Criteria for Hyperinflammation Developing in COVID-19: Analysis of 2 Cohorts From Different Periods of the Pandemic.

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.

Evaluation of the Association between Multilobar Involvement and ACE Inhibitor Use in SARS-CoV-2 Patients

Aim: Angiotensin-converting enzyme 2 (ACE2) acts not only as an enzyme but also as a thought to be central receptor by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters host cells. Angiotensin-converting enzyme inhibitors (ACEIs) are thought to $1 are central to SARS-CoV-2 progression. However, its effect on clinical outcomes is still not fully explained. In this study, we investigated the effects of ACEIs use on pulmonary computed tomography findings. Method(s): The data of the patients who were hospitalized for SARS-CoV-2 pneumonia and were using medications for the diagnosis of hypertension from 20th March to 20th June 2020 were evaluated retrospectively. Patients were divided into 2 groups patients using ACEIs and not using ACEIs. Result(s): The study was conducted with 107 patients. Mild cases without signs of pneumonia were excluded from this study. Moderate cases were accepted as patients with symptoms related to the respiratory system and pneumonia detected on imaging. SpO2<=93%, >=30 breaths/min respiratory rate, and patients who developed respiratory failure, mechanical ventilator need, shock, or multiorgan failure were included in the severe and critically ill cases group. Severe and critical cases were evaluated as a single group. When the radiological images of the patients were examined, it was remarkable that multilobar findings were less common in the ACEIs using group (p<0.001). At the clinical end point, mortality rates in patients using ACEIs (12.7%) were significantly lower than patients without using ACEIs (32.7%). Conclusion(s): In our study, we showed that SARS-CoV-2 progresses with less multilobar involvement in pulmonary computed tomography in patients using ACEI.Copyright © 2023 by The Medical Bulletin of Istanbul Haseki Training and Research Hospital The Medical Bulletin of Haseki published by Galenos Yayinevi.

The predictive research of the Coronavirus Disease-2019 outbreak in Turkey

Aim to evaluate the relationship between the number of newly confirmed Coronavirus Disease 2019 (COVID-19) cases and public concern in Turkey via Google TrendsTM. The data on relative search volumes for 5 keywords related to coronavirus and prevention from the disease (COVID-19, coronavirus, face mask, hand washing, disinfectant) were obtained between March 10, 2020, and June 16, 2020. The daily numbers of newly confirmed cases were obtained from the Ministry of Health's COVID-19 information platform. Time-lag correlations for the time lag between - 17 and + 17 days were used to assess whether search queries on Google predicted new COVID-19 cases. The relative search volumes for COVID-19 and coronavirus increased 2-3 weeks before cases, with the highest correlations between searches and cases observed - 9 and - 17 days early, respectively. Although relative search volumes for the terms of handwashing and disinfectant increased 13-14 days earlier, interest in face masks increased 4 days earlier. Public searches about disease prevention have negative correlations with the worldwide case/death rates in the first wave. The number of confirmed COVID-19 cases was predicted by examining the search behavior of the public using Google TrendsTM. © 2022,Journal of International Dental and Medical Research. All Rights Reserved.

A CASE OF REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA INDUCED IMMUNE THROMBOCYTOPENIC PURPURA SUCCESSFULLY TREATED WITH VENETOCLAX

