Medicine and Pharmacology

Abstract: Background/Objectives: For Heifetz stage III onychocryptosis, matricectomy is standard but carries drawbacks. Methods: This study evaluated a modified Vandenbos technique preserving matrix using CO₂ laser ，compared with Winograd procedure. Results: In 204 patients (166 Vandenbos, 38 Winograd), Vandenbos yielded significantly lower median pain (NRS 6.0 vs. 8.5; p<0.001), faster return to daily activities (3.0 vs. 7.0 days; p=0.0005), and higher surgical satisfaction (10.0 vs. 9.0; p=0.005). Cosmetic satisfaction favored Vandenbos (10 vs. 9, p=0.085, NS). Recurrence: 28.9% (V) vs. 18.4% (W), p=0.189. Infection: 0% (V) vs. 13.2% (W). Dressing duration: 16 vs. 14 days, p=0.503. Conclusions: Modified Vandenbos offers lower pain, faster recovery, negligible infection, and good cosmesis, with non-inferior recurrence; it is a viable matricectomy-sparing alternative, yet patient selection is advised.

Abstract: Vascular disruption defects (VDD) are congenital anomalies arising from the interruption of embryonic blood flow, and their environmental and behavioral determinants remain poorly characterized in low- and middle-income settings. We conducted a hospital-based case–control study at a tertiary referral center in Cali, Colombia, between April 2007 and March 2010 to evaluate associations between VDD and periconceptional environmental, behavioral, and social exposures. Forty-one newborns with clinically confirmed, non-chromosomal VDD and 111 controls matched by estimated date of conception were included. Exposures were ascertained by structured questionnaire; cadmium, lead, and zinc were measured by atomic absorption spectrophotometry in the periconceptional maternal-hair segment; and residential proximity to a municipal landfill was georeferenced. Crude and adjusted odds ratios (ORs) were estimated by logistic regression, with penalized and exact methods for sparse data. Increased odds of VDD were observed with maternal acetaminophen use (OR 3.18, 95% CI 1.10–11.20), marijuana (3.62, 1.20–11.00), natural remedies (3.87, 1.48–10.06), active (2.75, 1.10–6.74) and passive (3.03, 1.35–6.83) tobacco exposure, family history of congenital defects (18.0, 3.35–176.13), and vaginal infection (2.53, 1.07–5.94). Heavy-metal and landfill-proximity estimates were imprecise and non-informative. Potentially modifiable periconceptional exposures and social vulnerability were associated with VDD, supporting preconception counseling and environmental surveillance in vulnerable populations.

Abstract: Race remains embedded in clinical risk algorithms and therapeutic recommendations despite its limitations as a proxy for biological variation. As a sociopolitical construct, race captures aspects of social experience and structural inequality but does not reliably reflect an individual's genetic ancestry or pharmacogenomic profile. This distinction is increasingly important in genetically admixed populations, where broad racial and ethnic classifications can obscure substantial variation in allele frequencies, genetic architecture, and treatment response. Pharmacogenomics offers a more direct approach to individualized prescribing by identifying clinically actionable genetic variants that influence drug metabolism, transport, efficacy, and toxicity. However, realizing its potential requires addressing persistent gaps in the representation of diverse populations in genomic research, including the underrepresentation of non-European ancestry populations and insufficient resolution of variation within broad population categories. Genetic ancestry, subpopulation-level analyses, and individual genotypes can improve the characterization of genetic variation when appropriately matched to the research or clinical question. Yet genomic approaches alone cannot eliminate health disparities and may exacerbate inequities if testing, interpretation, and evidence-based interventions remain inaccessible to underserved populations. Advancing genomic equity therefore requires representative research, equitable access to pharmacogenomic services, responsible data governance, and meaningful community engagement. A precision-medicine framework should move beyond race as a biological proxy while retaining race and ethnicity as relevant variables for examining structural inequities and monitoring disparities in health outcomes.

