Evaluation and Resection of a Longitudinal Vaginal Septum in an Adult.

OBJECTIVE: The objective of this video is to demonstrate the diagnosis, evaluation, and techniques for surgical management of a longitudinal vaginal septum, a rare müllerian anomaly. DESIGN: This is a stepwise demonstration of evaluation and surgical techniques with video narration. SETTING: The incidence of müllerian defects, which can include any anomaly in the fallopian tube, uterus, cervix, or vagina, has been estimated to be 2% to 4% [1]; 30% to 40% of patients with müllerian defects also have associated renal anomalies [1,2]. In normal development, the müllerian ducts fuse at 10 weeks' gestation and the septum between the 2 ducts is absorbed in a caudal to cephalad direction [3]. The exact incidence of complete longitudinal vaginal septa is unknown as they are very rare [4]. Longitudinal vaginal septa may cause dyspareunia, inability to have penetrative intercourse, labor dystocia, or hygiene issues and be very emotionally distressing for patients [5]. INTERVENTIONS: Preoperative evaluation of an adult with longitudinal vaginal septum that included a careful physical examination and abdominal and pelvic imaging. Intraoperative resection with key strategies: (1) placing a Foley catheter to help avoid urinary tract injuries and (2) intermittent rectal examinations to retract the rectum away from the plane of dissection. CONCLUSION: Patients who present with longitudinal vaginal septa should undergo evaluation for uterine and renal anomalies. Here, we show that resection of longitudinal vaginal septa in adults is feasible and appropriate for patients who present with inability to have penetrative intercourse. Intraoperatively, care should be taken to avoid injuring the rectum or urinary tract.

Current state of bladder diary: a survey and review of the literature.

INTRODUCTION AND HYPOTHESIS: The objectives of this study are (1) to assess practice patterns among urogynecology/female pelvic medicine and reconstructive surgery (FPMRS) providers regarding the use of bladder diaries (BD) and (2) to review the literature regarding BD. METHODS: For the first objective, a survey was emailed to United States-based urogynecology providers in 2019 querying frequency of use of bladder diaries (FBD), indications, problems, patient education methods, and perception of utility. Chi-square tests and multiple logistic regression were performed. For the second objective, we reviewed literature published in English by searching the terms "voiding," "bladder," or "incontinence," in combination with "diary," "log," or "questionnaire." RESULTS: A total of 371 of 851 (43.5%) contacted providers responded. Nearly 80% were attending physicians, 75.5% of whom completed the FPMRS fellowship; 20.8% of all respondents and nearly 25% of fellowship-trained attendings reported FBD <20% in the last year. FPMRS providers were more likely to report FBD >80%. A total of 97.5% of respondents cited difficulty in using BD. Most (71.6%) taught patients to use BD themselves or shared responsibility with a nonphysician staff member (53.4%). BD is a validated and valuable instrument; however, there are obstacles to its use. Despite recent innovations including electronic and automated BD, there is a paucity of data regarding the provider-viewed challenges in implementing BD. CONCLUSIONS: The literature supports the use of BD; however, many survey respondents, including fellowship-trained attendings, never or rarely use BD. Most respondents reported difficulty in using BD. More research is needed to improve the ease, accuracy, and widespread adaptation of BD use in clinical practice.

Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms.

Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with COVID-19 with neurological symptoms, we find compartmentalized, CNS-specific T cell activation and B cell responses. All affected individuals had CSF anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are present only during brain infection and not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from an individual with COVID-19 and found that these monoclonal antibodies (mAbs) target antiviral and antineural antigens, including one mAb that reacted to spike protein and neural tissue. CSF immunoglobulin G (IgG) from 5 of 7 patients showed antineural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of individuals with COVID-19 and suggests a role of autoimmunity in neurologic sequelae of COVID-19.

Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection.

INTRODUCTION: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. METHODS AND FINDINGS: We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.

Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement.

One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients' CSF and show that these target both anti-viral and anti-neural antigens-including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients.

Tracking Smell Loss to Identify Healthcare Workers with SARS-CoV-2 Infection.

BACKGROUND: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals, like HCW. METHODS: We performed a prospective cohort study, tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, novel behavioral at-home assessment of smell function with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and RT-qPCR testing to identify SARS-CoV-2 infection. RESULTS: SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. Among the 17 infected HCW, 53% reported smell loss, and were more likely to report smell loss than COVID-negative HCW on both the at-home assessment and the screening questionnaire (P < .01). 67% reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among COVID-positive HCW who reported smell loss (P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of COVID-19 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.

Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT-qPCR primer-probe sets.

