Pharmacogenomics. 2022 Jun 7. doi: 10.2217/pgs-2022-0025. Online ahead of print.

ABSTRACT

Cystic fibrosis is a genetic, multiorgan system disease that involves the use of many medications to control symptoms associated with the underlying condition. Many of these medications have Clinical Pharmacogenetics Implementation Consortium evidence-based guidelines for pharmacogenomics that are available to guide dosing. The aim of this article is to review relevant literature and evaluate the utility of preemptive pharmacogenomics testing for persons with cystic fibrosis and propose a pharmacogenomics panel that could be considered standard of care for persons with cystic fibrosis.

PMID:35670256 | DOI:10.2217/pgs-2022-0025

Pediatr Pulmonol. 2022 Jun 6. doi: 10.1002/ppul.26026. Online ahead of print.

ABSTRACT

BACKGROUND: Video game-based systems have been proposed to improve effectiveness and compliance with exercise training in children and adolescents with non-cystic fibrosis bronchiectasis (NCFB). This study aimed to investigate the effects of aerobic and breathing video game-based exercises (VGE) on pulmonary function, respiratory and peripheral muscle strength, functional capacity, and balance in children and adolescents with NCFB.

METHOD: Thirty-nine children and adolescents aged between 8-18 years with NCFB were randomly allocated into three groups as "home-based chest physiotherapy group" (CP), "aerobic VGE given in addition to home-based chest physiotherapy group" (CP+aerobic VGE), and "breathing VGE given in addition to home-based chest physiotherapy group" (CP+breathing VGE). All 3 groups performed chest physiotherapy program twice a day for 7 days per week for 8 weeks. Pulmonary function, respiratory and peripheral muscle strength, functional capacity, and balance were assessed at baseline and after 8 weeks of training.

RESULTS: The improvement in maximum expiratory pressure and balance scores were significantly higher in both CP+aerobic and CP+breathing VGE groups. The significant improvement in maximum inspiratory pressure was greater in the CP+breathing VGE group. The changes in peripheral muscle strength and functional capacity were significantly higher in the CP+aerobic VGE group.

CONCLUSIONS: The present study showed that aerobic VGE provides additional benefits in improving peripheral muscle strength and functional capacity, while breathing VGE provides further increase in improving respiratory muscle strength. In addition, both aerobic and breathing VGE were effective in improving balance, but they were not superior to each other. This article is protected by copyright. All rights reserved.

PMID:35669989 | DOI:10.1002/ppul.26026

Rev Bras Farmacogn. 2022 May 30:1-11. doi: 10.1007/s43450-022-00262-w. Online ahead of print.

ABSTRACT

Humans being unable to synthesize beta-carotene, the provitamin A, depend on external sources as its supplement. Health benefits and dietary requirements of beta-carotene are interrelated. This orange-red coloured pigment has been enormously examined for its capacity to alleviate several chronic diseases including various types of cancer, cystic fibrosis, as well as COVID-19. However, this class of phytoconstituents has witnessed a broad research gap due to several twin conclusions that have been reported. Natural sources for these compounds along with their extraction methods have been mentioned. The current communication aims at contributing to the global scientific literature on beta-carotene's application in prevention and treatment of lifestyle diseases.

PMID:35669276 | PMC:PMC9150880 | DOI:10.1007/s43450-022-00262-w

Front Vet Sci. 2022 May 20;9:878952. doi: 10.3389/fvets.2022.878952. eCollection 2022.

ABSTRACT

For both human and veterinary patients, non-infectious intestinal disease is a major cause of morbidity and mortality. To improve treatment of intestinal disease, large animal models are increasingly recognized as critical tools to translate the basic science discoveries made in rodent models into clinical application. Large animal intestinal models, particularly porcine, more closely resemble human anatomy, physiology, and disease pathogenesis; these features make them critical to the pre-clinical study of intestinal disease treatments. Previously, large animal model use has been somewhat precluded by the lack of genetically altered large animals to mechanistically investigate non-infectious intestinal diseases such as colorectal cancer, cystic fibrosis, and ischemia-reperfusion injury. However, recent advances and increased availability of gene editing technologies has led to both novel use of large animal models in clinically relevant intestinal disease research and improved testing of potential therapeutics for these diseases.