Abstract: Dissociative identity disorder (DID) is a complex psychiatric condition characterised by disruptions in identity, memory, and the integration of conscious experience, frequently accompanied by psychiatric comorbidity and functional impairment. This structured narrative review examines the historical, psychopathological, clinical, and neurobiological literature on DID, with emphasis on diagnostic challenges, trauma-related associations, and implications for mental healthcare. Literature searches were conducted between 2024 and 2025 using PubMed, Scopus, SciELO, and the CAPES Journals Portal, with predefined search terms and Boolean operators, supplemented by academic reference works. The reviewed literature describes substantial clinical heterogeneity, frequent co-occurring psychiatric conditions, and associations with adverse experiences, while highlighting the limitations of causal interpretations. Structural neuroimaging studies report differences in regional grey matter volume, cortical thickness, and surface area; however, methodological heterogeneity and psychiatric comorbidity preclude their interpretation as validated DID-specific biomarkers. More rigorous studies, including well-characterised clinical comparison groups, independent replication, and systematic control of potential confounders, are required. Comprehensive clinical and psychiatric assessment remains essential, together with individualised, multidisciplinary care. This review identifies key evidence gaps and priorities for improving differential diagnosis and future research.

Abstract: Background: Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) is a radiation-free whole-body MRI technique that may provide an alternative to PET-CT for lung cancer evaluation. This study compared the diagnostic performance of DWIBS with that of PET-CT plus brain MRI for lung cancer staging and with PET-CT for postoperative recurrence detection. Methods: A total of 136 patients with lung cancer were evaluated. Clinical staging was assessed in 81 patients using DWIBS and PET-CT plus brain MRI. Postoperative recurrences were assessed in 55 patients, including 37 who underwent both DWIBS and PET-CT. Sensitivity, specificity, and accuracy were calculated. Paired differences in accuracy were evaluated using Newcombe's Method 10, and exploratory non-inferiority analyses were performed using margins of −5, −10, and −15 percentage points. Results: For clinical staging, DWIBS correctly classified 61 of 81 patients (75.3%), compared with 56 of 81 (69.1%) with PET-CT plus brain MRI. The observed difference in accuracy was +6.17 percentage points (95% CI, +0.30 to +12.27), supporting non-inferiority at all three margins. For postoperative recurrence detection, DWIBS demonstrated a sensitivity of 96.9%, specificity of 100.0%, and accuracy of 98.2%. Among the 37 patients who underwent both DWIBS and PET-CT, the accuracy was 100.0% for DWIBS and 91.9% for PET-CT. The observed difference was +8.11 percentage points (95% CI, −2.69 to +21.30), supporting non-inferiority at all three margins. Conclusions: DWIBS demonstrated diagnostic performance comparable to PET-CT-based imaging for lung cancer staging and postoperative recurrence detection. DWIBS may represent a useful radiation-free alternative to PET-CT.

Abstract: Background The claim that molecular hydrogen promotes intestinal peristalsis recurs throughout Chinese-language hydrogen-medicine writing and in industry material, where it is usually invoked without citation, yet it rests on a single ex vivo animal experiment. No controlled human study exists. That gap between how often the claim is repeated and how little supports it is itself a methodological problem worth examining.Argument This paper does not argue that hydrogen treats constipation. It argues that the evidence permits no conclusion in either direction, and that this is not because the hypothesis has failed but because three identifiable and correctable methodological errors have been made: the oral route has been treated as low-dose systemic dosing rather than as regionally targeted delivery; minute-scale acute responses and day-scale transit changes have been collapsed into a single endpoint; and non-response has been read as absence of effect, leaving the effect heterogeneity introduced by an endogenous gas out of account.Evidence base In isolated guinea-pig colon, direct intraluminal insufflation of hydrogen shortened transit time by 47% proximally and 10% distally. In dogs, methane slowed small-intestinal transit by 59%. One single-arm open-label study of 30 patients (28 completing) reported a 29.8% rise in complete spontaneous bowel movements with electrolysed hydrogen-rich alkaline reduced water. A double-blind trial in healthy adults showed stool form shifting toward Bristol type 4. Quantitative colonic gas studies supply the anchors: net hydrogen excretion was (35 ± 6.1) mL/24 h on a starch- and fibre-free diet, and (227.0 ± 60.7) mL after a 15 g lactulose load.Inferences Three falsifiable inferences follow. H1: because the oral route delivers hydrogen to the luminal surface while keeping systemic levels low, the exposure that should matter is the local one at the gut wall, not the concentration in blood. H2: any genuine acute component should fall inside the postprandial colonic motor response window (seconds to 2.5 h) and must be separated from the volume effect of water itself. H3: baseline breath methane acts as an effect modifier, blunting response in high-methanogenic phenotypes.Conclusion Section 6 sets out the evidence unfavourable to the framework, in order of severity. The most serious item is quantitative rather than conceptual: the ex vivo cornerstone holds intraluminal hydrogen at about 1 atm for the duration of the experiment, whereas one oral serving carries 0.124 mmol and, once partitioned into the lumen gas phase, sustains a tension of about 0.03 atm, one to two orders lower, with no concentration–response data to say where the threshold lies. The stratification hypothesis cannot separate cause from consequence, and the methane-flux arithmetic leaves only one of its two arms standing. Replacing stratified group comparison with the within-subject correlation between effect size and breath methane cuts the sample needed to screen for H3 from roughly 1000 to roughly 70; a two-arm design that keeps randomisation sits between the two at about 250. That reduction is the paper's main methodological contribution.

