Repurposing of poly-gamma-glutamic acid, immunotherapeutic drug for cervical intraepithelial neoplasia 1, as covid-19 treatment

Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.

Refractory circulatory failure in COVID-19 patients treated with veno-arterial ECMO: A retrospective single-center experience

Objectives: Data about COVID-19 patients treated with veno-arterial-ECMO (VA-ECMO) is limited. Reported survival rates range from 27.9% to 77.8%, depending on VA-ECMO indication. A subgroup of patients suffers from circulatory failure due to a COVID-19 associated hyperinflammatory state (CovHI). In these patients, differentiation between inflammation and sepsis is difficult but important. In this retrospective case series, differential diagnoses of COVID-19 associated refractory circulatory failure and survival rates in different indications for VA-ECMO are investigated. Method(s): Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO at the University Hospital Regensburg between March 2020 and May 2022. Specific treatment for COVID-19 was in accordance with respective guidelines. Mycotic infections were either invasive or met current definitions of COVID19-associated-pulmonary aspergillosis. Result(s): At VA-ECMO initiation, median age was 57.3 years (IQR: 51.4 - 61.8), SOFA score 16 (IQR: 13 - 17) and norepinephrine dosing 0.53mug/kg/min (IQR: 0.32 - 0.78). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Survival to hospital discharge was 39%. 17 patients were primarily supported with VA-ECMO only (survival 42%), 3 patients were switched from VV to VA-ECMO (survival 0%), and 8 patients were converted from VA to VAV or VV-ECMO (survival 50%). Indications for VA-ECMO support were pulmonary embolism (PE) (n=5, survival 80%), right heart failure due to secondary pulmonary hypertension (n=5, survival 20%), cardiac arrest (n=4, survival 25%), acute left heart failure (ALHF) (n=11, survival 36%) and refractory vasoplegia (n=3, survival 0%). Inflammatory markers at VA-ECMO initiation were higher in patients with ALHF or vasoplegia;in these patients a higher rate of invasive fungal infections (10/14, 71% vs. 4/14, 29%;p=0.023) compared to the other patients was found. Conclusion(s): Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decisions making. Circulatory failure due to vasoplegia should be considered very carefully as indication for VA-ECMO. A high rate of mycotic infections mandates an intense microbiological workup of these patients and must be considered as an important differential diagnosis to CovHI.

Two-year outcome of extracorporeal membrane oxygenation in COVID-19 related severe respiratory failure

Objectives: We sought to evaluate 2-year outcome of V-V ECMO support for COVID-19 related severe respiratory failure in our center. Method(s): Retrospective analysis of 41 consecutive patients (73% male, mean age 51.6+/-14.2 years, mean BMI 35.1+/-12.5 kg/m2) with critical hypoxemic and/or hypercapnic refractory respiratory failure (mean P/F ratio 67.9+/-14.3 mmHg, mean pCO2 77.6.0+/-185.7 mmHg, Murray Score 3.71+/-0.4) on V-V ECMO support from October 2020 to January 2022 Results: With mean support duration of 234.4+/-63.2 hours, 29 patients (70.7%) were successfully weaned off. Finally, 19 of them (46.3%) were discharged home with good neurological outcome (CPC 1,2). During followup, 30-day, 6-, 12-, and 24 -month survival rate was 61.3%, 46.2%, 41.9%, and 41,9% respectively. In survivor group shorter symptoms onset to respiratory failure time (4+/-4.7 vs. 7+/-6.7 days, p=0.04), higher P/F ration (86+/-41.5 vs. 65+/-37.5 mmHg, p=0.04) and norepinephrine support (0.03+/-0.06 vs. 0.09+/-0.12 ug/kg/min, p=0.04), and lower IL-6 level (12.3+/-7.5 vs. 25.9+/-8.8 ng/l, p=0.03) p=0.01) were analysed before cannulation. Mean in-ICU stay and in-hospital stay in survivors;groups reached 32.5+/-27.7 days and 42.6+/-35.8 days, respectively. All long-term survivors (17 patients) complained about slight functional health limitation only with normal 6MWT (542.6+/- 89.2 min), near to normal spirometry parameters (FEV/VC 87+/-7.4%, DLCO 63.1+/-13.7%, KCO 82.,1+/-19.4%) and minimal neurological disability (CPC 1-2) Conclusion(s): 2-year outcome of V-V ECMO support in COVID-19 severe respiratory failure is acceptable even in the scope of low-volume ECMO centre. Reported functional status of long-term survivors was good despite the complicated and prolonged in-hospital stay. (Table Presented).

Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Could out-of-centre initiation of extracorporeal membrane oxygenation with mobile equipment improve outcome and prognosis in COVID-19 patients? A retrospective study from the ECMO centre Regensburg

Objectives: Besides in-centre ECMO care, the certificated ECMO centre of the University Hospital Regensburg (UKR) offers out-of-centre ECMO initiation with mobile equipment. During the pandemic situation, this treatment was especially meant for patients with critical cardiopulmonary failure in remote hospitals who present themselves as too unstable for interhospital transfer. We evaluated if treatment with outof-centre ECMO initiation could benefit patients;outcome, by comparing this group with a group of COVID-19 patients who received ECMO therapy at the UKR by in-hospital initiation. Method(s): Retrospective single-centre study including 169 patients who received ECMO due to COVID-19- induced cardiopulmonary failure between March 2020 till March 2022. Patients;population was separated into two groups according to the location of ECMO initiation, out-of-centre or in-centre, and into two subgroups by the used ECMO mode, venovenous (VV) or venoarterial (VA). We compared demographics, treatment duration, adverse events and patient;s outcome. The primary endpoint of the investigation was patients;survival to hospital discharge rate or death on ECMO or after ECMO explant. Result(s): Regarding the total study population, 98 (58.0%) of the 169 patients could be discharged from the UKR. Before initiation of ECMO therapy and with regard to complications during the course of intensive care, such as renal failure requiring dialysis or bleeding, there were no relevant differences between the two groups and subgroups. The out-of-centre group showed a significantly higher survival rate with 70 (63.6%) survivors out of 110 externally cannulated patients. Conclusion(s): In the study population, external ECMO cannulation was beneficial in terms of survival, although the reasons did not show significant differences between the groups. A possible approach for the good overall survival of the study groups in international comparison could be the existing centre expertise. (Figure Presented).

The ProtekDuo in ECMO configuration for ARDS secondary to COVID-19 - a systematic review

Objectives: Assessment of the literature on the ProtekDuo cannula when used as venopulmonary (V-P) extracorporeal membrane oxygenation (ECMO) in ARDS secondary to COVID-19. Method(s): Systematic literature search in EMBASE, Medline (Pubmed) and NHS library using appropriate keywords as well as PICOS and PRISMA approach. Result(s): We found 285 publications, of which 5 publications met the search criteria and were included in this review. A total of 194 patients with COVID-19 related ARDS had a ProtekDuo placed to establish venovenous (V-V) ECMO and right ventricular (RV) support. Patients treated with the ProtekDuo cannula had survival rates between between the studies of 59 and 89%, with a significant survival compared to an invasive ventilation group or when compared to dual site V-V ECMO or other double lumen ECMO cannulas. One of the studies focused on extubation and early discontinuation of ventilator support, which the authors achieved in 100% of ProtekDuo patients. The incidence of acute kidney injury (AKI) and use of continuous renal replacement therapy (CRRT) was significantly reduced in the ProtekDuo versus other groups. Conclusion(s): The ProtekDuo displayed lower mortality rates, AKI occurrence and CRRT need as compared to other respiratory support modalities and has shown to be a game changer for ECMO support in patients suffering from COVID-19 ARDS. Many authors suggested the ProtekDuo for first line use in these patients.

