World Health Organization Score Research Articles

6479 Acute Estradiol and Progesterone Therapy In Hospitalized Adults With Moderate COVID-19: A Randomized Control Trial

Abstract Disclosure: D. Lovre: Research Investigator; Self; Novo Nordisk, Corcept Therapeutics. K.M. Bateman: None. L.Y. Saltzman,: None. M. Qadir: None. F. Mauvais-Jarvis: None. Background and Objective: COVID-19 outcomes are less severe in women vs men. Experimental studies show that estradiol (E2) and progesterone (P4) produce anti-inflammatory immune responses and immune tolerance and enhance antibody production. The effect of E2 and P4 combination on COVID-19 severity is unknown. The aim of the study was to evaluate the efficacy of a short systemic E2/P4 combination in mitigating COVID-19 severity in hospitalized men and women. Methods: Phase 2, double blind, placebo-equivalent controlled, single center trial of ten participants (men and women) who were hospitalized for COVID-19, with scores 3 to 5 on the 9-point World Health Organization (WHO) ordinal scale for clinical improvement. Participants were randomized into two arms and treated for five days: 1) E2 Cypionate (5 mg IM once) and micronized P4 (200mg, PO daily); and 2) Placebo-equivalent (normal saline (1ml, IM once) and folate (400mcgs, PO daily), in addition to standard of care (SOC). The primary outcome was the proportion of patients improving to scores 1 or 2 on the WHO scale on the day of discharge. Secondary outcomes included length of hospital stay (LOS), days on oxygen therapy (DOT), readmission rates (RR), adverse events (AEs) and change in inflammatory biomarkers assessed by untargeted proteomics. Findings: There were no significant differences between the treatment groups in COVID-19 severity by WHO score, LOS, DOT, RR or AEs. Patients in the E2/P4 arm exhibited a decrease in inflammatory biomarkers of respiratory and gastrointestinal disease (GI) and significant change in immune and inflammatory responses. Conclusions: Use of short-term systemic E2/P4 is associated with decrease in biomarkers of respiratory and GI disease inflammation and change in biomarkers of immune and inflammatory response. Presentation: 6/3/2024

A randomized single-blind non-inferiority trial of delayed start with drospirenone-only and ethinyl estradiol-gestodene pills for ovulation inhibition

We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18–45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and − 0.11 (95% CI: − 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7–9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001.

Toxicity in Older Patients with Cancer Receiving Immunotherapy: An Observational Study.

Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status. This study aims to investigate the association between clinical frailty and immune-related treatment toxicity, hospitalization, and treatment discontinuation due to immune-related treatment toxicity in older patients treated with checkpoint inhibitors. Patients aged 70years and older treated with checkpoint inhibitors were selected from the TENT study, IMAGINE study, and "Tolerability and safety of immunotherapy study". Clinical frailty was assessed by the Geriatric-8 test score and World Health Organization (WHO) status. Outcomes were grades 3-5 toxicity, hospitalization, and treatment discontinuation due to toxicity during treatment. Of 99 patients included, 22% had comorbidities. While 33% of the patients were considered frail based on an abnormal Geriatric-8 test score of <15, physical impairments were considered absent in 51% (WHO score of 0) and mild in 40% (WHO score of 1). Despite the limited sample size of the cohort, consistent trends were observed with patients with an abnormal Geriatric-8 test score of <15 or a higher WHO score of 1 for having higher odds of toxicity [odds ratio (OR) 2.32 (95% CI 0.41-13.02); OR 1.33 (95% CI 0.45-4.17)], treatment discontinuation due to immune-related treatment toxicity [OR 2.25 (95% CI 0.61-8.31); OR 2.18 (95% CI 0.7-6.73)], and hospitalization due to immune-related treatment toxicity [OR 3.72 (95% CI 0.39-35.4); OR 1.31 (95% CI 0.35-4.9)]. Moreover, in a sub-analysis, we observed that the treatment discontinuation due to immune-related treatment toxicity occurred often in patients with grade 1-2 toxicity as well. Although not statistically significant, in older patients treated with immunotherapy in a real-life population with cancer, we observed consistent trends towards increased toxicity, hospitalization, and treatment discontinuation with increasing frailty. Larger studies are needed to confirm these exploratory results. Moreover, older patients with a lower toxicity grade 1-2 experienced early treatment discontinuation frequently, suggesting a lower tolerance of toxicity.

