Polymyalgia Rheumatica Following Respiratory Syncytial Virus (RSV) Vaccination.

Introduction: Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder that causes stiffness and pain in the proximal joints, including the shoulders, hips and neck. The exact cause of polymyalgia rheumatica is yet to be fully understood, but research suggests that both genetic and environmental factors may contribute to it. Studies have previously linked the onset and relapse of polymyalgia rheumatica symptoms to the influenza and COVID-19 vaccines. The Food and Drug Administration approved the respiratory syncytial virus (RSV) vaccine, which is a recombinant protein vaccine for adults over 60, in May 2023. No previous reports of polymyalgia rheumatica onset or relapse have been linked to the RSV vaccine. The human proteome shares some peptides with the RSV F antigen, suggesting a high risk of cross-reactivity when using that antigen in vaccination formulations. Case description: A 72-year-old man experienced a new onset of bilateral shoulder pain and stiffness three days after receiving the Abrysvo® RSV vaccine. The symptoms lasted more than an hour (up until noon) and interfered with his activities of daily living. Inflammatory markers such as C-reactive protein were elevated. The patient's symptoms and inflammatory marker levels significantly improved with prednisone therapy. Conclusion: In patients with typical PMR symptoms, it is important for clinicians to carefully review immunisation history to rule out any potentially related adverse effects. LEARNING POINTS: Vaccines can trigger autoimmune diseases in some individuals.This case report suggests respiratory syncytial virus (RSV) vaccine is among the possible triggers for polymyalgia rheumatica.

PARP inhibitor-related acute renal failure: a real-world study based on the FDA adverse event reporting system database.

BACKGROUND: Current clinical trial data on PARP inhibitors (PARPis)-related acute renal failure (ARF) are not entirely representative of real-world situations. Therefore, in this study, the US Food and Drug Administration Adverse Event Reporting System (FAERS) was used to evaluate PARPis-related ARF. RESEARCH DESIGN AND METHODS: Data were obtained from 1 January 2015, to 30 September 2023. ARF event reports were analyzed based on four algorithms. The time-to-onset (TTO) and clinical outcomes of PARPis-associated ARF were assessed. RESULTS: The total included cases were 2726. Significant signals were observed for olaparib, niraparib, and rucaparib (reporting odds ratio (ROR): 1.62, 95% confidence interval (CI): 1.49-1.78, 1.25, 95% CI: 1.19-1.32 and 1.59, 95% CI: 1.47-1.72 respectively). The median TTO of ARF onset was 57, 36, and 85 days for olaparib, niraparib, and rucaparib, respectively. The proportion of deaths with olaparib (9.88%) was significantly higher than for niraparib (2.52%) and rucaparib (2.94%) (p < 0.005). The proportion of life-threatening adverse events associated with niraparib (4.89%) was significantly higher than for rucaparib (0.98%) (p < 0.005). CONCLUSIONS: ARF and PARPi were related, with the exception of talazoparib. More emphasis should be given to PARPis-related ARF due to the high proportion of serious AEs and delayed adverse reactions.

A real-world pharmacovigilance study of FDA adverse event reporting system events for atogepant.

BACKGROUND: Atogepant, an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist, is being investigated for the treatment of migraine. METHODS: We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Four algorithms (ROR, PRR, BCPNN, and EBGM) were used as measures to detect signals of atogepant-associated adverse events (AEs) in real-world data. RESULT: Of the 3,552,072 reports, 2876 expressly stated the use of atogepant. Women accounted for the majority of adverse events (AEs), with a notable age concentration of 45-65 years. The percentage of reported adverse events was the highest in the United States. Significant system organ categories (SOC) included nervous system disorders, gastrointestinal disorders, nervous system disorders, surgical and medical procedures, ear and labyrinth disorders. Notably, preferred terms (PTs) related to atogepant include migraine, constipation, nausea, vertigo, somnolence, decreased appetite, dizziness and fatigue. Unexpected adverse events such as abnormal dreams, self-injurious ideation, brain fog, tension headache, nightmare, brain neoplasm, feeling abnormal, euphoric mood, hyperacusis and post concussion syndrome were also identified. CONCLUSIONS: The present investigation has detected new and unexpected signals of atogepant-related adverse drug reactions (ADRs). In order to confirm these solve safety issues that were previously overlooked, more research is necessary.

