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BACKGROUND: The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. METHODS: Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. RESULTS: The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p < 0.001), while obesity was linked to a 13.9% reduction in mortality risk (p < 0.001). The protective effect of obesity on mortality was similar in patients with (HR = 0.85) and without AF (HR = 0.86). AF led to a slightly higher risk of mortality in patients without obesity (HR = 1.16) compared to those with obesity (HR = 1.13). Kaplan-Meier survival curves highlighted that non-obese patients with AF had the lowest survival rate, whereas the highest survival was observed in obese patients without AF. CONCLUSIONS: AF significantly increased 1-year mortality risk in critically ill patients, whereas obesity was associated with a decreased mortality risk. The most adverse survival outcomes were identified in non-obese patients with AF.
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BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.
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BACKGROUND: Electrocardiogram (ECG) abnormalities indicating right ventricular strain have been reported to have prognostic value in severe cases of acute pulmonary embolism (PE). We aimed to analyze the prognostic significance of other quantitative ECG parameters in non-high-risk acute PE. METHODS: Consecutive patients with non-high-risk acute PE were prospectively enrolled. The following baseline ECG parameters were collected: rhythm, heart rate, QRS axis, right bundle branch block (RBBB) pattern, S1Q3T3 pattern, T-wave inversion, ST-segment elevation, Qr in lead V1, PR Interval, QRS complex duration, QT interval, P-wave amplitude and duration, R- and S-wave amplitudes. The primary endpoint was early discharge within three days. Associations between ECG parameters and early discharge were analyzed. RESULTS: Overall, 383 patients were enrolled (median age: 67 years, 57% female): 277 (72.3%) with low-risk and 106 (27.7%) with intermediate-risk. The two groups of patients differed in several ECG signs of right ventricular strain and many other quantitative parameters like R- and S-wave amplitudes. In the multivariate logistic regression analysis, the S-wave depth in lead V5 (S-V5) was the only independent prognostic factor for early discharge (odds ratio = 0.137, 95% confidence interval = 0.031-0.613, p = 0.009). The optimum cutoff value of S-V5 for predicting early discharge derived from the receiver operative characteristic curve was 0.15 mv (c-statistic = 0.66, p =0.003). CONCLUSIONS: Several ECG signs of right ventricular strain and many other quantitative parameters were associated with disease severity in non-high-risk acute PE. An S-V5 lesser than 0.15 mv was predictive for early discharge in these patients.
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Electrocardiografía , Embolia Pulmonar , Humanos , Femenino , Anciano , Masculino , Pronóstico , Arritmias Cardíacas , Enfermedad Aguda , Embolia Pulmonar/complicacionesRESUMEN
INTRODUCTION: Many clinical studies reported the coexistence of Alzheimer's disease (AD) and multiple sclerosis (MS), but the common molecular signature between AD and MS remains elusive. The purpose of our study was to explore the genetic linkage between AD and MS through bioinformatic analysis, providing new insights into the shared signatures and possible pathogenesis of two diseases. METHODS: The common differentially expressed genes (DEGs) were determined between AD and MS from datasets obtained from Gene Expression Omnibus (GEO) database. Further, functional and pathway enrichment analysis, protein-protein interaction network construction, and identification of hub genes were carried out. The expression level of hub genes was validated in two other external AD and MS datasets. Transcription factor (TF)-gene interactions and gene-miRNA interactions were performed in NetworkAnalyst. Finally, receiver operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of hub genes. RESULTS: A total of 75 common DEGs were identified between AD and MS. Functional and pathway enrichment analysis emphasized the importance of exocytosis and synaptic vesicle cycle, respectively. Six significant hub genes, including CCL2, CD44, GFAP, NEFM, STXBP1, and TCEAL6, were identified and verified as common hub genes shared by AD and MS. FOXC1 and hsa-mir-16-5p are the most common TF and miRNA in regulating hub genes, respectively. In the ROC curve analysis, all hub genes showed good efficiency in helping distinguish patients from controls. CONCLUSION: Our study first identified a common genetic signature between AD and MS, paving the road for investigating shared mechanism of AD and MS.
