Exploring Shared Genetic Signatures of Alzheimer's Disease and Multiple Sclerosis: A Bioinformatic Analysis Study.

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.

The effect on brain volume in HIV-negative and non-transplant cryptococcal meningitis.

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.

Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient.

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.

The long-term survival in patients with chronic thromboembolic pulmonary hypertension: experience from a single center in China.

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.

Comparison of features and outcomes between HIV-negative patients with Cryptococcus gattii meningitis and Cryptococcus neoformans meningitis in South China.

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.

Clinical features and survival in Takayasu's arteritis-associated pulmonary hypertension: a nationwide study.

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.

Connexin32 activates necroptosis through Src-mediated inhibition of caspase 8 in hepatocellular carcinoma.

Necroptosis is an alternative form of programmed cell death that generally occurs under apoptosis-deficient conditions. Our previous work showed that connexin32 (Cx32) promotes the malignant progress of hepatocellular carcinoma (HCC) by enhancing the ability of resisting apoptosis in vivo and in vitro. Whether triggering necroptosis is a promising strategy to eliminate the apoptosis-resistant HCC cells with high Cx32 expression remains unknown. In this study, we found that Cx32 expression was positively correlated with the expression of necroptosis protein biomarkers in human HCC specimens, cell lines, and a xenograft model. Treatment with shikonin, a well-used necroptosis inducer, markedly caused necroptosis in HCC cells. Interestingly, overexpressed Cx32 exacerbated shikonin-induced necroptosis, but downregulation of Cx32 alleviated necroptosis in vitro and in vivo. Mechanistically, Cx32 was found to bind to Src and promote Src-mediated caspase 8 phosphorylation and inactivation, which ultimately reduced the activated caspase 8-mediated proteolysis of receptor-interacting serine-threonine protein kinase 1/3, the key molecule for necroptosis activation. In conclusion, we showed that Cx32 contributed to the activation of necroptosis in HCC cells through binding to Src and then mediating the inactivation of caspase 8. The present study suggested that necroptosis inducers could be more favorable than apoptosis inducers to eliminate HCC cells with high expression of Cx32.

GJA1-20k attenuates Ang II-induced pathological cardiac hypertrophy by regulating gap junction formation and mitochondrial function.

Cardiac hypertrophy (CH) is characterized by an increase in cardiomyocyte size, and is the most common cause of cardiac-related sudden death. A decrease in gap junction (GJ) coupling and mitochondrial dysfunction are important features of CH, but the mechanisms of decreased coupling and energy impairment are poorly understood. It has been reported that GJA1-20k has a strong tropism for mitochondria and is required for the trafficking of connexin 43 (Cx43) to cell-cell borders. In this study, we investigated the effects of GJA1-20k on Cx43 GJ coupling and mitochondrial function in the pathogenesis of CH. We performed hematoxylin-eosin (HE) and Masson staining, and observed significant CH in 18-week-old male spontaneously hypertensive rats (SHRs) compared to age-matched normotensive Wistar-Kyoto (WKY) rats. In cardiomyocytes from SHRs, the levels of Cx43 at the intercalated disc (ID) and the expression of GJA1-20k were significantly reduced, whereas JAK-STAT signaling was activated. Furthermore, the SHR rats displayed suppressed mitochondrial GJA1-20k and mitochondrial biogenesis. Administration of valsartan (10 mg· [Formula: see text] d-1, i.g., for 8 weeks) prevented all of these changes. In neonatal rat cardiomyocytes (NRCMs), overexpression of GJA1-20k attenuated Ang II-induced cardiomyocyte hypertrophy and caused elevated levels of GJ coupling at the cell-cell borders. Pretreatment of NRCMs with the Jak2 inhibitor AG490 (10 µM) blocked Ang II-induced reduction in GJA1-20k expression and Cx43 gap junction formation; knockdown of Jak2 in NRCMs significantly lessened Ang II-induced cardiomyocyte hypertrophy and normalized GJA1-20k expression and Cx43 gap junction formation. Overexpression of GJA1-20k improved mitochondrial membrane potential and respiration and lowered ROS production in Ang II-induced cardiomyocyte hypertrophy. These results demonstrate the importance of GJA1-20k in regulating gap junction formation and mitochondrial function in Ang II-induced cardiomyocyte hypertrophy, thus providing a novel therapeutic strategy for patients with cardiomyocyte hypertrophy.

Spermine promotes pulmonary vascular remodelling and its synthase is a therapeutic target for pulmonary arterial hypertension.

