暂无摘要。

OBJECTIVE: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT.
METHODS: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to <30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT.
RESULTS: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6-51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1-2 and S1-5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period.
CONCLUSIONS: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity.

UNASSIGNED: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has had an unprecedented impact on people around the world, particularly those who were suffering from autoimmune rheumatic diseases (AIRDs). The world community acknowledges the significance of COVID-19 vaccination in patients with autoimmune disorders and emphasizes the priority of this category to receive vaccination over the general population. Although many studies have been published since the first phases of vaccination all over the world, multiple related factors still need to be further investigated.
UNASSIGNED: We investigated the COVID-19 vaccination status in patients with AIRDs, by performing a cross-sectional, interview-based study filled in by patients attending their clinics in the Astana city, capital of Kazakhstan, from April to July 2023. The survey questionnaire consisted of a set of questions, concerning patient characteristics, treatment details, accepted vaccines and characteristics of COVID-19 infection. The study objectives were to evaluate vaccine hesitancy, adverse effects, breakthrough infections and flare of underlying rheumatic disease in this population subgroup.
UNASSIGNED: There were 193 participants, with a median age of 50.3 ±12.9 years. Among them, 62 (32.1%) were vaccinated with at least single dose of vaccine, 16 (25.8%) of whom were fully vaccinated. The commonest (89; 68%) reason for vaccine hesitancy was a fear of autoimmune disease worsening. Vaccine-related adverse effects (AEs) were reported by 66.7% of patients. We found that vaccination provoked AIRD exacerbation in 19% of patients with AEs. Eight patients reported flare of pre-existing rheumatic disease after vaccination. The incidence of breakthrough infections was similar in the groups of vaccinated individuals (n = 12), 12.9% of whom were partially and 6.5% fully vaccinated.
UNASSIGNED: The vaccination was found to be safe in patients with rheumatic diseases. Fear of autoimmune status was the major reason for vaccine reluctance. All reported adverse events were minor. The minority subgroup within the sample had subsequent breakthrough infections or autoimmune disease flare-ups.

OBJECTIVE: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease.
METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected.
RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination.
CONCLUSIONS: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

UNASSIGNED: Consumer perception of and satisfaction with vaccination services is a critical and commonly used indicator for evaluating the quality of services provided by concerned authorities. The present survey assessed maternal perceptions, hesitancy, satisfaction, and factors associated with childhood immunization services provided at the primary health centers (PHCs) of eastern Saudi Arabia.
UNASSIGNED: The current analytical cross-sectional study included mothers of childhood vaccine beneficiaries attending PHCs in Hafr Al-Batin. We collected data related to mothers\' perceptions, hesitancy, and satisfaction using a validated Arabic version of the data collection tool. Factors associated with low and high satisfaction with the immunization services were evaluated using logistic regression analysis. We performed Spearman correlation test to identify the correlation between the perception and satisfaction scores.
UNASSIGNED: Of the 675 participants, 87.4% were satisfied with the immunization services provided at the PHCs. The participants\' satisfaction was significantly associated with the immunized child\'s age group (adjusted odds ratio [AOR] = 1.89, 95% CI = 1.39-2.89, p = 0.037) and occupation status (AOR = 1.42, 95% CI = 1.17-1.74, p = 0.024). Vaccine hesitancy was significantly associated with the mother\'s age group (AOR = 1.89, 95% CI of AR = 1.35-3.39, P = 0.003) and number of children (AOR = 1.42, 95% CI of AR = 1.17-1.74, P = 0.024), Additionally, we found a significant positive correlation (Spearman\'s rho = 0.207, p < 0.001) between perception and satisfaction scores.
UNASSIGNED: We recommend targeted health education programs for mothers to improve their perceptions and the importance of all recommended childhood vaccines. Additionally, we suggest continuing maternal satisfaction assessments to enhance and maintain the quality of vaccination services.

OBJECTIVE: To examine the extent to which metformin increases the risk of vitamin B12 deficiency and borderline deficiency over time in participants with type 2 diabetes mellitus (T2DM).
METHODS: Using the All of Us database, adults aged ≥18 years with T2DM and a documented history of metformin use were included for the evaluation of B12 deficiency. Those with B12 deficiency before metformin use were excluded. Adjusted logistic regression models were used to evaluate the association between metformin use and long-term metformin use (≥4 years) and the risk of B12 deficiency. We conducted a subgroup analysis comparing differences in borderline B12 deficiency in metformin and non-metformin users.
RESULTS: Of 36 740 participants with T2DM, 6221 (16.9%) had documented metformin use. The mean age of metformin users was 65.3 years. B12 deficiency was confirmed in 464 (7.5%) metformin users, and 1919 of 30 519 participants (6.3%) did not use metformin. Metformin users had a 4.7% increased risk of developing B12 deficiency compared with nonmetformin users (P = .44). Each additional year of metformin use was associated with 5% increased likelihood of deficiency (P < .05). Metformin use for ≥4 years resulted in a 41.0% increased odds of B12 deficiency, compared with those who used <4 years of metformin (P < .05). Metformin use increased the odds of borderline B12 deficiency by 27.0% (P < .05).
CONCLUSIONS: Long-term metformin use was associated with an increased risk of B12 deficiency in patients with T2DM, with compounding risk over time.

