Objective screening for olfactory and gustatory dysfunction during the COVID‐19 pandemic: A prospective study in healthcare workers using self‐administered testing

BackgroundSmell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID‐19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID‐19 patients suggests that self‐reported measures are insufficient for capturing patients with chemosensory dysfunction.ObjectivesThe purpose of this study was to quantify the impact of recent COVID‐19 infection on chemosensory function and demonstrate the use of at‐home objective smell and taste testing in an at‐risk population of healthcare workers.MethodsTwo hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self‐administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one‐month follow‐up surveys were completed.ResultsAmong subjects with prior SARS‐CoV‐2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self‐reported smell and taste loss were both strong predictors of COVID‐19 positivity. Subjects with evidence of recent SARS‐CoV‐2 infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was a time‐dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab.ConclusionHealthcare workers with recent SARS‐CoV‐2 infection had reduced olfaction and normal gustation on self‐administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.     

Risk factors for an atherothrombotic event in patients with diabetic macular edema treated with intravitreal injections of bevacizumab

AIM: To identify risk factors for an atherothrombotic event (ATE) among patients who were treated for DME with intravitreal bevacizumab injections. METHODS: This retrospective study enrolled all consecutive patients with DME who were treated by intravitreal bevacizumab from 2009 through 2016 in a single center. They were divided into one group treated by bevacizumab and subsequently had an ATE and a second group also treated by bevacizumab and did not have an ATE. RESULTS: A total of 455 patients with DME were enrolled. Seventy-two of the patients had an ATE. A multivariate model adjusted for age, gender, smoking, body mass index, HbA1c, duration of diabetes, creatinine, and blood pressure revealed an increased risk for ATE in the patients with diabetic duration of more than 13y, a systolic blood pressure over 153 mm Hg at first treatment, or having been treated by more than 4 intravitreal bevacizumab injections. Additionally, patients that had an ATE within 3mo from the last intravitreal treatment underwent more bevacizumab injections (5.17±3.82 vs 3.08±1.96; P=0.0003). CONCLUSIONS: The risk factors for an ATE identified in this study were systolic blood pressure >153.5 mm Hg, a history of diabetic mellitus for more than 13y, and treatment with more than 4 intravitreal bevacizumab injections. These factors need to be borne in mind when bevacizumab is being considered in the management of patients with DME.     

Maternal Adnexal Torsion in Pregnancy Is Associated with Significant Risk of Recurrence

Study ObjectivesTo investigate the phenomenon of recurrent adnexal torsion during the same pregnancy, describe its risk factors, and suggest possible management of this entity.DesignRetrospective case-control study (Canadian Task Force classification II-3).SettingGynecologic endoscopy unit in a university hospital.Patients and interventionsPregnant women with surgically proved adnexal torsion were retrospectively identified from 1993 to 2007. Details of clinical presentation, method of conception, preoperative ultrasound findings, and operative findings were analyzed.InterventionComparison of characteristics of patients with recurrent episodes of adnexal torsion during the same pregnancy vs a single episode of torsion.Measurements and Main ResultsThirty-three pregnant women with 38 episodes of adnexal torsion were included in the study. Seventeen pregnancies (51.5%) were spontaneously conceived. Twenty-eight women had a single episode of torsion, and 5 women (15.1%) had recurrent episodes of torsion during the same pregnancy. No significant differences were found between the 2 groups in age, method of conception, and gestational age at time of torsion. However, ultrasound studies demonstrated that multicystic ovaries were significantly more common in women with recurrent torsion compared with women with a single episode of torsion (80% vs 25%; p = .02). The interval between the first and second episodes of torsion ranged from 1 to 4 weeks.ConclusionPregnant women are at risk for recurrent torsion, especially when the ovaries are enlarged and ultrasound studies demonstrate multiple cysts. Cyst aspiration may prevent recurrent torsion during the same pregnancy.     

Molecular mechanisms underlying membrane-potential-mediated regulation of neuronal K2P2.1 channels

The activity of background K_2P channels adjusts the resting membrane potential to enable plasticity of excitable cells. Here we have studied the regulation of neuronal K_2P2.1 (KCNK2, TREK-1) channel activity by resting membrane potential. When heterologously expressed, K_2P2.1 currents gradually increased at hyperpolarizing potentials and declined at depolarizing potentials, with a midpoint potential of ? 60 mV. As K_2P channels are not equipped with an integral voltage sensor, we sought extrinsic cellular components that could convert changes in the membrane electrical field to cellular activity that would indirectly modify K_2P2.1 currents. We propose that membrane depolarization activated the Gq protein-coupled receptor pathway, in the apparent absence of ligand, resulting in phosphatidylinositol-4,5-bisphosphate (PIP₂) depletion through the action of phospholipase C. Our results suggest a novel mechanism in which an indirect pathway confers membrane potential regulation onto channels that are not intrinsically voltage sensitive to enhance regulation of neuronal excitability levels.     