Abstract: Background: Primary thyroid lymphoma (PTL) is a rare extranodal malignancy accounting for 1%–5% of all thyroid neoplasms, with diffuse large B-cell lymphoma (DLBCL) being the most common and aggressive subtype. Due to its low incidence, clinical data remain limited. This study aims to describe the clinical features, diagnostic approaches, treatment and outcomes of primary thyroid DLBCL in a single-center case series. Methods: We retrospectively enrolled four consecutive patients with histopathologically verified primary thyroid DLBCL who received treatment at our institution between 2021 and 2026. All relevant clinical data were extracted from archived electronic medical records. No statistical comparative analyses were performed given the limited sample size. Results: The cohort comprised four females, with a mean age of 73.5 years (range, 50–88 years). All patients presented with a rapidly enlarging painless neck mass, and two (50%) exhibited compressive symptoms. Elevated thyroid autoantibodies (TPO-Ab and/or TG-Ab) were detected in three patients (75%), indicating underlying Hashimoto’s thyroiditis. Diagnostic procedures varied among individuals: fine-needle aspiration cytology (FNAC) and/or core-needle biopsy (CNB), partial thyroidectomy were applied for pathological confirmation. All cases were classified as DLBCL. One patient received R-CHOP immunochemotherapy, one received Pola-R-CHP, and two opted for observation management. Conclusion: This case series provides descriptive real-world observations of primary thyroid DLBCL among elderly Chinese with underlying Hashimoto’s thyroiditis. Findings from this small cohort cannot be generalized. Immunochemotherapy regimens including R-CHOP and Pola-R-CHP may be considered within individualized multidisciplinary strategies; further large-scale studies are required to validate therapeutic performance.

Abstract: Background/ Objectives: Hyperlactatemia is a nonspecific biochemical phenotype with a broad acquired and inherited differential, complicating genomic interpretation. We aimed to identify and curate genes associated with inherited metabolic hyperlactatemia and develop an evidence-tiered virtual diagnostic panel. Methods: NCBI Gene was searched on 8 August 2026 using four lactate-related terms. Human records were deduplicated by GeneID and curated for gene–disease validity, inheritance, mechanism, and lactate-specific clinical relevance. Targeted review of ClinGen, OMIM, GenCC, PanelApp, GeneReviews, and primary literature identified established causes missed by keyword retrieval. Results: The searches yielded 802 raw records. After removal of duplicate export blocks, 401 human query records resolved to 240 unique genes. Submission-version reconciliation identified 34 search-derived genes in the 85-gene active panel, while 206 search-derived genes were not retained and remain available for audit and future reanalysis. Targeted review contributed 51 additional active genes. The final panel comprised 40 Tier 1, 26 Tier 2, and 19 Tier 3 genes. Conclusions: Phenotype-keyword retrieval showed low specificity and incomplete sensitivity. Integrating gene–disease validity with lactate-specific relevance provides a transparent, updateable framework for phenotype-informed genomic prioritization.

Abstract: Diagnosing Mycoplasma pneumoniae (MP) has followed three technological paths — seeing the organism, reading the host's antibodies, reading the pathogen's genome — and the winners were rarely the best assays. Culture was analytically supreme and never adopted; serology ruled the clinic for fifty years despite documented misclassification; PCR outperformed both by 1990 yet took a decade and a half to reach routine use. We reconstructed 120 years of MP diagnostics as a diffusion dataset, scoring each technology on Rogers' five adoption attributes against its contemporaneous competitor, and tested the scores against regulatory archives (FDA, CE-IVD, China NMPA; search concluded 30 September 2026). Every documented displacement is consistent with four empirical laws: relative advantage in time-to-result outweighed analytic accuracy; workflow compatibility decided more contests than sensitivity; displacement occurred when a successor's turnaround crossed the clinical decision window; and adoption lagged roughly a decade behind technological maturity (mean 8.5 years across the eight measurable transitions) — a severity-gated lag that relaxed measurably after the 2023 resurgence. Applying the validated rubric prospectively, we predict that CRISPR-based point-of-care testing will obtain first regulatory approvals (NMPA before FDA) by end-2027 and achieve decisive adoption in pediatric emergency settings by end-2028, conditional on extraction-free, sample-to-answer workflow, while metagenomic sequencing consolidates in severe and atypical niches without crossing into first-line use before 2030. The predictions are falsifiable and dated — the archive is offered as an evaluation instrument, not an opinion.

