Therapeutic Strategy for the Deterrence of COVID-19 with Relevance to Probiotics

The epidemiology of novel corona virus disease (COVID-19) is attributed by cough, fever, fatigue, headache, sore throat, gastrointestinal disorders, and pneumonia. The frequency of COVID-19 infection is accelerating at great speed globally, and till date, there is no specific vaccine or drug available for prevention or cure of the disease. Therefore, certain measures are required to check the outbreak of this pandemic immediately. Current chapter concerns with the development of certain probiotics including a single or mixed culture of live microorganisms that could maintain the intestinal or lung microbiota of humans. Besides being beneficial bacteria, probiotics also possess antiviral activity. The stimulation of the immune system through probiotics is one of the approaches that have been emphasized for fighting against the viral infections. The immunomodulatory activities of probiotics include the enhancement of the phagocytic receptors like CR1, CR3, FccRI, and FcaR;induction of APC-derived pro- and anti-inflammatory cytokines such as IL-10, IL-12, IL-17, TNF-α, and IFN-α against foreign antigens;and an increase in the microbicidal function of neutrophils. The most common probiotics include Lactobacillus, Bifidobacterium, Leuconostoc, Pediococcus, and Enterococcus. Lactobacillus and Bifidobacterium are widely used in yogurts and other dairy products. Probiotics exert antiviral activity by production of antiviral in inhibitory metabolites. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Clinical features of patients with severe acute respiratory syndrome coronavirus 2 Delta variant infection and abnormal liver function in Guangdong Province, China. TT -? ? ? ? ? ?.

Objective To investigate the clinical features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection and abnormal liver function in Guangdong Province, China. Methods The patients with SARS-CoV-2 Delta variant infection who belonged to the same chain of transmission in Guangdong Province (Guangzhou and Foshan) and were admitted to Guangzhou Eighth People's Hospital, Guangzhou Medical University from May 21 to June 18, 2021 were enrolled in this study, and the judgment criteria for liver function were alanine aminotransferase (male/female) > 50/40 U/L, aspartate aminotransferase > 40 U/L, total bilirubin > 26 mumol/L, gamma-glutamyl transpeptidase > 60 U/L, and alkaline phosphatase (ALK) > 125 U/L. Abnormality in any one item of the above criteria was defined as abnormal liver function, and such patients were included in analysis (the patients, aged < 18 years, who had a mild or moderate increase in ALP alone were not included in analysis). Clinical data were compared between the patients with normal liver function and those with abnormal liver function, and the etiology and prognosis of abnormal liver function were analyzed. The Mann-Whitney U test was used for comparison of continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups. Results Among the 166 patients with SARS-CoV-2 Delta variant infection, 32 (19.3%) had abnormal liver function with mild-to-moderate increases in liver function parameters, and compared with the normal liver function group, the abnormal liver function group had a significantly higher proportion of critical patients (chi2=38.689, P < 0.001) and significantly higher age and inflammatory cytokines [C-reactive protein type, serum amyloid A, and interleukin-6 (IL-6)](all P < 0.05). Among the 32 patients with abnormal liver function, 13 patients had abnormal liver function on admission (defined as primary group), while 19 patients had normal liver function on admission but were found to have abnormal liver function by reexamination after treatment (defined as secondary group). For the primary group, the evidence of abnormal liver function was not found for 3 patients (3/13, 23.1%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. Among the 19 patients in the secondary group, 9 (47.4%) had mild/common type and 10 (52.6%) had critical type, and all critical patients had the evidence of liver injury indirectly caused by the significant increases in C-reactive protein type, serum amyloid A, and IL-6 and hypoxemia;the evidence of abnormal liver function was not found for only 1 patient (1/19, 5.3%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. All 32 patients with abnormal liver function had [JP2]significant reductions in liver function parameters after treatment including liver protection. Conclusion As for the patients with SARS-CoV-2 Delta variant infection who belong to the same chain of transmission in Guangdong Province, the critical patients show a significantly higher proportion of patients with abnormal liver function than the patients with other clinical types, and other factors except SARS-CoV-2 infection and indirect injury caused by SARS-CoV-2 infection are the main cause of liver injury.Copyright © 2022 Editorial Board of Jilin University. All rights reserved.

