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Background Cerebral arterial thromboses or ischemic strokes may be caused by cumulative or independent effects of a variety of risk factors. High factor VIII level is one of those important but less known risk factors for arterial and venous thrombosis. We hereby provide a comprehensive review of the role of high factor VIII levels as a risk factor of arterial thrombosis. Moreover, we present our views on inclusion of factor VIII testing in the etiology workup protocol of young patients with ischemic strokes and their treatment with anticoagulant therapy. Case presentation We illustrate a case of 32-year-old North Indian female patient with Ischemic stroke whose only identifiable risk factor was revealed to be an elevated factor VIII level. She was treated with oral anticoagulant with an uneventful follow-up of 6 months. Conclusions Elevated factor VIII levels have their independent and additive effects in causation and prognosis of arterial strokes. We herein discuss the mechanism of this association, the feasibility and yield of routine testing, appropriate cut-off levels, and further treatment protocol especially in young stroke patients.

Background: Ankle fracture is important in sense that ankle is distal most weight bearing joint and locomotion depends upon stability of ankle mortise. The best option for management of distal fibula fracture remains unclear due to availabity of various implant and different types of fractures. Aim: This study was conducted to know the indication for the two modalities of surgical fixation as this comparative study between close reduction internal fixation and open reduction internal fixation in lower fibula (at syndesmotic level: Weber type B) with lower tibia or medial malleolar fracture. Aim of the study was to perform randomised controlled trial to compare complication and functional modalities in fixation of fibula Materials and Methods: This was a randomised prospective and comparative study for the methods used for management of the lower fibula fracture (Weber type B) done In dept. of orthopaedics, civil hospital, Ahmedabad within time of 1st may 2019 to 1st may 2020 in total of 62 patient in which 39 patient were operated by CRIF and 23 patient operated by ORIF Results: There was significant difference in rate of union as platting was found superior to nailing there were less complication in nailing as compare to platting and better functional score found with nailing. Conclusion: Nailing in lower fibula fracture is a better technique with comminuted ankle fractures that provides better functional outcome with fewer complication than platting. By the syndesmotic point of view there is no such diffrence between crif and orif method for post weight bearing syndesmotic failure. There seems higher chances of ankle stiffness perticularly at syndesmotic level seen after orif method. Keywords: There was no significant difference in syndesmotic diastasis during cyclic loading or at maximal external rotation between the rod and plate groups. Post-cycle external rotation stiffness across the syndesmosis was significantly higher for the locking pla

The risk and determinants of HCC in patients with primary biliary cholangitis (PBC) are unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and risk factors associated with HCC risk among patients with PBC. We searched PubMed, EMBASE, MEDLINE, Cochrane databases and reference lists from relevant articles to identify cohort studies that examined incidence of HCC in patients with PBC from inception through November 2019. A total of 29 studies including 22,615 patients met the eligibility criteria. The median cohort size was 292 patients followed for an average of 76 months. The pooled incidence rate for patients with PBC was 4.17 per 1000 patient-years (95% CI 3.17–5.47). On subgroup analysis, the incidence of HCC in patients with PBC cirrhosis was 15.7 per 1000 patient-years (95% CI 8.73–28.24). The HCC incidence rate was 9.82 per 1000 person-years (95% CI 5.92–16.28) in men and 3.82 per 1000 person-years (95% CI 2.85–5.11) in women. Cirrhosis is the strongest risk factor for HCC in patients with PBC. Male gender was also a risk factor. Our meta-analysis supports current recommendations of HCC surveillance in patients with PBC cirrhosis. Further studies are needed to evaluate risk factors in this population.

It is unclear how hypertrophic cardiomyopathy (HCM) affects cardiac metabolic pathways at rest and with exercise. This case–control study compared 15 cases with HCM to 2 control groups without HCM. Metabolomic profiling of 210 metabolites was carried out at rest and at peak exercise. The 50 most discriminant metabolites differentially regulated during exercise were selected using partial least squares discriminant analysis. Pathway enrichment analysis was also performed. At rest, no significant difference was observed in metabolomic profiling of HCM cases as compared to controls. By contrast, there were significant differences in metabolomic profiling in response to exercise (p

Deep vein thrombosis (DVT) of the lower extremities can be associated with significant morbidity and may progress to pulmonary embolism and postthrombotic syndrome. Early diagnosis and treatment are important to minimize the risk of these complications. We systematically reviewed the accuracy of diagnostic tests for first-episode and recurrent DVT of the lower extremities, including proximal compression ultrasonography (US), whole leg US, serial US, and high-sensitivity quantitative D-dimer assays. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 43 studies. For any suspected DVT, the pooled estimates for sensitivity and specificity of proximal compression US were 90.1% (95% confidence interval [CI], 86.5-92.8) and 98.5% (95% CI, 97.6-99.1), respectively. For whole-leg US, pooled estimates were 94.0% (95% CI, 91.3-95.9) and 97.3% (95% CI, 94.8-98.6); for serial US pooled estimates were 97.9% (95% CI, 96.0-98.9) and 99.8% (95% CI, 99.3-99.9). For D-dimer, pooled estimates were 96.1% (95% CI, 92.6-98.0) and 35.7% (95% CI, 29.5-42.4). Recurrent DVT studies were not pooled. Certainty of evidence varied from low to high. This systematic review of current diagnostic tests for DVT of the lower extremities provides accuracy estimates. The tests are evaluated when performed in a stand-alone fashion, and in a diagnostic pathway. The pretest probability of DVT often assessed by a clinical decision rule will influence how, together with sensitivity and specificity estimates, patients will be managed.

