Case Report on a Rare Malignancy: Anorectal Melanoma

Introduction: Melanoma of the rectum is an extremely rare disease. The median survival rate is 2-5 years. Current treatment for this aggressive cancer is resection if possible and consider adjuvant or neoadjuvant radiotherapy;immunotherapy in nonresectable cases. Given the rapid spread of disease due to its submucosal growth and metastasis pattern, there is low success rates with treatments. Case Description/Methods: An 84-year-old male presented to the emergency department with an acute COVID-19 infection. The patient was also found to have gram-negative septicemia on blood cultures, so a CT abdomen/pelvis was performed (Figure 1a). The CT showed rectal wall thickening. A flexible sigmoidoscopy was planned for a future outpatient visit after recovering from his acute infection. The patient, however, developed an acute onset of dyspnea and had a high probability V/Q scan while in the hospital. He was started on anticoagulation, and shortly after starting therapy the patient developed bright red rectal bleeding. Due to the new onset of rectal bleeding it was decided to expedite the sigmoidoscopy. The sigmoidoscopy was performed in the hospital showing an ulcerated partially black pigmented non- obstructing medium-sized mass that was partially circumferential involving one-third of the lumen (Figure 1b). A biopsy of the lesion was taken using cold-forceps. The pathology stained positive for S100 consistent with melanoma. The diagnosis of anorectal melanoma was made, and colorectal surgery was consulted. The patient was deemed not to be a surgical candidate secondary to age and active COVID-19 infection. Oncology was consulted, and it was decided to start the patient on radiation and immunotherapy with a PD-1 inhibitor. Discussion(s): The symptoms of anorectal melanoma can be subtle and in this case report completely asymptomatic. Symptoms to be aware of are rectal bleeding and tenesmus. Diagnosing melanoma on sigmoidoscopy can be challenging as most tumors are not pigmented. Biopsies should be taken and sent for immunohistochemical staining for S100, if positive the patient should have a PET scan. Treatment choices for the tumor are based on staging. In a resectable tumor sphincter-saving local excision with radiotherapy to the site of the tumor and the pericolic and inguinal lymphatics is recommended. For unresectable tumors or tumors with distant metastasis, immunotherapy with PD-1 inhibitors (nivolumab and ipilimumab) is an emerging treatment choice.

Cool Your Jets Bro

History: Twenty-two year old male basic trainee was brought to the ED after collapsing during a routine ruck march. At mile 8/12, soldier was noted to develop an unsteady gate and had witnessed loss of consciousness. A rectal core temperature was obtained and noted to be >107degreeF. Cooling initiated with ice sheets and EMS was activated. On arrival to the ED, patient demonstrated confusion and persistently elevated core temperatures despite ice sheeting, chilled saline and cold water bladder lavage. Cooling measures were discontinued after patient achieved euthermia in the ED;however, his temperatures subsequently spiked>103degreeF. Given rebound hyperthermia, an endovascular cooling (EVC) device was placed in the right femoral vein and patient was transferred to the ICU. Multiple attempts to place EVC device on standby were unsuccessful with subsequent rebound hyperthermia. Prolonged cooling was required. Physical Exam: VS: HR 121, BP 85/68, RR 22 SpO2 100% RA, Temp 102.4degreeF Gen: young adult male, NAD, shivering, A&Ox2 (person and place only) HEENT: Scleral anicteric, conjunctiva non-injected, moist mucus membranes Neck: Supple, no LAD Chest: CTAB, no wheezes/rales/rhonchi CV: tachycardia, regular rhythm, normal S1, S2 without murmurs, rubs, gallops ABD: NABS, soft/non-distended, no guarding or rebound EXT: No LE edema, tenderness SKIN: blisters with broad erythematous bases on bilateral heels Neuro: CN II-XII grossly intact, 5/5 strength in all extremities. Differential Diagnosis: 216. Septic Shock 217. Hypothalamic Stroke 218. Exertional Heat Stroke (EHS) 219. Neuroleptic Malignant Syndrome 220. Thyroid Storm Test Results: CBC: 18.2>14.5/40.6<167 CMP: 128/3.5 88/1831/2.7<104, AST 264, ALT 80, Ca 8.8 Lactate: 7.1 CK: 11 460 Myoglobin: 18 017 TSH: 3.16 CXR: No acute cardiopulmonary process Blood Cx: negative x2 CSF Cx: Negative COVID/Influenza/EBV: Negative Brain MRI: wnl. Final Diagnosis: Exertional Heat Stroke. Discussion(s): No EVC protocols exist for the management of EHS or rebound/refractory hyperthermia. As a result, the protocol used for this patient was adapted from post-cardiac arrest cooling protocols. It is unclear if this adapted protocol contributed to his delayed cooling and rebound hyperthermia as it was not intended for this patient demographic/ pathophysiology. Furthermore, despite initiating empiric antibiotics upon admission, delayed recognition and tailored therapy for his bilateral ankle cellulitis may have contributed to the difficulty in achieving euthermia. In summary, more research needs to be done to evaluate and develop an EVC protocol for EHS. Outcome(s): Euthermia was achieved and maintained after 36 hours of continuous EVC, at which point it was discontinued. His CK, AST/ALT, creatinine and sodium down-trended after discontinuation of EVC. Patient's antibiotics were transitioned to an oral formulation for treatment of ankle cellulitis and he was prepared for discharge. He was discharged with regular follow-up with the Fort Benning Heat Clinic. Follow-Up: After discharge, patient had regularly scheduled visits with the Fort Benning Heat Clinic. His typical lab markers for exertional heat stroke were regularly monitored. He had continued resolution of his Rhabdomyolysis, acute kidney injury and hyponatremia with typical treatment. Soldier returned to duty after 10 weeks of close monitoring and rehabilitation.

