Tislelizumab monotherapy in patients with previously untreated early-stage classical Hodgkin lymphoma: a real-world study.

The anti-PD-1 antibodies have been reported to show a striking effect in relapsed and refractory(R/R) classical Hodgkin lymphoma (cHL), however, there is still limited real-world data assessing the role of anti-PD-1 antibody monotherapy in early-stage cHL. In this retrospective analysis, we reported the effectiveness and safety of tislelizumab monotherapy in the first-line therapy of early-stage cHL. Twenty-three consecutive patients (10 males and 13 females) with previously untreated stage I A-II B cHL were included. At interim evaluation after 2 doses of tislelizumab monotherapy, 11 of 23 patients (47.8%) achieved complete response (CR). At the end of tislelizumab monotherapy (EOTM), objective response was observed in 22 of 23 patients (95.7%), with CR in 16 patients (69.6%). Among six patients with PR-EOTM, two patients underwent 4 cycles of ABVD chemotherapy and one patient underwent 4 cycles of tislelizumab plus AVD. One patient who developed progressive disease (PD) after 4 doses of tislelizumab subsequently underwent 4 cycles of ABVD chemotherapy. Except for four patients with CR-EOTM, consolidative radiotherapy was given to 19 patients. All patients obtained CR at the end of all treatments. With a median follow-up time of 21.3 months (range, 6.9-32.7 months), the estimated 2-year PFS rate and 2-year OS rate were 95.65% and 100%, respectively. Except for grade 3 lymphocyte count decreased, no other grade 3/4 TRAE was observed. In addition, no serious AE was reported. Our preliminary data observed that tislelizumab monotherapy was safe and highly effective in previously untreated early-stage cHL.

Outcomes of COVID-19 in patients with lymphomas participating in registered clinical trials: A real-world study from China in the Omicron outbreak era.

BACKGROUND: This real-world study investigated the outcome of COVID-19 in lymphoma patients participating in registered clinical trials and explored potential risk factors with the outcome of COVID-19 during the first wave of the Omicron outbreak in China. METHODS: One hundred and ten patients participating in registered clinical trials and diagnosed with COVID-19 in our center between December 1, 2022, and January 31, 2023, were included. RESULTS: Four (3.6%) patients were identified as severe COVID-19 and 2 (1.8%) as critical COVID-19, respectively. The mortality rate observed was 2.73% for the entire cohort, 33.3% for the severe/critical COVID-19 group, and 18.8% for the hospitalized group. The 90-day OS was 98.2% for the entire cohort, 66.7% for the severe/critical COVID-19 group, and 87.5% for the hospitalized group. Advanced age (≥70 years), comorbidities, and PI3K inhibitor-containing regimen were significantly associated with the severity of COVID-19. Patients with indolent B-cell non-Hodgkin lymphomas were less likely to be hospitalized for COVID-19. CONCLUSION: This study reported similar clinical features of COVID-19 in our cohort with that of non-hematological malignancy (HM) patients, while the proportion of severe/critical COVID-19 and the mortality rate were relatively higher than non-HM patients. Our findings provided valuable experience to aid clinical researchers with managing lymphoma patients participating in registered clinical trials during the ongoing pandemic of the Omicron variant.

Improved Sleep Affects Epigastric Pain in Functional Dyspepsia by Reducing the Levels of Inflammatory Mediators.

INTRODUCTION: The pathogenesis of epigastric pain in functional dyspepsia (FD) is complex. The study aims to explore the effect of sleep improvement on this symptom. METHODS: In total, 120 patients with FD-associated epigastric pain and insomnia were randomly divided into experimental and control groups using the envelope method. After applying the exclusion criteria, 107 patients were enrolled in the experimental (56 patients) and control (51 patients) groups. Insomnia was graded according to the Pittsburgh Sleep Quality Index (PSQI). In the experimental group, eszopiclone 3 mg, eszopiclone 3 mg + estazolam 1 mg, and eszopiclone 3 mg + estazolam 2 mg were given to patients with mild, moderate, and severe insomnia, respectively. In the control group, patients were given 1, 2, or 3 tablets of vitamin B complex. Patient sleep quality was monitored with Sleepthing. Epigastric pain was evaluated with a Numeric Rating Scale. The serum levels of IL-1ß, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Pain scores, sleep parameters, and serum levels of inflammatory mediators were compared before and after treatment. RESULTS: After treatment, the pain scores, sleep parameters, and TNF-α and IL-6 levels in the experimental group were significantly lower than those in the control group (p < 0.05). PSQI insomnia scores were significantly associated with pain scores, IL-6, and TNF-α (p < 0.05) but not in IL-8 and IL-1ß levels (p > 0.05) among the three groups. CONCLUSIONS: Improving sleep with eszopiclone and/or estazolam alleviates FD-associated epigastric pain, possibly by inhibiting related downstream transmission pathways and reducing the release of inflammatory mediators.

The latest research trends in primary biliary cholangitis: a bibliometric analysis.

The bibliometric analysis uses the citation count of an article to measure its impact in the scientific community, but no study has been undertaken to determine the most influential papers in the field of primary biliary cholangitis (PBC). This study aimed to investigate the global research interest regarding PBC in dentistry using a bibliometric approach. We searched the Web of Science Core Collection database to find the top 100 most cited (T100) articles focusing on PBC. The information about each article including citations, authors, journals, countries, institutions, and keywords was recorded for bibliometric analysis. The T100 articles related to PBC were published from 1983 to 2019 and were originated from 26 countries. A total of 805 different authors were from 342 different institutions, and articles written by them were published in 35 journals. The five most frequently occurring keywords were "biochemical response," "ursodeoxycholic acid," "primary biliary cirrhosis," "antimitochondrial antibody," and "autoimmunity." The T100 articles were classified into different research focuses: pathogenesis (41%), treatment (20%), prognosis (12%), epidemiology (9%), diagnosis (8%), and others (10%). These 100 articles included 32 observational studies, 29 basic research articles, 15 reviews, eight meta-analyses, 12 clinical trials, and four clinical guidelines. The 100 top-cited articles are marked with the leading countries, institutions, journals, hotspots, and development trends in the PBC field that could provide the foundation for further investigations.

The basement membrane-related gene signature is associated with immunity and predicts survival accurately in hepatocellular carcinoma.

AIMS: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Expression defects and turnover of basement membrane (BM) proteins are key pathogenic factors in cancer. It is still uncertain how the expression of BM-related genes (BMGs) in HCC relates to prognosis. METHODS: All of the HCC cohort's RNA-seq and clinical information came from TCGA datasets. The least absolute shrinkage and selection operator (LASSO) regression algorithm was utilized to filter down the candidate genes and construct the prognostic model. Univariate and multivariate Cox analyses were run to examine if the risk score may serve as a standalone prognostic indicator. The single-sample gene set enrichment analysis (ssGSEA) was utilized to analyze examine immune cell infiltration and pathway activity. RESULTS: Five genes and their risk coefficients were eventually identified and patients with HCC were classified as either high or low risk based on the median of risk scores. Multivariate Cox regression analysis found a significant correlation between risk score and OS (p < 0.001). Subgroup analysis showed that BMGs signature had good prediction ability for HCC patients in age, gender, T stage, and AJCC stage (all p < 0.05). According to the ssGSEA, the high-risk subgroup showed higher levels of immune cell infiltration and immune-related pathways were more engaged in the high-risk group. CONCLUSIONS: Our research systematically built a prognostic model using risk score based on BMGs signature in HCC patients. The immune feature analysis of the BMGs signature indicated a potential regulation between tumor immunity and BM in HCC.

Combination of Anti-PD-1 Antibody, Anlotinib and Pegaspargase "Sandwich" With Radiotherapy in Localized Natural Killer/T Cell Lymphoma.

Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma (NKTL) treatment. However, these chemotherapy regimens inevitably cause relatively high incidence of treatment-related adverse events (TRAEs). Herein we retrospectively evaluated the efficacy and safety of the combined regimen of anti-PD-1 antibody, anlotinib and pegaspargase "sandwich" with radiotherapy in localized NKTL. Anti-PD-1 antibody and pegaspargase at 2500 U/m2 were administered on day 1, while anlotinib (12 mg once a day) was orally administered on days 1-14. The treatment was repeated every 3 weeks. All the eight patients included received 3 cycles of the regimen followed by radiotherapy and an additional 3 cycles. The overall response rate was 100%, and the complete response rate was 87.5%. With a median follow-up time of 35.5 months (range, 34.03-40.90 months), median PFS and OS times were not reached. The 3-year PFS and OS rates were 100% and 100%, respectively. All patients were alive at the last follow-up. No treatment-related death and no grade 4 TRAE was reported. No grade 3/4 hematological toxicity was detected, and half of the patients didn't report any hematological toxicity. This study indicates that anti-PD-1 antibody combined with anlotinib and pegaspargase is a promising chemoradiotherapy regimen for localized NTKL, with mild toxicity and good tolerance.

Motor and bladder dysfunctions in patients with vertebral fractures at the thoracolumbar junction.

OBJECTIVE: To present the motor deficits and type of neurogenic bladder dysfunction (NBD) in patients with vertebral fractures at thoracolumbar junction. METHODS: Fifty-two patients with single level vertebra fracture over T11-L2 with onset duration of longer than 3 years were enrolled. All participants provided basic demographic data, ambulatory status and received neurologic examination and urodynamic studies. The differences in distribution of NBD types, neurologic injury sites and functional walkers in patients with different levels of vertebral injury were analyzed. Receiver operating characteristic curve analysis was used to define the cutoff value of lower extremities motor score (LEMS) in functional walker and non-walker. RESULTS: Of the 52 patients, the injured levels were 3 (5.8%) in T11, 21 (40.4%) in T12, 22 (42.3%) in L1, and 6 (11.5%) in L2 vertebrae. Eight (15.4%) patients had upper lumbar cord lesions, 26 (50.0%) had epiconus and lumbar roots lesions, 18 (34.6%) had conus medullaris or/and cauda equina lesions. Mean LEMS was 0 ± 0, 5.4 ± 7.7, 11.1 ± 10.2, and 28.0 ± 11.0 for patients with T11, T12, L1, and L2 fractures, respectively. Patients with L2 fractures had higher LEMS than other levels (p < 0.001). The cutoff value of LEMS for functional walking was set at 20, and both the sensitivity and specificity was 100%. Thirty-one (59.6%) patients had spastic NBD, 18 (35.6%) had flaccid NBD, and 3 (5.8%) had mixed type NBD. Positive prediction value of ankle spasticity for bladder and sphincter spasticity was 95.2 and 100%, respectively. CONCLUSION: Half of the patients had epiconus lesion following thoracolumbar junction fracture, and they had a clinical presentation of flaccid legs and spastic NBD. Patients with L2 fracture had higher LEMS than patients with T11, T12, and L1 fracture. Patients whose LEMS was higher than 20 could all walk functionally. Fracture at the thoracolumbar junction may cause spastic, flaccid, or mixed type NBD, and urodynamic study is an essential tool for the correct diagnosis and management. Ankle spasticity has a high positive predictive value for spastic bladder or sphincter.