Postgraduate medicine最新文献

Chimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment landscape for hematologic malignancies. Although CAR-T cell therapy was traditionally administered in inpatient settings due to concerns related to acute toxicities, there is a growing trend toward outpatient administration. This review looks at the critical aspects of CAR T-cell therapy in outpatient settings, focusing on benefits, feasibility, limitations, and prospects. Implementation of careful selection criteria for outpatient therapy is found to achieve comparable efficacy and safety as in inpatient settings, particularly when supported by robust monitoring and rapid response protocols. Two major potential side effects of CAR-T cell therapy, namely, Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which appear to be key concerns related to outpatient administration, are discussed. Outpatient administration significantly lowers healthcare system costs, improves resource allocation, and, more importantly, increases patient psychological well-being. Despite these compelling factors, the outpatient model is not without risks and limitations, particularly necessitating comprehensive support strategies to ensure equitable and timely access and a specialized team of staff and resources for monitoring and timely management of the toxicity of CAR T-cell therapy. Continued development in CAR-T product design and remote monitoring technologies is of crucial importance to further establish and implement outpatient CAR-T therapy as a standard of care, expanding its reach and impact.

Objectives: The impact of short-chain fatty acids (SCFAs) on kidney outcomes in individuals with Type 2 diabetes (T2D) is not clearly understood. This prospective study aimed to investigate the relationship between serum SCFA levels and adverse kidney outcomes in T2D patients.

Methods: T2D patients were recruited between October 2016 and June 2020 and followed until December 2021. The serum levels of nine SCFAs were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were defined as a doubling of serum creatinine levels or progression to end-stage kidney disease (ESKD). Secondary outcomes included an annual decline in estimated glomerular filtration rate (eGFR) of more than 5 ml/min/1.73 m² or a rapid 25% reduction in eGFR during the follow-up period.

Results: The mean age of the 480 T2D participants was 62.0 years. The individuals in highest tertile of serum propionate (>18.91 μM), butyrate (>8.90 μM), and formate (>163.34 μM) levels were significantly associated with lower risk of experiencing a doubling of serum creatinine or progression to ESKD compared to those in the combined lower tertiles of serum propionate, butyrate and formate levels (adjusted hazard ratio (HR)=0.13, 0.20, 0.26, respectively). Adjusted logistical analysis showed that the individuals in highest tertile of serum propionate, butyrate, formate, and valerate (>3.93 μM) levels were significantly associated with lower risk for eGFR decline > 5 ml/min/1.73 m² per year compared to those in the combined lower tertiles of serum propionate, butyrate, formate, and valerate levels (adjusted odds ratio (OR)=0.38, 0.41, 0.46, 0.42, respectively).

Conclusions: Higher circulating levels of SCFAs, particularly propionate, butyrate, and formate, are associated with a substantially lower risk of kidney outcomes in T2D population. These SCFAs may serve as indicative biomarkers for kidney function deterioration in T2D individuals.

Background: Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein linked to atherosclerotic cardiovascular disease (CVD). Although well studied in adults, its familial determinants in children remain unclear. This systematic review and meta-analysis quantified Lp(a) across pediatric subgroups defined by familial cardiovascular risk, familial hypercholesterolemia (FH), sex, and ethnicity.

Methods: Following PRISMA 2020 guidelines, fifty-one observational studies were analyzed using random-effects models (Review Manager 5.4.1). Mean differences (MD) with 95% confidence intervals (CI) were calculated. Subgroup, sensitivity, and meta-regression analyses explored heterogeneity.

Results: Among children and adolescents with FH, those with a parental history of premature cardiovascular disease (pCVD) had significantly higher Lp(a) concentrations than FH children without parental pCVD (MD = 10.24 mg/dL; 95% CI 3.06-17.43; p = 0.005; I² = 79%). In otherwise healthy children, parental pCVD was similarly associated with elevated Lp(a) levels (MD = 11.88 mg/dL; p = 0.005). When parental CVD was considered, healthy offspring of affected parents also showed significantly higher Lp(a) concentrations (MD = 7.00 mg/dL; 95% CI 4.45-9.55; p < 0.00001; I² = 93%). Direct comparison between FH children and healthy controls demonstrated a modest but significant elevation in FH (MD = 1.31 mg/dL; 95% CI 0.19-2.44; p = 0.02; I² = 74%). Girls exhibited slightly higher Lp(a) levels than boys (MD =  -1.48 mg/dL; 95% CI - 2.52 to -0.43; p = 0.006), with minimal pubertal influence.

Conclusion: Elevated Lp(a) in children with parental CVD or pCVD reflects a strong heritable pattern from early life. FH was associated with modest but consistent Lp(a) elevation, indicating an independent risk-modifying role rather than a defining feature. Sex-related differences were minimal, whereas ethnic variation was prominent. These findings support targeted Lp(a) assessment in children with familial cardiovascular risk using ancestry-aware reference standards, with consideration of repeat evaluation in early adulthood in higher-risk individuals.

Background: Periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty (TJA), with traditional risk factors including diabetes and obesity. Emerging evidence suggests functional gastrointestinal disorders (FGIDs) may influence systemic inflammation and infection susceptibility. This study investigated whether preexisting FGIDs are independent risk factors for PJI.

Methods: A retrospective 1:1 matched case-control study analyzed 896 patients (448 PJI vs. 448 non-PJI) undergoing primary TJA (2013-2023). PJI was diagnosed using modified 2018 Musculoskeletal Infection Society criteria, and FGIDs (irritable bowel syndrome [IBS], functional diarrhea [FD], functional constipation [FC]) were classified per Rome IV criteria. Multivariable logistic regression identified PJI risk factors after adjusting for demographics, comorbidities, and surgical variables.

Results: Univariate analysis revealed significantly higher FC prevalence in PJI cases (14.3% vs. 8.3%, p = 0.0043), while IBS and FD showed no association. Multivariate analysis confirmed FC as an independent PJI risk factor (odds ratio [OR] = 1.844, 95% confidence interval [CI]:1.199-2.872, p = 0.0059), alongside diabetes (OR = 1.714, 95%CI:1.116-2.661, p = 0.0148), and surgery duration >2 hours (OR = 2.220, 95%CI:1.242-4.125, p = 0.0088). Perioperative antibiotic usage reduced PJI risk (OR = 0.405, 95%CI:0.232-0.686, p = 0.0010).

Conclusion: Functional constipation was identified as a novel independent risk factor for PJI, alongside established metabolic comorbidities and prolonged surgery. These findings underscore the gut-joint axis in PJI pathogenesis and advocate integrating FGID screening into preoperative risk stratification. Antibiotic prophylaxis remains critical for minimizing infection risk in TJA patients.

Background: This study investigates obstetric outcomes and factors influencing preterm birth among Chinese-American and American Indian or Alaskan Native women to address the gap in knowledge and inform targeted interventions.

Methods: A retrospective cohort study was conducted using 2022 data from the National Vital Statistics System (NVSS), covering 50 U.S. states and the District of Columbia. The study included 40,983 Chinese-American and 35,648 AIAN women aged ≥18 years. Based on gestational age(GA), preterm birth was defined as extremely preterm birth (GA <27^6/7 weeks), very preterm birth (GA 28^0/7 to 31^6/7 weeks), moderately preterm birth (GA 32^0/7 to 33^6/7 weeks) and late preterm infants (GA 34^0/7 to 36^6/7 weeks). Bivariate analyses and multivariable logistic regression were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for preterm birth predictors.

Results: The preterm birth prevalence was 7.56% in Chinese-American women (5.86% late preterm) and 12.09% in AIAN women (8.98% late preterm). In both groups, preterm birth was associated with higher rates of adverse infant outcomes (low birth weight, NICU admission, surfactant therapy) and maternal complications. For Chinese-American women, significant risk factors included maternal age ≥35 years (OR = 1.23), weight gain <5.0 kg (OR = 1.67), chronic hypertension (OR = 3.18), gestational hypertension (OR = 2.58), previous preterm birth (OR = 3.96), infertility treatment (OR = 1.30), and multiple pregnancies (OR = 21.17); protective factors included higher education (e.g. master's degree: OR = 0.73), prenatal care (OR = 0.54), and weight gain ≥13.6 kg (OR = 0.52). For AIAN women, key risk factors included age ≥35 years (OR = 1.27), weight gain <5.0 kg (OR = 1.39), chronic hypertension (OR = 2.85), gestational hypertension (OR = 2.79), previous preterm birth (OR = 3.30), and multiple pregnancies (OR = 16.18); protective factors included prenatal care (OR = 0.37) and weight gain ≥13.6 kg (OR = 0.67).

Conclusions: Preterm birth disparities exist between Chinese-American and AIAN women, with shared and population-specific risk/protective factors. Routine practice should prioritize targeted monitoring for high-risk groups and promote prenatal care and optimal weight gain.

Objective: P-wave peak time (PWPT), a novel electrocardiographic marker reflecting atrial conduction delay and structural remodeling, has been associated with diastolic dysfunction and elevated left atrial pressure. Albuminuria, a marker of renal microvascular damage, has also been linked to subclinical diastolic dysfunction. This study aimed to investigate whether PWPT is independently associated with albuminuria in hypertensive patients and to assess its potential diagnostic utility.

Methods: A total of 367 hypertensive patients were prospectively enrolled. Patients were categorized into albuminuria-positive (n = 110) and albuminuria-negative (n = 257) groups based on their spot urinary albumin-to-creatinine ratio (UACR). Those with UACR > 30 mg/g were classified as albuminuria-positive, and those with UACR < 30 mg/g were classified as albuminuria-negative. Comprehensive demographic, laboratory, electrocardiographic, and echocardiographic data were collected and compared between the two groups.

Results: PWPT was significantly prolonged in patients with albuminuria (48 ± 11 ms vs. 39 ± 9 ms, p < 0.001). In multivariate analysis, PWPT (OR = 2.688, 95% CI: 1.969-3.672, p < 0.001) remained an independent predictor of albuminuria, along with HbA1c, left atrial volume index, and heart rate. PWPT exhibited the highest discriminatory power among these variables (AUC = 0.771), with a cutoff of >42 ms yielding 76.4% sensitivity and 68.1% specificity.

Conclusion: PWPT is independently associated with albuminuria in hypertensive patients and may serve as a noninvasive marker of early renal microvascular involvement.

Background: Altered mental status (AMS) prompts rapid diagnostic evaluation in hospitalized patients, yet a low-cost, reversible cause - thiamine deficiency - often receives inconsistent attention outside alcohol-associated contexts. Although classically linked to alcohol misuse, contemporary evidence links thiamine depletion to a broad range of medical, surgical, oncologic, obstetric, and critically ill populations.

Discussion: In these settings, AMS may be the earliest clinical manifestation, while standard diagnostic tools such as MRI and serum thiamine levels frequently lack sensitivity early in the disease course. Delayed recognition leads to persistent cognitive and neurologic deficits, despite the safety, low cost, and ready availability of parenteral thiamine. This Perspective highlights why relying on alcohol history alone risks missing high-risk patients, outlines a pragmatic risk-based framework for hospitalists, and identifies key areas for future investigation.

Conclusions: Early empiric thiamine aligns with principles of high-value care and represents a simple, underutilized intervention that may prevent irreversible neurologic injury in hospitalized patients with AMS. Broader adoption of a more inclusive, clinically grounded approach is warranted until higher-quality evidence clarifies optimal screening and treatment strategies.

Objectives: Legionella is a common cause of community-acquired pneumonia and can affect multiple organ systems. An association with rhabdomyolysis and acute kidney injury (AKI) have been noted for several decades, but population-based studies are limited and could aid in better understanding the prevalence, associated risk factors, and clinical significance of this complication.

Methods: We performed a retrospective manual review of the electronic health record on 323 patients with legionellosis identified on the basis of urinary antigen or culture in a large, urban hospital system. Demographic and clinical data were extracted by four physician reviewers. Rhabdomyolysis was assessed on the basis of creatine kinase (CK) values ≥1,000 IU/L or suggestive urinalysis findings. AKI was classified according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Patients were excluded for missing data or potential alternative causes of rhabdomyolysis. Data were analyzed using appropriate parametric and non-parametric statistical tests and multivariate logistic regression analysis.

Results: A total of 210 patients were included in the analysis. Fifty patients (23.8%) had evidence of rhabdomyolysis, 20% of whom had severe rhabdomyolysis (CK ≥15,000 IU/L). Rhabdomyolysis was associated with male sex, black race, and age <65. Common comorbidities were not associated with rhabdomyolysis. Rhabdomyolysis was associated with AKI, including for mild cases (CK 1000-5000 IU/L), with longer hospital length of stay, and with higher likelihood of intensive care unit admission, but not with overall mortality, which was 5.1% in the patient cohort.

Conclusions: Rhabdomyolysis is a common feature of legionellosis, is associated with AKI, and may be a marker of more severe disease.

Objective: To evaluate the effect of lutikizumab intervention on patients with osteoarthritis (OA) and provide an evidence-based reference for the clinical application of lutikizumab intervention in patients with osteoarthritis.

Methods: Literature databases such as PubMed, Embase, web of science, and the Cochrane Library were searched to collect relevant data on randomized controlled trials (RCTs), clinical trials, and single/double arm non-randomized controlled trials studies of therapy interventions for patients with OA, and meta-analysis was performed using RevMan 5.4.

Results: A total of 6 randomized controlled studies were included, including 737 patients with osteoarthritis. Meta-analysis showed that compared with the control group, lutikizumab intervention had more gains, IL-α (0.3 mg/kg, Q2W, week2) (MD = -0.67, 95% CI [-1.25,-0.09]; Z = 2.26; p = 0.02), IL-1β (3 mg/kg,Q2W,week2) (MD = -0.58, 95% CI [-1.14, -0.02]; Z = 2.03; p = 0.04) and hsCRP (200 mg,Q2W,week8) (MD = -1.79, 95% CI [-2.09, -1.50]; Z = 11.80; p < 0.00001).

Conclusion: Reducing the OA process with lutikizumab provides a theoretical basis for further investigation of the function of lutikizumab in patients with OA.IL-1 is not only an inflammatory mediator in osteoarthritis, but also a key molecule connecting biomechanical abnormalities and tissue damage.IL-1 inhibitors precisely regulate the spatiotemporal expression of IL-1, and individualize the biomechanical intervention regimens or combination of multiple interventions to achieve optimal therapeutic effects.