Profiling Inconsistent/Non-Adopters of Infection Prevention Behaviours during the Covid-19 Pandemic for Targeted Public Health Education: A Population Study

Intro: With the relentless waves of coronavirus disease 2019(COVID-19), there is a need for widespread community adoption of infection prevention(IP) measures including hand hygiene, use of face masks, and staying at home when unwell. Understanding the profile of individuals who do not consistently practice IP can help target public health education. Method(s): We conducted a nationally-representative population survey from November 2020 to January 2021. Households were randomly selected from a proportionately stratified national census. The household member with the most recent birthday was invited to complete the survey. Three questions on a 5-point Likert-scale(never-rarely-occasionally-often-always) assessed IP behaviours(hand hygiene, face mask use when having a cough/cold, staying at home when having a cold/flu) before and during the pandemic. A multivariable logistic regression model was constructed to assess factors associated with the non- or inconsistent("never-rarely-occasionally") adoption of any of the three IP behaviours during the pandemic. Finding(s): Mean age of 2004 respondents was 44.5(SD 15.0) years, with 52% females and 65% being highly educated (diploma/degree holders). Although 12% reported consistently("often-always") adopting all 3 IP behaviours pre-pandemic, the majority(n=1752, 87%) reported doing so during the pandemic. After adjusting for age, educational level, and presence of chronic illness, males(AOR 1.71 [95%CI 1.30, 2.25], Chinese(AOR 1.48 [1.07, 2.05]), low-adopters of healthy lifestyle(AOR 1.59 [1.03, 2.45]) and those who did not or inconsistently adopted IP behaviours pre-pandemic(AOR 8.92 [3.28, 24.27]) were more likely not to or inconsistently adopt the 3 IP behaviours during the pandemic. Discussion(s): During the ongoing pandemic, educational messages and information channels on IP measures could be more targeted at males and Chinese. Additionally, the promotion of healthy lifestyle and consistent adoption of IP behaviours during non-pandemic times is critical for consistent adoption of IP behaviours during pandemics. Conclusion(s): Males, Chinese, and low-adopters of healthy lifestyle and IP behaviours pre-pandemic do not consistently practice IP during the pandemic.Copyright © 2023

Chronic Chilblain Like Lesions Associated with the Covid-19 Pandemic

Background/Aims We report the features of chronic chilblain-like digital lesions newly presenting since the start of the covid-19 pandemic. Comparison with primary perniosis and acrocyanosis, reveals a unique phenotype which appears to be a long-covid phenomenon. Methods The case records of 26 patients with new onset persistent chilblain-like lesions presenting to the Rheumatology service of St George's University Hospital, London between Autumn 2020 and Spring 2022 were reviewed. Demographic and clinical features, serology, imaging, treatment response and outcome up to Summer 2022 were collated retrospectively. Results Chilblain-like lesions first occurred between September and March;2019/ 2020 6 cases, 2020/2021 18 cases and 2021/2022 2 cases. Mean age 35.4 (17-60) years, 88% female, 85% white, all non-smokers. Median body mass index (BMI) 20.2, range 17.0 - 33.2. BMI underweight (<18.5) in 27%. All cases reported new red-purple-blue colour changes of the fingers, some with pain, swelling and pruritis, affecting both hands in 12, one hand in 6, and both hands and feet in 8 cases. There was a past history of cold sensitivity or primary Raynaud's in 54%. Covid was confirmed in 3 cases, 2 - 8 months prior to onset of chilblain-like symptoms. Possible covid, unconfirmed, was suspected in 5 cases, 1 - 11 months earlier. Affected digits appeared diffusely erythro-cyanotic in 81%, with blotchy discrete maculo-papular erythematous lesions in 42%, some with both features. Involvement was asymmetric in 54%, thumbs spared in 69%. Complement was low in 50% (8/16), ANA positive in 26% (6/23). MRI of hands showed phalangeal bone marrow oedema in keeping with osteitis in 4 of 7 cases. More severe signs and symptoms were associated with low BMI, low C3/4 and a past history of cold sensitivity or Raynauds. Cold avoidance strategies were sufficient for 58%. Pain prompted a trial of NSAIDs, aspirin, nitrates, calcium channel blockers, hydroxychloroquine, oral or topical corticosteroid or topical tacrolimus in 42%. In general, these were minimally effective or not tolerated. 4 severe cases received sildenafil or tadalafil, effective in 2. In 27% complete remission occurred during the first summer season after symptoms commenced, median duration 6 (range 2 - 10) months. In the remaining 19 cases, chilblain-like symptoms returned or worsened in the subsequent second winter period, with 6 of 19 entering remission the following summer. For the remaining 13 persistent cases the total duration of symptoms spans more than a year, and in four cases more than 2 years. Conclusion This series illustrates a distinct chronic chilblain-like condition. Features similar to primary perniosis include female predominance, middle age, pruritic painful blotchy lesions, asymmetry and low BMI. Features in keeping with acrocyanosis include chronicity, extensive diffuse erythro-cyanotic discoloration, relative improvement in warm weather and lack of association with smoking.

Mucosa-Associated Lymphoid Tissue Lymphoma of the Rectum Incidentally Found in a Patient with Ulcerative Colitis