Abstract: Ultrasound is a widely used imaging modality in clinical practice, and sonographic signs serve as valuable teaching tools that aid in pattern recognition and diagnosis. This review consolidates five novel sonographic signs previously proposed by the author, including the Cracked Earth Sign for subcutaneous edema, the Mushroom Cap Sign for localized gallbladder adenomyomatosis, the LTS Sign for dilated cardiomyopathy, the LTI Sign for endocardial fibroelastosis, and the Three Pipes Sign for the suprasternal long-axis view of the aortic arch. The SFH Sign for advanced cervical insufficiency and the Gentle Upslope Sign for the parvus–tardus waveform are proposed for the first time in this paper. Collectively, these seven signs span the fields of superficial ultrasound, abdominal ultrasound, echocardiography, and obstetric ultrasound. For each sign, its naming logic, definition, clinical implications, and teaching value are described. This review aims to facilitate a better understanding of these signs and to promote their use as teaching aids in ultrasound education.

Abstract: Background: Genetic therapies aim to create targeted interventions that treat, prevent or manage genetic disorders, holding substantial promise for many pediatric diseases with underlying genetic causes. As emerging genetic therapies are increasingly being tailored to individual patients, evaluating their efficacy is challenging. Standard N-of-1 trial designs that require repeated crossovers between experimental and control conditions are infeasible as many genetic therapies produce one-time, irreversible effects. Quasi-experimental single-participant designs with pre- and post- intervention periods are a promising alternative in this context where interrupted time series (ITS) analysis can be applied. Herein, we evaluated and compared different design and statistical elements for single participant studies of novel genetic therapies. Methods: We simulated designs using pre- and post-intervention treatment periods examined with ITS models under different assumptions about treatment effects. Changes in a continuous study outcome were assumed to be linear with varying standard deviations (SD). Different frequentist and Bayesian statistical models were compared. Trial performance was evaluated across varying pre-treatment lengths, effect sizes, outcome measurement frequencies, and outcome SD. Patient and family engagement examined the feasibility of study design elements. Results: Using frequentist methods, three selected statistical models achieved similar optimal performance for a study duration of 2 years, yielding power of approximately 80% or higher while maintaining type I error rates around 5%. Simulations suggested studies with balanced pre-post intervention period lengths, larger treatment effects, lower outcome SD, and more frequent outcome assessments had the highest statistical power. Type I error rates were insensitive to outcome SD changes. Less frequent outcome measurement improved trial feasibility from a family perspective. Similar performance was observed when applying Bayesian analyses with minimally informative priors under the same trial design assumptions. Incorporating patient and caregiver perspectives identified additional strategies to improve feasibility and acceptability of the trial designs beyond statistical considerations. Conclusions: Quasi-experimental single participant studies with ITS analysis provide a feasible framework for evaluating novel genetic treatment effect in rare diseases. Appropriate statistical approaches and design parameters are critical for achieving adequate power while maintaining type I error control. Meaningful patient and family engagement during study design is critical for feasibility.