A Case of Immune Aplastic Anemia during Combined Treatment with Atezolizumab and Chemotherapy for Non-Small Cell Lung Cancer.

Immune check point inhibitors (ICIs) have durable antitumor effects. However, autoimmune toxicities, termed immune-related adverse events, occur in some patients. We report a case of severe immune aplastic anemia (AA) in a patient with non-small cell lung cancer who was receiving atezolizumab with bevacizumab/carboplatin/paclitaxel. Although the cancer has not recurred, his bone marrow is depleted and he did not respond to immunosuppressive therapy. He has survived for 1.5 years with blood transfusions and infection control. Immune AA associated with ICIs is rare, and a treatment has not yet been established. This case report provides information on the management and treatment response of patients with AA caused by ICIs. Further studies should investigate the mechanism and pathogenesis of immune AA caused by ICIs.

Management and treatment of severe immune-related hepatotoxicity based on clinical and pathological characteristics.

BACKGROUND: The management of severe immune-related hepatotoxicity (irH) needs to be further optimized. This study aims to analyze the clinical characteristics of severe irH; improve the therapeutic strategy, especially salvage treatment in steroid-refractory irH; and determine the safety of immune checkpoint inhibitor (ICPi)-rechallenge. METHODS: This multicenter retrospective study included patients who developed severe irH and those without irH after immunotherapy between May 2019 and June 2023. Propensity score matching was used to match these two cohorts with similar baseline characteristics. RESULTS: Among 5,326 patients receiving ICPis, 51 patients developed severe irH. irH occurred after a median duration of 36 days and a median of two doses after the first ICPi administration. Patients receiving PD-L1 inhibitors faced a lower risk of developing severe irH. A higher dose of glucocorticoids (GCS) was administered to grade 4 irH than grade 3 irH. For steroid-sensitive patients, grade 4 irH individuals received a higher dosage of GCS than those with grade 3 irH, with no difference in time to resolution. Meanwhile, a significantly higher dose of GCS plus immunosuppression was needed in the steroid-refractory group. Liver biopsy of the steroid-refractory patients exhibited heterogeneous histological features. Twelve patients were retreated with ICPi. No irH reoccurred after a median follow-up of 9.3 months. CONCLUSION: irH requires multidimensional evaluation. PD-L1 inhibitors correlated with a lower risk of severe irH. Grade 4 irH demands a higher dose of GCS than recommended. Pathology may guide the salvage treatment for steroid-refractory irH. ICPi rechallenge in severe irH is feasible and safe.

Intralesional hyaluronidase injection to relieve non-hyaluronic acid filler-induced vascular adverse events.

BACKGROUND: Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers are still considered a challenging issue for both patients and practitioners. Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE. For VAEs induced by non-HA fillers, the absence of an "antidote" is regarded as exceptionally challenging. METHODS: This multicenter study describes a case series of three VAEs induced by non-HA fillers, for which ultrasound-guided hyaluronidase injections were incorporated into the treatment approach. RESULTS: Two cases of calcium hydroxylapatite and one case of poly-L-lactic acid-induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound-guided hyaluronidase injections. CONCLUSIONS: Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection-induced spasms could lead to long-lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs.

May the 4th be with you: mixed-methods best-evidence synthesis on 4th-generation alumina-zirconia ceramic bearings in total hip arthroplasty.