PMID:35669174 | PMC:PMC9164269 | DOI:10.3389/fvets.2022.878952

Front Pharmacol. 2022 May 20;13:876842. doi: 10.3389/fphar.2022.876842. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians, affecting more than 100,000 individuals worldwide. It is caused by pathogenic variants in the gene encoding CFTR, an anion channel at the plasma membrane of epithelial and other cells. Many CF pathogenic variants disrupt the biosynthesis and trafficking of CFTR or reduce its ion channel function. The most frequent mutation, loss of a phenylalanine at position 508 (F508del), leads to misfolding, retention in the endoplasmic reticulum, and premature degradation of the protein. The therapeutics available for treating CF lung disease include antibiotics, mucolytics, bronchodilators, physiotherapy, and most recently CFTR modulators. To date, no cure for this life shortening disease has been found. Treatment with the Triple combination drug therapy, TRIKAFTA®, is composed of three drugs: Elexacaftor (VX-445), Tezacaftor (VX-661) and Ivacaftor (VX-770). This therapy, benefits persons with CF, improving their weight, lung function, energy levels (as defined by reduced fatigue), and overall quality of life. We examined the effect of combining LAU-7b oral treatment and Triple therapy combination on lung function in a F508deltm1EUR mouse model that displays lung abnormalities relevant to human CF. We assessed lung function, lung histopathology, protein oxidation, lipid oxidation, and fatty acid and lipid profiles in F508deltm1EUR mice.

PMID:35668939 | PMC:PMC9163687 | DOI:10.3389/fphar.2022.876842

Allergy Asthma Clin Immunol. 2022 Jun 6;18(1):46. doi: 10.1186/s13223-022-00684-0.

ABSTRACT

RATIONALE: Patients with asthma who have neutrophilic bronchitis may have an underlying cause leading to increased susceptibility to airway infections.

METHODS: Retrospective review of patients with asthma who had a previous history of recurrent exacerbations that had been associated with airway or sinus infections referred to a tertiary asthma center between 2005 and 2020. Demographics, clinical features, and airway inflammation type determined by sputum cytometry were compared between CFTR carriers and non-carriers. Multiple linear regression was used to identify clinical predictors of CFTR carrier status. Response to nebulized hypertonic saline was assessed by comparing the number of infective exacerbations before and after its initiation.

RESULTS: 75 patients underwent CFTR mutation testing. Of these, 13 (17%) were CFTR carriers. The most common mutation was [Formula: see text]F508. CFTR carriers were older (adjusted odds ratio 1.06 (CI 95% 1.01, 1.13)) and had more frequent flares requiring hospitalization (4.19 (1.34, 24.74)). Neutrophilic airway inflammation was the most common inflammatory subtype in CFTR carriers, though 8/13 also had eosinophilic bronchitis. Nebulized hypertonic saline was well tolerated by most and reduced the frequency of infective exacerbations.

CONCLUSIONS: The prevalence of CFTR heterozygosity in this cohort with recurrent neutrophilic bronchitis is higher than in the general population. Respiratory disease in CFTR carriers is associated with older age and may cause significant morbidity. Airway neutrophilia is the most common inflammatory subtype, but > 50% had eosinophilic bronchitis requiring treatment. Hypertonic saline appears to be well tolerated and effective in reducing the number of infective exacerbations.

PMID:35668512 | DOI:10.1186/s13223-022-00684-0

Pediatr Pulmonol. 2022 Jun 6. doi: 10.1002/ppul.26032. Online ahead of print.

ABSTRACT

To conclude, assessing the incidence of CF in Tunisia is not only a first step for planning NBS but also a core for genetic counselling (accurate calculation of recurrence risks in families) and for health care needs. Our work may also help neighbouring countries facing similar issues to better evaluate the disease This article is protected by copyright. All rights reserved.

PMID:35668039 | DOI:10.1002/ppul.26032

J Cyst Fibros. 2022 Jun 3:S1569-1993(22)00149-7. doi: 10.1016/j.jcf.2022.05.011. Online ahead of print.

ABSTRACT

Chronic polymicrobial airway infections are a hallmark of cystic fibrosis (CF) lung disease. Antibiotic therapy is a primary treatment of CF pulmonary exacerbations (PEx); however, the impact of episodic antibiotic treatment on airway bacterial communities has not been well described. We analyzed sputum samples from adults with CF obtained immediately before and during antibiotic treatment of PEx. Sequencing of the V4 region of the bacterial 16S ribosomal RNA gene was used to assess changes in bacterial community structure during antibiotic treatment. The peak impact of antibiotic treatment was observed by day four or five of treatment. These findings advance our understanding of bacterial community dynamics during antibiotic treatment of PEx and complement recent and ongoing studies evaluating the optimal duration of antibiotic therapy for PEx.