Introduction: Mucosa-associated lymphoid tissue (MALT) lymphomas are extra-nodal marginal zone B-cell lymphomas, most commonly found in the stomach, associated with Helicobacter pylori infections, and generally not linked with inflammatory bowel disease. Rectal MALT lymphoma is very uncommon and often associated with painful defecation, change in bowel habits, or rectal pressure/prolapse. Here, we present a rare case of an asymptomatic female with ulcerative colitis (UC) found to have benign-appearing rectal polyps during a routine screening colonoscopy. Case Description/Methods: The patient is a 56-year-old female with a history of left-sided UC, diagnosed in 1993, with one flare after receiving the 2nd dose of the Moderna COVID-19 vaccine, taking oral Olsalazine 500 mg twice daily, low-dose Prednisone, and mesalamine suppositories as needed presenting for screening colonoscopy. The patient was asymptomatic, citing regular non-bloody bowel movements and normal stool consistency. Colonoscopy revealed two 7 mm sessile, non-bleeding rectal polyps, surrounded by congested, erythematous, friable, and ulcerated mucosa in the rectosigmoid colon. Cold forceps biopsies were taken. Hematopathology evaluation of the routine colon biopsy samples revealed chronic nonspecific colitis while pathology of the rectal polyps showed marked lymphoplasmacytic infiltrate and extra-nodal marginal zone lymphoma of MALT. Ancillary studies, immunohistochemistry, and molecular studies for B-cell gene rearrangement confirmed extra-nodal marginal zone lymphoma of MALT with prominent plasmacytic differentiation. The patient was informed and close follow-up in Gastroenterology clinic was arranged. (Figure) Discussion: Rectal MALT lymphoma is rare with unclear management options. Treatments of UC include watchful waiting, surgical resection, endoscopic mucosal resection, radiation, and/or chemotherapy. Helicobacter pylori infections, though strongly linked with gastric MALT lymphoma, have not been shown to be strongly correlated with rectal MALT lymphoma. Given that patients with UC have chronic UCassociated colonic inflammation, lymphoma is often difficult to distinguish visually during colonoscopy, frequently masked by ulcerations and pseudo-polyps. In cases like these, more definitive treatments such as surgical resection could therefore be warranted. Long-term follow-up data is sparse and definitive management remains a clinical conundrum, thus these patients require reliable long-term multidisciplinary close follow-up. (Figure Presented).

Mission Vaccine Suraksha - A Massive COVID 19 Vaccination Drive by Reliance Industries Limited

Introduction: Since the beginning of COVID 19 pandemic, more than 641 million cases and 6.63 million confirmed deaths were reported worldwide. A rapid development of COVID 19 Vaccine was the breakthrough in the prevention and control of COVID 19. India has commenced its vaccination drive from January 16, 2021 and has administered more than 219 crores vaccination to date it its people. On war foot, Reliance Industries Limited also launched its free vaccination coverage program - Mission Vaccine Suraksha for employees, family members, and community by collaborating with local authorities and governments. The organization also provided free vaccination to Kerala, Gujarat, Rajasthan, and Maharashtra besides various other national and regional organisations to speed up the vaccination drive. Methodology: A taskforce including stakeholders form the Medical Services, HR, Procurement, Logistics, transportation, digital systems was formed to oversee, implement, monitor, and evaluate a successful vaccine roll-out drive. The drive included Covishield and Covaxin COVID 19 vaccines. As a single point of contact, Reliance Foundation HN Hospital procured, stored, and transported vaccines to all locations. At par with Govt. protocols, Reliance developed its own workplace COVID vaccination centres (CVCs) at its corporate headquarters and 11 other manufacturing sites in Maharashtra and Gujrat. For Cold chain management, Reliance procured Ice Lined Refrigerators (ILRs), refrigerators, vaccine carriers, icepacks, etc. for each CVC. Dedicated medical and paramedical staffs were recruited and trained to carry out vaccination drive with all the COVID 19 protocols in place. Reliance tied up with multiple hospitals to carry out pan-India vaccination drive. The entire operation was digitally enabled by involving mediums such as Reliance's in-house app JioHealthHub (JHH) that included end-to-end vaccination journey, i.e., from slot booking, CoWIN registration, post-vaccination care, uploading of the certificates, etc. Vaccine inventory was monitored by Reliance's digital system named KiviHealth. A vaccination dashboard was created to track real time vaccination update. Result(s): 40 lakh vaccine doses were provided free of cost to support the nationwide vaccination programme. Till date, 31,63,870 beneficiaries were covered under R-Suraksha under which, 15,94,357 people received their 1st dosage, 13,36,613 received the 2nd dose, and 2,32,900 people have received the precautionary dose. Reliance also commenced vaccination for children aged 12 to 17 years covering 7369 children for 1st dose, 5802 children for 2nd dose. Reliance has achieved 100% compliance for 2 doses of COVID 19 vaccination for its employees and contract workers across manufacturing units. Precautionary dose was administered to 75% of employees and contract workers to date. 25 mild and 3 moderate Adverse Event Following Immunization (AEFI) cases were recorded during vaccination at workplace CVCs, which were managed and sent home. Conclusion(s): Reliance's Mission Vaccine Suraksha has reached to all corners of the country, including people with disabilities, the elderly, homeless, and those in far-flung locations. Reliance faced hurdles in procuring and storing of the vaccines at the beginning of the operation. However, this was tackled effectively with strategic approach. The initiative is still ongoing ensuring maximum precautionary dosage coverage for everyone.

Evaluation Effectiveness of in Vitro Cultivation of Bezoar on Mouse Model Combining Disease with Syndrome of Coronavirus Pneumonia with Yidu Xifei Syndrome.

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method: BALB/c mice were randomly divided into six groups according to their weight grade:normal group,HCoV-229E infection group,cold and damp group,a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome,and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar (0.128,0.064 g.kg-1 )was administrated by gavage for 3 days from the day of infection. The observation indexes included:general state observation of mice,inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the viral load in the lung tissues of mice. Serum levels of motilin(MTL),gastrin(GAS),and cytokines interleukin(IL)-10,IL-6, tumor necrosis factor-alpha(TNF-alpha)and interferon-gamma(IFN-gamma)in lung tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA). The percentages of CD4+ T lymphocytes,CD8+ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group, model group mice lung index increased significantly(P<0.01), nucleic acids significantly increased expression of lung tissue in mice(P<0.01),significantly higher serum MTL content in mice,GAS content significantly decreased(P<0.05,P<0.01),lung tissue cells in the immune factor TNF-alpha,IL-10 and IL-6 were significantly increased(P<0.01),peripheral blood lymphocyte CD4+ T cells in mice,The percentages of CD8+ T cells and B cells were significantly decreased(P<0.01). Compared with model group, in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower(P<0.01),the lung tissue of mice express nucleic acid decreased significantly(P<0.01),MTL content decreased significantly(P< 0.01),the lung tissue of mice in the IL-6,IL-10,the TNF-alpha,IFN-gamma levels were significantly lower(P<0.01), in vitro cultivation bezoar high dose group can significantly increase the CD4+ T cell percentage(P<0.05),in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation,pulmonary interstitial edema,as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice,improving the pathological damage of the lung tissue,adjusting the immune effective and inhibiting the clearing of inflammatory factors,and to provide a laboratory basis for clinical medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Clinical Evidence and Theory of COVID-19 by Traditional Chinese Medicine.