Purpose: To assess utility, benefits, and risks of 4th-generation alumina-zirconia ceramic pairings in elective total hip arthroplasty (THA). Methods: A comprehensive mixed-methods best-evidence synthesis using data from systematic reviews, randomized controlled trials (RCTs), prospective and retrospective cohort studies, as well as joint replacement registries, was conducted to estimate overall revision and survival rates, periprosthetic infection, bearing fractures, and noise phenomena with 4th-generation alumina-zirconia ceramic versus other tribological couplings in elective THA. The systematic review part across multiple databases was registered with PROSPERO (CRD42023418076), and individual study data were extracted for statistical re-analysis. Results: Twenty overlapping systematic reviews, 7, 17, and 8 references from RCTs, cohort studies, and joint replacement registries form the basis of this work. According to current best evidence, it is (i) 15-33 times more likely that 4th-generation alumina-zirconia pairings avoid a revision for infection than causing a revision for audible noise, (ii) 38-85 times more likely that 4th-generation alumina-zirconia pairings avoid a revision for infection than causing a revision for ceramic head fractures, and (iii) three to six times more likely that 4th-generation alumina-zirconia pairings avoid a revision for infection than cause a revision for ceramic liner fractures. Conclusion: Fourth-generation alumina-zirconia pairings in THA show a favorable benefit-risk ratio, with rare compound-specific adverse events and complications significantly outbalanced by long-term advantages, such as a markedly lower incidence of revision for infection.

Risk of emergency hospital admission related to adverse events after antibiotic treatment in adults with a common infection: impact of COVID-19 and derivation and validation of risk prediction models.

BACKGROUND: With the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common infections is crucial. This study aims to examines the changes in incidence rates of AEs during the COVID-19 pandemic and predict AE risk following antibiotic prescriptions for common infections, considering their previous antibiotic exposure and other long-term clinical conditions. METHODS: With the approval of NHS England, we used OpenSAFELY platform and analysed electronic health records from patients aged 18-110, prescribed antibiotics for urinary tract infection (UTI), lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), sinusitis, otitis externa, and otitis media between January 2019 and June 2023. We evaluated the temporal trends in the incidence rate of AEs for each infection, analysing monthly changes over time. The survival probability of emergency AE hospitalisation was estimated in each COVID-19 period (period 1: 1 January 2019 to 25 March 2020, period 2: 26 March 2020 to 8 March 2021, period 3: 9 March 2021 to 30 June 2023) using the Kaplan-Meier approach. Prognostic models, using Cox proportional hazards regression, were developed and validated to predict AE risk within 30 days post-prescription using the records in Period 1. RESULTS: Out of 9.4 million patients who received antibiotics, 0.6% of UTI, 0.3% of URTI, and 0.5% of LRTI patients experienced AEs. UTI and LRTI patients demonstrated a higher risk of AEs, with a noted increase in AE incidence during the COVID-19 pandemic. Higher comorbidity and recent antibiotic use emerged as significant AE predictors. The developed models exhibited good calibration and discrimination, especially for UTIs and LRTIs, with a C-statistic above 0.70. CONCLUSIONS: The study reveals a variable incidence of AEs post-antibiotic treatment for common infections, with UTI and LRTI patients facing higher risks. AE risks varied between infections and COVID-19 periods. These findings underscore the necessity for cautious antibiotic prescribing and call for further exploration into the intricate dynamics between antibiotic use, AEs, and the pandemic.

Machine learning algorithm for predicting 30-day mortality in patients receiving rapid response system activation: A retrospective nationwide cohort study.

This study investigated the accuracy of a machine learning algorithm for predicting mortality in patients receiving rapid response system (RRS) activation. This retrospective cohort study used data from the In-Hospital Emergency Registry in Japan, which collects nationwide data on patients receiving RRS activation. The missing values in the dataset were replaced using multiple imputations (mode imputation, BayseRidge sklearn. linear model, and K-nearest neighbor model), and the enrolled patients were randomly assigned to the training and test cohorts. We established prediction models for 30-day mortality using the following four types of machine learning classifiers: Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting, random forest, and neural network. Fifty-two variables (patient characteristics, details of RRS activation, reasons for RRS initiation, and hospital capacity) were used to construct the prediction algorithm. The primary outcome was the accuracy of the prediction model for 30-day mortality. Overall, the data from 4,997 patients across 34 hospitals were analyzed. The machine learning algorithms using LightGBM demonstrated the highest predictive value for 30-day mortality (area under the receiver operating characteristic curve, 0.860 [95 % confidence interval, 0.825-0.895]). The SHapley Additive exPlanations summary plot indicated that hospital capacity, site of incidence, code status, and abnormal vital signs within 24 h were important variables in the prediction model for 30-day mortality.

Transmesenteric internal hernia: an unexpected adverse event induced by colonoscopy.

