Pediatr Pulmonol. 2024 Jan 5. doi: 10.1002/ppul.26823. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve gastrointestinal absorption of nutrients and may result in changes in body mass index (BMI), serum lipids, and fat-soluble vitamin levels. We hypothesized that serum lipids and vitamin levels would increase with CFTR modulator therapy and that greater increase in lipids and vitamin levels would be related to greater increase in BMI.

METHODS: A retrospective study was performed to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on nutritional parameters, serum lipids, and fat-soluble vitamin levels. Pre-ETI values (<2 years prior) and post-ETI values (>1 month after) were compared. Linear regression was used to evaluate whether change in BMI is associated with the change in lipid and/or vitamin levels and whether modulator duration is associated with the degree of rise in lipid and/or vitamin levels.

RESULTS: Adults and adolescents with CF (n = 137) were evaluated before and 31-300 days after starting ETI. Median BMI (adults 21.9 vs. 23.5 kg/m2 ; adolescents 48 vs. 63 percentile) increased after initiation of ETI. Total cholesterol (126 vs. 154 mg/dL), low-density lipoprotein cholesterol (63 vs. 78 mg/dL), non-high-density lipoprotein cholesterol (84 vs. 102 mg/dL), and high density lipoprotein cholesterol (43 vs. 49 mg/dL) increased after ETI, while triglycerides and very low density lipoprotein did not change. Median values for vitamin D (34.5 vs. 38.0 ng/mL) and vitamin A (40.1 vs. 47.9 µg/dL) increased, while vitamin E did not change significantly. There was no significant correlation between BMI change or duration of modulator therapy with vitamin levels or lipid changes.

CONCLUSION: After initiation of ETI therapy, serum lipids increased in our population, but most values remained within the normal range. Vitamins A and D levels increased post-ETI and no changes were noted in vitamin E. No significant correlation between the degree of BMI change and the magnitude of increase in lipids or vitamin levels was found.

PMID:38179878 | DOI:10.1002/ppul.26823

Curr Genomics. 2023 Nov 22;24(3):136-145. doi: 10.2174/0113892029265046231011100327.

ABSTRACT

Epigenetic changes play an important role in the pathophysiology of autoimmune diseases such as allergic asthma, multiple sclerosis, lung diseases, diabetes, cystic fibrosis, atherosclerosis, rheumatoid arthritis, and COVID-19. There are three main classes of epigenetic alterations: post-translational modifications of histone proteins, control by non-coding RNA and DNA methylation. Since histone modifications can directly affect chromatin structure and accessibility, they can regulate gene expression levels. Abnormal expression and activity of histone deacetylases (HDACs) have been reported in immune mediated diseases. Increased acetylated levels of lysine residues have been suggested to be related to the overexpression of inflammatory genes. This review focuses on the effect of HDAC modifications on histone and non-histone proteins in autoimmune diseases. Furthermore, we discuss the potential therapeutic effect of HDAC inhibitors (HDACi) used in these diseases.

PMID:38178983 | PMC:PMC10761333 | DOI:10.2174/0113892029265046231011100327

Front Pediatr. 2023 Dec 19;11:1300968. doi: 10.3389/fped.2023.1300968. eCollection 2023.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a chronic multi-systemic disease that requires a complex daily treatment regimen. Therefore, there is sub-optimal adherence to CF therapies, and it was shown to impact its clinical and economic burden. Cystic fibrosis transmembrane conductance regulator modulators (CFTRm) are high-cost medications that demonstrated significant benefit in clinical trials. The aim of this study was to evaluate the safety, usability, and efficacy of the ReX platform in medication management of CFTRm for the treatment of people with CF (pwCF).