Use of novel oxygenated right ventricular assist device hybrid ECLS for adolescents with refractory hypoxemic respiratory dailure due to Covid-19 pneumonia

Objectives: To describe institutional experience using Oxygenated Right Ventricular Assist Device (OxyRVAD) Hybrid ECLS for adolescents with respiratory failure due to SARS-CoV-2 pneumonia. Method(s): Between September and December 2021, 44 Covid-19+ patients were admitted to our regional Pediatric Intensive Care Unit (PICU), including 4 adolescents who required Extracorporeal life support (ECLS) due to refractory hypoxemia. Two patients were initially cannulated onto Veno-Venous (VV) ECLS and converted to Oxy-RVAD ECLS due to refractory hypoxemia;the others were cannulated directly onto Oxy-RVAD ECLS. Two patients had observed right ventricular (RV) dysfunction or failure on echocardiography. Cannulations were performed in the cardiac catheterization suite by an interventional cardiologist using percutaneous technique under fluoroscopy. Circuit construction was varied and included the use of a dedicated RVAD cannula or standard cannula used for VA/VV ECLS. All patients were connected to Cardiohelp systems with built in centrifugal pumps and oxygenators. Result(s): Two patients were initially placed on VV-ECLS and converted to Oxy-RVAD ECLS days into their course due to severe, refractory hypoxemia with one having improvement in hypoxemia after the conversion. Two patients received renal replacement therapy (RRT) without complications, the others did not have indications for renal support. Two patients underwent tracheostomy on ECMO though none were able to separate from mechanical ventilation. Three patients survived to discharge. No incidents of circuit air or clotting were noted. The patient with the longest ECLS run required one circuit change and was the only patient to develop a superinfection: a successfully-treated fungal infection. All patients were mobilized on ECLS to sitting in a chair;one was able to ambulate. Conclusion(s): Oxy-RVAD hybrid ECLS can be used to effectively support adolescents with severe respiratory disease from conditions associated with RV dysfunction. Pediatric providers can collaborate with adult critical care colleagues to use novel methods to support these patients. RRT can also be used with this circuit. While more experience and data on this modality is needed, Oxy-RVAD ECLS should be considered in patients with severe RV dysfunction and associated refractory hypoxemia. (Figure Presented).

Non-invasive respiratory support in patients with severe community-acquired pneumonia.

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.

Unique vascular complication following extended VV-ECMO support

Objectives: To present an unusual complication related to prolonged ECMO support in a patient with COVID19 induced acute respiratory syndrome (ARDS). Method(s): Clinical chart review of the care process after obtaining the informed consent from the patient. Result(s): A 48-year-old female with COVID-19 infection during second wave of pandemic in August 2021 progressed to severe ARDS. She was put on VV-ECMO support after failing conventional therapy for refractory hypoxemia. Her cannulation configuration included a 25 F venous drainage cannula in the right femoral vein and a 21 F venous return cannula in the right Internal Jugular (IJ) vein. Cannulations were performed using the ;Seldinger technique;under USG guidance, and no difficulties or complications were reported. Her hospital course was notable for delirium, and intermittent bleeding from the cannula sites. After 80 days of support, she showed adequate respiratory improvement which allowed ECMO decannulation. She continued to show improvement, and was eventually discharged after 102 days of total hospital stay. During her 6 weeks follow-up clinic visit a palpable thrill was noted at the jugular ECMO cannula site. A CT angiogram of the neck demonstrated a large venous varix connecting the right IJ and the left common carotid artery with filling from the left common carotid artery. ECMO cannulation site complications such as aneurysm, clots, infections and stenosis are well known. What was unusual in this case is the nature of the aneurysm given that there were no arterial procedures performed on the left side of the neck. She was managed by an ;Amplatzer plug;to the carotid artery at the level of the connection to the varix without any complications. Conclusion(s): Longer duration of ECMO support needs careful follow-up for timely recognition and management of vascular complications. (Figure Presented).