PMID:35667975 | DOI:10.1016/j.jcf.2022.05.011

J Cyst Fibros. 2022 Jun 3:S1569-1993(22)00150-3. doi: 10.1016/j.jcf.2022.05.012. Online ahead of print.

NO ABSTRACT

PMID:35667974 | DOI:10.1016/j.jcf.2022.05.012

J Cyst Fibros. 2022 Jun 3:S1569-1993(22)00147-3. doi: 10.1016/j.jcf.2022.05.009. Online ahead of print.

ABSTRACT

BACKGROUND: Since 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA).

METHODS: We performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population.

RESULTS: A total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant.

CONCLUSIONS: Patients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.

PMID:35667973 | DOI:10.1016/j.jcf.2022.05.009

Rozhl Chir. 2022 Spring;101(5):239-243. doi: 10.33699/PIS.2022.101.5.239-243.

ABSTRACT

During the last 23 years of the National Lung Transplant Program in the Czech Republic, more than 500 lung transplantations, 4 retransplantations and one lobar retransplantation have been performed. We present the case report of a female patient with cystic fibrosis who underwent her first bilateral lung transplantation in January 2020. Due to a chronic lung allograft dysfunction, the patient required ECMO support and retransplantation. For the first time in the Czech Republic, a lung retransplantation with “ECMO bridge to (re)transplantation” preoperative support was performed in April 2021. The patient was discharged 39 days after retransplantation in a stable condition. At the day 90 follow-up visit, the patient was in a generally good condition with satisfying spirometric functions.

PMID:35667874 | DOI:10.33699/PIS.2022.101.5.239-243

Asian J Androl. 2022 Jun 3. doi: 10.4103/aja202236. Online ahead of print.

ABSTRACT

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.

PMID:35665694 | DOI:10.4103/aja202236

Front Physiol. 2022 May 18;13:899286. doi: 10.3389/fphys.2022.899286. eCollection 2022.

ABSTRACT

The five plasma membrane Na+/H+ exchanger (NHE) isoforms in the gastrointestinal tract are characterized by distinct cellular localization, tissue distribution, inhibitor sensitivities, and physiological regulation. NHE1 (Slc9a1) is ubiquitously expressed along the gastrointestinal tract in the basolateral membrane of enterocytes, but so far, an exclusive role for NHE1 in enterocyte physiology has remained elusive. NHE2 (Slc9a2) and NHE8 (Slc9a8) are apically expressed isoforms with ubiquitous distribution along the colonic crypt axis. They are involved in pHi regulation of intestinal epithelial cells. Combined use of a knockout mouse model, intestinal organoid technology, and specific inhibitors revealed previously unrecognized actions of NHE2 and NHE8 in enterocyte proliferation and differentiation. NHE3 (Slc9a3), expressed in the apical membrane of differentiated intestinal epithelial cells, functions as the predominant nutrient-independent Na+ absorptive mechanism in the gut. The new selective NHE3 inhibitor (Tenapanor) allowed discovery of novel pathophysiological and drug-targetable NHE3 functions in cystic-fibrosis associated intestinal obstructions. NHE4, expressed in the basolateral membrane of parietal cells, is essential for parietal cell integrity and acid secretory function, through its role in cell volume regulation. This review focuses on the expression, regulation and activity of the five plasma membrane Na+/H+ exchangers in the gastrointestinal tract, emphasizing their role in maintaining intestinal homeostasis, or their impact on disease pathogenesis. We point to major open questions in identifying NHE interacting partners in central cellular pathways and processes and the necessity of determining their physiological role in a system where their endogenous expression/activity is maintained, such as organoids derived from different parts of the gastrointestinal tract.

PMID:35665228 | PMC:PMC9159811 | DOI:10.3389/fphys.2022.899286

Mol Ther Nucleic Acids. 2022 May 4;28:685-701. doi: 10.1016/j.omtn.2022.04.033. eCollection 2022 Jun 14.

