J Pediatr Pharmacol Ther. 2022;27(3):214-227. doi: 10.5863/1551-6776-27.3.214. Epub 2022 Mar 21.

ABSTRACT

Intravenous beta-lactam antibiotics are the most prescribed antibiotic class in US hospitalized patients of all ages; therefore, optimizing their dosing is crucial. Bactericidal killing is best predicted by the time in which beta-lactam drug concentrations are maintained above the organism's minimum inhibitory concentration (MIC), rather than achievement of a high peak concentration. As such, administration of beta-lactam antibiotics via extended or continuous infusions over a minimum of 3 hours, rather than standard infusions over approximately 30 minutes, has been associated with improved achievement of pharmacodynamic targets and improved clinical outcomes in adult medical literature. This review summarizes the pediatric medical literature. Applicable studies include pharmacodynamic models, case series, retrospective analyses, and prospective studies on the use of extended infusion and continuous infusion penicillins, cephalosporins, carbapenems, and monobactams in neonates, infants, children, and adolescents. Specialized patient populations with unique pharmacokinetics and high-risk infections (neonates, critically ill, febrile neutropenia, cystic fibrosis) are also reviewed. While more studies are needed to confirm prospective clinical outcomes, the current body of evidence suggests extended and continuous infusions of beta-lactam antibiotics are well tolerated in children and improve achievement of pharmacokineticpharmacodynamic targets with similar or superior clinical outcomes, particularly in infections associated with high MICs.

PMID:35350159 | PMC:PMC8939270 | DOI:10.5863/1551-6776-27.3.214

Mol Genet Genomic Med. 2022 Mar 29:e1926. doi: 10.1002/mgg3.1926. Online ahead of print.

ABSTRACT

BACKGROUND: Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles.

RESULTS: We report a family with a complicated syndromic phenotype, which led to the suspicion not only of CF, but of a dominantly inherited skeletal dysplasia (SD). Whereas the molecular basis of the SD was not clarified, segregation analysis was central to make a correct molecular diagnosis of CF, as it allowed to identify three CFTR variants encompassing two known maternal mutations and a novel paternal microdeletion.

CONCLUSION: This case well illustrates possible pitfalls in the clinical and molecular diagnosis of CF; presence of complex phenotypes deflecting clinicians from appropriate CF recognition, and/or identification of two mutations assumed to be in trans but with an unconfirmed status, which underline the importance of an in-depth molecular CFTR analysis.

PMID:35348309 | DOI:10.1002/mgg3.1926

Magn Reson Med. 2022 Mar 29. doi: 10.1002/mrm.29184. Online ahead of print.

ABSTRACT

PURPOSE: To introduce a widely applicable workflow for pulmonary lobe segmentation of MR images using a recurrent neural network (RNN) trained with chest CT datasets. The feasibility is demonstrated for 2D coronal ultrafast balanced SSFP (ufSSFP) MRI.

METHODS: Lung lobes of 250 publicly accessible CT datasets of adults were segmented with an open-source CT-specific algorithm. To match 2D ufSSFP MRI data of pediatric patients, both CT data and segmentations were translated into pseudo-MR images that were masked to suppress anatomy outside the lung. Network-1 was trained with pseudo-MR images and lobe segmentations and then applied to 1000 masked ufSSFP images to predict lobe segmentations. These outputs were directly used as targets to train Network-2 and Network-3 with non-masked ufSSFP data as inputs, as well as an additional whole-lung mask as input for Network-2. Network predictions were compared to reference manual lobe segmentations of ufSSFP data in 20 pediatric cystic fibrosis patients. Manual lobe segmentations were performed by splitting available whole-lung segmentations into lobes.

RESULTS: Network-1 was able to segment the lobes of ufSSFP images, and Network-2 and Network-3 further increased segmentation accuracy and robustness. The average all-lobe Dice similarity coefficients were 95.0 ± 2.8 (mean ± pooled SD [%]) and 96.4 ± 2.5, 93.0 ± 2.0; and the average median Hausdorff distances were 6.1 ± 0.9 (mean ± SD [mm]), 5.3 ± 1.1, 7.1 ± 1.3 for Network-1, Network-2, and Network-3, respectively.