Membrane dysfunction in patients with severe COVID-19 treated with venovenous extracorporeal membrane oxygenation - analysis from a pooled data from a single centre

Objectives: It is well known that severe COVID-19 is associated with complex immunological and inflammatory dysregulation. Both these physiopathological events translate to a high risk of major thrombotic or hemorrhagic events. In patients treated with venovenous extracorporeal membrane oxygenation (VVECMO), membrane dysfunction might affect systemic oxygenation and limit its duration-expectancy. This study aimed to assess the possible causes of extracorporeal membrane failure in COVID-19 patients and its impact on outcome. Method(s): Retrospective, single-center, observational case-control study involving adult COVID-19 patients admitted to an ECMO referral centre in a tertiary university hospital. All patients required VVECMO for acute respiratory failure, including 48 cases who needed one or more extracorporeal membrane exchanges and 45 controls (no membrane exchange). These two groups were compared for demographic characteristics, severity of the disease using validated scores (SAPS II and SOFA), duration of ECMO run, coagulation assessment, cumulative anticoagulation dose, associated complications, and outcomes (ICU and hospital mortality). Result(s): Most patients were males (71.0%) and younger than 50 years (79.5%). Median ECMO run duration was significantly longer in the case group (35.0 vs 14.0 days, p <0.001), as well as ICU length-of-stay (45.5 vs 28 days, p <0.001). Membrane exchange tended to be associated with sepsis (56% vs 33%, p=0.037), major hemorrhage (58% vs 43%, p=0.022), heparin-induced thrombocytopenia (25% vs 9%, p=0.054), higher D-dimer title (17.36 ng/dL vs 7.5 ng/dL, p=0.07) and lower platelet counts (133.000/muL vs 154.000/muL). Median SAPS II (32.0 vs 33.0, p=0.20) and the mortality (27% vs 24%, p >0.99) were similar between these groups. Conclusion(s): In patients with SARS-CoV-2 pneumonia and severe hypoxemia treated with VVECMO support the emergence of infection, coagulopathy and inflammation were associated with high risk of membrane dysfunction. No impact on mortality could be confirmed from these data. Anticoagulation monitoring and dosing strategies should be reinforced to promote membrane protection.

Characteristics, management and outcomes of thirty COVID-19 ARDS patients supported with veno-venous extracorporeal membrane oxygenation at Rikshospitalet, Oslo University Hospital

Background: We reviewed patients with COVID-19 ARDS managed with VV-ECMO support at our center from March 2020 until February 2022. Material(s) and Method(s): We extracted data from electronic health records (Metavision and DIPS). We registered premorbid health status, ventilator-settings before initiation of ECMO, the time-course, and hospital mortality. Result(s): Thirty patients were managed at our hospital, with a median age of 57.2 years (28-65) and median BMI 28 (22-40). No patient had any serious comorbidity. Twenty-two patients received non-invasive ventilation prior to intubation (1-10 days). The median time on ventilator were 8.0 days (1-19) prior to ECMO and median tidal volume was 5.8 mL/kg PBW (3.1-7.5). Hypoxemia (median PaO2-FiO2 ratio 8 kPa, range 6-12 kPa) and hypercapnia (median PaCO2 11.9 kPa, range 4.2-18.5) [SEP1] despite lung protective ventilation were the main indications for VV-ECMO. Two patients had severe respiratory acidosis without hypoxemia. 18 patients developed serious complications while managed with ECMO (acute renal failure, clinically significant bleeding, sepsis, right ventricular heart failure, dislocation of cannulae). Seven patients received renal replacement therapy. Sixteen patients (53%) died. Thirteen patients (43%) died on ECMO, three (10%) after weaning, Twelve (40%) were discharged from hospital, two are currently in ICU (7%). The median duration of ECMO and ventilator treatment, was 27 (6-50) and 37 (9-78) days, respectively. Conclusion(s): Management of patients with COVID-19 ARDS with VV-ECMO is very resource-intensive, and accompanied by serious complications and high mortality. In-hospital mortality in our cohort was 53%, which is comparable with reports from other centers. However, the duration of ECMO, and pre-ECMO mechanical ventilation, were longer than typically reported.

Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

Oximetry at admission as a predictor of tomographic and functional impairment after 3-6 months in hospitalized patients with COVID-19.