Pathological mechanisms of pulmonary arterial hypertension (PAH) remain largely unexplored. Effective treatment of PAH remains a challenge. The aim of this study was to discover the underlying mechanism of PAH through functional metabolomics and to help develop new strategies for prevention and treatment of PAH.Metabolomic profiling of plasma in patients with idiopathic PAH was evaluated through high-performance liquid chromatography mass spectrometry, with spermine identified to be the most significant and validated in another independent cohort. The roles of spermine and spermine synthase were examined in pulmonary arterial smooth muscle cells (PASMCs) and rodent models of pulmonary hypertension.Using targeted metabolomics, plasma spermine levels were found to be higher in patients with idiopathic PAH compared to healthy controls. Spermine administration promoted proliferation and migration of PASMCs and exacerbated vascular remodelling in rodent models of pulmonary hypertension. The spermine-mediated deteriorative effect can be attributed to a corresponding upregulation of its synthase in the pathological process. Inhibition of spermine synthase in vitro suppressed platelet-derived growth factor-BB-mediated proliferation of PASMCs, and in vivo attenuated monocrotaline-mediated pulmonary hypertension in rats.Plasma spermine promotes pulmonary vascular remodelling. Inhibiting spermine synthesis could be a therapeutic strategy for PAH.

Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a large number of IPAH cases. METHODS: We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10 508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function. RESULTS: The gene encoding human bone morphogenetic protein 9 (BMP9) was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10-11). This association was authenticated in the independent replication cohort (p=1.0×10-5). Collectively, the rare coding mutations in BMP9 occurred in 6.7% of cases, ranking this gene second to BMPR2, comprising a combined significance of 2.7×10-19 (OR 21.2). Intriguingly, the patients with BMP9 mutations had lower plasma levels of BMP9 than those without. Functional studies showed that the BMP9 mutations led to reduced BMP9 secretion and impaired anti-apoptosis ability in pulmonary arterial endothelial cells. CONCLUSION: We identify BMP9 as an IPAH culprit gene.

Ventriculoperitoneal shunts in non-HIV cryptococcal meningitis.

BACKGROUND: Persistent and uncontrollable intracranial hypertension (ICH) and difficulty in reducing Cryptococcus count are severe problems in cryptococcal meningitis (CM) patients. The therapeutic effects of ventriculoperitoneal shunts (VPS) in non-HIV CM patients are not fully known, and the procedure is somewhat unusual. Here, our study offers a review to investigate the role of VPS in non-HIV CM. METHODS: We retrospectively collected data on 23 non-HIV CM patients with and without ventriculomegaly from 2010 to 2016. Their demographic data, clinical manifestations, cerebrospinal fluid (CSF) features and outcomes were analysed. RESULTS: We found that non-HIV CM patients without ventriculomegaly were older, had earlier treatment times and had shorter symptom durations than CM patients with ventriculomegaly. In both groups, headache, vomiting, fever and loss of vision were the most common clinical features. CSF pressure and Cryptococcus count were significantly decreased after operation. VPS could provide sustained relief from ICH symptoms such as headache. 13% of patients had poor outcomes because of serious underlying disease, while 87% of patients had good outcomes. CONCLUSIONS: The use of a VPS is helpful in decreasing ICH and fungal overload in non-HIV CM patients, and VPS should be performed before CM patients present with symptoms of severe neurological deficit.

Comparisons of presentations and outcomes of neuromyelitis optica patients with and without Sjögren's syndrome.

Patients with neuromyelitis optica (NMO) often have an accompanying autoimmune disease, most commonly, but not limited to Sjögren's syndrome (SS). The aim of this study was to compare clinical and laboratory features between NMO patients with and without SS and to investigate the prognosis of NMO in patients with and without SS. Twenty-three NMO patients with SS and 42 NMO patients without SS were included. Clinical and laboratory profiles were compared, including annual relapse rate and time from onset of NMO to Expanded Disability Status Scale (EDSS) scores of 4.0 and 6.0. More NMO patients with SS than those without SS had anti-nuclear antibody, anti-SS-A/Ro and anti-SS-B/La antibodies (91.3 vs. 35.7%, p < 0.001, 87.0 vs. 2.3%, p < 0.001, and 34.8 vs. 0.0%, p < 0.001, respectively). Serum immunoglobulins (IgA, IgM and IgG) were markedly increased in NMO patients with SS in comparison with those without SS. Annual relapse rate and the time from disease onset to an EDSS score of 4.0 and 6.0 were not significantly different between the two groups. No differences between the two groups were found for the other parameters, including AQP-4 antibody status, length of spinal cord lesion and brain lesions. These results imply that NMO in SS more likely represents coexistence with SS rather than representing the result of direct central nervous system involvement in SS. Autoimmune response appears to be more intense in the NMO group with SS, but did not cause a more severe prognosis in comparison with the group without SS, indicating that we should pay attention to the potential benefit of the antinuclear antibodies in NMO.

Elevated Lipid Profiles in Patients with Acute Transverse Myelitis.

