Invasive spinal cord stimulation (SCS) is used in selected patients with refractory chronic neuropathic pain and has also been explored in spinal cord injury, disorders of consciousness, and Parkinson's disease. However, the strength of evidence differs substantially across indications. This review summarizes the current clinical applications of invasive SCS and distinguishes relatively established pain indications from emerging neurological applications.

We conducted a structured search of PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Wanfang, and China National Knowledge Infrastructure. The search was supplemented by reference tracking for landmark studies and a targeted update of relevant publications from 2024 to 2026.

Randomized evidence is concentrated in chronic pain populations. Conventional SCS has shown benefit in selected patients with failed back surgery syndrome, while 10-kHz SCS produced greater pain reduction than conventional low-frequency stimulation in patients with chronic back and leg pain. Burst stimulation was noninferior to tonic stimulation in the SUNBURST trial and was preferred by most participants. Randomized evidence also supports 10-kHz SCS in refractory painful diabetic neuropathy. Evidence for complex regional pain syndrome suggests short- to intermediate-term pain relief, although long-term benefit remains uncertain. By contrast, applications in diabetic foot complications, spinal cord injury, and disorders of consciousness are supported mainly by small, heterogeneous, or uncontrolled studies. Recent blinded trials have not demonstrated a clear benefit of SCS for Parkinsonian gait impairment.

The clinical evidence supporting invasive SCS varies considerably across neurological indications. Its role is comparatively well supported in selected chronic neuropathic pain populations, particularly chronic back and leg pain after spinal surgery and painful diabetic neuropathy. Evidence for non-pain neurological disorders remains limited, and these applications should remain investigational until further controlled studies clarify patient selection, stimulation parameters, durability of response, and safety.

The coexistence of diabetic ketoacidosis (DKA) and severe acute pancreatitis (SAP) is a life-threatening metabolic emergency complicated by multiple organ dysfunction syndrome. The sequential development of Guillain-Barré syndrome (GBS) and Wernicke's encephalopathy (WE) in such critically ill patients is exceedingly rare and prone to missed diagnosis. A 26-year-old obese male was admitted with unconsciousness after excessive cola ingestion. He was diagnosed with DKA, SAP, pneumonia, sepsis. During hospitalization, the patient developed progressive visual impairment, dysphagia, hoarseness, and ophthalmoplegia. Neurological examination revealed diminished to absent tendon reflexes. Typical albumin-cytologic dissociation was detected in cerebrospinal fluid. Cranial magnetic resonance imaging showed characteristic hyperintense signals in the mammillary bodies and periaqueductal region, accompanied by reduced serum vitamin B1 levels, consistent with WE. The patient was eventually diagnosed with overlapping GBS and WE. He received repeated intravenous immunoglobulin therapy and thiamine supplementation. The patient's neurological function gradually recovered and he was discharged in stable condition. Critical illness-related systemic inflammation, metabolic derangements and infection can induce GBS, while inadequate thiamine supplementation and heightened consumption result in severe thiamine deficiency complicated by WE. Close neurological monitoring, timely thiamine supplementation, and standardized immunotherapy contribute to favorable clinical outcomes.

Semaglutide is effective for type 2 diabetes mellitus (T2DM) but limited by dose-dependent gastrointestinal adverse effects. As electroacupuncture (EA) possesses glucose-lowering effects, this study investigates the therapeutic potential and mechanism of combining EA with semaglutide to facilitate dose reduction while maintaining efficacy.

Male db/db mice were divided into: the model group(T2DM), the high/normal/low-dose semaglutide group (SH, SN, SL), the normal/low-dose semaglutide + EA at ST25 group (ST25N, ST25L), and the EA at ST25 group (ST25). The db/m mice served as the control group (CON). Blood glucose regulation was assessed via random/fasting blood glucose and oral glucose tolerance test (OGTT). To evaluate glycemic control and lipid profiles, HbA1c and insulin levels were quantified via ELISA, and T-CHO, TG, LDL-C, and HDL-C via biochemical kits. GLP-1R expression and β-cell abundance were assessed by immunofluorescence, and pancreatic apoptosis by TUNEL staining. PKA, pPKA, Bcl-2, Bax, and GLP-1R were analyzed by Western blot. Male Sprague-Dawley (SD) rats were separated into 2 groups: the normal-dose semaglutide rats group (RSN) and the normal-dose semaglutide + EA at ST25 rats group (RST25N). LC-MS/MS was employed to measure the concentrations of semaglutide in the plasma and pancreas, thereby evaluating the influence of EA.

