Background and Clinical Significance: Marfan syndrome (MFS) is an autosomal-dominant connective-tissue disorder caused by pathogenic FBN1 variants. Aortic-root dilation and dissection are the canonical complications, whereas spontaneous vertebral artery dissection (VAD) is described only sporadically. Yet, cerebrovascular events are several-fold more common in MFS, and up to 74% of patients exhibit increased vertebral artery tortuosity, a validated predictor of dissection; Case Presentation: A 32-year-old African man with hypertension, type 2 diabetes mellitus, tobacco use, and headaches labelled as migraine presented with acute agitation, visual disturbance, vertigo, dysarthria, and right-sided weakness of two hours' duration. Examination disclosed previously unrecognised marfanoid stigmata: arachnodactyly with positive wrist and thumb signs, reduced upper-to-lower segment ratio, increased arm-span-to-height ratio, dolichocephaly, pectus excavatum, and a high-arched palate. Non-contrast CT showed left occipital and posterior inferior cerebellar hypodensities. CT angiography demonstrated discontinuous intraluminal filling defects in the left vertebral artery at C4 and C2, and MR angiography confirmed long-segment occlusion/stenosis of the intracranial left vertebral artery. Echocardiography revealed mild aortic-root dilation (4.0 cm; Z-score +2.53) and a small patent foramen ovale (PFO) with a positive bubble study. The patient received intravenous thrombolysis followed by antiplatelet therapy, a high-intensity statin, antihypertensive therapy, and intensified glycaemic control. Because the infarct territory matched the dissected vessel and the small PFO carried no high-risk features (RoPE score 6; PASCAL category "unlikely"), VAD was designated the culprit lesion and the PFO incidental; Conclusions: Spontaneous VAD may be the inaugural manifestation of unrecognised MFS, antedating aortic complications. In young adults with cryptogenic posterior-circulation stroke and marfanoid features, early cervical imaging and Ghent assessment are warranted, and a coexistent PFO should not be assumed causal. Multidisciplinary evaluation supports accurate attribution and surveillance.

Type 1 diabetes mellitus (T1DM) is regarded as an autoimmune disorder characterized by a progressive loss of β-cells, culminating in insulin deficiency and hyperglycemia. Currently, T1DM is managed through exogenous insulin administration. Continued efforts to decipher T1DM pathogenesis have yielded significant progress, which can be harnessed to develop disease-modifying therapeutic modalities. Immunological and genetic studies have demonstrated pathogenetic mechanisms that underpin the sensitivity and risk of developing autoimmunity, ultimately leading to the destruction of β-cells. Genetic and immunological studies, therefore, suggest that certain individuals are at risk of developing T1DM; and that autoantibodies against β-cells develop and circulate years before the onset of symptomatic T1DM. Furthermore, the onset of autoimmunity has been associated with specific triggers in genetically susceptible individuals. Recent developments have revealed how viral infections, gut dysbiosis, dietary factors, and obesity trigger autoimmunity and β-cell damage. In this review, we present the current, consolidated understanding of T1DM pathogenesis, informed by recent research. We further identify opportunities for early-detection strategies and drug development targeting the asymptomatic phase of T1DM to slow disease progression. Currently, immunomodulatory strategies have yielded promising outcomes in clinical trials. These strategies seek to target immune cells and inflammatory mediators implicated in the pathogenesis of T1DM. Other strategies include tolerogenic strategies against autoimmune cells, whilst others employ β-cell protection. The emergence of regenerative therapies also offers promising avenues toward T1DM.

Chronic limb-threatening ischemia (CLTI) in patients with no conventional targets for revascularization presents a formidable challenge in limb salvage. Deep venous arterialization (DVA) is an emerging endovascular approach that redirects arterial blood flow into the venous system to perfuse the ischemic foot. Despite early promising results, appropriate wound management of the ischemic foot following a DVA procedure has been described in the literature, albeit infrequently and with limited standardization. Here, we present a case of an 85-year-old male with multiple comorbidities, including peripheral artery disease and a prior right above-knee amputation (AKA), who underwent a successful left-sided DVA following an open transmetatarsal amputation (TMA) for infection. A staged wound care approach with guillotine amputation, delayed revision and skin grafting ultimately preserved his only remaining limb and allowed for ambulation. This case underscores the potential of DVA as a limb-saving option in complex "no-option" patients when paired with multidisciplinary care and tailored wound management.