Prolonged oxygenator usage for VV ECMO for COVID ARDS: A clinical experience

Objectives: Its known that with the prolonged use of ECMO, because of the thrombogenic activations -minor/majorclot formations may ocur at the oxygenator and eventually it fails to function properly. Physicians take some precautions to prevent or postpone this process but usually exchange the circuit. In this study we share our follow up strategy and prolonged oxygenator use for the COVID-ARDS patients. Method(s): A total of 68 patients who were followed more than 7 days were included in this study. Sorin/LivaNova oxygenators and VV-ECMO circuit were used for all of the patients. Bivaluridin infusion was used for routine anticoagulation protocol. Result(s): Mean age of the patients was 44.1 +/-12.2 years. The patients were followed for a total of 2705 days with a total of 103 oxygenators [mean 26.2 +/-18.3(104-7) days for per oxygenator] Mean duration of ECMO support was 40.3 +/-24.4 days . The oxygenator use per patient was 1.5 +/-0.89. There was no major hypoxic period experience for the patients. Survival rate was 43.2 %. Conclusion(s): With using bivaluridin for anticoagulation, daily washing of oxygenators and close follow up methods we can protect the oxygenators and use them for longer periods safely like in our experience which can save us from serious additional costs and interventions.

Rehabilitation needs after critical illness: Referral outcomes from a ICU follow up clinic in Northern Ireland

Introduction: In 2019/20 a total of 171,900 people were admitted to adult general intensive care units (ICU) across England, Wales and Northern Ireland, with a survival rate of 79.6% at hospital discharge.1 Patients who survive critical illness and admission to ICU often experience ICU-related long-term physical and non-physical impairments and disability following hospital discharge.2 National guidance advocates multidisciplinary team (MDT) follow up to identify and manage the unmet health needs of this patient population.3-4 The UK has seen an increase in the number of follow up services available in the last 7 years.2 The Covid-19 pandemic further highlighted the need to provide this service, locally resulting in the establishment of the Belfast Health and Social Care Trust (BHSCT) ICU follow up clinic in July 2020. The follow up clinic is offered to patients aged = 18 years, an ICU length of stay of = 4 days, who have been discharged from an inpatient setting within the last 12 weeks and do not receive follow up from any other established care pathway. The clinic consists of an ICU Nurse, Doctor, Clinical Psychologist and Physiotherapist. Patients are offered either a virtual, face-to-face or telephone appointment. Objective(s): To identify unmet rehabilitation needs and onward referral requirements of patients presenting at an ICU follow-up clinic in Northern Ireland. Method(s): Data was gathered retrospectively using an excel database detailing patient demographics, appointment details and onward referrals generated from the clinic. Data was analysed for a set time period between the 01/12/2021 - 09/02/2022. The type of referral and the profession responsible were captured. Result(s): During the time period eight post ICU follow up clinics were completed. A total of 36 patient's attended (14 male and 22 female). Six appointments were attended virtually via MS Teams, 12 via telephone and 18 face-to-face. Twenty-three (64%) of the patients required at least one onward health referral. A total of 61 onward health referrals were generated from this population. Table 1 details the number of onwards referrals by speciality. Conclusion(s): Approximately 64% of patients who attended the post ICU follow up clinic, during a 10 week period, demonstrated unmet rehabilitation needs resulting in onward health referrals. This data supports the need for a post ICU follow up clinic at BHSCT to identify ongoing need, ensure transition of care to relevant services and optimise patient's physical and psychological outcomes. One limitation of this study is that not all recommended allied health professionals are commissioned for the clinic which may impact on the health needs identified. Future work should consider the impact of this and discussions regarding the need for a commissioned post ICU follow up clinic which is truly MDT for this patient population should be considered.

How to Ensure the Development of SMEs in Post-Pandemic Economy? A Start-ups Case Study

After the humanitarian crisis, caused by COVID-19, enterprises have to face a post-pandemic economic crisis. As small and medium-sized enterprises (SMEs) constitute 99% of EU enterprises and create every third workplace (European Parliament, 2021), it is important to monitor their situation not only to survive but also to develop and build strong economies in the future. The aim of this research is to investigate development trends and opportunities in (SMEs') development, with a special focus on start-ups (STPS) as representative of these. Also, special attention is paid to the concept of sustainable development (SD), which fulfils the UN 2030 Agenda for Sustainable Development Goals (SDGs). The proposed methodology consists of three stages: desk research, in-depth interviews, and primary data analysis, and uses a qualitative method. The article describes the findings of recent Polish studies undertaken to verify and augment earlier pilot research. The novelty of the article is the examination of the dependence between the STPS survival rate and the SD as a measure of SDGs' fulfilment. The limitation may be the specificity of the pandemic, as well as the study of post-pandemic trends that shows a strictly binding need to have a stable strategy for establishing, managing and developing enterprises and increasing their survival rates.

