Venous and arterial thrombosis in patients with VEXAS syndrome.

ABSTRACT: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, is an autoinflammatory disorder with diverse systemic manifestations. Thrombosis is a prominent clinical feature of VEXAS syndrome. The risk factors and frequency of thrombosis in VEXAS syndrome are not well described, due to the disease's recent discovery and the paucity of large databases. We evaluated 119 patients with VEXAS syndrome for venous and arterial thrombosis and correlated their presence with clinical outcomes and survival. Thrombosis occurred in 49% of patients, mostly venous thromboembolism (VTE; 41%). Almost two-thirds of VTEs were unprovoked, 41% were recurrent, and 20% occurred despite anticoagulation. The cumulative incidence of VTE was 17% at 1 year from symptom onset and 40% by 5 years. Cardiac and pulmonary inflammatory manifestations were associated with time to VTE. M41L was positively associated specifically with pulmonary embolism by univariate (odds ratio [OR]: 4.58, confidence interval [CI] 1.28-16.21, P = .02) and multivariate (OR: 16.94, CI 1.99-144.3, P = .01) logistic regression. The cumulative incidence of arterial thrombosis was 6% at 1 year and 11% at 5 years. The overall survival of the entire patient cohort at median follow-up time of 4.8 years was 88%, and there was no difference in survival between patients with or without thrombosis (P = .8). Patients with VEXAS syndrome are at high risk of VTE; thromboprophylaxis should administered be in high-risk settings unless strongly contraindicated.

Venous thromboembolism after COVID-19 vaccination in patients with thrombophilia.

Patients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID-19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID-19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD-10 codes. A total of 792 010 patients with at least one COVID-19 vaccination were identified. Six thousand sixty-seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53-1.23). In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.

Endocardial Fibroelastosis: A Comprehensive Review.

Endocardial fibroelastosis emerged as a challenging clinical phenomenon in the 1940s. It is characterized by an atypical proliferation of fibrous and elastic tissue within the heart and is primarily observed in childhood, occasionally displaying familial inheritance. While the precise cause remains elusive, various factors, including genetic, infectious, metabolic, autoimmune, oncologic, and medication-related influences, appear to play a role in its pathogenesis. The coexistence of endocardial fibroelastosis with multiple cardiac structural abnormalities manifests in symptoms of congestive heart failure and rhythm abnormalities. Despite its challenging diagnosis, various findings from ECG and imaging have proven beneficial in further evaluation of this condition. Finally, the treatment approach to endocardial fibroelastosis became complex due to addressing its concurrent cardiac abnormalities. Strategies for managing and preventing this condition are still under investigation. In this review, we intend to highlight the existing knowledge and illuminate future considerations regarding the etiology, diagnosis, and management of this disease.

Reduced calf muscle pump function is not explained by handgrip strength measurements.

OBJECTIVE: Reduced calf muscle pump function (CPF) is an independent risk factor for venous thromboembolism and mortality. We aimed to evaluate the relationship between handgrip strength (HGS) and CPF. METHODS: Patients referred to the Gonda Vascular Laboratory for noninvasive venous studies were identified and consented. Patients underwent standard venous air plethysmography protocol. CPF (ejection fraction) was measured in each lower extremity of ambulatory patients by comparing refill volume after ankle flexes and passive refill volumes. The cutoff for reduced CPF (rCPF) was defined as an ejection fraction of <45%. Maximum HGS bilaterally was obtained (three trials per hand) using a dynamometer. HGS and CPF were compared (right hand to calf, left hand to calf) and the correlation between the measures was evaluated. RESULTS: 115 patients (mean age, 59.2 ± 17.4 years; 67 females, mean body mass index, 30.83 ± 6.46) were consented and assessed for HGS and CPF. rCPF was observed in 53 right legs (46%) and 67 left legs (58%). CPF was reduced bilaterally in 45 (39%) and unilaterally in 30 (26%) patients. HGS was reduced bilaterally in 74 (64.3%), unilaterally in 23 (20%), and normal in 18 (15.7%) patients. Comparing each hand/calf pair, no significant correlations were seen between HGS and CPF. The Spearman's rank correlation coefficients test yielded values of 0.16 for the right side and 0.10 for the left side. CONCLUSIONS: There is no significant correlation between HGS and CPF, demonstrating that HGS measurements are not an acceptable surrogate for rCPF, indicating different pathophysiological mechanisms for each process.

