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).

Mesenchymal Stem/Stromal Cells: HUMAN MESENCHYMAL STEM CELL THERAPY IN SEVERE COVID-19 PATIENTS: 2-YEAR FOLLOW-UP RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background & Aim: The long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods, Results & Conclusion(s): A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4x107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. The outcomes measured included: 6-minute walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire, COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, MSC-related adverse events (AEs), and tumor markers. Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). On the SF-36 questionnaire, a marginally higher general health score was received by the MSC group at month 18 compared with the placebo group (50.00 vs. 35.00;95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.016). In contrast, there were no differences in the total severity score of lung imaging or the titer of neutralizing antibodies between the two groups. Meanwhile, there were no MSC-related AEs reported at the 18- or 24-month follow-ups. The serum levels of most of the tumor markers examined remained within normal ranges and were similar between the MSC and placebo groups. Long-term safety was observed for the COVID-19 patients who received MSC treatment. Yet few sustained efficacy of MSC treatment was observed at the end of the 2-year follow-up period. Funding(s): The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRCID202105,413FZT6). [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

A dePEGylated Lipopeptide-Based Pan-Coronavirus Fusion Inhibitor Exhibits Potent and Broad-Spectrum Anti-HIV-1 Activity without Eliciting Anti-PEG Antibodies.

We previously identified a lipopeptide, EK1C4, by linking cholesterol to EK1, a pan-CoV fusion inhibitory peptide via a polyethylene glycol (PEG) linker, which showed potent pan-CoV fusion inhibitory activity. However, PEG can elicit antibodies to PEG in vivo, which will attenuate its antiviral activity. Therefore, we designed and synthesized a dePEGylated lipopeptide, EKL1C, by replacing the PEG linker in EK1C4 with a short peptide. Similar to EK1C4, EKL1C displayed potent inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses. In this study, we found that EKL1C also exhibited broad-spectrum fusion inhibitory activity against human immunodeficiency virus type 1 (HIV-1) infection by interacting with the N-terminal heptad repeat 1 (HR1) of viral gp41 to block six-helix bundle (6-HB) formation. These results suggest that HR1 is a common target for the development of broad-spectrum viral fusion inhibitors and EKL1C has potential clinical application as a candidate therapeutic or preventive agent against infection by coronavirus, HIV-1, and possibly other class I enveloped viruses.

Ventilation dynamics using a portable device coupled to the six-minute walk test in people with long-COVID syndrome: a preliminary study.

OBJECTIVE: To investigated the dynamic ventilatory responses and their influence on functional exercise capacity in patients with long-COVID-19 syndrome (LCS). RESULTS: Sixteen LCS patients were subjected to resting lung function (spirometry and respiratory oscillometry-RO) and cardiopulmonary performance to exercise (Spiropalm®-equipped six-minute walk test-6MWT and cardiopulmonary exercise test-CPX). At rest, spirometry showed a normal, restrictive and obstructive pattern in 87.5%, 6.25% and 6.25% of participants, respectively. At rest, RO showed increased resonance frequency, increased integrated low-frequency reactance and increased difference between resistance at 4-20 Hz (R4-R20) in 43.7%, 50%, and 31.2% of participants, respectively. The median of six-minute walking distance (DTC6) was 434 (386-478) m, which corresponds to a value of 83% (78-97%) of predicted. Dynamic hyperinflation (DH) and reduced breathing reserve (BR) were detected in 62.5% and 12.5% of participants, respectively. At CPX, the median peak oxygen uptake (VO2peak) was 19 (14-37) ml/kg/min. There was a significant correlation of 6MWD with both R4-R20 (rs=-0.499, P = 0.039) and VO2peak (rs=0.628, P = 0.009). Our results indicate that DH and low BR are contributors to poor exercise performance, which is associated with peripheral airway disease. These are promising results considering that they were achieved with simple, portable ventilatory and metabolic systems.