The Association of COVID-19 Severity with Laboratory Parameters, Radiologic Findings, Maternal and Neonatal Outcomes in Pregnant Women: A Multicenter Study in Indonesia

Objectives: Severe acute respiratory syndrome-coronavirus 2/COVID-19 infection is still a global concern, with pregnant women are considered as vulnerable population. Until now, the characteristics of pregnant women in Indonesia who are infected with COVID-19, as well as pregnancy and neonatal outcomes, are still unknown. This study aims to obtain national data, which are expected to be useful for the prevention and management of COVID-19 in pregnant women in Indonesia. Method(s): There were 1,427 patients recruited in this retrospective multicenter study. This study involved 11 hospitals in 10 provinces in Indonesia and was carried out using secondary patient data from April 2020 to July 2021. COVID-19 severity was differentiated into asymptomatic-to-mild symptoms and moderate-to-severe symptoms. The collected data include maternal characteristics, laboratory examinations, imaging, pregnancy outcomes, and neonatal outcomes. Result(s): Leukocyte, platelets, basophil, neutrophils segment, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), urea, and creatinine were found to be significantly associated with severity differences (p < 0.05). Moderate-severe symptoms of COVID-19 also shown to have suggestive pneumonia findings on chest X-ray findings. Patients with asymptomatic-to-mild symptoms had significantly (p < 0.001) higher recovery rate, shorter hospital stay, less intensive care unit (ICU) admission, and had more vaginal delivery. Neonates from mother with mild symptoms also had significantly (p < 0.001) higher survival rate, higher birth weight, and higher APGAR score. Conclusion(s): Several laboratory and radiology components, as well as maternal and neonatal outcomes are related to the severity of COVID-19 in pregnant women in Indonesia.Copyright © The Author(s). 2023.

Clinical characteristics, complications, and outcomes of severe COVID-19 ARDS patients supported by ECMO and triaged for lung transplantations

Objectives: More than 200 patients have benefited from lung transplantation who failed to recover from COVID-19-induced acute respiratory distress (ARDS) with conventional ventilatory support and/ or extracorporeal membrane oxygenation support (ECMO) in USA. We aim to share our experience and lessons learned at our institute through this case series. Method(s): After IRB approval, we performed a retrospective chart review and identified 37 patients who received ECMO for COVID-19 induced ARDS between May 2020 through January 2022. Out of these, 12 received a formal consultation from the transplant team. We studied patient characteristics, interventions during ECMO support, and evaluation outcomes. Result(s): Most of our patients had single organ failure i.e., lung, except for two who required dialysis after ECMO initiation. Six out of the 12 patients received bilateral lung transplant. One patient received the transplant before ECMO initiation. However, the patient required two runs of ECMO after the transplant due to postop complications from suspected COVID19 reinfection and deceased on postoperative day 101. All the patients after transplant had an expedited recovery except one who required prolonged hospitalization before starting physical therapy. The median length of hospital stay for the transplant group was 148 (89- 194) days and for the non-transplant group was 114 (58-178) days. The 30-day survival rate was 100% for the transplant group. At a median follow-up of 207 (0- 456) days after discharge, 5(83.3%) patients in the transplant group and 3(50%) patients in the nontransplant group were alive. In the non-transplant group, 4 patients received ECMO support for more than 75 days and at last follow-up 2 were alive and functioning well without needing new lungs. This asks for an objective prospective study to define the timeline of irreversibility of the lung injury. Conclusion(s): Lung transplantation is a viable salvage option in patients with COVI-19 induced irreversible lung injury. However, the irreversibility of the lung injury and the timing of lung transplant remains to be determined case-by-case. (Figure Presented).

Once again about the new coronavirus infection COVID-19.