Objective We aimed to assess physicians’ perceptions of barriers to starting medication-assisted treatment (MAT) in the Emergency Department (ED), views of the utility of MAT, and abilities to link patients with opioid use disorder (OUD) to MAT programs in their respective communities. Methods This was a cross-sectional survey study of American emergency medicine (EM) physicians with a self-administered online survey via SurveyMonkey (Survey Monkey, San Mateo, California). The survey was emailed to the Council of Residency Directors in Emergency Medicine (CORD) listserv and HCA Healthcare affiliated EM residency programs’ listservs. Attendings and residents of all post-graduate years participated. Questions assessed perceptions of barriers to starting OUD patients on MAT, knowledge of the X-waiver, and knowledge of MAT details. Statistics were performed with JMP software (SAS Institute Inc., Cary, NC) using the two-tailed Z-test for proportions. Results There were 98 responses, with 33% female, 55% resident physicians, and an overall 17% response rate. Residents were more eager to start OUD patients on MAT (71% vs 52%, p=0.04) than attendings but were less familiar with the X-waiver (38% vs 73%, p=0.001) or where community outpatient MAT facilities were (21% vs 43%, p=0.02). Conclusion Barriers in the ED were identified as a shortage of qualified prescribers, the lengthy X-waiver process, and the poor availability of outpatient MAT resources. EM residents showed more willingness to prescribe MAT but lacked a core understanding of the process. This shows an area of improvement for residency training as well as advocacy among attendings.

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan failure in patients with coronavirus disease 2019 (COVID-19). However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved in endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through Toll-like receptor 2 (TLR2)/NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkably, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), HUB1-CoV, and influenza virus H1N1 did not activate endothelial cells. These findings are consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy and suggests that simvastatin, an FDA-approved lipid-lowering drug, may help prevent the pathogenesis and improve the outcome of COVID-19 patients. IMPORTANCE Coronavirus disease 2019 (COVID-19), caused by the betacoronavirus SARS-CoV-2, is a worldwide challenge for health care systems. The leading cause of mortality in patients with COVID-19 is hypoxic respiratory failure from acute respiratory distress syndrome (ARDS). To date, pulmonary endothelial cells (ECs) have been largely overlooked as a therapeutic target in COVID-19, yet emerging evidence suggests that these cells contribute to the initiation and propagation of ARDS by altering vessel barrier integrity, promoting a procoagulative state, inducing vascular inflammation and mediating inflammatory cell infiltration. Therefore, a better mechanistic understanding of the vasculature is of utmost importance. In this study, we screened the SARS-CoV-2 viral proteins that potently activate human endothelial cells and found that nucleocapsid protein (NP) significantly activated human endothelial cells through TLR2/NF-κB and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Our results provide insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.

Background Immune dysregulation is one of the main reasons for mortality and morbidity in coronavirus disease 2019 (COVID-19). Mycobacterium w (Mw) is recently approved for gram-negative sepsis. Moreover, it is also found effective in COVID-19 patients in previous studies. The traditional route of administration for Mw is intradermal, which has a limitation of administering 0.1 mL per injection and local injection site reaction. Intravenous (IV) administration of Mw has not been explored in COVID-19. We report the retrospective analysis of six critically ill COVID-19 patients who received Mw (IV). Patients and methods At baseline, all patients in this case series required O2 supplementation, and their inflammatory biomarkers were elevated. All patients received 0.6 mL Mw (high-dose) in normal saline along with the standard-of-care treatment. Results After Mw administration, gradual improvement in O2 requirement was observed and patients were discharged from the hospital with no mortality. A reduction in mean C-reactive protein (CRP) (51.48–18.52 mg/dL), interleukin-6 (IL-6) (260.22–14.47 pg/mL), and FiO2 (81.67–43.33) was also observed. No side effects were observed with the use of Mw by IV route. Conclusion Use of 0.6 mL Mw by IV route in this case series was associated with decreased O2 supplementation without any side effects in critically ill patients of COVID-19. How to cite this article Patel PS, Patel S, Shah V, Aswani V, Narwaria M. Early Experience of High-dose Intravenous Mycobacterium w in Critically Ill Patients of COVID-19. Indian J Crit Care Med 2021;25(9):1066–1068.

Background: Present study was done with an aim to study the clinical profile and its relation to spirometry and 2D ECHO in COPD patients. Methodology: Sixty COPD patients with anonymous rigorousness attending department of respiratory medicine, G.K. General Hospital Bhuj, were incorporated in the study from 2017 onward. The patients were subjected to spirometry and classified according to GOLD guidelines. Whole history concerning the symptoms, past history, smoking history, occupational history and other linked illnesses were taken and noted in a proforma. Echocardiographic assessments of right ventricular and left ventricular function were done. Results: COPD was more common in males (88.33%) as compared to females (11.66%) because of smoking prevalence high in male patients. COPD patients were having most common chest x-ray finding of Emphysema (75%), followed by increase bronchovascular markings (28.33%), cardiomegaly (6.66%), consolidation or mass (3.33%), calcification (3.33%), reticular pattern (3.33%) and bronchiectasis (3.33%). COPD patient were had mainly common ECG finding of normal (50%), p- pulmonale in (40%), right ventricular hypertrophy in (25%), right axis deviation in (18.33%), RBBB in (6.66%) and AF in (3.33%). Conclusions: Severity of COPD has straight relation connection with occurrence of ECG changes in COPD. In the present study 50% of the patients had normal ECG. LV diastolic dysfunction was present in 38.33% of the patients. As the severity increases, frequency of LV diastolic dysfunction on 2 D and Doppler echocardiography goes on escalating. Keywords: Chronic obstructive pulmonary diseases; Smoking; Spirometry.

Gastroesophageal reflux disease is an extremely prevalent illness in the United States; however, clinicians report that its association with chronic cough is often overlooked and undiagnosed. We used the CERNER Health Facts® database to analyze the statistical prevalence. Our findings indicate that there is a minority of patients who are untreated for this common complaint. We propose considering this on the differential diagnosis and following current treatment guidelines with proton pump inhibitors to effectively treat this complaint.

Chronic pruritus is a complex yet prevalent concern without a gold standard treatment. The mainstay therapy for chronic pruritus includes topical ointments such as corticosteroids, capsaicin, local anesthetics, antihistamines, and immunomodulators. There are many different subtypes of chronic pruritus, and each unique subtype may benefit from specialized treatments. This review article sheds light on the role of psychiatric, analgesic, and antiepileptic medications in chronic pruritus. We believe that further large-scale studies are needed to determine the true effectiveness of these medications in treating chronic pruritus.

