Developing DELPHI expert consensus rules for a digital twin model of acute stroke care in the neuro critical care unit.

INTRODUCTION: Digital twins, a form of artificial intelligence, are virtual representations of the physical world. In the past 20 years, digital twins have been utilized to track wind turbines' operations, monitor spacecraft's status, and even create a model of the Earth for climate research. While digital twins hold much promise for the neurocritical care unit, the question remains on how to best establish the rules that govern these models. This model will expand on our group's existing digital twin model for the treatment of sepsis. METHODS: The authors of this project collaborated to create a Direct Acyclic Graph (DAG) and an initial series of 20 DELPHI statements, each with six accompanying sub-statements that captured the pathophysiology surrounding the management of acute ischemic strokes in the practice of Neurocritical Care (NCC). Agreement from a panel of 18 experts in the field of NCC was collected through a 7-point Likert scale with consensus defined a-priori by ≥ 80% selection of a 6 ("agree") or 7 ("strongly agree"). The endpoint of the study was defined as the completion of three separate rounds of DELPHI consensus. DELPHI statements that had met consensus would not be included in subsequent rounds of DELPHI consensus. The authors refined DELPHI statements that did not reach consensus with the guidance of de-identified expert comments for subsequent rounds of DELPHI. All DELPHI statements that reached consensus by the end of three rounds of DELPHI consensus would go on to be used to inform the construction of the digital twin model. RESULTS: After the completion of three rounds of DELPHI, 93 (77.5%) statements reached consensus, 11 (9.2%) statements were excluded, and 16 (13.3%) statements did not reach a consensus of the original 120 DELPHI statements. CONCLUSION: This descriptive study demonstrates the use of the DELPHI process to generate consensus among experts and establish a set of rules for the development of a digital twin model for use in the neurologic ICU. Compared to associative models of AI, which develop rules based on finding associations in datasets, digital twin AI created by the DELPHI process are easily interpretable models based on a current understanding of underlying physiology.

Anticoagulation Prescribing Patterns in Intensive Care Unit Patients Admitted with Prehospital Direct Oral Anticoagulant Therapy: A Single Academic Center Experience.

OBJECTIVE: To describe the current prescribing practices of direct oral anticoagulants (DOACs) in intensive care unit (ICU) patients and the associated clinical outcomes, including the incidence of major bleeding episodes and the need for intervention (endoscopic, surgical, or interventional radiology guided). DESIGN: Observational, retrospective chart review. SETTING AND PARTICIPANTS: Single large academic center study. Participants included patients with critical illness who were admitted to the intensive care units (ICU) at Mayo Clinic from January 1st, 2012, until May 4th, 2018. Adult ICU patients with a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) listed as one of the active medications at the time of hospital admission were included. RESULTS: 37 249 patients in medical and surgical intensive care units were screened for the study period. After excluding patients who did not qualify, 558 unique encounters were included. The median age was 69 (IQR 59-78) years; most patients were male, white Caucasians, and had a median SOFA score of 4. After excluding the patients who had major bleeding episodes in the first 24 hours, 188 (39%) were continued on the same DOAC therapy, 204 (42%) were discontinued without transitioning to another agent, and 95 (20%) were transitioned to another agent. Finally, 410 (84%) were dismissed on DOAC therapy at the end of hospitalization. The difference in the continuation rate of the same DOAC agent beyond 24 hours, discontinuation without transition to an alternate agent, or discontinuation of DOAC with a transition to an alternate anticoagulation agent was not statistically significant (P = .60). A total of 52 major bleeding events were identified. Gastrointestinal bleeding was the most common bleeding complication [n (%): 34 (65)], followed by intra-abdominal and peri-procedural bleeding [7 (13.5) and 7 (13.5)]. Thirty-three (65%) patients had a major bleeding complication requiring intervention. CONCLUSIONS: Our single-center retrospective study describes the current prescribing practices and preliminary outcomes in ICU patients with prehospital use of DOACs. Up to 20% of the patients were transitioned to a different agent within 24 hours of ICU admission, whereas a significant proportion of patients (42%) had anticoagulation discontinued altogether. Most patients who suffered a major bleeding episode required either endoscopic or surgical intervention to control bleeding.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

