The researchers searched PubMed, Embase, Web of Science, the Cochrane Library, CINAHL and ClinicalTrials.gov from their inception through 1 April 2026. Eligible studies were randomized trials comparing robot-assisted gait training with conventional therapy in children with cerebral palsy or other central nervous system impairments. Risk of bias and methodological quality were assessed with the Cochrane Risk of Bias 2 tool and the PEDro scale. Random-effects meta-analysis calculated mean differences or standardized mean differences, and GRADE was used to assess the certainty of evidence.

For walking speed, the pooled standardized mean difference was 0.58 (95% confidence interval, 0.18 to 0.98; P = 0.005). The 6-minute walk distance improved by a pooled mean difference of 38.68 metres (95% CI, 22.61 to 54.75; P < 0.00001). The abstract rated the evidence for both outcomes as high certainty. An exploratory analysis of two studies also suggested a reduction in the Physiological Cost Index, although the abstract did not report a pooled effect estimate for that measure. No statistically significant between-group differences were found for GMFM-88, balance, spasticity or functional independence.

Exploratory subgroup analyses suggested larger effects on walking speed when interventions lasted at least eight weeks. Robot type was associated with a significant subgroup difference for 6-minute walk distance, but not for walking speed; both subgroup observations were described as preliminary and requiring further validation. The evidence was concentrated overwhelmingly in children with cerebral palsy. The limited spinal cord injury evidence and absence of acquired brain injury studies prevented definitive conclusions for those populations. The abstract stated that additional high-quality trials using uniform outcome measures are needed to assess broader functional endpoints and establish whether the findings extend beyond cerebral palsy.

Subject of Research: Effects of robot-assisted gait training on walking and motor outcomes in children with central nervous system impairments

Article Title: Effects of robot-assisted gait training on walking capacity and gross motor function in children with central nervous system impairments: a systematic review and meta-analysis predominantly based on cerebral palsy studies

Article References: Wu, X., Li, X., Liang, J., Chen, Z., Zhang, J., Yang, X., Fan, Q., Guo, H., Liao, L., & Du, Q. (2026). Effects of robot-assisted gait training on walking capacity and gross motor function in children with central nervous system impairments: a systematic review and meta-analysis predominantly based on cerebral palsy studies. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07359-4

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07359-4

Keywords: robot-assisted gait training, cerebral palsy, pediatric rehabilitation, walking speed, 6-minute walk distance, systematic review, meta-analysis, spinal cord injury, gross motor function, GRADE evidence, Effects, robot-assisted

The research team, led by Xiaozuo Lin and Rongxin He with senior author Man Luo, searched seven databases from their inception through May 31, 2026, hunting for randomized controlled trials that compared PCSK9 inhibitor plus statin therapy against statin monotherapy in patients with acute ischemic stroke. Two reviewers independently screened studies, extracted data, and assessed risk of bias, a rigorous double-checking process designed to minimize human error. The pooled analysis focused on outcomes that matter most to stroke patients and their families: whether patients regained functional independence, whether they suffered new strokes, how much their LDL cholesterol fell, and whether the added drug brought safety problems of its own.

The headline finding concerns recovery. Patients receiving the combination therapy were significantly more likely to achieve functional independence, defined as a score of 0 to 2 on the modified Rankin Scale, the standard yardstick of post-stroke disability where 0 means no symptoms and 2 means slight impairment but ability to look after one’s own affairs without help. The odds ratio of 2.17, with a 95 percent confidence interval of 1.29 to 3.64 and a P value of 0.003, indicates that the odds of achieving independence were more than doubled in the combination group. Importantly, the heterogeneity statistic, I squared, came in at a modest 48 percent, meaning the trials were reasonably consistent with one another on this outcome, which strengthens confidence in the pooled estimate.

Equally striking was the effect on stroke recurrence. Patients on combination therapy had roughly one-third the risk of a recurrent ischemic stroke compared with those on statins alone, with an odds ratio of 0.33, a confidence interval of 0.16 to 0.69, and, notably, zero heterogeneity across trials. In meta-analytic terms, an I squared of 0 percent means the direction and magnitude of the effect were uniform across every included study, a pattern that lends considerable weight to the result even though the GRADE assessment later rated the certainty of this evidence as low, reflecting the limited number and size of the underlying trials.

The mechanism behind these benefits likely runs through low-density lipoprotein cholesterol, the fatty particles that drive atherosclerosis, the gradual narrowing and destabilization of arteries that underlies most ischemic strokes. PCSK9, or proprotein convertase subtilisin/kexin type 9, is an enzyme that the liver uses to destroy LDL receptors on its own surface. By blocking PCSK9 with monoclonal antibodies such as evolocumab and alirocumab, the receptors survive longer, sweeping more LDL cholesterol out of the bloodstream. In this meta-analysis, combination therapy reduced LDL cholesterol by a mean difference of 0.66 millimoles per liter compared with statins alone, a substantial additional lowering on top of baseline statin therapy, though the heterogeneity here was high at 86 percent.

