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A new coronavirus infection caused by the SARS-CoV-2 virus is characterized by a systemic hyperinflammatory response with a pronounced increase in the content of pro-inflammatory cytokines. Materials and methods. The study was conducted on the basis of the Samara Regional Children's Infectious Diseases Hospital from 2021 to 2022. 40 patients with moderate (n = 20, group I) and severe forms (n = 20, group II) COVID-19 were studied, the comparison group consisted of patients with viral pneumonia of another etiology (n = 35, group III). Results. The infectious agent SARS-CoV-2 induces high levels of cytokines IL-6 (p < 0.005), IL-8 (p < 0.05) and a slight increase in TNF-alpha (p < 0.05). IL-8 was significantly associated with disease duration (p < 0.01). We assume that the value of this interleukin will increase in the post-COVID period. Conclusions. Changes in IL-6 and IL-8 levels in patients with COVID-19, along with clinical features, are important biomarkers for predicting the severity and duration of the disease.Copyright © Children Infections.All rights reserved
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Under the Chinese "Zero-COVID” policy, many laborers were forced out of work. Participating in educational compensation can effectively help unemployed laborers achieve re-employment. This paper selected Jining, Shandong Province, as the research area, analyzed the data using a questionnaire survey and key interviews, and observed factors that affect and change willingness to receive educational compensation (WTEC) and the willingness to accept the training duration (WTTD) of unemployed laborers. The study found that 77.78% of unemployed laborers are willing to receive educational compensation, and the WTTD is 12.05 days. Among them, eight factors affect WTEC, such as the years of education, the duration of unemployment, whether there are dependents in the family, and the family's size. Nine factors such as gender, age, education, unemployed duration, dependents, and other supportable incomes affect WTTD. Based on this, by taking measures from the government and laborers, WTEC and WTTD can be improved, and then the rate of re-employment can be enhanced, and finally, the employment problem can be ameliorated.
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Introduction: Automatic drug dispensers are now widely used in critical care.1-2 They can provide information about dispensed drugs. Good practice in sedation restricts the use of sedatives and titrates doses to defined responses.3-4 Objectives: To extract drug dispenser issuing records for sedatives and link these to patient records to evaluate sedative use. Method(s): in October 2019, we introduced two Omnicell XT automated dispensing cabinets (Omnicell inc. CA, USA) into a 42 bedded general/neurological unit. ICNARC (Intensive care national audit and research centre) and CCMDS (Critical care minimum data set) data was collected using the Ward Watcher program. Dispenser issuing records for alfentanil, propofol and midazolam were obtained as Excel files for 13 months from January 2020. Output time stamps were converted to dates and times. Outputs were linked to outputs of the ICNARC and CCMDS records for the patients that the drugs were issued to. All the outputs had patients identified by their unique hospital numbers. These were used in Excel "power queries" to produce a spread sheet with a single row per patient. Multiple admissions used the first diagnosis, the final outcome and the total length of stay. The total dose of sedatives was calculated from ampoule dose and number. The duration of treatment was calculated from the first and last issues of the drug. ICNARC codes were used to identify the primary system in the admission diagnostic code and those patients admitted for COVID-19. Variables were compared using Chi Squared, Mann-Whitney U and Kruskal Wallis Tests. The significance of associations was established using Spearman's Rho. Linear regression was used to define relationships more clearly. Result(s): Table one summarises the patient characteristics with respect to all admissions during the study period and for patients who had had the studied drugs issued to them. Midazolam was used in fewer patients, they were more likely to be male, heavier (p>0001) and to die than patients receiving Propofol or Alfentanil (p>0.001). With respect to diagnostic groups, all the sedatives, particularly Midazolam (p<0.001), were more likely to be used in patients with COVID-19. The relationship between the dose of sedative drugs and patient age and weight was explored using the dose per advanced respiratory day. All three drugs had a significant but weak negative relationship with age, lower doses being given to older people (Propofol r2 = 0.02, p=0.01. Alfentanil r2 = 0.04, p=0.00. Midazolam r2 = 0.07, p=0.00.). There was also a weak but significant relationship between increasing dose of Propofol with patient weight (r2 = 0.02, p=0.01), but there was no relation between weight and doses of the other drugs. Conclusion(s): Information from automatic drug dispensers can be interpreted and combined with other datasets to produce clinically relevant information. The limited weak relationships between drug dose and age and weight suggests that sedative drugs could have been better titrated to response.
