Nevin Manimala

Laryngoscope. 2026 Apr 30. doi: 10.1002/lary.70600. Online ahead of print.

ABSTRACT

OBJECTIVE: Preoperative systemic corticosteroids are frequently used in chronic rhinosinusitis with nasal polyps (CRSwNP). This meta-analysis aimed to evaluate the effect of preoperative systemic steroids on tissue eosinophil count (TEC) in CRSwNP.

DATA SOURCES: PubMed, EMBASE, and Cochrane Library.

REVIEW METHODS: Systematic searches were conducted through March 2026 for studies assessing TEC following preoperative systemic steroids in adult CRSwNP patients. Eligible designs included randomized controlled trials, cohort studies, and pre-post studies. TEC was reported as cells per high-power field (TEC/HPF) or as a percentage of eosinophils among inflammatory cells (%TEC). Pooled mean differences (MD) were calculated using random-effects models.

RESULTS: Seventeen studies (930 participants) were included, of which 13 were eligible for quantitative synthesis. Systemic steroids significantly reduced TEC/HPF (MD -36.57; 95% CI: -43.94 to -29.20) and %TEC (MD -18.14; 95% CI: -24.88 to -11.39). Reductions were consistent across steroid dose, duration, and concomitant intranasal steroid use. However, low dose (4.2-18.6 mg/day) given in ≤ 7-day regimens showed a non-significant reduction (MD -17.78; 95% CI: -62.62 to 27.05). Adverse events were not statistically different between the steroid and control groups (5.60% vs. 1.12%, odds ratio = 5.22, p = 0.12). No adverse events were reported in studies using low-dose or tapering regimens.

CONCLUSION: Preoperative systemic corticosteroids significantly reduce TEC in CRSwNP, regardless of the quantifying method. This effect may interfere with histologic assessment when biopsy is taken intraoperatively. To avoid misinterpretation, clinicians may consider either withholding preoperative systemic corticosteroids, using a less suppressive regimen, or obtaining a biopsy prior to steroid initiation.

LEVEL OF EVIDENCE: N/A.

PMID:42062802 | DOI:10.1002/lary.70600

Acta Anaesthesiol Scand. 2026 Jul;70(6):e70245. doi: 10.1111/aas.70245.

ABSTRACT

BACKGROUND: Trauma is a major public health concern that often leads to long-term psychological distress and chronic pain. Benzodiazepines (BZDs) are sometimes prescribed for anxiety, insomnia, or acute stress-related symptoms, but long-term use is associated with dependence and adverse outcomes. The extent to which BZDs are initiated after trauma, and their implications for long-term health, remain poorly understood. This study aimed to assess the association between trauma exposure and initiation of high-potency BZDs, identify risk factors within the trauma cohort and examine the association between new BZD use and long-term mortality.

METHODS: We conducted a population-based cohort study using data from a regional trauma registry linked to Swedish national health registers. New initiation of BZD prescriptions was defined as filling at least one prescription within 6 months after trauma. Multivariable logistic regression was used to assess associations between trauma exposure and BZD initiation and to identify risk factors within the trauma cohort. Cox proportional hazards regression evaluated the association between new BZD use and 6-18-month mortality.

RESULTS: The study included 12,206 BZD-naive trauma patients and 66,801 matched controls. Trauma exposure was independently associated with new high-potency BZD use. Within the trauma cohort, risk factors included older age, psychiatric comorbidity, substance abuse, pre-traumatic opioid or sedative-hypnotic drug use, penetrating trauma, and higher injury severity. New BZD use was associated with markedly elevated 6-18-month mortality (adjusted HR 2.9, 95% CI 2.0-4.2, p < 0.001), a finding that reflects the complex clinical and psychosocial vulnerability of this group.

CONCLUSIONS: Trauma exposure independently predicted initiation of high-potency BZDs among previously BZD-naive patients. Psychiatric comorbidity, substance use, and greater injury severity were important risk factors. The association between new BZD use and increased long-term mortality underscores the need for cautious prescribing and structured follow-up after trauma.

EDITORIAL COMMENT: This study examines initiation of high-potency benzodiazepines among previously naive survivors of severe trauma using linked registry data. It shows that trauma exposure is strongly associated with new benzodiazepine use, particularly in older, comorbid, and vulnerable patients. Initiation is also associated with higher subsequent mortality, likely reflecting underlying clinical and psychosocial risk rather than a causal drug effect.