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Enfermedad de Alzheimer , MicroARNs , Esclerosis Múltiple , Humanos , Enfermedad de Alzheimer/genética , Esclerosis Múltiple/genética , MicroARNs/genética , Biología Computacional , Bases de Datos FactualesRESUMEN
A 49-year-old woman with a rare autoimmune hematological disease, Evans syndrome, was admitted to the authors' hospital with immune reconstitution inflammatory syndrome-like reconstitution syndrome after effective antifungal therapy for cryptococcal meningitis. She initially improved after receiving corticosteroid treatment; after prednisone was tapered, her clinical presentation and brain imaging deteriorated but finally improved with the addition of thalidomide. Immune reconstitution inflammatory syndrome-like reconstitution syndrome is a rare complication in cryptococcal meningitis patients receiving immunosuppressive therapy. Thalidomide can be given in addition to corticosteroid therapy to effectively control the paradoxical inflammatory response and improve clinical outcomes.
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Infecciones por VIH , Síndrome Inflamatorio de Reconstitución Inmune , Meningitis Criptocócica , Humanos , Femenino , Persona de Mediana Edad , Meningitis Criptocócica/complicaciones , Antifúngicos/uso terapéutico , Síndrome Inflamatorio de Reconstitución Inmune/complicaciones , Talidomida/uso terapéutico , Corticoesteroides/uso terapéutico , Infecciones por VIH/complicacionesRESUMEN
BACKGROUND: Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD. METHODS: We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak VÌo2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (VÌe/VÌco2 slope), were recorded. RESULTS: The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak VÌo2 was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak VÌo2 (p = 0.003) and the highest VÌe/VÌco2 slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak VÌo2 (p = 0.003) compared with other patients. Peak VÌo2 was negatively correlated with pulmonary vascular resistance (r = -0.411, p < 0.001). CONCLUSIONS: Exercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.
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Complejo de Eisenmenger , Cardiopatías Congénitas , Insuficiencia Cardíaca , Hipertensión Arterial Pulmonar , Adulto , Humanos , Femenino , Masculino , Estudios Retrospectivos , Hipertensión Pulmonar Primaria Familiar , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Prueba de Esfuerzo , Consumo de OxígenoRESUMEN
Background: The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. Objectives: The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. Methods: In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. Results: A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. Conclusions: Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.
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Background: Chronic calcium channel blockers (CCBs) are indicated in children with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) and positive response to acute vasodilator challenge. However, minimal safety data are available on the long-term high-dose exposure to CCBs in this population. Methods: Patients aged 3 months to 18 years who were diagnosed with IPAH/HPAH and treated with CCB in the past 15 years were retrospectively reviewed. The maximum tolerated dose and the long-term safety of high-dose CCBs on the cardiovascular and noncardiovascular systems were assessed. Results: Thirty-two eligible children were enrolled in the study, with a median age of 9 (6-11) years old. Thirty-one patients were treated with diltiazem after diagnosis. The median maximum tolerated dose was 12.9 (9.8-16.8) mg/kg/day. Children younger than 7 years used higher doses than children in the older age group, 16.4 (10.5-28.5) mg/kg/day vs. 12.7 (6.6-14.4) mg/kg/day, P < 0.05. Patients were followed up for a median period of 6.2 (2.6-10.8) years. One patient died from a traffic accident, and others showed a stable or improved WHO functional class status. Thirteen (40.6%) and 10 (31.3%) patients developed arrhythmias and hypotension. Nine (28.1%) patients had sinus bradycardia, five (21.9%) had first-degree or second-degree type II atrial-ventricular blocks, and two (6.3%) had second-degree type II atrial-ventricular blocks. Most of these arrhythmias were transient and relieved after CCB dose adjustment. The most reported noncardiovascular adverse effect was gingival hyperplasia (13, 40.6%), accompanied by different degrees of dental dysplasia. No liver or kidney dysfunction was reported. Conclusion: Diltiazem was used in a very high dose for eligible children with IPAH/HPAH. The toxicity of long-term CCB use on the cardiovascular system is mild and controllable. Clinicians should also monitor the noncardiovascular adverse effects associated with drug therapy.