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Due to multiple COVID-19 lockdowns, individuals likely engaged in multiple activities, including viewing adult content. Even though a subscription-based pornographic content sharing (SPCS) website (e.g., OnlyFans or Fancentro) is operationally distinct from traditional sexual channels (e.g., Pornhub or Xvideos), no study has examined whether COVID-19 increased the visiting behaviors of these SPCS websites. Consequently, we attempted to address this void. The subscription to comScore services by Chulalongkorn Business School allowed us to utilize actual visitor behavior at three SPCS websites before and during COVID-19. The analysis of 17,477 visit sessions revealed that (1) pageviews and visit duration peaked before the pandemic, but (2) the average length of stay per pageview increased during the pandemic compared to before its introduction. In addition to providing theoretical insight into the relationship between COVID-19 and website-visiting behaviors of SPCS, our findings offer practical contributions. © 2023, International Journal of Economics and Finance Studies. All Rights Reserved.
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Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.
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Aim: To determine the intraoperative Ramsay sedation score after dexmedetomidine infusion in patients undergoing perineal surgery. Study design: Descriptive study. Place and duration of study: Department of Anaesthesia, JPMC, Karachi from 13th February 2021 to 13th August 2021. Methodology: One hundred and seventy four patients who met the diagnostic criteria were enrolled. Result(s): The mean age was 46.51 years with the standard deviation of +/-10.87. 66 (37.9%) were male and 108 (62.1%) were female. Whereas, mean duration of surgery, Ramsay sedation score at 5 minutes, 15 minutes, 30 minutes, height, weight and BMI in our study was 1.41+/-0.40 hours, 1.72+/-0.44, 3.51+/-0.60, 4.57+/-0.62, 165.62+/-8.23 cm, 68.34+/-8.23 kg and 24.85+/-3.34 kg/m2 respectively. Conclusion(s): Intraoperative dexmedetomidine proved beneficial in perineal surgeries and could be served as a potent sedative drug.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.
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Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.
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Background: The coronavirus disease 2019 (COVID-19) pandemic and its associated morbidities are a great global concern. Diabetes mellitus (DM) is associated with adverse clinical outcomes and high mortality in patients with COVID-19. Objective(s): This study examined the frequency of BM, newly diagnosed hyperglycemia, and their impacts on hospitalized patients with COVID-19. Method(s): This retrospective study examined 810 medical records of PCR-confirmed COVID-19 patients admitted to Razi Hospital, Ahvaz, Iran. The clinical presentations, severity, and impacts of COVID-19 were compared between patients with and without DM. Disease severity was determined based on the NEWS2 scoring system. Result(s): This study included 810 medical records of COVID-19 patients, of whom 326 had pre-existing DM, and 484 were non-DM. The rates of diabetes and newly diagnosed hyperglycemia were 40.2% and 11.2%, respectively. The most common underlying diseases were hypertension (35.3%), ischemic heart disease (17.9%), and chronic kidney disease (11.9%), which were higher in people with diabetes than non-diabetics. The rate of acute kidney injury was higher in patients with diabetes than in non-diabetics (30.7% vs. 19.2%;P < 0.001) and in patients with severe COVID-19 than in those whose disease was not severe (27.8% vs. 21.5%;P = 0.04). The rates of severe COVID-19 (46.3% vs. 34.7%;P = 0.093), ICU admission (40.7% vs. 27.4%;P = 0.012), and mortality (18.5% vs. 10.5%;P = 0.079) were higher in patients with newly diagnosed hyperglycemia than in euglycemic patients. Conclusion(s): This study showed that COVID-19 infection is linked with newly diagnosed hyperglycemia and pre-existing DM, both associated with severe COVID-19, more need for ICU admission, and mortality.Copyright © 2023, Author(s).