The COVID-19 pandemic continues to affect millions of people with increasing morbidity and mortality. Substantial variations exists in drug treatment of COVID-19. Extracorporeal membrane oxygenation (ECMO) facilitates survival of select critically ill patients with COVID-19 with about 25-45% survival rate;survivors tend to be younger and have a shorter duration from diagnosis to cannulation. The practioners found the severe complications including concomitant neurological manifestations (from headache, anosmia, ageusia to encephalopathy, stroke and others) and multisystem inflammation syndrome (MIS) predominantly in children few weeks after SARS-CoV-2 infection and characterized by persistent fever, vomiting, headache, Kawasaki - like rash and fatigue. Regarding MIS the authors did not find strong association between the complications rate and outcomes and regime of immunomodulation treatment. The neurological manifestations in pts with COVID-19 were associated with higher in-hospital mortality.Copyright © 2022 Sinergia Press. All rights reserved.

Hemoadsorption by CytoSorb in septic no-Covid and Covid patients: a case series

Background: Septic shock is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The reduction of pro-inflammatory and anti-inflammatory mediators by hemoadsorption represents a new tool in the treatment of sepsis. In the present case series, we evaluated the impact of CytoSorb on adult patients with septic shock. Method(s): Patients with septic shock, admitted to Intensive Care Unit (ICU) from March 1, 2021 to February 28, 2022 who received CytoSorb therapy within 72 hours of admission were enrolled in the study. The severity of clinical conditions at admission was assessed by the SAPS II and SOFA scores;The magnitude of the inflammatory response was estimated using the plasmatic levels of C reactive protein (CRP) and interleukin-6 (IL-6). The effect of CytoSorb therapy on the inflammatory state, was evaluated measuring the percentage reduction of IL-6 and CRP. Time elapsed from ICU admission and the start of CytoSorb therapy was also assessed. T-test was used to compare the means of the groups of Survivors and No survivors. Fisher's test was used to evaluated the difference in mortality between Covid and No covid patients. Result(s): Twelve patients were evaluated. Six patients tested positive for covid-19, while the other six did not. Table 1 shows the values of age, SAPSII, SOFA, IL-6, CRP, PCT and timing between the survivors and the no survivors. Overall, there was no significant difference between the two groups in terms of SAPSII, SOFA, age, CRP. There was a significant difference in the timing of Cytosorb start and percentage of IL-6 removal: In surviving patients the timing of intervention was shorter (3,3+/-1,8 vs 23,5+/-18,9 hours) than in non- survivors. The IL-6 removal rate was significantly higher in the survivor group (70,8+/-15,87 vs 33,2+/-12,26). Conclusion(s): In survivors the timing of CytoSorb therapy was shorter and the IL-6 removal rate was higher than in non-survivors. This suggest that the early applying of CytoSorb adsorber in combination with Continuous Renal Replacement Therapy (CRRT) techniques, could increase the survival rate of septic shock patients. Using CytoSorb was safe and well tolerated with no device-related adverse events during or after the treatment.

IL-6 as a predictor of survival rate in liver metastatic breast cancer patients with Covid-19 infection: A case series.

Introduction and importance: Breast cancer is the most common type of cancer in women, with 30 % being metastatic breast cancer. Cancer is known to be a comorbid Covid-19 infection. Interleukin-6 (IL-6) is one of the findings of inflammatory activity due to Covid-19 infection. We report IL-6 levels as a prognostic factor for survival rate in patients with liver metastatic breast cancer. Case presentation: We report five cases of liver metastatic breast cancer with various types of primary breast cancer. All patients are infected with Covid-19. IL-6 levels were reported to be elevated in all five patients. All patients were treated according to the national guidelines for the care of Covid-19 patients. All patients are reported to have deceased after being treated for Covid-19 infection. Clinical discussion: Metastatic breast cancer has a low prognostic rate. Cancer has been recognized as one of the comorbidities and increases the severity and mortality of Covid-19 infection. Elevated levels of IL-6 are caused by an immune response to infection, and can worsen the outcome of breast cancer patients. Changes in IL-6 levels implicate the survival rate of metastatic breast cancer patients and outcomes during the treatment of Covid-19 infection. Conclusion: Elevated levels of IL-6 can be a prognostic factor of the survival rate of metastatic breast cancer patients during the treatment of Covid-19 infection.