This study aims to investigate the etiology, pathogenic properties and pathogenic characteristics of corona virus disease-2019(COVID-19)in traditional Chinese medicine(TCM),so as to provide ideas for clinical treatment based on syndrome differentiation. Efforts were made to retrive relevant literature concerning clinical studies,theoretical discussions and TCM diagnosis and treatment schemes issued by the state and various provinces,municipalities,autonomous regions and municipalities directly under the central government in relation to TCM from China Knowledge Network(CNKI)and Wanfang Database,and to analyze and summarize the etiology,pathology,theoretical viewpoints,clinical symptoms and signs,syndrome differentiation and medication rules. Currently,the common understanding of the etiology of COVID-19 in the field of TCM is the infection of "pestilential pathogen". However,there is a dispute over cold and heat or mixed understanding of cold and heat in terms of pathogenic attributes. The pathogenic factors are different from each other in dampness,toxin,dryness,fire(heat),wind,filth,depression,etc. There are various understandings on the pathogenesis including dampness,cold,heat,toxin,stasis,phlegm,stagnation,knot,dryness,filth, deficiency,blocking,collapse and asthma,etc. The etiology and pathogenesis are often mixed up. Integration of cold and heat,dryness and dampness,and other contradictory pathogens or pathogenesis is widely seen,which lacks the logicality of theoretical systems,and does not in line with the thinking characteristics of TCM on the etiology,pathogenesis,and syndrome differentiation of exogenous diseases. The main idea of medication in treatment is to diffuse the lung,clear away heat,eliminate dampness,resolve phlegm and repel foulness with aromatics. Maxing Shigantang is used as the core prescription. Chosen warm acrid drugs are mainly the ones with the effect of fragrance,removing dampness,resolving phlegm,and invigorating spleen. They are not the ones with the effects of warming yang and dissipating cold,but the combination of cold and heat,suggesting the complexity of etiology and pathogenesis. COVID-19 is categorized as plaque in TCM,and its etiology is "pestilential pathogen". This pestilential pathogen possesses not only the basic properties of toxin and filth,but also the characteristics of dampness,heat and wind. Throughout the course of the disease,phlegm,stasis,stagnation and other secondary pathogenic factors also occur. The evolution of pathogenesis is characterized by depression,blocking,and deficiency. There are more evidences that the pestilential pathogen of COVID-19 belongs to heat property no matter in the aspects of clinical manifestation,transmission law(syndrome differentiation at different stages),or in compatibility of medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Covid-19: A Review Report

COVID-19 may be a very contagion caused by a recently discovered called corona virus. Novel corona virus was found in December 2019 in Wuhan, China. World Health Organization has declared the COVID-19 as pandemic disease and outbreak as a health emergency globally. Novel Corona Virus is additionally referred to as severe acute respiratory syndrome corona virus- 2. The foremost infected people with corona virus show commonly respiratory illness like- fever, cold, sneezing, cough, pneumonia, upper respiratory illness, GIT disease like nausea, vomiting as symptoms. Recently published evidences stated that light Fever and cough within the 80 % patients, shortness of breath in 30-35% patients and 10-15% patients show Muscle ache and other ache. Novel Corona virus enters through the membrane ACE-2 receptor within the human cell. Corona virus is spherical or pleomorphic, single stranded, enveloped ribose macromolecule and included club shaped glycoprotein. SARS, Respiratory (breathing) infections are often transmission via droplets of various diameter like >5-10 micrometer. Molecular test administered with respiratory samples, like throat swab, sputum and broncholveolar lavage and in some severe cases it reported in stool and blood also. After the WHO and other diagnostic guideline said that the PCR and RT-PCR test reported for corona diagnosis.Copyright © 2022 Dr. Yashwant Research Labs Pvt. Ltd.. All rights reserved.

Strategies to Mitigate the Impact of the Covid Pandemic on Trial Implementation, Closeout, Data Quality, and Analysis of a Large Multicenter Clinical Trial: The Glycemia Reduction Approaches in Diabetes Comparative Effectiveness Study (Grade)

