J Pediatr Gastroenterol Nutr. 2023 Nov 1;77(5):603-609. doi: 10.1097/MPG.0000000000003924. Epub 2023 Aug 22.

ABSTRACT

OBJECTIVE: Pediatric rectal prolapse is a common and often self-limited condition with multiple management options. Selecting the optimal approach requires personalization and remains a challenge for pediatricians and pediatric surgeons.

METHODS: A single-center retrospective review of 67 children with rectal prolapse undergoing surgical evaluation between 2010 and 2021. Patients with anorectal malformations, Hirschsprung disease, inflammatory bowel disease, and cystic fibrosis were excluded. We used multivariable logistic regression to compare medical management, sclerotherapy, and surgical correction (rectopexy or transanal resection) as initial treatment strategies, with a primary endpoint of prolapse resolution.

RESULTS: Younger patients (<5 years) were more likely to be initially treated with medical management alone (P < 0.001). Patients with a psychiatric diagnosis were more likely to be offered either sclerotherapy or surgery upfront (P = 0.009). The resolution rate with surgery as initial management was 79% (n = 11/14). The resolution rate with sclerotherapy as initial management was 54% (n = 13/24), with 33% (n = 8/24) resolving with sclerotherapy alone and 21% (n = 5/24) resolving after a subsequent surgical procedure (P = 0.011). Patients who underwent initial surgical management had an adjusted odds ratio of 8.0 (95% CI: 1.1-59.1; P = 0.042) for resolution of prolapse compared to patients who underwent sclerotherapy initially. Markers of severity (bleeding, need for manual reduction) were not associated with initial therapy offered (P = 0.064).

CONCLUSIONS: Surgical intervention (sclerotherapy, rectopexy, transanal resection) resolved rectal prolapse in most children (63%). Surgery as an initial management approach had a significantly higher success rate than sclerotherapy, even after controlling for severity of disease, psychiatric diagnosis, need for manual reduction, and age.

PMID:37889618 | DOI:10.1097/MPG.0000000000003924

Chron Respir Dis. 2023 Jan-Dec;20:14799731231210559. doi: 10.1177/14799731231210559.

ABSTRACT

OBJECTIVE: Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC.

METHODS: This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO ≥25 ppb; BEC ≥200/µL).

RESULTS: Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis.

CONCLUSIONS: Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients.

PMID:37889184 | DOI:10.1177/14799731231210559

Antimicrob Agents Chemother. 2023 Oct 27:e0092023. doi: 10.1128/aac.00920-23. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is a common multidrug-resistant pathogen in patients with cystic fibrosis (CF). The in vitro activity of imipenem/relebactam and imipenem was compared with other antipseudomonal antibiotics against 105 isolates from patients with CF from three US hospitals. Imipenem/relebactam, imipenem, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam susceptibilities were 77%, 55%, 58%, 90%, and 92%, respectively. Relebactam potentiates imipenem against CF P. aeruginosa by fourfold leading imipenem/relebactam to retain susceptibility against most isolates in this cohort.

PMID:37888987 | DOI:10.1128/aac.00920-23

Anal Methods. 2023 Oct 27. doi: 10.1039/d3ay01738a. Online ahead of print.

ABSTRACT

Sweat is a promising non-invasive biofluid that can provide valuable insights into the physiological state of the human body. However, a major obstacle to analyzing sweat in real-time is the fabrication of simple, fast-acting, accurate, and low-cost sensing constructs. To address this challenge, we introduced easily-prepared wearable hydrogel sensors that can be placed on the skin and used colorimetric techniques to assess sweat analytes without invasive procedures. Two typical sweat sensors, chloride ion (Cl-) responsive patches for cystic fibrosis (CF) analysis and glucose response patches for diabetic monitoring, were demonstrated for real sample analysis. The Cl- colorimetric sensor, with a detection limit down to 100 μM, shows a good linear response from 1.56 mM to 200 mM Cl-, and the glucose colorimetric sensor, with a detection limit down to 1 μM, exhibits an adequate linear response from 10 μM to 1 mM glucose. These colorimetric hydrogel sensors are also incorporated into a medical dressing to create wearable sensor devices for real-time sweat analysis. The acquired readings closely match the results obtained from the benchmark analyzing instrument, with a small deviation of less than 10%. Therefore, our simple colorimetric hydrogel sensing patches hold great potential to advance real-time sweat testing and contribute to the transitional development of wearable medical devices.