As the population ages, the impact of aging and comorbid lifestyle-related diseases on the prognosis of interstitial lung disease (ILD) has not been fully investigated. Therefore, we investigated the impact of age and comorbidities on the prognosis of patients with ILD who experienced acute exacerbations (AEs).

We retrospectively reviewed the medical records and chest computed tomography scans of all consecutive ILD patients, with or without AE, between May 2015 and July 2025. The survival times of cases with and without AE were investigated.

Median survival time (MST) for 443 ILD cases was 10 years, while the MST for the 158 cases who developed AE was 2 months. The prognosis of cases who developed AE at age 80 years or older was significantly poorer than that of cases younger than 80 years. Among cases younger than 80 years, the survival curve for those who survived 3 months after the onset of AE plateaued. Favorable factors among cases who developed AE were age younger than 80 years and absence of comorbidities such as hypertension, diabetes mellitus, and malignancy.

For ILD patients who developed AE, "80 years of age" was the threshold age distinguishing good from poor prognosis. Some patients, particularly those with ILD who were diagnosed early, appeared likely to have an improved prognosis. Some AE patients, particularly younger patients, could be expected to have a good long-term prognosis if they survive a certain period of time.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, and early detection remains challenging because conventional biomarkers lack sensitivity. MicroRNAs (miRNAs) have emerged as promising non-invasive biomarkers, but evidence remains inconsistent. This study systematically evaluated dysregulated miRNAs in DKD and their associations with clinical parameters across albuminuria stages. PubMed, Scopus, and Embase were searched for studies assessing miRNA expression in DKD. Standardised mean differences (SMDs) were pooled using random-effects models, and risk of bias was assessed using the Newcastle-Ottawa Scale. The SMD of urinary miRNA124 in normoalbuminuria was 2.04 (95% CI 1.16 - 2.92, I2 = 77.2%, p = <0.00001), microalbuminuria 7.76 (95% CI 5.67 - 9.84, I2 = 78.1%, p = <0.00001), and macroalbuminuria 13.04 (95% CI 10.94 -15.13, I²=40.8%, p<0.00001). Urinary and circulating miRNA21 showed progressive upregulation across normoalbuminuria, microalbuminuria, and macroalbuminuria with SMDs of 3.34 (95% CI -0.56 - 7.24, I2 = 95.9%, p = 0.0933) and 0.50 (95% CI -0.36 -1.36, I²=89.7%, p=0.2520); 4.02 (95% CI 2.69 -5.36, I²=80.0%, p<0.0001) and 1.78 (95% CI 0.00 -3.56, I²=96.7%, p=0.0499); and 4.61 (95% CI 0.18 - 9.03, I²=97.8%, p=0.0413) and 4.77 (95% CI -1.29 -10.82, I²=98.4%, p=0.1230), respectively. Circulating miRNA126 was consistently downregulated in normoalbuminuria, microalbuminuria, and macroalbuminuria with SMDs -0.85 (95% CI -1.87-0.18, I²=95.0%, p=0.1044), -1.59 (95% CI -2.67 - -0.52, I²=93.0%, p=0.0035), and -1.87 (95% CI -4.67- 0.93, I²=98.1%, p=0.1901). Urinary miRNA192 was downregulated, whereas circulating miRNA192 showed inconsistent expression. Correlation analyses demonstrated positive associations between urinary miRNA34a and UACR (r = 0.39) and HbA1c (r = 0.20), while circulating miRNA21 (r = -0.37) and miRNA192 (r = -0.26) were inversely associated with albuminuria. Overall, urinary miRNA124, miRNA21, and miRNA34a, together with circulating miRNA126 and miRNA192, show promise as biomarkers of DKD progression, although prospective validation studies are required.