OBJECTIVE: To investigate characteristics that may be associated with radiologic and functional findings following discharge in patients with severe coronavirus disease 2019 (COVID-19). METHODS: This single-center, prospective, observational cohort study comprised patients aged >18 years who were hospitalized with COVID-19 pneumonia, between May and October 2020. After 3 to 6 months of discharge, patients were clinically evaluated and underwent spirometry, a 6-minute walk test (6MWT), and chest computed tomography (CT). Statistical analysis was performed using association and correlation tests. RESULTS: A total of 134 patients were included (25/114 [22%] were admitted with severe hypoxemia). On the follow-up chest CT, 29/92 (32%) had no abnormalities, regardless of the severity of the initial involvement, and the mean 6MWT distance was 447 m. Patients with desaturation on admission had an increased risk of remaining CT abnormalities: patients with SpO2 between 88 and 92% had a 4.0-fold risk, and those with SpO2 < 88% had a 6.2-fold risk. The group with SpO2 < 88% also walked shorter distances than patients with SpO2 between 88 and 92%. CONCLUSION: Initial hypoxemia was found to be a good predictor of persistent radiological abnormalities in follow-up and was associated with low performance in 6MWT.

Use of Novel Oxygenated Right Ventricular Assist Device Hybrid ECLS for Adolescents with Refractory Hypoxemic Respiratory Failure due to Covid-19 Pneumonia

Objective: To describe institutional experience using Oxygenated Right Ventricular Assist Device Oxy-RVAD) Hybrid ECLS for adolescents with respiratory failure due to SARS-CoV-2 pneumonia. Method(s): Between September and December 2021, 44 Covid-19+ patients were admitted to our regional Pediatric Intensive Care Unit (PICU) including 4 adolescents who required Extracorporeal life support (ECLS) due to refractory hypoxemia. Two patients were initially cannulated onto Veno-Venous (VV) ECLS and converted to Oxy-RVAD ECLS due to refractory hypoxemia;the others were cannulated directly onto Oxy-RVAD ECLS. Two patients had observed right ventricular dysfunction (RV) or failure on echocardiography. Cannulations were performed in the cardiac catheterization suite by an interventional cardiologist using percutaneous technique under fluoroscopy. Circuit construction was varied and included the use of a dedicated RVAD cannula or standard cannula used for VA/VV ECLS. All patients were connected to CardiohelpTM systems with built-in centrifugal pumps and oxygenators. Result(s): Two patients were initially placed on VV-ECLS and converted to Oxy-RVAD ECLS days into their course due to severe, refractory hypoxemia with one having improvement in hypoxemia after the conversion. Two patients were cannulated directly to Oxy-RVAD ECLS support. Two patients received renal replacement therapy (RRT) without complications, the others did not have indications for renal support. Two patients underwent tracheostomy on ECMO though none were able to separate from mechanical ventilation. Three patients survived to discharge. No incidents of circuit air or clotting were noted. The patient with the longest ECLS run required one circuit change and was the only patient to develop a superinfection: a successfully-treated fungal infection. All patients were mobilized on ECLS to sitting in a chair;one was able to ambulate. Conclusion(s): Oxy-RVAD hybrid ECLS can be used to effectively support adolescents with severe respiratory disease from conditions associated with RV dysfunction. Pediatric providers can collaborate with adult-focused colleagues to use novel methods to support these patients. RRT can also be used with this circuit. While more experience and data on this modality is needed, Oxy-RVAD ECLS should be considered in patients with severe RV dysfunction and associated refractory hypoxemia.

Prone position in spontaneous ventilation? An induction problem: A scoping review

Intoduction: Prone position in spontaneous ventilation is not a recent strategy, and despite the many years it has been trying to consolidate, it has not been able to prove to be of real utility. During the recent pandemic, prone spontaneous ventilation re-emerged as a practical and simple alternative, although it was highly questioned due to its weak level of evidence. With time and experience, it was gradually relegated to become only an attractive hypothesis. Objective: This study aims to analyze the potential benefits of prone position in spontaneous ventilation in patients with hypoxemia caused by SARS-CoV-2. Methods: A panoramic review of the most relevant studies published in the MEDLINE, Embase and Scopus databases up to December 20, 2021 was performed. Results: After screening, 4 observational studies, 1 randomized clinical trial, and 3 systematic reviews were selected for analysis. Conclusions: By statistical analysis we concluded that prone position in spontaneous ventilation, although it could delay intubation, did not improve survival in hypoxemic subjects with viral pneumonia caused by coronavirus type 2. © 2023 Asociación Colombiana de Medicina Crítica y Cuidado lntensivo