In this session, we will present and discuss successful strategies and methods employed during the COVID pandemic from 2020 to 2021 by the Glycemia Reduction Approaches in the Diabetes Comparative Effectiveness (GRADE) Study to navigate the challenges of trial implementation and study closeout, and to maintain integrity of the study conduct, data collection, and analysis. During the period between July 2013 and August 2017, this National Institutes of Health (NIH)-funded, multicenter clinical trial enrolled and followed 5047 participants at 36 clinical centers and 9 clinical sites nationwide. Participants were followed quarterly and the study closeout (final patient visits) was planned to occur during the period from November 2020 to April 2021, the peak of the pandemic. The Research Group was able to complete study follow-up and closeout with almost 95% of final participant study visits completed and less than 1% of participants lost to follow-up. Most notably, there was continuity of participant management, treatment, and follow-up during the pandemic. Participants with type 2 diabetes (T2D) were recruited with an emphasis on including a cohort that broadly represented the T2D US population by race and ethnicity. We enrolled a diverse participant cohort with 20% of participants self-identified as Black/African American, and 19% Hispanic/Latino. Clinical sites enrolling Hispanic/ Latino participants had study-funded bilingual research staff. Each clinical center enrolled and followed approximately 150-200 participants for quarterly visits to collect study assessments. We will describe effective study communications with the study research group and participants, operational and clinic-level changes made to optimize the continuity of study treatment and management of participants, completion of visit assessments, and measures taken to ensure staff and participant safety during visits completed through the height of the pandemic. We will discuss problem-solving strategies, adjustments to visits and data collection, strategies employed to optimize data collection under varying constraints, pivoting to a hybrid of remote/in-clinic work for research staff and study visits, collection of laboratory specimens for study outcomes and participant safety, and the implementation of study closeout. We will present the mass utilization of a remote HbA1c collection kit by participants, essential for the primary outcome assessment. Early in the pandemic (March 2020), enhanced communication from the Executive Committee and Coordinating Center to the Study Group was key to keeping research sites up to date on continuity of operations, providing direction to prioritize study assessments, and addressing questions. Site communications with participants were essential for reassurance of continued care and treatment. We will describe the challenges imposed by the pandemic and solutions from several different research perspectives. Research staffing and study coverage were complicated by institution restrictions, working remotely without comparable communications/equipment, risk of COVID exposure, and temporary reassignment of research personnel at the site-level. Site clinical research managers will present experiences and innovative approaches implemented to communicate effectively with study participants, conduct visits, complete study assessments and data collection, and manage treatment changes to include initiation of insulin. We will present successful strategies implemented to handle study logistics, minimize participant and research staff risk, and navigate visit and institutional restrictions. About 96% of sites were closed for inperson clinical activities and conducted completely remote visits for some period of time during the early waves of the COVID pandemic. Sites pivoted to working under new conditions to maintain Health Insurance Portability and Accountability Act (HIPAA) protections while ensuring the integrity of data and sample collection. Two percent of sites did not resume in clinic visits by the end of the study in April 2021. We will also share innovative strategies used to remotely instruct participants on how to use new medications required per protocol. Protocol managers from the Coordinating Center will discuss key leadership decisions and communications implemented to facilitate follow-up that include methods for prioritizing of visit assessments, enhancing remote A1c collection, tracking of study visits and assessments, and monitoring of cold-chain drug shipments to clinical sites. The Coordinating Center implemented weekly WebEx meetings with clinical sites during the first 7 months of the COVID pandemic to facilitate site sharing of information, identify problems and problem solve, collect site information from dynamic surveys, and confirm priorities for study visits and maintaining participant and research staff safety. Site research staff frequently presented strategies or scenarios for discussion. In addition, the Coordinating Center rapidly implemented a COVID website with hot links to important documents. We will highlight modifications in research implementation made to optimize the conduct of clinical care, remote laboratory sample collections, development of a capillary collection kit for mass distribution and collection of key study data, and reports provided by the Coordinating Center to keep sites on track for visit completion. The Coordinating Center biostatistician will summarize the impact of COVID on data collection and discuss completeness of assessments, serious adverse event reporting during the pandemic, and sensitivity analyses to examine the integrity of results. The trial continued without changes to the protocol with about 95,000 total visits completed and 18% of visits completed during COVID. Talk titles: The Role of Leadership, Communications, Infrastructure, and Access to Tools and Resources in Implementing Wide-Scale Operational Changes During COVID-19. Institutional Restrictions and Site-Level Strategies for Communications and Protocol Implementation While Pivoting to Hybrid Work Arrangements and Remote/In-Clinic Visits. Executing a Large Multi-Center Trial During a Pandemic: Challenges and Lessons Learned from the GRADE Coordinating Center. Implementation of Successful Strategies for Study Closeout Visits, Final Data Collection, and Transition of Participant Clinical Care at Trial End. The Impact of COVID on Data Collection, Completeness of Visit Assessments, Serious Adverse Event Reporting, and Approaches to Analysis of Study Results and Reporting.

Evaluation Effectiveness of in Vitro Cultivation of Bezoar on Mouse Model Combining Disease with Syndrome of Coronavirus Pneumonia with Yidu Xifei Syndrome.

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method: BALB/c mice were randomly divided into six groups according to their weight grade:normal group,HCoV-229E infection group,cold and damp group,a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome,and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar (0.128,0.064 g.kg-1 )was administrated by gavage for 3 days from the day of infection. The observation indexes included:general state observation of mice,inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the viral load in the lung tissues of mice. Serum levels of motilin(MTL),gastrin(GAS),and cytokines interleukin(IL)-10,IL-6, tumor necrosis factor-alpha(TNF-alpha)and interferon-gamma(IFN-gamma)in lung tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA). The percentages of CD4+ T lymphocytes,CD8+ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group, model group mice lung index increased significantly(P<0.01), nucleic acids significantly increased expression of lung tissue in mice(P<0.01),significantly higher serum MTL content in mice,GAS content significantly decreased(P<0.05,P<0.01),lung tissue cells in the immune factor TNF-alpha,IL-10 and IL-6 were significantly increased(P<0.01),peripheral blood lymphocyte CD4+ T cells in mice,The percentages of CD8+ T cells and B cells were significantly decreased(P<0.01). Compared with model group, in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower(P<0.01),the lung tissue of mice express nucleic acid decreased significantly(P<0.01),MTL content decreased significantly(P< 0.01),the lung tissue of mice in the IL-6,IL-10,the TNF-alpha,IFN-gamma levels were significantly lower(P<0.01), in vitro cultivation bezoar high dose group can significantly increase the CD4+ T cell percentage(P<0.05),in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation,pulmonary interstitial edema,as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice,improving the pathological damage of the lung tissue,adjusting the immune effective and inhibiting the clearing of inflammatory factors,and to provide a laboratory basis for clinical medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Clinical Evidence and Theory of COVID-19 by Traditional Chinese Medicine.