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COVID-19 is a severe immunosuppressive disease that can cause changes in the clinical course of autoimmune diseases. Autoimmune thyroiditis (AIT) is no exception. It is relevant to study the features of the clinical course of existing AIT in the post-COVID-19 period. The work aims to study the changes in the structure and function of the thyroid in patients with AIT with subclinical and manifest compensated hypothyroidism who had moderate COVID-19. A total of 123 patients aged 21-49 with AIT with subclinical hypothyroidism - 43 (group 1, 12 of whom had moderate COVID-19) and manifest hypothyroidism in the stage of medical compensation - 80 (group 2, 32 of whom had moderate COVID-19). The duration of AIT ranged from 4 to 13 years. In all cases, upon inclusion in the study and 2 and 6 months after it, changes in the structure of the thyroid gland were studied according to ultrasound data, as well as its functional capacity and the degree of compensation of hypothyroidism according to the thyroid-stimulating hormone indicator. In all patients with AIT, COVID-19 caused the progression of structural changes in the thyroid within one of two variants of the ultrasound picture of thyroiditis - hypoechoic heterogeneous or pseudo micronodular. The hormone-producing function also changed: in 7 out of 12 patients of group 1 of the main subgroup, hypothyroidism changed from subclinical to manifest hypothyroidism in the postoperative period, and in all patients of group 2 of the main subgroup, a further decrease in hormone synthesis was noted. In the post-COVID-19 period, patients with AIT undergo a progression of structural changes in the thyroid gland and a decrease in the synthesis of thyroid hormones.Copyright © 2023 The Authors.
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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).
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Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
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Acute respiratory failure (ARF) is the leading cause of death in hospitalized patients with severe forms of COVID-19. At the beginning of COVID-19 pandemic the starting respiratory protocol suggested early use of intubation and artificial lung ventilation (ALV) in patients with severe pneumonia complicated by ARF. However, after the analysis of the published studies it was noted that the pathophysiology of the development of ARF in COVID-19 had features that determine the atypical clinical pattern - "silent hypoxemia". This leads to the late onset of respiratory support (RS) and, as a result, to the lower effectiveness of non-invasive RS methods. This article discusses the creation of an algorithm for the early use of various non-invasive RS methods in patients with COVID-19 complicated by ARF, that will decrease the frequency of hospitalization to the Intensive care units, tracheal intubation and ALV, reduce the duration of treatment and improve prognosis.Copyright © 2023 IRBIS LLC. All Rights Reserved.
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Objectives: The 90-day double-blind phase (DBP) of the Phase 3 EASE study demonstrated accelerated wound healing for Oleogel-S10 (birch triterpenes) versus control gel in epidermolysis bullosa (EB). Here, we report safety and total wound burden results from the 24-month open-label phase (OLP) in which all patients received treatment with Oleogel-S10. Method(s): Total wound burden was assessed using EB Disease Activity and Scarring Index (EBDASI) and Body Surface Area Percentage (BSAP). Data are reported without visit windows to reflect a realworld situation more accurately, particularly considering the COVID- 19 pandemic. Result(s): The patient population was made up of dystrophic EB (n = 178, 86.8%) and junctional EB (n = 25, 12.2%);71.7% (n = 147) of patients were aged <18 years. 141 patients (68.8%) completed the OLP. The mean (SD) treatment duration for all patients was 584.7 (246.1) days. Adverse events were reported in 77.1% of all patients in the OLP versus 81.7% of those receiving Oleogel-S10 in the DBP. Mean BSAP for patients treated with Oleogel-S10 in the DBP reduced from 12.1% at study entry to 6.1% with 27 months of treatment. Similarly, the mean EBDASI skin activity score in the Oleogel-S10 group improved from 19.6 to 15.1 after 27 months. In addition, reductions in both BSAP and EBDASI from OLP baseline were observed in patients who transitioned from control gel to Oleogel-S10 in the OLP. Discussion(s): These data support a reassuring long-term safety profile of Oleogel-S10. Furthermore, the reduction in wound burden previously reported with 15 months of Oleogel-S10 treatment is maintained to the end of OLP. This is encouraging given the nature of this chronic genetic disorder in which there is regular cycling of patients' fragile wounds.