Transmesenteric internal hernia is an uncommon cause of small bowel obstruction that occurs when small bowel loops protrude through a mesenteric defect into the abdominal cavity. Herein, we present an unexpected case of colonoscopy-induced transmesenteric internal hernia. An 81-year-old male patient presenting with intermittent hematochezia and constipation had undergone a laparoscopic left nephrectomy for ureteral cancer. A colonoscopy was performed to identify the etiology of his symptoms. He complained of severe abdominal pain 2 h after the examination despite uneventful endoscopic procedures, including cold snare polypectomy. Contrast-enhanced computed tomography revealed a strangulated small bowel obstruction with a closed-loop formation outside the descending colon. The small bowel loop was incarcerated into the left retroperitoneal space. Emergency laparotomy detected small bowel loops that prolapsed into the nephrectomy pedicle via a descending mesenteric defect, developed during the laparoscopic left nephrectomy. The incarcerated small bowel was detached from the hernia and returned to its normal position, and the mesenteric defect was closed. He demonstrated an uneventful postoperative course, with no internal hernia recurrence after discharge. This case indicates the risk of transmesenteric internal hernia through inadvertently created mesenteric defects should be borne in mind, especially when performing colonoscopies in patients who underwent laparoscopic nephrectomies.

Omission of alcohol skin cleansing and risk of adverse events in long-term care residents undergoing COVID-19 vaccination: A cohort study.

Despite a lack of clinical data demonstrating the effectiveness of alcohol swab cleansing prior to vaccinations as a prophylactic measure to prevent skin infections, it is recommended for vaccine administration by the Canadian Immunization Guide. The objective of this study was to evaluate the risk of adverse events after omitting alcohol skin cleansing in long-term care (LTC) residents receiving vaccinations during the COVID-19 pandemic. Two medium-sized LTC homes participated in a cohort study, whereby one LTC used alcohol swab cleansing prior to resident vaccinations and the other did not. All residents received two doses of the BNT162b2 COVID-19 vaccine separated by an average (SD) 29.3 (8.5) days. The electronic chart records of participants were reviewed by researchers blinded to group allocation to assess for the presence of adverse events following immunization (AEFI), including reactogenicity, cellulitis, abscess, or systemic reactions. Log-binomial regression was used to compute risk ratios (with 95% confidence intervals) of an AEFI according to alcohol swab status. 189 residents were included, with a total of 56 AEFI between the two doses. The risk of reactogenicity (adjusted RR 0.54, 95% CI 0.17-1.73) or systemic reactions (adjusted RR 0.75, 95% CI 0.26-2.13) did not differ for the residents that received alcohol skin antisepsis compared to those that did not. There were no cases of cellulitis or abscess. This study did not demonstrate an elevated risk of AEFI in LTC residents receiving two doses of the BNT162b2 mRNA COVID vaccine without alcohol skin antisepsis.

Tethered IL15-IL15Rα augments antitumor activity of CD19 CAR-T cells but displays long-term toxicity in an immunocompetent lymphoma mouse model.

BACKGROUND: Adoptive cell therapy using genetically modified T cells to express chimeric antigen receptors (CAR-T) has shown encouraging results, particularly in certain blood cancers. Nevertheless, over 40% of B cell malignancy patients experience a relapse after CAR-T therapy, likely due to inadequate persistence of the modified T cells in the body. IL15, known for its pro-survival and proliferative properties, has been suggested for incorporation into the fourth generation of CAR-T cells to enhance their persistence. However, the potential systemic toxicity associated with this cytokine warrants further evaluation. METHODS: We analyzed the persistence, antitumor efficacy and potential toxicity of anti-mouse CD19 CAR-T cells which express a membrane-bound IL15-IL15Rα chimeric protein (CD19/mbIL15q CAR-T), in BALB/c mice challenged with A20 tumor cells as well as in NSG mice. RESULTS: Conventional CD19 CAR-T cells showed low persistence and poor efficacy in BALB/c mice treated with mild lymphodepletion regimens (total body irradiation (TBI) of 1 Gy). CD19/mbIL15q CAR-T exhibits prolonged persistence and enhanced in vivo efficacy, effectively eliminating established A20 B cell lymphoma. However, this CD19/mbIL15q CAR-T displays important long-term toxicities, with marked splenomegaly, weight loss, transaminase elevations, and significant inflammatory findings in some tissues. Mice survival is highly compromised after CD19/mbIL15q CAR-T cell transfer, particularly if a high TBI regimen is applied before CAR-T cell transfer. CONCLUSION: Tethered IL15-IL15Rα augments the antitumor activity of CD19 CAR-T cells but displays long-term toxicity in immunocompetent mice. Inducible systems to regulate IL15-IL15Rα expression could be considered to control this toxicity.