This study aims to investigate the etiology, pathogenic properties and pathogenic characteristics of corona virus disease-2019(COVID-19)in traditional Chinese medicine(TCM),so as to provide ideas for clinical treatment based on syndrome differentiation. Efforts were made to retrive relevant literature concerning clinical studies,theoretical discussions and TCM diagnosis and treatment schemes issued by the state and various provinces,municipalities,autonomous regions and municipalities directly under the central government in relation to TCM from China Knowledge Network(CNKI)and Wanfang Database,and to analyze and summarize the etiology,pathology,theoretical viewpoints,clinical symptoms and signs,syndrome differentiation and medication rules. Currently,the common understanding of the etiology of COVID-19 in the field of TCM is the infection of "pestilential pathogen". However,there is a dispute over cold and heat or mixed understanding of cold and heat in terms of pathogenic attributes. The pathogenic factors are different from each other in dampness,toxin,dryness,fire(heat),wind,filth,depression,etc. There are various understandings on the pathogenesis including dampness,cold,heat,toxin,stasis,phlegm,stagnation,knot,dryness,filth, deficiency,blocking,collapse and asthma,etc. The etiology and pathogenesis are often mixed up. Integration of cold and heat,dryness and dampness,and other contradictory pathogens or pathogenesis is widely seen,which lacks the logicality of theoretical systems,and does not in line with the thinking characteristics of TCM on the etiology,pathogenesis,and syndrome differentiation of exogenous diseases. The main idea of medication in treatment is to diffuse the lung,clear away heat,eliminate dampness,resolve phlegm and repel foulness with aromatics. Maxing Shigantang is used as the core prescription. Chosen warm acrid drugs are mainly the ones with the effect of fragrance,removing dampness,resolving phlegm,and invigorating spleen. They are not the ones with the effects of warming yang and dissipating cold,but the combination of cold and heat,suggesting the complexity of etiology and pathogenesis. COVID-19 is categorized as plaque in TCM,and its etiology is "pestilential pathogen". This pestilential pathogen possesses not only the basic properties of toxin and filth,but also the characteristics of dampness,heat and wind. Throughout the course of the disease,phlegm,stasis,stagnation and other secondary pathogenic factors also occur. The evolution of pathogenesis is characterized by depression,blocking,and deficiency. There are more evidences that the pestilential pathogen of COVID-19 belongs to heat property no matter in the aspects of clinical manifestation,transmission law(syndrome differentiation at different stages),or in compatibility of medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Chilblain: a brief history of cold comfort remedies

Chilblain, also known as pernio, has gained publicity in recent years as a result of its association with 'COVID toes' during the COVID-19 pandemic. Long before this, chilblain had left its mark throughout history and literature. The word 'chilblain' has Anglo-Saxon roots. 'Chil' comes from Old English ciele meaning 'chill' or 'frost', while 'blain' comes from the Old English blegen meaning 'inflammatory swelling' or 'sore'. The two words were brought together in the 1540s. The choice of words somehow acknowledges that cold is the aetiological factor that brings on this painful swelling. The Victorian novel Jane Erye, written by Charlotte Bronte in 1847, described the physical hardships that children had to struggle with through the winter at Lowood, the charity school for poor and orphaned girls. Her work masterfully sculptured the essence of chilblain and its effects on the children. Multiple notable figures proposed various remedies to treat the bothersome symptoms of chilblains. Pedanius Dioscorides was a Greek physician and botanist whose monumental work De Materia Medica in the first century AD compiled a list of topical remedies for chilblains, including quince oil, fenugreek oil, frankincense gum, burnt figs in wax, a mixture of gentian, crab ashes and honey, burnt ass hooves, bear grease and decoction of turnip as a warm pack. To cure chilblains, Nicholas Culpeper, an English herbalist, advised grating horseradish and applying it as a mustard plaster. We now know grated horseradish root produces a powerful mustard oil that acts as a rubefacient, which irritates the skin and increases its blood flow. Dr Lewis Johns was a recognized medical officer in the field of medical electricity in charge of the Electrical Department of St Bartholomew's Hospital. He noted a reduced incidence of chilblains in children with poliomyelitis who were treated with a warm electric footbath in 1899. The beneficial effects most likely originated from the warm bath rather than the electricity itself. Sir Thomas Lewis, a British cardiologist, investigated skin responses to injury and vascular reactions of the skin to cold exposure. His careful observations and descriptions of chilblains published in the British Medical Journal in 1941 remain true to this day. Practices such as praying to the statue of St Benignus of Dijon with chilblains, wearing electric patent socks (invented in 1882) and using an electrical vacuum tube in 1922 had also made their way into the lives of sufferers as a potential cure. Despite the epidemiological study of chilblain in over 3000 servicewomen, carried out by the Auxiliary Territorial Service in the winter of 1942, no specific remedy was found. When it comes to chilblain, prevention is better than cure by keeping the hands and feet warm and dry and staying active, and chilblains usually resolve spontaneously within a few weeks.

OCCUPATIONAL AND ENVIRONMENTAL INFLUENCES ON HYPERTENSION

In this brief review I shall try to discuss several topics related to hypertension which maybe associated with occupational and environmental effects. Effects of dietary sodium will not be discussed as these are extensively discussed elsewhere. Occupational stress is difficult to define but there seems to be a relationship between high demands and relatively low control, and blood pressure in both men and women despite different professional distribution. Noise, a relatively less recognized stressor that may be associated with hypertension Both industrial noise and urban noise. Recently due to the Covid19 lockdown and reduction of aircraft noise in relevant areas a reduction of bloodpressure was noted. Seasonal variation with rise of blood pressure during cold and perhaps shorter daytime light seasons, and subsequent reduction in the summer with its higher temperatures and longer light hours is one environmental factor. Air pollution, especially that associated with high level small particulate matter equal to, or smaller than 0.25 μm, was associated with hypertension in several studies, with quite and ethnic and geographic variability. High altitude exposure (higher than 2500 m), involves hypoxemia (in addition to radiation, cold temperatures, and dehydration because of dryness of inhaled air), resulting in renin angiotensin system activation and sympathetically induced vascular contraction, and elevation of pulse rate and blood-pressure at rest and an exaggerated increase during exercise. Immigration seems to be associated with hypertension through different mechanisms in different populations. Mechanisms of these effects are not well understood though some must be mediated through sympathetic activation, others through the renin angiotensin system though, hypoxemia, altered redox state and inflammation all might participate along with other mechanisms.