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Sparse data are available on the female-specific features of chronic thromboembolic pulmonary hypertension (CTEPH). We prospectively enrolled 160 consecutive female patients who were firstly diagnosed with CTEPH between 2013 and 2019 to explore their clinical phenotypes, treatment patterns, and long-term survival. The patients' mean age was 54.7 ± 13.8 years, 70.6% provided a confirmed history of venous thromboembolism, 46 (28.8%) patients underwent pulmonary endarterectomy (PEA), 65 (40.6%) received balloon pulmonary angioplasty (BPA), and 49 (30.6%) were treated with medical therapy alone. The patients were followed for a median of 51 (34-70) months; three patients were lost to follow-up, and twenty-two patients died. The estimated survival rates at 1, 3, 5, and 7 years were 98.1% (95% CI 96.0-100), 96.9% (95% CI 94.2-99.6), 85.1% (95% CI 78.1-92.2), and 76.2% (95% CI 65.2-87.2), respectively. After adjusting for the confounders, the results of the multivariate Cox analysis showed that the presence of anemia (5.56, 95% CI 1.6-19.22) was associated with an increased risk of all-cause death, and compared with medical treatment, receiving PEA and BPA decreased the risk of death by 74% (0.26, 95% CI 0.07-0.97) and 86% (0.14, 95% CI 0.04-0.57), respectively. In conclusion, in the modern era of CTEPH treatment, invasive revascularization combined with targeted therapy display good clinical outcomes for females; anemia should be actively modified, which may lead to clinical improvements. (ClinicalTrials.gov Identifier: NCT05360992).
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To explore the brain volume (BV) changes of HIV-negative and non-transplant cryptococcal meningitis (CM) in 1 year after initial therapy. Case data were collected from 78 CM patients who underwent magnetic resonance imaging (MRI) scanning at least 3 times in 1-year interval after initial therapy. The assessment of BV was measured by a non-commercial software, uAI Research Portal. Linear mixed model was used to investigate the association between clinical characteristics and the changes in BV. Longitudinal study showed a decrease in total brain volume (-4.65 cm3, P = .005), regional brain volume including white matter (-2.86 cm3, P = .031) and basal ganglia (-0.25 cm3, P = .007), and increase in cerebrospinal fluid (CSF) volume (3.58 cm3, P = .013) in CM patients in 1 year after initial therapy. Ventricular volume in patients with ventriculoperitoneal shunts (VPS) was lower than that in patients without VPS (-7.5 cm3, P < .05). Ventricular volume in patients with post-infectious inflammatory response syndrome (PIIRS) was larger than that in patients without PIIRS (7.1 cm3, P < .01). In addition, temporal lobe atrophy was associated with corticosteroid therapy (-6.8 cm3, P < .01). The present study suggested that brain atrophy, especially regional BV decrease, could happen in HIV-negative and non-transplant CM patients over a 1-year interval.
We investigated the evolution of brain volume changes in different regions among HIV-negative and non-transplant cryptococcal meningitis (CM) patients within 1 year after initial therapy. To assess whether brain atrophy occurs among HIV-negative and non-transplant CM patients.
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Infecciones por VIH , Meningitis Criptocócica , Corticoesteroides/uso terapéutico , Animales , Atrofia/complicaciones , Atrofia/patología , Atrofia/veterinaria , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Infecciones por VIH/complicaciones , Infecciones por VIH/veterinaria , Estudios Longitudinales , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/veterinaria , Estudios RetrospectivosRESUMEN
OBJECTIVES: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM). METHODS: We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China. RESULTS: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p < .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035). CONCLUSIONS: This study demonstrated that species identification helps to guide therapy and predict outcomes.
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Criptococosis , Cryptococcus gattii , Cryptococcus neoformans , Infecciones por VIH , Meningitis Criptocócica , Adulto , Anciano , Criptococosis/microbiología , Cryptococcus gattii/genética , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Meningitis Criptocócica/líquido cefalorraquídeo , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Objective: To explore the comparative clinical efficacy and safety outcomes of anticoagulation before (pre-) or following (post-) thrombolytic therapy in systemic thrombolytic therapy for pulmonary embolism (PE). Methods: PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched from inception through 1 May 2021. All randomized clinical trials comparing systemic thrombolytic therapy vs. anticoagulation alone in patients with PE and those that were written in English were eligible. The primary efficacy and safety outcomes were all-cause mortality and major bleeding, respectively. Odds ratios (OR) estimates and associated 95% confidence intervals (CIs) were calculated. A Bayesian network analysis was performed using R studio software, and then the efficacy and safety rankings were derived. Results: This network meta-analysis enrolled 15 trials randomizing 2,076 patients. According to the plot rankings, the anticoagulant therapy was the best in terms of major bleeding, and the post-thrombolysis anticoagulation was the best in terms of all-cause mortality. Taking major bleeding and all-cause mortality into consideration, the most safe-effective treatment was the post-thrombolysis anticoagulation in patients who needed thrombolytic therapy. The net clinical benefit analysis comparing associated ICH benefits vs. mortality risks of post-thrombolysis anticoagulation demonstrated a net clinical benefit of 1.74%. Conclusion: The systemic thrombolysis followed by anticoagulation had a better advantage in all-cause mortality and major bleeding than the systemic thrombolysis before anticoagulation. The adjuvant anticoagulation treatment of systemic thrombolytic therapy should be optimized.