Management of Acquired von Willebrand Syndrome During Prolonged VV-ECMO

Acquired von Willebrand syndrome (AVWS) contributes to bleeding during extracorporeal membrane oxygenation (ECMO) support. Although it is recognized that AVWS rapidly resolves after ECMO decannulation, this approach may often be clinically unsuitable. In such cases, optimal AVWS management during ECMO support is not well established. We report our approach to managing AVWS in a patient on veno-venous (VV) ECMO for 59 days. A 19-year-old male developed hypoxemic respiratory failure from SARS-CoV-2 pneumonia. Following intubation, he progressed to VV-ECMO support for refractory hypoxemia and was started on bivalirudin for systemic anticoagulation. Two days later, he developed refractory gastrointestinal and oro-nasopharyngeal bleeding despite blood product transfusions and discontinuing bivalirudin. He was started on pantoprazole along with infusions of octreotide and aminocaproic acid. Upper endoscopy on ECMO day 5 revealed an ulcerative bleeding vessel in the duodenum that was clipped. Recurrent mucosal bleeding precluded resumption of systemic anticoagulation. On ECMO day 23, AVWS was diagnosed based on elevated von Willebrand factor (VWF) activity (207%, normal 55-189%) and antigen (234%, normal 50-210%) levels with abnormally low VWF high-molecular-weight multimers. Factor VIII complex was administered twice over the following week. Between doses, the ECMO circuit was exchanged to empirically mitigate suspected shear-related VWF consumption from the fibrin burden, and a repeat endoscopy controlled additional intestinal bleeding with local hemostatic agents. He received 36 units of red blood cells, 2 units of platelets, 2 units of plasma, and 7 pooled units of cryoprecipitate over 31 days leading into these combined interventions. In the 28 days afterwards, he received 3 units of red blood cells, 3.5 pooled units of cryoprecipitate, and no additional platelets or plasma. Our patient was maintained off systemic anticoagulation for 54 of 59 days of VV-ECMO support without any thrombotic complications occurring. With no subsequent clinical evidence of bleeding, repeat VWF testing was done two months post-decannulation and showed near-normal VWF activity (54%) and normal multimer distribution. Our patient rehabilitated well without any neurologic deficits and on discharge was requiring supplemental oxygen with sleep and strenuous activity. Avoiding systemic anticoagulation, repleting VWF, maintaining circuit integrity, and providing local hemostasis, when possible, may be a safe and effective management strategy of AVWS on ECMO support when decannulation is not a viable option.

Pulmonary surfactant and COVID-19: A new synthesis

Chapter 1: COVID-19 pathogenesis poses paradoxes difficult to explain with traditional physiology. For instance, since type II pneumocytes are considered the primary cellular target of SARS-CoV-2;as these produce pulmonary surfactant (PS), the possibility that insufficient PS plays a role in COVID-19 pathogenesis has been raised. However, the opposite of predicted high alveolar surface tension is found in many early COVID-19 patients: paradoxically normal lung volumes and high compliance occur, with profound hypoxemia. That 'COVID anomaly' was quickly rationalised by invoking traditional vascular mechanisms-mainly because of surprisingly preserved alveolar surface in early hypoxemic cases. However, that quick rejection of alveolar damage only occurred because the actual mechanism of gas exchange has long been presumed to be non-problematic, due to diffusion through the alveolar surface. On the contrary, we provide physical chemical evidence that gas exchange occurs by an process of expansion and contraction of the three-dimensional structures of PS and its associated proteins. This view explains anomalous observations from the level of cryo-TEM to whole individuals. It encompasses results from premature infants to the deepest diving seals. Once understood, the COVID anomaly dissolves and is straightforwardly explained as covert viral damage to the 3D structure of PS, with direct treatment implications. As a natural experiment, the SARS-CoV-2 virus itself has helped us to simplify and clarify not only the nature of dyspnea and its relationship to pulmonary compliance, but also the fine detail of the PS including such features as water channels which had heretofore been entirely unexpected.Copyright ©

Venovenous extracorporeal membrane oxygenation and late ductal stenting for infant with transposition of the great arteries, pulmonary stenosis and SARS, -CoV-2 pneumonia