Abstract: Background/Objectives: The palatine tonsil changes with age and with chronic inflammation, and morphometric studies rarely separate the two. We asked whether the normal tonsil changes between 4 and 40 years and whether all components of the chronic tonsillitis lesion develop on the same time course. Methods: Twelve morphometric parameters were measured on hematoxylin and eosin and Masson trichrome sections of 340 palatine tonsils from patients of both sexes aged 4 to 40 years: histologically normal tonsils removed at surgery for benign non-inflammatory oropharyngeal lesions (n = 160) and tonsils removed for chronic tonsillitis (n = 180). The effect of age was tested by one-way analysis of variance across six age periods, separately within each group, and each parameter was expressed as a ratio of diseased to normal tissue within the same age period. Results: In normal tonsils no parameter varied with age (all p > 0.05). In chronic tonsillitis, epithelial thickness, epithelial erosion, stromal fibrosis and the composite tissue inflammatory index varied with age after correction for twelve tests (F = 17.56 to 36.50; all p < 0.001). Crypt depth (4.8 to 5.5 times normal), capsular thickness (3.4 to 3.7 times), cryptal detritus and the follicular parameters kept the same ratio from 4 to 7 years to 36 to 40 years. Erosion, fibrosis and the inflammatory index were close to normal at 4 to 7 years and diverged from 8 to 12 years onward. Conclusions: The lesion of chronic tonsillitis has two components with different kinetics: remodeling of the crypt and follicle apparatus that is complete in early childhood, and epithelial and stromal damage that accumulates later, consistent with repeated cycles of injury and repair. Cryptal, capsular and follicular measurements can be compared across ages, whereas epithelial and stromal measurements need age-specific reference values.

Abstract: Hereditary sensory and autonomic neuropathy type IV [HSAN IV] is a rare ge-netic disorder of children characterized by the inability to feel pain and to sweat [anhidrosis]. There is insensitivity to temperature. Dysfunction of the sensory nerves which are responsible for pain and temperature causes the sensory loss. NTRK1 gene variants cause this disorder, inherited in an autosomal recessive pattern. This review aims to synthesize current research on the clinical, molecular, and diagnostic aspects of Hereditary Sensory and Autonomic Neuropathy -IV [HSAN IV] and identify gaps for future research. The objectives include reviewing studies on HSAN's clinical features and genetic variations, assessing the effectiveness of diagnostic methods, genetic testing and highlighting inconsist-encies in genotype-phenotype correlations. We searched PubMed, Scopus, Web of Science, Embase and Google Scholar using terms 'HSAN' and 'genetic vari-ants', with no time frame restrictions. The literature on the clinical and molec-ular characteristics, diagnostics, therapeutics including recent advances of HSAN IV has been reviewed. This review highlights advancements in understanding HSAN's clinical and genetic aspects, while emphasizing the need for further re-search to address gaps in genetic knowledge and improve diagnosis and treatment outcomes.

Abstract: Echocardiography is an important imaging modality in the assessment of cardiovascular diseases. Several echocardiographic signs have been described to aid in the diagnosis of specific clinical conditions and to help clinicians remember the key sonographic features. This review summarizes five classic signs in echocardiography, including the McConnell’s Sign, the D-Sign, the 60:60 Sign, the SAM Sign, and the Swinging Heart Sign, as well as three novel signs, the Three Pipes Sign, the LTRD Sign, and the LTI Sign. This review aims to provide an overview of the classic echocardiographic signs, focusing on their naming logics, definitions, and clinical implications to facilitate a better understanding of them, and to first propose three novel signs, the Three Pipes Sign, the LTRD Sign, and the LTI Sign, which may aid in diagnosis and serve as teaching aids in echocardiography.

Abstract: The traditional framework for forward head posture (FHP) attributes its maintenance to muscle imbalance and behavioral habits. The deep sclerotic fibrous tissue of the dorsocervical hump—rather than its superficial fat pad—is usually treated as a secondary consequence or a co-localized accompanying phenomenon, with its mechanical contribution considered secondary to that of muscle and behavioral factors. We propose a falsifiable mechanical hypothesis: in individuals with long-standing FHP, deep sclerotic fibrous tissue at the cervicothoracic junction—investing fascial fibrosis with increased stiffness—may have evolved from a secondary consequence into a dominant passive constraint and may constitute the main mechanical resistance to returning the head to a neutral position. The hypothesis targets sclerosis (increased stiffness), not increased volume or fat accumulation. Dominance is operationalized by two criteria: a mechanical threshold criterion, which is necessary but not sufficient, and a joint model criterion, which directly compares the explanatory power of passive constraint, muscle function, and behavioral factors. Deep sclerotic tissue is an operational designation for a mechanical functional unit and does not presuppose equal degrees of fibrosis across the investing fascia, fibrous septa, and nuchal ligament attachment sites. Literature-based support includes load-induced fascial fibrosis, posture-related nuchal fascial stiffening, coexistence of posterior cervical structural changes with FHP, quantitative shear-wave elastography (SWE) of cervical fibrosis, layered anatomy of the posterior cervical fat pad, high SWE reliability, PIEZO2 expression in trapezius fascia, and a fibrosis-dominant pathological subtype with collagen content >38.4%. The hypothesis comprises three falsifiable components—weight, independence, and removal effect—and yields four testable predictions with a three-tier validation pathway. If validated, intervention logic may shift in part from posture correction alone toward relief of passive constraint; before rigorous controlled validation, this hypothesis should not be read as evidence for any specific treatment as a routine management option for FHP.

