Ruxolitinib plus standard of care in severe hospitalized adults with severe fever with thrombocytopenia syndrome (SFTS): an exploratory, single-arm trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS. METHODS: We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching. RESULTS: Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported. CONCLUSIONS: Our findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed. TRAIL REGISTRATION: ChiCTR2200063759, September 16, 2022.

Cytokines and lymphocyte subsets are associated with disease severity of severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). Previous studies have indicated that SFTS patients have a high mortality rate, which may be related to cytokine storm and immune dysfunction. In our study, we analyzed differences in cytokines and lymphocyte subsets between severe and non-severe SFTS patients, with the aim of identifying predictors of severity. METHODS: We retrospectively analyzed demographic characteristics, clinical data, cytokine profiles, and lymphocyte subsets from 96 laboratory confirmed SFTS patients between April 2021 and August 2023. RESULTS: A total of 96 SFTS patients were enrolled, with a mean age of 65.05 (± 7.92) years old. According to our grouping criteria, 35 (36.5%) of these patients were classified as severe group, while 61 (63.5%) were classified as non-severe group. Univariate analysis revealed that age, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-α (IFN-α), CD4 + T cell, and CD8 + T cell counts were risk predictors for the severity of SFTS. Further multivariable logistic regression analysis confirmed age, IL-6 levels, and CD4 + T cell counts as independent predictors of SFTS severity. CONCLUSIONS: Severe SFTS patients may experience cytokine storms and immune dysfunction. Aging, elevated levels of IL-6, and decreased CD4 + T cell count may serve as independent predictors for the severity of SFTS.

Investigation of predictors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome.

Patients with severe fever with thrombocytopenia syndrome (SFTS) had been confirmed to have immune dysfunction and were prone to invasive pulmonary aspergillosis (IPA), which was directly related to the increased mortality. The aim of this study was to investigate the predictors for IPA in SFTS patients, and the results were expected to be helpful for early identification of IPA and initiation of anti-fungal therapy. The study was performed to review laboratory confirmed SFTS patients in two tertiary hospitals in Shandong province (Qilu Hospital of Shandong University and Shandong Public Health Clinical Center) from April 2021 to August 2022. The enrolled patients were further divided into IPA group and non-IPA group. Demographic characteristics, clinical manifestations and laboratory parameters between IPA group and non-IPA group patients were analyzed and compared to identify the independent predictors for IPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent predictors were evaluated by receiver operating characteristic (ROC) curve analysis. In total, 67 SFTS patients were enrolled with an average age of 64.7 (± 8.4) years old. The incidence of IPA was 32.8% (22/67). Mortality of patients in IPA group was 27.3% (6/22), which was significantly higher than that in non-IPA group. Results of univariate analysis showed that uncontrolled diabetes, central nervous system symptoms, platelet < 40 × 109/L, CD4+ T cell < 300/µL and CD8+ T cell < 400/µL were risk factors for development of IPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that uncontrolled diabetes, platelet < 40 × 109/L, CD4+ T cell < 300/µL and CD8+ T cell < 400/µL could be recognized as independent predictors for IPA in SFTS patients. In conclusion, IPA is a serious complication for SFTS patients and increases mortality. It is necessary to early identify predictors of IPA for improving survival of SFTS patients.

The presence of foci of Rickettsia conorii infection in China.

China is not considered as an endemic area of Rickettsia conorii, so there is no routine clinical way to diagnose this infection. This study aims to determine whether 2 febrile patients who had a tick bite in East China were indeed infected with R. conorii. The citrate synthase gene (gltA) was amplified with universal rickettsial primers by real-time fluorescent PCR from the patients' blood samples. Nested PCR was used to amplify the outer membrane protein A gene (ompA) for positive specimens. PCR products were further identified and analyzed through nucleic acid sequencing. Positive amplification of the gltA and ompA genes was found in both patients. The nucleotide sequences (303 bp) of the ompA gene of the 2 patients had high homology (99%) with the R. conorii Indian tick typhus strain in GenBank. A more than 4-fold increase in IgG against R. conorii provided supportive evidence of SFG Rickettsia infection. And the rapid recovery after doxycycline treatment also supported a rickettsial cause for the disease. Physicians in East China should be aware of human infections with R. conorii. PCR-based diagnostic methods offer a rapid and precise way to diagnose rickettsiosis, improving patient identification and management.

Myocarditis Induced by Immune Checkpoint Inhibitors: Mechanisms and Therapeutic Prospects.

Under physiological conditions, immune checkpoint molecules downregulate the activation and effector function of myocardial antigen-reactive T cells through an immunosuppressive pathway, thus enabling myocardial T cells to maintain immune homeostasis under the action of central and peripheral tolerance mechanisms. The PD-1/PD-L1 signalling pathway is particularly important for limiting the ability of T cells to attack the heart. Immune checkpoint inhibitors (ICIs) specifically block this PD-1/PD-L1-mediated restriction of T cell activation and other immunosuppressive pathways by targeting immune checkpoints. In recent years, with the wide use of ICIs in cancer treatment, even though the incidence of immunomyocarditis is low, it has attracted increasing attention because of its complex clinical symptoms, rapid progression of disease and high mortality rates. The pathogenesis, genetic susceptibility factors and predictive biomarkers of immunomyocarditis still need to be understood, and multidisciplinary cooperation in the clinical treatment of this complication is necessary.

Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial.

BACKGROUND AND AIM: Bowel preparation is an important determinant of the quality of colonoscopy. The traditional split-dose regimen of 4 L polyethylene glycol (PEG) solutions for bowel preparation is effective but poorly tolerated. The aim of this was to study the efficacy and tolerability of using linaclotide as an adjunctive agent with low-volume PEG for bowel preparation. METHODS: This was an endoscopist-blinded, randomized, controlled trial of 432 patients randomly assigned to three groups: 2 L PEG, 4 L PEG and 2 L PEG + 290 µg linaclotide (2 L PEG + L group). The primary outcome measure was efficacy of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), with secondary outcomes of patients' tolerance, defecating frequency, complications, sleeping quality, cecal intubation rate, preparation-to-colonoscopy interval, withdrawal time, cecal intubation time, and adenoma and polyp detection rates. RESULTS: The percentage of adequate bowel preparation in the 2 L PEG + L group was higher than that of the 2 L PEG group (87.9% vs. 77.0%; P = 0.017), but not the 4 L PEG group (87.9% vs. 91.4%; P = 0.339). In terms of the mean (SD) BBPS score for the total and segmental colons, the bowel cleansing efficacy of 2 L PEG + L was superior to that of 2 L PEG and similar to that of 4 L PEG. Patient's tolerance (including complications, willingness to repeat and sleeping quality) were compatible between the 2 L and 2 L + L group, and the 4 L group was the worst among these three groups. CONCLUSION: Two liters of PEG combined with 290 µg linaclotide was an effective and well-tolerated bowel preparation regimen.

Endoscopic resection of benign esophageal schwannoma: Three case reports and review of literature.

BACKGROUND: Esophageal schwannomas are uncommon esophageal submucosal benign tumors and are usually treated with surgery. CASE SUMMARY: Here, we report three cases of middle/lower thoracic esophageal schwannoma treated successfully with endoscopic resection. These lesions were misdiagnosed as leiomyoma on preoperative imaging. During the endoscopic resection of such tumors, there is a risk of esophageal perforation due to their deep location. If possible, submucosal tunneling endoscopic resection should be used. CONCLUSION: For larger schwannomas, endoscopy combined with thoracoscopy can be considered for en bloc resection. We performed a mini literature review in order to present the current status of diagnosis and treatment for esophageal schwannoma.