That heterogeneity was not entirely mysterious. Subgroup analysis showed it was partially explained by the type of statin used, with atorvastatin and rosuvastatin producing significantly different additional LDL reductions when paired with the inhibitor, a difference that reached statistical significance at P equals 0.02. This finding echoes a broader pharmacological reality: statins differ in potency, metabolism, and interaction profiles, and the LODESTAR trial’s secondary analyses have previously shown meaningful differences between atorvastatin and rosuvastatin in coronary patients. For clinicians, the implication is that the size of the lipid benefit from adding a PCSK9 inhibitor may depend on which statin backbone is chosen, a nuance that future trials should account for explicitly.

Not every outcome favored the combination. Scores on the National Institutes of Health Stroke Scale, a clinical measure of neurological deficit, showed no significant difference between the groups, with a mean difference of 2.38 points and a confidence interval spanning from minus 0.63 to 5.39. The heterogeneity for this outcome was extreme, at 98 percent, and the authors report that it was largely driven by a single study, a situation their leave-one-out sensitivity analysis was designed to probe. The GRADE certainty for the NIHSS result was rated very low, meaning that no firm conclusion about short-term neurological scores can be drawn from the current evidence base. Functional independence measured weeks to months later, it appears, may capture recovery benefits that a bedside deficit score in the acute phase does not.

Safety, often the deciding factor for any new drug combination, came out reassuringly neutral. Rates of abnormal liver function, a well-known concern with statins, were comparable between groups, with an odds ratio of 0.67 that actually trended in favor of the combination arm. Major adverse cardiovascular events showed no significant difference, and total adverse events were likewise similar, with an odds ratio of 0.85. For a therapy that involves adding an injectable monoclonal antibody to an existing oral regimen, the absence of excess harm in these short-term outcomes is a meaningful signal, particularly given that the trials enrolled patients in the fragile days and weeks immediately following a stroke.

The authors are careful, and rightly so, about the limits of what this evidence can support. Under the GRADE framework, which grades certainty from high down to very low based on study limitations, inconsistency, indirectness, and imprecision, the evidence was moderate for functional independence, low for recurrent stroke, LDL reduction, and safety outcomes, and very low for NIHSS scores. Many of the included trials were small, several were conducted in Chinese clinical settings, and the pooled populations cannot yet speak to every stroke subtype or patient demographic. The authors conclude that PCSK9 inhibitor adjunctive therapy may improve functional recovery and reduce recurrence with acceptable short-term safety, but that the evidence remains preliminary and requires confirmation in larger, adequately powered randomized trials.

Even with those caveats, the analysis lands at a consequential moment. Stroke imposes an enormous global burden of death and disability, and the cumulative exposure of arteries to LDL cholesterol over a lifetime is increasingly recognized as a central driver of atherosclerotic risk. Recent trials such as INSPIRES have intensified interest in aggressive early lipid management after acute cerebral ischemia, and theoretical cost-effectiveness work on PCSK9 inhibitors in intracranial atherosclerosis is already appearing in the literature. If larger trials confirm the signals reported here, the combination of a statin with a PCSK9 inhibitor could shift from a cardiovascular specialty strategy toward a standard component of acute stroke care, offering survivors not just lower cholesterol numbers on a lab report but a better chance of walking out of the hospital and staying stroke-free. For now, the message is one of cautious optimism: a promising therapy, a consistent early signal, and a clear call for the definitive trials that will decide whether it becomes standard practice.

Subject of Research: Efficacy and safety of PCSK9 inhibitor and statin combination therapy in acute ischemic stroke

Article Title: Efficacy and safety of PCSK9 inhibitors combined with statins in acute ischemic stroke: a systematic review and meta-analysis

Article References: Lin, X., He, R., Zhang, X., Zeng, Y., Wang, T., Chen, S., Chen, L., & Luo, M. (2026). Efficacy and safety of PCSK9 inhibitors combined with statins in acute ischemic stroke: a systematic review and meta-analysis. Journal of Neurology, 273(10), Article 652. https://doi.org/10.1007/s00415-026-14199-w

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14199-w

Keywords: acute ischemic stroke, PCSK9 inhibitors, statins, meta-analysis, LDL cholesterol, functional independence, stroke recurrence, modified Rankin Scale, evolocumab, alirocumab, randomized controlled trials, GRADE evidence

The research team, led by Jiayi Song and colleagues at Xiyuan Hospital of the China Academy of Chinese Medical Sciences, together with collaborators at Beijing University of Chinese Medicine, pooled data from 20 randomized controlled trials involving 1,414 patients. The team searched nine databases from their inception through July 2025, including Web of Science and several Chinese-language sources such as the China National Knowledge Infrastructure, the China Science and Technology Journal Database, and the China Biomedical Medicine database. The trials covered both radiation dermatitis, the skin damage that develops over irradiated areas, and radiation oral mucositis, the painful ulceration of the mouth and throat that afflicts many patients treated for head and neck cancers.

