Annals of medicine最新文献

Background: Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects.

Objective: This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and ≥3 grades for analysis.

Patients/materials and methods: Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed.

Results: Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade ≥3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001.

Conclusion: Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

Purpose: Cuproptosis has been proven to be a novel mode of cell death, distinct from other types of cell death such as necrosis, ferroptosis, pyroptosis, and apoptosis. This study aims to systematically review the molecular mechanisms of cuproptosis in recent years and its research progress in pancreatic diseases.

Methods: By searching PubMed and Web of Science databases, 113 key literatures were included for thematic analysis, covering the molecular mechanism of cuproptosis and its role in the occurrence and development of pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cyst, pancreatic injury and pancreatic neuroendocrine tumor.

Results: Cuproptosis refers to the accumulation of copper ions in cells, which leads to instability of ferritin and aggregation of acylated proteins, resulting in oxidative stress-related cell death. Recent studies have shown that cuproptosis plays an important role in the occurrence and development of various pancreatic diseases, such as pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cysts, pancreatic injuries and pancreatic neuroendocrine tumor. The inducers of cuproptosis, such as disulfiram, chloroquinolones, and perilla phenols, alleviate pancreatic cancer by promoting cell cuproptosis. Copper chelators such as tetraethylenepentamine and tetrathiomolybdate promote the recovery of pancreatic injury by inhibiting cell cuproptosis.

Conclusions: Cuproptosis plays a crucial role in the pathogenesis of pancreatic diseases. Further research on the cuproptosis pathway may become a potential target for the treatment of pancreatic diseases.

Introduction: This study evaluated perioperative changes in serum zinc levels following different bariatric procedures and provided evidence-based recommendations for postoperative monitoring and supplementation.

Methods: PubMed, Embase, the Cochrane Library, Web of Science and CNKI were systematically searched from inception to July 2025. Eligible studies compared pre- and postoperative serum zinc levels in individuals with obesity undergoing bariatric surgery. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was graded using the GRADE approach. Pooled analyses were conducted with StataSE 17.0.

Results: Twelve studies including 2,529 participants were analysed, with overall quality rated as high. Compared with baseline, pooled standardized mean differences (SMDs) in serum zinc at 3 months, 6 months, 1 year, and 2 years postoperatively were -0.12 (95% CI: -0.27 to 0.04, I² = 57.9%, τ² = 0.0265, p = 0.149), -0.36 (95% CI: -0.58 to -0.14, I² = 82.2%, τ² = 0.1043, p = 0.001), -0.35 (95% CI: -0.53 to -0.16, I² = 81.9%, τ² = 0.0769, p = 0.001), and -0.36 (95% CI: -0.95 to 0.24, I² = 97.2%, τ² = 0.3515, p = 0.240), respectively. Subgroup analysis showed no significant changes at 3 months across procedures. However, zinc levels significantly decreased at 6 and 12 months after Roux-en-Y gastric bypass (RYGB) and mini-gastric bypass (MGB), but not after sleeve gastrectomy (SG). At 2 years, no significant reduction was observed in any group. The certainty of evidence for zinc changes was rated as moderate.

Conclusion: Serum zinc levels decline significantly during the first postoperative year, particularly after RYGB and MGB, while SG shows minimal impact. Routine zinc monitoring and individualized supplementation are recommended within the first year after surgery to prevent deficiency-related complications.

Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251138846.

Objective: The purpose was to investigate the effects of respiratory-swallow coordination training with bimodal signal biofeedback on swallowing function in patients with post-stroke dysphagia.

Methods: Post-stroke dysphagia Patients were randomly assigned to either the control group or the experimental group. The control group received conventional rehabilitation, while the experimental group underwent additional respiratory-swallow coordination training based on biofeedback. The training protocol consisted of three phases, conducted at an intensity of 30 min/day, 6 days/week, for two consecutive weeks. Outcome measures included the Functional Oral Intake Scale (FOIS) score, the Rosenbek Penetration-Aspiration Scale (PAS) score, respiratory-swallow coordination, and videofluoroscopic swallowing study temporal and kinematic parameter. Assessments were conducted at baseline, post-treatment, and at a one-month follow-up.