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The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.
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INTRODUCTION: Pregnancy is characterized by an altered pattern of emotions and sleep. The aim of this study was to examine the effect of emotional distress on objective sleep parameters in underserved pregnant women during the COVID-19 pandemic. METHODS: Institutional review board approval was obtained for the study. This was a longitudinal observation study in which we administered weekly validated self-reported surveys (Patient Health Questionnaire-2, Generalized Anxiety Disorder-2, COVID-19-related anxiety, and life-related stressors) to consented pregnant women over the course of their second and third trimesters (n=13). The independent variable, subjective emotional distress, was derived from a sum score of these weekly surveys. A wearable device was used to measure objective sleep physiological data, such as the rapid eye movement (REM), deep, and light sleep stages. The dependent variables were obtained from weekly average scores of the sleep data. Multilevel analysis was conducted, controlling for relevant covariates. RESULTS: Adjusting for gestational age, maternal age at enrollment, and prepregnancy body mass index, higher emotional distress was associated with a shorter duration of deep sleep (b=−.65, P <.05) and longer duration of REM sleep (b=.79, P <.01). There was no significant relationship between emotional distress and light sleep. CONCLUSION: Our study appears to be the first to provide preliminary evidence that emotional distress negatively affects sleep in terms of decreased deep sleep and increased REM sleep during pregnancy. Findings suggest that further research is needed to understand the role of sleep in the relationships between emotional distress and adverse maternal and infant health outcomes. [ FROM AUTHOR] Copyright of Obstetrics & Gynecology is the property of Lippincott Williams & Wilkins 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.)
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Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Background: The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. It is unknown whether concurrent CPI and Sars-COV-2 vaccine administration increases the risk of irAEs. This retrospective study examined the incidence of severe irAEs in cancer patients receiving CPI therapy at the time of vaccination against Sars CoV-2. Method(s): Following IRB approval, pts with solid tumors who received any approved CPI since FDA authorization of the COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received one or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation of CPI due to irAE. Data was analyzed using descriptive statistics. Result(s): 290 pts with bladder, head/neck, liver, skin (melanoma, SCC), renal, and gynecologic cancer were included in analysis. The median age was 67 years (IQR: 59.0-74.0) and 66% pts were male. At the time of vaccination, 201 pts (69.3%) received CPI monotherapy, 53 pts (18.3%) received combination (combo) CPI therapy, and 36 pts (12.4%) received other therapies (chemo, TKIs, etc.) with CPI. The vaccine manufacturer was Pfizer Bio-N-Tech in 162 pts (55.9%), Moderna in 122 pts (42.1%), and Johnson and Johnson in 6 pts (2.1%). The number of vaccinations received was >/= 3 in 214 pts, 2 in 64 pts, and 1 in 11 pts. 30 pts (11.5%) experienced severe irAEs following vaccination. The rate of severe irAEs was 10.3% (30/290) in the total population [6% (12/201) with CPI monotherapy, 19% (10/53) with combo CPI, and 22% (8/36) in the combo CPI-other group]. Severe irAEs occurred after the first vaccine dose in 5 pts (16.7%), second dose in 16 pts (53.3%), and third dose in 9 pts (30%) pts. The median time between CPI treatment and vaccination in pts who experienced irAE was15.5 days (IQR: 10.2-23.0). Hospitalization was required for 19 patients (63.3%). 24 pts (80.0%) required immunosuppressive therapy with a median therapy duration of 98.5 days (IQR 40.2-173.0). 16 pts (53.5%) discontinued CPI therapy following severe irAEs Conclusion(s): In this retrospective study, we observed a 10.3% rate of severe irAE in cancer pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI.
