Comparative Analysis of De Novo Immune Thrombocytopenia Following mRNA COVID-19 Vaccine Versus Non-mRNA Vaccines and COVID-19: A Global Database Analysis.

Introduction Autoimmune diseases have been linked to COVID-19 vaccines. An increasing number of cases have reported de novo immune thrombocytopenia (ITP) following mRNA COVID-19 vaccines. This study aims to investigate the incidence of de novo ITP following the mRNA COVID-19 vaccine in comparison to other non-mRNA vaccines and COVID-19. Methods Data were collected from the TriNetX global health research network, which covers over 117 million patients. Four different patient cohorts were included: those who received the mRNA COVID-19 vaccine (between 12/15/2020 - 5/1/2023), the influenza vaccine (between 01/01/2010 - 01/01/2020), tetanus, diphtheria, and pertussis/tetanus and diphtheria (Tdap/Td) vaccines (between 01/01/2010 - 01/01/2020), and those who had COVID-19 (between 01/01/2020 - 05/01/2023). A comparative analysis was conducted to examine the occurrence of de novo ITP within three weeks after receiving mRNA COVID-19 vaccine, non-mRNA vaccines, or upon diagnosis of COVID-19. Additionally, a comparative analysis was performed after 1:1 propensity score matching to balance baseline characteristics (age, sex, and race). Results The overall event rate was 0.07 per 10,000 for the mRNA COVID-19 vaccine, 0.25 per 10,000 for the influenza vaccine, and 0.28 per 10,000 for the Tdap/Td vaccines. Additionally, the incidence of de novo ITP following COVID-19 was 0.30 per 10,000. Those who received the influenza vaccine and Tdap/Td vaccines had higher rates of de novo ITP compared to the mRNA COVID-19 vaccine group, with a relative risk of 3.48 and 3.88, respectively. The occurrence of de novo ITP following COVID-19 was significantly higher compared to that following the mRNA COVID-19 vaccine, with a relative risk of 4.27. Post-propensity score matching analysis produced similar outcomes. Conclusions The findings of this study suggest that the incidence of de novo ITP is significantly lower following mRNA-based COVID-19 vaccines compared to non-mRNA vaccines and COVID-19.

Outcomes of COVID-19 in Adult Males With Hemophilia A: A Propensity Score-Matched Analysis.

Background Hypercoagulability is a major pathologic event in COVID-19. Factor VIII plays an important role in hemostasis, and high levels of factor VIII have been shown to be associated with an increased risk of thrombosis and severe disease. Little is known about the impact of COVID-19 on clinical outcomes in patients with hemophilia A. Methodology Retrospective data of adult male patients with COVID-19 with and without hemophilia A were retrieved from the TriNetX database (Cambridge, USA). The 1:1 propensity score-matching was performed to balance baseline characteristics. Patients were matched for age, race, body mass index, and medical comorbidities. Thirty-day outcomes were assessed. Results We identified 1,758 patients with pre-existing hemophilia A diagnosis prior to COVID-19 diagnosis and 5,191,908 comparators. After 1:1 propensity score matching, groups were balanced on demographics and comorbidities. All-cause mortality rates were similar between the two groups (HR 0.805; 95% CI 0.467-1.389). The frequency of severe infection, ICU admission, and composite thrombotic events did not differ between the groups. Patients with hemophilia A were hospitalized more frequently than those without a history of hemophilia A (19.2% vs. 14.4%; p<0.05). Additionally, gastrointestinal (GI) bleeding and composite bleeding events occurred more frequently in patients with hemophilia A (3.2% vs. 2.2%; p<0.05 and 4.0% vs. 2.8%; p<0.05, respectively). Conclusions The mortality of individuals with hemophilia A due to COVID-19 is comparable to the general population but with higher risks of hospitalization and bleeding.

Improving compliance with appropriateness of testing for heparin-induced thrombocytopaenia: a quality improvement report.

Heparin-induced thrombocytopaenia (HIT) is a serious complication of heparin therapy. Evidence-based guidelines recommend the use of the 4Ts scoring system to calculate pretest probability of HIT. However, this scoring system is often underused, and inappropriate testing can lead to increased morbidity, medical costs and length of hospital stay. We identified that inappropriate testing for HIT was common at our institution and implemented structured multicomponent educational interventions to evaluate the impact of education on the appropriateness of HIT testing. The educational interventions led to a significantly increased rate of appropriateness of HIT testing (69% vs 35%; p=0.001). In addition, the 4Ts score documentation rate significantly improved following the intervention (52% vs 17%; p=0.001). The rates of discontinuation of heparin products and initiation of alternative anticoagulation increased, although not statistically significantly. Educational interventions can improve compliance with evidence-based guidelines on appropriateness of testing for HIT.

Oxacillin-induced leukocytoclastic vasculitis.