The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for accurate and rapid diagnostic assays to prompt clinical and public health interventions. Currently, several quantitative reverse transcription-PCR (RT-qPCR) assays are being used by clinical, research and public health laboratories. However, it is currently unclear whether results from different tests are comparable. Our goal was to make independent evaluations of primer-probe sets used in four common SARS-CoV-2 diagnostic assays. From our comparisons of RT-qPCR analytical efficiency and sensitivity, we show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 viral RNA copies per reaction. The exception for this is the RdRp-SARSr (Charité) confirmatory primer-probe set which has low sensitivity, probably due to a mismatch to circulating SARS-CoV-2 in the reverse primer. We did not find evidence for background amplification with pre-COVID-19 samples or recent SARS-CoV-2 evolution decreasing sensitivity. Our recommendation for SARS-CoV-2 diagnostic testing is to select an assay with high sensitivity and that is regionally used, to ease comparability between outcomes.

Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19.

BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. CONCLUSION: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

Septic cavernous sinus thrombosis-Case series and review of the literature.

BACKGROUND AND PURPOSE: Septic cavernous sinus thrombosis (CST) is a rare, life-threatening disease with infectious thrombosis causing associated complications resulting in high morbidity and mortality. We report a series of CST patients with assessment of arterial and intracranial complications. METHODS: We used the radiology database from a large, academic tertiary care center to collect all patients treated with CST between 2002 and 2019. Patient demographics, source of infection, treatment course and outcomes were evaluated. A review of the recent literature was also performed for similar reported complications from CST. RESULTS: 14 patients with CST treated during this time period were assessed. Of the 14 patients, 1 patient died. 7 patients had unilateral narrowing of ICA while 3 patients had bilateral narrowing. The ICA narrowing was reversible in 10/12 patients and improvement but persistent narrowing in one patient. One patient had an infectious pseudo aneurysm that was treated by coiling. Extension of thrombosis to the transverse- sigmoid sinuses and internal jugular vein were seen in 3 patients. Three patients had subdural empyema which was treated surgically. CONCLUSION: The prognosis of CST has improved with advancement in treatment, but complications are not infrequent.

Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19.

BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. CONCLUSION: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

SARS-CoV-2 infection of the placenta.

BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.

Meta-analysis of recent literature on utility of follow-up imaging in isolated perimesencephalic hemorrhage.

OBJECTIVES: Isolated perimesencephalic subarachnoid hemorrhage is an uncommon, distinct subtype of subarachnoid hemorrhage with a more benign prognosis. A negative computed tomographic angiogram has been shown to be reliable in excluding aneurysmal rupture as the underlying etiology. However, some studies continue advocating for more imaging to determine a vascular cause in perimesencephalic subarachnoid hemorrhage. The objective of this study is to evaluate the evidence for use and utility of repeat angiographic imaging after a negative computed tomographic angiogram in patients with perimesencephalic subarachnoid hemorrhage. PATIENTS AND METHODS: Retrospective institutional analysis of patients with perimesencephalic subarachnoid hemorrhage was performed from 2014 to 2017 for number and types of follow-up angiographic imaging studies performed. Updated meta-analysis of literature was performed from 2014 onwards to assess the utility of follow-up imaging after a negative initial angiographic study. RESULTS: The institutional review revealed no utility of additional imaging after a negative computed tomographic angiogram in 6 patients with isolated perimesencephalic subarachnoid hemorrhage. Literature review and metaanalysis of 13 studies with 588 patients revealed a vascular etiology in 3 patients with isolated perimesencephalic subarachnoid hemorrhage from a single study- 2 aneurysms and 1 patient with vasculitis. CONCLUSIONS: Use of repeat angiographic imaging after a negative computed tomographic angiogram for perimesencephalic subarachnoid hemorrhage patients remains not uncommon, despite previous meta-analysis. Review of the more recent literature is consistent with previously published meta-analysis and shows limited benefits despite frequent use. In patients with a strictly defined perimesencephalic subarachnoid hemorrhage pattern and clinical picture consistent with perimesencephalic subarachnoid hemorrhage, an initial negative computed tomographic angiogram should be adequate and repeated follow-up studies can be avoided.

Cost-effectiveness of Magnetic Resonance Imaging in Cervical Clearance of Obtunded Blunt Trauma After a Normal Computed Tomographic Finding.