CONCLUSION: Recurrent neural network lung lobe segmentation of 2D ufSSFP imaging is feasible, in good agreement with manual segmentations. The proposed workflow might provide access to automated lobe segmentations for various lung MRI examinations and quantitative analyses.

PMID:35348244 | DOI:10.1002/mrm.29184

Am J Physiol Lung Cell Mol Physiol. 2022 Mar 29. doi: 10.1152/ajplung.00487.2021. Online ahead of print.

ABSTRACT

Excessive production, secretion and retention of abnormal mucus is a pathologic feature of many obstructive airways diseases including asthma, chronic obstructive pulmonary disease, cystic fibrosis and bronchiectasis. Azithromycin is an antibiotic that also possesses immunomodulatory and mucoregulatory activities, which may contribute to the clinical effectiveness of azithromycin in these obstructive airway diseases. The current study investigated these non-antibiotic activities of azithromycin (or saline) in mice exposed daily to intranasal house dust mite (HDM) extract (or SHAM inoculation) for 10 days. HDM-exposed mice exhibited airways hyperresponsiveness to aerosolised methacholine, a pronounced mixed eosinophilic and neutrophilic inflammatory response, increased airway smooth muscle (ASM) thickness and elevated levels of epithelial mucin staining (compared to SHAM mice). Azithromycin (50 mg/kg s.c., 2 h prior to each HDM exposure) significantly attenuated HDM-induced airways hyperresponsiveness to methacholine, airways inflammation (bronchoalveolar lavage eosinophil and neutrophils numbers, and cytokine/chemokine levels), and epithelial mucin staining (mucous metaplasia) (P<0.05, 2-way ANOVA). Isolated tracheal segments of HDM-exposed mice secreted Muc5ac and Muc5b (above baseline levels) in response to exogenous ATP. Moreover, ATP-induced secretion of mucins was significantly attenuated in segments obtained from azithromycin-treated, HDM-exposed mice (P<0.05, 2-way ANOVA). In additional ex vivo studies, ATP-induced secretion of Muc5ac from HDM-exposed tracheal segments was inhibited by in vitro exposure to azithromycin. In vitro azithromycin also inhibited ATP-induced secretion of Muc5ac and Muc5b in tracheal segments from IL-13-exposed mice. In summary, azithromycin inhibited ATP-induced mucin secretion and airways inflammation in HDM-exposed mice, both of which are likely to contribute to suppression of airways hyperresponsiveness.

PMID:35348023 | DOI:10.1152/ajplung.00487.2021

Genomics. 2022 Mar 25:110350. doi: 10.1016/j.ygeno.2022.110350. Online ahead of print.

ABSTRACT

Robust protocols to examine 3D chromatin structure have greatly advanced knowledge of gene regulatory mechanisms. Here we focus on the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which provides a paradigm for validating models of gene regulation built upon genome-wide analysis. We examine the mechanisms by which multiple cis-regulatory elements (CREs) at the CFTR gene coordinate its expression in intestinal epithelial cells. Using CRISPR/Cas9 to remove CREs, individually and in tandem, followed by assays of gene expression and higher-order chromatin structure (4C-seq), we reveal the cross-talk and dependency of two cell-specific intronic enhancers. The results suggest a mechanism whereby the locus responds when CREs are lost, which may involve activating transcription factors such as FOXA2. Also, by removing the 5' topologically-associating domain (TAD) boundary, we illustrate its impact on CFTR gene expression and architecture. These data suggest a multi-layered regulatory hierarchy that is highly sensitive to perturbations.

PMID:35346781 | DOI:10.1016/j.ygeno.2022.110350

Curr Diabetes Rev. 2022 Mar 28. doi: 10.2174/1573399818666220328145046. Online ahead of print.

