A meta analysis on the utility of Anakinra in severe COVID-19 disease.

BACKGROUND AND OBJECTIVE: The most important presentation of COVID-19 is hyper inflammatory condition and cytokine storm that occurs due to excessive increase of the inflammatory mediators specially, pro-inflammatory interleukins such as IL-1ß, IL-6 and tumor necrosis factor-α which have an important role in the cytokine storm pathway. Up till now there is not a definitive treatment for COVID-19 disease, but according to the pathophysiology of the disease, Anakinra (Interleukin- 1 inhibitor) is an adjuvant treatment option in patients with severe COVID-19 by blocking the effect of IL-1. So, we aimed to summarize the studies that evaluated the safety and efficacy of Anakinra in patients diagnosed with COVID-19. METHODS: We performed a search in PubMed, Cochrane Library, Scopus, and Web of Science (WOS) databases from inception till 7 Jan 2022. Additionally, we searched randomized and non-randomized clinical trials, cohort, case series, case control, case report more than 3 patients which contain confirmed cases of COVID-19 who received Anakinra (Interleukin- 1 inhibitor) for the management of hyper-inflammatory condition associated with COVID-19 disease. A meta-analysis was conducted using review manager 5.4. RESULTS: We included 44 articles in the systematic review. Ultimately, 23 studies were incorporated in the meta-analysis with a total number of 3179 patients. Our analysis showed statistically significant difference in the following outcomes: duration of ICU stays [MD = -0.65, 95% CI (-1.09, -0.03), p = 0.04], the number of patients who needed invasive mechanical ventilation [RR = 0.57, 95% CI (0.39, 0.84), p = 0.004], and number of deaths [RR = 0.80, 95% CI (0.66, 0.99), p = 0.04]. Our analysis showed no statistically significant difference in the following outcomes: length of hospital stays [MD = -0.16, 95% CI (-0.42, 0.11), p = 0.26], oxygen-free days [MD = -0.81, 95% CI (-3.81, 2.20), p = 0.60], and the number of patients who needed non-invasive mechanical ventilation [RR = 1.09, 95% CI (0.47, 2.52), p = 0.84]. CONCLUSION: Anakinra showed some promising results in important outcomes related to COVID-19 as it significantly reduced the rate of mortality and the need of invasive mechanical ventilation. It should be used in severe cases more than mild and moderate cases to avoid possible immunosuppression complications. Anakinra use is safe in cases of COVID-19 at dose less than 100 mg. Another important outcome was significant reduction is the D-dimer level. Anakinra may be effective in the treatment of specific immunocompromised cases, but it should be used cautiously.

Emergence of Nosocomial Pneumonia Caused by Colistin-Resistant Escherichia coli in Patients Admitted to Chest Intensive Care Unit.

(1) Background: Colistin is a last-resort antibiotic used in treating multidrug-resistant Gram-negative infections. The growing emergence of colistin resistance in Escherichia coli (E. coli) represents a serious health threat, particularly to intensive care unit (ICU) patients. (2) Methods: In this work, we investigated the emergence of colistin resistance in 140 nosocomial E. coli isolated from patients with pneumonia and admitted to the chest ICU over 36 months. Virulence and resistance-related genes and E. coli pathotypes in colistin-resistant and colistin-sensitive isolates were determined. (3) Results: Colistin resistance was observed in 21/140 (15%) of the nosocomial E. coli isolates. The MIC50 of the resistant strains was 4 mg/L, while MIC90 was 16 mg/L. Colistin-resistant isolates were also co-resistant to amoxicillin, amoxicillin/clavulanic, aztreonam, ciprofloxacin, and chloramphenicol. The mechanism of colistin resistance was represented by the presence of mcr-1 in all resistant strains. Respectively, 42.9% and 36.1% of colistin-resistant and colistin-sensitive groups were extended-spectrum ß-lactamase (ESBL) producers, while 23.8% and 21% were metallo ß-lactamase (MBL) producers. blaTEM-type was the most frequently detected ESBL gene, while blaIMP-type was the most common MBL in both groups. Importantly, most resistant strains showed a significantly high prevalence of astA (76.2%), aggR (76.2%), and pic (52.4%) virulence-related genes. Enteroaggregative E. coli (76%) was the most frequently detected genotype among the colistin-resistant strains. (4) Conclusion: The high colistin resistance rate observed in E. coli strains isolated from patients with nosocomial pneumonia in our university hospital is worrisome. These isolates carry different drug resistance and virulence-related genes. Our results indicate the need for careful monitoring of colistin resistance in our university hospital. Furthermore, infection control policies restricting the unnecessary use of extended-spectrum cephalosporins and carbapenems are necessary.