PMID:37888873 | DOI:10.1039/d3ay01738a

Pediatr Pulmonol. 2023 Oct 27. doi: 10.1002/ppul.26734. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is now routinely diagnosed through newborn screening (NBS), but the tests employed in the USA have been evolving for two decades as missed cases become recognized and lab methods improve in association with more knowledge about CF genetics. New Jersey was among the first states to implement CF NBS in 2001 when it introduced the original two-tiered method that combined measurements of immunoreactive trypsinogen (IRT) with detection of the principal pathogenic variant (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

OBJECTIVE: With continuation of the IRT/DNA (F508del) algorithm for two decades and identification of screening false negative children, we decided to examine the condition of some missed cases with special attention to their respiratory status.

METHODS: To strengthen the arguments for quality improvement in New Jersey's CF NBS program, we reviewed and evaluated false negative cases to determine the potential extent of preventable patient suffering as a consequence of delayed diagnoses.

RESULTS: Five children with CF who had false negative screening results were studied in detail. In each case there was a different cause of the negative screening results. They all had clinically significant/severe lung disease, ranging from chronic cough with CF pathogens on respiratory culture at a young age to respiratory failure.

CONCLUSION: This case series highlights the consequences of false negative screening results, which served as the impetus to upgrade New Jersey's CF NBS algorithm. Implemented changes include lowering the IRT cutoff to 70 ng/mL and expanding to a 139 variant CFTR panel. In 2023, a floating IRT cutoff is anticipated to be implemented.

PMID:37888495 | DOI:10.1002/ppul.26734

Cells. 2023 Oct 15;12(20):2455. doi: 10.3390/cells12202455.

ABSTRACT

Epithelial transport is a multifaceted process crucial for maintaining normal physiological functions in the human body. This comprehensive review delves into the pathophysiological mechanisms underlying epithelial transport and its significance in disease pathogenesis. Beginning with an introduction to epithelial transport, it covers various forms, including ion, water, and nutrient transfer, followed by an exploration of the processes governing ion transport and hormonal regulation. The review then addresses genetic disorders, like cystic fibrosis and Bartter syndrome, that affect epithelial transport. Furthermore, it investigates the involvement of epithelial transport in the pathophysiology of conditions such as diarrhea, hypertension, and edema. Finally, the review analyzes the impact of renal disease on epithelial transport and highlights the potential for future research to uncover novel therapeutic interventions for conditions like cystic fibrosis, hypertension, and renal failure.

PMID:37887299 | DOI:10.3390/cells12202455

Intern Med J. 2023 Oct 27. doi: 10.1111/imj.16258. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The experience of outpatient care may differ for select patient groups. This prospective study evaluates the adult patient experience of multidisciplinary outpatient cystic fibrosis (CF) care with videoconferencing through telehealth compared with face-to-face care the year prior.

METHODS: People with CF without a lung transplant were recruited. Patient-reported outcomes were obtained at commencement and 12 months into the study, reflecting both their face-to-face and telehealth through videoconferencing experience, respectively. Three patient cohorts were analysed: (i) participants with a regional residence, (ii) participants with a nonregional including metropolitan residence and (iii) participants with colonised multiresistant microbiota.

RESULTS: Seventy-four patients were enrolled in the study (mean age, 37 ± 11 years; 50% male; mean forced expiratory volume in the first second of expiration, 60% [standard deviation, 23]) between February 2020 and May 2021. No differences between models were observed in the participants' rating of the health care team, general and mental health rating, and their confidence in handling treatment plans at home. No between-group differences in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) were observed. Travel duration and the cost of attending a clinic was significantly reduced, particularly for the regional group (4 h, AU$108 per clinic; P < 0.05). A total of 93% respondents preferred to continue with a hybrid approach.

