Borrelia miyamotoi is a relapsing-fever spirochete that conventional tick-borne testing does not detect. We report a case notable for two findings not emphasized in prior series: creatine kinase elevation to 1464 U/L and glucose concentrations above 500 mg/dL without ketoacidosis in a pump-treated patient with type 1 diabetes mellitus. A 36-year-old man with frequent wooded exposure presented with fever, headache, myalgias, and rash, along with leukopenia, thrombocytopenia, and mild transaminitis. Lyme serology, Babesia smear, Anaplasma and Ehrlichia PCR, spotted-fever group Rickettsia serology, and blood cultures were negative; blood real-time PCR identified B. miyamotoi after discharge. The hyperglycemia was attributable to infection-related insulin resistance and interruption of pump delivery. Seventeen days of doxycycline produced full clinical and laboratory recovery. Exercise and dehydration may have contributed to the hyperCKemia. This case supports early blood PCR during the febrile illness in culture-negative tick-borne disease and illustrates that insulin requirements may rise sharply when infection coincides with failure of insulin-delivery technology.

Subcutaneous insulin resistance (SIR) is a rare condition characterized by impaired responsiveness to subcutaneous insulin despite preserved intravenous insulin efficacy. The coexistence of SIR with rapid loss of endogenous insulin secretion following exogenous insulin exposure has rarely been reported.

A 47-year-old Chinese man initially classified as having type 2 diabetes (T2D) had preserved endogenous insulin secretion (random C-peptide, 4.59 ng/mL) and negative insulin autoantibody (IAA), glutamic acid decarboxylase antibody, and insulinoma-associated protein 2 antibody at diagnosis. Shortly after initiation of subcutaneous insulin therapy, he developed pruritic, erythematous, and indurated injection-site lesions with progressive hyperglycemia and subsequently presented with diabetic ketoacidosis. C-peptide became undetectable, whereas IAA increased to >175 IU/mL. Intravenous insulin consistently restored glycemic control, while several subcutaneous insulin preparations were initially ineffective, indicating a marked route-dependent difference in insulin responsiveness. Subcutaneous insulin responsiveness later recovered, first with biphasic protamine human insulin 40/60 and subsequently with insulin analogues, despite persistent IAA positivity. At recent follow-up, 14-day continuous glucose monitoring showed a mean glucose of 7.6 mmol/L, time in range of 80%, and time below range of 3%. A heterozygous WFS1 variant (NM_006005.3:c.2147C>G, p.Ala716Gly) was identified as an exploratory finding of uncertain clinical significance.

This case highlights the coexistence of rapid loss of endogenous insulin secretion and severe but reversible SIR following exogenous insulin exposure. Preserved intravenous insulin responsiveness and recovery of subcutaneous insulin efficacy despite persistent IAA positivity underscore the dynamic and route-specific nature of this phenotype. The underlying mechanism remains uncertain, and no causal relationship with the WFS1 variant can be inferred. Recognition of this pattern may facilitate appropriate insulin delivery and longitudinal monitoring.

Maturity-onset diabetes of the young (MODY) comprises a heterogeneous group of autosomal dominant monogenic diabetes disorders; accurate molecular diagnosis is essential, as different subtypes require fundamentally distinct management strategies.

In a Chinese pedigree initially misdiagnosed as MODY10 based on an incidental INS variant, we aimed to identify the true genetic etiology through comprehensive genetic analysis (including copy number variation [CNV] detection) and continuous glucose monitoring (CGM), and to illustrate the clinical consequences of rigorous variant interpretation.

Detailed clinical evaluation, whole-exome sequencing (WES), whole-genome sequencing (WGS), multiplex ligation-dependent probe amplification (MLPA), segregation analysis, and CGM monitoring were performed across three generations of the pedigree.

We identified a 1, 171 bp GCK deletion (chr7:44, 228, 224-44, 229, 394 [GRCh37], encompassing the β-cell promoter, exon 1, and part of intron 1) that co-segregated with diabetes across three generations. This deletion removes the β-cell promoter while leaving the hepatic promoter intact, predicting selective loss of the pancreatic glucokinase isoform. The deletion was classified as pathogenic under ACMG/AMP criteria using the ClinGen Monogenic Diabetes Expert Panel specifications. Segregation analysis revealed that an INS variant (NM_000207.3:c.4G>A, p.Ala2Thr; rs535989053) did not co-segregate with diabetes: it was inherited from the euglycaemic maternal grandfather (fasting glucose 5.0 mmol/L, HbA1c 5.2%) and was absent in the proband. Under ACMG/AMP criteria, the INS variant meets criteria for a benign allele (BS1, BP2). The proband (isolated MODY2) exhibited a characteristic "plateau-like" stable mild hyperglycemia (coefficient of variation [CV] 14.35%). The elder brother, who carries both variants, showed a similar stable pattern (CV 13.41%). The mother, who also carries both variants, had been treated with insulin for ten years under the erroneous MODY10 diagnosis; upon discontinuation of insulin, her glycemic control remained stable, with CGM metrics comparable to those of her children.