Outcomes of Sars-Cov-2 Infection in Patients with Anca Associated Vasculitis. Data from the National Sar-Covid Registry

Objectives: To describe the clinical characteristics and outcomes of SARSCoV-2 infection in patients with systemic vasculitis. Method(s): Observational, multicenter, cross-sectional analytical study in patients 18 or older diagnosed with systemic vasculitis with confirmed SARSCoV-2 infection (RT-PCR or serology) included in the SAR-COVID registry. Patients were evaluated from July 2020 to February 2022. Patients diagnosed with ANCA-associated vasculitis (AAV), other systemic vasculitides (Giant cell arteritis, Takayasu), and a control group of patients with other rheumatological diseases matched by age, sex, comorbidities, and date of SARS-CoV-2 infection. The survival curve of the groups was studied by Kaplan-Meier and compared through the Log-Rank Test. A Cox regression model will be performed to adjust survival for different variables (sex, age, treatments for underlying disease, treatments for viral infection, smoking, obesity, d-dimer level, and disease activity). Result(s): A total of 282 out of 2694 patients in the SAR-COVID registry were included, 57.4%women with a mean age of 55.7 years (SD 14.1). Fifty-four patients in the AAV group, 32 in the other vasculitis group, and 196 controls were studied. Hospitalization was required in 53.7% of the AAV group, 37.5% in other vasculitides, and 26.2% in the control group. 5.6% of patients in the control group presented acute respiratory distress syndrome (ARDS), 15.6% in the other vasculitis group, and 22.2% in the AAV group (p alpha 0.001). Complete recovery was observed in 82.3% of patients in the control group, 75%in the other vasculitis group, and 63%in the AAV group.We observed that 5.7% of the patients in the control group died from COVID-19, 9.4%from other vasculitides, and 27.8% in the AAV group (p alpha 0.001). We found a lower survival in the AAV group compared to the control group (p alpha 0.005). In the multivariate Cox regression model, older age (HR:1.05 IC95%1.01-1.09 p = 0.01), BMI > 40 (HR:13.2 IC95% 2.1-83.2 p = 0.01), and high activity of the underlying disease (HR:16 95% CI 3.7-69.4 p alpha 0.005) were associated with lower survival. Conclusion(s): In conclusion, patients diagnosed with AAV presented a worse disease course during SARS-CoV-2 infection with a more frequent requirement for invasive mechanical ventilation. Likewise, these patients showed lower survival compared to patients with other autoimmune diseases.

The Survival Probability of Covid-19 Patients with Type 2 Diabetes Mellitus during Pandemic at Al Ihsan Hospital, West Java Province, Indonesia

BACKGROUND: The high prevalence of diabetes mellitus (DM) in the population causes DM to become one of the most common comorbidities of coronavirus disease 2019 (COVID-19). Patients with diabetes have a higher risk of experiencing serious complications from COVID-19 and even death. AIM: This study was aimed to determine the difference in survival probability of COVID-19 patients, based on their DM status and to determine the association between type 2 DM and COVID-19 mortality at Al Ihsan Hospital, West Java Province, Indonesia. METHOD(S): The population of this retrospective cohort study were COVID-19 patients, aged >=18 years and were treated at Al Ihsan Hospital, from March 2020 to December 31, 2021. Differences in survival probability were obtained from survival analysis with Kaplan-Meier. Cox Proportional Hazard regression was used to determine the association between type 2 DM and COVID-19 mortality. RESULT(S): Totally, 308 confirmed positive COVID-19 patients were recruited in this study. During the 21 days of observation, survival probability of COVID-19 patients with type 2 DM was significantly lower than those without type 2 DM (71.24% vs. 84.13% respectively, with p = 0.0056). There was a statistically significant association between type 2 DM and COVID-19 mortality after controlling for age, cough symptoms, acute respiratory distress syndrome, vaccination, chronic kidney disease, ventilator use, antiviral therapy, and the percentage of bed occupation rate COVID-19 isolation at admission. The adjusted hazard ratio showing association between type 2 DM and COVID-19 mortality in the final model of multivariate analysis was 2.68 (95% CI 1.24-5.73). CONCLUSION(S): The survival probability of COVID-19 patients with type 2 DM was significantly lower than those without type 2 DM. COVID-19 patients with DM in Al Ihsan Hospital were almost 3 times more likely to be fatal as compared COVID-19 patients without DM.Copyright © 2023 Oka Septiriani, Mondastri Korib Sudaryo, Syahrizal Syarif, Citra Citra.