The importance of accessory protein variants in the pathogenicity of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2) with an estimated fatality rate of less than 1%. The SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 possess putative functions to manipulate host immune mechanisms. These involve interferons, which appear as a consensus function, immune signaling receptor NLRP3 (NLR family pyrin domain-containing 3) inflammasome, and inflammatory cytokines such as interleukin 1ß (IL-1ß) and are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins were observed across six continents of all complete SARS-CoV-2 proteomes based on the data reported before November 2020. A decreasing order of percentage of unique variations in the accessory proteins was determined as ORF3a > ORF8 > ORF7a > ORF6 > ORF10 > ORF7b across all continents. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. These findings suggest that the wide variations in accessory proteins seem to affect the pathogenicity of SARS-CoV-2.

Periodically aperiodic pattern of SARS-CoV-2 mutations underpins the uncertainty of its origin and evolution.

Various lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have contributed to prolongation of the Coronavirus Disease 2019 (COVID-19) pandemic. Several non-synonymous mutations in SARS-CoV-2 proteins have generated multiple SARS-CoV-2 variants. In our previous report, we have shown that an evenly uneven distribution of unique protein variants of SARS-CoV-2 is geo-location or demography-specific. However, the correlation between the demographic transmutability of the SARS-CoV-2 infection and mutations in various proteins remains unknown due to hidden symmetry/asymmetry in the occurrence of mutations. This study tracked how these mutations are emerging in SARS-CoV-2 proteins in six model countries and globally. In a geo-location, considering the mutations having a frequency of detection of at least 500 in each SARS-CoV-2 protein, we studied the country-wise percentage of invariant residues. Our data revealed that since October 2020, highly frequent mutations in SARS-CoV-2 have been observed mostly in the Open Reading Frame (ORF) 7b and ORF8, worldwide. No such highly frequent mutations in any of the SARS-CoV-2 proteins were found in the UK, India, and Brazil, which does not correlate with the degree of transmissibility of the virus in India and Brazil. However, we have found a signature that SARS-CoV-2 proteins were evolving at a higher rate, and considering global data, mutations are detected in the majority of the available amino acid locations. Fractal analysis of each protein's normalized factor time series showed a periodically aperiodic emergence of dominant variants for SARS-CoV-2 protein mutations across different countries. It was noticed that certain high-frequency variants have emerged in the last couple of months, and thus the emerging SARS-CoV-2 strains are expected to contain prevalent mutations in the ORF3a, membrane, and ORF8 proteins. In contrast to other beta-coronaviruses, SARS-CoV-2 variants have rapidly emerged based on demographically dependent mutations. Characterization of the periodically aperiodic nature of the demographic spread of SARS-CoV-2 variants in various countries can contribute to the identification of the origin of SARS-CoV-2.

Coronavirus disease 2019 and mechanical circulatory support devices: a comprehensive review.

Coronavirus disease (COVID-19) can cause circulatory shock refractory to medical therapy. Such patients can be managed with mechanical circulatory support (MCS) devices like IABP, Impella, VA ECMO, and Left Ventricular Assist Devices (LVADs). Moreover, patients on long-term durable LVADs are a special population having increased susceptibility and mortality to COVID-19 infection. In this narrative review, we searched PubMed and Medline for studies on COVID-19 patients on short-term MCS devices. We found 36 papers with 110 patients who met our review criteria, including 89 LVAD patients and 21 COVID-19 patients who needed MCS device therapy. These studies were used to extract patient demographics, clinical presentation, MCS device details, management, and outcomes. Mean age of patients with COVID-19 infection on LVADs was 60, 73% were male, and HeartMate 3 was the most common device (53%). Most patients (77.5%) needed hospitalization, and mortality was 23.6%. Among the 21 reported cases of critically ill COVID-19 patients who required MCS, the mean age was 49.8 years, 52% were women, and the most common MCS device used was VA ECMO (62%) in conjunction with an Impella for LV venting. Comorbidities were not present in 43%, but 71% had abnormal ventricular function on echocardiography. MCS is a viable option for managing severe COVID-19 infection with shock, with many reported cases of favorable outcomes.

