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Background Oral anticoagulation (OAC) can reduce stroke risk at the cost of increased bleeding risk in those with atrial fibrillation (AF). Observational data have shown that higher-risk patients with AF most likely to benefit from OAC are less likely to receive OAC at hospital discharge. Methods We used data from ORBIT-AF Registry, a cohort of 9,589 AF patients enrolled among 173 participating outpatient practices. OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using the CHADS2 and ATRIA scores, respectively. Results The study population had a mean age of 73.5 years; 57.8% were men. Overall, 76.4% of patients received OAC. Use of OAC rose with increasing CHADS2 stroke risk, from 67% for CHADS2 <1 to 80% for CHADS2 ≥2 (p<0.0001). OAC use fell slightly with increasing ATRIA bleeding risk, from 77% for ATRIA score ≤3 to 74% with ≥5 (p=0.002 for trend). Among patients with low bleeding risk, rates of OAC increased commensurate with stroke risk (p<0.0001 for interaction; see figure). Higher bleeding risk tended to decrease rates of OAC among patients with a CHADS2 score ≥2 (p=0.13 for interaction). Conclusions In community-based outpatients with AF, use of OAC rose with increasing thromboembolic risk and declined with higher bleeding risk. These findings suggest that the risk-treatment paradox may be less that previously reported. Provision of OAC in community practice appears to appropriately consider patients' stroke and bleeding risks. Further research is required to understand how quality improvement initiatives can further improve stroke prevention.

Background : In 2001, the Adult Treatment Panel III guidelines expanded the definition of high risk by including coronary heart disease (CHD) risk equivalent conditions. Low-density lipoprotein cholesterol (LDL-C) goals for all high-risk patients were intensified to < 100 mg/dL. This study investigates the size of the high-risk U.S. population with and without CHD and the percent LDL-C goal achievement across six years. Methods : Data from three National Health and Nutrition Examination Surveys: 1999–2000, 2001–2002, and 2003–2004 were analyzed to identify U.S. residents at high risk per ATP III guidelines. The size of each survey’s high-risk cohort and percentage LDL-C goal achievement was stratified by presence of CHD or CHD risk equivalent conditions. Results : Across the three surveys, the high-risk population was 22.2, 23.8 and 28.0 million. The percentage of all high-risk individuals with LDL-C < 100 mg/dL was 22.9%, 31.5% and 32.9%. Goal achievement in those without CHD was 20.2%, 26.0% and 31.5%. In CHD patients, goal achievement increased from 27.0% (1999–2000) to 40.9% (2001–2002) but then dropped to 35.1% (2003–2004). Conclusions : Across six years from 1999 to 2004, U.S. residents at high risk increased by 26.2% (5.8 million) compared to a 5.2% (8.3 million) rise in eligible population. Improvement in LDL-C goal achievement for those without CHD was consistent across the three surveys. Those with CHD also had a robust improvement from 1999–2000 to 2001–2002. However, while a greater absolute number of those with CHD met goal in 2003–2004, the percentage was reduced. This suggests a need for renewed attention to LDL-C goal achievement in individuals with CHD. High Risk Cholesterol Goal Achievement by CHD status

Type I hypersensitivity reactions (HSR) to dabrafenib are rare but have been previously described. We present a case where a 72-year-old woman with recurrent, metastatic BRAF-mutated melanoma developed a type I HSR to dabrafenib. We, therefore, developed a desensitization protocol with encorafenib, a similar class agent, to allow the patient to continue with treatment. Patients with a history of HSR to dabrafenib may be considered for encorafenib desensitization when other therapeutic options are limited.

Objectives: Procedures which utilize bilateral mucosal flaps with an interposition graft are frequently used when attempting closure of a septal perforation. Concurrent surgical management of the nasal valve or an aesthetic deformity may be indicated. The objective of this study is to report our experience using auricular perichondrium for the interposition graft when auricular cartilage is harvested for structural or aesthetic graft material. Methods: A retrospective medical record review was performed for septal perforation repairs performed at Mayo Clinic in Arizona from January 2010 through January 2020. Patients identified for this study underwent a procedure utilizing bilateral nasal mucosal flaps with an auricular perichondrium interposition graft. Results: Forty-four patients (31 females) with a mean age of 53.3 years met study criteria. The most common presenting symptoms were nasal obstruction, crusting, and epistaxis. Prior septal surgery was the most common perforation etiology (45.5%). Mean perforation length was 11.8 (range, 3-26) mm and height, 9.1 (range, 2-16) mm. Auricular cartilage was harvested for nasal valve surgery in 43 patients. Complete perforation closure was noted in 95.3% (41/43) of patients with a minimum post-operative follow-up of 3 (mean, 20.4) months. Four patients underwent revision surgery for persistent postoperative nasal obstruction. Conclusion: The ear can provide both cartilage and perichondrium for use in septal perforation surgery. Our study demonstrates the successful use of auricular perichondrium as the interposition graft for a perforation closure procedure utilizing bilateral nasal mucosal flaps.