Esophageal Squamous Cell Carcinoma: An Unfavorable Complication of Achalasia

Introduction: Achalasia is a motility disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter and loss of peristalsis in the distal esophagus. It is a rare condition with an annual incidence of 0.5-1.2 per 100,000 individuals. The etiology of primary achalasia is unknown, however secondary achalasia can be attributed to malignancy, infections or systemic diseases such as amyloidosis. An infrequent complication of achalasia is esophageal squamous cell carcinoma which has a prevalence of 26 in every 1,000 cases. We present a case of interval locoregionally advanced esophageal squamous cell carcinoma only 2 years after a normal upper endoscopy. Case Description/Methods: A 67-year-old female with known achalasia and previous pneumatic dilation in her 30s presented to our outpatient clinic in 2019 with complaints of worsening chronic dysphagia. EGD was performed which revealed a significantly dilated esophagus with candida esophagitis. Despite completing antifungal therapy, she continued to experience dysphagia to solids and liquids. Barium swallow demonstrated absent peristalsis with pooling of contrast within the esophagus. High-Resolution Manometry testing demonstrated absent peristalsis. She opted for surgical myotomy, however due to COVID restrictions, the procedure was delayed. Repeat EGD was performed in 2022 for pre-surgical evaluation and showed a large obstructing friable esophageal mass in the lower third of the esophagus. Pathology was consistent with invasive poorly differentiated squamous cell carcinoma. PET scan showed locoregional disease with FDG-avid esophageal and gastrohepatic node lesions. She was started on chemoradiation with Paclitaxel and Carboplatin (Figure). Discussion(s): The risk of esophageal squamous cell carcinoma in achalasia has significantly increased with incidence of approximately 1 in 300 patients. The presumed mechanism of malignancy in achalasia is poor emptying resulting in food stasis, bacterial overgrowth and inflammation leading to dysplasia and development of carcinoma. Given the relatively low incidence, there are currently no guidelines on routine endoscopic screening to assess for malignancy in patients with achalasia. Survival rates are poor as patients are often diagnosed at advanced stages. This case aims to illustrate the importance and need for interval screening in individuals with long standing achalasia to improve outcomes.

CBD Treatment Improves Fatal Inflammatory Response Exhibited in SEB-Induced ARDS

The novel SARS-CoV-2 virus known to cause the COVID-19 outbreak has resulted in a global healthcare crisis that has persisted the past 3 years. Thus, understanding the mechanisms underlying this disease are vital at this time. While there are issues of research infrastructure to handle the virus and because of the refractoriness of rodents to this disease, the availability of these tools is still limited. The cytokine storm and fatality presented in patients with severe COVID-19 can be mimicked with Staphylococcal enterotoxin B (SEB)-induced Acute Respiratory Distress Syndrome (ARDS). Within ~7 days, the survival rate drops to 0% for C3H/HeJ mice exposed to a dual dose of SEB. In this study, we administered cannabidiol (CBD) intraperitoneally for 3 days pre- and post-SEB dosing and found that the clinical outcomes improved significantly. Initial evaluation of scRNASeq data from lungs comparing naive to SEB-induced ARDS mice illustrated an increase in infiltrating immune cells, and a loss in pulmonary epithelial cells in the latter group. When evaluating the effect of CBD treatment on SEB-induced ARDS, we were able to demonstrate that CBD reduced the macrophage population. To characterize the mechanism by which CBD treatment ameliorated the inflammatory response, we found that CBD treated mice had significant reduction in infiltrating immune cells and alveolar thickening. This same histology and infiltration is presented in ARDS. MicroRNA expression analysis showed a significant increase in the expression mmu-miR-298-5p and mmu-miR- 566 with CBD treatment. Ingenuity Pathway Analysis (IPA) indicated that the dysregulated miRNAs were also implicated in pathways associated with macrophage activation, respiratory disease and inflammation, interferon stimulated genes, as well as genes which have been upregulated in the disease state of this model. These targets include but are not limited to Cebpb, Efhd2, Stat3, Socs3, Cxcl5, Gbp2, and Birc3. This finding offers insights for the development of preventive and therapeutic strategies in the treatment of ARDS, including that induced in COVID-19. Supported by NIH grants P01AT003961, P20GM103641, R01ES003961, R01AI129788, R01AI123947, R01AI160896 to MN and PSN and K99GM147910 to KW.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Covid-19 Outcome in Patients with and without Cirrhosis