ABSTRACT

Histological manifestations of diabetic kidney disease (DKD) include mesangiolysis, mesangial matrix expansion, mesangial cell proliferation, thickening of the glomerular basement membrane, podocyte loss and foot process effacement, hyalinosis of the glomerular arterioles, interstitial fibrosis and tubular atrophy. Glomerulomegaly is a typical finding. Histological features of DKD may occur in the absence of clinical manifestations, having been documented in patients with normal urinary albumin excretion and normal glomerular filtration rate. Furthermore, the histological picture progresses over time while clinical data may remain normal. Conversely, histological lesions of DKD improve with metabolic normalization, following effective pancreas transplantation. Insulin resistance has been associated with the clinical manifestations of DKD (nephromegaly, glomerular hyperfiltration, albuminuria, and kidney failure). Likewise, insulin resistance may underlie the histological manifestations of DKD. Morphological changes of DKD are absent in newly diagnosed type 1 diabetes patients (with no insulin resistance), but appear afterwards when insulin resistance develops. In contrast, structural lesions of DKD are typically present before the clinical diagnosis of type 2 diabetes. Several heterogeneous conditions that share the occurrence of insulin resistance, such as aging, obesity, acromegaly, lipodystrophy, cystic fibrosis, insulin receptor dysfunction, and Alström syndrome, also share both clinical and structural manifestations of kidney disease, including glomerulomegaly and other features of DKD, focal segmental glomerulosclerosis, and C3 glomerulopathy, which might be ascribed to reduction in the synthesis of factor H binding sites (such as heparan sulfate) that leads to uncontrolled complement activation. Alström syndrome patients show systemic interstitial fibrosis markedly similar to that present in diabetes.

PMID:35346008 | DOI:10.2174/1573399818666220328145046

Dis Markers. 2022 Mar 19;2022:4798136. doi: 10.1155/2022/4798136. eCollection 2022.

ABSTRACT

BACKGROUND: Complications of cystic fibrosis-associated liver disease (CFLD) are a leading nonpulmonary cause of death. Noninvasive tests enabling early detection of liver changes, especially in children are sought. The aim of the study was to assess the scale of liver fibrosis with the use of elastography in paediatric patients with diagnosed cystic fibrosis (CF) and its comparison with other tests (APRI and Fibrotest).

METHODS: We examined 41 children, in the age range 2-21 years, with diagnosed CF. The analysis a included clinical picture, laboratory parameters of liver damage, and cholestasis. Aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrotest were done in all patients. Liver stiffness measurements were acquired using shear-wave elastography (SWE).

RESULTS: CFLD was diagnosed in 16/41 patients (39%). Abnormal elastography was observed in 19/41 patients (46.3%), and in 5/41 (12.2%), the changes were advanced (F4). Abnormal elastography was observed in 12/16 (75%) of the patients with CFLD, and in 7/25 (28%), there were no lesions observed in the liver in the course of cystic fibrosis. In all patients with F4, we observed abnormal results of the APRI and Fibrotest. In most patients with small changes in elastography, we found normal results of the APRI and Fibrotest.

CONCLUSION: Elastography seems to be a noninvasive examination useful in everyday clinical work in detecting early liver changes and monitoring of progression in paediatric patients with diagnosed cystic fibrosis, ahead of changes in laboratory tests. The cost-effectiveness of this test, the possibility of its repetition, and its availability are additional benefits.

PMID:35345868 | PMC:PMC8957431 | DOI:10.1155/2022/4798136

Case Rep Transplant. 2022 Mar 25;2022:7323755. doi: 10.1155/2022/7323755. eCollection 2022.

ABSTRACT

Lung transplant recipients experience a high rate of invasive pulmonary aspergillosis infections, for which voriconazole is the treatment of choice. We report a patient who developed voriconazole-induced myositis that relapsed after one dose of isavuconazole. Our patient was a 38-year-old man who received a single sequential lung transplantation and liver transplantation because of end-stage cystic fibrosis. He presented to our emergency room with acute pain in both forearms at 3 weeks after voriconazole was initiated for invasive pulmonary aspergillosis infection. Levels of voriconazole were normal during the course of therapy. After stopping voriconazole, the symptoms decreased but relapsed after one dose of isavuconazole. Other causes of muscle pain and inflammation were excluded. Magnetic resonance imaging of both arms showed muscle edema in both arms, including involvement of the fascia, consistent with myositis. There were no signs of necrosis. Isavuconazole was discontinued, and the corticosteroid dose was temporarily increased, with rapid resolution of all complaints. Our patient is the fourth reported case of voriconazole-induced myositis, and the first whose symptoms relapsed after initiating isavuconazole.