METHODS: ReX is a patient engagement platform consisting of a cloud-based management system and a cell-enabled handheld device intended to dispense oral medication into the patient's mouth, following a pre-programmed treatment protocol. It provides real-time adherence data to caregivers and timely, personalized reminders to patients. This is a prospective multi-center open study for pwCFs older than 12 years, who had been prescribed CFTRm [elexacaftor/tezacaftor/ivacaftor (ETI) or tezacaftor/ivacaftor (TI)], and provided consent to use ReX platform to receive CFTRm and record their health condition. Study duration was 12-24 months, with clinic visits where physical examination, body mass index (BMI), and pulmonary function tests were performed, and user experience questionnaires were filled in.

RESULTS: Ten pwCFs from two CF centers in Israel were included. The mean age was 31.5 years (range 15-74 years); eight were taking ETI and two TI. Median adherence to CFTRm was 97.5% (range 70%-100%) in the first year and 94% (range 84%-99%) in the second year, which is higher than the previously reported CFTRm adherence of ∼80%. No adverse events related to the use of the platform were reported. Patients reported ReX to be valuable to their treatment management and user friendly. Estimated mean forced expiratory volume in 1 s (FEV1%) increased from 74.4% to 80.8% (p = 0.004) over 2 years. Similarly, estimated BMI percentile increased from 53.5 to 59.0 (p < 0.001).

CONCLUSIONS: Using the ReX platform in medication management of pwCF treated by CFTRm is safe, easy to use, and effective in improving the adherence to treatment and the clinical outcomes. Consequently, this device may potentially reduce costs to healthcare providers. Further larger and long-term studies are required to examine the clinical benefits of the ReX platform.

PMID:38178914 | PMC:PMC10766369 | DOI:10.3389/fped.2023.1300968

AIMS Microbiol. 2023 Aug 10;9(4):612-646. doi: 10.3934/microbiol.2023032. eCollection 2023.

ABSTRACT

This review addresses the topic of biofilms, including their development and the interaction between different counterparts. There is evidence that various diseases, such as cystic fibrosis, otitis media, diabetic foot wound infections, and certain cancers, are promoted and aggravated by the presence of polymicrobial biofilms. Biofilms are composed by heterogeneous communities of microorganisms protected by a matrix of polysaccharides. The different types of interactions between microorganisms gives rise to an increased resistance to antimicrobials and to the host's defense mechanisms, with the consequent worsening of disease symptoms. Therefore, infections caused by polymicrobial biofilms affecting different human organs and systems will be discussed, as well as the role of the interactions between the gram-negative bacteria Pseudomonas aeruginosa, which is at the base of major polymicrobial infections, and other bacteria, fungi, and viruses in the establishment of human infections and diseases. Considering that polymicrobial biofilms are key to bacterial pathogenicity, it is fundamental to evaluate which microbes are involved in a certain disease to convey an appropriate and efficacious antimicrobial therapy.

PMID:38173971 | PMC:PMC10758579 | DOI:10.3934/microbiol.2023032

Front Physiol. 2023 Dec 20;14:1323865. doi: 10.3389/fphys.2023.1323865. eCollection 2023.

ABSTRACT

Introduction: Club cells are precursors for mucus-producing goblet cells. Interleukin 1β (IL-1B) is an inflammatory mediator with pro-mucin activities that increases the number of mucus-producing goblet cells. IL-1B-mediated mucin production in alveolar adenocarcinoma cells requires activation of the cAMP response element-binding protein (CREB). Whether the pro-mucin activities of IL-1B require club cell CREB is unknown. Methods: We challenged male mice with conditional loss of club cell Creb1 and wild type littermates with intra-airway IL-1B or vehicle. Secondarily, we studied human "club cell-like" H322 cells. Results: IL-1B increased whole lung mRNA of secreted (Mucin 5ac, Mucin 5b) and tethered (Mucin 1, Mucin 4) mucins independent of genotype. However, loss of club cell Creb1 increased whole lung mRNA of member RAS oncogene family (Rab3D), decreased mRNA of the muscarinic receptor 3 (M3R) and prevented IL-1B mediated increases in purinergic receptor P2Y, (P2ry2) mRNA. IL-1B increased the density of goblet cells containing neutral mucins in wildtype mice but not in mice with loss of club cell Creb1. These findings suggested that club cell Creb1 regulated mucin secretion. Loss of club cell Creb1 also prevented IL-1B-mediated impairments in airway mechanics. Four days of pharmacologic CREB inhibition in H322 cells increased mRNA abundance of forkhead box A2 (FOXA2), a repressor of goblet cell expansion, and decreased mRNA expression of SAM pointed domain containing ETS transcription factor (SPDEF), a driver of goblet cell expansion. Chromatin immunoprecipitation demonstrated that CREB directly bound to the promoter region of FOXA2, but not to the promoter region of SPDEF. Treatment of H322 cells with IL-1B increased cAMP levels, providing a direct link between IL-1B and CREB signaling. Conclusion: Our findings suggest that club cell Creb1 regulates the pro-mucin properties of IL-1B through pathways likely involving FOXA2.

