Remdesivir-Related Cardiac Adverse Effects in COVID-19 Patients: A Case-Control Study.

BACKGROUND: There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients. METHODS: The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patient's medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured. RESULTS: Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisher's exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications. CONCLUSION: Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications.

Baricitinib and Pulse Steroids Combination Treatment in Hyperinflammatory COVID-19: A Rheumatological Approach in the Intensive Care Unit.

Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.

Mechanism of Abnormal Activation of MEK1 Induced by Dehydroalanine Modification.

Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.

Relationship between adherence to bictegravir/emtricitabine/tenofovir alafenamide fumarate and clinical outcomes in people with HIV in Japan: a claims database analysis.

A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80- < 90%, and < 80% groups, respectively. Across all PDC groups, more than 90% of patients who received B/F/TAF were receiving treatment at 1 year. There was no significant difference in the risk of discontinuation between the lower PDC groups (80- < 90% and < 80%) and the PDC ≥ 90% group (0.400 [0.096, 1.661]; 2.244 [0.663, 7.594], hazard ratio [95% confidence interval], respectively). A drug resistance test was implemented for 15 patients, none of whom discontinued B/F/TAF after the test. The results suggest that events that could cause discontinuation, such as virologic failure, were not associated with PDC.

Ecofriendly micellar mediated spectrofluorimetric method for ultrasensitive quantification of the antiparkinsonian drug safinamide in pharmaceutical formulation and spiked human plasma.

A novel, highly sensitive and eco-friendly micellar-mediated spectrofluorimetric method was developed and validated for the determination of the novel antiparkinsonian drug safinamide mesylate in the presence of its related precursor impurity, 4-hydroxybenzaldehyde. The proposed approach relies on increasing the inherent fluorescence emission at 296 nm of safinamide, by forming hydrogen bonds between the mentioned drug and sodium dodecyl sulfate in the micellar system using 0.1 N HCl as a solvent, following excitation at 226 nm. A thorough investigation was conducted into the experimental factors affecting spectrofluorimetric behavior of the studied drug. A linearity plot of safinamide over the concentration range of 10.0-1000.0 ng/mL against the relative fluorescence intensities was established. The proposed method demonstrated excellent sensitivity down to the nano-gram level with detection and quantitation limits of 1.91 and 5.79 ng/mL, respectively. The studied drug was effectively determined in Parkimedine® Tablets. Furthermore, the proposed method allows for ultrasensitive quantification of safinamide in spiked human plasma, with satisfactory percentage recovery (98.97-102.28%). Additionally, the greenness assessment using the advanced green certificate classification approach, the complementary green analytical procedure index (Complex-GAPI), and the analytical GREEness metric approach (AGREE), along with the practicality check using the Blue Applicability Grade Index in addition to the all-inclusive overall whiteness evaluation using the RGB-12 model were carried out. The outcomes demonstrated the effectiveness and whiteness of the proposed technique. Clearly, the suggested approach has the advantages of being simple, requiring no pretreatment steps, and relying solely on direct measuring procedures.

Remdesivir alleviates skin fibrosis by suppressing TGF-ß1 signaling pathway.

Fibrotic skin diseases, such as keloids, are pathological results of aberrant tissue healing and are characterized by overgrowth of dermal fibroblasts. Remdesivir (RD), an antiviral drug, has been reported to have pharmacological activities in a wide range of fibrotic diseases. However, whether RD function on skin fibrosis remains unclear. Therefore, in our study, we explored the potential effect and mechanisms of RD on skin fibrosis both in vivo and in vitro. As expected, the results demonstrated that RD alleviated BLM-induced skin fibrosis and attenuates the gross weight of keloid tissues in vivo. Further studies suggested that RD suppressed fibroblast activation and autophagy both in vivo and in vitro. In addition, mechanistic research showed that RD attenuated fibroblasts activation by the TGF-ß1/Smad signaling pathway and inhibited fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. In summary, our results demonstrate therapeutic potential of RD for skin fibrosis in the future.

The effect of early versus late remdesivir treatment in hospitalized mild to moderate COVID-19 patients in the Omicron era: A retrospective study.

Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0-3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, P = .03). Delaying remdesivir treatment ≥ 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18-32.44; P = .03) and Charlson comorbidity index ≥ 3 (aOR, 9.62; 95% CI, 1.65-56.10; P = .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.

Early progression during or after cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy indicates poor outcome with rescue protocols in dogs with multicentric lymphoma.

BACKGROUND: Dogs with lymphoma that fail cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (CHOP) before completion of their protocol are commonly thought to have poor long-term outcome, but no previous studies have evaluated the effect of early relapse on progression-free interval (PFI) or overall survival time (OST) for patients undergoing rescue chemotherapy. OBJECTIVE: Correlate rescue treatment outcomes in dogs with multicentric lymphoma with outcomes after 1st-line CHOP chemotherapy. METHODS: Data were collected from 6 previous retrospective or prospective studies in 187 dogs with multicentric lymphoma that received 1st-line CHOP chemotherapy and then received either lomustine (CCNU), L-asparaginase and prednisone (LAP), or rabacfosadine (RAB, Tanovea), with or without prednisone or L-asparaginase. RESULTS: The PFI after initiation of CHOP chemotherapy was significantly associated with response rate postprogression, PFI, and postrescue survival time (ST) for both rescue protocols. Immunophenotype (B- vs T-cell) was not significantly associated with response, PFI or OST for LAP but was significantly associated with response and PFI for RAB. CONCLUSION: Dogs that experience short PFI during or after 1st-line CHOP chemotherapy had lower response rates to rescue treatment, with shorter PFI and ST. Immunophenotype did not significantly affect outcome with LAP but was associated with PFI for RAB.

Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model.

Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function is thought to play a key role in Long COVID. Despite its importance, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells, mucus-secreting HT29 cells and Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin-1, occludin, and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir, the fusion inhibitor EK1 and the transmembrane serine protease 2 inhibitor Camostat inhibited SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.

DA-9601 has protective effects comparable to those of proton pump inhibitor and rebamipide against nonsteroidal anti-inflammatory drugs-induced upper and lower gastrointestinal bleeding in patients with rheumatoid arthritis: A nationwide study using Korean Health Insurance Review and Assessment Service database.

DA-9601 extracted from Artemisia asiatica contains a bioactive compound - eupatilin - that can protect against gastric mucosal damage through anti-inflammatory and anti-oxidative properties and is approved for treating acute and chronic gastritis in Korea, but their ability to protect gastrointestinal (GI) bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is unclear. We aimed to compare the protective effects of DA-9601 to those of proton pump inhibitors (PPI) and rebamipide against upper and lower GI bleeding in patients with rheumatoid arthritis (RA) undergoing long-term NSAIDs therapy using the Korean Health Insurance Review and Assessment database. In this nationwide retrospective cohort study, we evaluated patients with RA who concurrently received NSAIDs for >3 months with DA-9601, PPI, or rebamipide between January 2015 and December 2017. The index date was the date of NSAIDs initiation, and all patients were followed up until December 2020 to detect upper and lower GI bleeding. In total, 24,258 patients with RA were eligible, and 5468 (22.5%), 4417 (18.2%), and 14,373 (59.3%) received DA-9601, PPI, or rebamipide, respectively, on the index date. During follow-up, upper and lower GI bleeding occurred in 508 (2.1%) and 402 (1.6%) patients with RA, respectively. The incidence rate of upper and lower GI bleeding was 615/100,000 and 485/100,000 person-years, respectively. Among patients with RA receiving DA-9601, PPI, or rebamipide, the frequencies of NSAIDs-induced upper GI bleeding were 0.5%, 0.4%, and 1.2%, respectively. The frequencies of NSAIDs-induced lower GI bleeding were 0.4%, 0.4%, and 0.9%, respectively. The incidence of NSAIDs-induced upper GI bleeding in patients with RA receiving DA-9601, PPI, and rebamipide was 601/100,000, 705/100,000, and 596/100,000 person-years, respectively, while the incidence of NSAIDs-induced lower GI bleeding in the same groups was 449/100,000, 608/100,000, and 465/100,000 person-years, respectively. In the multivariate Cox regression analysis, no significant difference was observed in lower and upper GI bleeding hazards between patients with RA using DA-9601, PPI, and rebamipide. Our results suggest that DA-9601 may exhibit protection against NSAIDs-induced GI bleeding that is comparable to those of PPI and rebamipide in patients with RA.