Outcomes of Patients With Coronavirus Disease 2019 Receiving Organ Support Therapies: The International Viral Infection and Respiratory Illness Universal Study Registry.

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.

Timing of ARDS Resolution (TARU): A Pragmatic Clinical Assessment of ARDS Resolution in the ICU.

PURPOSE: Lack of a pragmatic outcome measures for acute respiratory distress syndrome (ARDS) resolution is a barrier to meaningful interventional trials of novel treatments. We evaluated a pragmatic, electronic health record (EHR)-based approach toward the clinical assessment of a novel outcome measure: ICU ARDS resolution. METHODS: We conducted a retrospective observational cohort study evaluating adult patients with moderate-severe ARDS admitted to the medical intensive care unit (ICU) at Mayo Clinic in Rochester, MN, from January 2001 through December 2010. We compared the association of ICU ARDS resolution vs non-resolution with mortality. ICU ARDS resolution was defined as improvement in P/F > 200 for at least 48 h or (if arterial blood gas unavailable) SpO2:FiO2 (S/F) > 235, or discharge prior to 48 h from first P/F > 200 without subsequent decline in P/F, as documented in EHR. RESULTS: Of the 254 patients included, ICU ARDS resolution was achieved in 179 (70%). Hospital mortality was lower in patients who met ICU ARDS resolution criteria as compared to those who did not (23% vs. 41%, p < 0.01). After adjusting for age, gender, and illness severity, the patients who met ICU ARDS resolution criteria had lower odds of hospital mortality [odds ratio 0.47, 95% CI 0.25-0.86; p = 0.015]. CONCLUSION: The electronic health record-based pragmatic measure of ICU ARDS resolution is associated with patient outcomes and may serve as an intermediate outcome assessing novel mechanistic treatments.

Tocilizumab in Hospitalized Patients with COVID-19: A Meta Analysis of Randomized Controlled Trials.

BACKGROUND: To date, only dexamethasone has been shown to reduce mortality in coronavirus disease-19 (COVID-19) patients. Tocilizumab has been recently added to the treatment guidelines for hospitalized COVID-19 patients, but data remain conflicting. STUDY DESIGN AND METHODS: Electronic databases such as MEDLINE, EMBASE, and Cochrane central were searched from March 1, 2020, until March 10, 2021, for randomized controlled trials evaluating the efficacy of tocilizumab in hospitalized COVID-19 patients. The outcomes assessed were all-cause mortality, mechanical ventilation, and time to discharge. RESULTS: Nine studies (with 6490 patients) were included in the analysis. In total, 3358 patients received tocilizumab, and 3132 received standard care/placebo. Pooled analysis showed a significantly decreased risk of all-cause mortality (RR 0.89, 95% CI 0.80-0.98, p = 0.02) and progression to mechanical ventilation (RR 0.80, 95% CI 0.71-0.89, p < 0.0001) in the tocilizumab arm compared to standard therapy or placebo. In addition, there was a trend towards improved median time to hospital discharge (RR 1.28, 95% CI 1.12-1.45, p = 0.0002). CONCLUSIONS: Tocilizumab therapy improves outcomes of mortality and need for mechanical ventilation, in hospitalized patients with COVID-19 infection compared with standard therapy or placebo. Our findings suggest the efficacy of tocilizumab therapy in hospitalized COVID-19 patients and strengthen the concept that tocilizumab is a promising therapeutic intervention to improve mortality and morbidity in COVID-19 patients.

