Evidence of Thrombogenesis Recurrence Induced by IgA Antiphospholipid Antibody ß2 Glycoprotein I-Dependent in Early Adulthood.

Antiphospholipid antibodies (aPLs) against Beta-2 glycoprotein-I (ß2GPI) are considered to be the center of pathogenesis of antiphospholipid syndrome (APS). Autoimmune aPLs are pathogenic as patients are at increased risk of enhancing thrombin generation at a young age. There are only three aPLs considered as diagnostic laboratory markers for APS - IgM, IgG, and IgA isotypes. However, the association of the IgA isotypes with clinical thrombosis remains highly controversial. A 30-year-old male with a past medical history of childhood asthma initially presented to the hospital with acute left middle cerebral artery ischemic stroke, which did not get resolved with tissue plasminogen activator (tPA) but was successfully resolved with thromboembolectomy. It was speculated to be associated with a clot from mitral valve prolapse found subsequently on echocardiogram. Twenty-eight days later, the patient presented again with a high-grade luminal narrowing of his mid- and distal left internal carotid artery with 80% narrowing and an acute dissection of his left internal carotid artery. The recurrence of thrombosis was evaluated through hypercoagulable state workup, which demonstrated evidence of antiphospholipid syndrome with elevated beta-2 glycoprotein IgA antibody titers of more than 150 U/mL. This is one of the first cases reported nationwide as evidence of thrombogenesis recurrence induced by IgA antiphospholipid antibody ß2 glycoprotein I-dependent in early adulthood. IgA anti- ß2GPI antibodies are found to have an association with many clinical manifestations of antiphospholipid syndrome and thrombotic events, particularly arterial thrombosis. To determine the link between the IgA-aß2GPI antibodies and APS-events in asymptomatic individuals before recommending preventive treatments, there needs to be a broader intention to standardize IgA-aß2GPI assays as a diagnostic criterion for APS.

Ciliated respiratory epithelium encapsulating Pseudomonas brain abscess due to prior trauma.

Bacterial brain abscesses are typically spread through a haematogenous route. Open head wounds and neurosurgical interventions are uncommon aetiologies. Ectopic tissue found in the cerebral cortex is usually ascribed almost entirely from carcinomas. Here, we describe a 57-year-old gentleman who, 22 years after a fireworks related traumatic injury to the left orbit, presented with headaches and altered behaviour. Imaging revealed an abscess immediately superior to the orbit, whose bacterial aetiology was identified to be Pseudomonas aeruginosa, encapsulated by ciliated respiratory epithelium. This represents a case in which tissue was displaced during the initial trauma or craniofacial reconstructive surgery from the frontal sinus.

Anticoagulation Management and Outcomes in Patients With Covid-19 With Propensity Score Matching: A Multicenter Retrospective Cohort Study.

BACKGROUND: Therapeutic doses of anticoagulation have been administered to patients with coronavirus-19 disease (Covid-19) without thromboembolism, although there is a lack of robust evidence supporting this practice. STUDY QUESTION: To compare outcomes between patients admitted to the hospital for Covid-19 who received full-dose anticoagulation purely for the indication of Covid-19 and patients who received prophylactic doses of anticoagulation. STUDY DESIGN: This is a multicenter retrospective cohort study, including 7 community hospitals in Michigan. Patients were >18 years of age, confirmed positive for Covid-19 by polymerase chain reaction, and admitted to the hospital between March 10 and May 3, 2020. Exposed group: Patients receiving therapeutic dose anticoagulation for Covid-19 for any duration excluding clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction; control group: Patients receiving prophylactic anticoagulation. Propensity score matching was used to adjust for the nonrandomized nature of the study. MEASURES AND OUTCOMES: The primary endpoint: 30-day in-hospital mortality. Secondary endpoints: intubation, length of hospital stay, and readmissions in survivors. RESULTS: A total of 115 exposed and 115 control patients were analyzed. Rates of 30-day in-hospital mortality were similar (exposed: 33.0% vs. control: 28.7%). Controlling for institution, there was no significant association between treatment and 30-day in-hospital mortality (hazard ratio: 0.63; 95% confidence interval: 0.37-1.06). Survivors had statistically similar length of hospital stay and readmission rates. CONCLUSIONS: We found no difference in mortality in patients with Covid-19 without clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction who received therapeutic versus prophylactic doses of anticoagulation.

When Do Ring-Enhancing Brain Lesions Need to Be Biopsied, and Should They Be Treated Empirically First?

Other than acute cerebrovascular accidents, multiple ring-enhancing lesions are among the most common lesions encountered in neuroimaging. We herein describe the case of a 63-year-old diabetic man presenting with altered mental status, hyperglycaemia and community-acquired pneumonia who was found to have two ring-enhancing lesions involving the left frontal lobe and left basal ganglia. The lesions were biopsied to reveal positive fungal cultures and toxoplasma cysts. RPR titres returned reactive for non-treponemal antibodies and a suppressed CD4 count was found without evidence of HIV infection. LEARNING POINTS: An approach is discussed that will direct clinicians to decide whether to treat ring-enhancing brain lesions empirically or biopsy them first.

Unusual Manifestations of Acute Cytomegalovirus Infection in Solid Organ Transplant Hosts: A Report of Two Cases.

Cytomegalovirus (CMV) infection is a common cause of morbidity and mortality in immunocompromised hosts. Tissue-invasive CMV disease causing ulcerative skin disease or esophageal necrosis is rare. We herein describe two cases: a 47-year-old renal and pancreas transplant recipient who presented with skin ulcerations on his elbow and a 50-year-old renal transplant recipient who presented with acute esophageal necrosis. In both, tissue biopsy revealed CMV inclusion bodies by immunohistochemical staining of infected endothelial and mucosal cells. Ganciclovir was given to both cases and full remission occurred. Due to the varying presentations of acute CMV infection in immunosuppressed hosts, high suspicion and early tissue biopsy are vital for proper diagnosis and treatment when any suspicious cutaneous or mucosal manifestations are present.

Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species.

Angiotensin II (AII) plays a major role in the progression of chronic kidney diseases. Podocytes are essential components of the ultrafiltration apparatus, and are targets for AII signaling. AII has been shown to increase generation of reactive oxygen species (ROS) in podocytes. Canonical transient receptor potential-6 (TRPC6) channels stimulate Ca(2+) influx in podocytes, and have been implicated in glomerular disease. We observed that AII increased cationic currents in rat podocytes in an isolated glomerulus preparation in which podocytes are still attached to the underlying capillary. This effect was completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by endogenously expressed angiotensin II receptors in these cells. These responses were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor D-609, and by inhibition of G protein signaling. The pan-protein kinase C inhibitor chelerythrine had no effect. Importantly, pretreating podocytes with the ROS quencher manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) eliminated AII activation of TRPC6. Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). These data suggest that ROS production permits activation of TRPC6 channels by G protein and PLC-dependent cascades initiated by AII acting on AT1Rs in podocytes. This pathway also provides a basis whereby two forms of cellular stress-oxidative stress and Ca(2+) overload-converge on common pathways relevant to disease.