Leukocytoclastic vasculitis (LCV) refers to a histopathological pattern of neutrophil predominant inflammatory process of small vessels associated with fibrinoid necrosis. Cutaneous LCV usually presents as symmetrically distributed palpable purpuric nodules of the lower extremities with or without systemic involvement. Although 50% of LCV cases are idiopathic, it can be secondary to identifiable causes such as malignancy, autoimmune conditions, infections, and medications. Medications have been implicated in up to 25% of cases; sulfonamides, NSAIDs, and beta-lactams have the most frequent association. We herein present a 32-year-old female who developed palpable purpura over hands and lower limbs 12 days after exposure to oxacillin administered for infective endocarditis. Punch biopsy from the skin lesions confirmed the diagnosis of LCV. Given the temporal relationship between oxacillin administration and development of skin findings, the diagnosis of oxacillin-associated LCV was suspected. Discontinuation of drug resulted in resolution of the lesions confirming the diagnosis. To our knowledge, this is the second case of oxacillin-induced cutaneous LCV described in literature.

Acute histopathological responses of testicular tissues after different fractionated abdominal irradiation in rats.

PURPOSE: To compare the effects of different fractionated doses of abdominal radiation therapy on acute histopathological responses of testicular tissues in rats. METHODS: Thirty-three 3-week-old Wistar albino rats were randomized into 6 groups: group 1 (n = 5), control; group 2 (n = 4), hypofractionated total abdominal irradiation (TAI) of 6 Gy/1 fraction/day for 2 days; group 3 (n = 6), hypofractionated TAI of 4 Gy/1 fraction/day for 3 days; group 4 (n = 6), hypofractionated TAI of 3 Gy/1 fraction/day for 4 days; group 5 (n = 6), conventionally fractionated TAI of 2 Gy/1 fraction/day for 6 days; group 6 (n = 6), conventionally fractionated TAI of 1.7 Gy/1 fraction/day for 7 days. Mean epithelial length and diameter of seminiferous tubules of testicular tissues were determined after euthanasia. RESULTS: Initially, a highly significant decrease in both the mean tubular diameter and epithelial height of the seminiferous tubules was demonstrated in all irradiated rats compared with the control group. No significant differences regarding both damage parameters were found between different hypofractionated radiation therapies. Both conventional radiation therapies reduced the epithelial height and mean diameter of the seminiferous tubules to a lesser extent when compared with 6 Gy/1 fraction/day hypofractionated therapy. It was further shown that parameter values were comparable between rats that received 3 Gy/day hypofractionated therapy and rats that received either of the two conventional therapies. Furthermore, although 4 Gy/day hypofractionation decreased tubular diameter and epithelial length to a greater degree compared with the conventional therapy of 1.7 Gy/1 fraction/day, no statistically significant difference was found when compared with conventional therapy of 2 Gy/1 fraction/day. Additionally, no statistically significant difference was demonstrated between the two types of conventional radiotherapy application. CONCLUSION: The present study demonstrated that hypofractionated abdominal irradiation leads to more prominent tissue damage in the testes than conventional irradiation.

Monocyte CD40 expression in young healthy female smokers and/or oral contraceptives users without additional risk factors for atherosclerosis.

OBJECTIVE: Atherosclerosis, as an inflammatory disease, is characterized by pathologically altered levels of cytokines. We investigated whether smoking and/or oral contraceptives (OCs) affect the CD40/CD40L plasma levels and expression in young females without other risk factors for atherosclerosis. PATIENTS AND METHODS: A case-control single-center design was used. Expression levels of CD40/CD40L were analyzed in healthy non-pregnant, pre-menopausal, non-smoking women who did not take OCs (n=49), women who currently smoke and take OCs (n=40), and women who are only smokers (n=40) or currently take OCs (n=42). RESULTS: In OC users, there was a significant increase in CD40 mRNA expression in circulating monocytes as compared with smokers and control group. However, there were no significant differences in CD40 mRNA expression in monocytes between smokers and non-smokers. Interestingly, CD40 mRNA expression in women taking OCs and currently smoking was significantly decreased compared to only OC users (p<0.001). With regard to plasma CD40 levels there were significant differences between OC-users and control group. However, contrary to our expectations, there were no significant differences in expression levels of CD40L between four groups. In vitro experiments demonstrated enhanced CD40 mRNA and surface expression in human monocyte-derived macrophages stimulated with estrogens. Furthermore, nicotine pretreatment led to a suppression of estrogens stimulated CD40 induction. CONCLUSIONS: In young healthy females without additional risk factors for atherosclerosis, OCs, but not smoking, are associated with dramatic changes in CD40 gene and plasma levels. These findings may be providing an important link between OCs and enhancement of pro-inflammatory and atherothrombotic conditions in healthy women.