A review of the presentation and outcome of takotsubo cardiomyopathy in COVID-19.

Although the most frequent presentation of the novel Coronavirus disease-2019 (COVID-19) is a respiratory syndrome, cardiac involvement is being increasingly recognized. One such entity is takotsubo cardiomyopathy. We sought to review the various cases of takotsubo cardiomyopathy reported during the COVID-19 pandemic and consolidate the information available on its clinical features, evaluation and treatment. We performed a PubMed search using the MeSH terms "Takotsubo Cardiomyopathy" or "Stress Cardiomyopathy" and "COVID-19", and identified 16 case reports, two case series, and one retrospective cohort study. There was a total of 24 reported patients with COVID-19 infection, who developed takotsubo cardiomyopathy, and two patients without COVID-19 who developed takotsubo cardiomyopathy due to the emotional stress associated with the global pandemic. The mean age of the patients was 67.19 years (SD 15.83) and 16(59.3%) were women. Chest pain was reported in only ten patients (38.46 %) and ST-elevation was seen in 11 patients (42.3%). While most patients had typical takotsubo cardiomyopathy, four patients had inverted(reverse) takotsubo cardiomyopathy, two had bi-ventricular involvement, one had median takotsubo and another had global takotsubo with apical sparing variant. Most patients had a positive outcome with complete or near-complete reversal of cardiac dysfunction at the time of discharge. Five deaths (19.23%) were reported. Takotsubo cardiomyopathy is a rare, but increasingly reported reversible cardiomyopathy that can be seen in patients with COVID-19 infection and the diagnosis must be actively sought for in these patients.

Pneumothorax and pneumomediastinum in COVID-19 acute respiratory distress syndrome.

COVID-19 has involved numerous countries across the globe and the disease burden, susceptible age group; mortality rate has been variable depending on the demographical profile, economic status, and health care infrastructure. In the current clinical environment, COVID-19 is one of the most important clinical differential diagnoses in patients presenting with respiratory symptoms. The optimal mechanical ventilation strategy for these patients has been a constant topic of discussion and very importantly so, since a great majority of these patients require invasive mechanical ventilation and often for an extended period of time. In this report we highlight our experience with a COVID-19 patient who most likely suffered barotrauma either as a result of traumatic endotracheal intubation or primarily due to COVID-19 itself. We also aim to highlight the current literature available to suggest the management strategy for these patients for a favorable outcome. The cases described are diverse in terms of age variance and other comorbidities. According to the literature, certain patients, with COVID-19 disease and spontaneous pneumothorax were noted to be managed conservatively and oxygen supplementation with nasal cannula sufficed. Decision regarding need and escalation to invasive mechanical ventilation should be taken early in the disease to avoid complications such as patient self-inflicted lung injury (P-SILI) and barotrauma sequelae such as pneumothorax and pneumomediastinum Recent systematic review further supports the fact that the use of non-invasive ventilation (NIV) in certain patients with COVID-19 pneumonia may give a false sense of security and clinical stabilization but has no overall benefit to avoid intubation. While invasive mechanical ventilation may be associated with higher rates of barotrauma, this should not mean that intubation and invasive mechanical ventilation should be delayed. This becomes an important consideration when non-intensivists or personnel with less experience provide care for this vulnerable patient population who may rely too heavily on NIV to avoid intubation and mechanical ventilation.

Risk of Future Type 2 Diabetes Mellitus in Patients Developing Steroid-Induced Hyperglycemia During Hospitalization for Chronic Obstructive Pulmonary Disease Exacerbation.