ABSTRACT

Nonsense mutations or premature termination codons (PTCs) comprise ∼11% of all genetic lesions, which result in over 7,000 distinct genetic diseases. Due to their outsized impact on human health, considerable effort has been made to find therapies for nonsense-associated diseases. Suppressor tRNAs have long been identified as a possible therapeutic for nonsense-associated diseases; however, their ability to inhibit nonsense-mediated mRNA decay (NMD) and support significant protein translation from endogenous transcripts has not been determined in mammalian cells. Here, we investigated the ability of anticodon edited (ACE)-tRNAs to suppress cystic fibrosis (CF) causing PTCs in the cystic fibrosis transmembrane regulator (CFTR) gene in gene-edited immortalized human bronchial epithelial (16HBEge) cells. Delivery of ACE-tRNAs to 16HBEge cells harboring three common CF mutations G542XUGA-, R1162XUGA-, and W1282XUGA-CFTR PTCs significantly inhibited NMD and rescued endogenous mRNA expression. Furthermore, delivery of our highly active leucine-encoding ACE-tRNA resulted in rescue of W1282X-CFTR channel function to levels that significantly exceed the necessary CFTR channel function for therapeutic relevance. This study establishes the ACE-tRNA approach as a potential standalone therapeutic for nonsense-associated diseases due to its ability to rescue both mRNA and full-length protein expression from PTC-containing endogenous genes.

PMID:35664697 | PMC:PMC9126842 | DOI:10.1016/j.omtn.2022.04.033

STAR Protoc. 2022 May 27;3(2):101419. doi: 10.1016/j.xpro.2022.101419. eCollection 2022 Jun 17.

ABSTRACT

Here, we present a standardized protocol for isolation, maintenance, and polarization of the respiratory epithelial primary cells from patient samples acquired from nasal brushing, polyp specimens, or lung explants. This protocol generates a clearly defined polarized layer of epithelial cells on filters, with a good number of ciliated cells and a thin layer of mucus. We detail the steps for samples prepared from patients with cystic fibrosis as well as from subjects without cystic fibrosis.

PMID:35664255 | PMC:PMC9157560 | DOI:10.1016/j.xpro.2022.101419

Int J Pediatr Adolesc Med. 2022 Jun;9(2):78-82. doi: 10.1016/j.ijpam.2021.06.002. Epub 2021 Jun 22.

ABSTRACT

BACKGROUND: Internationally, Cystic fibrosis-associated liver disease (CFLD) is considered the third leading cause of death, following lung disease and transplantation complications.

AIMS: To identify the prevalence of CFLD in cystic fibrosis (CF) patients.

METHODOLOGY: A retrospective chart review for all patients with CF liver disease from a tertiary care center.

RESULT: A total of 341 CF patients were included. The mean age at the diagnosis of liver disease is 13.5 (7.6) years.The first elevated ALT was reported in 190/341 patients (56%), elevated AST in 124 patients (36%), elevated alkaline phosphatase (ALP) in 166 patients (49.1%), elevated GGT in 57 patients (23%), and elevated bilirubin in 24 patients (7%). There was an improvement of the liver enzyme values during the follow-up period, P-value = (<0.05).Ultrasound liver assessments were performed in 258/341 patients (75.7%). One hundred and twelve patients (43%) had abnormal findings. In 14 patients (5.4%), assessment exhibited advanced liver disease (liver cirrhosis and periportal fibrosis). Out of 190 patients, who were given ursodeoxycholic acid for elevated liver enzymes, 180 (94.7%) exhibited improvement. One patient underwent liver transplant at the age of 12. Four patients were submitted for liver biopsy; periportal fibrosis was observed in 4 patients (1.6%), and liver cirrhosis by ultrasound (US) in 10 patients (4%).

CONCLUSION: Patients with CF should be screened early for liver enzymes, and should undergo the US study to detect liver disease at early stages and to prevent its progression.

PMID:35663788 | PMC:PMC9152554 | DOI:10.1016/j.ijpam.2021.06.002

Int J Pediatr Adolesc Med. 2022 Jun;9(2):108-112. doi: 10.1016/j.ijpam.2021.07.001. Epub 2021 Jul 7.

ABSTRACT

INTRODUCTION: Bacterial infections in CF patients are common and start early in life. The prognosis of the disease is substantially dependent on chronic respiratory infection and inflammation. Pseudomonas aeruginosa (PA) infection or chronic colonization have been established to cause a chronic decline in pulmonary function (PFT), and/or increase CF mortality.

OBJECTIVES: To obtain the prevalence of all bacterial pathogens in our CF patients and assess their evolution over time.

METHOD: A retrospective review of 327 patients with confirmed CF of all age groups, who had respiratory culture samples at the first visit and on a regular follow-up between January 1, 1990 and December 2018, was conducted.