Effects of parathyroid hormone-related peptide on the large conductance calcium-activated potassium channel and calcium homeostasis in vascular smooth muscle cells.

AIM: To demonstrate the impact of the parathyroid hormone-related peptide (PTHrP) on the large conductance calcium-activated potassium (BKCa) channels in vascular smooth muscle cells (VSMC) and hyperpolarization of the cell membrane and its dependence on calcium. MATERIALS AND METHODS: VSMC were isolated from rat aorta and further subcultured. Four experiments were conducted in calcium-release measurements and each of them consisted of a control group, PTHrP, chemical substance, and PTHrP + chemical substance. Chemical substances used were: iberiotoxin, xestospongin C, xestospongin D, and thapsigargin, respectively. Fura-2 imaging was used to determine changes in calcium release of VSMC. In membrane-potential experiments, groups were designed similarly to the Fura-2 imaging experiments: iberiotoxin, BAPTA, and xestospongin D were added, in respective order. Changes in the membrane potential were examined using the fluorescence dye (DiBAC). RESULTS: Given in a dose between 0.01 and 1.0 µmol/L, PTHrP caused a concentration-dependent decrease in fluorescence intensity, with a maximum effect at 0.5 µmol/L. The decrease, therefore, demonstrated a PTHrP-induced hyperpolarization of the VSMC. The effect was blocked by use of iberiotoxin (100 nmol/L), a highly selective inhibitor of BKCa. Furthermore, when the calcium chelator BAPTA (10 µmol/L) was added, there was a significant reduction in PTHrP-induced hyperpolarization. Use of PTHrP (0.5 µmol/L) also decreased the fluorescence intensity of the indicator for intracellular calcium, Fura-2AM (a membrane-permeable derivative of Fura 2). This effect was re-blocked by use of iberiotoxin. Xestospongin C (3 µmol/L) and xestospongin D (6 µmol/L), both inhibitors of the inositol 1,4,5 trisphosphate-triggered calcium release, inhibited the effects of PTHrP. Additionally, thapsigargin (1 µmol/L), a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor, inhibited the effect of PTHrP. CONCLUSION: The results of our study show that PTHrP induces hyperpolarization and activates BKCa in VSMC. The activation of BKCa channels is calcium dependent; activation is linked to the inositol 1,4,5 trisphosphate-triggered calcium release and is also dependent on the endo/sarcoplasmic reticulum calcium pump.

The impact of statins on FGF-2-stimulated human umbilical vein endothelial cells.

AIM: To determine the effects of different types of statins on proliferative and migrative behaviors of basic fibroblastic growth factor (FGF)-2-stimulated endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated and cultured. Groups were arranged in order to observe the impact of each individual substance alone, or under stimulation with statin on FGF-2-stimulated endothelial cells. Endothelial cells were stimulated with human growth factor (HGF), statins, methyl-ß-cyclodextrin (ß-MCD), and either farnesyl pyrophosphate (FPP) ammonium salt, or geranylgeranyl-pyrophosphate (GGPP), respectively. Cell proliferation analyses were performed 48 hours after stimulation and gaps between migration borders were used in migration analyses. RESULTS: The statins showed significant antiproliferative and anti-migrative effects and inhibited the proliferative behavior of FGF-2. However, endothelial cell proliferation and migration were significantly increased after mevalonate co-incubation. Experiments with ß-MCD indicated that the destruction of lipid rafts had a negative impact on the action of FGF-2. Stimulation of statin-incubated cells with FPP had no additional effect on proliferation or migration. Notably, although FGF-2 exerted a pro-migrative effect, the effect was not shown in the FPP + FGF-2 group. The anti-migrative actions of statins along with disruption of membrane integrity were reversed by the addition of GGPP. CONCLUSION: The angiogenic effect of FGF-2 is suppressed through inhibition of the intracellular cholesterol biosynthesis via statins. Inhibitory effects of statins on FGF-2-stimulated HUVECs were observed to result from both the inhibition of isoprenylation and the destruction of lipid rafts on the cell membrane.

Discovery of asymptomatic Krukenberg tumors diagnosed during caesarean section: therapy with hyperthermic intraperitoneal chemotherapy.

We report a case of the discovery of asymptomatic Krukenberg tumors in a 37-year-old woman in the 37th week of pregnancy during caesarean section. Subsequent gastroscopy revealed an adenocarcinoma of the stomach as the primary tumor site. The patient was treated with hyperthermic intraperitoneal chemotherapy (HIPEC). Tumor surgery (Partial parietal peritonectomy and partial gastrectomy) and HIPEC treatment were successful, with no complications found during follow-up. Use of HIPEC seems to be a promising option after radical surgery, including its use in patients with gastric tumors that are in advanced stages, and use in patients who have tumors with poor prognoses, such as Krukenberg tumors.