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BackgroundThe underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability.MethodsTBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes.ResultsA total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2–22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06–2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42–5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11–2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68–4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06–0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50–2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19–2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98–4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82–35.12) for meningeal enhancement and 3.39% (95% CI, 1.22–6.91) for hydrocephalus.ConclusionNeuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

BackgroundThe prevalence and prognostic significance of malnutrition risk remain unclear in Chinese patients with pulmonary tuberculosis. Therefore, we aimed to investigate the malnutrition risk in Chinese patients and explore the relationship between malnutrition risk and follow-up outcomes.MethodsWe conducted a hospital-based cohort study from January 2020 to December 2020. Malnutrition risks were evaluated using nutritional scales, including the Nutritional Risk Screening 2002 (NRS-2002), the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI). The primary outcome was all-cause mortality at a one-year follow-up. Malnutrition risk was calculated, and the relationship between malnutrition and follow-up outcomes was analyzed. We assessed the performance of malnutrition risks to predict clinical outcomes in prognostic models.ResultsA total of 1,075 patients were included. According to NRS-2002, CONUT, GNRI, and PNI, 818 (76.09%), 954 (88.74%), 682 (63.44%), and 364 (33.86%) patients were at risk of malnutrition, respectively. Before 1-year follow-up, a total of 99 patients (9.2%) had died. After adjustment for risk factors, the association between severe malnutrition in CONUT (HR = 4.78, 95% CI: 1.14–20.11, P = 0.033), GNRI (HR = 3.53, 95% CI: 1.70–7.34, P = 0.001), or PNI (HR = 2.94, 95% CI: 1.76–4.88, P < 0.001) and death before 1-year follow-up remained significant. The addition of the nutritional scales to prognostic models improved death prediction, as validated by the integrated discrimination index (all P-values of

Abstract Background In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. Methods All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events. Results Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P

Abstract Background The outcomes of immediate autologous breast reconstruction (IABR) after partial mastectomy followed by postoperative radiotherapy (RT) in terms of aesthetics, treatment-related complications, and local control are unclear. In this study, we evaluated the efficacy of IABR after partial mastectomy with or without breast RT, and thus the impact of radiation on autologous flap transfer. Method A retrospective cohort study involving consecutive breast cancer patients who underwent IABR after partial mastectomy between July 2011 and December 2017 at Shengjing Hospital was performed. Patients were divided into two groups based on whether or not they received RT after IABR. We compared aesthetic outcomes and changes in the flap size over the three-dimensional coordinates at various timepoints (pre-RT, 1, 6, and 12 months post-RT), as well as postoperative complications, survival, and recurrence rates between the two groups. Results In total, 84 breast cancer patients were enrolled, with 32 patients in the RT group and 52 in the non-RT group. At a median follow-up time of 33.3 months, no significant difference was found in the rate of regional recurrence between the two groups (3.13% vs. 3.85%, P = 1.00), and no local recurrences occurred in either group. At the timepoints pre-RT, 1, and 6 months post-RT (approximately 4, 7, and 12 months after IABR, respectively), 77 (91.7%), 70 (83.3%), and 83 (98.8%) patients, respectively, had achieved very good or good cosmetic outcomes, and only changes in breast skin color at 1 month after RT significantly differed between the RT and non-RT groups, with very good or good cosmetic result rates of 62.5% vs. 96.2%, respectively (P 0.05). Additionally, no grade 3 or greater RT-associated adverse events occurred during or after RT. Conclusion RT following IABR provides aesthetically satisfactory results without intolerable adverse complications and may safely be performed in patients who underwent IABR after partial mastectomy.