PMID:42062780 | DOI:10.1111/aas.70245

Clin Pharmacol Ther. 2026 Apr 30. doi: 10.1002/cpt.70277. Online ahead of print.

ABSTRACT

Critical limits represent quantitative decision thresholds for drugs that require immediate clinician notification and potential life-saving intervention. United States hospitals lack a national standard for drug critical limits. We collected critical limits from 417 US hospitals across all 50 states and Washington, D.C.; of these, 411 maintained drug critical limit lists. We classified hospitals by US Census division and network-affiliated vs. independent status. We applied non-parametric statistical analyses, examined critical limits for 111 drugs, and observed significant inter-institutional variability. Listing frequencies were highest for digoxin 99.8% (410/411), theophylline 72.3% (297/411), lithium 94.9% (390/411), and acetaminophen 86.9% (357/411). Non-therapeutic measurands also appeared, led by ethanol 47.2% (194/411). Kruskal-Wallis analysis revealed highly significant differences (P < 0.01) across census divisions. Mann-Whitney U analysis comparing network vs. independent hospitals yielded significant differences (P < 0.05) in 16 analytes. Qualitative critical values were listed for volatile alcohols and methotrexate. All digoxin critical limits exceeded levels associated with increased hazard ratios. Only 33.9% of hospitals aligned with consensus guidelines for acetaminophen poisoning. Vancomycin and aminoglycoside critical limits showed wide ranges, overlapping peaks and troughs, and random values inconsistently aligned with peak and troughs. Immunosuppressant critical limits often exceeded thresholds associated with toxicity. Psychotropic drugs, including antiepileptics, tricyclic antidepressants, and lithium, demonstrated variability and misalignment relative to consensus guidelines. Drugs of abuse did not appear in critical notification lists. Results provide hospitals with references that will enhance hospital notification practices and patient safety. We encourage sharing of critical notification lists to foster future research efforts and enhance standards of care.

PMID:42062777 | DOI:10.1002/cpt.70277

Ther Innov Regul Sci. 2026 Apr 30. doi: 10.1007/s43441-026-00974-4. Online ahead of print.

ABSTRACT

BACKGROUND: The U.S. Food and Drug Administration conducts Good Clinical Practice (GCP) assessments and provides recommendations through Clinical Inspection Summary (CIS) reports to inform marketing application reviews. Despite their integral role in regulatory oversight, the characteristics of GCP assessments and recommendations have not been comprehensively evaluated.

METHODS: This 10-year retrospective descriptive study analyzed CIS reports supporting marketing applications from 2015 to 2024. Data were extracted from FDA internal databases and analyzed. CIS reports were categorized into Tier 1-3, a framework developed by the authors for this study. In Tiers 1 and 2, data were recommended as acceptable to support the marketing application. In Tier 3, specific actions were recommended to address data quality issues.

RESULTS: The analysis included 1,200 CIS reports supporting regulatory review of predominantly New Drug Applications (69.9%) and Biologics License Applications (29.9%), with 68.0% supporting original submissions. The most frequent recommendation tier was Tier 1 (69.5%), followed by Tier 3 (22.5%), and Tier 2 (8.0%). Within Tier 3, most CIS reports contained a single type of recommended action (66.7%), and the most common recommended actions involved requesting additional information (32.8%), conducting additional statistical analyses (28.3%), and incorporating updated data (24.8%).

CONCLUSIONS: GCP oversight largely supported data acceptability for marketing applications, with specific actions recommended to address data quality issues, underscoring its critical role in ensuring reliable clinical data.

PMID:42062756 | DOI:10.1007/s43441-026-00974-4

Odontology. 2026 Apr 30. doi: 10.1007/s10266-026-01397-1. Online ahead of print.