Association of renal function with mortality among hospitalized patients treated with remdesivir for COVID-19.

BACKGROUND AND AIM: Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function. METHODS: We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups. RESULTS: The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30-59; OR 1.46 for eGFR 15-29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2. CONCLUSIONS: Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir.

Is Antiviral Treatment with Remdesivir at the Acute Phase of SARS-CoV-2 Infection Effective for Decreasing the Risk of Long-Lasting Post-COVID Symptoms?

The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study was performed. Hospitalized COVID-19 survivors who had received intravenous Remdesivir during the acute phase (n = 216) were matched by age, sex, body mass index, and vaccination status with survivors who did not receive antiviral treatment (n = 216). Participants were asked to self-report the presence of any post-COVID symptom (defined as a symptom that started no later than three months after infection) and whether the symptom persisted at the time of study (mean: 18.4, SD: 0.8 months). Anxiety levels (HADS-A), depressive symptoms (HADS-D), sleep quality (PSQI), and severity/disability (FIC) were also compared. The multivariate analysis revealed that administration of Remdesivir at the acute COVID-19 phase was a protective factor for long-term COVID development (OR0.401, 95%CI 0.256-0.628) and specifically for the following post-COVID symptoms: fatigue (OR0.399, 95%CI 0.270-0.590), pain (OR0.368, 95% CI 0.248-0.548), dyspnea at rest (OR0.580, 95%CI 0.361-0.933), concentration loss (OR0.368, 95%CI 0.151-0.901), memory loss (OR0.399, 95%CI 0.270-0.590), hair loss (OR0.103, 95%CI 0.052-0.207), and skin rashes (OR0.037, 95%CI 0.005-0.278). This study supports the potential protective role of intravenous administration of Remdesivir during the COVID-19 acute phase for long-lasting post-COVID symptoms in previously hospitalized COVID-19 survivors.

Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure.

BACKGROUND/AIM: Reports regarding the association of remdesivir use for the treatment of Coronavirus disease 2019 (COVID-19) with the development of acute kidney injury (AKI) are inconsistent, and the associations between the use of other antivirals and AKI remain unclear. Therefore, this study investigated whether the use of antiviral drugs for the treatment of COVID-19 is a risk factor for the development of AKI. PATIENTS AND METHODS: This study analyzed 176,197 reports submitted to the Japanese Adverse Event Reporting Database between 2020 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (95%CIs) for AKI that were associated with the use of antiviral drugs in patients with COVID-19 were calculated after adjusting for potential confounders. RESULTS: Overall, 5,879 of the reports analyzed were associated with AKI. Signs of AKI were detected with the use of remdesivir [crude ROR (cROR)=2.45; 95%CI=1.91-3.14] and nirmatrelvir/ritonavir (cROR=6.07; 95%CI=4.06-9.06). These results were maintained even after adjusting for potential confounders [remdesivir: adjusted ROR (aROR)=2.18; 95%CI=1.69-2.80, nirmatrelvir/ritonavir: aROR=5.24; 95%CI=3.48-7.90]. However, when analyzing data stratified by reporting year, the association between remdesivir and AKI appeared to diminish over time and was not sustained. CONCLUSION: Nirmatrelvir/ritonavir use may be associated with developing AKI. This knowledge may be useful in helping patients with COVID-19 avoid AKI complications.

Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial).

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

Electrophysiological Profile of Different Antiviral Therapies in a Rabbit Whole-Heart Model.

Antiviral therapies for treatment of COVID-19 may be associated with significant proarrhythmic potential. In the present study, the potential cardiotoxic side effects of these therapies were evaluated using a Langendorff model of the isolated rabbit heart. 51 hearts of female rabbits were retrogradely perfused, employing a Langendorff-setup. Eight catheters were placed endo- and epicardially to perform an electrophysiology study, thus obtaining cycle length-dependent action potential duration at 90% of repolarization (APD90), QT intervals and dispersion of repolarization. After generating baseline data, the hearts were assigned to four groups: In group 1 (HXC), hearts were treated with 1 µM hydroxychloroquine. Thereafter, 3 µM hydroxychloroquine were infused additionally. Group 2 (HXC + AZI) was perfused with 3 µM hydroxychloroquine followed by 150 µM azithromycin. In group 3 (LOP) the hearts were perfused with 3 µM lopinavir followed by 5 µM and 10 µM lopinavir. Group 4 (REM) was perfused with 1 µM remdesivir followed by 5 µM and 10 µM remdesivir. Hydroxychloroquine- and azithromycin-based therapies have a significant proarrhythmic potential mediated by action potential prolongation and an increase in dispersion. Lopinavir and remdesivir showed overall significantly less pronounced changes in electrophysiology. In accordance with the reported bradycardic events under remdesivir, it significantly reduced the rate of the ventricular escape rhythm.