Introduction: The SARS-CoV-2 pandemic has affected medical decision-making in all practice areas, including the pediatric cardiac intensive care unit (CICU), sometimes necessitating the use of innovative management strategies. Venovenous extracorporeal membrane oxygenation (VV-ECMO) and, particularly, late ductal stenting are infrequently applied interventions in the CICU. Here we present a critically ill infant with d-transposition of the great arteries (d-TGA), ventricular septal defect (VSD), pulmonary stenosis (PS), and patent ductus arteriosus (PDA), in which VV-ECMO and late ductal stenting were utilized successfully in the setting of active SARS-CoV-2 infection to treat worsening PS and pulmonary venous desaturation, thereby delaying surgical intervention and its associated risks during active infection. Case Description: A 3 month old male with d-TGA, VSD, and PS, initially managed with a balloon atrial septostomy at birth, was admitted to the CICU after presenting with respiratory distress and hypoxemia. He was found to be SARS-CoV-2 positive, requiring only nasal cannula initially. Admission echocardiogram demonstrated known d-TGA, VSD, severe pulmonary stenosis (peak gradient 95-110mmHg), unrestrictive atrial communication, and preserved systolic function. A tiny, hemodynamically insignificant PDA was also noted. While admitted, the patient exhibited intermittent, severe desaturations requiring escalating respiratory support. He was started on a prostaglandin infusion with aim to promote additional pulmonary blood flow through the PDA, thereby limiting the severity and frequency of desaturations. However, the patient ultimately became severely hypoxemic, despite multiple interventions to improve oxygenation. Echocardiogram at this time demonstrated preserved ventricular function, so the decision was made to escalate to VVECMO therapy. Following ECMO cannulation, the patient's hypoxemia quickly resolved, and he remained hemodynamically stable. Given the persistence of his PDA and the desire to avoid the risks of cardiac surgery in the setting of acute COVID infection, percutaneous intervention to augment pulmonary blood flow was attempted. Despite its diminutive size, his PDA was able to be successfully cannulated and stented the day after ECMO initiation. He was able to be quickly weaned from ECMO support and was decannulated the following day. He was subsequently extubated and ultimately discharged home with planning for definitive surgical intervention underway. Discussion(s): Here we present an interesting case of an infant with d-TGA, VSD, PS, and PDA in which VV-ECMO and PDA stenting were successfully applied to treat acute hypoxemia in the setting of SARS-CoV-2 infection and severe pulmonary stenosis. These therapies may be considered in appropriate patients for whom the risks of cardiac surgery are significant.

Fetal impact of cystic fibrosis transmembrane conductance regulator modulator use during assisted and natural reproduction and partner pregnancy in men with cystic fibrosis

Background: Increasing availability of highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapy (HEMT) has improved the quality of life and long-term prognosis for many people with CF. Thus, more people with CF are considering parenthood. Almost all menwith CF (MwCF) are infertile because of congenital bilateral absence of the vas deferens (CBAVD). Based on CF animal models, CBAVD occurs early in gestation and is unlikely to be reversible using HEMT, but assisted reproductive techniques (ARTs) can enable MwCF to father children using the sperm in their testes. Animal reproductive models suggest no HEMT teratogenicity, and the amount of exposure of the fetus to HEMT via absorption of seminal fluid through the vaginal wall is predicted to be negligible, although to ensure no sperm exposure to HEMT, the life span of sperm would require MwCF to discontinue CFTR modulators for approximately 3 months before ART. Because abrupt discontinuation of CFTR modulators may result in health decline, MwCF and their providers must consider all potential risks. There are no published data in MwCF regarding use of HEMT during conception and partner pregnancy. Method(s): Beginning in August 2021, CF center staff in the United States, United Kingdom, and Australia completed a two-page anonymous questionnaire regarding MwCF who used CFTR modulators during ART (sperm retrieval and in vitro fertilization) or natural conception with subsequent partner pregnancy. Result(s): Providers have submitted 34 surveys for MwCF on CFTR modulators whose partner became pregnant after use of ART (n = 32) or natural conception (n = 2). The median age of the samplewas 32 (range 24- 43). Fifteen were homozygous for F508del, median percentage predicted forced expiratory volume in 1 second was 76% (range (22-111%), and median body mass index was 24 kg/m2 (range 18.5-32.1). Twenty-three were taking elexacaftor/tezacaftor/ivacaftor. The median time that MwCF were taking CFTR modulators before partner conception was 18 months (range 0-82). One newly diagnosed man initiated HEMT after sperm retrieval. Four MwCF stopped CFTR modulators before sperm retrieval, one of whom experienced pulmonary decline. None of the 19 MwCF whose condom use during pregnancy was known used condoms. Fetal complications in partners of MwCF included three first-trimester miscarriages, two* COVID, two breech presentation, two* vaginal bleeding, and one vasa previa. None of the complications were deemed definitively related to use of CFTR modulators. One MwCF experienced testicular infection after sperm retrieval#. Postpartum complications included three# infants with hypoxemia requiring neonatal intensive care unit stay, three maternal blood loss, one forceps delivery, and one caesarean section. No congenital anomalies were reported for any infant. (*/# overlap). Conclusion(s): Use of CFTR modulator therapy during partner conception and pregnancy in 34 MwCF has not resulted in higher-than-expected miscarriage rates or congenital anomalies. Providers should consider the risk to the health of MwCF combined with the lack of teratogenicity in animal reproductive models and limited safety data in the human fetus before discontinuing CFTR modulators before ART or natural partner conception. Survey collection is ongoing;results will be updated for presentationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Predictors of hypoxia severity in patients with COVID pneumonitis