CONCLUSION: In this pilot study, participants' experience of care and quality of life were no different with face-to-face and virtual care between the groups. Time and cost-savings, particularly for patients living in regional areas, were observed. Most participants preferred to continue with a hybrid model for outpatient care.

PMID:37886890 | DOI:10.1111/imj.16258

J Thorac Imaging. 2023 Oct 5. doi: 10.1097/RTI.0000000000000751. Online ahead of print.

NO ABSTRACT

PMID:37884355 | DOI:10.1097/RTI.0000000000000751

Eur Respir J. 2023 Oct 26;62(4):2301253. doi: 10.1183/13993003.01253-2023. Print 2023 Oct.

NO ABSTRACT

PMID:37884293 | DOI:10.1183/13993003.01253-2023

Eur Arch Otorhinolaryngol. 2023 Oct 26. doi: 10.1007/s00405-023-08236-x. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a severe systemic disease that affects many aspects of patients' lives. It is known that the progression of the disease adversely affects lower and upper airways including the paranasal sinuses. However, its impact on sinus development in the pediatric population is not fully examined. The purpose of this study was to evaluate the development of the paranasal sinuses in a pediatric population with CF and compare it to a control group consisting of healthy children.

METHODS: The results of computed tomography (CT) scans of children with the disease and the control group were evaluated. The study included 114 CT images of children in the study group and 126 images of healthy children aged 0-18 years. The volumes of maxillary, frontal, and sphenoid sinuses were analyzed. The obtained results were compared with those of the control group and analyzed statistically.

RESULTS: The volume and the development of the paranasal sinuses in both groups increased with age, but statistically significant differences were found between the study and the control group.

CONCLUSIONS: The obtained results provide valuable knowledge regarding the impact of the CF on sinuses development. Also, they may be important in understanding the progression of the disease and its influence on the quality and length of life of patients. The results may contribute to enhanced diagnostics and have implications for improving therapy for patients with chronic sinusitis associated with CF.

PMID:37882847 | DOI:10.1007/s00405-023-08236-x

Diabetes. 2023 Oct 26:db230009. doi: 10.2337/db23-0009. Online ahead of print.

ABSTRACT

The endocrine and exocrine compartments of the pancreas are spatially related but functionally distinct. Multiple diseases affect both compartments, including type 1 diabetes (T1D), pancreatitis, cystic fibrosis, and pancreatic cancer. To better understand how the exocrine pancreas changes with age, obesity, and diabetes, we performed systematic analysis of wellpreserved tissue sections from the pancreatic head, body, and tail of organ donors with T1D (n = 20), type 2 diabetes (T2D, n = 25), and donors with no diabetes (ND, n = 74). Among ND donors, we found that acinar-to-ductal metaplasia (ADM), angiopathy, and pancreatic adiposity increased with age, while ADM and adiposity also increased with BMI. Compared to age- and sex-matched ND organs, T1D pancreata had greater acinar atrophy and angiopathy with fewer intralobular adipocytes. T2D pancreata had greater ADM, angiopathy, and total T lymphocytes, but no difference in adipocyte number, compared to ND organs. While total pancreatic fibrosis was increased in both T1D and T2D, the pattern was different with T1D pancreata having greater periductal and perivascular fibrosis, whereas T2D pancreata had greater lobular and parenchymal fibrosis. Thus, the exocrine pancreas undergoes distinct changes as individuals age or develop T1D or T2D.

PMID:37881846 | DOI:10.2337/db23-0009

NIHR Open Res. 2023 Apr 14;3:18. doi: 10.3310/nihropenres.13384.1. eCollection 2023.

ABSTRACT

BACKGROUND: Gastrointestinal symptoms in cystic fibrosis (CF) are common and intrusive to daily life. Relieving gastrointestinal symptoms was identified as an important research priority and previously explored in an international survey in 2018. However, following the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators in 2019, the landscape of CF treatment has changed. We repeated an online survey to further describe gastrointestinal symptoms and their effect on quality of life (QoL) in the CFTR modulator era.