This case underscores the critical importance of CNV analysis and segregation studies in monogenic diabetes diagnostics. The identification of a large GCK deletion corrected the initial misdiagnosis of MODY10-based on an incidental INS variant-and enabled appropriate genetic counseling and discontinuation of unnecessary insulin therapy. CGM emerges as a valuable ancillary tool for distinguishing MODY2 from MODY10 and for reassuring patients that pharmacological treatment is not required.

Gastrointestinal mucormycosis is a rare, life-threatening invasive fungal infection that is often diagnosed late because of nonspecific clinical and endoscopic findings. Khat or Qat (Catha edulis) leaves may harbor environmental fungi, including Mucor species, and chronic chewing may contribute to gastrointestinal mucosal injury. However, a possible association between Qat use and gastrointestinal mucormycosis has not been established. We report a case of a 60-year-old man with diet-controlled type 2 diabetes mellitus and long-standing Qat chewing who was admitted after an out-of-hospital cardiac arrest secondary to acute myocardial infarction. He had no history of malignancy, transplantation, neutropenia, or immunosuppressive therapy. Return of spontaneous circulation was achieved after 34 min of cardiopulmonary resuscitation, followed by temporary venoarterial extracorporeal membrane oxygenation. On hospital day 14, coffee-ground material was observed through the nasogastric tube, accompanied by a decline in hemoglobin from 14.0 to 9.5 g/dL. Esophagogastroduodenoscopy revealed a fungating, ulcerated lesion involving the gastric fundus and body. Histopathological examination demonstrated extensive necrosis, angioinvasion, and broad, ribbon-like, pauci-septate fungal hyphae with irregular branching, consistent with gastric mucormycosis. Intravenous liposomal amphotericin B was initiated at 8 mg/kg/day. Gastrointestinal bleeding resolved without surgery. Repeat endoscopy one month later showed marked healing, and follow-up biopsy revealed no residual fungal elements. The patient completed six weeks of antifungal therapy and achieved clinical and histopathological resolution. Fungal culture and molecular identification were not performed, precluding species-level confirmation.‏ In conclusion, this case describes gastric mucormycosis in a patient without profound immunosuppression but with severe physiological stress and chronic Qat exposure. Critical illness, gastric hypoperfusion, and mucosal disruption may have facilitated fungal invasion. Qat chewing is presented as a hypothesis-generating factor because of possible fungal contamination of leaves and repeated mucosal injury; nevertheless, causality cannot be inferred from a single case. Further microbiological and epidemiological studies are required to investigate this potential association.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease worldwide. Accurate non-invasive identification of advanced fibrosis is essential for risk stratification and management. The Fibrosis-6 (FIB-6) score is a recently developed serum-based index, but its performance in MASLD remains unclear.

In this retrospective cross-sectional study, 397 adults with MASLD who underwent FibroScan were included. FibroScan-derived liver stiffness categories were used as the surrogate comparator for fibrosis assessment. The diagnostic performance of FIB-6 was evaluated using ROC analysis for significant fibrosis (F2-F4), advanced fibrosis (F3-F4), and cirrhosis (F4), and compared with FIB-4, APRI, NAFLD fibrosis score (NFS), and AST-to-ALT ratio (AAR).

Among participants (mean age 47.8 ± 13.0 years; 49.4% male), significant fibrosis was present in 18.4%, advanced fibrosis in 7.6%, and cirrhosis in 4.8%. FIB-6 showed AUROC values of 0.643 for significant fibrosis, 0.749 for advanced fibrosis, and 0.760 for cirrhosis. Among 30 patients with FibroScan-defined advanced fibrosis, FIB-6 identified 29 of 30 cases (96.7%) and had an NPV of 99.4%. Among 19 patients with FibroScan-defined cirrhosis, all cases were identified (19/19), resulting in an NPV of 100% (95% CI: 83.2-100.0); however, these estimates should be interpreted cautiously because of the low prevalence of advanced disease. Outcome-specific optimal cut-offs were identified using the Youden index (1.88 for significant fibrosis and 1.84 for advanced fibrosis/cirrhosis). While FIB-4 and NFS showed slightly higher AUROCs, differences were not statistically significant.