Introduction/Aim: The COVID-19 Delta strain outbreak in New South Wales resulted in significantly increased hospitalisations for respiratory infection across the state. The most common cause of hospitalisation was hypoxaemia resulting from COVID pneumonitis. We aimed to identify predictors of oxygen requirements and disease trajectory in COVID pneumonitis (predominantly delta strain) from clinical data, laboratory and radiological testing. Method(s): Retrospective cohort study on 194 patients admitted with COVID pneumonitis in the Westmead COVID Respiratory ward from July 2021 to September 2021. We collected patient demographics, Charlson comorbidity index, blood tests on admission, chest X-ray (CXR) findings, and treatments received. Outcomes included peak FiO 2 required to maintain saturations>92%, duration of oxygen therapy, support device used, ICU admission and mortality. Patients were divided into three groups based on highest amount of supplemental oxygen needed to maintain saturations >92%: (i) Mild: no oxygen requirement;(ii) Moderate: FiO 2 up to 36% or nasal prongs 1-4 L and (iii) Severe: FiO 2 > 36%, requiring HFNP, NIV or intubation. We compared continuous data between groups with ANOVA and post-hoc multiple group comparisons with Bonferroni correction, and Chi-square tests for categorical data. Result(s): Mean age was 51.8 years;110 (57.7%) were male and 151 (78%) patients were unvaccinated. Average length of stay was 12.2 days and with mean duration of oxygen use was 8.9 days. Age and Charlson Comorbidity Index were found to be significant predictors of degree of hypoxia, with significant differences between the severity groups. There were significant differences in LDH, neutrophil-lymphocyte ratio, CRP and CXR severity between the three severity groups. Conclusion(s): Age, comorbidities and non-English speaking background were predictors of hypoxemia severity. While various biomarkers demonstrated utility in predicting severity of hypoxia, the strongest predictors in our study were CRP, procalcitonin, LDH, neutrophil-lymphocyte ratio and degree of radiological abnormalities.

Hypoxemia as a risk factor for acute kidney injury in COVID-19.

OBJECTIVE: To demonstrate if in patients with COVID-19 hypoxemia is a risk factor of acute kidney injury. MATERIALS AND METHODS: Cross-sectional, retrospective, descriptive, analytical study was done from May 1st to September 30th, 2020, including patients over 18 years of age admitted to the emergency service of a COVID-19 care medical center with the criteria of a suspected case of COVID-19 plus chest tomography with suggestive images. They were classified by the serum creatinine (SCr) value: Group 1 (G1) without acute kidney injury and group 2 (G2) with acute kidney injury. RESULT(S): One hundred and five patients were recruited. G1 included 32 patients (30.5%) and G2 73 (69.5%). Median SCr at admission was 0.7 and 1.0 mg/dL for G1 and G2, respectively (p = 0.05). The median PaO2/FiO2 at admission for G1 was 90 mmHg and for G2 105 mmHg (p = 0.76) without finding association with admission acute kidney injury;arterial oxygen saturation (SatO2) equal or higher than 92% to the moment of admission to the emergency department presented a negative correlation for the development of acute kidney injury (Pearson: -0.537, p = 0.04). CONCLUSION(S): In the initial phase of COVID-19, hypoxemia is not a triggering factor for acute kidney injury;however, SatO2 can be a distracting marker of respiratory stability since persistent hypoxemia would be one more conditioning of acute kidney injury.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Hipoxemia severa durante ECMO veno-venoso: a propósito de un caso clínico