METHODS: An electronic survey consisting of closed questions and free text responses was distributed via social media and professional networks for a period of one month between March - April 2022. People with CF (pwCF), their family and friends, and healthcare professionals (HCPs) were invited to take part.

RESULTS: There were 164 respondents: 88 pwCF (54%), 22 (13%) family, and 54 (33%) healthcare professionals (HCPs). A total of 89/110 (81%) pwCF or family members reported CFTR modulator treatment. The most commonly reported symptoms were wind / gas, rumbling stomach noises, loose motions (modulator) and bloating (no modulator). Abdominal pain and bloating had the greatest impact on QoL.For those on a CFTR modulator, the proportion of pwCF reporting "no change" or "worse" for all of the symptoms surveyed was greater than the proportion reporting an improvement. Following modulator introduction, dietary changes were recommended by 28/35 (80%) of HCPs and reported by 38/76 (50%) lay respondents. Changes in medication were recommended by 19/35 (54%) HCPs and reported by 44/76 (58%) of patients and family members.

CONCLUSION: This survey has shown that gastrointestinal symptoms remain prevalent in pwCF in the CFTR modulator era, though the nature of these symptoms may have changed. A better understanding of the underlying pathophysiology of these symptoms is essential. Future clinical studies should focus on improving symptoms and QoL.

PMID:37881465 | PMC:PMC10593346 | DOI:10.3310/nihropenres.13384.1

NIHR Open Res. 2022 Dec 19;2:64. doi: 10.3310/nihropenres.13347.1. eCollection 2022.

ABSTRACT

BACKGROUND: Chest physiotherapy is an established cornerstone of care for people with cystic fibrosis (pwCF), but is often burdensome. Guidelines recommend at least one chest physiotherapy session daily, using various airway clearance techniques (ACTs). Exercise (with huffs and coughs) may offer an alternative ACT, however the willingness of pwCF to be randomised into a trial needs testing. The 'ExACT-CF: Exercise as an Airway Clearance Technique in people with Cystic Fibrosis' trial will test the feasibility of recruiting pwCF to be randomised to continue usual care (chest physiotherapy) or replace it with exercise ACT (ExACT) for 28-days. Secondary aims include determining the short-term clinical impact (and safety) of stopping routine chest physiotherapy and replacing it with ExACT, and effects on physical activity, sleep, mood, quality of life and treatment burden, alongside preliminary health economic measures and acceptability.

METHODS: Multi-centre, two-arm, randomised (1:1 allocation using minimisation), pilot trial at two sites. Fifty pwCF (≥10 years, FEV 1 >40% predicted, stable on Elexacaftor/Tezacaftor/Ivacaftor (ETI)) will be randomised to an individually-customised ExACT programme (≥once daily aerobic exercise of ≥20-minutes duration at an intensity that elicits deep breathing, with huffs and coughs), or usual care. After baseline assessments, secondary outcomes will be assessed after 28-days, with additional home lung function and exacerbation questionnaires at 7, 14 and 21-days, physical activity and sleep monitoring throughout, and embedded qualitative and health-economic components. Feasibility measures include recruitment, retention, measurement completion, adverse events, interviews exploring the acceptability of trial procedures, and a trial satisfaction questionnaire.

DISCUSSION: Co-designed with the UK CF community, the ExACT-CF pilot trial is the first multi-centre RCT to test the feasibility of recruiting pwCF stable on ETI into a trial investigating ExACT. This pilot trial will inform the feasibility, design, management, likely external validity for progression to a main phase randomised controlled trial.

REGISTRATION: Clinicaltrials.gov ( NCT05482048).

PMID:37881306 | PMC:PMC10593342 | DOI:10.3310/nihropenres.13347.1

Fetal Diagn Ther. 2023 Oct 25. doi: 10.1159/000534374. Online ahead of print.