A physiologic flow chamber model to define intravascular ultrasound enhancement of fibrin using echogenic liposomes

RATIONALE AND OBJECTIVES: Echogenic immunoliposomes (ELIP) for enhancement of vasoactive and pathologic components of endothelium and atherosclerosis have been developed. A physiologic flow chamber model has been developed to define intravascular ultrasound enhancement of a fibrin interface. METHODS: A IgG ELIP was used, which nonspecifically associated with fibrin, to demonstrate the suitability of this model. With varying doses of IgG ELIP, the fibrin wells were imaged at 1, 2, 4, 6, and 9 minutes. RESULTS: IgG ELIP enhanced fibrin versus saline (P < 0.005) was visible at 1 minute, lasted at least 9 minutes, and at 6 minutes the interface enhanced 27% +/- 6.1%. Enhancement was caused by increases in interface thickness and brightness. Enhancement increased with dose up to 8 mg lipid (n = 4 per time point). CONCLUSION: This model can quantitate the components of IVUS enhancement of an interface produced by ELIP. This model may allow for further development and understanding of ELIP and other targeted ultrasound contrast agents.     

White matter hyperintensities on magnetic resonance imaging of the brain in children with psychiatric disorders

The current study sought to determine the prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance imaging assessments of children and adolescents with psychiatric disorders. Seventy-one percent (N = 934) of children admitted to the McLean Hospital Child and Adolescent inpatient treatment unit were evaluated with the Diagnostic Interview Schedule for Children (DISC) within 7 days of admission during the period 1988 to 1993 (total, 1,308 admissions). Four hundred eight of these subjects (43.7%) were referred for brain magnetic resonance imaging (MRI) scans and became our study subjects (mean age, 12.4 years [SD = 2.7]; male/female, 230/178). Study subjects were grouped according to a hierarchical diagnostic system as follows: schizophrenia (n = 42), bipolar disorder (n = 56), unipolar depression (n = 94), conduct disorder/attention deficit disorder (n = 103), and other neurotic disorders (n = 30). Subjects without any level 2 diagnosis on DISC (n = 83) constituted the comparison group. Bipolar disorder, unipolar depression, and conduct disorder/attention deficit disorder groups were significantly more likely to have severe levels of WMH than the comparison group (prevalence rates: 17.9%, 13.8%, 13.6% v 1.2%). In addition, the bipolar disorder group was significantly more likely to have severe levels of WMH than the schizophrenia group (prevalence rates: 17.9% v 2.4%). The frontal lobes were the predominant locations of WMH in the bipolar disorder and unipolar depression groups (76.9% and 60.0%, respectively) and also the most frequent location for the conduct disorder/attention deficit disorder group (35.7%). The current study reports an increased prevalence and severity of WMH in children with bipolar disorder, unipolar depression, and conduct disorder/attention deficit disorder relative to the comparison group and in children with bipolar disorder compared to those with schizophrenia. The development of brain WMH, especially in the frontal lobes, may play a role in the pathophysiology of affective disorders in children and adolescents.     

Erythropoietin signaling promotes invasiveness of human head and neck squamous cell carcinoma

Erythropoietin (Epo) is used for managing anemia in cancer patients. However, recent studies have raised concerns for this practice. We investigated the expression and function of Epo and the erythropoietin receptor (EpoR) in tumor biopsies and cell lines from human head and neck cancer. Epo responsiveness of the cell lines was assessed by Epoetin-alpha-induced tyrosine phosphorylation of the Janus kinase 2 (JAK2) protein kinase. Transmigration assays across Matrigel-coated filters were used to examine the effects of Epoetin-alpha on cell invasiveness. In 32 biopsies, we observed a significant association between disease progression and expression of Epo and its receptor, EpoR. Expression was highest in malignant cells, particularly within hypoxic and infiltrating tumor regions. Although both Epo and EpoR were expressed in human head and neck carcinoma cell lines, only EpoR was upregulated by hypoxia. Epoetin-alpha treatment induced prominent JAK2 phosphorylation and enhanced cell invasion. Inhibition of JAK2 phosphorylation reduced both basal and Epo-induced invasiveness. Our findings support a role for autocrine or paracrine Epo signaling in the malignant progression and local invasiveness of head and neck cancer. This mechanism may also be activated by recombinant Epo therapy and could potentially produce detrimental effects in rhEpo-treated cancer patients.     

Early and frequent histological recurrence of Crohn's disease in small intestinal allografts

BACKGROUND: Recurrence of Crohn's disease in small intestinal allografts, although rarely described, can cause serious morbidity and jeopardize graft survival among transplant recipients with Crohn's disease. However, systematic studies to determine the frequency, predictors, and clinical implications of recurrent Crohn's disease have not been reported METHODS: We analyzed our transplant program's experience with small intestinal allografts in patients with Crohn's disease based on retrospective review of clinical and pathological records and corresponding pathology slides. RESULTS: Of 67 patients undergoing 70 transplantations between 1998 and 2004, six adults (three males, three females; mean age 48.1 years) had Crohn's disease complicated by short gut syndrome and total parenteral nutrition failure. Four survivors surveyed endoscopically for a mean 29 (range, 20-40) months and underwent a mean 37 endoscopic examinations with biopsies (range, 31-44) while on maintenance immunosuppression. Despite absence of any endoscopic or clinical manifestations of Crohn's disease throughout this period, two patients had granulomatous enteritis characteristic of Crohn's disease in multiple biopsies, one patient in 8/44 examinations (18%) ranging from 34 days to 20 months postoperatively and the other in 6/32 examinations (19%) ranging from 20 days to 22 months postoperatively. No comparable changes occurred in 57 other patients without Crohn's disease followed endoscopically under the same protocol CONCLUSIONS: Histological recurrence of Crohn's disease may occur in small intestinal allografts despite the absence of endoscopic and clinical disease manifestations. Such recurrences are probably not rare, may occur as early as 3 weeks after transplantation, and do not necessarily portend early clinical recurrence or mandate aggressive therapy to prevent allograft loss.