Resiliency among Older Adults Receiving (Roar) Lung Cancer Treatment: A Feasibility Study

PURPOSE/HYPOTHESIS: Poor physical performance and negative mood are two risk factors for functional decline among older adults with lung cancer. Yet, targeted interventions to maintain independence prevent functional decline are not well studied. Our primary objective was to assess the feasibility of a novel virtual health physical therapy (PT) plus progressive muscle relaxation (PMR) intervention with longitudinal microbiome biospecimen collection delivered to older adults with advanced lung cancer. Secondary objectives were to characterize functional status and clinical factors pre and post-study intervention. NUMBER OF SUBJECTS: We accrued adults aged >=60 years with advanced non-small cell or extensive-stage small cell lung cancer receiving treatment at The Ohio State University James Comprehensive Cancer Center (OSU-JCCC) in the Thoracic Oncology department (N=22). There were no exclusion criteria pertaining to Eastern Cooperative Oncology Group (ECOG) performance status, laboratory values, prior cancer diagnoses, presence of comorbidities, or brain metastases. MATERIALS AND METHODS: Participants were asked about functional status, symptoms, mood through the PHQ-9, GAD-7, POMS, and acceptability questions about the program. PT evaluation and assessment included SPPB and 2- or 6-minute walk test outcomes. The study sought to collect gut microbiome samples for every in-person visit and activity monitoring data (Actigraph) on a subset. Feasibility was defined as successfully collecting specimens, wearing an Actigraph activity monitor, and adhering to the intervention. PT and psychologists evaluated participants in-person at the first and final visit. The rest of the 12-week intervention was conducted via virtual health. Physical therapy intervention consisted of endurance, strength, and flexibility exercises. RESULT(S): In total, 22 patients consented and 18 started the intervention (81.8%). Seven microbiome samples were collected from four participants. Six patients collected activity monitoring data. Among the 18 participants, 11 participants (61.1%) completed 70% or more of all the intervention visits. The SPPB data show a moderate effect size (Cohen's d=0.24) from pre- to post-data. On average patients improved by 1.8 total points on the SPPB. Patients demonstrated improvement on timed walk tests throughout intervention from an average of 108 feet pre-intervention to an average of 138.4 feet post intervention. CONCLUSION(S): Despite the challenges of the COVID-19 pandemic, longitudinal biospecimen and correlative data collection were feasible in the context of PT and PMR intervention among older adults with advanced lung cancer. Virtual physical therapy interventions can be safely delivered to improve physical performance as demonstrated by a moderate effect size for the SPPB in this patient population. CLINICAL RELEVANCE: Based on the feasibility study results, delivering a virtual PT intervention to older patients with lung cancer can improve SPPB score leading to decreased frailty and improve quality of life among patients.

Posterior Mediastinal Mass: Unraveling a Non-Traumatic Herniation of the Caudate Lobe of the Liver

Introduction: Posterior mediastinal mass is most likely due to neurogenic tumor, meningocele or thoracic spine lesions. Caudate lobe of the liver herniation presenting as posterior mediastinal mass is a rare occurrence. Diaphragmatic herniation (DH) of the caudate lobe presents in various way including dyspnea, dyspepsia or incidental finding on imaging. We present a case of diaphragmatic hernia of the caudate lobe of the liver presenting as a posterior mediastinal mass found during evaluation of dyspnea. Case Description/Methods: A 75-year-old female presented to her physician with worsening shortness of breath from her baseline of 3 days duration. She had a history of sarcoidosis, COVID pneumonia over 1 year ago, COPD, diastolic heart failure, and hypertension. She was initially evaluated for COVID re-infection, which was negative and a CT of the chest with contrast to check for sarcoidosis flare revealed posterior mediastinal mass measuring 4.5 x 6.5 x 6.4 cm. Further work up with CT chest and abdomen with contrast revealed that the posterior mediastinal mass had similar attenuation as the liver and appears continuous with the caudate lobe of the liver. This was confirmed by NM scan of liver. Review of her records from an outside organization revealed similar finding on imaging a few years ago. Patient denied any history of trauma and laboratory work up revealed normal liver functions. After pulmonologist evaluation she was started on 2 L home oxygen following six-minute walk test, and also CPAP following a positive sleep study. Pulmonary function tests were performed and inhalers were continued. Given the chronicity of her symptoms and co-morbidities with stable caudate lobe herniation, conservative management was advised with surgery warranted if symptoms persist despite treatment (Figure 1). Discussion(s): DH is typically found on the left side with stomach or intestine while the right side is usually guarded by the liver. Isolated herniation of part of the liver into the thoracic cavity is rarely reported and is mostly acute from traumatic or spontaneous rupture requiring immediate repair. Our patient was initially evaluated for the posterior mediastinal mass for concerns of tumor, followed by the finding of what was thought to be acute herniation of the caudate lobe of liver into the thoracic cavity. Review of records showed this to be a stable lesion, we suspect that the patient had congenital diaphragmatic defect. Chronic and stable liver herniation into thoracic cavity can be managed conservatively if uncomplicated.