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. Approximately 2% of patients with CLL develop immune thrombocytopenic purpura (ITP) during the course of the disease. When resistant to steroids, this constitutes as indication for treatment of the CLL. Here we report a patient with refractory ITP secondary to CLL successfully treated with venetoclax. Aims: To present an interesting case with CLL related refractory ITP treated successfully with novel agent venetoclax. Methods: Patient data was taken from the patient herself and Hospital records. Informed consent to publish the case is obtained from patient. Permission for off-label venetoclax and eltrombopag was obtained from Ministry of Health of Turkey. Results: 46-year-old female patient presented with lumps on her neck that were present for the last 9 months in November 2020. She has a history of frequent pneumonia and otitis but no constitutional symptoms. Her physical examination reveals multiple 2cm lymphadenopathies on her neck and no organomegaly or other pathological features. Blood work shows mild lymphocytosis (6800/mm3) with no serious cytopenias. Peripheral blood smear, flow cytometry and bone marrow biopsy were all compatible with CLL. She was classified as Binet A CLL and was followed up with no treatment after appropriate vaccinations against capsulated pathogens. In July and August 2021 she received two doses of mRNA vaccination against COVID-19. On 1st November 2021 she experienced excessive menstrual bleeding and blood work showed platelet count of 23000/mm3, she was started on steroids (1 mg/kg/day) and after 4 days platelet count has risen to 55000/mm3, she discontinued steroids on her own against medical advice. On 13th of November she presented with extensive petechiae and purpura and was again started on steroids and was given the courses of intravenous immunoglobulins (IVIG) without any sustained response. She was refractory to platelet transfusions too. She was transferred to our clinic. She was found to have del11q and del13q. She refused bone marrow examination. She was treated with rituximab, steroids, vincristine, IVIG and eltrombopag for ITP without success (Fig. 1). She had a minimal response to IVIG only. She received two courses of bendamustine (90 mg/kg for two days) also without success. Three courses of plasmapheresis yielded no response either. After mild success with immunadsorbtion apharesis she was started on venetoclax plus rituximab with ramp-up. Sustained response was achieved within the first week of venetoclax therapy. (Figure Presented ) Summary/Conclusion: Gordon et al. reported 2 CLL cases one with ITP and other with Evans syndrome successfully treated with venetoclax. We think, this treatment should be considered in patients with refractory immune cytopenias secondary to CLL and assessed with prospective clinical trials.

Investigation of descriptive characteristics of randomized controlled trials of COVID-19 vaccines

INTRODUCTION: The aim of this study was to examine the descriptive characteristics of randomized controlled trials published in PubMed on COVID-19 vaccines until May 30, 2021. METHODS: Seventy three articles reached by scanning the keywords "vaccine" and "COVID 19" in the PubMed database were reviewed by researchers, 33 randomized controlled trials (RCTs) related to COVID 19 vaccines were included in the study. According to the 17-item questionnaire created by the researchers, the descriptive features of included studies were examined. RESULTS: The total number of investigative authors in 33 RCT articles published in approximately one and a half years from the outbreak of the pandemic was 946, and the average number of authors per article was 28.67+or-18.56.39.3% of the articles were published in The Lancet and 27.2% in The New England Journal of Medicine. Of the vaccines used in the studies, 36.3% mRNA vaccine, 21.2% Inactivated vaccine, 18.1% Recombinant adenovirus vaccine, 12.1% Chimpanzee adenovirus-based vector vaccine, 6% BCG vaccine. 22.5% of vaccines are Phase 1, 12.9% Phase 2, 19.3% Phase 3, 3.2% Phase 4, 32.3% Phase 1-2, 9%,6 of them are Phase 2-3 studies. DISCUSSION AND CONCLUSION: The majority of randomized controlled trials on COVID-19 vaccines are phase 1 and phase 2 trials for mRNA vaccines and inactivated vaccines. Studies have generally been conducted on the adult age group and studies are needed to evaluate the effect of vaccines on the pediatric age group. In studies, the safety of vaccines has been examined more, and there is limited information on efficacy and effectiveness of vaccines.

Ileal rhabdomyosarcoma in a patient with a history of squamous cell lung cancer

Rhabdomyosarcoma is an infrequent muscular cancer seen in adults. We present a case of ileal intussusception due to pleomorphic rhabdomyosarcoma in a patient diagnosed previously with squamous cell carcinoma of the lung (SCCL). The patient was a 68-year-old man with a history of SCCL. He was admitted to the emergency department for nausea, emesis and obstipation. Surgical investigation of the abdomen revealed an intussusception caused by a tumour located 160cm distal of the ligament of Treitz. Pathological examination showed that tumour was a primary rhabdomyosarcoma of the ileum. This case contributes to the literature by defining an infrequent presentation of rhabdomyosarcoma causing ileal intussusception in an adult patient.