OBJECTIVE: We evaluated the future risk of developing impaired glucose tolerance and type 2 diabetes mellitus (T2DM) in patient without T2DM who develop hyperglycemia with short-term systemic glucocorticoid therapy during hospitalization. METHODS: Retrospective analysis was performed on charts of non-diabetic patients admitted with COPD exacerbation and treated with a course of high dose systemic corticosteroid during hospitalization. Patients with BMI over 40 kg/m2, endocrinopathy and on medications that could impair glucose tolerance were excluded. Patient data were collected for 1 year after initial hospitalization. Diagnosis of T2DM or IGT was based on the ADA criteria. 311 charts were reviewed, of which 64 patients met our inclusion criteria. Depending on the blood glucose readings during hospitalization, the patients were categorized into two groups: hyperglycemic (> 140 mg/dL; n = 42) and normoglycemic (≤ 140 mg/dL; n = 22). RESULTS: In the hyperglycemic group, 17/42 (40%) patients developed prediabetes and 5/42 (12%) developed T2DM on follow-up. Interestingly, none of the patients developed IGT or T2DM in the normoglycemic group. Both the groups were well matched in terms of family history of DM, history of hypertension, hyperlipidemia, BMI > 25 kg/m2, weight change, tobacco and alcohol use, corticosteroid therapy duration, and cumulative steroid dose. After adjusting for all these risk factors, on logistic regression analysis, hyperglycemic patients had 37 times higher chance of developing IGT, compared to normoglycemic patients (p = 0.003). CONCLUSIONS: Our study suggests that patients without T2DM with acute exacerbation of COPD who develop steroid-induced hyperglycemia in response to systemic corticosteroid treatment have an increased risk for developing future IGT or T2DM. Bigger studies are needed to support our findings since results drawn from our study have the limitations of smaller sample size (wider confidence interval) in a single center.

Quantifying and reporting cardiac findings in imaging of COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a public health emergency and a pandemic of international concern. As of April 31st,  the reported cases of COVID-19 are three million in 186 countries. Reported case fatality has crossed 200 thousand among which more than fifty thousand has been in the USA. Most patients present with symptoms of fever, cough, and shortness of breath following exposure to other COVID-19 patients. Respiratory manifestations predominate in patients with mild, moderate, severe illness. Imaging of patients with COVID-19 consistently reports various pulmonary parenchymal involvement. In this article we wanted to reinforce and review the various reported imaging patterns of cardiac and mediastinal involvement in COVID-19 patients. Among patients with COVID 19 who underwent various imaging of chest various cardiac findings including pericardial effusion, myocarditis, cardiomegaly has been reported. Most of these findings have been consistently reported in patients with significant acute myocardial injury, and fulminant myocarditis. Acute biventricular dysfunction has also been reported with subsequent improvement of the same following clinical improvement. Details of cardiac MRI is rather limited. In a patient with clinical presentation of acute myocarditis, biventricular myocardial interstitial edema, diffuse biventricular hypokinesia, increased ventricular wall thickness, and severe LV dysfunction has been reported. Among patients with significant clinical improvement in LV structure and function has also been documented. With increasing number of clinical cases, future imaging studies will be instrumental in identifying the various cardiac manifestations, and their relation to clinical outcome.

COVID-2019: update on epidemiology, disease spread and management.

With each passing day, more cases of Coronavirus disease (COVID-2019) are being detected and unfortunately the fear of novel corona virus 2019 (2019-nCoV) becoming a pandemic disease has come true. Constant efforts at individual, national, and international level are being made in order to understand the genomics, hosts, modes of transmission and epidemiological link of nCoV-2019. As of now, whole genome sequence of the newly discovered coronavirus has already been decoded. Genomic characterization nCoV-2019 have shown close homology with bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Structural analysis of the receptor binding site has confirmed that 2019-nCoV binds with the same ACE 2 receptor protein as human SARS virus. Compared to the previous coronavirus outbreaks, the overall mortality rate is relatively low for COVID-2019 (2-3%). Suspected cases must be quarantined till their test comes positive or they clear infection. At present, treatment of COVID-2019 is mostly based on the knowledge gained from the SARS and MERS outbreaks. Remdesivir, originally develop as a treatment for Ebola virus disease and Marburg virus infections, is being studied for it effectiveness against 2019-nCoV infection. Many other antiviral agents and vaccines are being tested but most of them are in phase I or II and hence unlikely to be of any benefit immediately with regards to current outbreak. Hence, the standard infection control techniques and preventive steps for healthy individuals and supportive care for the confirmed cases is the best available strategy to deal with current viral outbreak. .