Covid-19, HLA, and race common link: A novel hypothesis.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accountable for the coronavirus disease 2019 (Covid-19) prompted a catastrophic pandemic striking millions of people with diverse presentations, from asymptomatic to severe, potentially lethal disease requiring unprecedented levels of specialized care and extraordinary resources that have overwhelmed healthcare systems around the world. In this detailed communication we postulating a novel hypothesis, based on the viral replication and transplantation immunology. This based on reviewing published journal articles and text book chapters to account for variable mortality and degrees of morbidity among various race and origins. Homo sapiens evolution over millions of years, for that the matter the origin of any biologic form of life form initiated by microorganisms. The entire body of a human has several millions of bacterial and viral genomes incorporated over millions of years. Perhaps the answer or a clue lies how compatible a foreign genomic sequence fits into three billion copies of human genome.

One-minute-sit-to-stand-test elicits less desaturation than 6MWT in advanced respiratory disease

Introduction: During the COVID-19 pandemic pulmonary rehabilitation moved to a telehealth platform and the 1-min sit-to-stand test (1minSTS) was often used instead of the 6-min walk test (6MWT) to evaluate functional exercise capacity. We sought to determine;(i) the extent to which the six-minute walk distance (6MWD) could be estimated from the number of repetitions achieved during the 1minSTS and, (ii) agreement in cardiorespiratory responses elicited collected during the tests. Method(s): Data were extracted from medical records on all people who attended the advanced lung disease service at Fiona Stanley Hospital between September 2021 and January 2022. Pulse rate and oxygen saturation (SpO 2) were measured continuously during both tests using a pulse oximeter. Symptoms were quantified using the Borg scale (0 to 10). Result(s): Data were available on 80 participants (43 males;age 64 +/- 10 years;FEV 1 1.65 +/- 0.77 L). Compared with the 6MWT, the 1minSTS resulted in a higher nadir (mean difference [MD] 4%, 95% CI 3 to 5), higher peak pulse rate (MD 8 bpm, 95% CI 5 to 11), similar intensity of dyspnoea (MD -0.3, 95% CI -0.6 to 0.1) and greater leg fatigue (MD 1.1, 95% CI 0.6 to 1.6). Of those who demonstrated severe desaturation (SpO 2 nadir <85%) on the 6MWT (n = 18), 5 and 10 were classified as moderate (SpO 2 nadir 85% to 89%) or mild desaturators (SpO 2 nadir >= 90%), respectively on the 1minSTS. The equation that represented the relationship between 6MWD and 1minSTS was: 6MWD (m) = 247 + (7 x number of transitions achieved during the 1minSTS;r 2 = 0.44). Conclusion(s): The 6MWT elicited greater desaturation, a lower peak pulse rate and greater leg fatigue than the 1minSTS. A smaller proportion of people will be classified as 'severe desaturators' using the 1minSTS test. The capacity to estimate the 6MWD using results of the 1minSTS is limited.

Effect of pulmonary rehabilitation program on post hospitalization severe COVID-19 patients (Experimental study)

Background: COVID-19 infection was discovered to be the major global cause of a serious respiratory illness toward the end of 2019. The majority of COVID-19 patients experience mild disease, while about 14% go on to have severe disease and 6% end up in critical condition. An evidence-based standard of therapy called pulmonary rehabilitation includes exercise-training, education, and behavior modification to help people had a lung illness feel better physically and mentally. Aim(s): current study aimed to evaluate the effect of pulmonary rehabilitation program on severe post covid19 patients (post hospitalization) regarding pulmonary function tests and dyspnea score. Method(s): Randomized control experimental study design enrolled 100 patients of post hospitalization due to severe COVID 19 infection. Dyspnea score, Spirometry and 6-minute walk test were performed upon discharge. Pulmonary rehabilitation program in the form of respiratory exercises and walking exercise was done to 50 patients. Follow up assessment of the same parameters was done 6 weeks after the program. Other 50 patients had no pulmonary rehabilitation program to them. Result(s): Post COVID-19 cases in the experimental group show much improvement in percentage of normal breathing score (mMRC) 30% versus no cases in control group. In addition, the experimental group showed a significant higher percentage of normal spirometry findings (66% versus 28% in control group). As regards oxygen saturation, 6MWT score and distance, it showed a higher mean after practicing the exercise program. Conclusion(s): pulmonary rehabilitation program was effective in achieving much improvement in recovery of severe cases of COVID 19 infection.Copyright © 2021 Muslim OT et al.