Staging Extramitral Cardiac Damage in Mitral Annular Calcification With Mitral Valve Dysfunction.

BACKGROUND: Mitral annular calcification (MAC) is a progressive degenerative process associated with comorbidities and increased mortality. A staging system that considers extramitral cardiac damage in MAC may help improve patient selection for mitral valve interventions. OBJECTIVES: This study sought to develop a transthoracic echocardiogram (TTE)-based cardiac staging system in patients with MAC and significant mitral valve dysfunction and assess its prognostic utility. METHODS: We retrospectively evaluated all adults who underwent TTE over 1 year at Mayo Clinic with MAC and significant mitral valve dysfunction defined as mitral stenosis and/or at least moderate mitral regurgitation. Patients were categorized into 5 stages according to extramitral cardiac damage by TTE. All-cause mortality and heart failure hospitalization were assessed. RESULTS: For the 953 included patients, the mean age was 76.2 ± 10.7 years, and 54.0% were women. Twenty-eight (2.9%) patients were classified in stages 0 to 1, 499 (52.4%) in stage 2, 115 (12.1%) in stage 3, and 311 (32.6%) in stage 4. At the 3.8-year follow-up, mortality was significantly higher in patients in stages 2 to 4 compared to stages 0 to 1 and increased with each stage. Survival differences were maintained after adjustment for age, diabetes mellitus, and glomerular filtration rate. The rate of heart failure hospitalization was significantly higher in stages 3 and 4 compared to stages 0 to 1. Similar results were observed in subgroup analysis in patients with moderate or severe MAC, predominant mitral stenosis, or predominant mitral regurgitation. CONCLUSIONS: Using the proposed extramitral cardiac damage staging system in patients with MAC and significant mitral valve dysfunction, more advanced stages are associated with higher mortality.

Calf rEF: Impact of Calf Muscle Pump Dysfunction With Reduced Ejection Fraction on All-Cause Mortality.

OBJECTIVE: To evaluate mortality outcomes by varying degrees of reduced calf muscle pump (CMP) ejection fraction (EF). PATIENTS AND METHODS: Consecutive adult patients who underwent venous air plethysmography testing at the Mayo Clinic Gonda Vascular Laboratory (January 1, 2012, through December 31, 2022) were divided into groups based on CMP EF for the assessment of all-cause mortality. Other venous physiology included measures of valvular incompetence and clinical venous disease (CEAP [clinical presentation, etiology, anatomy, and pathophysiology] score). Mortality rates were calculated using the Kaplan-Meier method. RESULTS: During the study, 5913 patients met the inclusion criteria. During 2.84-year median follow-up, there were 431 deaths. Mortality rates increased with decreasing CMP EF. Compared with EF of 50% or higher, the hazard ratios (95% CIs) for mortality were as follows: EF of 40% to 49%, 1.4 (1.0 to 2.0); EF of 30% to 39%, 1.6 (1.2 to 2.4); EF of 20% to 29%, 1.7 (1.2 to 2.4); EF of 10% to 19%, 2.4 (1.7 to 3.3) (log-rank P≤.001). Although measures of venous valvular incompetence did not independently predict outcomes, venous disease severity assessed by CEAP score was predictive. After adjusting for several clinical covariates, both CMP EF and clinical venous disease severity assessed by CEAP score remained independent predictors of mortality. CONCLUSION: Mortality rates are higher in patients with reduced CMP EF and seem to increase with each 10% decrement in CMP EF. The mortality mechanism does not seem to be impacted by venous valvular incompetence and may represent variables intrinsic to muscular physiology.

Administration of Silver Nanoparticles in Diabetes Mellitus: A Systematic Review and Meta-analysis on Animal Studies.