PMID:35345837 | PMC:PMC8957034 | DOI:10.1155/2022/7323755

Microbiol Resour Announc. 2022 Mar 28:e0122021. doi: 10.1128/mra.01220-21. Online ahead of print.

ABSTRACT

Burkholderia cenocepacia is able to cause infections in cystic fibrosis patients. B. cenocepacia phage Paku has a 42,727-bp genome sharing a phiKMV-like genome arrangement. T7-like tail components were identified in parallel with a tyrosine integrase, suggesting that Paku might exhibit a temperate lifestyle, an atypical feature for an Autographiviridae phage.

PMID:35343779 | DOI:10.1128/mra.01220-21

Bratisl Lek Listy. 2022;123(3):149-152. doi: 10.4149/BLL_2022_025.

ABSTRACT

OBJECTIVES: Evaluation of selected inflammatory parameters and serum malondialdehyde (MDA) significance in the post-inflammatory period in adult patients with cystic fibrosis.

BACKGROUND: Laboratory biomarkers can be integrated into clinical practice as part of monitoring the effectiveness of treatment.

METHODS: After recovery from an acute exacerbation of lung infection, selected inflammatory parameters (fibrinogen, IL-1, IL-6, SAA, hs-CRP) and serum MDA were examined in 30 adult patients with cystic fibrosis. Their correlation with FEV1, frequency and duration of subsequent hospitalizations and 6-year prognosis in terms of mortality or need for lung transplantation was evaluated.

RESULTS: FEV1 negatively correlated with fibrinogen, but positively with MDA. No significant correlation with hs-CRP, IL-1, IL-6 and SAA was recorded. Plasma fibrinogen predicted the frequency and duration of subsequent hospitalizations. The 6-year prognosis was negatively associated with plasma fibrinogen whereas its association with MDA was positive. However, the prognosis of patients in the multivariate analysis was significantly associated only with FEV1.

CONCLUSION: Plasma fibrinogen examined in the post-inflammatory period is a marker of lung damage in patients with cystic fibrosis and can be used to predict the prognosis. The positive correlation of serum MDA with FEV1 in the post-inflammatory period may be important to the interpretation of treatment interventions (Tab. 3, Fig. 2, Ref. 17).

PMID:35343745 | DOI:10.4149/BLL_2022_025

J Clin Transl Endocrinol. 2022 Mar 21;28:100296. doi: 10.1016/j.jcte.2022.100296. eCollection 2022 Jun.

ABSTRACT

BACKGROUND: Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease.

METHODS: In this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained.

RESULTS: Participants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1).

CONCLUSION: In this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.

PMID:35342717 | PMC:PMC8942823 | DOI:10.1016/j.jcte.2022.100296

J Mol Biol. 2022 Mar 24:167561. doi: 10.1016/j.jmb.2022.167561. Online ahead of print.

ABSTRACT

Single cell RNA-sequencing has accurately identified cell types within the human airway that express the Cystic Fibrosis Transmembrane Conductance regulator (CFTR) gene. Low abundance CFTR transcripts are seen in many secretory cells, while high levels are restricted to rare pulmonary ionocytes. Here we focus on the mechanisms coordinating basal CFTR expression in the secretory compartment. Cell-selective regulation of CFTR is achieved within its invariant topologically associating domain by the recruitment of cis-regulatory elements (CREs). CRE activity is coordinated by cell-type-selective transcription factors. One such factor, Krüppel-Like Factor 5 (KLF5), profoundly represses CFTR transcript and protein in primary human airway epithelial cells and airway cell lines. Here we reveal the mechanism of action of KLF5 upon the CFTR gene. We find that depletion or ablation of KLF5 from airway epithelial cells changes higher order chromatin structure at the CFTR locus. Critical looping interactions that are required for normal gene expression are altered, the H3K27ac active chromatin mark is redistributed, and CTCF occupancy is modified. However, mutation of a single KLF5 binding site within a pivotal airway cell CRE abolishes CFTR expression. Hence, KLF5 has both direct activating and indirect repressive effects, which together coordinate CFTR expression in the airway.