Abstract: Background and Objectives: Passive release — a release technique performed while the target tissue is held in a passively stretched position — applies to the joint capsule, ligaments, tendons, muscles, peripheral nerves, vessels and subcutaneous tissue; when the release is delivered by injection it is termed “passive release with hydrorelease”. In our experience, no local anesthetic is required, the stretched position makes tender stacking fascia easier to localize, and range of motion tends to improve more than with hydrorelease in a relaxed position. The aim of this article is to describe, in a reproducible form, the treatment points and ultrasound technique of passive release with hydrorelease across multiple body regions. Materials and Methods: This protocol is based on our clinical experience. Eight treatment points in six regions (forearm; shoulder; hip, anterior and posterior; gluteal region; posterior thigh; posterior knee) were selected from our practice. For each point, the patient position, the assistant-maintained passive stretch, the ultrasound visualization, the release procedure, and the safety considerations are described with demonstration videos. Results: The protocol is presented as eight point-by-point descriptions (P1–P8), each pairing a passively stretched position with hydrorelease of the target fascia, ligament or capsule, with the anatomical rationale and corresponding video (Videos S1–S8). Conclusions: This article describes passive release with hydrorelease as a reproducible multi-region protocol. It is a technique description based on our clinical experience; no claim of effectiveness is made, the technique is proposed as one element of multimodal care rather than as a stand-alone treatment, and its prospective evaluation remains a task for future studies.

Abstract: Background and Objectives: Although the diagnosis of chronic spontaneous urticaria (CSU) is primarily clinical, detailed history taking and selected laboratory findings are important for patient evaluation and management. Materials and Methods: This explorative prospective study included 41 CSU patients who were followed for 3 months during antihistamine treatment. Saliva and blood samples were collected, and disease-related questionnaires were completed at baseline (T1) and at follow-up (T2). Salivary IL-6 and amylase, serum IL-6, and standard laboratory parameters, including differential blood count, erythrocyte sedimentation rate and/or C-reactive protein (CRP), total IgE, TSH, T4, and anti-TPO antibodies, were measured and compared with disease activity (UAS7), disease control (UCT), and quality of life (DLQI and CU-Q2oL). Results: Salivary IL-6 showed a weak correlation with serum CRP. Neither salivary nor serum IL-6 showed a consistent association with CSU severity, disease control, or quality-of-life scores. Serum IL-6 showed significant correlations with selected inflammatory and thyroid-related parameters. Salivary IL-6 values at baseline (T1) were more frequently increased in patients experiencing a major disease impact on quality of life (CU-Q2oL-measured) than in those with a moderate impact on CU-specific quality of life. Also, higher salivary IL-6 values were expressed in patients with uncontrolled CSU than in well-controlled CSU, as measured by the UCT questionnaire, although without significant difference between these parameters. Conclusions: Salivary IL-6 showed a weak correlation with CRP, but no consistent association with CSU clinical features. Salivary IL-6 is of exploratory interest, but larger controlled studies are needed before any clinical utility can be inferred.