Confronting the inevitable: When a urologist feels like a second victim.

There are many opportunities for urologists to be emotionally impacted, and possibly injured, in the regular course of their work. In particular, urologists are vulnerable to become Second Victims as a result of errors, adverse events, and distressing clinical events. This article reviews best practices that individuals, training programs, hospitals, and healthcare systems can implement to intentionally and programmatically mitigate the short and long-term effects on healthcare professionals.

Chronic immune-related adverse events arising from immune checkpoint inhibitors: an update.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, improving outcomes for many patients. However, toxicities termed immune-related adverse events (irAEs) are limitations of these revolutionary treatments. These irAEs may resolve with treatment or ICI cessation (acute) or persist many months beyond therapy cessation (chronic). Acute irAEs were the first to be recognized and are thus more well studied. However, chronic irAEs have been highlighted in recent years and are becoming a topic of more intensive investigation. These chronic irAEs have been noted to affect many different organ systems, including endocrine, rheumatologic, gastrointestinal, dermatologic, neurologic, and cardiovascular systems. In this review, we discuss current knowledge surrounding the frequency, time course, and risk factors associated with chronic irAEs affecting various organ systems, treatment approaches, and future directions.

Brivaracetam effectiveness and tolerability in older and younger adults with epilepsy: EXPERIENCE, a pooled analysis of international data from retrospective studies.

This analysis assessed the effectiveness and tolerability of brivaracetam (BRV) in older (≥65 years of age) and younger (≥16 to <65 years of age) adults with epilepsy. This was a subgroup analysis from EXPERIENCE/EPD332, a pooled analysis of individual patient records from multiple independent, non-interventional studies of patients with epilepsy starting BRV in Australia, Europe, and the United States. Included patients had ≥6 months of follow-up data. Outcomes included responders (≥50 % reduction from baseline in seizure frequency), seizure freedom (no seizures within 3 months before the time point), and continuous seizure freedom (no seizures from baseline) at 12 months; BRV discontinuation during the whole study follow-up; and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were deemed non-responders/not seizure-free. Analysis populations included the Full Analysis Set (FAS; patients who received ≥1 BRV dose and had seizure type and age documented at baseline) and the modified FAS (FAS patients who had ≥1 seizure recorded during baseline). The FAS was used for all outcomes except seizure reduction. The FAS included 147 (8.9 %) patients aged ≥65 years and 1497 (91.1 %) aged ≥16 to <65 years. Compared with the younger subgroup, patients aged ≥65 years had a longer median epilepsy duration (33.0 years [n = 144] vs 17.0 years [n = 1460]) and lower median seizure frequency at index (2.0 seizures/28 days [n = 129] vs 4.0 seizures/28 days [n = 1256]), and less commonly had >1 prior antiseizure medication (106/141 [75.2 %] vs 1265/1479 [85.5 %]). At 12 months, a numerically higher percentage of patients aged ≥65 years versus the younger subgroup achieved ≥50 % seizure reduction (46.5 % [n = 71] vs 36.0 % [n = 751]), seizure freedom (26.0 % [n = 100] vs 13.9 % [n = 1011]), and continuous seizure freedom (22.0 % [n = 100] vs 10.7 % [n = 1011]). During the whole study follow-up, 43/147 (29.3 %) patients aged ≥65 years and 508/1492 (34.0 %) aged ≥16 to <65 years discontinued BRV. The incidence of TEAEs since the prior visit was similar in both subgroups at 3 months (≥65 years vs ≥16 to <65 years: 38/138 [27.5 %] vs 356/1404 [25.4 %]), 6 months (19/119 [16.0 %] vs 176/1257 [14.0 %]), and 12 months (8/104 [7.7 %] vs 107/1128 [9.5 %]). This real-world analysis suggests BRV was effective in patients aged ≥65 years and ≥16 to <65 years, with numerically higher effectiveness in the older subgroup. BRV was well tolerated in both subgroups.