Recombinant LL-37 Lactococcus lactis (Oral LL-37) was designed to prevent progression of COVID-19 by targeting virus envelope, however, effectiveness and safety of Oral LL-37 in clinical application was unclear. A total of 238 adult inpatients, open-labelled, randomized, placebo-controlled, single-center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS-CoV-2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL-37 could significantly shorten NCT (LL-37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL-37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27-fold higher than 7-day-later (HR: 6.276, 95% confidence interval [CI]: 3.631-10.848, p < 0.0001), and the adjusted HR of Oral LL-37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239-4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow-up investigation. This study shows that early intervention of Oral LL-37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns.

Use of d,l-sotalol for rhythm control in patients with atrial fibrillation (AF) has raised safety concerns. Previous randomized studies are few and not designed for mortality outcome.
The purpose of this study was to compare the incidences of mortality and ventricular arrhythmias in AF patients treated with d,l-sotalol for rhythm control vs matched control patients treated with cardioselective beta-blockers.
This population-based cohort study included AF patients from the Swedish National Patient Registry (2006-2017) who underwent rhythm control after a second cardioversion. Incidence rates (IRs) and adjusted hazard ratios (aHRs) for mortality and a composite endpoint of cardiac arrest/death and ventricular arrhythmias were calculated for the overall cohort and a 1:1 propensity score matched cohort of d,l-sotalol vs beta-blocker treatment.
Among patient treated with d,l-sotalol (n = 4987) and beta-blocker (n = 27,078) (mean follow-up 458 days), all-cause mortality was lower in patients treated with d,l-sotalol: IR 1.21; 95% confidence interval 0.95-1.52 vs 2.42 (2.26-2.60) deaths per 100 patient-years; aHR 0.66 (0.52-0.83). The difference in mortality persisted in the propensity score matched comparison (n = 4953 in each group): aHR 0.63 (0.48-0.86). No differences were observed in the composite outcome: IR in propensity cohorts 2.13 (1.78-2.52) vs 2.07 (1.73-2.53) events per 100 years; aHR 1.01 (0.78-1.29).
There was no excess mortality with d,l-sotalol compared with cardioselective beta-blockers in patients undergoing rhythm control treatment for AF after a second cardioversion. Our results indicate that the risk associated with d,l-sotalol treatment for AF can be mitigated by careful patient selection and strict adherence to follow-up protocols.

BACKGROUND: Major bleeding in patients undergoing therapeutic plasma exchange (TPE) has been studied in large databases; but without standardizing bleeding definitions. Therefore, we used standardized definitions to evaluate major bleeding in hospitalized patients undergoing TPE using public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III).
METHODS: In a retrospective cross-sectional analysis, we identified TPE-treated adults in a first inpatient encounter. We evaluated major bleeding prevalence using (1) International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) codes, (2) packed red blood cell (PRBC) transfusion, or (3) hemoglobin (Hgb) decline. Patients with major bleeding prior to their first TPE were excluded from the analysis.
RESULTS: Among 779 patients undergoing TPE, major bleeding by at least one of the three bleeding definitions occurred in 135 patients (17.3%). For each of the ICD/CPT, PRBC, and Hgb definitions, the prevalence of major bleeding was 2.8% (n = 31), 7.4% (n = 81), and 5.4% (n = 59), respectively. Only 3.7% of bleeds (5/135) were captured by all three definitions and 19.3% (26/135) exclusively by any two pairwise definitions. The addition of PRBC transfusion and Hgb decline to ICD/CPT code definitions increased bleeding prevalence threefold.
CONCLUSIONS: Among hospitalized adults undergoing TPE in the REDS-III study, the prevalence of major bleeding was 17.3%. The addition of PRBC and Hgb decline to ICD codes increased bleeding prevalence threefold. Future studies are needed to develop validated models that identify patients at risk for major bleeding during TPE.

Background: This study aimed to determine the real-world safety and effectiveness of remdesivir in hospitalized adult COVID-19 patients with moderate-to-critical disease in Indonesia. Methods: A multicenter, retrospective cohort study was conducted at four COVID-19 referral hospitals in Jakarta. A total of 587 patients were included, of whom 243 received remdesivir within 72 h of admission. The safety endpoints were the proportions of patients with any adverse event (AE), any grade 3 AE, and AE of each system organ class. The effectiveness endpoints were ICU admission >24 h from baseline, live discharge and mortality at day 14, live discharge and mortality at day 28, and virologic conversion. Patients who received remdesivir within 72 h of admission were considered the treatment group, and those who did not were the control group. Multivariate adjustments were performed using a modified Poisson regression. Results: The study found no significant differences in safety endpoints between the two groups. However, the effectiveness endpoints showed that remdesivir was associated with a decreased risk of ICU admission >24 h from baseline (RR 0.71, 95% CI 0.52-0.96), an increased probability of live discharge at day 14 (RR 1.37, 95% CI 1.08-1.74), and an increased probability of live discharge at day 28 (RR 1.28, 95% CI 1.05-1.57). The rate of virologic conversion was not significantly different between the two groups. Conclusion: The study concludes that remdesivir is safe and effective in the treatment of moderate-to-critical COVID-19 in a real-world setting in Indonesia.