ABSTRACT

Fetal inguinal hernia (FIH) is a rare event, and only a few cases were published in the medical literature. In the present study, we aimed to characterize the sonographic features, clinical presentation, management, outcomes, and differential diagnoses of FIH. Accordingly, we reviewed all 17 cases of FIH published in the medical literature, including one new case evaluated by our group. All 17 cases (100%) were male, and FIH presented as a scrotal mass with a mean diameter of 38±9.5 mm. The right side was dominant (62%). Peristalsis was reported in 80% of the cases, and blood flow was reported in two-thirds. Most cases were diagnosed in the third trimester (88%) at a mean gestational age (GA) of 33.1±5.2W. Sixty percent of the cases had isolated FIH, and 40% had another sonographic or genetic abnormality. Three cases (18%) were syndromic with multiple malformations: trisomy 18, skeletal anomalies due to Jarcho-Levin syndrome, and undefined multiple joint contractures. Two cases (12%) had co-pathologies in the gastrointestinal tract: one had an echogenic bowel due to homozygosity for cystic fibrosis and the other had low anorectal malformation. Bowel loop dilatation was observed prenatally in both cases and in one isolated case (18%). GA at delivery was 38±1.8W, and the median time between diagnosis and delivery was 3 weeks. All three cases of neonatal death occurred in syndromic fetuses. All patients with non-syndromic inguinal hernias underwent definitive surgical repair at a median of 13 days postpartum. No signs of strangulation and only one case of edematous bowel without necrosis have been reported. In conclusion, FIH should be suspected in male fetuses when an intra-scrotal mass with peristalsis is diagnosed during the third trimester. Close follow-up until term in the absence of signs of bowel obstruction is reasonable, and in isolated FIH, the prognosis is favorable.

PMID:37879314 | DOI:10.1159/000534374

J Cyst Fibros. 2023 Oct 23:S1569-1993(23)00880-9. doi: 10.1016/j.jcf.2023.08.013. Online ahead of print.

ABSTRACT

BACKGROUND: High daily doses of pancreatic enzyme replacement therapy (PERT) were historically associated with risk of fibrosing colonopathy (FC) in people with cystic fibrosis (pwCF), leading to development of PERT dosing guidelines and reformulated products. This study quantified incidence of FC in pwCF treated with PERT following those measures.

METHODS: This large prospective cohort study included eligible pwCF enrolled in the Cystic Fibrosis Foundation Patient Registry with ≥1 clinic visit in 2012-2014 and follow-up through 2020. Data on PERT exposure, demographics, and medical history were collected. Clinical data, imaging, and histopathology of suspected cases were examined by an independent adjudication panel of physicians familiar with this complication.

RESULTS: Base Study Population included 26,025 pwCF who contributed 155,814 person-years [mean (SD) 6.0 (2.0) years] of follow-up. Over 7.8 years, 29 pwCF had suspected FC; three cases were confirmed by adjudication, 22 cases were confirmed as not FC, and four cases were indeterminate. There were 22,161 pwCF exposed to any PERT, with mean PERT use time of 5.583 person-years and mean daily dose of 8328 U lipase per kg per day. All three confirmed cases and four indeterminate cases of FC occurred during current use of PERT. Incidence rates per 1000 person-years exposed were 0.0242 (95 % CI [0.0050, 0.0709]) for confirmed FC and 0.0566 (95 % CI [0.0227, 0.1166]) for indeterminate or confirmed FC.

CONCLUSIONS: The incidence of FC in pwCF is very low in the era of current treatment guidelines and more stringent quality standards for PERT products.

PMID:37880023 | DOI:10.1016/j.jcf.2023.08.013

Ann Am Thorac Soc. 2023 Oct 25. doi: 10.1513/AnnalsATS.202304-317OC. Online ahead of print.

ABSTRACT

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease (ACFLD) is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2-years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1s (FEV1) ≤40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modelled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1 30.9±5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex and FEV1, revealed percent predicted peak oxygen uptake (V ̇O2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional ten percent predicted were 0.60 (95% confidence interval, 0.43-0.90, P=0.008) and 0.60 (0.48-0.82, P<0.001). Tree-structured regression models, including a set of twelve prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ≤49.2% predicted versus 10.9% for those with a Wpeak >49.2% predicted, P<0.001. Conclusions: CPET provides prognostic information in ACFLD and Wpeak appears to be a promising marker for LTX referral and candidate selection.