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BACKGROUND: Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome. CASE PRESENTATION: A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions. CONCLUSIONS: This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging.
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Criptococosis , Cryptococcus neoformans , Meningitis Criptocócica , Meningoencefalitis , Adulto , Antifúngicos/uso terapéutico , Criptococosis/complicaciones , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Humanos , Masculino , Meningitis Criptocócica/complicaciones , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/tratamiento farmacológico , Meningoencefalitis/complicaciones , Síndrome , VoriconazolRESUMEN
BACKGROUND: Cytomegalovirus (CMV) infections in the population are mostly subclinical, inapparent, or latent. However, it is rare in brain tissue. Most reported CMV encephalitis cases were patients with immunodeficiency. The diagnosis and detection rate of CMV encephalitis in patients with normal immune function needs to be further improved. CASE SUMMARY: An 86-year-old male was admitted due to a sudden onset of unconsciousness for 3 h. The patient developed status epilepticus and was relieved after antiepileptic treatment. Encephalitis was considered due to the high signals of diffusion-weighted imaging sequences in the right central region by magnetic resonance imaging. Metagenomic next-generation sequencing (mNGS) of blood and cerebrospinal fluid revealed CMV, with unique reads number being 614 and 1, respectively. Simultaneous quantitative PCR results showed CMV positive in blood samples and negative in cerebrospinal fluid samples. The patient was finally diagnosed as CMV encephalitis with status epilepticus. After the antiviral, hormonal, and γ-globulin pulse therapy, the patient's condition improved, and he was finally discharged. CONCLUSION: mNGS could be a reliable approach for the diagnosis of CMV encephalitis, with high efficiency, sensitivity, and specificity.
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BACKGROUND: Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to Takayasu arteritis-associated pulmonary hypertension (TA-PH), another chronic obstructive pulmonary vascular disease, remains unclear. OBJECTIVES: This study sought to investigate the efficacy and safety of PTPA for TA-PH. METHODS: Between January 1, 2016, and December 31, 2019, a total of 50 patients with TA-PH who completed the PTPA procedure (the PTPA group) and 21 patients who refused the PTPA procedure (the non-PTPA group) were prospectively enrolled in this cohort study. The primary outcome was all-cause mortality. The safety outcomes included PTPA procedure-related complications. RESULTS: Baseline characteristics and medical therapies were similar between the PTPA group and the non-PTPA group. During a mean follow-up time of 37 ± 14 months, deaths occurred in 3 patients (6.0%) in the PTPA group and 6 patients (28.6%) in the non-PTPA group, contributing to the 3-year survival rate of 93.7% in the PTPA group and 76.2% in the non-PTPA group (P = 0.0096 for log-rank test). The Cox regression model showed that PTPA was associated with a significantly reduced hazard of all-cause mortality in TA-PH patients (HR: 0.18; 95% CI: 0.05-0.73; P = 0.017). No periprocedural death occurred. Severe complications requiring noninvasive positive pressure ventilation occurred in only 1 of 150 total sessions (0.7%). CONCLUSIONS: PTPA tended to be associated with a reduced risk of all-cause mortality with acceptable safety profiles and seemed to be a promising therapeutic option for TA-PH patients.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Arteritis de Takayasu , Angioplastia/efectos adversos , Angioplastia/métodos , Estudios de Cohortes , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Estudios Retrospectivos , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/diagnóstico , Arteritis de Takayasu/terapia , Resultado del TratamientoRESUMEN
There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.