Genomic sequencing profile of SARS-CoV-2 in different parts of western Odisha, India

Genetic lineages of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) have continued to emerge and circulate around the world since the onset of the COVID-19 pandemic. There are numerous variants of SARS-CoV-2, the virus that causes corona virus disease 2019 (COVID-19). Like other viruses, SARS-CoV-2 evolves over time. Most mutations in the SARS-CoV-2 genome have no impact on viral function, but certain variants have gained worldwide attention because of their rapid emergence within populations, evidence of transmission, and clinical implications. During the pandemic, most parts of India were affected, including Odisha, leading to high rates of morbidity and mortality. For the present study, 368,303 samples were received by the COVID-19 lab i.e., medical college level (Virus Research Diagnostic Laboratory) VRDL from six districts of western Odisha, including approximately 25,000 COVID-19-positive samples. The diagnostic method of the quantitative RT-PCR cannot be used to distinguish among the variants created by mutation of the genes initially, therefore selected positive clinical samples were sent in cold chain for whole genome sequencing (WGS), using the Illumina Seq. at ILS, BBSR for variant detection. The reported observation from the next generation sequencing (NGS) based sequenced samples of western Odisha updated in the INSACOG-WGS portal confirms the presence of Delta (B.1.617.2) and Delta sublineages, Omicron (BA.2), and Omicron (B.1.1.529). Maximum infection was caused by Delta sublineages (83.5%) irrespective of age, sex, and geographic area followed by Delta and Omicron. Molecular diagnosis and WGS based study reveal the widespread transmission of the fatal virus, significantly affecting every corner of the globe. Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Molecular Medical Diagnosis of COVID-19 and Omicron Variant

Genetic lineages of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) have continued to emerge and circulate around the world since the onset of the COVID-19 pandemic. There are numerous variants of SARS-CoV-2, the virus that causes corona virus disease 2019 (COVID-19). Like other viruses, SARS-CoV-2 evolves over time. Most mutations in the SARS-CoV-2 genome have no impact on viral function, but certain variants have gained worldwide attention because of their rapid emergence within populations, evidence of transmission, and clinical implications. During the pandemic, most parts of India were affected, including Odisha, leading to high rates of morbidity and mortality. For the present study, 368,303 samples were received by the COVID-19 lab i.e., medical (Virus Research Diagnostic Laboratory) VRDL from six districts of western Odisha, including approximately 25,000 COVID-19-positive samples. The diagnostic method of the quantitative RT-PCR cannot be used to distinguish among the variants created by mutation of the genes initially. Therefore, selected positive clinical samples were sent in cold chain for whole genome sequencing (WGS), and disease severity was sequenced using the Illumina Seq at ILS, BBSR for variant detection. The reported observation from the next generation sequencing (NGS) based sequenced samples of western Odisha updated in the INSACOG-WGS portal confirms the presence of Delta (B.1.617.2) and Delta sub lineages, Omicron (BA.2), and Omicron (B.1.1.529). Maximum infection was caused by Delta sub lineages 83.5%) irrespective of age, sex, and geographic area followed by Delta and Omicron. Molecular diagnosis and WGS based study reveal the widespread transmission of the fatal virus, significantly affecting every corner of the globe. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Effect of Lockdown in the COVID-19 Pandemic on Dietary Habits and Self-Medication Practice in People Living in Jordan

Background: The pandemic of the coronavirus disease 2019 (COVID-19) has impacted Jordanian society, particularly on health. Aim(s): This study examined the effect of the COVID-19 pandemic lockdown on Jordanian society's dietary habits and self-medication practices. Method(s): We surveyed 1252 Jordanians of both genders between the ages of 18 and 65 years by questionnaire. Three questions were asked to evaluate the frequency of foods/drinks consumption, general eating habits, and self-medication practice of individuals of both genders during the lockdown. Result(s): Dietary habits and food quality affected weight (increase or decrease) by 69.5% during the lockdown. The highest percentages of 'very high' consumption per week for fruits, processed juices, and fried foods were 37.6 %, 36.7%, and 29.4%, respectively. The highest percentage of 'very little' consumption per week for drinking water, milk, and soft drinks were 12.5%, 8.5%, and 7.4%, respectively. The percentage of respondents who had taken medicine without a doctor's prescription was 84.7%. The highest percentage (74%) was in using self-medication as a preventive measure against the coronavirus, followed by treating a cold/flu (61.4%), in both genders and age groups. The largest percentage (78.5%) was for using paracetamol, followed by ibuprofen and azithromycin (78.1% and 77.1%), respectively. Conclusion(s): Dietary habits and the quality of the foods consumed during lockdown affected participants' weight (increase or decrease) by 69.5%. The percentage of participants who self-medicated was 84.7%. Copyright © 2022 International Journal of Nutrition, Pharmacology, Neurological Diseases Published by Wolters Kluwer - Medknow.

Surgical Training during the Covid-19 Pandemic at a Designated "Cold" Site: Are We Meeting the Challenge?