To our knowledge,this is the first report of 31 Y F has no family history and usually,patients do not manifest symptoms if they are heterozygous.Individuals heterozygous for C282Y who have a coexisting insult to the liver,associated with the use of medications,may present with overt manifestations of iron overload.

The Coronavirus outbreak globally has changed the medical system and also led to a shortage of medical facilities in both developing and underdeveloped countries. The COVID19 disease, being novel in nature along with high infectivity and frequent mutational rate, has been termed to be fatal across the globe. The advent of infection by SARS-CoV-2 has brought a myriad of secondary complications and comorbidities resulting in additional challenges to the health care system induced by novel therapeutic procedures. The emerging variant with respect to the Indian subcontinent and the associated genetic mutations have worsened the situation at hand. Proper clinical management along with epidemiological studies and clinical presentations in scientific studies and trials is necessary in order to combat the simultaneous waves of emerging strains. This article summarizes three of the major fungal outbreaks in India namely mucormycosis, candidiasis and aspergillosis, and elaborates their subtypes, pathogenesis, symptoms and treatment and detection techniques. A detail of future therapeutics under consideration are also elaborated along with a general hypothesis on how COVID19 is related to immunological advances leading to major widespread fungal infection in the country. The factors that contribute in promoting virus proliferation and invasive fungal infections include cell-mediated immunity, associated immunocompromised conditions and treatment protocols that slows down immune mechanisms. To better comprehend a fungal or bacterial outbreak, it is very important to conduct audits mediated through multicenter national and state research teams for recognizing patterns and studying current cases of fungal infection in both healthy and comorbid groups of COVID19 patients.

TOPIC: Occupational and Environmental Lung Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: E-cigarette or vaping product use-associated lung injury (EVALI) encompass a host of pulmonary complications including diffuse alveolar hemorrhage, lipoid pneumonia, hypersensitivity pneumonitis, and rarely, acute eosinophilic pneumonia (AEP) [1]. AEP presents as an acute febrile illness with hypoxemia, diffuse pulmonary infiltrates, and eosinophilia on bronchoalveolar lavage (BAL) without evidence of prior infection or atopic illness [2]. Presented is a young adult patient with a history of continuous vaping and extended exposure to kitchen smoke who developed acute hypoxemic respiratory failure later diagnosed as AEP. CASE PRESENTATION: An 18-year-old male with no significant past medical history presented to the emergency department with acute onset malaise, fever, non-productive cough, and shortness of breath over 12 hours. Social history revealed 3-week workplace exposure to smoke as a barbeque cook and a 5-year history of daily vaping with reported cessation 3 weeks prior. Vitals were notable for hypoxemia which was corrected with administration of 8L of oxygen via nasal cannula. Quickly after admission, he had worsening respiratory status: tachypnea, increased oxygen requirement, use of accessory muscles, and bilaterally diminished breath sounds. He was transferred to the medical intensive care unit for emergent endotracheal intubation. Laboratory testing revealed a neutrophil predominant leukocytosis of 19.3x109/L. COVID-19, rapid influenza A and B, and urine antigens for streptococcus and legionella were negative as were autoimmune serologies. A computed tomography (CT) scan of the chest revealed diffuse bilateral consolidative opacities [Figure 1] with worsening over the next 24 hours [Figure 2]. Further investigation was undertaken with bronchoscopy. A BAL was obtained, and cell count and cultures were sent. BAL cell count was remarkable for 33% eosinophilia. The diagnosis of AEP was made, and the patient was started on systemic glucocorticoids, with significant improvement within 24 hours. DISCUSSION: The modified Philit criteria is used to make the diagnosis of AEP, which the patient satisfied [3]. Although a 5-year vaping history was present, no previous significant respiratory symptoms were reported. Prior studies have demonstrated a relationship between workplace smoke exposure and AEP [3]. Based on the modified Philit criteria, we suspect that the patient had acute respiratory failure from AEP as a result of chronic EVALI acutely exacerbated by workplace smoke exposure. The treatment of AEP treatment involves high-dose intravenous glucocorticoids followed by a prolonged oral steroid taper. CONCLUSIONS: Obtaining occupation history as well as smoke exposure is as important as obtaining vaping history in an otherwise healthy young patient who presents with acute hypoxemic respiratory failure with bilateral diffuse opacities on imaging. REFERENCE #1: Winnicka L, Shenoy MA. EVALI and the Pulmonary Toxicity of Electronic Cigarettes: A Review. J Gen Intern Med. 2020;35(7):2130-2135. doi:10.1007/s11606-020-05813-2 REFERENCE #2: Allen JN, Pacht ER, Gadek JE, Davis WB. Acute Eosinophilic Pneumonia as a Reversible Cause of Noninfectious Respiratory Failure. N Engl J Med. 1989;321(9):569-574. doi:10.1056/nejm198908313210903 REFERENCE #3: Philit F, Etienne-Mastroianni B, Parrot A, Guerin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: A study of 22 patients. Am J Respir Crit Care Med. 2002;166(9):1235-1239. doi:10.1164/rccm.2112056 DISCLOSURES: No relevant relationships by Nurjahan Khatun, source=Web Response No relevant relationships by Parth Patel, source=Web Response No relevant relationships by Naleen Patel, source=Web Response No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response No relevant relationships by Rodger Wilhite, source=Web Response

Sesamoid pain can arise from avascular necrosis, fracture, osteochondrosis, and advanced degeneration. Disorders of the sesamoids in athletes can be debilitating. Total sesamoidectomy of the involved sesamoid is considered an effective surgical treatment when conservative measures have failed. There is limited literature evaluating the outcome of sesamoidectomy in athletically active patients. Our 2-center study reports on 68 patients (70 procedures; 2 male patients were operated on both feet in separate procedures approximately 3 years apart; 41 (58.6%) tibial and 29 (41.4%) fibular sesamoidectomies; 24 males and 44 females, average age 28.4 ± 12.2 years) who underwent total sesamoidectomy from 01/2001 to 12/2019. In our cohort, the average time to return to activity (RTA) was 11.1 ± 5.1 weeks, with no statistically significant difference between gender and age, or between fibular and tibial sesamoidectomy in relation to RTA. There was a minimum follow-up of 1 year, with an average of 106.6 ± 66.6 months. The total incidence of complication rate was 5.7%. In athletes in whom conservative management has failed, sesamoidectomy is safe, and allows predictable return to their chosen sport. To our knowledge, none of the patients subsequently developed pathology to the remaining sesamoid.