EA enhances the effects of semaglutide on improving glycemic control and lipid metabolism, with significant reductions in random/fasting blood glucose, HbA1c, TCHO, TG and LDL-C levels, improvements in OGTT, insulin and HDL-C levels, and longer duration of controlled blood glucose within the target range, Furthermore, EA combined with semaglutide showed a marked increase in pancreatic β-cells, with the increased expression of pancreatic GLP-1R, PKA, pPKA and Bcl-2, the reduced expression of Bax, increased concentration of semaglutide in plasma and pancreas.

EA combined with normal- or low-dose semaglutide achieved glycemic control comparable to, or even better than, high-dose semaglutide alone, and its mechanism may be related to its enhancement of GLP-1R to inhibit β-cell apoptosis and the increased concentration of semaglutide in plasma and pancreas. EA thus has great potential to reduce the dose of semaglutide to alleviate its side effects while ensuring its clinical efficacy.

Gestational diabetes mellitus (GDM) affects approximately 14% of pregnancies and is associated with adverse pregnancy outcomes and a substantially increased risk of long-term cardiometabolic disease. Although glucose levels often normalise postpartum, women with prior GDM have a ten-fold increased risk of developing type 2 diabetes mellitus (T2DM), particularly when early postpartum prediabetes is present. Current prevention strategies, including lifestyle modification and metformin, have in general shown limited effectiveness in this high-risk population.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve glycaemic control, promote weight loss, and reduce cardiovascular risk in people with T2DM and/or obesity. Given the central role of insulin resistance and weight retention in progression from GDM to T2DM, these therapies represent a promising strategy for postpartum diabetes prevention. However, available evidence in women with prior GDM is limited and largely derived from small, short-term studies not adequately powered to assess sustained diabetes prevention or long-term outcomes. Whether GLP-1 RA therapy should be considered an early preventive strategy in this high risk population remains therefore uncertain. The evidence base is now evolving, with the first large multicentre randomised controlled trial (RCT) with a potent GLP-1 RA in women with early postpartum prediabetes following GDM currently underway. In parallel, sodium-glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated robust cardiovascular and renal benefits in T2DM, independent of glycaemic status, and may offer additional preventive potential. Their insulin-independent mechanism and favourable cardiovascular profile are particularly attractive in women with prior GDM, who face elevated long-term cardiometabolic risk. However, uncertainties persist regarding safety in women of reproductive age, use during lactation, optimal timing, and patient selection, highlighting the gap between therapeutic promise and dedicated postpartum trial data.

This Debate examines the emerging role of GLP-1 RA and SGLT-2 inhibitors in preventing T2DM after GDM. Despite their potential, important uncertainties remain regarding long-term efficacy and safety. While these therapies may provide a shift beyond lifestyle intervention and metformin, robust trial data and careful consideration of reproductive factors are required before routine implementation. We discuss how pharmacological prevention strategies could be integrated into postpartum care for this high-risk population.

Adults with disabilities face multiple barriers to cancer screening services. Few studies have examined screening receipt across multiple disability domains via standardized measures in contemporary nationally representative samples.

Data were pooled from the 2021 and 2023 National Health Interview Survey. Prevalence of United States Preventive Services Task Force recommendation concordant breast, cervical, and colorectal cancer screening was estimated according to disability domain (vision, hearing, mobility, cognition, communication, and self-care) and difficulty level ("substantial," "some," and "none"), which were defined according to the Washington Group Composite Disability Indicator.