Cerebrovascular events in COVID-19 patients.

Neurological manifestations in patients with COVID-19 are more frequently being reported. Cerebrovascular events have been reported in around 3% of patients. In this review we summarize the published literature on cerebrovascular events in patients with COVID-19 as available on the PubMed database. So far, 3 studies have reported cerebrovascular events. Cerebrovascular events were identified on screening patients with decreased consciousness or in the presence of focal neurological deficits. These events were common in elderly, critically ill patients and in patients with prior cardio-cerebrovascular comorbidities. The diagnosis of cerebrovascular events was confirmed with computed tomography of the brain in most studies reporting neurological events. Multiple pathological mechanisms have been postulated regarding the process of neurological and vascular injury among which cytokine storm is shown to correlate with mortality. Patients with severe illness are found to have a higher cardio- cerebrovascular comorbidity. With an increasing number of cases and future prospective studies, the exact mechanism by which these cerebrovascular events occur and attribute to the poor outcome will be better understood.

Gonococcal cellulitis: an (un)friendly bite.

BACKGROUND: Gonococcal infection can present with wide spectrum of symptoms, most commonly involving the genitals. This case highlights a rare presentation of Neisseria gonorrhoeae infection primarily with skin involvement without uro-genital disease. CASE: A 33-year-old male was admitted to the hospital with complaints of painful swelling of his penis. In the emergency room, he underwent incision and drainage of the abscess under local anaesthesia. After microbiological evaluation, he was found to have skin abscess caused by N. gonorrhoeae and was treated with intravenous ceftriaxone and changed to oral agent amoxicillin-clavulanate with complete resolution. CONCLUSION: The manifestations of gonococcal infection have changed significantly over the last few years, with more involvement of extra genital sites attributed to changes in sexual practices. Our patient was treated for cellulitis and abscess caused by N. gonorrhoeae in the absence of systemic or urethral disease. Recommendations regarding treatment of gonococcal infection have been widely published. However, there is a paucity of evidence-based guidelines regarding the therapy of primary cutaneous gonococcal infection. Pooled data from similar cases may help determine the optimum therapy.

Recurrent Pulmonary Embolism and Hypersensitivity Pneumonitis Secondary to Aspergillus, in a Compost Plant Worker: Case Report and Review of Literature.

Activation of blood coagulation pathways as a component of an allergic response has been studied in animal models. In patients with allergic diseases, clot qualities have been noted to be different in terms of denser fibrin clot with reduced plasmin-mediated clot lysis. Correlation between occupational hypersensitivity pneumonitis (HP) with thromboembolic events is scarce in the general patient population. We present a case of a 52-year-old man with recurrent venous thromboembolism with HP secondary to bioaerosol exposure in a compost plant. Biochemical evaluation found no evidence of underlying hypercoagulable state, with only remarkable findings of elevated levels of total serum immunoglobulin E and raised Aspergillus sp. IgG antibodies. The patient decided to change his working environment to one without exposure to compost or other fungal elements. His symptoms and pulmonary function tests gradually improved without any subsequent intervention. The patient chose against the advice of his care providers to discontinue warfarin anti-coagulation that had been recommended for lifelong duration after recurrent pulmonary thromboembolism. At a 4-year follow-up he has remained free of any further episodes of venous thromboembolic events without any anti-coagulation. Repeated imaging studies after cessation of exposure demonstrated clearance of multiple lung nodules and improvement in DLco.