FIB-6 demonstrates acceptable diagnostic performance, particularly for excluding advanced fibrosis and cirrhosis in MASLD. Although not superior to established scores, its high negative predictive value and simplicity suggest potential as a rule-out tool pending external validation.

Airflow obstruction detected on spirometry is a hallmark of chronic obstructive pulmonary disease (COPD) and is needed for the diagnosis of COPD. Sparse data in high-income countries (HICs) have reported high prevalence of underdiagnosed COPD with poor clinical outcomes. Data are missing for low-income and middle-income countries (LMICs) to inform the burden and clinical outcomes of underdiagnosed COPD.

In this multinational, prospective cohort study, spirometry data were systematically collected from adults (aged 35-70 years) in urban and rural communities across 25 HICs and LMICs. Adults with spirometry airflow obstruction with physician-diagnosed airway diseases were categorised as diagnosed COPD and those without physician-diagnosed airway diseases were categorised as underdiagnosed COPD. Individuals with normal spirometry and no known airway diseases were categorised as no COPD. Data on baseline characteristics were collected via standardised interview questionnaires and follow-up data were collected every 3 years on vital status and clinical events. We examined the association between COPD status with baseline characteristics and follow-up clinical events.

Between July 11, 2002, and July 28, 2025, we collected data on 119 252 participants (baseline median age 51 years [IQR 43-59], 71 039 [59·6%] females and 48 213 (40·4%) males) with technically acceptable spirometry. The prevalence of airflow obstruction was 9·5% (11 306/119 252), of which 89·2% (10 080/11 306) constituted underdiagnosed COPD. The prevalence of airflow obstruction varied across geographical regions (6·1% [n=521/8601] in southeast Asia to 20·4% [n=785/3846] in sub-Saharan Africa) and was higher in LMICs (9·8% [n=10 120/103 758]) than in HICs (7·7% [n=1186/15 494]), with a prevalence of 90·7% (9175/10 120) for underdiagnosed COPD in LMICs. Baseline characteristics associated with underdiagnosis were younger age (≤50 years), low symptom burden, high lung function, being current or never smokers, and living in an LMIC. Compared with no COPD, underdiagnosed and diagnosed COPD were associated with higher mortality (hazard ratio 1·53 [95% CI 1·44-1·63] for underdiagnosed and 2·09 [1·83-2·40] for diagnosed COPD), respiratory events (1·97 [1·82-2·12] for underdiagnosed and 3·70 [3·25-4·21] for diagnosed COPD), and cardiovascular events (1·20 [1·13-1·27] for underdiagnosed and 1·35 [1·17-1·56] for diagnosed COPD). This association was consistent across country-income levels, age groups, smoking status, and symptom burden.

The high prevalence of underdiagnosed COPD and related poor outcomes suggest that a large burden of COPD is under-recognised. Since underdiagnosed COPD is mainly early and mild disease, this presents missed opportunities for early intervention that can modify disease trajectory and improve long-term health outcomes.

AstraZeneca, Population Health Research Institute, Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Canadian Institutes of Health Research's Strategy for Patient Oriented Research, Ontario SPOR Support Unit, and Ontario Ministry of Health and Long-Term Care.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease and a multisystem cardiometabolic disorder. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in this population. This review examines disparities in the recognition and management of coexisting cardiovascular and metabolic liver disease.

Shared metabolic and inflammatory pathways link liver disease with obesity, type 2 diabetes, hypertension, and CVD. Differences in measured disease prevalence across racial and ethnic groups must be interpreted separately from genetic susceptibility and in the context of structural inequities, diagnostic practices, and access to care. Socioeconomic disadvantage and sex- and gender-related barriers may further affect diagnosis and treatment. Resmetirom and semaglutide have expanded treatment options for selected adults with metabolic dysfunction-associated steatohepatitis (MASH), but unequal access to fibrosis assessment, insurance coverage, and longitudinal care may limit their benefits. An equity-centered cardio-hepatology framework should integrate early risk identification, stepwise noninvasive fibrosis assessment, individualized cardiovascular prevention, and access to indicated liver-directed therapies. Treatment and quality measures should reflect clinical eligibility rather than medication use alone. Inclusive research and coordinated long-term care are needed to evaluate whether these strategies narrow disparities.