Telerehabilitation in the 'real-world': Implementation of remotely delivered pulmonary rehabilitation

Introduction: Pulmonary rehabilitation (PR) is an effective treatment for people with chronic respiratory disease but is delivered to <5% of eligible individuals. Home-based telerehabilitation achieves similar clinical outcomes to centre-based PR in clinical trials. We aimed to evaluate the clinical implementation of telerehabilitation. Method(s): Suitable individuals with respiratory disease referred for PR at Alfred Health have been offered the option of an 8-week home-based telerehabilitation program (one home visit followed by twice-weekly exercise training sessions, with real time supervision, for 8-weeks). Equipment was provided to patients, as necessary. Standard PR assessments were conducted pre and post program. Program completion was defined as undertaking >=70% of prescribed sessions. Real-world implementation was evaluated against the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Result(s): Reach: Across 2-years (Sept 2020-22), 269 people were referred with 55 (21%) undertaking telerehabilitation (25 female, mean (SD) age 61 (11) years, 6-min walk distance (6MWD) 430 (120) metres, Chronic Respiratory Questionnaire Dyspnoea (CRQD) domain 16 (6)). Participant diagnoses included COPD (n = 11), ILD (n = 15), bronchiectasis (n = 5), asthma (n = 2), post COVID-19 (n = 9), and pulmonary hypertension (n = 4). Forty participants (73%) completed >=70% of prescribed sessions. Effectiveness: Significant and clinically meaningful improvements were demonstrated (CRQD MD 4 (95% CI 1, 6);6MWD MD 24 m (95% CI 8, 41)). Adoption: Training to deliver telerehabilitation and perform home visits was completed by PR clinicians (n = 7 and n = 4 respectively). Implementation: All participants independently supplied Wi-Fi, and 40% used their own exercise equipment or internet-enabled device. Most participants had an in-person home visit (n = 45), and undertook cycle-based training (n = 46). Fifteen participants required additional support for iPad or videoconferencing navigation. There were no serious adverse advents. Maintenance will be evaluated following this pilot period. Conclusion(s): 'Real-world' telerehabilitation achieves clinically meaningful outcomes for patients and provided access to an effective model of PR particularly when centre-based programs were unavailable due to COVID-19 restrictions.

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

Pulmonary function abnormality in patients recovered from Covid 19 pneumonia, in a tertiary care hospital in India.

Background: One of the most dreaded complications of COVID pneumonia is post-COVID residual lung fibrosis and lung function impairment. Objectives: To find out the extent and type of pulmonary function abnormality using spirometry, diffusion capacity, and 6-minute walk test and to co-relate with the clinical severity at the time of infection, in patients who have recovered from COVID19 pneumonia, in a tertiary care hospital in India. Materials and Methods: This is a prospective, cross-sectional study with a total 100 patients. Patients who have recovered from COVID pneumonia after one month of onset of symptoms and before 3 months who come for follow-up and have respiratory complaints undergo pulmonary function test will be recruited in the study. Results: In our study, the most common lung function abnormality detected was restrictive pattern in 55% of the patients (N = 55) followed by mixed pattern in 9% of patients (N = 9), obstructive in 5% of patients (N = 5), and normal in 31% of patients (N = 31). In our study, total lung capacity was reduced in 62% of the patients and normal in 38% of the patients and diffusion capacity of lung was reduced in 52% of the patients recovered from 52% of the individuals. Also, a 6-minute walk test was reduced in 15% of the patients and normal in 85% of the patients. Conclusion: Pulmonary function test can serve as an important tool in both diagnosis and follow-up of post-COVID lung fibrosis and pulmonary sequalae.