High-risk subgroups were not identified to benefit from thromboprophylaxis after hospitalization for COVID-19

BackgroundThe Accelerating COVID-19 Therapeutic Interventions and Vaccines-4c (ACTIV-4c) trial investigated prophylactic apixaban for 30 days following hospitalization for COVID-19. The overall incidence of early postdischarge death or thromboembolism was low, and the trial was closed early. ObjectivesTo identify a high-risk patient population who might benefit from postdischarge thromboprophylaxis through subgroup analyses stratified by age, race/ethnicity, obesity, D-dimer elevation, World Health Organization score, and modified International Medical Prevention Registry on Venous Thromboembolism score on 30-day composite outcome of all-cause death, arterial thromboembolism (ATE), and venous thromboembolism (VTE). MethodsCumulative incidences of all-cause death, ATE, and VTE within 30 days were described for each subgroup. Time to death, ATE, or VTE by 30 days was analyzed using Cox proportional hazard models with interaction testing for each subgroup. ResultsAmong 1217 patients randomized to apixaban or placebo group, 32% were >60 years old. Modified International Medical Prevention Registry on Venous Thromboembolism score was ≥4 in 2% and 2 or 3 with an elevated D-dimer in an additional 9% of participants. The overall incidence of the primary endpoint was 2.13% in the apixaban group and 2.31% in the placebo group. At day 30, similar rates of the primary endpoint occurred within subgroups, except for participants aged >60 years. No benefit of thromboprophylaxis was seen in any subgroup. ConclusionThe combined incidence of 30-day death, ATE, and VTE was low in patients who survived COVID-19 hospitalization, except in patients over age 60 years. Due to the limited number of events, the findings remain inconclusive; nonetheless, the study did not identify a high-risk subgroup that would derive benefits from extended thromboprophylaxis.

Analysis of clinical characteristics and treatment efficacy in two pediatric cases of ANKRD26-related thrombocytopenia

ANKRD26-related thrombocytopenia (ANKRD26-RT or THC2, MIM 188 000), an autosomal dominant thrombocytopenia, is unresponsive to immunosuppressive therapy and susceptible to hematological malignancies. A large number of pediatric patients are diagnosed with immune thrombocytopenia (ITP) every year; however, thrombocytopenia of genetic origin is often missed. Extensive characterization of ANKRD26-RT will help prevent missed diagnosis and misdiagnosis. Furthermore, identification of ANKRD26-RT will help in the formulation of an accurate diagnosis and a treatment plan. In our study, we report cases of two Chinese pediatric patients with ANKRD26-RT and analyze their clinical characteristics, gene mutations, and treatment modalities. Both patients were 1-year-old and presented with mild bleeding (World Health Organization(WHO) score grade 1), different degrees of platelet reduction, normal mean platelet volume, and megakaryocyte maturation impairment not obvious. Genetic tests revealed that both patients had ANKRD26 gene mutations.Patient 1 had a mutation c.-140C>G of the 5’ untranslated region (UTR), and patient 2 had a mutation of c.-127A>T of 5’UTR. Both patients were treated with eltrombopag, and the treatment was no response, with no adverse reactions.

Unveiling sex-based impact of TYK2 rs2304256 polymorphism on interferon beta-1alpha responsiveness in COVID-19 patients

Interferon beta-1a was one of the medications suggested by the World Health Organization in the COVID-19 therapy protocol in early 2020. IFNb-1a has previously been used to treat symptoms in multiple sclerosis patients. Previous studies have revealed that TYK2 and HLA genes play crucial roles in immune responses. The current study examined the relationship between TYK2 rs2304256, HLA-DQA1 rs9272105, and rs1448673 and the therapeutic response to IFNb-1a in COVID-19 patients from Kurdish ethnicity. A total of 124 patients with mild COVID-19 were included in this study. These patients received three injections of IFNb-1a every other day. The severity of COVID-19 symptoms and treatment response was determined using the World Health Organization (WHO) scoring method. Changes in WHO scores were assessed after five days, and patients with a difference of <0 were classified as responders (n = 74), whereas those with a difference of 0 or >0 were considered non-responders (n = 50). PCR techniques were used to genotype polymorphisms. The AG rs9272105 genotype reduced the treatment response (codominant model, OR = 0.37, P = 0.027; overdominant model, OR = 0.33, P = 0.011). Stratification by sex revealed that the AC and CC genotypes of rs2304256 reduced response to treatment in female and male patients, (p < 0.05), respectively. The rs2304256 and rs9272105 polymorphisms may play a role in the response to IFNb-1a treatment in COVID-19 patients.

Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial

ObjectiveTo evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial).DesignOpen label, randomised clinical trial.SettingCORIMUNO-19 cohort...

Point-of-Care Ultrasonography for the Assessment of Dehydration in Children: A Systematic Review.

Accurate estimation of the degree of dehydration remains a diagnostic challenge. The primary objective was to systematically review the literature on the role of ultrasound in assessment of the degree of dehydration in children. Data sources included Ovid MEDLINE, Web of Science Core Collection, Current Index to Nursing and Allied Health Literature, Cochrane Library, ClinicalTrials.gov , and Trip Pro Database. Two independent reviewers used screening protocol to include articles on assessment of dehydration in children with the use of point-of-care ultrasonography (POCUS). The level of evidence was assessed in accordance with the "The Oxford 2011 Levels of Evidence." The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate risk of bias. We identified 108 studies, and 8 studies met our inclusion criteria. All studies were prospective cohort studies (level of evidence, 3-4). The authors of 5 studies used difference between ill weight and weight after rehydration as the reference standard for dehydration, and the authors of 3 studies used clinical dehydration scale. Two studies from the United States showed acceptable areas under the curve for inferior vena cava to aorta (IVC/Ao) diameter ratio at 0.72 and 0.73 for prediction of significant dehydration (>5% weight loss). The IVC/Ao ratio with cut-off at 0.8 had sensitivity of 67% and 86% and specificity of 71% and 56% for prediction of significant dehydration. Studies from the resource-limited settings were more heterogeneous. One study with acceptable risk of biases reported poor sensitivity (67%) and specificity (49%) of Ao/IVC ratio with cut-off of 2.0 for predicting severe dehydration (>9% weight loss) with area under the curve at 0.6. Three studies showed increase in IVC diameter with fluid resuscitation with mean change in IVC diameter by 30% in children with significant dehydration (>5% weight loss) and by 22% without significant dehydration (<5% weight loss). Metaanalysis was not completed due to high heterogeneity. This study showed that the quantity and quality of research on the application of POCUS for the assessment of dehydration in children is limited. There is no criterion standard for assessing the degree of dehydration and no universal definition of the degree of dehydration. Thus, more methodologically rigorous studies are required. Current systematic review does not support the routine use of US to determine the severity of dehydration in children. Despite these limitations, the use of POCUS in children with dehydration demonstrates potential. Given the clear increase in IVC size with rehydration, repeated IVC US scans may be helpful in guiding fluid resuscitation in children with dehydration. From different proposed US parameters, IVC/Ao ratio has better diagnostic accuracy in detecting significant dehydration than Ao/IVC ratio and IVC collapsibility index. Despite low to moderate diagnostic performance, US still showed better assessment of dehydration than physician gestalt and World Health Organization score.

Acute Lymphoblastic Leukemia (B-ALL) with co-expression of CD33 and CD13

Link of Video Abstract: https://www.youtube.com/watch?v=AC472eZBXII Background: Most acute leukemias can be classified into myeloid or lymphoid strains based on the expression of several specific phenotypes. However, some cases of acute leukemia express both phenotypes (myeloid and lymphoid phenotypes). To establish the diagnosis of acute leukemia with co-expression of myeloid markers or mixed phenotype acute leukemia (MPAL), we need a system that can differentiate between the two, namely by using the scoring system from The European Group for the Immunological Characterization of Leukemias (EGIL) and The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues 2016. Case Presentation: A 10-year-old boy was admitted to the hospital because of repeated nosebleeds for 3 weeks before entering the hospital. Patients also complain of decreased appetite, nausea, vomiting, and joint pain. On physical examination, anemic conjunctiva was found, and no abnormalities were found on other physical examinations. Hemoglobin examination: 8.2 g/dl, leukocytes 112.10×103/µl, platelets 10×103/µl. Examination of peripheral blood smear: acute lymphoblastic leukemia. Examination results of bone marrow aspiration acute lymphoblastic leukemia (ALL L1). Immunophenotype analysis found blast cells with positive expression for CD34, CD79a, CD10, HLA-DR, CD33 and CD13. Conclusion: The diagnosis in this patient was B-ALL with myeloid marker co-expression based on the EGIL and WHO scoring systems.

