Clinical characteristics and influencing factors of severe fever with thrombocytopenia syndrome complicated by viral myocarditis: a retrospective study.

OBJECTIVE: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. METHODS: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. RESULTS: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001-1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. CONCLUSION: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.

Systemic inflammatory response syndrome in patients with severe fever with thrombocytopenia syndrome: prevalence, characteristics, and impact on prognosis.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. METHODS: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. RESULTS: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS. CONCLUSIONS: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality.

Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan and has quickly spread across the world. The mortality rate in critically ill patients with COVID-19 is high. This study analyzed clinical and biochemical parameters between mild and severe patients, helping to identify severe or critical patients early. METHODS: In this single center, cross-sectional study, 143 patients were included and divided to mild/moderate and sever/critical groups. Correlation between the disease criticality and clinical features and peripheral blood biochemical markers was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. RESULTS: Significantly, disease severity was associated with age (r = 0.458, P < 0.001), comorbidities (r = 0.445, P < 0.001), white cell count (r = 0.229, P = 0.006), neutrophil count (r = 0.238, P = 0.004), lymphocyte count (r = - 0.295, P < 0.001), albumin (r = - 0.603, P < 0.001), high-density lipoprotein cholesterol (r = - 0.362, P < 0.001), serum potassium (r = - 0.237, P = 0.004), plasma glucose (r = 0.383, P < 0.001), total bilirubin (r = 0.340, P < 0.001), serum amyloid A (r = 0.58, P < 0.001), procalcitonin (r = 0.345, P < 0.001), C-reactive protein (r = 0.477, P < 0.001), lactate dehydrogenase (r = 0.548, P < 0.001), aspartate aminotransferase (r = 0.342, P < 0.001), alanine aminotransferase (r = 0.264, P = 0.001), erythrocyte sedimentation rate (r = 0.284, P = 0.001) and D-dimer (r = 0.477, P < 0.001) . CONCLUSIONS: With the following parameters such as age > 52 years, C-reactive protein > 64.79 mg/L, lactate dehydrogenase > 245 U/L, D-dimer > 0.96 µg/mL, serum amyloid A > 100.02 mg/L, or albumin < 36 g/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Lymphocyte count, serum potassium, high-density lipoprotein cholesterol and procalcitonin may also be a prognostic indicator.

Disseminated Acanthamoeba castellanii infection in a patient with AIDS: a case report and literature review.

Background: Acanthamoeba castellanii infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this condition, and successful treatment reports are scarce. Case presentation: We present a case of Acanthamoeba castellanii infection in a 63-year-old female patient with AIDS, who was admitted to our hospital with symptoms of fever, skin ulcers, subcutaneous nodules, and food regurgitation from the nose while eating. After initial empirical treatment failed, a biopsy of the subcutaneous nodule was performed, and metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microorganisms in both the biopsy specimen and blood samples. The results revealed Acanthamoeba castellanii infection. Additionally, histopathological examination of the biopsy specimen and cytological examination of the secretions from the ulcer surface also confirmed this pathogenic infection. The patient's symptoms significantly improved upon discharge after adjusting the treatment regimen to a combination of anti-amebic therapy. Conclusion: Immunocompromised patients presenting with unexplained fever and skin or sinus lesions should be evaluated for Acanthamoeba castellanii infection. Multi-drug combination therapy is required for this organism infection, and a standard treatment protocol still needs further research. Metagenomic next-generation sequencing is a valuable tool for early diagnosis of unknown pathogen infections.

Diagnostic values of BALF metagenomic next-generation sequencing, BALF real-time PCR and serum BDG for Pneumocystis jirovecii pneumonia in HIV-infected patients.