Pulmonary embolism (PE) is a common, potentially life-threatening yet treatable condition. Prompt diagnosis and expeditious therapeutic intervention is of paramount importance for optimal patient management. Our objective was to systematically review the accuracy of D-dimer assay, compression ultrasonography (CUS), computed tomography pulmonary angiography (CTPA), and ventilation-perfusion (V/Q) scanning for the diagnosis of suspected first and recurrent PE. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. 2 investigators screened and abstracted data. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 61 studies. The pooled estimates for D-dimer sensitivity and specificity were 0.97 (95% confidence interval [CI], 0.96-0.98) and 0.41 (95% CI, 0.36-0.46) respectively, whereas CTPA sensitivity and specificity were 0.94 (95% CI, 0.89-0.97) and 0.98 (95% CI, 0.97-0.99), respectively, and CUS sensitivity and specificity were 0.49 (95% CI, 0.31-0.66) and 0.96 (95% CI, 0.95-0.98), respectively. Three variations of pooled estimates for sensitivity and specificity of V/Q scan were carried out, based on interpretation of test results. D-dimer had the highest sensitivity when compared with imaging. CTPA and V/Q scans (high probability scan as a positive and low/non-diagnostic/normal scan as negative) both had the highest specificity. This systematic review was registered on PROSPERO as CRD42018084669.

Small noncoding microRNAs (miRNAs) are important regulators of skeletal muscle size, and circulating miRNAs within extracellular vesicles (EVs) may contribute to atrophy and its associated systemic effects. The purpose of this study was to understand how muscle atrophy and regrowth alter in vivo serum EV miRNA content. We also associated changes in serum EV miRNA with protein synthesis, protein degradation, and miRNA within muscle, kidney, and liver. We subjected adult (10 mo) F344/BN rats to three conditions: weight bearing (WB), hindlimb suspension (HS) for 7 days to induce muscle atrophy, and HS for 7 days followed by 7 days of reloading (HSR). Microarray analysis of EV miRNA content showed that the overall changes in serum EV miRNA were predicted to target major anabolic, catabolic, and mechanosensitive pathways. MiR-203a-3p was the only miRNA demonstrating substantial differences in HS EVs compared with WB. There was a limited association of EV miRNA content to the corresponding miRNA content within the muscle, kidney, or liver. Stepwise linear regression demonstrated that EV miR-203a-3p was correlated with muscle mass and muscle protein synthesis and degradation across all conditions. Finally, EV miR-203a-3p expression was significantly decreased in human subjects who underwent unilateral lower limb suspension (ULLS) to induce muscle atrophy. Altogether, we show that serum EV miR-203a-3p expression is related to skeletal muscle protein turnover and atrophy. We suggest that serum EV miR-203a-3p content may be a useful biomarker and future work should investigate whether serum EV miR-203a-3p content is mechanistically linked to protein synthesis and degradation.

Trichoblastoma is a rare, slow-growing, benign cutaneous tumor derived from follicular germinative cells. Trichoblastoma commonly appears as an asymptomatic, symmetrical, well-circumscribed, skin-colored to brown or blue-black papule or nodule. It may appear clinically and histologically similar to basal cell carcinoma, making its diagnosis challenging. Even on dermoscopy, it is challenging to differentiate trichoblastoma from basal cell carcinoma. In practice, it is important to differentiate the two, because the choice of treatment and resulting prognosis differ between the lesions. Surgical biopsy to analyze histopathological and immunohistochemical differences is the gold standard for diagnosing and differentiating trichoblastoma from basal cell carcinoma. Trichoblastoma typically has a favorable prognosis, with a low incidence of recurrence, progression or association with malignancy. This paper provides a review of the epidemiology, clinical presentation, dermoscopy, histology, immunochemistry, treatment, and prognosis of trichoblastoma.

Necrotising soft-tissue infections can be defined as infections of any of the layers within the soft tissue compartment that are associated with necrotising changes. NSTI is an uncommon but life-threatening. To resolve this, some authors have developed different diagnostic adjuncts such as finger tests, skin biopsies, bedside ultrasounds and laboratory parameters in distinguishing NSTI from other soft-tissue infections (LRINEC laboratory risk indicator for necrotizing fasciitis score). Material and Method : An observational study was conducted in 50 patients (clinically diagnosed necrotising soft tissue infection). clinical observations supported by relevant investigations were documented on the attached proforma and the data so obtained was statistically analysed. Observation and result : The results suggested that maximum number of affected individuals are males, middle aged individuals. Majority of patients had normal pulse with mean body temperature of 37.3°C, normal blood pressure,INR, normal serum level of sodium, potassium and bilirubin. High level of RBS (more than 200mg/dl). Tenderness was the most commonly elicited clinical sign of NSTI, crepitus was noted in only 20% patients. Maximum number of patients were found to be infected by streptococcus pyogenes (42%). The mean level was -hemoglobin -10.2+2.3 g/dl, WBC -13,340 + 6116 /mm3, serum creatinine value of s 1.6mg/l. High discrepancy noted in value of CRP. High prevalence of NSTI involving the extremities ranging from 64.39% to 93.The mean value of LRINEC score is 6±2.92 36 % of patients having 6. Conclusion : It can be concluded that the local clinical findings are of paramount importance rather than clinical features of systemic toxicity such as fever and tachycardia.