The headline finding is striking in its statistical consistency. Patients who received curcumin were significantly less likely to develop severe radiation injury, with a risk ratio of 0.55, meaning the odds of severe injury were cut nearly in half. The 95 percent confidence interval ran from 0.44 to 0.68, and, notably, the heterogeneity statistic I-squared was 0.0 percent, indicating that the included trials produced remarkably uniform results on this outcome. In clinical research, where heterogeneity across trials often muddies pooled estimates, a zero percent heterogeneity figure for a primary outcome is unusual and lends considerable weight to the conclusion.

Beyond preventing severe injury outright, curcumin appeared to blunt the overall severity of radiation damage when used prophylactically, before and during the course of radiotherapy. The standardized mean difference in severity scores was -0.81, with a confidence interval of -1.08 to -0.53, a moderate-to-large effect by conventional benchmarks, though the heterogeneity here was high at 84.1 percent, signaling substantial variation in how the trials measured and reported severity. When curcumin was used therapeutically, that is, to treat injuries that had already developed, the pooled analysis of the limited available trials showed a reduction in severity scores with a standardized mean difference of -1.06, with zero heterogeneity, although the wide confidence interval of -2.03 to -0.08 and the small number of therapeutic trials temper enthusiasm.

Pain relief emerged as another consistent benefit. Among patients using curcumin preventively, pain scores improved with a standardized mean difference of -1.06, and among those using it to treat established injury, the mean difference in pain scores was -2.22 on the scales used, with zero heterogeneity and a confidence interval running from -1.90 to -2.53. For patients whose mucositis makes swallowing agonizing or whose irradiated skin cracks and weeps, an analgesic effect of this magnitude, delivered by a dietary compound rather than an opioid, would represent a meaningful improvement in quality of life during an already grueling treatment course.

The methodological apparatus behind the analysis deserves attention, because it reflects the current gold standard in evidence synthesis. The authors assessed the risk of bias in each trial using the Cochrane Risk of Bias 2.0 tool and graded the certainty of the evidence with the GRADE framework. Rather than relying on a naive pooling method, they performed a random-effects meta-analysis with the Hartung-Knapp adjustment, a technique that produces more conservative and better-calibrated confidence intervals when the number of studies is small. All computations were carried out in R version 4.5.1, and the protocol was prospectively registered as CRD42024601503.

The team also interrogated the data for the distortions that plague meta-analyses of complementary therapies. Publication bias, the tendency for positive studies to be published while negative ones languish in file drawers, was assessed with funnel plots, Egger’s regression test applied when at least ten studies were available, and the trim-and-fill method, which estimates how many hypothetical missing studies would be needed to restore symmetry. Galbraith plots were used to visualize heterogeneity, and leave-one-out sensitivity analyses were performed to identify whether any single influential trial was driving the pooled results. This layered approach to robustness testing is precisely the kind of scrutiny that separates credible syntheses from the promotional meta-analyses that have historically inflated claims about natural products.

Safety, a perennial question for any compound proposed for use alongside cancer treatment, appears reassuring but under-documented. The incidence of adverse events showed no significant difference between curcumin and control groups, with a risk ratio of 0.84 and a confidence interval of 0.01 to 96.58. The authors themselves flag the problem: that extraordinarily wide interval reflects limited adverse event reporting across the included trials rather than genuine uncertainty about harm. The finding should therefore be read as an absence of detected signals rather than proof of safety, and the authors explicitly caution that the safety evidence requires careful interpretation. Curcumin is also known to interact with certain drug-metabolizing pathways, which makes systematic adverse event collection in future trials essential.

The biological plausibility of the findings rests on curcumin’s well-characterized anti-inflammatory and antioxidant pharmacology. Ionizing radiation kills tumor cells in part by generating reactive oxygen species, but those same radicals damage healthy tissue in the radiation field, triggering inflammation, lipid peroxidation, and impaired wound healing. Curcumin scavenges free radicals and modulates inflammatory signaling pathways, which is the mechanistic rationale for using it as a radioprotector. The drug-medicine continuum framing adopted by the authors is apt: turmeric has been consumed as a spice and used in traditional medicine for centuries, and its principal constituent now faces the same randomized-trial scrutiny as any pharmaceutical candidate.