Introduction: This study aimed to assess the diagnostic values of bronchoalveolar lavage fluid (BALF) real-time polymerase chain reaction (PCR) and BALF metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PJP) in patients infected with human immunodeficiency virus (HIV). Methods: A total of 99 HIV-infected PJP patients and 61 HIV-infected patients diagnosed with non-PJP pneumonia between March 2019 and December 2022 were enrolled. P. jirovecii and multiple other co-pathogens detected in BALF by mNGS were analyzed. The clinical final diagnosis was employed as a benchmark. We compared the diagnostic performance of mNGS in PJP with serum BDG and BALF real-time PCR. The mixed infections detected by mNGS and modifications of antimicrobial treatment were also analyzed. Results: The sensitivity of mNGS test of BALF samples reached 85.86%, which was significantly higher than serum BDG (39.39%, P < 0.001). The sensitivity of BALF P. jirovecii PCR (84.85%) was similar with mNGS (P > 0.05). The specificity of mNGS (100%) was also same as PCR (100.0%), and superior to serum BDG (88.52%, P < 0.001). Besides, mNGS performs remarkably well in identifying co-pathogens of PJP patients infected with HIV. In addition to P. jirovecii, 82 cases (82.83%) of other co-pathogens were identified based on mNGS. Moreover, thirty-four patients (34.34%) increased therapeutic dose of trimethoprim-sulfamethoxazole (TMP-SMZ) based on BALF P. jirovecii PCR. Based on the mNGS results, initial antimicrobial treatment was modified in 86.87% (86/99) of PJP patients. Conclusion: BALF mNGS and real-time PCR are two powerful techniques for rapid diagnosis of PJP with high specificity and sensitivity. Moreover, the benefit of mNGS is that it may identify other organisms besides PJP and it may benefit proper and prompt treatment.

Prevalence and clinical characteristics of increased pancreatic enzymes in patients with severe fever with thrombocytopenia syndrome.

BACKGROUND AND AIM: The increased pancreatic enzymes have recently been reported in patients with severe fever with thrombocytopenia syndrome (SFTS). However, its significance has not been elucidated clearly. The aim of this study was to explore the prevalence, clinical characteristics of elevated pancreatic enzymes (amylase and lipase) and its association with AP in patients with SFTS. METHODS: Data of demographics, comorbid conditions, clinical symptoms, laboratory parameters and survival time of patients with SFTS were collected. Patients were assigned into the non-AP and AP groups according to the diagnostic criteria of AP. Patients in the non-AP group were divided into the normal (3×ULN) groups according to the serum amylase and lipase levels, and then their clinical data were compared. RESULTS: A total of 284 patients diagnosed with SFTS were retrospectively enrolled, including 248 patients in the non-AP group and 36 patients in the AP group. Patients in the non-AP group were composed of 48, 116 and 84 patients in the normal, EPE and HPE groups, respectively. Compared with patients in the normal and EPE groups, patients in the HPE group had higher serum levels of laboratory parameters referring to liver, kidney, heart and coagulation system injury, as well as higher viral load. The cumulative survival rate of patients in the HPE group was significantly lower than that of patients in the normal group. In addition, patients in the AP group also had higher serum levels of laboratory variables reflecting liver, heart, coagulation dysfunction and viral load than patients in the HPE group. The cumulative survival rate of patients in the AP group was significantly lower than that of patients in the HPE group. CONCLUSION: The increased pancreatic enzymes are very common in patients with SFTS, but they are not always associated with AP. Though AP accounts for the majority of deaths for patients with elevated pancreatic enzymes, patients with pancreatic enzymes >3×ULN except for AP also have a high in-hospital mortality rate.

Clinical characteristics and outcomes of acute kidney injury in patients with severe fever with thrombocytopenia syndrome.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis caused by a novel bunyavirus. Until recently, the SFTS related acute kidney injury (AKI) was largely unexplored. This study aimed to investigate the clinical characteristics and outcomes of AKI in patients with SFTS. Methods: The non-AKI and AKI groups were compared in terms of general characteristics, clinical features, laboratory parameters and cumulative survival rate. The independent risk factors for in-hospital mortality in patients with SFTS were analyzed by multivariate logistic regression to identify the population with poor prognosis. Results: A total of 208 consecutive patients diagnosed with SFTS were enrolled, including 153 (73.6%) patients in the non-AKI group and 55 (26.4%) patients in the AKI group. Compared with patients without AKI, patients with AKI were older and had a higher frequency of diabetes. Among these laboratory parameters, platelet count, albumin and fibrinogen levels of patients with AKI were identified to be significantly lower than those of patients without AKI, while ALT, AST, ALP, triglyceride, LDH, BUN, uric acid, creatine, Cys-C, ß2-MG, potassium, AMY, lipase, CK-MB, TnI, BNP, APTT, thrombin time, D-dimer, CRP, IL-6, PCT and ESR levels were significantly higher in patients with AKI. A higher SFTS viral load was also detected in the AKI patients than in the non-AKI patients. The cumulative survival rates of patients at AKI stage 2 or 3 were significantly lower than those of patients without AKI or at AKI stage 1. However, there was no significant difference in the cumulative survival rates between patients without AKI and those with stage 1 AKI. Univariate and multivariate binary logistic regression analyses demonstrated that stage 2 or 3 AKI was an independent risk factor for in-hospital mortality in patients with SFTS. Conclusion: AKI is associated with poor outcomes in patients with SFTS, especially patients at AKI stage 2 or 3, who generally have high mortality. Our findings support the importance of early identification and timely treatment of AKI in patients with SFTS.

Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B.

Hepatitis E virus (HEV) infection is a major cause of morbidity in endemic areas. Its consequences among chronic hepatitis B (CHB) patients have been under-reported. The aim of this study was to assess the impact of superinfective HEV infection (acute and past) on virological and clinical features of patients with CHB infection. Clinical, biochemical, virological and immunological data of 153 CHB patients including 98 with hepatitis B virus (HBV) monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan, China. An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients. HBV-HEV superinfection patients showed significantly higher rate of complications (ascites, hepato-renal syndrome & encephalopathy) (all with P=0.04), cirrhosis (P<0.001) and acute-on-chronic liver failure (P<0.001) than HBV monoinfection patients. They also displayed elevated ALTs (P<0.001) and total serum bilirubin (P<0.001) with diminished albumin (P<0.001) and HBV viral load (P<0.001). Cytokines assay revealed increased expression of IL-6 (P=0.02), IL-10 (P=0.009) and TNF-α (P=0.003) in HBV-HEV superinfection patients compared to HBV monoinfection patients. Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation, which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis. HEV was also associated with repressed HBV replication, but the underlying mechanism requires further investigation.

Lycorine inhibits melanoma A375 cell growth and metastasis through the inactivation of the PI3K/AKT signaling pathway.

Malignant melanoma, one of the most aggressive skin cancers, has a very high mortality rate. Currently, the number of drugs to treat melanoma is low. Although new immunotherapeutic approaches based on the use of antibodies against immune checkpoints have shown long term responses, it is urgent to develop novel anti-melanoma drugs with a high efficiency and a low toxicity in a large number of patients. Lycorine, a natural product, has been reported to exert antitumor effects on some cancers. However, the impact of lycorine on melanoma cells is still unknown. Using the CCK8 assay, we found that lycorine can suppress the proliferation of melanoma A375 cells in a dose-time-dependent manner. Moreover, a transwell assay showed that lycorine inhibited the migration and invasion of A375 cells significantly. Further, lycorine treatment could induce the apoptosis of the A375 cells. Biochemical analyses showed that the expression level of the anti-apoptosis Bcl-2 protein decreased, while the expression of the pro-apoptosis protein Bax and active caspase-3 increased after lycorine treatment. Finally, using western blot assay, we found that the antitumor effects of lycorine on A375 cells might be through the inactivation of the PI3K/Akt signaling pathway. Based on these observations, we suggest that lycorine may be an interesting candidate for further studies on its ability to represent a novel antitumor drug for human melanoma treatment in the future.

miR-25 Promotes Melanoma Progression by regulating RNA binding motif protein 47.

Melanoma is the most aggressive skin cancer, and accounts for the major part of skin cancer-related deaths in the world. In addition, the underlying mechanism of tumor progression in melanoma remains far from being elucidated. In this study, we have evaluated the function of miR-25 in melanoma. First, we examined the expression of miR-25 in four melanoma cell lines (A875, MV3, M14 and uacc-257) and in a normal melanocyte cell line (HEM-a). Then, we overexpressed miR-25 in M14 cells. Our results show that miR-25 promotes M14 cell proliferation and migration. We found that miR-25 up-regulates the PI3K/Akt/mTOR signaling pathway in these tumor cells. Furthermore, a luciferase-based reporter gene assay showed that miR-25 could directly target the RNA-binding motif protein 47 (RBM47). Taken together, our findings suggest that RBM47 is a promising target for the treatment of melanoma.

Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis.

AIM: To evaluate the differences in acute kidney injury (AKI) between acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) patients. METHODS: During the period from December 2015 to July 2017, 280 patients with hepatitis B virus (HBV)-related ACLF (HBV-ACLF) and 132 patients with HBV-related DC (HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver-type fatty acid binding protein (L-FABP), cystatin C (CysC), and kidney injury molecule-1 (KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS: AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively (25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers (NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI (ACLF-AKI), compared with that in patients with HBV-DC and AKI (DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients (49.3% vs 17.9%, P = 0.013). Forty-three patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLF-AKI patients was significantly lower than that of patients with DC-AKI (32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups (P < 0.001). CONCLUSION: AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.