Prompt evaluation and therapeutic intervention of suspected pulmonary embolism (PE) are of paramount importance for improvement in outcomes. We systematically reviewed outcomes in patients with suspected PE, including mortality, incidence of recurrent PE, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included 22 studies with 15 865 patients. Among patients who were diagnosed with PE and discharged with anticoagulation, 3-month follow-up revealed that all-cause mortality was 5.69% (91/1599; 95% confidence interval [CI], 4.56-6.83), mortality from PE was 1.19% (19/1597; 95% CI, 0.66-1.72), recurrent venous thromboembolism (VTE) occurred in 1.38% (22/1597; 95% CI: 0.81-1.95), and major bleeding occurred in 0.90% (2/221%; 95% CI, 0-2.15). In patients with a low pretest probability (PTP) and negative D-dimer, 3-month follow-up revealed mortality from PE was 0% (0/808) and incidence of VTE was 0.37% (4/1094; 95% CI: 0.007-0.72). In patients with intermediate PTP and negative D-dimer, 3-month follow-up revealed that mortality from PE was 0% (0/2747) and incidence of VTE was 0.46% (14/3015; 95% CI: 0.22-0.71). In patients with high PTP and negative computed tomography (CT) scan, 3-month follow-up revealed mortality from PE was 0% (0/651) and incidence of VTE was 0.84% (11/1302; 95% CI: 0.35-1.34). We further summarize outcomes evaluated by various diagnostic tests and diagnostic pathways (ie, D-dimer followed by CT scan).

A previously healthy 53-year-old male with primary membranous nephropathy (positive anti phospholipase A2 antibody) presented to our hospital with worsening cough, shortness of breath, hypotension, and malaise. During his hospital stay, he quickly progressed to overt respiratory failure requiring mechanical ventilation. Upon further workup, he met clinical criteria for tumor lysis syndrome due to an unknown diffuse large B-cell lymphoma, who underwent rapid cytolysis after starting stress dose steroids.

Introduction Canadians are living longer than before, and a large proportion of them are living with obesity. The present study sought to describe how older participants in the Canadian Longitudinal Study on Aging (CLSA) who are living with obesity are aging, through an examination of measures of social, functional and mental well-being. Methods We used data from the first wave of the CLSA for people aged 55 to 85 years in this study. We used descriptive statistics to describe characteristics of this population and adjusted generalized logistic models to assess measures of social, functional and mental well-being among obese participants (body mass index ≥ 30 kg/m2) relative to non-obese participants. Findings are presented separately for females and males. Results More than half of the participants reported living with a low personal income (less than $50 000); females were particularly affected. Less than half of the participants were obese; those who were had higher odds of multimorbidity than those who were not living with obesity (among those aged 55–64 years: odds ratio [OR] 2.7, 95% CI: 2.0–3.5 males; OR 2.8, 95% CI: 2.2–2.5 females). Low social participation was associated with obesity among older female participants, but not males. Physical functioning issues and impairments in activities of daily living were strongly associated with obesity for both females and males. While happiness and life satisfaction were not associated with obesity status, older females living with obesity reported negative impressions of whether their aging was healthy. Conclusion The odds of multimorbidity were higher among participants who were obese, relative to those who were not. Obese female participants tended to have a negative perception of whether they were aging healthily and had lower odds of involvement in social activities, while both sexes reported impairments in functional health. The associations we observed, independent of multimorbidity in older age, highlight areas where healthy aging initiatives may be merited.

Background: Cumulative data on radiation monotherapy for Merkel cell carcinoma (MCC) is lacking. Objective: We sought to synthesize all available data on treatment outcomes for radiation monotherapy for inoperable stage I-III MCC. Methods: We performed a systematic review of the current literature. Articles published in English in the PUBMED database up to July 29, 2016 were evaluated. Results: Eight case reports, 4 case series, and 6 retrospective studies, yielding 68 patients, were included in our analysis. Of the 24 stage I/II patients treated with local irradiation, 6 (25%) relapsed and 1 (4%) died from MCC. Of the 24 stage I/II patients treated with local and regional nodal irradiation, 5 (21%) relapsed and 2 (8%) died from MCC. Of the 20 stage III patients treated with local and regional nodal irradiation, 12 (60%) relapsed and 7 (35%) died from MCC. Conclusions: Radiation monotherapy appears to be a reasonable treatment modality for patients with inoperable stage I-III MCC. Further investigation with prospective studies is needed to draw definitive conclusions.

Backgroud Modern day cataract surgery aims at a spectacle free vision which becomes difficult in cases with pre-operative astigmatism more than 1.5 D. Implantation of toric intra-ocular lenses (IOL) after phacoemulsification in such eyes is one of the ways to counteract this problem. Methods Thirty eyes with pre-operative astigmatism between 1.5 D and 4.5 D were implanted with toric IOLs following uneventful phaco-emulsification. The estimation of the axis of implantation of this toric IOL included calculating the surgically induced astigmatism (SIA) of the surgeon. Results Post-operatively, 20 (66.67%) patients had a visual acuity 6/9 or better and 17 (57%) had a visual acuity of 6/6 at 12 weeks. The mean postoperative uncorrected visual acuity (UCVA) was 0.12 ± 0.15 at 12 weeks. The difference between means of preoperative best corrected visual acuity (BCVA) LogMAR and postoperative UCVA at 12 wk LogMAR was found to be statistically significant at p = 0.001. Mean (SD) scores of pre-op astigmatism of study group was −2.20 (0.67) and residual astigmatism was −0.32 (0.44). Conclusions The difference between means of pre-op astigmatism and residual astigmatism in the study group was significant at p = 0.001 with 95% CI −2.22 to −1.50. This significant difference was because of the toric IOL implantation.

There is however potential for morbidity and even mortality if proper and timely treatment is not provided. The standard treatment of liver abscess is the use of appropriate antibiotics and supportive care. Needle aspiration can be used as an additional mode of therapy and has been promoted by some authors for routine use in the treatment of uncomplicated liver abscess. It is suggested that needle aspiration can improve response to antibiotics treatment,reduce hospital stay and the total cost of treatment. Although USG guided needle aspiration is fairly safe, it is nonetheless an invasive procedure requiring the passage of a wide bore needle in to a highly vascular organ, and can be associated with the risk of bleeding. Needle aspirations, especially at the time of intervention has therefore remained a debatable issue and it seems important to determine its possible role in the treatment of liver abscess.

Guillain-Barre syndrome (GBS) is the most common cause of flaccid paralysis in affected patients. Here we present a case of GBS presenting with flaccid paralysis as well as hyponatremia. The association of hyponatremia in GBS is discussed, as well as other potential causes and risk factors.