PMID:35341742 | DOI:10.1016/j.jmb.2022.167561

J Cyst Fibros. 2022 Mar 24:S1569-1993(22)00083-2. doi: 10.1016/j.jcf.2022.03.006. Online ahead of print.

NO ABSTRACT

PMID:35341695 | DOI:10.1016/j.jcf.2022.03.006

J Cyst Fibros. 2022 Mar 24:S1569-1993(22)00085-6. doi: 10.1016/j.jcf.2022.03.008. Online ahead of print.

ABSTRACT

BACKGROUND: Despite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life.

METHODS: We examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017.

RESULTS: Lung function trajectories were calculated for 119 children with CF from childhood (median 5.0 [25%-75%=5.0-5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4-13.8] years). Lung function fell progressively, with mean (standard deviation) annual change -0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV1) Z-score (p<0.001), -1.277 (0.221) for FEV1/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence, in multivariable analyses, were hospitalisation for respiratory exacerbations in the first 5-years of life (FEV1/FVC p = 0.001, FEF25-75p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1p = 0.05, FEF25-75p = 0.02). No examined factor predicted a decline in the FVC Z-score.

CONCLUSIONS: Action in the first 5-years of life to prevent and/or treat respiratory exacerbations and counteract neutrophilic inflammation in the lower airways may reduce lung function decline in children with CF, and these should be targets of future research.

PMID:35341694 | DOI:10.1016/j.jcf.2022.03.008

Case Rep Womens Health. 2022 Apr;34:e00406. doi: 10.1016/j.crwh.2022.e00406. Epub 2022 Mar 23.

ABSTRACT

A 16-year-old primigravida was diagnosed with COVID-19 in her second trimester. She decompensated quickly and had to be admitted to hospital and intubated. She was diagnosed with a fetal demise after being intubated and neurology suspected myasthenia gravis due to neurologic symptoms. Due to pan-sinusitis and increased mucus secretion, cystic fibrosis screening was ordered. After she was extubated, cervical ripening and induction was performed with eventual vaginal delivery without maternal complications. Myasthenia gravis and cystic fibrosis carrier status were confirmed after the patient was discharged.

PMID:35340780 | PMC:PMC8940761 | DOI:10.1016/j.crwh.2022.e00406

ISME J. 2022 Mar 25. doi: 10.1038/s41396-022-01221-y. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa dominates the complex polymicrobial cystic fibrosis (CF) airway and is a leading cause of death in persons with CF. Oral streptococcal colonization has been associated with stable CF lung function. However, no studies have demonstrated how Streptococcus salivarius, the most abundant streptococcal species found in individuals with stable CF lung disease, potentially improves lung function or becomes incorporated into the CF airway biofilm. By utilizing a two-species biofilm model to probe interactions between S. salivarius and P. aeruginosa, we discovered that the P. aeruginosa exopolysaccharide Psl promoted S. salivarius biofilm formation. Further, we identified a S. salivarius maltose-binding protein (MalE) that is required for promotion of biofilm formation both in vitro and in a Drosophila melanogaster co-infection model. Finally, we demonstrate that promotion of dual biofilm formation with S. salivarius is common among environmental and clinical P. aeruginosa isolates. Overall, our data supports a model in which S. salivarius uses a sugar-binding protein to interact with P. aeruginosa exopolysaccharide, which may be a strategy by which S. salivarius establishes itself within the CF airway microbial community.

PMID:35338335 | DOI:10.1038/s41396-022-01221-y

J Cyst Fibros. 2022 Mar;21(2):199-201. doi: 10.1016/j.jcf.2022.03.004.