A total of 1712, 1147, and 3106 sample respondents eligible for breast, cervical, and colorectal screening had disabilities, respectively, which translates to 6.02 million, 5.10 million, and 11.17 million when population weighted. Breast and cervical screening prevalence decreased with increasing difficulty level for self-care, vision, mobility, and cognition domains, with the lowest receipt among those reporting substantial versus no self-care difficulties (breast: 52% vs. 79%; adjusted prevalence ratio [aPR], 0.69; 95% CI, 0.58-0.82; cervical: 37% vs. 78%; aPR, 0.63; 95% CI, 0.51-0.78). Communication disability was associated with lower cervical screening (35% substantial vs. 78% none; aPR, 0.65; 95% CI, 0.52-0.82) but not for other screenings. Conversely, stool testing for colorectal screening was higher among adults with substantial mobility difficulties (22% vs. 16% none; aPR, 1.24; 95% CI, 1.12-1.38) and some self-care, mobility, and vision difficulties, compared to those with none.

Addressing barriers for individuals with self-care limitations could improve suboptimal screening levels across multiple cancer screenings. Self-sampling modalities, including stool testing, may mitigate accessibility issues, and warrant further evaluation.

Differentiated thyroid carcinoma (DTC) responses to initial post-operative I-131 therapy are heterogeneous. Standard binary models combine incomplete responses into a 'non-excellent' category, obscuring transitional states (indeterminate response [IDR] and biochemical incomplete response [BIR]) and outcome-specific drivers. We developed and validated an interpretable four-class machine learning framework to separate these dynamic trajectories and support pre-therapeutic decisions.

Data from 948 DTC patients were partitioned into training (n = 663) and test (n = 285) cohorts, with an independent temporal validation cohort (n=150). Four algorithms (Random Forest [RF], eXtreme Gradient Boosting [XGBoost], Light Gradient Boosting Machine [LightGBM] and Multi-Layer Perceptron [MLP]) were evaluated to predict excellent response (ER), IDR, BIR and structural incomplete response (SIR). Performance was assessed via area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA). Shapley Additive exPlanations (SHAP) and multivariable logistic regression quantified category-specific drivers.

Random forest achieved a micro-average AUC of 0.894 (95% CI: 0.842-0.901) in the test cohort and 0.885 (95% CI: 0.832-0.912) in validation. SHAP analysis revealed that pre-treatment stimulated thyroglobulin (pre-sTg) and stimulated thyroglobulin to thyroid-stimulating hormone ratio (LOG(sTg/TSH)) dominated ER, IDR and BIR predictions (pre-sTg peak weight: 31.9% in BIR), whereas diagnostic whole-body scintigraphy (Dx-WBS) was definitive for SIR (45.1% weight). Distant metastasis on Dx-WBS dramatically elevated SIR risk (OR: 171.89); pre-sTg ≥ 10 ng/mL significantly increased both SIR (OR: 7.18) and BIR (OR: 5.48) risks.

This four-class framework separates biochemical and structural drivers of post-I-131 responses, providing a practical risk-stratification tool for personalized management before therapy.

Thyroid nodules have a high incidence, but a low malignancy rate, placing demands on imaging specificity. Photoacoustic imaging is being studied as a method that could potentially help increase the unsatisfactory specificity of ultrasound, the current first-line imaging method, which would decrease the number of unnecessary clinical interventions.

We employ a digital thyroid phantom and numerical simulations to evaluate photoacoustic probe designs on their suitability for thyroid nodule risk estimation.

Using the SIMPA toolkit, we examined 1080 probe configurations with varying illumination geometry, detector shape, pitch, and wavelength combinations. The performance of each probe was quantified on its sensitivity and its accuracy of oxygen saturation estimation.

Optimal performance was found using wavelengths 757 and 800 nm, and a curved detector (0.5 split, 0.40 mm pitch) for external illumination. However, performance increases significantly with endotracheal illumination, using wavelengths of 700 and 800 nm, and a curved detector (0.25 split, 0.40 mm pitch).