Background and Objectives: While the impact of maternal factors on birth outcomes are widely reported, the extent to which paternal involvement and varying cultural family dynamics influence birth outcomes particularly in an international context, remain understudied. The purpose of this study was to assess the relationship between paternal involvement and adverse birth outcomes in South Gujarat, India. Methods: An in-person questionnaire was administered to adult women at delivery or during the one-month postpartum visit at New Civil Hospital, in South Gujarat, India between May and June 2016 to assess level of paternal support and attendance at prenatal appointments and household structure. Pregnancy variables including birthweight and gestational age at delivery were collected from maternal and newborn record/chart review. Chi-square and t-test were used to assess demographics, as appropriate. Logistic regression was used to examine the association between paternal involvement and pregnancy birth outcomes. Results: Of the 404 infants born during the study period, 26.7% were premature (

Background & Aims The risk of nonalcoholic fatty liver disease (NAFLD) and its progression may differ between men and women. We conducted a systematic review and meta-analysis to determine the relationship between sex and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis. Methods Studies reporting sex-stratified NAFLD prevalence among population-based samples and either NASH or advanced fibrosis among patients with biopsy-proven NAFLD were identified from MEDLINE, EMBASE, and Cochrane databases through December 2017. We calculated pooled relative risk ratios comparing women vs men for each outcome. Results Our final analysis comprised 54 studies. Samples sizes were 62,239 for the NAFLD analysis, 5428 for the NASH analysis, and 6444 for the advanced fibrosis analysis. Women had a 19% lower risk of NAFLD than men in the general population (pooled risk ratio [RR], 0.81; 95% CI, 0.68–0.97; I2 = 97.5%). Women had a similar risk of NASH (RR, 1.00; 95% CI, 0.88–1.14; I2 = 85.1%), and a 37% higher risk of advanced fibrosis (RR, 1.37; 95% CI, 1.12–1.68; I2 = 74.0%) than men. Age modified the effect of sex on NAFLD severity. Risks of NASH (RR, 1.17; 95% CI, 1.01–1.36) and advanced fibrosis (RR, 1.56; 95% CI, 1.36–1.80; I2 = 0) were substantially higher in women in study populations with average ages of 50 years and older; sex differences in NASH and advanced fibrosis were attenuated in younger populations. Conclusions In a systematic review and meta-analysis, we found women to have a lower risk of NAFLD than men. However, once NAFLD is established, women have a higher risk of advanced fibrosis than men, especially after age 50 years.

After deep vein thrombosis (DVT) is diagnosed, prompt evaluation and therapeutic intervention are of paramount importance for improvement in patient-important outcomes. We systematically reviewed patient-important outcomes in patients with suspected DVT, including mortality, incidence of pulmonary embolism (PE) and DVT, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, Ovid Medline, Embase for eligible studies, references lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Nine studies with 5126 patients were included for lower extremity DVT. Three studies with 500 patients were included for upper extremity DVT. Among patients with lower extremity DVT, 0.85% (95% confidence interval [CI], 0% to 2.10%) and 0% developed recurrent DVT and PE, respectively, at 3 months. Among patients with upper extremity DVT, 0.49% (95% CI, 0% to 1.16%) and 1.98% (95% CI, 0.62% to 3.33%) developed recurrent DVT and PE, respectively, at 3 months. No major bleeding events were reported for those anticoagulated, which is lower than in other systematic reviews. For both upper and lower extremity DVT, low pretest probability patients with a negative D-dimer had a comparable incidence of VTE at 3 months (∼1%) as patients with a negative ultrasound (US). At higher pretest probabilities, negative US testing with or without serial US appears to be the safer option. In this review, we summarized the outcomes of patients evaluated by various diagnostic pathways. In most instances, there was significant limitation due to small population size or lack of direct evidence of effects of using a specific pathway. This systematic review was registered at PROSPERO as CRD42018100502.

Introduction: Sudden cardiac arrest is a leading cause of mortality in the United States, with over 475,000 people dying annually. Bystander CPR significantly improves the odds of neurologically intact survival, yet nationally is performed in only 46% of out of hospital cardiac arrests. Significant regional variation exists in the performance of bystander CPR, with our community performing lower than national norms (26%). We sought to assess our community’s awareness of current American Heart Association (AHA) recommendations and the perceived barriers to performing bystander CPR. Methods: Adult study volunteers were recruited within the community (Norfolk, VA; pop. 244,703) and completed a 15-question anonymous survey that assessed knowledge of AHA recommendations, willingness to perform, and perceived barriers to performing CPR. Results: A total of 1,017 respondents completed all or part of the survey (40% male; 60% female). Knowledge of the importance of CPR was high. Of the respondents, 78% (n=708) indicated they would know if CPR was required, 84% (n=756) recognized the importance of performing CPR on a person who is unconscious and not breathing, and 89% (n=733) agreed CPR should not be delayed until the arrival of an ambulance. Though 70% (n=597) of respondents indicated they had been previously trained to perform CPR, only 44% (n=397) had been trained to perform “hands-only” CPR. Several barriers to performing CPR were identified. Forty-nine percent of respondents (n=402) believed they must perform “mouth to mouth” during CPR while 32% (n=284) were concerned they could catch a disease. Fear of doing something wrong while performing CPR was a concern for 28% (n=257). Twenty-six percent (n=237) reported concerns about the legal consequences of performing CPR. Conclusions: Though the importance of bystander CPR is well recognized in our community, misunderstandings regarding requirements and risks continue to exist. Education efforts should focus on increasing community awareness of current AHA recommendations.