Gestational Trophoblastic Neoplasia—A Retrospective Analysis of Patients Treated at a Tertiary Care Oncology Center in North India

Objectives The aim of this study was to do a retrospective analysis of patients of gestational trophoblastic neoplasia (GTN) treated at our center concerning their clinical features and treatment outcomes. Materials and Methods Patients diagnosed and treated from May 2018 to December 2021 were included. All relevant information pertaining to eligible patients was retrieved from the electronic medical records. Patients were risk-stratified based on the World Health Organization (WHO) risk scoring system with a score of seven and above being classified into the high-risk category. Patients were monitored for response by measuring β-human chorionic gonadotrophin (β-HCG) levels before each consecutive cycle. Statistical Analysis Appropriate statistical analysis was performed using SPSS version 26. Results Records of 39 eligible patients were analyzed for clinical features out of which 38 were eligible for response assessment. The median age of presentation was 28 years with the majority of patients (79.4%) diagnosed based on β-HCG levels and clinical history alone. The most common symptom was bleeding per vagina (64%), while the majority of antecedent pregnancies were abortions (59%).Of the 14 low-risk category patients, 12 received single-agent methotrexate/actinomycin D, while 2 received etoposide, methotrexate actinomycin D (EMACO) regimen. Overall response rates were 85.7% with the others responding to the second-line EMACO regimen. Five patients in this group had a WHO score of 5 or 6 and all of them responded to single-agent treatment. Among the 25 high-risk category patients, all received the EMACO regimen with high-dose methotrexate added to those with brain metastasis. The response rate was 87.5% with all the nonresponders having features of ultra-high risk of liver/brain metastasis and/or a WHO score of more than 12. While one nonresponder had expired despite treatment, the other two responded to the etoposide methotrexate and actinomycin D/ etoposide and cisplatin regimen. Conclusion Our results are in consonance with other reported studies. The subcategories of low-risk GTN with a WHO score of 5 and 6 and high-risk GTN with ultra-high-risk features deserve further research in the form of multicenter prospective studies.

Remdesivir Use in Pediatric Patients for SARS-CoV-2 Treatment: Single Academic Center Study.

Millions of children in the United States have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many infections leading to hospitalization. For pediatric patients, especially younger children, treatment options are limited. Remdesivir has demonstrated a positive safety and efficacy profile in adults, but little data is published regarding remdesivir use in pediatric patients. Additional data for SARS-CoV-2 treatments in pediatric patients is required to prevent further SARS-CoV-2-related morbidity and mortality. At a single pediatric academic medical center, the safety and efficacy of remdesivir was evaluated. A retrospective review of patients admitted to a pediatric academic medical center who received remdesivir over a 17-month period was completed. All pediatric patients who received at least 1 dose of remdesivir were included. Safety and efficacy were assessed using national organization's definitions of clinical improvement, bradycardia, hypertension, acute kidney injury and drug-induced liver injury. There were 48 pediatric patients included in this study with 29% of patients admitted to the pediatric intensive care unit. Less than one-third of patients received the full treatment course of remdesivir, with over half of patients not completing therapy due to symptomatic improvement or hospital discharge. Majority of patients required some level of supplemental oxygen support. The median World Health Organization score was consistent throughout all 5 days of therapy. No patients experienced significant bradycardia, hypertension, acute kidney injury, or drug-induced liver injury. Remdesivir may correlate with clinical stability or improvement and demonstrates safety when used in pediatric patients. A randomized controlled trial is needed to confirm these findings.

Anti-PF4 antibodies associated with disease severity in COVID-19

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.

Diagnostic performance of lactate dehydrogenase (LDH) isoenzymes levels for the severity of COVID-19.

Lactate dehydrogenase (LDH) levels predict coronavirus disease 2019 (COVID-19) severity. We investigated LDH isoenzyme levels to identify the tissue responsible for serum LDH elevation in patients with COVID-19. Hospitalised COVID-19 patients with serum LDH levels exceeding the upper reference limit included. LDH isoenzymes were detected quantitatively on agarose gels. The radiological severity of lung involvement on computed tomography was scored as 0-5 for each lobe (total possible score, 0-25). Disease severity was determined using the World Health Organization (WHO) clinical progression scale. In total, 111 patients (mean age, 59.96 ± 16.14), including 43 females (38.7%), were enrolled. The serum levels of total LDH and all five LDH isoenzymes were significantly higher in the severe group. The levels of all LDH isoenzymes excluding LDH5 positively correlated with the WHO score. LDH3 levels correlated with chest computed tomography findings (r2 = 0.267, p = 0.005). On multivariate analysis, LDH3 was an independent risk factor for the deterioration of COVID-19. LDH3 appears to be an independent risk factor for deterioration in patients with COVID-19. LDH elevation in patients with COVID-19 predominantly resulted from lung, liver and muscle damage.