Background: Severe outcomes of COVID-19 are associated with advancing age, and multiple medical comorbidities. The impact of COVID-19 on the clinical course of patients with cirrhosis has not been well studied. We determined the effect of SARS-CoV-2 infection on the hospitalization and survival rates of patients with cirrhosis. Method(s): Using ICD-10-CM codes, we identified all Veterans with a diagnosis of cirrhosis in the VA Corporate Data Warehouse and COVID-19 Shared Data Resource. Study cohort included Veterans who were tested for SARS-CoV-2 and had no history of organ transplantation or malignancies. Each SARS-CoV-2 positive case was propensity-score matched by demographics and comorbidities with up to two SARS-CoV-2 negative controls. The primary endpoints were acute care hospitalization, admission to intensive care, respiratory support, or death. Result(s): Of 1,115,037 individuals tested for SARS-CoV-2, 31,680 were noted to have cirrhosis and among them 5,047 (16%) were SARS-CoV-2 positive. After exclusions and propensity-score matching, 5,047 SARS-CoV-2 positive and 9,913 propensity score matched SARS-CoV-2 negative individuals were included in the analysis cohort. Median age was 67 years, 95% were men and 25% were of black race. Median BMI was 30 and history of hypertension, diabetes, cardiovascular and chronic pulmonary disease was noted among 81%, 54%, 56% and 32% respectively. Among all cirrhotic individuals, SARS-CoV-2 positive individuals less frequently progressed to hepatic decompensation (3.1% vs 4.8%, P< 0.0001) or hospitalization (35.7% vs 38.2%, P=0.002), but more frequently required ICU admission 15% vs 12.2%, P< 0.0001) or respiratory support (7.3% vs 8.4%, P=0.01). Among those admitted, length of hospital stay was longer among SARS-CoV-2 positive individuals (7 vs 4 days, P< 0.0001). In Cox regression analysis, SARS-CoV-2 positivity was associated with a higher risk of all-cause mortality (HR 1.37, 95% CI 1.19,1.56). Conclusion(s): Although patients with cirrhosis and COVID-19 were less often hospitalized, they had longer duration of hospitalization and were at higher risk of severe or critical illness and death. (Figure Presented).

CORONAVIRUS DISEASE SURVIVAL TIME MODEL FOR FORECASTING

The term "survival analysis" refers to statistical techniques for data analysis where the time until the occurrence of the desired event serves as the outcome variable. Time to event analysis is another name for survival analysis. Applications for survival analysis are fairly broad and include things like calculating a population's survival rate or contrasting the survival of two or more groups. Cox regression analysis is a highly well-liked and frequently applied technique among them. Data on disease states are typically obtained at random epochs or at periodic epochs during follow-up in research looking at biological changes between states of Coronavirus infection and the start of COVID-19 in the human immune system. For instance, after the COVID enters a person's bloodstream by a route of transmission, it progresses through numerous stages that are linked to the depletion of B cells before becoming COVID-19. This study presents the Cox's approach for simulating the link between variables influencing the development of two disease states, namely I= the time epoch of COVID infection and P= the time epoch of COVID-19. Incubation period (IP) or survival time is the precise interval of time between "P and I." It is shown how Cox's model works with several personal infective factors and how well it can estimate the percentage of COVID-19 victims with the same completed length of IP. Such forecast values are then established for a synthetically simulated data set. [ FROM AUTHOR] Copyright of Journal of Pharmaceutical Negative Results is the property of ResearchTrentz and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)