Postgraduate medicine最新文献

Objectives: This study evaluated the effectiveness and safety of maintenance therapy with capecitabine ± bevacizumab in Vietnamese patients with mCRC after disease control following first-line chemotherapy.

Methods: A retrospective cohort study was conducted at Vietnam National Cancer Hospital (March - May 2025). Eligible patients had mCRC, achieved response or stable disease after CAPOX plus bevacizumab, and received maintenance capecitabine alone or with bevacizumab. The primary endpoint was progression-free survival (PFS). Safety was assessed using CTCAE v5.0. Kaplan - Meier and Cox regression analyses were performed.

Results: Among 148 patients, 54 (36.5%) received capecitabine alone and 94 (63.5%) received bevacizumab - capecitabine. Baseline characteristics were balanced. Median PFS was 9.9 months (95% CI: 7.5-12.4) with bevacizumab - capecitabine vs. 5.8 months (95% CI: 4.3-7.4) with capecitabine alone (HR = 0.477, p = 0.001). Multivariable analysis showed that bevacizumab use (HR = 0.384, p = 0.001), achieving CR/PR after induction (HR = 0.416, p = 0.003), and absence of peritoneal metastases (HR = 1.758, p = 0.046) were independently associated with improved PFS. Both regimens were well tolerated, with no treatment-related deaths. The most common toxicity was hand - foot syndrome (27.7% vs. 25.9%). Hypertension and rare events (GI perforation, thrombosis) occurred only in the bevacizumab group but were infrequent. Grade 3-4 adverse events were uncommon and manageable.

Conclusions: In this first real-world study from Vietnam, maintenance therapy with bevacizumab plus capecitabine significantly improved PFS compared to capecitabine alone, with acceptable safety. These findings support the use of biologic-based maintenance strategies in appropriate patients and provide valuable evidence for guiding mCRC treatment in resource-constrained settings.

Background: Microvascular dysfunction (MD) is advocated as one of the main pathogenic mechanisms of Takotsubo syndrome (TTS). Several studies investigated MD in TTS using different techniques; however, no systematic review of these data is currently available.

Methods: We searched the main scientific database (Embase, Medline, Scopus, PubMed) for articles written in English language using the following keywords: ('takotsubo' OR 'broken heart' OR 'apical ballooning' OR 'stress cardiomyopathy') AND ('microvascular'). Case reports: studies not performed in human subjects or investigating microvascular function in organs other than the heart were excluded.

Results: 35 studies matched the inclusion criteria. Microvascular function was assessed by standard coronary angiography-derived indexes (n = 17), invasive measurement (n = 10, index of microcirculatory resistance (IMR) in n = 7), echocardiography (n = 5), nuclear medicine (n = 3), and cardiac magnetic resonance imaging (CMR) in n = 2, with some studies applying more than 1 technique. When established cutoff values were used, MD prevalence largely varied (35% to 100%). Although comprehensive clinical correlates were scarcely reported, MD was consistently associated with higher systolic impairment. Blood-based inflammatory biomarkers analysis was performed in one study only, providing inconclusive results. Clinical outcomes associated with MD were reported in four studies including higher rates of major cardiovascular events and long-term mortality.

Conclusions: MD in TTS has a variable prevalence. It is absent in a relevant proportion of the cases, making it questionable as it should be considered a pre-requisite for disease onset. The presence and extent of MD in TTS is a promising prognostic marker; no data in humans currently confirm its role as a therapeutic target.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most globally prevalent chronic liver disorder. Thus, this study aimed to evaluate the association of serum endocan and endoglin levels with fibrosis severity in patients with MASLD.

Methods: In the study, between December 2023 and November 2024, 58 MASLD patients and 30 healthy controls were enrolled; sample size was based on a power analysis. Vibration-controlled transient elastography, reporting controlled attenuation parameter, and liver stiffness in kilopascals was used to quantify hepatic steatosis and fibrosis, and serum endocan and endoglin levels were measured. Comparisons were made between the MASLD and control groups, and within the MASLD group between patients with advanced-stage fibrosis versus those with lower-stage fibrosis. Discriminative ability of the biomarkers was evaluated by receiver operating characteristic (ROC) analysis. Independent associations between serum biomarkers and kilopascals values in the patient group were assessed by regression analysis.

Results: Serum endocan and endoglin were significantly elevated in the MASLD group compared with controls. In the MASLD group, patients with advanced fibrosis exhibited higher endocan and endoglin levels than those with lower-stage fibrosis. In ROC analysis for discriminating advanced fibrosis, endoglin demonstrated strong discriminative ability and endocan exhibited good accuracy for fibrosis assessment. Multivariate regression analysis revealed that log-transformed kilopascals values were independently associated with serum endocan and endoglin.

Conclusion: Endoglin and endocan are promising, accessible noninvasive biomarkers that may support fibrosis triage and referral decisions in general internal medicine for MASLD. Prospective validation is warranted.