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Clinical presentation and outcomes of chronic dialysis patients with COVID-19: A single center experience from Greece

BACKGROUNDCoronavirus disease 2019 (COVID-19) is still a menacing pandemic, especially in vulnerable patients. Morbidity and mortality from COVID-19 in maintenance hemodialysis (MHD) patients are considered worse than those in the general population, but vary across continents and countries in Europe. AIMTo describe the clinical course and outcomes of hospitalized MHD patients with COVID-19 in a retrospective observational single center study in Greece. METHODSWe correlated clinical, laboratory, and radiological data with the clinical outcomes of MHD patients hospitalized with COVID-19 during the pandemic. The diagnosis was confirmed by real-time polymerase chain reaction. Outcome was determined as survivors vs non-survivors and “progressors” (those requiring oxygen supplementation because of COVID-19 pneumonia worsening) vs “non-progressors”.RESULTSWe studied 32 patients (17 males), with a median age of 75.5 (IQR: 58.5-82) years old. Of those, 12 were diagnosed upon screening and 20 with related symptoms. According to the World Health Organization (WHO) score, the severity on admission was mild disease in 16, moderate in 13, and severe in 3 cases. Chest computed tomography (CT) showed 1-10% infiltrates in 24 patients. Thirteen “progressors” were recorded among included patients. The case fatality rate was 5/32 (15.6%). Three deaths occurred among “progressors” and two in “non-progressors”, irrespective of co-morbidities and gender. Predictors of mortality on admission included frailty index, chest CT findings, WHO severity score, and thereafter the increasing values of serum LDH and D-dimers and decreasing serum albumin. Predictors of becoming a “progressor” included increasing number of neutrophils and neutrophils/lymphocytes ratio.CONCLUSIONPatients on MHD seem to be at higher risk of COVID-19 mortality, distinct from the general population. Certain laboratory parameters on admission and during follow-up may be helpful in risk stratification and management of patients.

Long-Term Outcomes After Percutaneous Transluminal Pulmonary Angioplasty in Patients With Takayasu Arteritis and Pulmonary Hypertension.

ObjectiveTo investigate the long-term efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) in patients with Takayasu arteritis (TA) and pulmonary artery stenosis and pulmonary hypertension (PH).MethodsData from 183 lesions from 79 surgeries performed on 32 patients with TA and PH were analyzed. Symptoms, laboratory investigation results, World Health Organization (WHO) functional class, 6-min walk distance (6 MWD), hemodynamic parameters, and prognosis were analyzed at baseline and follow-up.ResultsThe mean (± SD) age of the 32 patients (28 female, 4 male) was 42.8 ± 11.9 years, and the median follow-up was 49.5 months (interquartile range, 26–71 months). Compared with baseline, changes in total bilirubin, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, 6 MWD, and WHO score functional class demonstrated significant differences (P<0.001). Echocardiography findings, right and left ventricular diameter, tricuspid annular plane systolic excursion, and estimated pulmonary artery systolic pressure were all improved (P=0.016, P<0.001, P<0.001, and P=0.005, respectively). Importantly, repeat right heart catheterization revealed that mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac index also improved significantly at follow-up (P<0.001, P<0.001, and P=0.011, respectively). Pulmonary angiography revealed post-procedure restenosis in 64 (35.0%) lesions underwent PTPA within three to six months. Among three patients who underwent stent implantation, one experienced restenosis. Two patients died during the follow-up period, one from aggravation of right heart failure after lung infection, and the other in a traffic accident.ConclusionsResults of this study indicated that PTPA significantly improved clinical symptoms, exercise tolerance, and hemodynamic parameters in patients with TA pulmonary artery stenosis and PH. More importantly, reperfusion pulmonary edema significantly decreased, and no patient died of PTPA-related complications with guidance from the pressure wire.

Inducible Nitric Oxide Synthase (iNOS): Why a Different Production in COVID-19 Patients of the Two Waves?