With the long-standing controversy surrounding the use of prostate-specific antigen (PSA) for the detection, evaluation, and surveillance of prostate cancer, there is a need for a minimally invasive technique to identify and risk-stratify these patients. Additionally, in an effort to reduce the number of unnecessary biopsies and identify clinically significant prostate cancer (csPCa), there has been a shift in practice towards the use of multiparametric magnetic resonance imaging (mpMRI) in conjunction with decision-making regarding prostate cancer diagnosis and management. In the current review, we summarize the data regarding the use of mpMRI in the detection, evaluation, and surveillance of csPCa. Recent prospective clinical trials have determined that a pre-biopsy mpMRI may rule out insignificant prostate cancers, thereby reducing the number of patients who require a biopsy. The anatomic information gathered from these pre-biopsy mpMRI performed during MRI fusion biopsy in csPCa increases the accuracy of pathologic staging in terms of Gleason scores. In regard to active surveillance, prospective trials suggest little to no clinical utility for mpMRI and fusion biopsy in the surveillance of prostate cancer despite conflicting findings from retrospective studies. Recent trials suggest that mpMRI can play an important role in the detection and evaluation of csPCa. The ideal role for mpMRI in active surveillance remains limited.

“Head Start” 4 (HS 4) is a prospective randomized clinical trial that tailors treatment based on medulloblastoma molecular subgroups and response to induction chemotherapy to compare the efficacy of one versus three (tandem) cycles of myeloablative therapy. Advances in RNA and DNA profiling have identified four core molecular subgroups of medulloblastoma with prognostic significance: Sonic Hedgehog (SHH) subtype, WNT subtype, Group 3, and Group 4. In HS 4 trial, we utilize a combination of histopathology and immunohistochemistry (pathology/IHC), as well as chromosomal microarray analysis (CMA) utilizing OncoScanTM (Thermo Fisher) to classify medulloblastoma samples into either SHH, WNT, or non-WNT/non-SHH (Group 3/4) subgroups at the time of diagnosis. NanoString based 22-gene assay is performed retrospectively to test concordance. We have pathology/IHC, CMA, and NanoString data on 26 infants and young children with medulloblastoma enrolled on HS 4. Pathology/IHC was able to assign samples to SHH, WNT, and non-WNT/non-SHH subgroups in all but two cases: one case was classified as Group 3, and the second as SHH by both CMA and NanoString. CMA was indeterminate in six cases, of which, pathology/IHC was able to assign all six samples aforementioned three subgroups. NanoString was indeterminate in two cases: one case was classified as SHH by CMA and pathology/IHC, and the second case was indeterminate by CMA but was assigned as non-WNT/non-SHH on pathology/IHC. There is excellent correlation between NanoString and combination of histopathology and CMA for core medulloblastoma subgrouping on HS 4. Methylation studies are ongoing.

Background: clavicle fractures account for approximately 2.6% of all fractures. Middle third fractures account for 80% of all clavicle fractures. Historically, clavicle fractures have been treated mostly nonoperatively with clavicular brace, but due to increase rate of complications such as nonunion and malunion, clavicle fractures are now increasingly being treated surgically which results in lower rate of such complications, besides improved patient oriented outcome and early mobilization.Methods: Current study is a prospective and observational comparative study, conducted over 30 patients diagnosed with displaced clavicle fractures coming to the department of orthopaedics in a tertiary care hospital in South Rajashthan between January 2019 to June 2020. Patients were then allotted alternatively into two groups. Patients selected for conservative treatment were treated with the figure of eight clavicle brace and arm sling pouch. Patients selected for operative treatment were treated with plating. Functional outcomes were assessed using Constant and Murley score in every follow up at 3 month and 6 month; and fracture union was assessed by serial radiographs taken at sixth week, third month and sixth month.Results: Among 30 patients, 15 patients were treated conservatively and rest 15 patients were treated surgically with plating. Functional outcome at the end of third and sixth months of follow up were measured by using Constant Murley score and found significantly higher in operative group than conservative group.Conclusions: In our study, it was found that at the end of 6 month follow up, patients treated surgically with plating had better functional outcomes than conservatively treated patients as measured by Constant and Murley score. It was also seen that, the duration of union and the incidence of complications was less in the operative group as compared to the conservative group.

Background: Spondylolisthesis is condition in which one vertebra slips over other vertebra. This study has been done to compare the functional outcome and complications of two techniques: posterior lumbar fusion (intertransverse fusion) and posterior lumbar interbody fusion.Methods: Total 20 patients with spondylolisthesis admitted in a tertiary care centre in Rajasthan were allotted alternatively in posterior lumbar fusion (PLF) group and posterior lumbar interbody fusion (PLIF) group. In PLF, fusion was done by placing bone graft between transverse processes and around facets. In PLIF, fusion was bone by placing cage in between vertebral bodies.Results: 20 patients were included in our study with female predominance (65%). Mean age was 54.2 years (PLF=58.4 and PLIF=50.2). 70% patients have L4-L5 level spondylolisthesis. Average operative time was less in PLF group, which is statistically significant. Functional outcome was measured by using visual analogue scale (VAS) score and Japanese orthopedics association score (JOAS) at 3 weeks, 3 months and 6 months. There is a significant decrease between preoperative VAS and at 6 months, in both PLF and PLIF group. JOAS was significantly increased at 6 months in both PLF and PLIF group as compared to preoperative score. But difference in JOAS at 6 months is not significant between PLF and PLIF.Conclusions: Both PLF and PLIF are equally effective for spondylolisthesis. Both techniques have same satisfactory results. As PLIF is more invasive technique, more operative time and more complications are seen.

Treatment of cancer is a furtive problem in the current era in spite of significant advancement in drug delivery systems and identification of new therapeutic molecules. The ration of lab to market translation of therapeutic research is quite low in anticancer therapy due to hidden and unnameable disease causing and disease progression mechanisms. Oncogene activation disturbs normal cell processes such as cell growth and apoptosis, which ultimately leads to cancer. Different ways, such as RNAi, antisense oligonucleotides, Translation suppressing oligonucleotide and external guide sequences which silences oncogenes are key techniques under investigation currently. The emerging way of formulating nanoparticles containing antisense oligonucleotides and the targeting approaches is illustrated with the brief information on key materials used for the same purpose. Gene targets identified and investigated by various companies and research groups are enumerated and reviewed for their potential to consider antisense gene therapy. Nanocarrier systems which have been reported to enhance feasibility of selective antisense oligonucleotides to treat the disease are assessed for their pros and cons.