Family-based interventions offer a promising solution to the pressing global health concern of childhood obesity by addressing the interconnected behaviours of parents and children. Nevertheless, limited evidence identifies which families benefit most when outcomes are evaluated at the parent-child dyad level.

To identify which parent-child dyads experienced clinically meaningful improvements in weight status over 1- and 2-year periods within the Feel4Diabetes study, a school- and community-based intervention targeting European families at risk for Type 2 diabetes.

Data were drawn from 2402 high-risk families across six European countries. For participants with overweight/obesity, improvement meant ≥ 5% parental weight loss and a ≥ 0.15-unit child BMI-z reduction. Multiple logistic regression models identified socio-demographic and contextual predictors of dyadic improvement.

After 2 years, 5.3% of families achieved improvements in both parent and child. Significant predictors of dyadic success included intervention group participation [OR = 2.56 (95% CI: 1.31-5.03)] and residing in high-income countries under austerity measures [OR = 2.44 (1.00-6.02)]. Girls were more likely to improve than boys, while full-time maternal employment was associated with lower odds of dyadic improvement.

Sustained benefits were observed in a subset of families, highlighting the need for tailored, context-sensitive family-centred obesity prevention strategies.

Although hypertension is a major contributor to cardiovascular complications, real-world blood pressure (BP) control in primary care and the role of hypertension specialists remain incompletely characterized. We evaluated BP control and associated factors using the Japan Medical Association Database of Clinical Medicine (J-DOME), a nationwide primary care registry. This cross-sectional study included patients with hypertension registered in 2024, categorized by treatment by specialists certified by the Japanese Society of Hypertension. Multivariable logistic regression identified factors associated with achieving office BP < 130/80 mmHg. Among 2663 patients (43.6% women; mean age, 71.4 years), 545 were treated by hypertension specialists. Mean BP was 134.4/74.8 mmHg, and the mean number of antihypertensive drugs was 1.6. Systolic BP was similar between specialist- and non-specialist-treated patients (135.1 vs. 134.2 mmHg; p = 0.28), whereas diastolic BP (76.1 vs. 74.5 mmHg; p = 0.0060) and the number of drugs (1.9 vs. 1.6; p < 0.0001) were higher in the specialist-treated group. Target BP achievement rate was lower in the specialist-treated group (30.8% vs. 37.3%; p = 0.0058), however, this difference was not observed among patients aged <75 years (33.2% vs. 35.4%; p = 0.55). The multivariable-adjusted model revealed that diabetes mellitus (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.08-1.61) and a higher number of drugs (OR per additional drug, 1.12; 95% CI, 1.04-1.22) were associated with higher target achievement, whereas overweight (OR, 0.70; 95% CI, 0.58-0.85), obesity (OR, 0.57; 95% CI, 0.42-0.77), and specialist treatment (OR, 0.77; 95% CI, 0.61-0.96) were associated with lower achievement. Office BP control remains suboptimal in Japanese primary care. Lower achievement among specialist-treated patients despite more drugs may reflect the concentration of difficult-to-control hypertension in specialist care. Continued efforts to improve hypertension management, particularly in patients with obesity, are warranted.

Multiple system atrophy (MSA) and Parkinson's disease (PD) exhibit distinct patterns of autonomic dysfunction, but differences in sudomotor function remain incompletely characterized. We investigated whether electrochemical skin conductance (ESC) measured by Sudoscan provides autonomic information complementary to ¹²³I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. We retrospectively analyzed 15 patients with MSA (12 MSA-C, 3 MSA-P) and 48 with PD who underwent Sudoscan after excluding patients with diabetes mellitus or Sjögren's syndrome; MIBG data were available in 9 and 43 patients, respectively. The feet-hands ESC gradient was designated as the primary outcome for the present analyses. The gradient was significantly lower in MSA than in PD (median -3.5 vs. 10.9 μS, p < 0.001), and feet ESC was lower in MSA (63.7 vs. 77.7 μS, p = 0.005), whereas hands ESC did not differ significantly. A negative gradient was observed in 53% of patients with MSA and 8% with PD. MIBG myocardial scintigraphy showed relatively preserved cardiac sympathetic innervation in MSA compared with PD (delayed H/M ratio 3.67 vs. 1.49, p < 0.001). Exploratory analyses showed no significant correlations between the ESC gradient and disease duration, available clinical severity measures, or MIBG parameters. These findings suggest that Sudoscan and MIBG myocardial scintigraphy provide complementary information for autonomic phenotyping in parkinsonian disorders.