Profound clinical differences between the first and second waves of COVID-19 were observed in Europe. Nitric oxide (NO) may positively impact patients with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection. It is mainly generated by inducible nitric oxide synthase (iNOS). We studied serum iNOS levels together with serum interleukin (IL)-6 and IL-10 in patients with SARS-CoV-2 infection in the first wave (n = 35) and second wave (n = 153). In the first wave, serum iNOS, IL-6, IL-10 levels increased significantly, in line with the World Health Organization (WHO) score severity, while in the second wave, iNOS did not change with the severity. The patients of the second wave showed lower levels of iNOS, IL-6, and IL-10, as compared to the corresponding subgroup of the first wave, suggesting a less severe outcome of COVID-19 in these patients. However, in the severe patients of the second wave, iNOS levels were significantly lower in patients treated with steroids or azithromycin before the hospitalization, as compared to the untreated patients. This suggests an impairment of the defense mechanism against the virus and NO-based therapies as a potential therapy in patients with low iNOS levels.

Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19

COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.

Randomized controlled study to evaluate the impact of flexible patient-controlled visits in people with type 1 diabetes: The DiabetesFlex Trial.

The objective of this study was to assess the impact of health care-initiated visits versus patient-controlled flexible visits on clinical and patient-reported outcomes in people with type 1 diabetes. The DiabetesFlex trial was a randomized controlled, pragmatic non-inferiority 15-month follow-up study comparing standard care (face-to-face visits every 4months) with DiabetesFlex (patient-controlled flexible visits using patient-reported, outcome-based telehealth follow-up). Of 343 enrolled participants, 160 in each group completed the study. The primary outcome was mean change in HbA1c from baseline to 15-month follow-up. Secondary outcomes were blood pressure, lipid levels, frequency of visits, the World Health Organization score-five well-being-index (WHO-5), the Problem Areas In Diabetes (PAID) scale and experience of participation in own care (participation score). The adjusted mean difference in HbA1c between standard care and DiabetesFlex was similar and below the predefined non-inferiority margin of 0.4% (-0.03% [95%CI: 0.15, 0.11]/-0.27mmol/mol [-1.71, 1.16]). No intergroup mean changes in lipid or blood pressure were observed. Conversely, DiabetesFlex participants presented an increased mean WHO-5 index of 4.5 (1.3, 7.3), participation score of 1.1 (0.5, 2.0), and decreased PAID score of -4.8 (-7.1, -2.6) compared with standard care. During follow-up, DiabetesFlex participants actively changed 23% of face-to-face visits to telephone consultations, cancelled more visits (17% vs. 9%), and stayed away without cancellation less often (2% vs. 8%). Compared with standard care, flexible patient-controlled visits combined with patient-reported outcomes in participants with metabolic controlled type 1 diabetes and good psychological well-being further improved diabetes-related well-being and decreased face-to-face visits while maintaining safe diabetes management.

Cytoreductive Surgery and Intraperitoneal Chemotherapy in Advanced Serous Epithelial Ovarian Cancer: A 14-Year French Retrospective Single-Center Study of 124 Patients.

Ovarian cancer (OC) is the most lethal gynecological cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy appears to increase survival, and normothermic intraperitoneal chemotherapy (IPC) could improve overall survival (OS). Furthermore, intraperitoneal epinephrine could decrease the toxicity of chemotherapy by decreasing the systemic absorption of chemotherapy. The goal of this study was to assess the effects of CRS and IPC with intraperitoneal epinephrine, as first-line therapy, on the survival of patients with serous epithelial OC (EOC) with peritoneal metastases. A prospective monocentric database was retrospectively searched for all patients with advanced serous EOC treated by interval or consolidative CRS plus IPC with intraperitoneal epinephrine after neoadjuvant chemotherapy. OS and disease-free survival (DFS), postoperative complications, and prognostic factors were analyzed. From January 2003 to December 2017, 124 patients with serous EOC were treated with interval (n = 58) or consolidative (n = 66) complete CRS plus IPC with intraperitoneal epinephrine. The median follow-up was 77.8 months, the median OS was 60.8 months, and the median DFS was 21.2 months. In our multivariate analysis, a higher Peritoneal Cancer Index (PCI) and positive lymph node status resulted in worse OS, while higher World Health Organization score, higher PCI score, and positive lymph node status were risk factors for worse DFS. Grade 3 or higher surgical morbidity occurred in 27.42% of cases; only 3.2% had grade 3 renal toxicity and mortality was 0.8%. CRS and IPC with intraperitoneal epinephrine in stage III EOC offer good OS and DFS with acceptable morbidity and mortality rates.