These results could provide design guidance for optimizing photoacoustic hardware, assisting with the clinical adoption of PAI, which could improve the diagnosis of thyroid nodules.

Undifferentiated carcinoma with osteoclastic giant cells (UCOGC) of the urinary bladder is a recently described entity classified as a subtype of poorly differentiated urothelial carcinoma, which is a form of invasive urothelial carcinoma. It is an extremely rare and aggressive malignancy that occurs predominantly in elderly men. The rarity of this neoplasm and its morphological similarity to other giant cell-rich lesions may present diagnostic challenges. Here, we present a case of urinary bladder carcinoma with a biphasic appearance. Histomorphological examination and immunohistochemical studies are important for identifying this entity and differentiating it from other carcinomas with similar features, given the significant prognostic and therapeutic differences among these entities.

Suspicious thyroid lesions are often evaluated using fine-needle aspiration (FNA) with the Bethesda System for Reporting Thyroid Cytopathology (TBSRCT) to estimate malignancy risk and guide management. Indeterminate findings create a diagnostic gray zone where neither molecular testing nor imaging alone can provide certainty. We report the case of a 57-year-old female with a progressively enlarging right-sided thyroid nodule, classified as Bethesda IV on FNA cytology, with a positive neuroblastoma rat sarcoma viral oncogene homolog (NRAS) mutation on ThyroSeq v3, suggestive of high-risk malignancy. Preoperative imaging also revealed suspicious cervical lymphadenopathy concerning for metastatic disease. Given these findings, the patient underwent a total thyroidectomy. Final pathology demonstrated benign nodular hyperplasia with no evidence of carcinoma, revealing a false-positive molecular result. Notably, excised cervical lymph nodes revealed non-necrotizing granulomas, raising suspicion for sarcoidosis or other granulomatous diseases. Infectious and malignant etiologies were excluded. Subsequent evaluation with chest computed tomography (CT) confirmed pulmonary sarcoidosis, despite a normal serum angiotensin-converting enzyme (ACE) level. This case highlights the diagnostic challenges of evaluating indeterminate thyroid nodules where radiographic, cytologic, and molecular findings may obscure the distinction between granulomatous inflammation and malignancy. This patient's presentation illustrates the importance of maintaining a broad differential diagnosis and using a multimodal approach to optimize clinical management and navigate diagnostic uncertainty.

Variants of uncertain significance (VUS) in mismatch repair (MMR) genes represent a persistent bottleneck in germline interpretation for Lynch syndrome, creating a critical opportunity to leverage tumor biology to refine pathogenicity assessment. Although tumor features such as microsatellite instability (MSI) and immunohistochemistry (IHC) are routinely evaluated, they are typically interpreted separately from germline classification, and their quantitative contribution within ACMG/AMP frameworks remains poorly defined. We therefore analyzed paired germline and tumor sequencing data from 1110 tumors across 1073 patients with colorectal or endometrial cancer to determine whether mismatch repair-deficient (MMR-d) mutational signatures can be quantitatively integrated into Bayesian germline variant interpretation. Using COSMIC single-base substitution signatures, tumors were classified as MMR-d or MMR proficient, and an empirically derived likelihood ratio (LR) quantified the association between MMR-d signatures and pathogenic germline MMR variants. The presence of an MMR-d signature increased the likelihood of an underlying pathogenic germline MMR variant approximately eightfold (LR ≈ 8; log10 LR ≈ 0.90), whereas its absence provided moderate-to-strong benign evidence (LR ≈ 0.156; log10 LR ≈ -0.81). Applying this integrative framework to 45 germline MMR VUS, joint modeling of tumor mutational signatures with additional somatic and variant-level evidence resulted in clinically significant reclassification of 38 (84.4%) variants, including three reclassified as pathogenic or likely pathogenic and 35 as likely benign. A total of 16 downgraded variants were independently downgraded by Invitae. These findings demonstrate that tumor mutational signatures can be formally incorporated into Bayesian germline interpretation, transforming tumor data into quantitative pathogenicity evidence and offering a principled strategy to reduce VUS burden in hereditary cancer genetics.