PMID:38173934 | PMC:PMC10761479 | DOI:10.3389/fphys.2023.1323865

Heliyon. 2023 Dec 12;10(1):e23428. doi: 10.1016/j.heliyon.2023.e23428. eCollection 2024 Jan 15.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is associated with dysregulated immune responses, exaggerated inflammation and chronic infection. CF transmembrane conductance regulator (CFTR) modulator therapies directly target the underlying protein defects and resulted in significant clinical benefits for people with CF (pwCF). This study analysed the effects of triple CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) on CF-associated inflammation, especially systemic chemokines.

METHODS: A bead-based immunoassay was used to quantify proinflammatory chemokines (IL-8, IP-10, Eotaxin, TARC, RANTES, MIP-1α, MIP-1β, MIP-3α, MIG, ENA-78, GROα, I-TAC) in plasma samples from pwCF collected before, at three, and at six months after starting ETI therapy.

RESULTS: Fifty-one pwCF (47 % female; mean age 32 ± 10.4 years) were included. At baseline, 67 % were already receiving CFTR modulator therapy with tezacaftor/ivacaftor or lumacaftor/ivacaftor. After initiation of ETI therapy there was a significant improvement in percent predicted forced expiratory volume in 1 s (+12.7 points, p < 0.001) and a significant decrease in sweat chloride levels (-53.6 %, p < 0.001). After 6 months' treatment with ETI therapy there were significant decreases in plasma levels of MIP-3α (-68.2 %, p = 0.018), GROα (-17.7 %, p = 0.013), ENA-78 (-16.3 %, p = 0.034) and I-TAC (-3.4 %, p = 0.032). IL-8 exhibited a reduction that did not reach statistical significance (-17.8 %, p = 0.057); levels of other assessed cytokines did not change significantly from baseline.

CONCLUSIONS: ETI appears to affect a distinct group of chemokines that are predominately associated with neutrophilic inflammation, demonstrating the anti-inflammatory properties of ETI therapy.

PMID:38173511 | PMC:PMC10761561 | DOI:10.1016/j.heliyon.2023.e23428

Respir Res. 2024 Jan 3;25(1):3. doi: 10.1186/s12931-023-02636-7.

ABSTRACT

Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression of such diseases. Therefore, lung epithelial cells are a valuable target for therapeutic intervention. Here, we present a 3D airway lung organoid platform for the preclinical testing of active substances with regard to senescence, toxicity, and inflammation under standardized conditions in a 96 well format. Senescence was induced with doxorubicin and measured by activity of senescence associated galactosidase. Pharmaceutical compounds such as quercetin antagonized doxorubicin-induced senescence without compromising organoid integrity. Using single cell sequencing, we identified a subset of cells expressing senescence markers which was decreased by quercetin. Doxorubicin induced the expression of detoxification factors specifically in goblet cells independent of quercetin. In conclusion, our platform enables for the analysis of senescence-related processes and will allow the pre-selection of a wide range of compounds (e.g. natural products) in preclinical studies, thus reducing the need for animal testing.