Abstract: Background and Objective: Neutrophil extracellular trap (NET) formation has been proposed as a potential component of the inflammatory response associated with hemodialysis (HD). However, direct assessment of NET formation by neutrophils during HD has been limited. This study evaluated NET-associated signals in neutrophils during HD using flow cytometry and compared these findings with circulating NET-associated biomarkers. Methods: Ten clinically stable outpatients receiving regular HD with H₂-enriched dialysate (H₂-HD) participated in a prospective within-subject repeated-measures exploratory study. Patients underwent H₂-HD for 1 week (phase 1), standard HD (SHD) for 1 week (phase 2), and H₂-HD again for 1 week (phase 3). Blood samples were obtained immediately before and after the third HD session in each phase. NET-associated signals were assessed in isolated polymorphonuclear leukocyte preparations by flow cytometry using SYTOX Green and anti-myeloperoxidase (MPO) staining. Plasma cell-free DNA (cfDNA) and MPO-DNA complexes were also measured. Results: The proportion of SYTOX Green/MPO double-positive events in the predefined extracellular fraction increased significantly after HD during phase 2 (SHD), whereas no significant increase was observed during phases 1 or 3 (H₂-HD). Changes in the NET-associated signal did not differ significantly among the three phases. The change in the NET-associated signal was strongly correlated with the change in MPO-positive events (r=0.966, P<0.001), but not with changes in cfDNA or MPO-DNA complexes. Plasma cfDNA increased after HD before correction for hemoconcentration but not after correction. MPO-DNA levels decreased after HD after correction for hemoconcentration. Conclusions: Flow cytometry detected a neutrophil-associated NET signal that increased during SHD, providing evidence consistent with NET-associated extracellular DNA formation during HD. The discordant responses of flow cytometric and circulating NET-associated biomarkers suggest that these assays may reflect different aspects or temporal phases of the dialysis-associated neutrophil response. The effect of H₂-HD on NET formation remains uncertain.

Abstract: A large proportion of registered clinical trials fail to post their data even after a year of completion. No causal factor appears to explain this failure other than deliberate selective reporting in commercial interest. Since regulators, journal editors and academics appear to have failed to arrest this, citizen science needs to take active steps and challenge the concerned researchers, regulators and journal editors too.

Abstract: Background: Buffalo hump is often oversimplified as localized fat accumulation, but its tissue composition is heterogeneous, and its clinical significance extends beyond cosmetic concerns. Neck circumference has accumulated relatively consistent evidence in cardiometabolic epidemiology, but most integrated analyses have used metabolic risk factors or metabolic syndrome as endpoints rather than hard endpoints such as stroke. Whether enlargement of the buffalo hump leads to an increase in neck circumference, and whether interventions that reduce the buffalo hump or neck circumference can translate into stroke prevention, remain unresolved. This narrative review examines the evidence linking buffalo hump and neck circumference to stroke risk and identifies structural gaps that currently preclude translation into prevention strategies.Methods: PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure were searched through March 2026 using terms for buffalo hump or dorsocervical fat, neck circumference, stroke or carotid atherosclerosis, and physical therapy or exercise. Population studies, intervention studies, mechanistic studies, and systematic reviews/meta-analyses reporting neck circumference, buffalo hump, carotid imaging, or stroke/cardiovascular endpoints were included. Case reports alone, narrative reviews without quantitative outcomes, and duplicate publications were excluded. After deduplication, title/abstract screening, and full-text assessment, 42 articles were included. As a narrative review, screening was performed by a single author without independent dual screening; selection bias cannot be excluded, and exhaustive retrieval according to systematic review standards is not claimed. Results: Buffalo hump is morphologically heterogeneous and frequently co-occurs with obesity and metabolic disorders. Increased neck circumference is associated with ischemic stroke and its subclinical precursor, independently of overall obesity. In a cohort of 3,009 patients with type 2 diabetes, high neck circumference was associated with an approximately 2.3-fold higher risk of a composite cardiovascular endpoint that included stroke; this estimate was not stroke-specific. The association was relatively robust in women in some East Asian cohorts; however, a cohort using the same cutoffs reported stronger predictive performance in men, and negative results from the Jackson Heart Study and the Framingham Offspring Cohort indicate that the direction and presence of the association are not uniform across populations. Pericarotid fat density and perivascular adipose tissue attenuation show incremental predictive signals beyond plaque burden in some studies, but this incremental value has not been consistently quantified, and their quantitative relationship with neck circumference has not been established. Surgical debulking, diet, physical therapy, and exercise have preliminary evidence, but none has reported postintervention neck circumference change in relation to stroke endpoints. Forward head posture remains an untested candidate pathway. Conclusions: The existing evidence supports treating buffalo hump and neck circumference as surface markers of stroke risk and potential intermediate targets, but it is still insufficient to support the clinical conclusion that treating or reducing buffalo hump, or lowering neck circumference, can prevent stroke. Concurrent collection of neck circumference, buffalo hump subtype, carotid imaging parameters, obstructive sleep apnea (OSA) severity, atrial fibrillation, forward head posture parameters, and stroke endpoints, together with systematic tracking of postintervention neck circumference trajectories, may translate the current descriptive associations into testable prevention hypotheses.