ABSTRACT

The aim of the study was to compare the clinical efficacy of Platelet Lysate (PL) versus Hyaluronic Acid (HA) after arthrocentesis in the management of patients with anterior disc displacement with reduction. This randomized clinical trial was conducted on 60 patients (17 males and 43 females) with anterior disc displacement with reduction confirmed with magnetic resonance imaging (MRI). The patients were split into two equal groups at random based on the type of treatment that was used. Group 1: arthrocentesis plus PL, Group 2 arthrocentesis plus HA. The pain intensity, clicking sound, maximum inter-incisal opening (MIO) and range of lateral mandibular excursions were measured. All the measured parameters were statistically analyzed. After 6 months, both groups demonstrated a significant improvement in all the parameters that were measured. The PL Group showed a statistically better resolution of clicking compared to HA Group with an Absolute Risk Difference of 33.3% (P < 0.05). The MIO between-group difference was 4.867 mm (P < 0.001), so exceeding the Minimum Clinically Important Difference (MCID). On the other hand, although the PL Group demonstrated statistical superiority in pain scores and range of lateral mandibular excursions (P < 0.05), the clinical magnitude of the between-group difference was modest. PL appears to be a safe and effective adjunctive intra-articular therapy after arthrocentesis for the management of patients with anterior disc displacement with reduction. It provides a clinical advantage over HA in resolving joint clicking and improving MIO. For pain reduction and range of lateral mandibular excursions, the therapeutic benefits of PL and HA are clinically comparable. Trial registration: On 4/12/2024, it was registered in Clinical-Trials.gov PRS ( https://register.clinicaltrials.gov ) with identification number NCT06441279.

PMID:42062696 | DOI:10.1007/s10266-026-01397-1

Curr Environ Health Rep. 2026 May 1;13(1):20. doi: 10.1007/s40572-026-00538-6.

ABSTRACT

PURPOSE OF REVIEW: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have been linked to environmental exposures, yet the underlying neurobiological mechanisms remain poorly understood. Magnetic resonance imaging (MRI) offers an important in vivo tool for examining how environmental neurotoxicants impact brain development. This scoping review synthesizes current evidence on the associations between air pollution, metals, environmental tobacco smoke, and endocrine-disrupting chemicals (EDCs) assessed from pregnancy through childhood and neuroimaging findings in children diagnosed with NDDs.

RECENT FINDINGS: We identified 14 studies examining associations between environmental exposures and MRI outcomes in children with NDDs. Air pollution exposure was linked to reduced volumes in the caudate nucleus and corpus callosum. Metal exposure was associated with changes in cortical thickness and functional connectivity, varying by metal and diagnosis. Tobacco smoke exposure correlated with reduced volumes in the cerebellum and frontal cortex and disruptions in white matter and neural networks. EDCs were linked to cortical thinning and altered task-related brain activity, with some studies reporting associations with symptom severity among children with ADHD. Overall, the literature suggests that exposure to neurotoxicants may disrupt brain development in children with NDDs. Future research should prioritize longitudinal, transdiagnostic designs with repeated exposure assessments and multimodal imaging, as well as advanced statistical modeling, to better capture the complex relationships between exposure and outcome. These findings underscore the importance of public health interventions to mitigate exposure to neurotoxicants and minimize potential neurodevelopmental risks.

PMID:42062691 | DOI:10.1007/s40572-026-00538-6

Methods Mol Biol. 2026;2995:119-127. doi: 10.1007/978-1-0716-5027-1_8.

ABSTRACT

Understanding complex diseases such as cancer requires insight into both the intrinsic properties of individual cells and their interactions within the tumor microenvironment. Integrating single-cell RNA sequencing (scRNA-seq), which captures transcriptional states, with spatial proteomics, which provides spatially resolved protein expression data, offers a powerful opportunity to unravel disease mechanisms. In this protocol, we describe a framework that unifies scRNA-seq and spatial proteomics into a joint graph-based representation. This approach enables accurate prediction of disease pathologies and reveals critical cell-cell interactions that drive disease progression.

PMID:42062682 | DOI:10.1007/978-1-0716-5027-1_8

Spine Deform. 2026 Apr 30. doi: 10.1007/s43390-026-01383-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate pelvic incidence (PI) as a reliable parameter for analysing sagittal profiles in patients with adolescent idiopathic scoliosis (AIS).

METHODS: This retrospective cohort study included 100 patients with AIS (aged 12-17 years) who underwent posterior spinal deformity correction and had a 2-year follow-up. Radiographic parameters-Pelvic Incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA), and T1 pelvic angle (TPA)-were evaluated preoperatively, at 6 months, and at 2 years postoperatively. Sagittal profiles were classified using the theoretical Roussouly system. Statistical analysis used repeated-measures ANOVA with Tukey HSD post hoc testing to assess temporal variability and Pearson correlation coefficients to assess associations between pelvic and spinal parameters.