PMID:38172839 | DOI:10.1186/s12931-023-02636-7

Biol Pharm Bull. 2024;47(1):159-165. doi: 10.1248/bpb.b23-00672.

ABSTRACT

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat non-small cell lung cancer with EGFR mutations. However, first-generation erlotinib and second-generation afatinib often cause diarrhea, which may develop because of the association between EGFR-TKIs and the chloride channel or abnormalities in the intestinal microbiota due to disruption of the intestinal immune system. As reports on the effects of EGFR-TKIs on intestinal immunity are lacking, we aimed to determine whether the intestinal immune system is involved in the molecular effects of EGFR-TKIs on chloride channels using Caco-2 cells. Initially, we evaluated the association of chloride channels with α-defensin 5 (DEFA5), a marker of intestinal immunity. Erlotinib and afatinib significantly increased the extracellularly secreted DEFA5 level and autophagy-related 16-like 1 and X-box binding protein 1 transcript levels, indicative of enhanced granule exocytosis. Conversely, intracellular DEFA5 and Toll-like receptor 4 protein expression and tumor necrosis factor-α transcript levels decreased significantly, suggesting that Toll-like receptor 4 suppression repressed DEFA5 production. Furthermore, among the chloride channels, DEFA5 was found to significantly increase the transcript levels of cystic fibrosis transmembrane conductance regulators. These results indicate that DEFA5 plays a significant role in the mechanism of chloride channel-mediated diarrhea induced by EGFR-TKIs. Therefore, we successfully elucidated the potential host action of DEFA5 in cancer therapy for the first time.

PMID:38171775 | DOI:10.1248/bpb.b23-00672

Biol Pharm Bull. 2024;47(1):1-13. doi: 10.1248/bpb.b23-00820.

ABSTRACT

Cl- influx and efflux through Cl- channels play a role in regulating the homeostasis of biological functions. Therefore, the hyperfunction or dysfunction of Cl- channels elicits pathological mechanisms. The Cl- channel superfamily includes voltage-gated Cl- (ClC) channels, Ca2+-activated Cl- channels (ClCa; TMEM16A/TMEM16B), cystic fibrosis transmembrane conductance regulator channels, and ligand-gated Cl- channels. These channels are ubiquitously expressed to regulate ion homeostasis, muscle tonus, membrane excitability, cell volume, survival, neurotransmission, and transepithelial transport. The activation or inhibition of Cl- channels changes the membrane potential, thereby affecting cytosolic Ca2+ signals. An elevation in cytosolic [Ca2+] triggers physiological and pathological responses in most cells. However, the roles of Cl- channels have not yet been examined as extensively as cation (Na+, Ca2+, and K+) channels. We recently reported the functional expression of: (i) TMEM16A/ClCa channels in portal vein and pulmonary arterial smooth muscle cells (PASMC), pinealocytes, and brain capillary endothelial cells; (ii) TMEM16B/ClCa channels in pinealocytes; (iii) ClC-3 channels in PASMC and chondrocytes; and (iv) ClC-7 channels in chondrocytes. We also showed that the down-regulation of TMEM16A and ClC-7 channel expression was associated with cirrhotic portal hypertension and osteoarthritis, respectively, whereas the enhanced expression of TMEM16A and ClC-3 channels was involved in the pathogenesis of cerebral ischemia and pulmonary arterial hypertension, respectively. Further investigations on the physiological/pathological functions of Cl- channels will provide insights into biological functions and contribute to the screening of novel target(s) of drug discovery for associated diseases.

PMID:38171770 | DOI:10.1248/bpb.b23-00820

mBio. 2024 Jan 3:e0310923. doi: 10.1128/mbio.03109-23. Online ahead of print.