Resumen La membrana de oxigenación extracorpórea (ECMO) brinda un soporte vital en casos de falla respiratoria aguda severa y refractaria al manejo convencional. A pesar de la mejoría de la sobrevida en pacientes seleccionados con SDRA severo, durante el soporte no es infrecuente eventos de hipoxemia severa, para lo cual es necesario identificar las causas e intervenir prontamente en el paciente y en el circuito del ECMO. La recirculación, el disbalance aporte consumo de oxígeno, la falla del oxigenador y la disminución de la función pulmonar residual son las principales causas de la hipoxemia severa aun durante el ECMO. Se describe el caso de un paciente obeso con SDRA severo y refractario por SARS-CoV-2 con necesidad de soporte ECMO, el cual durante su evolución presentó episodios de hipoxemia severa aun en ECMO, por lo que fueron necesarias múltiples intervenciones tanto en el circuito como en el paciente para solventar esta complicación. Este artículo presenta un caso clínico, una revisión de la literatura, y un algoritmo diagnóstico y terapéutico para una oportuna resolución de la hipoxemia severa en ECMO. Extracorporeal membrane oxygenation (ECMO) provides life support in cases of severe acute respiratory failure refractory to conventional management. Despite the improvement in survival in selected patients with severe ARDS, events of severe hypoxemia are not uncommon during support, for which it is necessary to identify the causes and promptly intervene in the patient and in the ECMO circuit. Recirculation, oxygen consumption imbalance, oxygenator failure, and decreased residual lung function are the main causes of severe hypoxemia even during ECMO. A case of an obese patient with severe ARDS and refractory to SARS CoV-2 in need of ECMO support is described, who during his evolution presented episodes of severe hypoxemia even on ECMO, for which multiple interventions were necessary both in the circuit and in the patient to solve this complication. This article presents a clinical case, a review of the literature, and a diagnostic and therapeutic algorithm for timely resolution of severe hypoxemia on ECMO.

ECMO in COVID–ARDS

Acute respiratory distress syndrome (ARDS) is a complex pathologic manifesto of acute lung injury that causes noncardiogenic pulmonary edema in different clinical presentations and increases the mortality rate up to 40%. The main physiologic changes are alveolar collapse/de-recruitment, decreased lung compliance, higher pulmonary vascular resistance, and gas-exchange disturbance, which may be combined with the patient's own respiratory response or assisted ventilatory support due to regional heterogeneity of the underlying lung injury. Since the main clinical features of COVID-19 (coronavirus disease 2019) pneumonia are hypoxemia and dyspnea, noninvasive oxygen therapy or mechanical ventilation remains the cornerstone of managing more severe cases. The aim of this chapter is to summarize the current state of knowledge on the worst pulmonary manifestation of the long COVID-19 syndrome, namely, COVID–ARDS, including parenchymal and functional abnormalities, follow-up strategies for early identification, and timely therapeutic interventions including veno-venous extracorporeal membrane oxygenation (vv-ECMO) management. Although only a limited proportion of COVID-19 patients develop severe respiratory failure refractory to advanced conventional treatments, it is of utmost importance to clearly define criteria for the use of vv-ECMO in this steadily growing patient population. The use of vv-ECMO in COVID–ARDS is a rescue treatment, if mechanical ventilation cannot guarantee appropriate gas exchange anymore, resulting in life-threatening or organ-damaging hypoxia and/or hypercapnia, whereas the vv-ECMO treatment modality still has a high all mortality rate in COVID–ARDS (> 50%). © 2023 Elsevier Inc. All rights reserved.