Elevated International Normalized Ratio and Mortality in Hospitalized Patients Treated with Direct Oral Anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) are associated with a prolongation of the prothrombin time and an increased international normalized ratio (INR). The clinical significance of these changes is unclear. This study aimed to examine the association between an elevated INR on admission and in-hospital death and long-term survival in patients treated with DOACs. METHODS: Data were retrospectively retrieved from records of hospitalized patients at the Sheba Medical Center between November 2008 and July 2023. Patients were selected based on DOAC treatment, coagulation profile, and INR test done within 48 hours of hospitalization. The outcomes were in-hospital mortality and mortality in the year following hospitalization. RESULTS: The study included 11,399 hospitalized patients treated with DOACs. Patients with elevated INR had a 180% higher risk of in-hospital mortality (adjusted odds ratio 2.80; 95% confidence interval, 2.30-3.39) and a 57% increased risk of death during the following year (adjusted hazard ratio 1.57; 95% confidence interval, 1.44-1.71). Similar results were observed in subgroup analyses for each DOAC. CONCLUSIONS: An elevated INR on admission is associated with a higher risk for in-hospital death and increased risk for mortality during the first year following hospitalization in hospitalized patients treated with DOACs. This highlights that elevated INR levels in patients on DOACs should not be dismissed as laboratory variations due to DOAC treatment, as they may serve as a prognostic marker.

The COVID-19 pfizer BioNTech mRNA vaccine and the frequency of seizures.

OBJECTIVE: A nationwide vaccination operation against Coronavirus disease 2019 (COVID-19) using the BNT162b2 mRNA vaccine commenced in Israel in December 2020. People older than 60 were prioritized, and most were vaccinated shortly after. Seizures are not infrequently attributed to the vaccine despite a lack of supporting evidence. People with epilepsy (PWE) are often reluctant to get the vaccine due to concerns of seizure aggravation. We aim to examine the effect of the vaccine effort on the frequency of both new-onset seizures and recurrent seizures in PWE. METHODS: All adults who presented to the emergency department (ED) of Tel Aviv Sourasky Medical Center between January 1st and May 31st, 2017-2021, and were diagnosed with seizures were included. Demographic, clinical, and vaccination status parameters were collected using MDClone, a data acquisition tool. Vaccination rates in the general population were obtained from official governmental publications. Statistics included a sub-analysis of patients with the highest vaccination rate, people older than 60. RESULTS: 1675 cases were included. The numbers of ED visits and hospital admissions due to seizures in 2021 were comparable to preceding years after adjusting for the total number of ED visits at the same time. Out of 339 cases in 2021, 134 patients older than 60 years old presented to the ED (39.5%) compared to 124-151 in 2017-2019 (37-44%) and 103 in 2020 (33%). The vaccination rate among patients hospitalized due to seizures was similar to the general population of the same age group during the same period in Israel. There was no temporal relation between vaccination and hospitalization due to a seizure. SIGNIFICANCE: Despite very high vaccination rates in the general population in Israel and especially among people older than 60 years, no increase was observed in ED presentations due to seizures. No temporal relation was observed between vaccination and hospitalization due to a seizure. We conclude that the mass vaccination with the Pfizer BioNTech mRNA vaccine is not associated with increased seizure propensity.

Radiation Therapy Before Repeat Wide Resection for Unplanned Surgery of Soft Tissue Sarcoma ("Oops" Operation) Results in Improved Disease-Free Survival.

Purpose: The main goal of treatment of soft-tissue sarcomas is achieving wide negative margins to improve local control and prevent recurrence. The role of radiation therapy (RT) is well established in sarcomas of the extremities; however, its role in unplanned surgery of soft-tissue sarcoma (when a mass presumed to be benign is resected and the pathology comes back as sarcoma, usually referred to as an "oops" operation) is inconclusive. This article reports on the effect of RT after an unplanned surgery before the reresection. Methods and Materials: A total of 65 patients who had undergone an unplanned resection of a postoperatively diagnosed soft-tissue sarcoma were treated with RT and/or surgery and retrospectively evaluated for disease progression. Treatment started with RT in 49 cases (75.4%), including 8 cases of no further surgery. A repeat wide resection was performed directly after the initial surgery in 16 patients, followed by RT in 15 of them. Results: The disease recurred in 7 out of 49 patients (14.3%) who received RT first and in 9 out of 16 (56.25%) who underwent reoperation before RT (P = .001). Disease-free progression was higher in cases of low-grade malignancy (P = .049). A clinical diagnosis of lipoma was associated with a better outcome than a diagnosis of nonlipoma (P = .034). The presence of residual tumor at reoperation did not affect disease control. Patient age, time between symptom onset and diagnosis, hospital level of initial diagnosis (tertiary versus nontertiary), anatomic site, tumor size, and margin status at the initial excisional biopsy were not significantly correlated with the outcome. Conclusion: Initiating treatment with RT followed by unplanned "oops" resection of soft-tissue sarcoma before the reresection improved disease-free survival as opposed to vice versa.

BNT162b2 mRNA COVID-19 vaccine three-dose safety and risk of COVID-19 in patients with myasthenia gravis during the alpha, delta, and omicron waves.

COVID-19 affects the respiratory parenchyma and may potentially contribute to the tendency of myasthenia gravis (MG) patients to develop respiratory failure. It is, therefore, important to study the safety of vaccines against SARS-CoV-2 and to assess the risk of COVID-19 in MG patients. The safety of the three-dose BNT162b2 mRNA vaccine and outcomes of COVID-19 during the alpha, delta, and omicron waves were studied in MG patients as well as the rate of exacerbations and safety for a period of up to 6 weeks from each vaccine dose and patient morbidity and mortality during COVID-19 compared to the general population. 430 vaccine doses were administered across 150 patients. Thirteen patients (8.7%) complained of exacerbation within 6 weeks of each vaccine dose. Both MG onset rate and exacerbation rate were similar to previous years. MG exacerbation rate among fifteen patients who had COVID-19 was significantly higher (40%) compared to the rate following vaccination. During the alpha and delta waves, COVID-19 mortality and severe disease were significantly higher (26.7%) compared to the general population (0.96%). All of them were unvaccinated and had generalized MG. During the omicron wave, all the MG patients who contracted COVID-19 were vaccinated and had mild disease. We concluded that COVID-19 is hazardous for generalized MG patients, while the vaccination did not raise the risk for either exacerbation or new onset of MG and was associated with a reduced risk for severe COVID-19. Hence, it is recommended for generalized MG patients to get vaccinated.