The caveats remain substantial. Heterogeneity was high for several outcomes, potential publication bias was detected, and the GRADE assessment of evidence quality was constrained by the limitations of the underlying trials. The authors conclude that curcumin may prevent the occurrence of severe radiation injury and may reduce injury severity and pain in both prophylactic and therapeutic use, but they insist the conclusions be interpreted with caution. Still, the convergence of a halved risk of severe injury, consistent pain relief, and no detected excess of adverse events across 20 trials and more than 1,400 patients makes a compelling case that this kitchen-spice derivative has earned a place in large, rigorously designed confirmatory trials. If those trials replicate the effect, radiotherapy’s most common side effects could one day be softened by one of the oldest remedies in the pantry.

Subject of Research: Clinical efficacy and safety of curcumin for preventing and treating radiation injury in cancer patients

Article Title: Clinical efficacy and safety of curcumin for the prevention and treatment of radiation injury: a systematic review and meta-analysis of randomized controlled trials

Article References: Song, J., Fu, L., Dong, J., Hu, Y., Liu, L., Shi, J., Gu, S., Zhang, Z., Bu, Z., Liu, Z., & Xu, Y. (2026). Clinical efficacy and safety of curcumin for the prevention and treatment of radiation injury: a systematic review and meta-analysis of randomized controlled trials. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05528-7

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05528-7

Keywords: curcumin, radiation injury, radiotherapy, meta-analysis, randomized controlled trials, radiation dermatitis, oral mucositis, radioprotection, turmeric, cancer supportive care, GRADE evidence, publication bias

The methodology behind the analysis reflects the modern standards of evidence synthesis. The research team searched MEDLINE through PubMed, Embase, Scopus, and Web of Science from database inception to July 2026, casting a wide net for observational studies that evaluated laboratory-confirmed enteric infections against stunting outcomes in children. Nineteen studies passed the quality threshold for the qualitative synthesis, and fourteen contributed effect estimates to the quantitative meta-analysis. The authors followed the PRISMA 2020 reporting guidelines, pooled odds ratios using random-effects models, and assessed risk of bias with the Newcastle–Ottawa Scale. Certainty of evidence was judged using the GRADE framework, the same structured approach that underpins World Health Organization guideline development. This combination of transparent searching, formal bias assessment, and pre-specified subgroup analyses gives the review a methodological rigor that many entries in the stunting literature have lacked.

The headline number deserves unpacking. An odds ratio of 1.94 means that children with laboratory-confirmed enteric infections had roughly 94 percent higher odds of being stunted, defined as height-for-age more than two standard deviations below the reference median, compared with children without such infections. That is a substantial association in a field where effect estimates often hover close to unity. But the pooled figure came with an I-squared statistic of 85.6 percent, indicating that more than eight-tenths of the variability among studies reflected real differences between populations and methods rather than random noise. In practical terms, the pooled odds ratio describes an average of a highly heterogeneous body of evidence, and the authors were careful not to oversell it. Heterogeneity of this magnitude is common in observational meta-analyses of infection and nutrition, where study settings range from urban slums to rural highlands and diagnostic tools range from microscopy to multiplex PCR.

To probe that heterogeneity, the team conducted pre-specified subgroup analyses across pathogen domains: bacterial, viral, protozoal, helminthic, and non-specific parasitic infections. The most consequential finding of the review may be what did not emerge. Despite wide differences in the biology of these organisms, the associations with stunting were broadly comparable across domains, with no statistically significant differences between pathogen groups. Bacteria such as enteroaggregative Escherichia coli, viruses such as rotavirus, protozoa such as Giardia and Cryptosporidium, and soil-transmitted helminths all appeared to leave children at similar elevated risk of growth faltering. The authors interpret this convergent pattern as evidence that multiple enteric pathogens may impair child growth through shared biological pathways rather than through pathogen-specific mechanisms.

That interpretation aligns with two decades of research into environmental enteric dysfunction, a subclinical condition of the small intestine that has become a central hypothesis in child growth biology. Repeated exposure to fecal pathogens is thought to provoke chronic mucosal inflammation, villous atrophy, increased intestinal permeability, and malabsorption, collectively blunting the child’s ability to convert food into linear growth. Studies cited in the review, including the Environmental Enteric Dysfunction Biopsy Initiative and work linking the condition to carnitine deficiency and altered fatty acid oxidation, describe a gut that is chronically inflamed and metabolically compromised even in children who never present with overt diarrhea. Chronic inflammation also suppresses the growth hormone–insulin-like growth factor-1 axis, the endocrine engine of linear growth, providing a plausible mechanistic bridge from a fecal-contaminated environment to a stunted child.