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Presión Atrial/fisiología , Reglas de Decisión Clínica , Hipertensión Pulmonar/fisiopatología , Mortalidad , Embolia Pulmonar/fisiopatología , Adulto , Anciano , Anemia/sangre , Anemia/complicaciones , Angioplastia de Balón , Antihipertensivos/uso terapéutico , Índice de Masa Corporal , Enfermedad Crónica , Endarterectomía , Antagonistas de los Receptores de Endotelina/uso terapéutico , Activadores de Enzimas/uso terapéutico , Epoprostenol/análogos & derivados , Femenino , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Péptido Natriurético Encefálico/sangre , Nomogramas , Fragmentos de Péptidos/sangre , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Pronóstico , Modelos de Riesgos Proporcionales , Arteria Pulmonar/cirugía , Embolia Pulmonar/sangre , Embolia Pulmonar/complicaciones , Embolia Pulmonar/terapia , Presión Esfenoidal Pulmonar , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Reproducibilidad de los Resultados , Tasa de SupervivenciaRESUMEN
Depression is a common but serious mental disorder and can be caused by the side effects of medications. Evidence from abundant clinical case reports and experimental animal models has revealed the association between the classic anti-acne drug 13-cis-retinoic acid (13-cis-RA) and depressive symptoms. However, direct experimental evidence of this mechanism and information on appropriate therapeutic rescue strategies are lacking. Herein, our data revealed that chronic administration of 13-cis-RA to adolescent mice induced depression-like behavior but not anxiety-like behavior. We next demonstrated that chronic 13-cis-RA application increased neural activity in the dentate gyrus (DG) using c-Fos immunostaining, which may be critically involved in some aspects of depression-like behavior. Therefore, we assessed electrophysiological functions by obtaining whole-cell patch-clamp recordings of dentate granule cells (DGCs), which revealed that chronic 13-cis-RA treatment shifted the excitatory-inhibitory balance toward excitation and increased intrinsic excitability. Furthermore, a pharmacogenetic approach was performed to repeatedly silence DGCs, and this manipulation could rescue depression-like behavior in chronically 13-cis-RA-treated mice, suggesting DGCs as a potential cellular target for the direct alleviation of 13-cis-RA-induced depression.
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Depresión , Isotretinoína , Animales , Ansiedad , Giro Dentado/fisiología , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Fenómenos Electrofisiológicos , Humanos , Isotretinoína/farmacología , Ratones , NeuronasRESUMEN
The long-term prognosis of patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving different treatments is deserved to be analyzed in modern era of CTEPH treatment. From 2013 to 2019, a total of 364 patients diagnosed with CTEPH were retrospectively included, 14 patients were lost during follow-up. Among 350 patients included in the final analysis: 123 underwent pulmonary endarterectomy (PEA), 121 received balloon pulmonary angioplasty (BPA), and 106 treated with targeted drug alone. The median period of follow-up was 51.2 months, the estimated survival at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% for the whole cohort; 100%, 99.20%, 96.5% and 92.5% in PEA group; 98.4%, 97.4%, 95.3% and 89.3% in BPA group;92.5%, 81.9%, 70.1% and 66.8% in patients who received targeted drug alone. In comparing with targeted treatment along, results of multivariate Cox analysis after adjusting the confounders showed that receiving PEA decreased the risk of death by 83% (HR [hazard ratio] 0.17, 95% CI [Confidence interval] 0.07-0.44) and receiving BPA decreased the risk of death by 89% (HR 0.11, 95% CI 0.04-0.29). In conclusion, the estimated survival of CTEPH patients at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% respectively. The intervention of revascularization, including PEA and BPA, were preferred than treating with targeted drug alone in the view of long-term prognosis of CTEPH.
Asunto(s)
Angioplastia de Balón , Hipertensión Pulmonar , Embolia Pulmonar , Angioplastia de Balón/métodos , Enfermedad Crónica , Endarterectomía/métodos , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/cirugía , Arteria Pulmonar/cirugía , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Estudios RetrospectivosRESUMEN
Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes , Meningitis Criptocócica , Antifúngicos/uso terapéutico , Enfermedades Autoinmunes/complicaciones , Fluconazol/uso terapéutico , Infecciones por VIH , Humanos , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/tratamiento farmacológicoRESUMEN
AIMS: This study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu's arteritis-associated pulmonary hypertension (TA-PH). METHODS AND RESULTS: We conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu's arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77-16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03-1.06), P < 0.001], and mean right atrial pressure [adjusted HR 1.07 (1.01-1.13), P = 0.015]. CONCLUSION: Patients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators' personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.