Comparative Study of Treatment Outcome with Tenofovir Alafenamide and Entecavir in Patients with HBV Related Acute on Chronic Liver Failure.

Major causes of acute insult in Hepatitis B virus related acute on chronic liver failure in the Asian region are reactivation of Hepatitis B virus and super infection with hepatitis A and E virus (ACLF). Anti viral therapy should be started as soon as possible in the ACLF patients at presentation while waiting for confirmation by HBV DNA level. This randomized controlled trial was carried out at the Department of Hepatology, BSMMU, Bangladesh from September 2019 to august 2020 with Hepatitis B virus related ACLF patient. This trial was conducted among twenty seven HBV acute on chronic liver failure patient to compare Child Turcotte pugh (CTP) score, Model for end stage liver disease (MELD) score, Asia Pacific Association for study of Liver (APASL) ACLF Research consortium (AARC) score, survival of the patients and HBV DNA level at 3 months with antiviral therapy between tenofovir alafenamide (25mg) and entecavir (0.5mg) group. CTP score, MELD score and AARC score were significantly (p<0.05) decline from baseline to all subsequent follow-up at 1st (at 7 days), 2nd (at 14 days), 3rd (at 30 days) and 4th (at 90 days) in each group but non significant (p>0.05) difference occurred between two group. All twenty seven patients had detectable HBV DNA level at pre-treatment and all survived patients became undectable at 4th, 90 days follow-up. Total 10 patients (37.07%) were survived at 90 days follow-up, out of them seven patients (70.0%) were in tenofovir alafenamide group and three patients (30.0%) were in entecavir group which was statistically significant (p<0.05) in between two group. Hepatic encephalopathy and hepatorenal syndrome were most common causes of death in both groups. Both drugs tenofovir alafenamide and entecavir significantly improves liver functions but the former one is superior regarding survival.

COVID-19 pneumonia in lung transplant recipients: understanding risk factors and treatment outcomes in Japan.

Lung transplant (LTx) recipients face a significant risk from coronavirus disease 2019 (COVID-19), with elevated hospitalization mortality rates even post-vaccination. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) typically induces pneumonia in even healthy individuals, it can also infect the transplanted lungs of LTx recipients, potentially leading to graft dysfunction. Despite the prevalence of COVID-19 pneumonia in LTx recipients, data on its characteristics and associated risk factors remain limited. This retrospective study analyzed data from LTx recipients at Tohoku University Hospital between January 2001 and November 2023. COVID-19 cases were identified, and patient records, including thoracic computed tomography (CT) evaluations, were reviewed. Patient characteristics, vaccination history, immunosuppressant use, and comorbidities were assessed. Descriptive analysis was utilized for data presentation. Among 172 LTx recipients, 39 (22.7%) contracted COVID-19, with 9 (23%) developing COVID-19 pneumonia. COVID-19 incidence in LTx recipients aligned with national rates, but pneumonia risk was elevated. Delayed antiviral therapy initiation was noted in pneumonia cases. Remdesivir was uniformly administered and remained the primary treatment choice. LTx recipients are susceptible to COVID-19 pneumonia, warranting vigilance and tailored management strategies. Pre-transplant vaccination and prompt COVID-19 diagnosis and treatment are imperative for optimizing outcomes in this population.

Continuous co-prescription of rebamipide prevents upper gastrointestinal bleeding in NSAID use for orthopaedic conditions: A nested case-control study using the LIFE Study database.

BACKGROUND: Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age. METHODS: A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users. FINDINGS: Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users. CONCLUSIONS: Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age.

Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.