Meta-regression added a second layer of insight by identifying participant age and adjustment status as significant sources of between-study heterogeneity. The association between enteric infection and stunting was strongest among children younger than two years, which the authors read as a signal about the first 1000 days of life, the window from conception through roughly the second birthday during which linear growth velocity is highest and the developing gut and immune system are most vulnerable to disruption. This timing matters for intervention design. A child whose gut is repeatedly infected during the period of most rapid growth may sustain deficits that nutritional supplementation later in childhood cannot fully reverse, echoing longitudinal findings from the MAL-ED birth cohort across eight low- and middle-income country sites, which documented that even asymptomatic enteropathogen infections measurably depressed linear growth.

The finding that statistical adjustment for confounders shaped the observed effect estimates is equally important for readers interpreting the evidence. Observational studies of infection and stunting must contend with a dense thicket of confounding: household wealth, maternal education, water and sanitation access, breastfeeding practices, and diet all influence both infection risk and growth. Studies that adjusted more comprehensively for these factors produced different effect estimates than those that did not, and the meta-regression captured this as a source of heterogeneity. The very low GRADE rating applied to the pooled evidence reflects these inherent limitations. Association is not causation, reverse causality remains possible, since malnourished children may be more susceptible to infection as well as more harmed by it, and the Review authors are explicit that their pooled estimate should guide hypothesis formation and intervention priority-setting rather than be read as a precise causal coefficient.

The geographical scope of the underlying studies, spanning Ethiopia, Bangladesh, Indonesia, Peru, Zambia, Madagascar, the Philippines, Zimbabwe, and other low- and middle-income settings, underscores that the stunting–infection relationship is concentrated where sanitation infrastructure is weakest. Several included studies examined the interaction between enteric infections and environmental enteric dysfunction directly, and others evaluated how water, sanitation, and hygiene interventions perform in children carrying different pathogen burdens. Collectively, this literature suggests that the classic nutrition-centric framing of stunting, in which food insecurity is treated as the dominant driver, captures only part of the story. A child can consume adequate calories and still fail to grow if a chronically inflamed gut cannot absorb them.

For policymakers, the practical implications of the review are captured in its stated impact summary: the findings support integrating infection prevention, sanitation, and nutritional interventions into child stunting reduction programs, rather than pursuing these strategies in silos. That means pairing supplementary feeding and dietary diversification with safe water, improved sanitation, deworming where helminth burden is high, and, where available, vaccination against enteric pathogens. The absence of differences between pathogen domains complicates any pathogen-by-pathogen targeting strategy and instead argues for broad environmental measures that reduce exposure to the fecal–oral pathway as a whole. The vulnerability of children under two further suggests that interventions should begin in pregnancy and infancy, when the marginal return on preventing gut disruption is highest.

The review, published on 26 September 2026 with the DOI 10.1038/s41390-026-05520-4, arrives at a moment when the global health community is assessing why stunting prevalence has declined more slowly than under-five mortality. By quantifying a roughly twofold elevation in stunting odds associated with enteric infections across bacterial, viral, protozoal, and helminthic domains, and by flagging the first 1000 days as the period of maximal vulnerability, it offers both a synthesis of a fragmented literature and a clear agenda for what must come next: longitudinal studies with molecular diagnostics, better confounder control, and intervention trials that test whether breaking the infection–inflammation cycle unlocks growth that nutrition alone cannot deliver. The evidence may be graded very low in certainty, but the direction of the signal, and the scale of the population at risk, give it a weight that few will ignore.

Subject of Research: The association between enteric infections across four pathogen domains and childhood stunting in low- and middle-income countries

Article Title: Enteric infections and childhood stunting: a systematic review and meta-analysis across four pathogen domains

Article References: Pauzi, R. Y., Iqhrammullah, M., Ihtiaringtyas, S., Ilmi, A. N., Kumaratih, L. W., Yuliana, P. T., Aqila, R. A., & Raizma, E. Z. N. (2026). Enteric infections and childhood stunting: a systematic review and meta-analysis across four pathogen domains. Pediatric Research. https://doi.org/10.1038/s41390-026-05520-4

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05520-4

Keywords: childhood stunting, enteric infections, meta-analysis, systematic review, environmental enteric dysfunction, gut microbiology, pediatric growth, first 1000 days, soil-transmitted helminths, water sanitation and hygiene, low- and middle-income countries, GRADE evidence

Neonatal hypoglycaemia is far from a rare curiosity. Up to 15% of otherwise healthy newborns experience blood glucose levels low enough to be flagged in the first hours of life, and among infants with risk factors such as prematurity, being small or large for gestational age, or maternal diabetes, the incidence can climb to roughly half. The transition from the constant glucose supply of the placenta to independent metabolic regulation is inherently precarious, and many healthy babies dip transiently while adapting to life outside the womb. The concern is what happens when the dip is prolonged or severe: prior research has linked severe neonatal hypoglycaemia to abnormal fine motor function, deficits in visual-motor integration and symptoms consistent with attention-deficit/hyperactivity disorder later in childhood. That long shadow is what drives clinicians to monitor, feed and, when necessary, treat aggressively.