ABSTRACT

Upon infection in the cystic fibrosis (CF) lung, Pseudomonas aeruginosa rapidly acquires genetic mutations, especially in genes involved in antimicrobial resistance (AMR), often resulting in diverse, treatment-resistant populations. However, the role of bacterial population diversity within the context of chronic infection is still poorly understood. In this study, we found that hypermutator strains of P. aeruginosa in the CF lung undergoing treatment with tobramycin evolved increased sensitivity to tobramycin relative to non-hypermutators within the same population. This finding suggests that antimicrobial treatment may only exert weak selection pressure on P. aeruginosa populations in the CF lung. We further found no evidence for collateral sensitivity in these clinical populations, suggesting that collateral sensitivity may not be a robust, naturally occurring phenomenon for this microbe.

PMID:38171021 | DOI:10.1128/mbio.03109-23

Front Oncol. 2023 Dec 19;13:1292046. doi: 10.3389/fonc.2023.1292046. eCollection 2023.

ABSTRACT

Breast cancer is the most common malignant neoplasm in women. Despite progress to date, 700,000 women worldwide died of this disease in 2020. Apparently, the prognostic markers currently used in the clinic are not sufficient to determine the most appropriate treatment. For this reason, great efforts have been made in recent years to identify new molecular biomarkers that will allow more precise and personalized therapeutic decisions in both primary and recurrent breast cancers. These molecular biomarkers include genetic and post-transcriptional alterations, changes in protein expression, as well as metabolic, immunological or microbial changes identified by multiple omics technologies (e.g., genomics, epigenomics, transcriptomics, proteomics, glycomics, metabolomics, lipidomics, immunomics and microbiomics). This review summarizes studies based on omics analysis that have identified new biomarkers for diagnosis, patient stratification, differentiation between stages of tumor development (initiation, progression, and metastasis/recurrence), and their relevance for treatment selection. Furthermore, this review highlights the importance of clinical trials based on multiomics studies and the need to advance in this direction in order to establish personalized therapies and prolong disease-free survival of these patients in the future.

PMID:38169859 | PMC:PMC10758476 | DOI:10.3389/fonc.2023.1292046

Recenti Prog Med. 2024 Jan;115(1):35-39. doi: 10.1701/4169.41644.

ABSTRACT

This project of Health technology assessment was aimed at defining the impacts of offering a cystic fibrosis (CF) carrier screening to the general population, compared to the current situation, where the test is offered to individuals at high-risk to give birth to a child with CF. Results revealed: i) a lack of robust and updated data; ii) a return on investment up to six years from the screening's introduction, despite important economic and organizational efforts; iii) a general positive attitude of healthcare professionals, people with CF, families and general population; iv) possible issues related to the social impact.

PMID:38169359 | DOI:10.1701/4169.41644

J Bacteriol. 2024 Jan 3:e0028623. doi: 10.1128/jb.00286-23. Online ahead of print.

ABSTRACT

Cystic fibrosis is an autosomal recessive disease that disrupts ion transport at mucosal surfaces, leading to mucus accumulation and altered physiology of both the lungs and the intestines, among other organs, with the resulting altered environment contributing to an imbalance of microbial communities. Culture media representative of the CF airway have been developed and validated; however, no such medium exists for modeling the CF intestine. Here, we develop and validate a first-generation culture medium inclusive of features that are altered in the CF colon. Our findings suggest this novel medium, called CF-MiPro, as a maintenance medium for CF gut microbiome samples and a flexible tool for studying key drivers of CF-associated gut dysbiosis.

PMID:38169295 | DOI:10.1128/jb.00286-23

Eur J Med Chem. 2023 Dec 20;265:116073. doi: 10.1016/j.ejmech.2023.116073. Online ahead of print.