Top 10 Signs and Symptoms of Psychotropic Adverse Drug Events to Monitor in Long-Term Care Residents.

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials.

INTRODUCTION: We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210 mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. MATERIALS AND METHODS: PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: Six trials (7990 patients; follow-up period, 6-12 months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12 months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12 months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12 months. CONCLUSION: Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).

Neuroradiological features of contrast-induced neurotoxicity: A systematic review and pooled analysis.

BACKGROUND: Contrast-induced neurotoxicity (CIN), is an increasingly recognised complication of endovascular procedures, presenting as a spectrum of neurological symptoms that mimic ischaemic stroke. The diagnosis of CIN remains a clinical challenge, and stereotypical imaging findings are not established. This study was conducted to characterise the neuroimaging findings in patients with CIN, to raise diagnostic awareness and improve decision making. METHODS: We performed a systematic review of PubMed and Embase databases from inception (1946/1947) to June 2023 for reports of CIN following administration of iodinated contrast media. Studies with a final diagnosis of CIN, which provided details of neuroimaging were included. All included cases were pooled and descriptive analysis was conducted. RESULTS: A total of 84 patients were included, with a median age of 64 years. A large proportion of patients had normal imaging (CT 40.8 %, MRI 53.1 %). CT abnormalities included cortical/subarachnoid hyperattenuation (42.1 %), cerebral oedema/sulcal effacement (26.3 %), and loss of grey-white differentiation (7.9 %). Frequently reported MRI abnormalities included brain parenchymal MRI signal change (40.8 %) and cerebral oedema (12.2 %), most commonly observed on FLAIR sequences (26.5 %). Characterisation of imaging findings according to anatomical location and clinical symptoms has been conducted. CONCLUSIONS: Neuroimaging is an essential part of the diagnostic workup of CIN. Analysis of the anatomical location and laterality of imaging abnormalities may suggest relationship between radiological features and actual clinical symptoms, although this remains to be confirmed with dedicated study. Radiological abnormalities, particularly CT, appear to be transient and reversible in most patients.

Association between specific human leukocyte antigen alleles and development of thyroid immune-related adverse event.

Aim: Inherent variations in human leukocyte antigen (HLA) alleles have been revealed epidemiologically to influence the development of autoimmune diseases. HLA alleles may thus also be associated with the development of immune-related adverse events (irAEs), such as thyroid irAE. Materials & methods: In this case-control study, 71 cancer patients who received immune checkpoint inhibitors were enrolled and HLA-genotyped and the frequency of HLA alleles was compared. Results: A*26:01, DPA1*01:03 and DPB1*02:01 were significantly more frequent in patients with thyroid irAE than in patients without any irAEs (35.0 vs 3.2% [p = 0.004], 80.0 vs 45.2% [p = 0.020] and 55.0 vs 25.8% [p = 0.044], respectively). Conclusion: A*26:01, DPA1*01:03 and DPB1*02:01 appear to be associated with thyroid irAE.

Everyone has a unique combination of human leukocyte antigens (HLAs) in their body that help the immune system identify threats. HLAs were named from the fact that they were first identified on the surface of human leukocytes. Afterward, HLAs were also found on all human cells. HLAs present antigens to immune cells. These HLAs also influence how the immune system attacks cancer cells. Immune checkpoint inhibitors are drugs that can help the immune system fight cancer, but they sometimes cause severe adverse events. In this study, we investigated whether specific HLA genes are related to the development of an adverse event that affects the thyroid in cancer patients treated with immune checkpoint inhibitors. We found an association between three HLA genes (A*26:01, DPA1*01:03 and DPB1*02:01) and the development of the thyroid adverse event. However, larger studies are needed to confirm and generalize these initial exploratory findings.

Analysis of post-market adverse events of tafamidis base on the FDA adverse event reporting system.

Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention.