enhanced the antibacterial activity of scar-associated macrophages rather than dampening it. The key mediator of this effect turned out to be transcriptional repression of a gene called ACOD1, which encodes aconitate decarboxylase 1, an enzyme tied to itaconate metabolism and inflammatory regulation.

According to the study, ACOD1 expression is induced in scar-associated macrophages during acute-on-chronic liver failure. In other words, as the disease takes hold, these macrophages ramp up ACOD1, and this shift appears to compromise their ability to engulf and destroy bacteria. When the researchers genetically removed ACOD1, the consequences were striking: loss of the enzyme mitigated hepatic destruction and prolonged survival in male mice with acute-on-chronic liver failure. The protective effect was traced to enhanced phagocytic function, the capacity of macrophages to swallow and neutralize invading pathogens, which is a cornerstone of host defense in a liver constantly exposed to gut-derived microbes.

This chain of evidence, from EP300 to ACOD1 to phagocytosis to survival, sketches a coherent mechanistic pathway. EP300, by supporting ACOD1 transcription in scar-associated macrophages, inadvertently disarms the liver’s antibacterial frontline at the worst possible moment. Inhibiting EP300 lifts that repression, restoring the cells’ appetite for bacteria and thereby limiting the infectious cascade that drives much of the mortality in acute-on-chronic liver failure. Bacterial infection and sepsis are among the most common precipitants of acute decompensation in cirrhotic patients, which makes a therapy that strengthens bacterial clearance particularly attractive.

The translational implications are considerable. Liver transplantation remains the definitive treatment for acute-on-chronic liver failure, but donor organs are scarce, and many patients deteriorate or die while waiting. Supportive care in intensive care units can manage complications, yet it does not reverse the underlying hepatic collapse. A pharmacological strategy that reprograms immune cells within the scarred liver to fight infection more effectively would address a mechanism that existing treatments ignore entirely. The authors describe EP300 inhibition as a promising therapeutic strategy for the syndrome, one that operates through ACOD1-dependent reprogramming of scar-associated macrophages.

Several caveats temper the enthusiasm. The survival benefit from ACOD1 loss was demonstrated in male mice, and rodent models of acute-on-chronic liver failure, while informative, cannot fully capture the heterogeneity of human disease, which arises on diverse backgrounds of viral hepatitis, alcohol-associated liver disease and metabolic dysfunction. The study’s human dimension, built on specimens contributed by organ donors and their families, with support from clinicians at Renji and Ruijin Hospitals of Shanghai Jiao Tong University, links ACOD1 induction and impaired macrophage function to poor outcomes, but clinical trials will be needed to establish whether EP300 inhibitors can deliver the same benefit in patients. EP300 also participates in many processes throughout the body, so systemic inhibition raises questions about safety that a liver-directed or disease-windowed approach would need to answer.

The work also adds to a growing appreciation that macrophage metabolism and epigenetics are intertwined levers of immune function. ACOD1 sits within the itaconate branch of the tricarboxylic acid cycle, a pathway that immunologists have increasingly recognized as a regulator of inflammation and antimicrobial activity. By showing that an epigenetic enzyme controls ACOD1 expression in a disease-relevant macrophage subset, the study connects chromatin regulation, immunometabolism and phagocyte function in a single axis. That kind of mechanistic clarity is exactly what the field has lacked, since acute-on-chronic liver failure has historically been treated as a clinical syndrome defined by organ failure scores rather than by targetable molecular pathways.

For researchers, the immediate agenda will be to identify which EP300 inhibitors are best suited to hepatic indications, to define the precise chromatin events through which EP300 drives ACOD1 transcription, and to test whether pharmacological repression of ACOD1 reproduces the genetic findings in models that more closely mirror human decompensation. For clinicians, the study offers a biomarker lead: scar-associated macrophage ACOD1 expression could eventually help stratify patients at highest risk of infection-driven deterioration. And for patients with cirrhosis living one insult away from liver failure, the research provides something rare in this field, a concrete molecular mechanism and a druggable node standing between a scarred liver and catastrophic collapse. The findings appeared in Nature Communications on 7 October 2026, in an open-access article by Chen and colleagues.

Subject of Research: EP300 inhibition and ACOD1-dependent reprogramming of scar-associated macrophages in acute-on-chronic liver failure

Article Title: EP300 inhibition alleviates acute-on-chronic liver failure through modulation of scar-associated macrophages

Article References: Chen, P., Huang, B., Chen, W., Lin, X., Yang, C., Wang, C., Su, W., Zeng, Z., Ren, Y., Fan, S., Song, Y., Fu, R., Xu, Y., Chen, X., Xiang, X., Li, G., Chen, K., Ma, X., Wang, Y., … Luo, C. (2026). EP300 inhibition alleviates acute-on-chronic liver failure through modulation of scar-associated macrophages. Nature Communications. https://doi.org/10.1038/s41467-026-78245-x

Image Credits: AI Generated

DOI: 10.1038/s41467-026-78245-x

Keywords: acute-on-chronic liver failure, EP300, ACOD1, scar-associated macrophages, macrophages, phagocytosis, epigenetics, histone acetyltransferase, liver fibrosis, immunometabolism, bacterial infection, Nature Communications

The research team, led by corresponding author Ying Xu of the Department of Clinical Laboratory, enrolled febrile patients admitted to the hospital between 2021 and 2023. From this population, 457 eligible patients were classified into three etiological groups—bacterial, viral, or fungal infection—based on final clinical diagnoses corroborated by microbiological results. Rather than hunting for the pathogen itself, the investigators turned the diagnostic lens inward, asking whether the patient’s own immune response could reveal the identity of the invader. The rationale rests on a well-established biological principle: different classes of pathogens trigger distinct patterns of cytokine signaling, the chemical messengers through which immune cells coordinate their defense.

The biomarker panel the team evaluated combined six cytokines—interleukin-2 receptor (IL2R), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β)—with three routine inflammatory markers: procalcitonin (PCT), C-reactive protein (CRP), and the neutrophil-to-lymphocyte ratio (NLR). Each component carries distinct immunological meaning. IL-6 is an early-response cytokine that drives the acute-phase reaction and is often markedly elevated in bacterial infections. IL-10, an anti-inflammatory cytokine, rises when the immune system attempts to restrain excessive inflammation, and the balance between the two—captured by the IL-6/IL-10 ratio—reflects the net inflammatory tone of the host. IL-8 is a chemokine that recruits neutrophils to sites of infection, while PCT, a prohormone of calcitonin, is released by extra-thyroid tissues under bacterial endotoxin stimulation and has long been regarded as one of the more specific markers of bacterial insult. The NLR, a simple calculation from a standard complete blood count, indexes the relative dominance of innate, neutrophil-driven immunity over adaptive, lymphocyte-driven immunity.

To translate these measurements into clinically usable decision rules, the researchers performed receiver operating characteristic (ROC) curve analysis, a statistical technique that plots diagnostic sensitivity against the false-positive rate across all possible cut-off values. The area under the ROC curve (AUC) quantifies overall discriminative ability, with 0.5 indicating performance no better than chance and 1.0 representing perfect classification. From these analyses, the team derived optimal threshold values for each marker and then combined them into multivariable models tailored to specific diagnostic questions. The result is not a single test but a sequential pathway: first determine whether the infection is bacterial or viral, then, if bacterial, determine whether the pathogen is Gram-negative or Gram-positive, and finally assess whether the bacterial infection has progressed to sepsis.

The first step of this hierarchy addresses the most common and consequential dilemma in febrile patients—separating bacterial from viral disease. A model combining an IL-6/IL-10 ratio greater than 1.13, IL-8 above 28.70 picograms per milliliter, and an NLR above 2.96 achieved an AUC of 0.80 (95% confidence interval: 0.74–0.87) for this distinction. In practical terms, an AUC of 0.80 indicates good discriminative ability, meaning the model correctly ranks a randomly chosen bacterial case above a randomly chosen viral case about four times out of five. The logic behind the chosen variables is coherent: a high IL-6/IL-10 ratio signals unopposed pro-inflammatory activity typical of bacterial stimulation, elevated IL-8 reflects intense neutrophil recruitment, and a high NLR confirms the neutrophil-dominant blood picture that accompanies acute bacterial infection. Viral infections, by contrast, tend to provoke lymphocyte-dominated responses with comparatively restrained IL-6 and IL-8 production.