RESULTS: A total of 327 patients had a respiratory culture obtained at presentation. Two hundred and sixteen (66%) of 327 patients are alive, while 111 (34%) have died. Respiratory cultures were taken from nasopharyngeal aspiration (NPA) in 199 patients (61%), tracheal aspirate in 9 (3%), bronchoalveolar lavage (BAL)in one (0.29%), and in 124 patients (38%), sputum was induced. The eastern province contributed to the highest number of patients (122, 37.7%). There is a persistent increase in the prevalence of the common bacteria over the follow-up period of 7 years, namely Hemophilus influenzae (H. influenzae), Staphylococcus aureus (S. aureus), and all Pseudomonas (P. aeruginosa) culture types.Comparing cultures from the first and last follow-up visits, there was an increase in the prevalence of all (P. aeruginosa) cultures from 120 (34%) to 137 (53%), and a decrease in the prevalence of (S. aureus) and (H. influenzae) during the same follow-up period.

CONCLUSION: There is a progressive increase in the number of patients with the most pathogenic types of bacteria because of the advanced age at presentation. As more adult patients are enrolled, there is a need for improved awareness regarding the early eradication of pathogenic bacteria to prevent progressive pulmonary damage.

PMID:35663786 | PMC:PMC9152558 | DOI:10.1016/j.ijpam.2021.07.001

Int J Pediatr Adolesc Med. 2022 Jun;9(2):104-107. doi: 10.1016/j.ijpam.2021.10.003. Epub 2021 Nov 29.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a multisystemic chronic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. These mutations are classified in to six classes. Ivacaftor is a CFTR potentiator which partially restores the CFTR function for class III mutations. In Oman, p.Ser549Arg (class III) is the most common mutation (65% of cases). Our study prospectively evaluated the tolerance and clinical efficacy of ivacaftor.

METHODS: A prospective observational study was conducted at the Royal Hospital, Oman. All children aged 6-18 years who are followed and carry at least one copy of the p.Ser549Arg mutation were started on Ivacaftor and included in the study. Data collected included weight, height, forced expiratory volume in first second (FEV1), sweat chloride concentration, stool elastase level and liver enzymes at baseline and at 12, 24, 36, and 48 weeks after initiation of treatment. The number of CF pulmonary exacerbations one year before and during treatment were compared.

RESULTS: Twenty one children were started on Ivacaftor (90% homozygous for p.Ser549Arg). The mean age was 10.8 (SD ±3.5) years. When compared to baseline, FEV1 significantly improved by a mean of 10.8 (SD ±13.5) percentage points (pp) and 14.3 (SD ±7.5) pp at 12 and 48 weeks respectively. The sweat chloride level significantly dropped from a mean of 107 (SD ±8.5) mmol/l to 38.5 (SD ±22.3) mmol/l at 12 weeks and remained low. The Body Mass Index (BMI) improved by a mean of 1.37 (SD ±1.3) kg/m 2 and 1.9 (SD ±1.35) kg/m 2 at 24 and 48 weeks of treatment respectively. The number of admissions the year before and during treatment reduced significantly from a mean of 2.2 (SD± 1.9) to 0.7 (SD ±1) admission per year. Two children developed transaminitis.

CONCLUSION: Ivacaftor is well tolerated and resulted in a significant improvement in FEV1, BMI and sweat chloride level in children with p.Ser549Arg CFTR mutation.

PMID:35663785 | PMC:PMC9152560 | DOI:10.1016/j.ijpam.2021.10.003

Front Nutr. 2022 May 17;9:873890. doi: 10.3389/fnut.2022.873890. eCollection 2022.

ABSTRACT

The progressions of a number of lung diseases, including acute lung injury, cystic fibrosis, asthma, chronic obstructive pulmonary disease, pneumonia and tuberculosis (TB) are found to be highly associated with inflammatory responses. As a signaling nutrient, Vitamin D modulates the activities of dendritic cells, monocytes/macrophages, T and B cells, and tissue epithelial cells in the body to induce inflammatory responses and boost immune functions. Given the high prevalence of vitamin D deficiency among pulmonary insufficiency and inflammation-related cases, researchers indicated vitamin D supplementation could have a potential role in the prevention and treatment of lung disease, especially tuberculosis. In this paper, we reviewed published studies on the role of vitamin D in the prevention and treatment of tuberculosis. The paper identified vitamin D's potential as an adjunctive therapy and demonstrated its safety so as to provide an impetus for further studies and clinical applications.

PMID:35662926 | PMC:PMC9159148 | DOI:10.3389/fnut.2022.873890

Lancet Respir Med. 2022 Jun 2:S2213-2600(22)00216-8. doi: 10.1016/S2213-2600(22)00216-8. Online ahead of print.

NO ABSTRACT

PMID:35662407 | DOI:10.1016/S2213-2600(22)00216-8