Results: Thirty patients were enrolled. Both groups showed significant improvement in FOIS scores from baseline to both two-week post-treatment and one-month follow-up (p < 0.001). Compared to the controls, the experimental group demonstrated significantly greater FOIS scoreimprovement at both post-treatment and follow-up (p < 0.001). The proportion of patients with a ≥ 2-point increase in FOIS scores was significantly higher in the experimental group than in the control group at both post-treatment (p < 0.01) and one-month follow-up (p < 0.01). After two weeks of treatment, the percentage of PAS scores ≥6 was significantly lower in the experimental group than in the control group (p < 0.001). Additionally, the percentage of optimal respiratory-swallow pattern was significantly higher in the experimental group than in the control group (p < 0.001).

Conclusion: Bimodal signal biofeedback-based respiratory-swallow coordination training can effectively improve respiratory-swallow coordination and swallowing function in patients with post-stroke dysphagia.

Background: To validate the clinical efficacy of non-invasive prenatal diagnosis (NIPD) for spinal muscular atrophy (SMA) in the first trimester and extend its applicability to families without probands.

Method: From December 2020 to October 2024, 288 high-risk pregnancies were recruited prospectively, with 81 qualifying for NIPD after genetic counseling. Among the eligible cases, parent-based haplotypes were successfully constructed in 75 families (92.6%), while grandparent-based haplotype reconstruction was performed for the remaining 6 cases (7.4%) where proband samples were unavailable. Through targeted sequencing of the SMN1/SMN2 gene and flanking informative SNPs in maternal plasma, fetal haplotypes were inferred by analyzing dosage changes in cell-free DNA (cfDNA) using Bayes factor. All NIPD results were subsequently validated through invasive diagnostic procedures (chorionic villus sampling or amniocentesis).

Results: The haplotypes were successfully constructed in 81 families through parents or grandparents of the identified variant carriers. 76 families (93.8%) successfully obtained NIPD results, among which the earliest gestational week for successful NIPD was 7⁺³weeks, with a minimum fetal fraction of 1.9%. 5 cases were classified 'no call' results due to pathogenic variant-adjacent recombination events (2/5), insufficient or unevenly distributed informative SNPs (2/5), and subthreshold fetal fraction (1/5). The average gestational age of NIPD blood drawing is 9 weeks. Validation test showed the NIPD results accuracy was 100%.

Conclusion: This study demonstrates the clinical feasibility of grandparent-assisted haplotype construction for SMA families without probands and enables accurate early prenatal diagnosis of SMA in first-trimester pregnancies.

Background: Disease stability is an achievable goal in chronic obstructive pulmonary disease (COPD) management. However, the clinical implications of disease stability in patients with COPD remain unclear.

Methods: We conducted a single-center retrospective cohort study using the electronic medical records of treated patients with symptomatic COPD. Patients who had newly initiated inhaler therapy with long-acting β2-agonist/long-acting muscarinic antagonist (LABA/LAMA) or inhaled corticosteroid/LABA/LAMA combinations were included. Disease stability was defined over a one-year assessment period as meeting all of the following criteria: (1) symptom stability; (2) no moderate or severe exacerbations; and (3) no rapid decline in lung function. The outcomes included acute exacerbations and all-cause mortality.

Results: Of the 725 screened patients, 405 were eligible for inclusion in the study. Among them, 158 (39.0%) achieved disease stability. The proportions of patients who met each criterion were 70.4% for symptom stability, 63.7% for no exacerbations, and 71.4% for a non-rapid lung function decline. Only 5.9% met none of these criteria. During the follow up duration of median 62 (interquartile ranges, 30-90) months, disease stability was significantly associated with a reduced risk of moderate-to-severe (adjusted hazard ratio [aHR] 0.521, 95% confidence interval [CI] 0.392-0.692) and severe (aHR 0.393, 95% CI 0.279-0.553) exacerbations after adjusting for confounders. It was also associated with a decreased mortality risk (aHR 0.345, 95% CI 0.135-0.883).

Conclusion: Disease stability was associated with a lower risk of exacerbation and mortality, suggesting its potential role as a treatment target and outcome measure for COPD.

Background: Pathogenic autoantibody subclass switch has been found in lots of autoimmune disease. However, the information on anti-phospholipase A2 receptor antibody subclass switch in membranous nephropathy (MN) is limited and controversial. Here, we aim to uncover the subclass change during the PLA2R-associated MN progression.

Methods: Biopsy-proven PLA2R-associated MN cases with sufficient tissue for light microscopy, immunofluorescence, and electron microscopy (October 2022 - March 2023) were included. Serum levels of PLA2R-IgG4 and PLA2R-IgG were measured by TRFIA. The correlation of the ratio with EM stage and other clinical parameters was analyzed.

Results: Among 116 enrolled patients, glomerular IgG1 (r = 0.15, p = .01; r = 0.18, p = .002) and IgG3 (r = 0.17, p = .005; r = 0.27, p < .001) intensities were positively correlated with C3 and C1q intensities, respectively. The PLA2R-IgG4/PLA2R-IgG ratio was significantly positively correlated with serum albumin (r = 0.26, p = .005) but inversely correlated with both the intensity of glomerular IgG1 (r = -0.20, p = .03) and IgG3 deposits (r = -0.24, p = .009), as well as with C1q staining intensity (r = -0.27, p = .004). The median PLA2R-IgG4/PLA2R-IgG ratio significantly increased with pathological stage (Stage I: 18.92%; Stage II: 39.74%; Stage III: 59.38%; Stage IV: 68.99%) and was strongly positively correlated with EM stage (r = 0.52, p < .001). Advanced EM stages were observed more frequently with higher PLA2R-IgG4/PLA2R-IgG ratio.

Conclusions: During the disease progression, EM stages were correlated with altered autoantibody IgG subclass profiles: early stages featured IgG1 or IgG3 autoantibodies, while late EM stages shifted to IgG4 predominance.

Background: Transbronchial cryobiopsy (TBCB) is a minimally invasive technique that yields larger specimens than conventional transbronchial forceps biopsies (TBFB) and demonstrates superior diagnostic rates for interstitial lung diseases. However, the efficacy of TBCB compared to TBFB in evaluating peripheral pulmonary lesions (PPLs) is not well established. This study aims to examine the diagnostic performance of TBCB relative to TBFB in PPLs.

Material and methods: Between May 2021 and December 2023, patients with PPLs were enrolled and underwent TBFB followed by TBCB. These procedures were performed either in a hybrid operating room (HOR) or a standard bronchoscopy room without fluoroscopy. The study compared histopathology diagnostic yield between the two methods.

Results: The study included 84 patients. The median lesion size was 37 mm (interquartile range: 26, 54), with 16 lesions (19.0%) measuring less than 2.0 cm. Among the participants, 44 (52.4%) were diagnosed with lung cancer, and 28 (33.3%) had infectious diseases. TBCB yielded significantly larger tissue samples [60 mm³ (range: 30, 144) vs. 4 mm³ (range: 2, 6), p < 0.001] and higher diagnostic yields (94.0% vs. 77.1%, p < 0.001) than TBFB. The higher diagnostic yield for TBCB were consistent in both the bronchoscopic room (97.2% vs. 77.8%, p = 0.008) and HOR (91.5% vs. 76.6%, p = 0.033). The incidence of ≥ grade 3 bleeding was 7.1%.

Conclusion: TBCB significantly improves the diagnostic yield for PPLs, irrespective of fluoroscopic guidance, and is effective for both malignant and benign lesions. Furthermore, it is associated with minimal complications, affirming its safety and efficacy as a diagnostic procedure.HighlightsTBCB consistently provided a higher pathological yield compared to TBFB, independent of lesion size, use of fluoroscopy, or the nature of the pathology (benign or malignant)TBCB yielded larger tissue sample and had high successful rates for NGS testing.Combination of an ultrathin bronchoscope, augmented fluoroscopy, ROSE, and TBCB can lead to high diagnostic yields.

Background: Pediatric sepsis represents a significant factor in the mortality rates among children, with survivors remaining highly fragile during the period following discharge. While in-hospital and short-term mortality have been widely studied, the long-term mortality of pediatric sepsis is not adequately synthesized or appreciated. This study aims to estimate the long-term mortality associated with pediatric sepsis, providing a basis for optimizing post-discharge surveillance and care protocols.

Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251137504). Exhaustive searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published from the inception of each database to June 30, 2025. Studies reporting long-term mortality in pediatric sepsis patients diagnosed using international consensus criteria were included. After literature screening, long-term mortality was pooled using a random effects meta-analysis in R statistical software.

Results: A total of 72,065 records were identified through database searching. After removing duplicates and screening, six studies comprising 11,318 pediatric sepsis patients were included. The pooled long-term mortality in pediatric sepsis was 11% (95% CI: 7-16%), though significant heterogeneity was observed (I² = 98.2%, p < 0.001). Sensitivity analyses yielded similar results, and evidence of publication bias was limited.

Conclusion: Long-term mortality after pediatric sepsis was 11%, highlighting the persistent risk of mortality after hospital discharge. Further high-quality longitudinal studies are required to identify modifiable risk factors and guide evidence-based follow-up and personalized care.