Objective: To investigate the value of sex differences in baseline CT-derived body composition parameters for predicting the interim efficacy of the R-CHOP regimen in DLBCL patients.

Methods: We retrospectively included DLBCL patients who received R-CHOP and pre-treatment CT (January 2015-August 2023). Gender-stratified analysis compared L1-L5 visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle (SM) volumes, alongside L3 area measurements. Multivariate logistic regression identified sex-specific predictors of poor efficacy, visualized using nomograms.

Results: A total of 169 patients were divided into remission (n = 129) and non-remission (n = 40) groups. In males, VAT volume (p = 0.004) and SAT volume density (p = 0.002) were independent risk factors for poor efficacy, while SM volume (p = 0.023) was the key risk factor for females. Gender-specific nomograms were developed for outcome predictionand were then utilized to achieve accurate prediction of treatment outcomes for four patients with varying body composition. No significant association was found between body composition areas and Chemotherapy efficiency (p > 0.05).

Conclusions: Increased VAT volume and SAT volume density are linked to poor efficiency in male DLBCL patients, while increased SM volume relates to poor outcomes in females. Sex differences in body composition play a crucial role in personalized DLBCL treatment.

Objectives: Heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) frequently coexists with atrial fibrillation (AF), leading to worse prognosis and greater therapeutic complexity. Although beta-blockers (BBs) are a cornerstone of HF treatment, their benefit in patients with AF remains unclear.

Methods: We analyzed 1088 patients with stable chronic HF and left ventricular ejection fraction < 50% enrolled in the multicentre FAR NHL registry. Patients were stratified by the presence of AF and achieved BB dose: low ( < 25%), medium (25-49%), or high (≥50% of target). The primary endpoint was a composite of all-cause mortality, hospitalization for acute HF, left ventricular assist device (LVAD) implantation, or heart transplantation.

Results: AF was present in 379 patients (34.5%). BBs were prescribed to 94% of patients, but only 17% achieved high-dose therapy. The event rate was higher in AF patients (28.0%) than in those without AF (20.5%, p = 0.005). High BB dose was independently associated with a lower risk of the primary endpoint (HR 0.62, 95% CI 0.48-0.80; p < 0.001), consistently across both rhythm group.

Conclusion: Higher BB doses were associated with improved outcomes in patients with chronic HF, regardless of AF status. These real-world data support up-titration of BBs as a key component in optimized guideline-directed therapy, even in patients with coexisting AF.

Background: Chemotherapy-induced myocarditis (CIM) is a rare but life-threatening complication with limited guidelines regarding venoarterial extracorporeal membrane oxygenation (VA-ECMO) as salvage therapy.

Case report: We present the case of a 32-year-old female with metastatic thymoma who developed fulminant CIM following paclitaxel-based chemotherapy. Despite aggressive multimodal immunosuppressive therapy, she progressed to refractory cardiogenic shock and pulseless ventricular tachycardia, necessitating emergent VA-ECMO. Hemodynamic stability was achieved, and she was successfully decannulated after a period of support with signs of improving cardiac function. However, she suffered a sudden cardiac arrest due to ventricular fibrillation shortly after decannulation. Although return of spontaneous circulation (ROSC) was achieved, life-sustaining therapies were subsequently withdrawn per family's decision in light of the grave prognosis.

Conclusions: This case demonstrates that VA-ECMO can serve as a crucial salvage bridge in fulminant CIM. However, it starkly highlights the precarious nature of recovery. The fatal arrhythmia post-decannulation underscores that the resolution of life-threatening electrical instability may lag significantly behind the recovery of systolic function, a critical learning point for managing such cases. This dissociation, combined with the unique challenges in immunocompromised oncology patients, demands meticulous patient selection, prolonged post-weaning monitoring, and proactive multidisciplinary decision-making.

Background: Sepsis is a major health concern with high mortality, which is associated with immunosuppression. CD28, a co-stimulatory molecule on T lymphocytes, promotes T cell proliferation, survival, and cytokine production. CD4⁺CD28⁺ T cells play an important role in immune activation and regulation. This study aimed to determine whether CD4⁺CD28⁺ T lymphocytes were associated with 28-day mortality in patients with sepsis.

Methods: A retrospective analysis was performed in 80 adult patients with sepsis admitted to the department of intensive care unit. Peripheral blood CD4⁺CD28⁺ T cells were measured within 24 h of admission using flow cytometry. Independent predictors of 28-day mortality were identified using univariate and multivariate Cox regression analyses.