The second step of the pathway tackles a subtler question: once a bacterial infection is confirmed, is the culprit Gram-negative or Gram-positive? This distinction matters because the two bacterial classes differ in cell-wall structure, antibiotic susceptibility profiles, and clinical behavior. The study found that no single universal model sufficed; instead, site-specific models were required, reflecting the fact that the immune signature of a bacterial infection is shaped by both the pathogen’s Gram status and the anatomical location of the infection. Notably, in bloodstream infections, a model incorporating IL-6 above 44.91 picograms per milliliter and PCT above 2.30 nanograms per milliliter yielded an AUC of 0.82 (95% confidence interval: 0.70–0.93). The pairing is immunologically sensible—Gram-negative organisms release endotoxin, a potent inducer of both IL-6 and PCT, so elevated values of these two markers together point toward a Gram-negative etiology.

The third and final step addresses severity stratification: among patients with confirmed bacterial infection, which ones have developed sepsis, the life-threatening dysregulated response that demands immediate aggressive intervention? Here the combination of IL-8 above 72.45 picograms per milliliter and PCT above 1.60 nanograms per milliliter achieved an AUC of 0.80 (95% confidence interval: 0.72–0.89). Very high IL-8 concentrations likely reflect the massive neutrophil activation and endothelial inflammation that characterize septic physiology, while elevated PCT tracks the systemic bacterial burden. Together, the three steps of the pathway achieved AUC values of 0.80 to 0.82 across the key diagnostic decisions—a consistent level of performance that, while not replacing microbiological confirmation, is sufficient to guide early therapeutic choices in the critical first hours of illness.

The practical appeal of this strategy lies in its accessibility. Every marker in the panel—cytokines, PCT, CRP, and the NLR—can be measured with routine laboratory instrumentation, and many are already part of standard workups for febrile patients. The study’s authors emphasize that the approach constitutes a cost-effective, rapid decision-support tool designed to facilitate early clinical decisions and antibiotic stewardship, with particular relevance for medical institutions that lack access to expensive molecular diagnostics such as multiplex PCR panels or next-generation sequencing. In resource-limited settings, where blood cultures may take days or be unavailable altogether and where antibiotic misuse is often most severe, a tiered pathway built from existing assays could meaningfully shorten the time to targeted therapy. The work was supported by the National Natural Science Foundation of China and by Science and Technology Projects funding from Guangzhou.

As with any biomarker study, the findings come with caveats that will shape future validation. The analysis was retrospective, drawing on existing medical records from a single center, and the classification of patients depended on final clinical diagnoses, which themselves carry inherent uncertainty. Cut-off values derived from one population may require recalibration in others, and the confidence intervals around some models—particularly the Gram-negative versus Gram-positive bloodstream infection model—indicate a degree of statistical uncertainty that larger cohorts could narrow. Nonetheless, the study demonstrates a compelling concept: that the immune system’s own chemical conversation, read through a carefully chosen panel of cytokines and routine markers, can be decoded into a structured diagnostic pathway. By sequencing the questions—etiology, pathogen subtype, severity—the strategy converts a scatter of laboratory values into an actionable clinical narrative, offering a template for how host-response diagnostics might complement, and in some cases temporarily stand in for, the slower tools of classical microbiology.

Subject of Research: Host immune response biomarkers for rapid differentiation of bacterial, viral, and fungal infections

Article Title: A rapid diagnostic strategy of pathogen infection using host markers of immune response

Article References: Cai, C., Zhong, R., Zheng, S., Li, J., Lin, D., Zhang, R., Duan, C., & Xu, Y. (2026). A rapid diagnostic strategy of pathogen infection using host markers of immune response. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14518-6

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14518-6

Keywords: biomarkers, cytokines, interleukin-6, interleukin-8, procalcitonin, neutrophil-to-lymphocyte ratio, bacterial infection, viral infection, sepsis, antibiotic stewardship, diagnostic markers, ROC analysis