Biological features of silver nanoparticles in rising the insulin level of diabetic animal models were considered in recent years, which resulted in decreasing hyperglycemia condition. We reviewed the published literature to investigate the possible role of silver nanoparticles (Ag-NPs) throughout the treatment of diabetes mellitus in animal studies. In this systematic review and meta-analysis, we performed a search throughout the English literature of electronic databases, including Scopus, PubMed, and ISI Web of Science, up to the date of May 22, 2020. Primary outcomes and data regarding fast blood sugar (FBS), lipid profile, and liver enzyme were collected from the available articles, while the studies that did not provide sufficient information on the effects of silver nanoparticles through the course of diabetes mellitus were excluded. Our search yielded 1283 results that included five animal studies in the meta-analysis. The comparison between the plasma insulin level of the diabetic group treated by Ag-NPs with the diabetic control group displayed no significant differences with the P values = 0.299. In addition, significant differences were revealed by comparing the FBS level of the diabetic group treated by Ag-NPs with the diabetic control group (P value < 0.001). According to the present meta-analysis, the application of Ag-NPs in animal models resulted in displaying the anti-diabetic effects, which can be applied in future treatments. Furthermore, a correlation was noticed between these nanoparticles and the reduction of serum FBS among diabetic cases.

Rhinitis as the Presenting Symptom of Pineal Region Epidermoid Tumor: A Case Report.

Brain tumors are the rarest cause of cerebrospinal fluid rhinorrhea. Non-traumatic cerebrospinal fluid rhinorrhea is also a relatively rare condition. It may be misdiagnosed as allergic rhinitis or chronic sinusitis and lead to unsuitable treatment. We described a 34-year-old man who came to our allergy clinic with a chief complaint of clear rhinorrhea from his left nostril with more than four years of duration. Onlyhypertrophy of left inferior concha was found in the clinical examination. His rhinorrhea aggravated when bending forward. So we were suspicious of CSF rhinorrhea. MRI was done for him and demonstrated a large tumor in the pineal region. The patient underwent surgery with resection of the mass via an infratentorial-supracerebellar approach. This case showed the role of maintaining differential diagnosis for a common complaint; rhinitis which is seen as usual.

Effect of oral ginger on prevention of nausea and vomiting after laparoscopic cholecystectomy: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) are among the most frequent complications following laparoscopic cholecystectomy. Recently, some studies have shown ginger, as an herbal medicine, to be effective and safe in PONV prevention; however, there is no evidence of its efficacy in the Iranian population. OBJECTIVE: The aim of this study was to determine the effect of oral ginger on PONV prevention after laparoscopic cholecystectomy. METHODS: This double-blind, randomized, placebo-controlled clinical trial was performed on women who were undergoing laparoscopic cholecystectomy in Imam Raza Hospital, Mashhad, Iran between April and November, 2016. Patients were divided randomly into two groups of G) intervention group (n=75, received 2 capsules containing 250 mg ginger) and P) placebo group (n=75, received 2 placebo capsules) one hour before surgery. Nausea severity and vomiting frequency were evaluated at 2, 4, 6, and 12 hours after the operation. Data analysis was done by SPSS version 16.0 software with Chi-square test, Independent-sample-t-test, repeated measure ANOVA and Mann-Whitney U test. RESULTS: The two groups were homogenous in terms of age, gender and surgery duration. The severity of nausea was lower in the ginger group at the 2, 4, 6, and 12 hours after the operation; however, these differences were statically significant only at 2 (p=0.034) and 12 hours (p=0.043). Although the incidence of vomiting was higher in the placebo group in the 2nd and 12th hours after surgery, the number of vomiting episodes in 2, 4, 6 and 12 hours after surgery was statistically similar in the two groups (p>0.05). The nausea severity was significantly changed during 12 hours of study in both groups (p=0.001), however the nausea severity was always lower in the ginger group (p=0.078). CONCLUSION: This study demonstrated that 500mg oral ginger one hour before surgery in women who were undergoing laparoscopic cholecystectomy is effective in decreasing severity of PONV. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2016122222218N2. FUNDING: The study was financially supported by Deputy of Research of Mashhad University of Medical Sciences.

Cardiac Calcified Amorphous Tumor of the Mitral Valve Presenting as Transient Ischemic Attack.

Cardiac calcified amorphous tumors (CATs) are an extremely rare nonneoplastic intracardiac masses. They have been reported in the literature in only a few cases. Thus, the incidence, pathogenesis, and best approach to the treatment are not certain. We report a case of CATs on the atrial surface of the anterior mitral valve leaflet in a 37-year-old female who was diagnosed by histopathological examination after surgical removal.