Results: In total, 80 patients with sepsis were included, of whom 15 (18.8%) died within 28 days. Most patients were older than 60 years (56/80, 70.0%) and male (52/80, 65.0%). The predominant sources of infection were the lung (47/80, 58.8%) and abdomen (28/80, 35.0%), with bacteria being the most common pathogens (68/80, 85.0%). Compared to non-survivors, survivors had lower Sequential Organ Failure Assessment (SOFA) scores, lower rates of septic shock and acute kidney injury (AKI), a higher proportion of CD4⁺CD28⁺ T cells > 75.9%, and a lower proportion of CD8⁺ CD28⁺ T cells ≤39.9%. Receiver operating characteristic analysis depicted that CD4⁺CD28⁺ T cells (cutoff value was 75.9%) showed an area under the curve of 0.732, a sensitivity of 66.67%, and a specificity of 80.00%. The Kaplan-Meier analysis demonstrated significantly better survival in patients with CD4⁺CD28⁺ T cells > 75.9% than in those with ≤75.9%. In univariate Cox regression analysis, SOFA score ≥6, septic shock, AKI, CD8⁺CD28⁺ T cells ≤39.9%, and CD4⁺CD28⁺ T cells ≤75.9% were associated with 28-day morality in patients with sepsis. Multivariate Cox analysis indicated that SOFA score ≥6, AKI, and CD4⁺CD28⁺ T cell ≤75.9% were independent risk factors for 28-day morality of sepsis patients.

Conclusion: A low percentage of CD4⁺CD28⁺ T lymphocytes (≤75.9%) is an independent risk factor for 28-day mortality in patients with sepsis.

Objective: This study aimed to evaluate the progression rate of undifferentiated connective tissue disease (UCTD) to defined CTDs by applying two sets of UCTD criteria alongside the most recent CTD classification criteria.

Methods: A retrospective review was conducted on 1342 patients who underwent antinuclear antibody (ANA) testing at a rheumatology outpatient clinic between February 2021 and February 2023. UCTD was defined in patients exhibiting autoimmune features without meeting criteria for a specific CTD. Patients were categorized into two groups: (1) ANA-positive with disease duration ≥3 years (Mosca) and (2) positive finding for at least one of the following serological markers (ANA, rheumatoid factor, anti-scl 70, SS-A or SS-B, Jo-1 antibody, sedimentation rate (two times normal), C-reactive protein) in the absence of infection, regardless of disease duration (Kinder).

Results: A total of 119 patients with UCTD (95% women) were evaluated, with a median follow-up time of 34.1 (IQR: 21.4-52.7) months. Sixteen patients (13%) progressed to defined CTDs or rheumatoid arthritis (RA): primary Sjögren's syndrome (n = 7), RA (n = 5), systemic sclerosis (n = 3), and systemic lupus erythematosus (n = 1). The median time for evolution was 34.8 (IQR: 17.9-54.8) months. Approximately half of the patients met either set of UCTD criteria. There was no difference in either the progression rate (12.1% vs. 14.8%, p = 0.81) or the time to classification as CTD or RA [28.2 (11.7-39.9) vs. 39.2 (24.6-67.4) months, p = 0.14] when using the Kinder or Mosca criteria.

Conclusion: Application of the most recent CTD classification criteria revealed a 13% progression rate from UCTD to defined CTDs or RA during a three-year median follow-up. In patients with suspected CTD, evaluation of serological markers beyond ANA may contribute to the diagnosis of UCTD. The establishment of standardized definitions for UCTD is essential to improve the methodological consistency of future studies and to facilitate more accurate prognostic assessments.

Objectives: Recent studies have suggested that serum 25-hydroxyvitamin D₃ (s25-OHD₃) may modulate immune responses in allergic diseases. However, the relationship between s25-OHD₃ levels, allergic rhinitis (AR) severity, and allergen sensitization remains unclear. This study aimed to investigate the association between s25-OHD₃ levels and AR severity, including the potential role of allergen sensitization.

Methods: This retrospective study, conducted at Ankara Bilkent City Hospital between 2019 and 2024, included 343 children with AR aged 2 to 18 years. Patients were evaluated for s25-OHD₃ levels, allergen sensitization (via skin prick test and/or serum-specific IgE), and clinical characteristics. AR severity was classified according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, and clinical response to vitamin D supplementation was reassessed after 12 weeks. Risk factors for increased AR severity were identified by regression analysis.

Results: The median s25-OHD₃ level was 16.0 ng/mL (IQR: 10.8-22.0). An inverse correlation was observed between age and s25-OHD₃ levels (r_s = -0.202, p < 0.001). Lower s25-OHD₃ levels were significantly associated with greater AR severity (p < 0.001). Additionally, patients with concomitant allergic diseases - particularly those with allergic conjunctivitis, asthma, and atopic dermatitis - had significantly lower s25-OHD₃ levels (p = 0.004, p = 0.032, and p = 0.042, respectively). Notably, sensitization to cat dander was also associated with reduced s25-OHD₃ levels (p = 0.043). Multivariable regression analysis identified lower s25-OHD₃ levels, coexisting allergic conjunctivitis, pollen sensitization, and polysensitization as independent risk factors associated with increased AR severity. Furthermore, a significant reduction in AR severity was observed following vitamin D supplementation (p < 0.001).

Conclusion: This study underscores the impact of s25-OHD₃ deficiency on the severity of AR and highlights the importance of evaluating s25-OHD₃ levels in the management of pediatric AR to support the development of targeted therapeutic approaches.