The informative value of CD3+CD4+ and CD3+CD8+ T-cell count and cHIS scale as predictors of severe COVID-19 when using interleukin-6 receptor blockers in the in-hospital setting.

BACKGROUND: Clinical and laboratory signs of hyperinflammatory response in COVID-19 may serve as prognostic markers of the disease scenario. In real-world practice, there is an unmet need to determine the optimal timing of identifying predictors of SARS-CoV-2 adverse outcomes in the context of patient stratification to improve the effectiveness of anti-IL-6R therapy. Lymphopenia has a high informative value for the adverse prognosis of the COVID-19 course; however, the informative value of CD3+CD4+, CD3+CD8+ T-cell count remains questionable. In addition to lymphocyte phenotyping, a six-criterion additive scale (cHIS) was used in the study. AIM: To study the informative value of CD3+CD4+, CD3+CD8+ T-cell phenotyping and cHIS scale as predictors of severe COVID-19 when using IL-6R blockers. MATERIALS AND METHODS: A single-center, bi-directional study included 179 patients with SARS-CoV-2-induced community-acquired pneumonia with severe acute inflammation and progressing respiratory failure. Data were obtained from electronic patient records. Anti-IL-6R was administered in addition to standard therapy in the cohorts. The following disease outcomes were used to determine the informative value of the studied parameters: mortality and hospital discharge. Inflammatory markers were measured before and after administering anti-IL-6R, followed by monitoring. Statistical analysis was performed using SPSS (version 25.0). The quantitative indices were described using the median and interquartile range. Quantitative indices were compared using nonparametric methods: Mann-Whitney U-test, Kruskal-Wallis test. The groups were compared by qualitative characteristics using Pearson's chi-square test. Correlation analysis of quantitative indicators was performed using Spearman rank correlation. For additional analysis of the cHIS scale, odds ratio and decision tree methods were used. Differences were considered statistically significant at р≤0,05. RESULTS: Immunophenotyping of lymphocytes as a predictor of the severe SARS-CoV-2 requires further research. The cHIS scale may be implemented in routine clinical practice due to its high predictive value. A cHIS score of ≥2 on the first day of admission is a critical threshold for intensification and revision of therapy. The prognosis with cHIS is logically relevant in the first three days of hospitalization. CONCLUSION: The main result of the study is the definition of target groups of patients with community-acquired SARS-CoV-2 pneumonia for the IL-6R-blockers, considering the timing of their effective use in real clinical practice.

The effect of long-term oxygen therapy on 6-minute walking distance, clinical parameters and hemodynamics in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. A prospective, randomized, controlled trial (SOPHA Study)

Background Current recommendations suggest oxygen (O2) supplementation in patients with pulmonary hypertension (PH). The effect of long-term O2 administration is though merely investigated among these patients. Thus, the aim of this study is to investigate the effect of long term O2 treatment in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) on exercise capacity, clinical parameters and hemodynamics. Methods In this prospective, randomized, controlled trial, 20 patients with PAH or CTEPH under stable PH therapy experiencing O2 desaturations at rest and/or during physical activity will be randomised to receive O2 or standard of care (SoC) for 12 weeks. To patients receiving SoC, O2 therapy will be offered after 12 weeks (cross over design). The primary endpoint is the change of the distance walked in 6 minutes after 12 weeks of treatment. Secondary endpoints include change in clinical parameters and hemodynamics. Results Overall 20 patients (O2 n = 10 vs. SoC n = 10) have already been randomized and 15 have completed the study. Two patients died, one patient due to SARS-CoV2 pneumonia in the oxygen arm and one due to right heart failure in the SoC arm. The O2 therapy is so far well tolerated by all patients. Further results are expected in due course. The study is expected to be completed by the end of December 2022. Conclusion Oxygen therapy is well tolerated. Further results are expected soon. The effect of long-term oxygen supplementation should be furtherly investigated in larger controlled-trials.