Background While the overall incidence rate of colorectal cancer (CRC) in Canada has been decreasing, some countries show an increasing incidence in those under the age of 50. We examined the trends in CRC incidence and associated lifestyle risk factors in Canadians aged 15⿿49. Methods Incidence data for colorectal, colon and rectum/rectosigmoid cancers were obtained for 1969⿿2010 from the Canadian Cancer Registry, and trends in age-standardized incidence rates (ASIRs) were examined by Joinpoint regression for three age groups (15⿿29, 30⿿39, 40⿿49 years) and by sex. Trends in the prevalence of some CRC risk factors were similarly examined from national health surveys for various periods ranging from 1970 to 2012. Results In both sexes combined, ASIRs rose by 6.7%/year (1997⿿2010) for 15⿿29-year-olds, 2.4%/year (1996⿿2010) for 30⿿39-year-olds, and 0.8%/year (1997⿿2010) for 40⿿49-year-olds. Similar trends were observed by sex. The rise in ASIR was more rapid for cancers of the rectum/rectosigmoid compared to colon for all age groups. Risk factor trends varied: excess weight rose substantially, vegetables and fruit consumption increased slightly, physical inactivity rates declined but remained high, alcohol consumption changed little, and smoking rates declined. Data on red/processed meat consumption were unavailable. Conclusion The ASIR of CRC in young Canadians has increased since about the mid-1990s. The rising prevalence of excess weight in younger generations has likely played a role in the CRC trend, but more research is needed.

Pulmonary involvement in Henoch‐Schonlein purpura (HSP) although rare is an important treatable cause of hospital admission in patients. Its diagnosis is difficult due to the vague symptoms and non-specific radiographic findings. We present one such case of a known case of HSP presenting with pulmonary involvement and treated successfully with steroids and immunosuppressant medications after ruling out all other causes. This particular case could also have an additional component of methotrexate induced lung involvement. Overall it is an interesting case with some much needed learning points.

The original version of the article unfortunately contained an error in the first name and the surname of the third author.

Introduction: Factors such as anatomic complexity and extensive surgical procedures increase the risk of serious, sometimes fatal complications post-surgical treatment for head and neck cancer squamous cell carcinoma (HNSCC). Thirty-day (30-day) mortality is a common quality metric that evaluates short-term survival; however, no study has described disparities associated with 30-day mortality following surgery in HNSCC United States population. The aim of this study was to identify disparities and factors (clinical and nonclinical) associated with 30-day postoperative mortality in patients with HNSCC treated with and without adjuvant therapy. Methods: In this retrospective study, we utilized a patient cohort of 102,877 confirmed HNSCC cases from the National Cancer Database (2004-2013) who were treated surgically with curative intent for the primary head and neck cancer. The effects of adjuvant therapy and other clinical and nonclinical factors on 30-day postoperative mortality were estimated via multivariate logistic regression with adjustment for time-varying nature of adjuvant therapy. Outcome was defined as any-cause-death within 30 days after definitive surgery of primary cancer. We controlled for several clinical and nonclinical covariates, including age, race, sex, health insurance status, primary tumor site, stage of presentation, and Charlson-Deyo comorbidity score. Results: There were 859 patients who died within 30 days of definitive surgery for cancer, yielding a 30-day mortality rate of 0.83%. Treatment differences were associated with mortality, and patients who received adjuvant therapy had were significantly more likely to die within 30 days compared with those treated with surgery alone (aOR: 3.51; 95% CI 1.85, 6.66). Increasing number of comorbidities was also associated with greater odds of 30-day mortality (Charlson-Deyo comorbidity scores of 1: aOR: 1.45; 95% CI 1.23, 1.71, and Charlson-Deyo comorbidity scores of 2+ aOR: 2.52; 95% CI 2.05, 3.09). There were also sociodemographic disparities associated with 30-day mortality. Odds of 30-day mortality were significantly increased among patients with Medicaid insurance (aOR: 1.99; 95% CI 1.48, 2.68), as well as those who lived in neighborhoods with little education (≥ 29% missing high school diploma: aOR: 1.43; 95% CI 1.08, 1.88). Conclusions: Disparities impact short-term mortality in the head and neck cancer population. Patients that were significantly more likely to die within 30 days of surgical treatment were those treated with adjuvant therapy, those with greater burden of comorbidities, those with little education, and those covered by Medicaid. To our knowledge, this is the largest study to document short term (30-day) mortality disparities among patients with head and neck cancer post-surgery in the United States. To improve short-term survival among head and neck cancer patients, it is important to account for these disparities found in this study. Citation Format: Aleksandr R. Bukatko, Parth Patel, Vindhya Kakarla, Matthew C. Simpson, Eric A. Boakye, Katherine A. Stamatakis, Nosayaba Osazuwa-Peters. Disparities and factors associated with 30-day mortality following surgical treatment for squamous cell head and neck cancer with or without adjuvant therapy [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B085.

Asthma affects more than 300 million people worldwide and is increasing in prevalence. Asthma is most likely a common phenotype resulting from numerous combinations of genetic, environmental and age-related factors. Genetic variant studies have not come close to explaining the hereditability of asthma that is observed clinically. Such studies have been limited by disease heterogeneity, costs, and the complexity of the human DNA. Nonetheless, large-scale gene variant studies known as genome-wide association studies have identified asthma susceptibility loci that are both highly-significant and reproducible across populations. Several loci identified by these studies ended up being close to cytokines (e.g., IL-33 and TSLP) whose importance to asthma was perhaps underappreciated at the time. By directing both research and treatment efforts, these discoveries are already leading to new and improved therapies. At the same time, a gene expression signature identifying the Type 2 inflammatory response was identified in airway epithelial cells. This simple discovery has had important ramifications in patient phenotyping—a process that has advanced disease understanding and helped better personalize treatment recommendations. By connecting genetic variants to altered gene and protein expression, global gene expression will also have an important future role in connecting gene variants to disease mechanisms. By connecting DNA epigenetic changes to environmental and age-related factors, epigenetics will likely play a similarly important role in connecting environmental influences to disease. Although full of surprises and frustrations, genomic science offers excitingly new opportunities to greatly advance our understanding and treatment of asthma.