Diabetes mellitus‑induced erectile dysfunction (DMED) is a common diabetic complication characterized by endothelial dysfunction and corpus cavernosum (CC) remodeling. Although circular RNAs (circRNAs) have been implicated in diabetic vascular diseases, their roles in DMED remain largely unknown. The present study investigated the biological function and underlying mechanism of circRNA_013145 in DMED. CircRNA microarray analysis identified circRNA_013145 as a significantly upregulated circRNA in penile tissue from DMED rats. Its biological function was evaluated using loss‑of‑function and rescue experiments in high glucose (HG)‑treated CC smooth muscle cells (CCSMCs), human umbilical vein endothelial cells (HUVECs) and a DMED rat model. circRNA_013145 expression was markedly increased in DMED penile tissue and HG‑treated cells. circRNA_013145 knockdown attenuated HG‑induced oxidative stress, inflammation, apoptosis, autophagy and phenotypic transformation, while improving endothelial function and cell viability. Mechanistically, circRNA_013145 served as a molecular sponge for miR‑185‑5p, thereby positively regulating RhoA expression. Rescue experiments demonstrated that inhibition of miR‑185‑5p partially abolished the protective effects of circRNA_013145 knockdown. Furthermore, adenovirus‑mediated knockdown of circRNA_013145 significantly improved erectile function and alleviated cavernosal pathological injury in DMED rats, as evidenced by an increased intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio, enhanced CD31 expression and reduced collagen deposition. In conclusion, circRNA_013145 promotes the progression of DMED through the miR‑185‑5p/RhoA axis. Targeting circRNA_013145 may represent a potential therapeutic strategy for DMED.

The long-term clinical role of laparoscopic adjustable gastric banding (LAGB) remains uncertain in the contemporary era of metabolic surgery, and very long-term outcome data from Asian populations are limited. This study evaluated very long-term outcomes of LAGB in a Japanese cohort, focusing on weight change, metabolic comorbidities, and reoperations.

We retrospectively reviewed consecutive patients who underwent LAGB between 2005 and 2010 at a single institution. Changes in body weight, metabolic comorbidities, and reoperation were assessed for up to 15 years. Weight outcomes were evaluated using percent total weight loss (%TWL) and percent excess weight loss (%EWL).

A total of 28 patients were included. Mean %EWL was 49% at 1 year, 62% at 5 years, 64% at 10 years, and 59% at 15 years, indicating sustained long-term weight reduction despite partial weight regain. Early improvements in metabolic comorbidities were observed; however, recurrence of diabetes mellitus, hypertension, and dyslipidemia increased after 5-10 years, whereas hepatic comorbidities remained relatively stable. Reoperation was required in 7 of 28 patients (25%), mainly because of device-related complications or insufficient weight loss.

This study provides very long-term outcome data of LAGB in an Asian cohort. Although LAGB achieved sustained weight reduction in selected patients, metabolic improvements showed limited long-term durability and a substantial proportion of patients required reoperation. These findings highlight the limitations of a purely restrictive and device-dependent bariatric procedure in the contemporary era of metabolic surgery.

Kallmann syndrome (KS), a rare genetic disorder, is characterized by congenital hypogonadotropic hypogonadism (CHH) and anosmia or hyposmia.

We report a case of KS with type 2 diabetes mellitus (T2DM) associated with a novel hemizygous missense variant in ANOS1 (NM_000216.4; exon 4; c.505G >C;p.(Gly169Arg)). A 33-year-old male presented with persistent hyperglycemia, delayed pubertal development with absent secondary sexual characteristics, and lifelong anosmia. Olfactory testing, magnetic resonance imaging (MRI) of the pituitary region, and a gonadotropin-releasing hormone (GnRH) stimulation test supported a clinical diagnosis of KS. Trio-based exome sequencing (ES) revealed the aforementioned hemizygous variant in ANOS1. Notably, neither parent harbored this variant, supporting a de novo origin, which is consistent with the variant's potential pathogenicity. Multiple sequence alignment showed that Gly169 is highly conserved across species, suggesting it may be functionally important for the protein. Furthermore, a three-dimensional protein model generated using SWISS-MODEL predicted marked conformational changes in the protein attributable to this amino acid substitution at a highly conserved residue, suggesting a potential functional impact. Notably, emerging evidence has linked ANOS1 variants to dysregulated glucose metabolism, supporting a potential association with T2DM in this case. For treatment, insulin and oral hypoglycemic agents were used for glycemic control, and a GnRH pump was initiated. At the sixth follow-up visit, the patient had achieved satisfactory glycemic control; however, serum testosterone levels remained low despite GnRH pump therapy, so testosterone replacement therapy was subsequently initiated.