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Introduction: Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a global health crisis. Initially considered a respiratory tract pathogen, it can cause multiple organ dysfunction. It has also been described to predispose to venous and arterial thromboembolism;however, limited published data is available regarding mesenteric thrombosis COVID-19. Clinicians should be aware of the life-threatening situation in COVID-19 patients. Method(s): A case series analysis of 9 patients admitted and managed under department of operation over a duration of 13 months from September 2020 to September 2021 Results: Out of the total of 9 cases of intestinal ischemia, 3 were COVID-19 positive (rapid antigen, RT PCR or CORADS 4 or higher), overall mortality being 55.5% and patients with COVID- 19 were found to have 100% mortality in the study. Mortality in conservatively managed patients was 100%, Mortality in surgically managed patients was 42.8%. Pre operative acidosis, hypoxia and hypotension were found to be important determinants of outcome of the disease. Conclusion(s): Treatment of COVID - 19 and intestinal Ischemia should go simultaneously and in line with the latest evidence based guidelines of COVID 19, Patients who survive an acute event are likely to die of other complications related to the COVID-19 like ARDS, Disseminated Intravascular Coagulation etc that could have predisposed them to intestinal ischemia. Perioperative acidosis, hypoxia and hypotension are important determinants of the outcome of the course of the disease.
ABSTRACT
Background: B-cell lymphoma-2 (Bcl-2) proteins play an important role in multiple myeloma (MM) cell survival and represent an attractive therapeutic target. In prior trials, a subgroup analysis of patients with t(11;14)-positive relapsed/refractory (R/R) MM showed the combination of a Bcl-2 inhibitor, a proteasome inhibitor, and dexamethasone improved progression-free survival with no increased mortality. BGB-11417, a Bcl-2 inhibitor, is more potent and selective than venetoclax. BGB-11417- 105 (NCT04973605) is a phase 1b/2 study assessing the safety and efficacy of BGB-11417 monotherapy, in combination with dexamethasone, or with dexamethasone+carfilzomib in patients with t(11;14)-positive R/R MM. Preliminary safety results for the combination of BGB-11417 + dexamethasone are presented. Method(s): Eligible patients had t(11;14)-positive R/R MM and had been exposed to a proteasome inhibitor, immunomodulatory agent, and anti-CD38 therapy. Patients received 80-, 160-, 320-, or 640-mg BGB-11417 daily with 40-mg dexamethasone weekly until death, intolerability, or disease progression. Dose escalation was guided by a mTPI-2 design and overall review by a safety monitoring committee. Pharmacokinetics (PK) were also assessed. Result(s): As of 1 July 2022, 10 patients were enrolled in the 80-, 160-, and 320-mg (3 patients each) and 640-mg (1 patient) dose-escalation cohorts of BGB-11417 + dexamethasone. The median age was 69 years (range, 52-81) and median prior lines of therapy was 3 (range, 1-5). The median treatment duration was 3.2 months (range, 0.5-6.5). No patients experienced dose-limiting toxicity at any dose level. Three patients died whilst on study: 1 due to COVID-19 complications 157 days after treatment discontinuation (day 208), 1 due to progressive disease 50 days after treatment discontinuation (day 89), and 1 due to COVID-19 whilst on study treatment (day 78). No deaths were associated with study treatment. Two patients experienced Grade >= 3 treatment-emergent adverse events (TEAEs). One patient in the 160-mg cohort experienced Grade 3 increase in liver enzymes and lymphopenia. One patient in the 320-mg cohort experienced Grade 3 lymphopenia. The most common TEAEs were insomnia (50%), fatigue (30%), arthralgia (20%), back pain (20%), lymphopenia (20%), and nausea (20%). BGB-11417 exposure increased dose-dependently from 80 mg to 320 mg with high interpatient PK variability. BGB-11417 exposures after single and multiple doses appeared similar, indicating limited accumulation. Conclusion(s): BGB-11417 plus dexamethasone was generally well-tolerated in patients with R/R MM harbouring t(11;14) at doses <=640 mg. Efficacy data are forthcoming. Recruitment is ongoing in the US, Australia, and New Zealand;the BGB-11417, dexamethasone, and carfilzomib combination arm will open in the future.