BACKGROUND: The associations and clinical relevance of serum lipid profiles in patients with acute transverse myelitis (ATM) are unknown. Our study aimed at investigating the status of serum lipid variables (including total cholesterol (TC), triglycerides (TGs), high/low density lipoproteins (HDL/LDL), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB) and cholesterol to HDL ratio) in ATM, and to explore whether there was a correlation between serum lipid levels and disease characteristics of ATM. METHODS: We retrospectively evaluated serum lipid levels of 92 patients with ATM, 43 with multiple sclerosis (MS) on relapse and 112 healthy controls (HC). The changes of serum lipid profiles were analyzed. RESULTS: We found that ATM patients had higher serum TC, TG, LDL levels and T/H ratio than HC, but had lower levels of serum ApoA-I and ApoB. Besides, there were no significant differences between ATM and MS on relapse (except ApoB). Third, longer disease duration was associated with higher TG; higher HDL was associated with a trend for lower Expanded Disability Status Scale scores. CONCLUSIONS: Our findings showed that serum lipid levels were elevated in patients with ATM, among serum TG and HDL might be associated with clinical features. These results illustrate that a long-term follow-up and regular monitoring of serum lipid profiles are important for ATM patients.

Lower socioeconomic status is associated with worse outcomes in pulmonary arterial hypertension.

RATIONALE: Lower socioeconomic status (SES) confers a heightened risk of common cardiovascular and pulmonary diseases and increased mortality. The association of SES with outcomes in patients with pulmonary arterial hypertension (PAH) is less clear. OBJECTIVES: To determine the association between SES and outcomes in patients with PAH. METHODS: We performed a prospective cohort study at a national referral center for patients with PAH in China. Two hundred sixty-two consecutive incident patients aged 18 to 65 years with a diagnosis of idiopathic PAH were recruited between January 2007 and June 2011 and followed up until November 2011. The primary endpoint was all-cause mortality. An SES score for each patient was derived from their educational level, annual household income, occupation, and medical reimbursement rate. MEASUREMENTS AND MAIN RESULTS: Patients with a lower SES had higher unadjusted mortality rates, with 3-year survival estimates of 50.1, 70.8, and 86.0% in increasing tertiles of SES (P for trend < 0.001). After adjustment for clinical features, hemodynamics, and type of PAH treatment, the hazard ratios for death were 2.98 (95% confidence interval, 1.51-5.89) in the lowest tertile of SES and 1.80 (95% confidence interval, 0.89-3.63) in the middle tertile of SES compared with the upper tertile (P for trend = 0.006). CONCLUSIONS: A lower SES is strongly associated with a higher risk of death in idiopathic PAH. This association was independent of clinical characteristics, hemodynamics, and treatment. Addressing the health disparities associated with a lower SES may improve the outcomes of patients with PAH.

Prognostic significance of quantitative electrocardiographic parameters in patients with non-high-risk pulmonary embolism.

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.

Joint effect of atrial fibrillation and obesity on mortality in critically ill patients.

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.

Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis.

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.

Distinct serum apolipoprotein A-I levels in neuromyelitis optica and acute transverse myelitis.

OBJECTIVE: NMO and ATM are intertwined both clinically and pathologically. Apolipoprotein (apo) A-I, the main apolipoprotein of HDL, plays an important role in lipid metabolism in the cerebrospinal fluid and is known to suppress pro-inflammatory cytokines generated by activated T cells in some autoimmune diseases as an immune regulator. However, the differences in the levels of serum apoA-I between NMO and ATM patients are unclear. METHODS: In the present study, serum apo A-I levels were measured in 53 NMO patients, 45 ATM patients and 49 healthy subjects. We tested serum apoA-I levels in all participants and investigated EDSS scores of patients with NMO and ATM. Statistical analyses were performed by using SPSS statistical software. RESULT: We found that serum apoA-I levels in patients with NMO were significantly lower in comparison to those with ATM. We also found that serum levels of apoA-I was lower in male subjects in comparison to the female subjects in all groups although these differences were not statistically significant in patients with NMO or ATM. It is also shown in our study that serum apoA-I levels in patients with NMO were significantly elevated after receiving a high dosage of intravenous corticosteroids over a period of one week. However, we did not find any correlation between the apoA-I levels and disease disability. CONCLUSION: From this study, we concluded that serum levels of apoA-I were lower in NMO patients compared to patients with ATM. Serum apoA-I studies might provide some useful clues to differentiate NMO cases from ATM cases.

Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease.

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 V̇o2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (V̇e/V̇co2 slope), were recorded. RESULTS: The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇o2 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 V̇o2 (p = 0.003) and the highest V̇e/V̇co2 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 V̇o2 (p = 0.003) compared with other patients. Peak V̇o2 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.

Neurological worsening during treatment of HIV-negative cryptococcal meningitis in a patient with Evans syndrome.

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.