Conventional management relies on early identification of at-risk infants, prompt feeding, frequent glucose checks and, for symptomatic or severe cases, intravenous dextrose. The problem is that IV dextrose is invasive, demands NICU admission, separates mother and baby, interrupts breastfeeding and generates anxiety and cost. Oral 40% dextrose gel promised a way around all of that. It is cheap, stable, easy to administer through the buccal mucosa and works within minutes without displacing a feed. The landmark Sugar Babies trial in New Zealand, published in 2013, appeared to prove the concept: at-risk late preterm and term infants treated with dextrose gel were less likely to fail treatment and less likely to be admitted to the NICU for hypoglycaemia. The much larger hPOD multicentre trial later confirmed a modest reduction in hypoglycaemia incidence but found no reduction in NICU admission, planting the first seeds of doubt.

Since then, the picture has grown murkier rather than clearer. Some recent trials reported no significant difference between dextrose gel and control in treatment success, while others suggested the gel helps maintain blood glucose in specific subgroups such as infants of diabetic mothers or late preterm babies. A previous meta-analysis had concluded that the gel significantly lowered NICU admissions, but it included fewer studies and roughly 1,000 fewer participants than the new synthesis. Motivated by that expanding but inconsistent evidence base, an international team of researchers registered a protocol with PROSPERO and set out to pool every available randomized trial of 40% dextrose gel for both prevention and treatment of neonatal hypoglycaemia, following the PRISMA 2020 reporting standards.

The search strategy was exhaustive. The team combed PubMed, Embase, Web of Science, Scopus and the Cochrane Library from inception to March 2026, retrieving 1,332 records. After deduplication, 1,285 studies were screened by title and abstract, 58 went to full-text review, and eight randomized controlled trials ultimately met the eligibility criteria. Together they enrolled 4,368 neonates, 2,256 assigned to 40% dextrose gel and 2,112 to control. The trials spanned New Zealand, Australia, India, Argentina, Italy, Ireland and the Czech Republic, and they varied enormously in design: some gave the gel prophylactically in the delivery room or at one hour of life, others used it to treat established asymptomatic hypoglycaemia; comparators ranged from placebo gel to breastfeeding alone to formula milk; and hypoglycaemia thresholds ranged from below 1.8 mmol/L to below 2.6 mmol/L or below 45 mg/dL.

The pooled results were uniformly null. Across five prevention trials involving 3,618 infants, dextrose gel did not significantly reduce the incidence of hypoglycaemia, with a pooled risk ratio of 0.92 and a 95% confidence interval of 0.76 to 1.11, accompanied by moderate heterogeneity. In three treatment trials covering 750 infants, treatment success, defined as avoiding IV dextrose, showed no significant difference, with a risk ratio of 1.10 and striking heterogeneity of 95%. Recurrent hypoglycaemia, NICU admission, breastfeeding at discharge and any formula feeding all likewise showed no statistically significant differences. The NICU result deserves particular attention: the pooled risk ratio was 0.87, but when the massive hPOD trial was excluded in sensitivity analysis, heterogeneity collapsed and the estimate became a statistically significant 24% reduction in admissions, hinting that protocol differences, such as a single prophylactic dose versus multiple doses, may determine whether the gel delivers on its promise.

The authors are careful to stress what these numbers do and do not mean. Non-significant findings, they emphasize, are not evidence of equivalence. The confidence intervals for several outcomes, particularly treatment success and NICU admission, are wide enough to encompass both clinically meaningful benefit and potential harm. For treatment success, the interval spans a possible 23% reduction to a 57% increase. Certainty of evidence, graded using the GRADE framework, ranged from moderate for breastfeeding at discharge down to very low for treatment success, reflecting serious risk of bias in one trial, substantial inconsistency and imprecision across outcomes. Publication bias assessments using Doi plots and trim-and-fill adjustments did not materially change the conclusions, but with fewer than ten studies per outcome, those methods have limited power.

Why might the gel underperform expectations? The review offers several technical explanations. Doses varied from a single 200 mg/kg dose to multi-dose regimens totalling up to 1,000 mg/kg, and timing ranged from the delivery room to two hours after birth, yet no clear dose-response or timing effect emerged. Comparators mattered too: in the Argentine trial, formula-fed controls actually achieved higher treatment success than gel-treated babies, since formula feeding is itself an effective hypoglycaemia remedy. Definitions of hypoglycaemia differed across trials, and measurement methods varied from laboratory glucose oxidase assays to bedside glucometers, introducing misclassification that biases estimates toward the null. Subgroup signals persisted, however: infants of diabetic mothers in one Indian trial showed a marked benefit, and late preterm infants in an Italian study had higher glucose levels with gel, while extremely preterm infants under 32 weeks in the GEHPPI trial showed none, with identical hypoglycaemia rates of 29% in both arms.