Beta 2 Adrenergic Receptor Genetic Polymorphisms in Bronchial Asthma: Relationship to Disease Risk, Severity, and Treatment Response.

BACKGROUND: The ß2-adrenergic receptor gene is one of the most extensively studied genes with respect to asthma prevalence and severity. The Arg16Gly and Gln27Glu polymorphisms in the ß2-adrenergic receptor gene cause changes in the amino acids sequence of the receptor which may cause alteration in response to bronchodilators and the risk of asthma. OBJECTIVE: The purpose of the study was to determine the association between ß2-adrenergic receptor gene polymorphisms and asthma risk, severity and response to therapy. SUBJECTS AND METHODS: 58 asthmatic patients and 38 healthy subjects were included. The ß2-adrenergic receptor polymorphisms genotyping was done using Real-Time polymerase chain reaction. RESULTS: The allelic frequencies for the Arg16Gly polymorphism were 15.5%, 48.3%, and 36.2% for the homozygous A wild, heterozygous, and homozygous G mutant alleles in asthmatics (P < 0.01) and 5.3%, 47.4%, and 47.4% in healthy subjects (P < 0.01). For the Gln27Glu polymorphism, the allelic frequencies for the homozygous C wild, heterozygous and homozygous G mutant alleles were 51.7%, 41.4%, and 6.9% in asthmatics (P < 0.01) and 44.7%, 39.5%, and 15.8% in healthy subjects (P < 0.01). The heterozygous Arg16Gly and Gln27Glu were found in most of severe asthma cases (7/13, 53.8% each). While homozygous wild and mutant seemed to be protective and associated with mild disease in both alleles. Finally, 75% of Arg16Gly heterozygous group were good responders (P < 0.01), 81% of homozygous G mutant were bad responders. For Gln27Glu polymorphism, 60% of C wild group were good responders and 75% of G mutant group were bad responders. CONCLUSIONS: The findings suggest that the Arg16Gly and Gln27Glu polymorphisms in the ß2-AR gene are associated with asthma severity and response to therapy and might be used in personalized treatment for these patients in the future. This work is registered in ClinicalTrial.gov with ID: NCT03118869.

Association between hand grip strength with weaning and intensive care outcomes in COPD patients: A pilot study.

BACKGROUND: In COPD, weight loss and muscle wasting contribute significantly to morbidity, disability, and handicap. Dominant-handgrip strength for evaluation of muscle strength has not been tested as a parameter to predict outcome of weaning from mechanical ventilation (MV). OBJECTIVES: To evaluate the association between handgrip strength and the duration and success of weaning and extubation outcome. MATERIALS AND METHODS: This prospective study included 34 COPD patients requiring MV for at least 48 hours. Recovery from sedation and muscle relaxants was assessed before recruitment. Serial meseaurment of handgrip strength were assessed by trained personnel. RESULTS: There was a significant negative correlation between baseline hand grip and duration of MV (P = .047, r = -.343). The mean day 5 hand grip was significantly lower in person who died compared to survivors (5.7 ± 5.5 vs 18.2 ± 14.5, P = .044). The mean day 5 hand grip was significantly lower in patients who needed reintubation compared to those in patients who did not need reintubation (2.8 ± 2 vs 17.2 ± 13.9, P = .029). There was no significant difference in the mean baseline, day 2, day 3, day 4 and day 5 hand grip in weaning success compared to those in failure (P > .05). CONCLUSION: Handgrip strength may be good predictor for duration of MV, extubation outcome, ICU mortality and prognosis.