RESULTS: The mean age was 13.3 years, with females comprising 66% of the cohort; Lenke type 5 was the most common curve type. Roussouly type 3 predominated at all time points. Pelvic parameters (PI and SS) remained stable (p > 0.1), whereas spinal parameters showed significant changes in LL (p = 0.000) and TK (p = 0.001). Global alignment shifted in SVA (p = 0.014), while TPA remained unchanged (p > 0.3). PI consistently correlated with PT (r = 0.60), SS (r = 0.64), and LL (r = – 0.55) across intervals.

CONCLUSION: PI showed minimal temporal variability, confirming its reliability as a morphological parameter in AIS. These findings support the role of PI in sagittal alignment assessment and reinforce the applicability of the Roussouly classification in AIS patients.

PMID:42062673 | DOI:10.1007/s43390-026-01383-1

Oncol Ther. 2026 Apr 30. doi: 10.1007/s40487-026-00436-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Laryngeal cancer (LC) constitutes almost one third of the head and neck cancers, and its main risk factors, alcohol use and smoking, are well established. Our aim was to explore the variation in the incidence of LC between different occupations.

METHODS: This study was based on data from the Nordic Occupational Cancer Study (NOCCA), involving 14.9 million individuals from Denmark, Finland, Iceland, Norway, and Sweden. Occupational data from censuses were linked to cancer registry data from a period of up to 45 years (21,166 LC diagnoses) using personal identity codes. Standardized incidence ratios (SIRs) were calculated for different occupations, using the respective national populations as a reference.

RESULTS: Of the 21,166 patients with LC, 18,488 (87%) were men. The highest SIRs in men were noted among waiters (3.31, 95% confidence interval [CI] 2.69-4.02), beverage workers (2.51, 95% CI 1.91-3.24), and cooks and stewards (2.25, 95% CI 1.82-2.74). Among women, the highest SIRs were observed among building hands (7.37, 95% CI 3.53-13.55) and public safety workers (3.60, 95% CI 1.17-8.40). Farming and teaching occupations showed reduced SIRs in both sexes. The SIRs among male farmers, teachers, gardeners, and technical workers were reduced in all countries. The SIRs remained elevated and stable among cooks and stewards, waiters, packers, seamen, sales agents, and economically inactive males across the three 15-year periods from 1961 to 2005.

CONCLUSION: The study confirms a major variation in the incidence of LC between occupations. The findings underscore the importance of considering lifestyle factors typical of each occupation in cancer risk assessments and the potential benefits of targeted prevention efforts.

PMID:42062661 | DOI:10.1007/s40487-026-00436-9

Curr Environ Health Rep. 2026 May 1;13(1):19. doi: 10.1007/s40572-026-00536-8.

ABSTRACT

PURPOSE OF REVIEW: Exposure to endocrine disrupting chemicals (EDC) is linked to numerous adverse health outcomes. However, limiting exposure to EDCs remains a significant challenge due to their widespread uses and persistence in the environment. Adequate micronutrient status supports optimal health and may offer actionable strategies for mitigating the adverse health effects of EDCs. This scoping review aimed to summarize the epidemiologic evidence on micronutrients as potential mitigators of EDC-related health outcomes, with the goal of guiding future research and methodologies.

RECENT FINDINGS: We identified 71 epidemiologic studies assessing micronutrients as mitigators of EDC-outcome relations, focused primarily on exposures during pregnancy (n = 34). Most studies examined phthalates and/or environmental phenols (n = 25), per- and polyfluoroalkyl substances (n = 15), polycyclic aromatic hydrocarbons (n = 10), and self-reported pesticide exposure (n = 6). Most studies suggested higher levels of some micronutrients attenuated adverse associations of EDCs with some health outcomes, particularly iodine (thyroid hormones); folic acid (fertility, birth outcomes, neurodevelopment); vitamin D (lung function, neurodevelopment); and antioxidants (birth outcomes, aging, metabolic health). However, included studies assessed a wide range of micronutrients, EDCs, and outcomes, with limited overlap across studies. This scoping review identified few topics with substantial evidence to warrant focused systematic reviews, suggesting that additional prospective research is needed, especially in at-risk populations and sensitive periods outside of pregnancy. Future epidemiologic research should consider the co-occurrence of EDCs and micronutrients in foods and include multiple methods for assessing micronutrients. Finally, to strengthen causal inference, future research should thoughtfully model potential confounding, mediation, effect measure modification, and/or statistical interaction.

PMID:42062659 | DOI:10.1007/s40572-026-00536-8