Coronavirus disease 2019 (COVID-19) was initially recognized in late December 2019 and has quickly spread globally with over 114 million reported cases worldwide at the time of this publication. For the majority of patients infected with COVID-19, the clinical manifestations are absent or mild. In more advanced cases, severe respiratory dysfunction is the leading cause of morbidity and mortality. However, increasingly, there have been reports of increased thrombotic complications including pulmonary embolism and deep vein thrombosis seen in these patients. We present herein a series of cases of concomitant COVID-19 pneumonia and venous thromboembolism. These cases highlight the importance of clinical and radiologic vigilance to ensure this often clinically silent complication is not missed.

ObjectiveReporting patient symptoms due to nasal septal perforation (NSP) has been hindered by the lack of a validated disease‐specific symptom score. The purpose of this study was to develop and validate an instrument for assessing patient‐reported symptoms related to NSP.Study DesignValidation study.SettingA tertiary care center.MethodsThe Nasal Obstruction Symptom Evaluation (NOSE) scale was used as an initial construct to which 7 nonobstruction questions were added to measure septal perforation symptoms. The proposed NOSE‐Perf instrument was distributed to consecutive patients evaluated for NSP, those with nasal obstruction without NSP, and a control group without rhinologic complaints. Questionnaires were redistributed to the subgroup with NSP prior to treatment of the perforation.ResultsThe study instrument was completed by 31 patients with NSP, 17 with only nasal obstruction, and 22 without rhinologic complaint. Internal consistency was high throughout the entire instrument (Cronbach α = 0.935; 95% CI, 0.905‐0.954). Test‐retest reliability was demonstrated by very strong correlation between questionnaires completed by the same patient at least 1 week apart (r = 0.898, P <. 001). Discriminant validity was confirmed via a receiver operating characteristic (P <. 001, area under the curve = 0.700). The NOSE‐Perf scale was able to distinguish among all 3 study groups (P <. 001) and between NSP and nasal obstruction (P =. 024). When used alone, the NOSE scale could not discriminate between NSP and nasal obstruction (P =. 545).ConclusionsThe NOSE‐Perf scale is a validated and reliable clinical assessment tool that can be applied to adult patients with NSP.

Abstract The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.

ObjectiveThis study reviews a cohort of patients in whom septal perforation repair was performed concurrently with endoscopic sinus surgery. We present an endonasal perforation repair technique using bilateral mucosal flaps with an autogenous interposition graft. Intraoperative and postoperative management of the combined surgical patient is discussed and perforation closure outcomes are reported.Study DesignCase series.SettingTertiary care center.MethodsIn this institutional review board–approved retrospective chart review, adult patients who underwent concurrent bilateral mucosal flap septal perforation repair and endoscopic sinus surgery from March 1992 to March 2020 were identified. Data on demographics, clinical presentations, perforation size, surgical techniques, and outcomes were extracted and analyzed for patients with a minimum of 3 months of follow‐up.ResultsFifty‐six patients met study inclusion criteria. Nasal obstruction/congestion was the most frequent symptom reported (80.4%), followed by crusting and epistaxis. Mean perforation size measured at the time of surgery was 14.7 (range, 3‐41) mm in length by 9.3 (range, 2‐23) mm in height. Temporalis fascia was the most frequent (57.9%) interposition graft material used. Complete perforation closure at the time of the last follow‐up was noted in 51 (91.1%) patients. Only 1 failure was noted in the last 48 attempted repairs.ConclusionPatients with a perforated septum may have coexistent chronic sinusitis. The feasibility of attempting concurrent sinus surgery and perforation repair has been questioned. Our review demonstrates a high perforation closure rate when a bilateral mucosal flap procedure is performed after sinus surgery is performed at the same setting.

Variables in cardiology fellowship applications have not been objectively analyzed against applicants' subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors' academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the United States. The outcome was clinical performance as measured by a mean of faculty evaluation scores during clinical training. The overall mean evaluation score was 4.07 ± 0.18 (scale, 1–5). After multivariable analysis, evaluation scores were associated with Alpha Omega Alpha designation (β=0.13; 95% CI, 0.01–0.25; P=0.03), residency program reputation (β=0.13; 95% CI, 0.05–0.21; P=0.004), and strength of comparative statements in recommendation letters (β=0.08; 95% CI, 0.01–0.15; P=0.02), particularly in letters from residency program directors (β=0.05; 95% CI, 0.01–0.08; P=0.009). Objective factors to consider in the cardiology fellowship application include Alpha Omega Alpha membership, residency program reputation, and comparative statements from residency program directors.

Abstract Background Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined. Methods CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis. Results Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited oncogenesis. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy. Conclusions Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.