Aim: There has been a marked reduction in surgical operative training opportunities during the COVID-19 pandemic. This may be improved by the establishment of "cold" sites for NHS elective surgery. We investigated the training opportunities at a newly designated elective surgery cold site in the West Midlands, UK. Method(s): An observational retrospective study was undertaken to include all gastrointestinal and urological elective surgery at a single "cold" site during the first peak of the pandemic. Patient demographics, details of surgery, and data relating to surgical training such as primary surgeon and portfolio index procedure were collected. Factors affecting the likelihood of trainees being the primary surgeon were analysed using logistic regression models. Result(s): There were 880 patients, with a median age of 62 (IQR 48-74). 658 (74.8%) procedures were defined as "index procedures" for ST4 level (409/509 (80.4%) for Urology;155/235 (66%) for Colorectal;and 94/136 (69.1%) for Upper GI). Only 253/880 (28.8%) procedures were performed by a trainee as the primary surgeon (201/509 (39.4%) for Urology;21/235 (8.9%) for Colorectal;and 31/136 (22.8%) for Upper GI). The likelihood of a trainee being the primary surgeon was reduced for major surgery (P < 0.001) and for gastrointestinal surgery when compared to urology (P < 0.001). Conclusion(s): Surgical training was facilitated at an elective surgery "cold" site during the COVID-19 pandemic, but at lower levels than anticipated. Type of surgery influenced trainee participation. Surgical training should be incorporated into "cold" site elective surgical services if trainees are to be prepared for the future.

Colorectal Cancer Care in the Covid-19 Era, Outcomes from a "Mixed Site" Model

Aim: The COVID-19 pandemic has presented many challenges to colorectal cancer (CRC) care. Many organisations opted to perform CRC resections in "cold" sites. Infrastructure in Northumbria Healthcare NHS Foundation Trust (NHCT) necessitated co-locating CRC care with "hot" COVID streams but with additional precautions. This study aimed to evaluate that approach for a consecutive series of CRC cases, diagnosed before and during the COVID-19 pandemic. Method(s): A prospectively populated dataset of CRC patients diagnosed between 01/04/2019 and 30/09/2020 was used. Patients presenting before 01/04/2020 were considered "Pre-COVID" and those subsequently "COVID era". Result(s): Three hundred and forty-four cases were diagnosed in the 12 months "Pre-COVID" and 166 in the 6 months of the "COVID era". The median days from referral to diagnosis (21 vs 20, P = 0.373) and operation (63 vs 61, P = 0.208) were unchanged. The "COVID era" saw an increase in the proportion of radiological diagnoses (39.5% vs 53.0% P = 0.004) with an associated decrease in endoscopic diagnoses (56.7% vs 45.8%, P = 0.021). Rates of inoperable (1.5% vs 1.2%, P = 0.821), obstructing (11.0% vs 16.2%, P = 0.272) and perforated tumours (0.6% vs 1.5%, P = 0.492) remained the same. One patient developed COVID-19 peri-operatively. Rates of laparoscopic operation (59.5% vs 61.8%, P = 0.751), anastomotic leak (6.4% vs 5.9%, P = 0.891), re-operative surgery (10.4% vs 4.4%, P = 0.138), primary stoma (40.5% vs 32.4%, P = 0.244) and 90-day mortality (0.6% vs 1.5%, P = 0.492) did not change. Conclusion(s): With appropriate infection control measures, it may be safe to continue providing standard elective and urgent CRC care without access to a "COVID clean" site.

Severe Autoimmune Hemolytic Anemia in a Young Child with Active Covid-19 Infection

INTRODUCTION: Autoimmune hematological complications related to COVID-19 are rare. There are only 5 pediatric case reports of autoimmune hemolytic anemia (AIHA) among 14 million pediatric COVID-19 cases in USA. Four were older (13-17 years), two had underlying autoimmune/hematologic conditions. Immunologic analysis varied, with cold, warm & mixed hemolytic anemias described. We present a previously healthy child with COVID-19 associated severe AIHA with peripheral reticulocytopenia. DESCRIPTION: A 3-year-old male presented with lethargy, fever, tachycardia and jaundice 10 days after COVID-19 diagnosis. Pertinent labs include hemoglobin (Hgb) 3.8 g/dL, Hct 9.9%, bilirubin 3.6 mg/dL, platelets 321,000/muL, RBC count 1.2 M/muL, WBC 35,600/muL, MCV 82.5fL. Reticulocyte count (RC) was only 2.8%. Peripheral blood smear showed anisocytosis, poikilocytosis, nucleated RBCs and left shifted granulocytosis. Bone marrow biopsy revealed erythroid hyperplasia without underlying malignancy;myeloid:erythroid ratio of 0.3:1. The outside hospital reported cold C3 agglutination following 4degreeC incubation, while our laboratory identified spontaneous agglutination at room temperature (warm agglutination). IV fluids, O2, and methylprednisolone (4 mg/kg/day) were started and two packed RBC transfusions (total 30 ml/kg) given for symptomatic anemia with Hgb < 4 g/dL. LDH peaked at 2255 U/L on Day 3. Reticulocyte count was low (2.8%-3.8%) Days 1-3, increased to 6.5% on Day 4 and peaked at >30.0% on Day 7. He was changed to oral prednisone 2 mg/kg/day on Day 12 and discharged on Day 13 with Hgb 7.0 g/dL and RC 29.9%. Most recent Hgb is 13.0 g/dL and RC 2.6%. DISCUSSION: COVID-19 associated AIHA is rare, and previously reported mostly in older children. Our patient was previously healthy, and demonstrated a strong bone marrow response with erythroid hyperplasia. Peripheral reticulocytosis was delayed, and correlated with initiation of systemic steroid therapy. Our patient had both cold and warm agglutination supporting extensive autoimmune destruction of early red cell lineage. These findings support immune activation during acute COVID-19 infection and COVID-19 as a trigger for AIHA. Patients developing AIHA may need to be tested for COVID-19 and carefully monitored for complications.