Importance: Magnetic resonance imaging (MRI) continues to be performed for cervical clearance of obtunded blunt trauma, despite poor evidence regarding its utility after a normal computed tomographic (CT) finding. Objective: To evaluate the utility and cost-effectiveness of MRI vs no follow-up after a normal cervical CT finding in patients with obtunded blunt trauma. Design, Setting and Participants: This cost-effectiveness analysis evaluated an average patient aged 40 years with blunt trauma from an institutional practice. The analysis used a Markov decision model over a lifetime horizon from a societal perspective with variables from systematic reviews and meta-analyses and reimbursement rates from the Centers for Medicare & Medicaid Services, National Spinal Cord Injury Database, and other large published studies. Data were collected from the most recent literature available. Interventions: No follow-up vs MRI follow-up after a normal cervical CT finding. Results: In the base case of a 40-year-old patient, the cost of MRI follow-up was $14 185 with a health benefit of 24.02 quality-adjusted life-years (QALY); the cost of no follow-up was $1059 with a health benefit of 24.11 QALY, and thus no follow-up was the dominant strategy. Probabilistic sensitivity analysis showed no follow-up to be the better strategy in all 10 000 iterations. No follow-up was the better strategy when the negative predictive value of the initial CT was relatively high (>98%) or the risk of an injury treated with a cervical collar turning into a permanent neurologic deficit was higher than 25% or when the risk of a missed injury turning into a neurologic deficit was less than 58%. The sensitivity and specificity of MRI were varied simultaneously in a 2-way sensitivity analysis, and no follow-up remained the optimal strategy. Conclusions and Relevance: Magnetic resonance imaging had a lower health benefit and a higher cost compared with no follow-up after a normal CT finding in patients with obtunded blunt trauma to the cervical spine, a finding that does not support the use of MRI in this group of patients. The conclusion is robust in sensitivity analyses varying key variables in the model. More literature on these key variables is needed before MRI can be considered to be beneficial in the evaluation of obtunded blunt trauma.

Utility of MRI for cervical spine clearance in blunt trauma patients after a negative CT.

PURPOSE: To determine the utility of cervical spine MRI in blunt trauma evaluation for instability after a negative non-contrast cervical spine CT. METHODS: A review of medical records identified all adult patients with blunt trauma who underwent CT cervical spine followed by MRI within 48 h over a 33-month period. Utility of subsequent MRI was assessed in terms of findings and impact on outcome. RESULTS: A total of 1,271 patients with blunt cervical spine trauma underwent both cervical spine CT and MRI within 48 h; 1,080 patients were included in the study analysis. Sixty-six percent of patients with a CT cervical spine study had a negative study. Of these, the subsequent cervical spine MRI had positive findings in 20.9%; 92.6% had stable ligamentous or osseous injuries, 6.0% had unstable injuries and 1.3% had potentially unstable injuries. For unstable injury, the NPV for CT was 98.5%. In all 712 patients undergoing both CT and MRI, only 1.5% had unstable injuries, and only 0.42% had significant change in management. CONCLUSIONS: MRI for blunt trauma evaluation remains not infrequent at our institution. MRI may have utility only in certain patients with persistent abnormal neurological examination. KEY POINTS: • MRI has limited utility after negative cervical CT in blunt trauma. • MRI is frequently positive for non-specific soft-tissue injury. • Unstable injury missed on CT is infrequent.

Cost-effectiveness of Magnetic Resonance Imaging in Cervical Spine Clearance of Neurologically Intact Patients With Blunt Trauma.

STUDY OBJECTIVE: Use of magnetic resonance imaging (MRI) for cervical clearance after a negative cervical computed tomography (CT) scan result in alert patients with blunt trauma who are neurologically intact is not infrequent, despite poor evidence in regard to its utility. The objective of this study is to evaluate the utility and cost-effectiveness of using MRI versus no follow-up in this patient population. METHODS: A modeling-based decision analysis was performed during the lifetime of a 40-year-old individual from a societal perspective. The 2 strategies compared were no follow-up and MRI. A Markov model with a 3% discount rate was used with parameters from the literature. Base cases and probabilistic and sensitivity analyses were performed to assess the cost-effectiveness of the strategies. RESULTS: The cost of MRI follow-up was $11,477, with a health benefit of 24.03 quality-adjusted life-years; the cost of no follow-up was $6,432, with a health benefit of 24.08 quality-adjusted life-years. No follow-up was the dominant strategy, with a lower cost and a higher utility. Probabilistic sensitivity analysis showed no follow-up to be the better strategy in all 10,000 iterations. No follow-up was the better strategy irrespective of the negative predictive value of initial CT result, and it remained the better strategy when the incidence of missed unstable injury resulting in permanent neurologic deficits was less than 64.2% and the incidence of patients immobilized with a hard collar who still received cord injury was greater than 19.7%. Multiple 3-way sensitivity analyses were performed. CONCLUSION: MRI is not cost-effective for further evaluation of unstable injury in neurologically intact patients with blunt trauma after a negative cervical spine CT result.