Pulmonary function and functional capacity at 3, 6 and 12 months in COVID-19 patients and effect of physical activity on recovery

BACKGROUND: Long-term sequelae due to Coronavirus disease 2019 (COVID-19) are now under investigation. Aim of this study was to evaluate the one-year clinical impact of COVID-19 on respiratory function and relation with physical activity. METHOD(S): One hundred four patients were evaluated 3, 6 and 12 months after SARS-CoV-2 diagnosis. Clinical conditions, symptomatology, 6-minute walking test (6MWT), pulmonary function test with spirometry and diffusing capacity of carbon monoxide (DLCO) were analyzed. RESULT(S): Eighty-six (82.7%) patients referred at least one symptom at 3 months, 46 (44.2%) at 6 months and 24 (23.1%) at 12 months. At the 3-months visit, patients with moderate COVID showed a slight decrease of distance at the 6MWT, with an improvement at 12 months (P=0.04). Patients with severe COVID-19 showed a recovery of SpO2 at rest (P<0.001), DLCO (P=0.001), DLCO/VA (P=0.002), forced vital capacity (P=0.01) and 6MWT distance (P=0.002) at 6 and 12 months. Patients with critical COVID-19 showed a remarkable reduction of DLCO at 3 months (65+/-21%). Then a subsequent gradual improvement of DLCO was recorded (78+/-18% at 6 months, 85+/-16% at 12 months, P=0.01). Patients with DLCO<80% of predicted at 12 months were older (P=0.02), with higher prevalence of cardio-vascular disease (P=0.006), diabetes (P=0.01) and critical COVID-19 (P=0.003). The improvement of 6MWT distance and DLCO during the three visits did not correlate with physical activity. CONCLUSION(S): Patients with COVID-19 lung involvement showed a progressive improvement in respiratory function and physical performance at 6 and 12 months after acute disease.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Predictive Six Sigma for Turkish manufacturers: utilization of machine learning tools in DMAIC

PurposeThis study aims to emphasize utilization of Predictive Six Sigma to achieve process improvements based on machine learning (ML) techniques embedded in define, measure, analyze, improve, control (DMAIC). With this aim, this study presents selection and utilization of ML techniques, including multiple linear regression (MLR), artificial neural network (ANN), random forests (RF), gradient boosting machines (GBM) and k-nearest neighbors (k-NN) in the analyze and improve phases of Six Sigma DMAIC.Design/methodology/approachA data set containing 320 observations with nine input and one output variables is used. To achieve the objective which was to decrease the number of fabric defects, five ML techniques were compared in terms of prediction performance and best tools were selected. Next, most important causes of defects were determined via these tools. Finally, parameter optimization was conducted for minimum number of defects.FindingsAmong five ML tools, ANN, GBM and RF are found to be the best predictors. Out of nine potential causes, "machine speed” and "fabric width” are determined as the most important variables by using these tools. Then, optimum values for "machine speed” and "fabric width” for fabric defect minimization are determined both via regression response optimizer and ANN surface optimization. Ultimately, average defect number was decreased from 13/roll to 3/roll, which is a considerable decrease attained through utilization of ML techniques in Six Sigma.Originality/valueAddressing an important gap in Six Sigma literature, in this study, certain ML techniques (i.e. MLR, ANN, RF, GBM and k-NN) are compared and the ones possessing best performances are used in the analyze and improve phases of Six Sigma DMAIC.

Physical Therapy Management of Postacute Sequelae of COVID-19 in Outpatient Settings: A Scoping Review

Purpose:The devasting effects of the coronavirus disease 2019 (COVID-19) pandemic have warranted the rapid development of evidence surrounding the physical therapy (PT) management of the disease within inpatient settings. However, the medical community is still working to define the long-term effects of COVID-19, referred to as Postacute Sequalae of SARS-CoV-2 (PASC), and ways for physical therapists to manage them in outpatient settings. The primary objective of this review was to summarize the available evidence related to the PT management of PASC in outpatient settings. Method(s):A systematic search in PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane CENTRAL, Academic Search Complete, and MedLine yielded systematic and scoping reviews and randomized controlled trials, among others. Data extraction was performed independently by 2 reviewers with 8 studies included. Result(s):Only 3 publications were specific to the outpatient setting area, with 5 more studies that focused on outpatient practice as part of a multisetting study, or the postacute setting. Although the limited number and quality of publications creates challenges applying the interventions provided across a population, each were specific to PASC. Conclusion(s):This review supports the need for further research focused on the PT management of patients who are experiencing PASC in outpatient settings.Copyright © Cardiovascular and Pulmonary Section, APTA.