ABSTRACT

Blocking iron uptake and metabolism has been emerging as a promising therapeutic strategy for the development of novel antimicrobial compounds. Like all mycobacteria, M. abscessus (Mab) has evolved several countermeasures to scavenge iron from host carrier proteins, including the production of siderophores, which play a crucial role in these processes. In this study, we solved, for the first time, the crystal structure of Mab-SaS, the first enzyme involved in the biosynthesis of siderophores. Moreover, we screened a small, focused library and identified a compound exhibiting a potent inhibitory effect against Mab-SaS (IC50 ≈ 2 μM). Its binding mode was investigated by means of Induced Fit Docking simulations, performed on the crystal structure presented herein. Furthermore, cytotoxicity data and pharmacokinetic predictions revealed the safety and drug-likeness of this class of compounds. Finally, the crystallographic data were used to optimize the model for future virtual screening campaigns. Taken together, the findings of our study pave the way for the identification of potent Mab-SaS inhibitors, based on both established and unexplored chemotypes.

PMID:38169270 | DOI:10.1016/j.ejmech.2023.116073

Clin Nutr. 2023 Dec 27;43(2):413-445. doi: 10.1016/j.clnu.2023.12.017. Online ahead of print.

ABSTRACT

BACKGROUND: Nutritional status is paramount in Cystic Fibrosis (CF) and is directly correlated with morbidity and mortality. The first ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with CF were published in 2016. An update to these guidelines is presented.

METHODS: The study was developed by an international multidisciplinary working group in accordance with officially accepted standards. Literature since 2016 was reviewed, PICO questions were discussed and the GRADE system was utilized. Statements were discussed and submitted for on-line voting by the Working Group and by all ESPEN members.

RESULTS: The Working Group updated the nutritional guidelines including assessment and management at all ages. Supplementation of vitamins and pancreatic enzymes remains largely the same. There are expanded chapters on pregnancy, CF-related liver disease, and CF-related diabetes, bone disease, nutritional and mineral supplements, and probiotics. There are new chapters on nutrition with highly effective modulator therapies and nutrition after organ transplantation.

PMID:38169175 | DOI:10.1016/j.clnu.2023.12.017

Mol Biol Evol. 2024 Jan 3:msad288. doi: 10.1093/molbev/msad288. Online ahead of print.

ABSTRACT

In recent times, pathogen genome sequencing has become increasingly used to investigate infectious disease outbreaks. When genomic data is sampled densely enough amongst infected individuals, it can help resolve who infected whom. However, transmission analysis cannot rely solely on a phylogeny of the genomes but must account for the within-host evolution of the pathogen, which blurs the relationship between phylogenetic and transmission trees. When only a single genome is sampled for each host, the uncertainty about who infected whom can be quite high. Consequently, transmission analysis based on multiple genomes of the same pathogen per host has a clear potential for delivering more precise results, even though it is more laborious to achieve. Here we present a new methodology that can use any number of genomes sampled from a set of individuals to reconstruct their transmission network. Furthermore, we remove the need for the assumption of a complete transmission bottleneck. We use simulated data to show that our method becomes more accurate as more genomes per host are provided, and that it can infer key infectious disease parameters such as the size of the transmission bottleneck, within-host growth rate, basic reproduction number and sampling fraction. We demonstrate the usefulness of our method in applications to real datasets from an outbreak of Pseudomonas aeruginosa amongst cystic fibrosis patients and a nosocomial outbreak of Klebsiella pneumoniae.

PMID:38168711 | DOI:10.1093/molbev/msad288

Microbiol Spectr. 2024 Jan 3:e0170923. doi: 10.1128/spectrum.01709-23. Online ahead of print.

ABSTRACT

Bacteria living in biofilms produce a protective matrix which makes them difficult to kill. Patients with severe respiratory disease often have biofilms. Polymyxin B is an antibiotic commonly used in topical medications, such as eye drops and nasal sprays. Ethylenediaminetetraacetic acid (EDTA) is used widely as a preservative in medication but also has antimicrobial properties. It has been hypothesized that Polymyxin B and EDTA could have a synergistic relationship: when used in combination their antimicrobial effect is enhanced. Here, we evaluated the levels at which Polymyxin B and EDTA work together to kill common pathogens Pseudomonas aeruginosa and Staphylococcus aureus. We found that Polymyxin B and EDTA were synergistic. This synergy may be useful in the management of planktonic infection with P. aeruginosa and S. aureus, or biofilm infection with P. aeruginosa. This synergy may be beneficial in the treatment of respiratory biofilms, in which P. aeruginosa biofilms are common.

