Lung function decline is mitigated following liver transplantation in people with cystic fibrosis: A retrospective cohort study.

There is paucity of literature on the health outcomes following liver transplantation (LT) in people with cystic fibrosis (pwCF). We aim to evaluate changes in lung function following LT in pwCF. We performed a retrospective cohort study of pwCF who underwent LT between 1987 and 2019 in the United States and Canada. Simultaneous lung-liver transplants and individuals who had lung transplant prior to LT were excluded. We analyzed pre-LT and post-LT percent predicted forced expiratory volume in 1 second, body mass index, rates of pulmonary exacerbation, and post-LT overall survival. A total of 402 LT recipients were included. The median age of transplant was 14.9 years and 69.7% of the transplants were performed in children less than 18 years old. The rate of decline in percent predicted forced expiratory volume in 1 second was attenuated after LT from -2.2% to -0.7% predicted per year with a difference of 1.5% predicted per year (95% CI, 0.8, 2.2; p < 0.001). Following LT, the rate of decline in body mass index was reduced, and there were fewer pulmonary exacerbations (0.6 pre vs. 0.4 post; rate ratio 0.7, p < 0.01). The median survival time post-transplant was 13.9 years and the overall probability of survival at 5 years was 77.6%. Those with higher lung function pre-LT had a lower risk of death post-LT, and those with genotypes other than F508 deletion had worse survival. LT in pwCF occurs most often in children and adolescents and is associated with a slower rate of decline in lung function and nutritional status, and a reduction in pulmonary exacerbations.

Clinical manifestations and treatment outcomes of human brucellosis at a tertiary care center in Saudi Arabia.

BACKGROUND: Brucellosis, which has profound public health and economic consequences, is endemic to Saudi Arabia. Brucella is transmitted to humans by direct contact with infected animals or by consumption of unpasteurized dairy products. Manifestations of brucellosis are protean and require a combination of drugs to prevent the emergence of resistance. The WHO recommends the use of doxycycline with rifampicin or an aminoglycoside for brucellosis, but experts in Saudi Arabia prefer to avoid the use of rifampicin and aminoglycosides to lessen the possibility of emergence of drug-resistant tuberculosis. OBJECTIVES: Compare rifampicin and doxycycline in the treatment of human brucellosis versus various combinations of doxycycline, with either trimethoprim-sulfamethoxazole (co-trimoxazole), quinolones or aminoglycosides, and describe the clinical manifestations of brucellosis. DESIGN: Retrospective medical record review. SETTING: Single tertiary care center. PATIENTS AND METHODS: Diagnosis of brucellosis was based on positive serology by standard agglutination test (SAT), or isolation by culture of Brucella species from blood, body fluid or tissue. MAIN OUTCOME MEASURES: Cure rate with the use of doxycycline in combination with either co-trimoxazole, quinolone or aminoglyco-sides in comparison to doxycycline/rifampicin and the clinical features of brucellosis. SAMPLE SIZE: 123. RESULTS: In 118 (96%) patients, the median IgG/IgM antibody titers at diagnosis and at 6 and 12 months were 1:1280/1:1280, 1:640/1:640, and 1:320/1:160, respectively. There were no differences in outcome between treatment regimens, as evidenced by a significant decrease in SAT titers and symptom resolution within six months. Five (4%) patients relapsed from non-adherence to treatment, but responded well to a second course of treatment. Blood cultures were positive in 50 patients (41%) patients. Fever, arthralgia and back pain were the most common symptoms. Good serological and clinical responses were achieved in 96% of patients. Relapse in 4% (n=5) was due to self-reported non-adherence. LIMITATIONS: Retrospective, relatively small sample size. CONCLUSIONS: Doxycycline with co-trimoxazole is as efficacious as doxycycline/rifampicin in non-focal brucellosis and is preferred in countries with a high prevalence of tuberculosis. CONFLICT OF INTEREST: None.

Serum ß2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

ß2-microglobulin (ß2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed ß2-m is measurable in circulation, and various disorders are accompanied by increases in ß2-m levels, including several viral infections. Therefore, we explored whether ß2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum ß2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean ß2-m level was 3.25±1.68 mg/l (reference range 0.8-2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean ß2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean ß2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean ß2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression ß2-m levels were the only significant predictor of disease severity. Our findings suggest that higher ß2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of ß2-m measurements. The role of ß2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.

Role of Fluorodeoxyglucose Positron Emission Tomogram Scan in Sirolimus-Induced Lung Toxicity: A Rare Case Report.

Lung toxicity is a rare but serious side effect of sirolimus, a mammalian target of rapamycin inhibitor used as an immunosuppressive agent in solid-organ transplant recipients. We report a case of 67-year-old man who had living-related renal transplant 12 years previously that was complicated by chronic allograft dysfunction. He presented with fever, cough, and shortness of breath, and his chest imaging showed bilateral patchy and ground glass opacities. Before symptoms of lung toxicity, the patient's sirolimus levels were in the range of high normal. Bronchoalveolar lavage ruled out infection, and a transbronchial biopsy was inconclusive. A fluorodeoxyglucose positron emission tomogram scan showed high uptake in the area of lung opacities with a standard uptake value of 4.7. His symptoms improved after he was switched from sirolimus to tacrolimus, and a thoracic computed tomography scan after 6 weeks showed complete resolution. Pulmonary toxicity should be considered in any patient on sirolimus with respiratory symptoms and opacities on chest imaging. The role of fluorodeoxyglucose positron emission tomogram scan in evaluation of sirolimus-induced lung toxicity has not been previously described, and this is the first report of this type of scan finding indicating intense inflammation in this condition.