On the reassuring side, the gel appears harmless to breastfeeding. Despite concerns that any neonatal supplementation can delay breastfeeding initiation and shorten duration, the pooled analysis found no difference in breastfeeding at discharge or formula use, with zero heterogeneity across trials. No adverse events were reported in any of the included studies, though the authors caution that long-term neurodevelopmental safety remains untested. Clinically, the team suggests the gel’s low cost, safety profile and ease of administration still justify a role as an adjunctive therapy, particularly in resource-limited settings or while awaiting IV access, but not as a replacement for intravenous dextrose when clearly indicated, and always within standardized protocols covering dosing, monitoring and escalation.

The research agenda that follows is demanding. The authors call for dose-finding trials comparing multi-dose regimens with single-dose prophylaxis, population-specific trials stratified by the underlying mechanism of hypoglycaemia, continuous glucose monitoring to replace intermittent heel-prick checks, and long-term neurodevelopmental follow-up. Until such trials arrive, the humble sugar gel remains what it has arguably always been: a plausible, cheap and safe tool whose true value, for whom, at what dose and at what hour of life, medicine has not yet pinned down.

Subject of Research: The efficacy of 40% oral dextrose gel for preventing and treating neonatal hypoglycaemia, assessed in an updated systematic review and meta-analysis of randomized controlled trials.

Article Title: Efficacy of Oral Dextrose Gel for Neonatal Hypoglycaemia: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials With 4368 Patients

Article References: Al‐Enezi, R. T., Alshebeeb, F. A., Panikulam, J. R., AlKhaldi, D. B., Almutairi, R. B., Alenezi, R. T., Aljassar, A. M., Aldosari, R. B., Alkandari, F. A., Dashti, A. A., Aldhahi, K. A., Abdul‐Hafez, H. A., & Alharran, A. M. (2026). Efficacy of Oral Dextrose Gel for Neonatal Hypoglycaemia: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials With 4368 Patients. Endocrinology, Diabetes &amp; Metabolism, 9(5), Article e70327. https://doi.org/10.1002/edm2.70327

Image Credits: AI Generated

DOI: 10.1002/edm2.70327

Keywords: neonatal hypoglycaemia, oral dextrose gel, systematic review, meta-analysis, randomized controlled trials, NICU admission, newborn health, breastfeeding, intravenous dextrose, GRADE evidence, neonatal intensive care, glucose monitoring

The review, led by Ali Msheik of Hamad Medical Corporation in Doha, Qatar, together with colleagues in trauma surgery, neurocritical care, and medical ethics, synthesized all available systematic reviews of viscoelastic hemostatic assays in neurocritical illness. These assays, which include thromboelastography known as TEG, TEG Platelet Mapping, and rotational thromboelastometry known as ROTEM, differ fundamentally from standard coagulation tests. Instead of isolating plasma and timing a single clotting reaction, they measure the actual physical behavior of clot formation in whole blood: how quickly the clot initiates, how strongly it propagates, how firm the final clot becomes, and how readily fibrinolysis breaks it down. In principle, this gives clinicians a real-time picture of hemostasis that standard tests cannot capture.

To assess the accumulated evidence, the researchers followed PRISMA 2020 reporting guidelines, the Joanna Briggs Institute manual for umbrella reviews, and MOOSE recommendations, searching PubMed, Embase, Scopus, the Cochrane Library, and Web of Science from database inception to January 2026. Two physician reviewers with experience in neurocritical care independently screened records, extracted data, and appraised methodological quality. The screening funnel was dramatic: of 272 records identified, 199 were screened after duplicate removal, and only four systematic reviews survived full-text assessment. The authors emphasized that this narrowing reflects the strict restriction to review-level evidence with reproducible methods and extractable neuro-specific data, not a post hoc reshaping of the question.

Those four reviews encompassed 73 study occurrences representing 63 unique primary studies, spanning traumatic brain injury, subarachnoid hemorrhage, and mixed populations with ischemic stroke and coronary artery disease. A corrected covered area analysis quantified how much the underlying evidence overlapped, finding only slight overall redundancy at 5.3 percent. Within traumatic brain injury, however, the two dedicated reviews shared 12 primary studies, a corrected covered area of 29.4 percent, while the subarachnoid hemorrhage and antiplatelet therapy reviews shared no studies with other clusters. This low overall overlap means the field is not merely recycling the same small trials, an encouraging sign for the maturity of the evidence base even as quality concerns remain.