PMID:38168683 | DOI:10.1128/spectrum.01709-23

medRxiv. 2023 Dec 17:2023.12.16.23300077. doi: 10.1101/2023.12.16.23300077. Preprint.

ABSTRACT

BACKGROUND: The human gut microbiome develops rapidly during infancy, a key window of development coinciding with maturation of the adaptive immune system. However, little is known of the microbiome growth dynamics over the first few months of life and whether there are any generalizable patterns across human populations. We performed metagenomic sequencing on stool samples (n=94) from a cohort of infants (n=15) at monthly intervals in the first six months of life, augmenting our dataset with seven published studies for a total of 4,441 metagenomes from 1,162 infants.

RESULTS: Strain-level de novo analysis was used to identify 592 of the most abundant organisms in the infant gut microbiome. Previously unrecognized consortia were identified which exhibited highly correlated abundances across samples and were composed of diverse species spanning multiple genera. Analysis of a cohort of infants with cystic fibrosis identified one such novel consortium of diverse Enterobacterales which was positively correlated with weight gain. While all studies showed an increased community stability during the first year of life, microbial dynamics varied widely in the first few months of life, both by study and by individual.

CONCLUSION: By augmenting published metagenomic datasets with data from a newly established cohort we were able to identify novel groups of organisms that are correlated with measures of robust human development. We hypothesize that the presence of these groups may impact human health in aggregate in ways that individual species may not in isolation.

PMID:38168439 | PMC:PMC10760300 | DOI:10.1101/2023.12.16.23300077

J Physiol. 2024 Jan 3. doi: 10.1113/JP286135. Online ahead of print.

NO ABSTRACT

PMID:38167788 | DOI:10.1113/JP286135

J Am Acad Orthop Surg. 2023 Dec 27. doi: 10.5435/JAAOS-D-23-00783. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients with cystic fibrosis (CF) are living longer and may be considered for total hip arthroplasty (THA) or total knee arthroplasty (TKA). Perioperative outcomes and implant survival after these procedures performed for those with CF have not been previously described.

METHODS: Using the M151 PearlDiver database, a large, national, administrative database, THA and TKA patients with and without CF were identified and matched 1:10 based on age, sex, and Elixhauser Comorbidity Index. Ninety-day perioperative outcomes and 2-year revision rates were assessed and compared with multivariable logistic regression.

RESULTS: For THA, 185 patients with CF were matched with 1,846 control subjects without CF. Patients with CF were at significantly increased odds of 90-day postoperative events including sepsis (odd radio [OR] 4.15), pneumonia (OR 3.40), pleural effusion (OR 2.77), minor events (OR 1.73), any adverse event (OR 1.64), urinary tract infection (UTI) (OR 1.63), and severe events (OR 1.60) (P < 0.05 for each). For TKA, 505 patients with CF were matched with 5,047 control subjects without CF. Patients with CF were at significantly increased odds of 90-day postoperative events including pneumonia (OR 4.95), respiratory failure (OR 4.31), cardiac event (OR 2.29), minor events (OR 2.16), pleural effusion (OR 2.35), severe events (OR 2.06), urinary tract infection (OR 2.06), any adverse event (OR 1.96), atelectasis (OR 1.94), and acute kidney injury (OR 1.61) (P < 0.05 for each). For both THA and TKA, those with CF were not at greater odds of 2-year rates of revision.

DISCUSSION: After THA and TKA, those with CF were found to be at increased odds of multiple defined postoperative events (predominantly infectious/pulmonary), but not 2-year revision rates. These findings help define areas in need of focused optimization and are reassuring regarding risks of surgery.

PMID:38165956 | DOI:10.5435/JAAOS-D-23-00783