Assessment of cardiac and pulmonary function in children with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time (IRT) compared to control. Regarding pulmonary function tests, children with JIA showed significant decrease in FVC, PEF, Pimax, Pemax and DLCO compared to normal controls. This decrease was not related to age, height or weight of these patients. There was significant inverse correlation between lung function parameters and the rheumatoid factor titer, erythrosedimentation rate, disease duration and the duration of methotrexate use (P < 0.01). Despite of an asymptomatic cardiopulmonary status, significant systolic and diastolic functional abnormalities exist in children with JIA. Also, both restrictive and obstructive lung impairments were found.

Risk of lung cancer in patients with preinvasive bronchial lesions followed by autofluorescence bronchoscopy and chest computed tomography.

OBJECTIVES: To assess risk of lung cancer (LC) in patients with preinvasive bronchial lesions and to identify factors associated with higher risk. METHODS: 124 patients with one or more preinvasive bronchial lesions and normal chest computed tomography (CT) (mean age 66.7 years, 121 males and 3 females), followed-up by white light and autofluorescence bronchoscopy (AFB) every 4-6 mo and chest CT every 6-12 mo, end points were development of carcinoma in situ (CIS) or LC. RESULTS: Among 124 patients with 240 preinvasive bronchial lesions, 20 CIS or LC lesions were detected during follow-up in 20 (16%) patients, 7 were detected as new endobronchial lesions, 10 as new peripheral lesions and 3 as local progression from severe dysplasia to CIS. Median time to progression from the same site or development of CIS/LC elsewhere was 24 months (range: 6-54 mo). The Cumulative risk of development of CIS/LC was 7% at one year, 20% at three years and 44% at 5 years. Among detected lung cancers, 80% were stage 0 or stage I and underwent treatment with curative intent. Diagnosis of new SD during follow-up (p=0.0001), chronic obstructive pulmonary disease (COPD) (p=0.001) or smoking index >52 pack-year (p=0.042) was associated with higher risk. Even after controlling for other risk factors, COPD was associated with risk for lung cancer. Baseline lesion grade was not predictive of patient outcome (p=0.146). CONCLUSION: Patients with preinvasive bronchial lesions, especially those with new SD during follow-up, COPD or smoking >52 pack-year are at high risk of LC, AFB and CT follow-up facilitated early detection and treatment with curative intent.

Changes in pulmonary function in patients with ulcerative colitis.

OBJECTIVES: Information on the occurrence and frequency of pulmonary involvement in patients with ulcerative colitis (UC) is inconsistent. Some authors reported pulmonary impairment with UC by standard pulmonary function tests (PFTs) and documented a reduced diffusing capacity for carbon monoxide (DLCO) especially in patients with active disease, whereas others could not detect differences in routine PFTs between UC patients and controls. AIM: The aim of this prospective study was to determine the frequency and type of pulmonary dysfunction in patients with UC with respect to disease activity. Furthermore, to evaluate the influence of smoking, nutritional status, sputum cytology and sulphasalazine therapy on PFT parameters. PATIENTS AND METHODS: Twenty-six patients with UC (20 with active disease, 6 inactive) and 16 age and sex matched healthy controls were investigated with respect to the following pulmonary function tests, forced vital capacity (FVC), forced expiratory volume in the 1s (FEV(1)%) and their ratio (FEV(1)/FVC) and forced expiratory flow 25-75% (FEF25-75%) as well as oxygen saturation. For UC patients, colonoscopy and biopsy were done. Disease activity was assessed by Truelove index for UC. Induced sputum was sampled for cytology. Smoking habit, body mass index (BMI) and medications were recorded. RESULTS: Fifteen out of 26 patients with UC (57.6%) exhibited at least one pathological pulmonary function test (<80% of predicted value). Small airway obstruction was reported in the 15 patients, restrictive dysfunction in 30.7% and obstructive dysfunction in 11.5%. The impairment of PFTs was significant and more pronounced in patients with active disease, FVC (-14% of predicted), FEV(1) (-9% of predicted) and FEF25-75% (-32% of predicted), P<0.01, 0.05 and 0.01, respectively. There was no significant influence of smoking and medications on PFTs. CONCLUSIONS: UC patients show significantly decreased lung function tests in comparison to healthy controls. The impairment in active disease exceeded that during the remission. Early recognition is important, as they can be strikingly steroid responsive.