ANOS1 variants are genetically diverse and may contribute to both KS pathogenesis and the development of comorbid T2DM, though further studies are needed to confirm this link. For KS patients, close monitoring of fasting glucose, glycated hemoglobin, and oral glucose tolerance test results is advisable to detect diabetes and prediabetes early.

Pyoderma gangrenosum is a rare neutrophilic dermatosis with potential for relapse after healing, yet recurrence in real-world settings remains unknown. We aimed to evaluate recurrence patterns to inform clinical practice and future research.

Data were abstracted from a uniquely, prospectively maintained pyoderma gangrenosum registry. A cohort of patients with pyoderma gangrenosum seen between December 1st, 2019 and March 1st, 2026 who healed within this timeframe was identified. Two subgroups were then created: those who remained healed, and those who had a recurrence. Descriptive statistics summarised recurrence characteristics; Kaplan-Meier methods estimated a cumulative incidence of recurrence, and Cox proportional hazards modelling identified predictors of recurrence.

Of 116 patients with healed pyoderma gangrenosum, 41 (35%) experienced a recurrence, generating a recurrence proportion of 35·3% (95% CI 26·7-44·8). Nominal associations with recurrence on univariable analysis included history of diabetes mellitus (hazard ratio 2·1, 95% CI 1·1-4·0, p = 0·024) and ever-smoking (1·8, 1·0-3·4, p = 0·057). Baseline characteristics differing between recurrence and non-recurrence groups included age (p = 0·033), history of diabetes (p = 0·0060), and ulcer age at presentation (p = 0·046). Cumulative recurrence risk was calculated as 27% (95% CI 18·1-35·0) at 1 year and 41·3% (95% CI 30·4-50·5) at 5 years.

Pyoderma gangrenosum recurred in approximately a third of patients. A history of diabetes showed a borderline association with recurrence, while the univariable signal for smoking was attenuated after adjustment. Recurrence risk remains elevated five years after initial healing, and peristomal pyoderma gangrenosum is associated with higher recurrence rates, suggesting that maintenance therapy may be necessary for certain patient populations after achieving ulcer closure. Our data highlight the need for prospective evaluation of maintenance approaches. Future work will focus on individual recurrence predictors.

This is an unfunded study.

Cardiovascular autonomic neuropathy (CAN), defined as impaired autonomic control of the cardiovascular system, is a highly prevalent yet frequently underdiagnosed microvascular complication of diabetes. The triglyceride-glucose (TyG) index, a well-validated surrogate marker of insulin resistance, may have considerable clinical relevance for CAN. Nevertheless, the association between the TyG index and CAN in patients with type 2 diabetes mellitus (T2DM) remains unclear.

A total of 230 hospitalized patients with T2DM were recruited from the Department of Endocrinology and Metabolism, Shanghai General Hospital. CAN status was evaluated using the cardiovascular autonomic reflex test (CART) and heart rate variability (HRV) measurements. Meanwhile, demographic characteristics and relevant clinical data were collected, and the TyG index was calculated based on fasting blood glucose and triglyceride levels for subsequent statistical analysis.

The prevalence of CAN in our cohort of 230 patients was 61.3% (141 cases). Patients with CAN exhibited a significantly higher TyG index compared to those without CAN. The TyG index demonstrated positive correlations with CART parameters (E:I difference, r = 0.301; Valsalva ratio, r = 0.362; 30:15 ratio, r = 0.166; BP change, r = 0.229; all P < 0.05) and inverse correlations with HRV indices (SDNN, r = -0.257; RMSSD, r = -0.226; pNN50, r = -0.226; VLF, r = -0.221; LF, r = -0.253; HF, r = -0.212; TP, r = -0.249; all P < 0.01). Moreover, after adjusting for demographic and metabolic confounders, the TyG index remained a significant independent predictor of CAN. ROC curve analysis indicated that the TyG index possesses favorable discriminatory power for CAN, with an AUC of 0.854 (95% CI: 0.796-0.911, P < 0.001).

The TyG index shows a distinct association with CAN assessment parameters. As a well-established, effective, and practical surrogate marker of IR, this finding highlights the clinical relevance of the TyG index in diabetes-related complications.