NO ABSTRACT

PMID:35337600 | DOI:10.1016/j.jcf.2022.03.004

Pharmaceuticals (Basel). 2022 Feb 23;15(3):274. doi: 10.3390/ph15030274.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease affecting the lungs and pancreas and causing progressive damage. CF is caused by mutations abolishing the function of CFTR, a protein whose role is chloride's mobilization in the epithelial cells of various organs. Recently a therapy focused on small molecules has been chosen as a main approach to contrast CF, designing and synthesizing compounds acting as misfolding (correctors) or defective channel gating (potentiators). Multi-drug therapies have been tested with different combinations of the two series of compounds. Previously, we designed and characterized two series of correctors, namely, hybrids, which were conceived including the aminoarylthiazole (AAT) core, merged with the benzodioxole carboxamide moiety featured by VX-809. In this paper, we herein proceeded with molecular modeling studies guiding the design of a new third series of hybrids, featuring structural variations at the thiazole moiety and modifications on position 4. These derivatives were tested in different assays including a YFP functional assay on models F508del-CFTR CFBE41o-cells, alone and in combination with VX-445, and by using electrophysiological techniques on human primary bronchial epithelia to demonstrate their F508del-CFTR corrector ability. This study is aimed (i) at identifying three molecules (9b, 9g, and 9j), useful as novel CFTR correctors with a good efficacy in rescuing the defect of F508del-CFTR; and (ii) at providing useful information to complete the structure-activity study within all the three series of hybrids as possible CFTR correctors, supporting the development of pharmacophore modelling studies, taking into account all the three series of hybrids. Finally, in silico evaluation of the hybrids pharmacokinetic (PK) properties contributed to highlight hybrid developability as drug-like correctors.

PMID:35337072 | DOI:10.3390/ph15030274

Vaccines (Basel). 2022 Mar 3;10(3):390. doi: 10.3390/vaccines10030390.

ABSTRACT

The genus mycobacterium includes several species that are known to cause infections in humans. The microorganisms are classified into tuberculous and non-tuberculous based on their morphological characteristics, defined by the dynamic relationship between the host defenses and the infectious agent. Non-tuberculous mycobacteria (NTM) include all the species of mycobacterium other than the ones that cause tuberculosis (TB). The group of NTM contains almost 200 different species and they are found in soil, water, animals-both domestic and wild-milk and food products, and from plumbed water resources such as sewers and showerhead sprays. A systematic review of Medline between 1946 and 2014 showed an 81% decline in TB incidence rates with a simultaneous 94% increase in infections caused by NTM. Prevalence of infections due to NTM has increased relative to infections caused by TB owing to the stringent prevention and control programs in Western countries such as the USA and Canada. While the spread of typical mycobacterial infections such as TB and leprosy involves human contact, NTM seem to spread easily from the environment without the risk of acquiring from a human contact except in the case of M. abscessus in patients with cystic fibrosis, where human transmission as well as transmission through fomites and aerosols has been recorded. NTM are opportunistic in their infectious processes, making immunocompromised individuals such as those with other systemic infections such as HIV, immunodeficiencies, pulmonary disease, or usage of medications such as long-term corticosteroids/TNF-α inhibitors more susceptible. This review provides insight on pathogenesis, treatment, and BCG vaccine efficacy against M. leprae and some important NTM infections.

PMID:35335022 | DOI:10.3390/vaccines10030390

Nutrients. 2022 Mar 13;14(6):1216. doi: 10.3390/nu14061216.

ABSTRACT

Cystic fibrosis has historically been characterized by malnutrition, and nutrition strategies have placed emphasis on weight gain due to its association with better pulmonary outcomes. As treatment for this disease has significantly improved, longevity has increased and overweight and obesity have emerged issues in this population. The effect of excess weight and adiposity on CF clinical outcomes is unknown but may produce similar health consequences and obesity-related diseases as those observed in the general population. This review examines the prevalence of overweight and obesity in CF, the medical and psychological impact, as well as the existing evidence for treatment in the general population and how this may be applied to people with CF. Clinicians should partner with individuals with CF and their families to provide a personalized, interdisciplinary approach that includes dietary modification, physical activity, and behavioral intervention. Additional research is needed to identify the optimal strategies for preventing and addressing overweight and obesity in CF.

PMID:35334873 | DOI:10.3390/nu14061216