The methodological appraisal revealed uneven rigor. Using AMSTAR-2, a validated tool for assessing systematic reviews, only one review, a 2021 meta-analysis of thromboelastography in traumatic brain injury by Cannon and colleagues, achieved moderate confidence, supported by a registered protocol, a comprehensive search, duplicate screening, and structured bias assessment. The remaining reviews earned low or critically low confidence ratings owing to absent protocols, incomplete reporting of excluded studies, and limited transparency. When the authors then applied GRADE criteria to rate certainty in individual outcomes, most estimates in traumatic brain injury and subarachnoid hemorrhage fell to low or very low certainty, a consequence of predominantly observational designs, inconsistent definitions, and imprecise effects.

Within those constraints, the prognostic signal was remarkably consistent. Across two reviews covering 32 unique studies in traumatic brain injury, viscoelastic assays repeatedly identified clinically relevant coagulation disturbances. Abnormal clot strength and disturbed fibrinolytic activity were associated with mortality across 18 observational studies, with radiographic hemorrhage progression in 14 studies, and with the need for neurosurgical intervention in nine, though confounding and heterogeneous outcome definitions limited those latter findings. In subarachnoid hemorrhage, a single review of 19 primary studies found that hypercoagulable profiles, particularly increased clot firmness, were consistently linked to delayed cerebral ischemia in six studies and to early brain injury severity in four. These associations make biological sense: dysregulated clot formation and breakdown plausibly contribute to secondary brain injury, hemorrhage expansion, and delayed ischemia after aneurysm rupture.

The therapeutic story was different. No review provided convincing evidence that viscoelastic-guided interventions improved outcomes in traumatic brain injury or subarachnoid hemorrhage, meaning the assays currently function as crystal balls rather than steering wheels in these conditions. The one bright spot came from mixed ischemic populations: moderate-certainty evidence from a meta-analysis of ten studies, including randomized trials, suggested that TEG-guided antiplatelet therapy in patients with ischemic stroke and coronary artery disease was associated with fewer composite ischemic and bleeding events than standard care. Mortality effects, however, remained uncertain because reporting was sparse and inconsistent, and because the population blended cardiac and cerebrovascular patients, the finding cannot be directly transferred to pure stroke care without further validation.

The authors are explicit about what this means for practice. Viscoelastic assays, they conclude, may be most appropriately used as adjunctive diagnostic and prognostic tools in neurocritical care rather than as standalone guides for transfusion or hemostatic treatment decisions in brain trauma and aneurysmal hemorrhage. The finding challenges a seductive assumption, one that has driven adoption in trauma and cardiac surgery, that simply identifying a coagulation disturbance and acting on it automatically improves outcomes. In the neurocritical setting, the leap from detection to benefit has not yet been demonstrated in rigorous trials, and current clinical guidelines accordingly do not recommend routine viscoelastic testing in these populations.

Several structural obstacles help explain the gap between prognostic promise and therapeutic proof. Included studies frequently came from single centers using institution-specific protocols, with inconsistent assay platforms, variable clinical cutoffs, and differing transfusion and antiplatelet practices. Without harmonized thresholds and standardized definitions of what counts as an actionable abnormality, clinicians cannot translate an abnormal tracing into a uniform treatment decision, and trialists cannot pool results meaningfully. These limitations reduce generalizability and complicate the interpretation of every association reported to date.

The research agenda that follows is clear. The authors call for large prospective neuro-specific cohorts using standardized viscoelastic thresholds, randomized trials testing VHA-guided transfusion or reversal strategies specifically in traumatic brain injury and subarachnoid hemorrhage, harmonization of assay parameters and clinical definitions, mechanistic studies linking viscoelastic abnormalities to neurovascular pathophysiology, and targeted evaluation of TEG-guided antiplatelet therapy in stroke populations alone. Until that work is done, the review suggests, clinicians and policymakers should read abnormal viscoelastic findings as important prognostic information, valuable for risk stratification and communication, while resisting the temptation to build treatment algorithms on evidence that has yet to bear their weight. For a technology that has already transformed hemostasis management in trauma and cardiac surgery, neurocritical care remains the unfinished frontier.

Subject of Research: Viscoelastic hemostatic assays for prognosis and treatment guidance in neurocritical illness

Article Title: The utility of viscoelastic hemostatic assays in neurocritical illness

Article References: Msheik, A., Peralta, R., Al-Rumaihi, G., Rizoli, S., Al Mokdad, Z., de Oliveira Manoel, A. L., & Al-Thani, H. (2026). The utility of viscoelastic hemostatic assays in neurocritical illness. Journal of Emergency and Disaster Medicine, 2(1), Article 10. https://doi.org/10.1007/s44467-026-00012-1

Image Credits: AI Generated

DOI: 10.1007/s44467-026-00012-1

Keywords: viscoelastic hemostatic assays, thromboelastography, ROTEM, traumatic brain injury, subarachnoid hemorrhage, ischemic stroke, coagulopathy, neurocritical care, umbrella review, antiplatelet therapy, delayed cerebral ischemia, GRADE evidence