Phase Ib study of the safety and efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in patients with relapsed or refractory CD33+ acute myeloid leukemia: Big Ten Cancer Research Consortium BTCRC-AML17-113

Background:AML is predominantly a disease of the elderly, yet outcomes remain dismal, particularly for relapsed/refractory (R/R) AML patients (pts). Gemtuzumab Ozogamicin (GO) is a monoclonal antibody targeting CD33-commonly expressed on AML blasts, and, critically, AML stem cells (LSC)-linked to the cytotoxin calicheamicin. GO resistance mechanisms include (i) decreased/aberrant blast CD33 expression, (ii) p-glycoprotein export of calicheamicin, and (iii) apoptosis resistance due to deficient activation of mitochondrial outer membrane permeabilization, a process highly dependent on BCL-2 expression. GO-induced apoptosis depends on the pro-apoptotic proteins Bax and Bak and is inhibited by overexpression of the anti-apoptotic proteins BCL-2 or BCL-XL. Venetoclax (VEN) is a BH3 mimetic, binding BCL-2, dislodging its binding to Bak/Bax, and thus facilitating apoptosis. LSC overexpress BCL-2, however VEN monotherapy is not effective in AML, as resistance develops rapidly. Hypothesis: VEN targeting of BCL-2 proteins that protect LSC from GO-induced apoptosis will synergistically increase GO efficacy. Correlative studies include pre-treatment AML blast BH3 profiling, CD33 expression (including sequencing for isoforms), and BCL-2, BCL-XL, and MCL-1 protein levels;MRD measurement at post-therapy time points using digital drop PCR technology;and quality of life assessments (EORTC QLQ-C30, FACT-Fatigue) MethodsThis is a single arm, open-label, multi-center (BTCRC), dose-escalation phase Ib study of combination of VEN and GO in R/R AML pts (18-75y), using a 3+3 design. Major eligibility: ECOG 0-2, adequate organ function, CD33+ in ≥ 20% AML blasts, ≤ 3 lines of prior therapy, and no prior use of GO or VEN, previous VOD, BMT within 2 months, CNS disease, or history of HIV. Induction: 3-day VEN ramp-up to the target dose of 200 (cohort i), 400 (ii), or 600 (iii) mg daily x 28 d, with GO 3mg/m2 infused days 1, 4, and 7. If CR/CRi achieved, pts proceed to BMT if applicable, otherwise, if in CR/CRi (provided ANC > 1000, plts > 100K) or PR (regardless of counts), they are consolidated with VEN at the prescribed dose x 28d and GO 3mg/m2 on days 1 and 4 (Cycle 2). If BMT not applicable, and pt remaining in CR/CRi or PR (as above), then proceed to VEN alone as Maintenance in cycles 3+ until progression or toxicity. The primary endpoint is MTD of VEN with GO. Secondary endpoints include ORR, antileukemic activity, characterization of AEs, and estimates of RFS, EFS, and OS. Progress: This study is currently open to its second dosing cohort and has enrolled 5 pts to date. No dose-limiting toxicities have been encountered. However, the COVID-19 pandemic has had a negative impact on enrollment, which is expected to improve as vaccinations expand. ClinicalTrials.gov NCT04070768.

A survey analyzing reflections of COVID-19 on patients and their relatives

Aim: In this study, we aimed to analyze the level of knowledge about Coronavirus disease-2019 (COVID-19) in patients and their relatives presented to the emergency department. Methods: In this study, a 25-item questionnaire was applied to patients and their relatives. The participants were stratified into three groups as primary-secondary school, high school or university graduation. The responses were analyzed among education groups at a significant level of p<0.05. Results: In this study, of the 212 participants, 62.7% were male. The proportion of the participants thinking “COVID-19 also affected younger individuals” was higher in participants having an education level of high school or higher (p=0.009). The willingness to receive the vaccine was significantly high among all education levels. The idea that traditional soups and gargling with salty water prevent disease was found to be more common among participants with an education level of high school or lower (p<0.05). The benefit from the opinion of the expert on media about protection against the virus was significant in participants with an education level below high school (p<0.05). Conclusion: The revision of key messages of public health specialists according to education levels will have an important role in reorganizing inaccurate knowledge in the community. © Copyright 2021 by The Medical Bulletin of Istanbul Haseki Training and Research Hospital The Medical Bulletin of Haseki published by Galenos Yayinevi.