PurposeThe role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for patients with EGFR-mutant non-small cell lung cancer (NSCLC) has not been clarified. A pooled analysis of prospective clinical trials was conducted to evaluate the efficacy and safety of neoadjuvant EGFR-TKI therapy.MethodsThe PubMed, Embase, Web of Science, and Cochrane Library databases, as well as meeting abstracts were searched for prospective clinical trials evaluating the efficacy and safety of neoadjuvant EGFR-TKI for treatment of EGFR-mutant NSCLC. The main outcomes included the objective response rate (ORR), downstaging rate, surgical resection rate (SRR), pathologic complete response (pCR) rate, progression-free survival (PFS), and adverse events.ResultsA total of five, phase II, prospective, clinical trials involving 124 patients with resectable or potentially resectable EGFR-mutant NSCLC treated with neoadjuvant erlotinib or gefitinib treatment were included in this pooled analysis. The median neoadjuvant medication time was 42 (range, 21–56) days and the median time of response evaluation was 45 (range, 42–56) days. The pooled ORR was 58.5% [95% confidence interval (CI), 45.5%–71.8%] and the surgical resection and complete resection (R0) rates were 79.9% (95% CI, 65.3%–94.5%) and 64.3% (95% CI, 43.8%–84.8%), respectively. In the stage IIIA subgroup (n = 68), the pooled ORR, SRR, and R0 rate were 51.4%, 72.9%, and 57.0%, respectively, while the downstaging and pCR rates were 14.0% and 0.0%, respectively. The pooled median PFS and overall survival were 13.2 and 41.9 months, respectively. Of the most common grade 3/4 adverse events in the overall group, the incidences of hepatotoxicity and skin rash were 5.3% and 14.7%, respectively. The most commonly reported postoperative complications were lung infection, arrhythmia, and pneumothorax.ConclusionNeoadjuvant EGFR-TKI therapy provides a feasible treatment modality for patients with resectable or potentially resectable EGFR-mutant NSCLC, with satisfactory surgical outcomes and low toxicity. Although further phase III clinical trials are needed to confirm these findings, it is necessary to explore the feasibility of a more effective EGFR-TKI combination neoadjuvant therapy given the modest downgrade and pCR rates for EGFR-TKI alone.

CD4+ T-cell differentiation plays an important role in allergic airway diseases. Tumor necrosis factor receptor 2 (TNFR2) has been shown to regulate CD4+ T-lymphocyte differentiation, but its role in allergic airway inflammation is not clear. Here, we investigated the role of TNFR2 in allergic airway inflammation. The mouse model was generated by immunization with ovalbumin and intranasal administration of TNFR2 antibody. Airway inflammation and CD4+ T-cell differentiation were measured in vivo and in vitro. Inhibited TNFR2 signaling aggravated airway inflammation and increased the expression of inflammatory cytokines (IL-4, IL-5, IL-17, and TNF-α) in serum and bronchoalveolar lavage fluid. Impaired TNFR2 signaling promoted Th2 and Th17 polarization but inhibited Th1 and CD4+CD25+ T-cell differentiation in vivo. Furthermore, TNFR2 signaling inhibition promoted Th2 and Th17 polarization in vitro, which may occur through the activation of TNF receptor-associated factor 2 and NF-κB signaling. Therefore, our findings indicate that impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Early administration of antiplatelet agents in acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) is a potential therapeutic strategy, however, safety and efficacy are not well established. We hypothesize that antiplatelet pretreatment (AP) before IVT have a similarly role as initiation of AP within the first 24 hours following IVT. We aimed to explore the effect of AP on platelet aggregation and clinical outcomes in thrombolysis-treated AIS patients. We enrolled AIS patients treated with IVT at the Neurology Department of the Nanjing First Hospital from January 2016 to June 2018. Prior use of antiplatelet agent was recorded. Light transmittance aggregometry was used to estimate the maximum platelet aggregation (MPA). Linear regression model was performed to investigate the factors associated with MPA. Multivariate logistic regression was used to analyse the association between AP and clinical outcomes. A total of 59 patients were included; 23 (38.9 %) were taking antiplatelet agent before stroke. Prior AP (β = -20.209, SE mean=6.574; P=0.004) was significantly lower the arachidonic acid-induced MPA at the time point of 3h after thrombolysis. AP did not increase of the risk for sICH (OR=3.41, 95%CI 0.16-7.20, p=0.436) or mortality (OR=3.55, 95%CI 0.39-8.52, p=0.260). There were no associations between AP and improved clinical outcomes (all P>0.05). In thrombolysis-treated AIS patients, AP was associated with lower MPA after thrombolysis. AP is safe in these patients, however, further studies are required to confirm the efficacy.