PMID:37879036 | DOI:10.1513/AnnalsATS.202304-317OC

Ann Am Thorac Soc. 2023 Oct 25. doi: 10.1513/AnnalsATS.202306-509OC. Online ahead of print.

ABSTRACT

RATIONALE: Lung transplant can extend life for individuals with advanced cystic fibrosis (CF). Until March, 2023 the United States used the lung allocation score (LAS) to determine transplant priority. Certain clinical events/attributes ("risk events") that were not included in the LAS (e.g., massive hemoptysis) are relatively common and prognostically important in CF, and may prompt an exception request in order to increase priority for donor lungs. The new composite allocation score (CAS) also allows for exceptions using the same principles.

OBJECTIVE: Evaluate the frequency of LAS exceptions in PwCF listed for lung transplant and assess whether LAS exceptions are associated with improved waitlist outcomes for persons with CF (PwCF) compared to similarly "at-risk" individuals without LAS exceptions.

METHODS: A merged dataset combining CF Foundation Patient Registry and Organ Procurement and Transplantation Network data (2005-2019) was used to identify PwCF listed for lung transplant. We compared waitlist outcomes between PwCF with a LAS exception to those without an exception despite having a "risk event". "Risk events" were defined as, in the prior 12 months, having an episode of massive hemoptysis, pneumothorax, ≥ 3 moderate/severe pulmonary exacerbations, and/or a FEV1 decline by ≥ 30% (absolute) of predicted. Analyses were performed using competing risk regression with time to transplant as the primary outcome and death without transplant as a competing risk.

RESULTS: Of 3,538 listings from 3,309 candidates, 2% (n=81) of listings had ≥ 1 exception. Candidates with an exception and those with a risk event but no exception both received lung transplant more slowly than people without an exception or risk event (subdistribution hazard ratio (95% CI) - LAS exception cohort: 0.66 (0.52, 0.85); "risk event" cohort without exception: 0.79 (0.72, 0.86). There was no difference comparing those with LAS exceptions and those "at-risk" without LAS exceptions: 0.84 (0.66, 1.08).

CONCLUSIONS: LAS exceptions are rare in PwCF listed for lung transplant. LAS exceptions resulted in a similar time to transplant for PwCF when compared with similarly "at-risk" individuals. As we enter the CAS-era, these LAS-based results are pertinent to improve upon risk stratification among PwCF being considered for lung transplant.

PMID:37878995 | DOI:10.1513/AnnalsATS.202306-509OC

Urol Res Pract. 2023 Sep;49(5):312-315. doi: 10.5152/tud.2023.23061.

ABSTRACT

OBJECTIVE: As patients with cystic fibrosis live longer into their reproductive years, fertility concerns are rising. We hypothesized that while patients with cystic fibrosis may be informed of the impact of their disease on their reproductive potential, they remain unaware of the promising role of assisted reproductive technology in helping them conceive biological children.

METHODS: We distributed a voluntary and anonymous survey to cystic fibrosis patients and organizations to assess patient understanding of cystic fibrosis-related infertility. The survey questions aimed to capture demographic information, their reproductive education regarding cystic fibrosis, and their preferences for future fertility.

RESULTS: Forty respondents completed the survey (median age of 36 ± 14 years). The median age reported for learning about cystic fibrosis-associated infertility was 18 years. Respondents preferred that reproductive and infertility education be provided early; 43% reported the optimal age of education was younger than 18 years while 50% reported between 18 and 24 years. Of the respondents trying to conceive, 43% of patients have been trying to conceive for 1-3 years qualifying for infertility. Yet, the majority of those patients (69%) have not been offered a semen analysis and 90% have not had previous fertility treatments.

CONCLUSION: Our findings highlight that cystic fibrosis patients are knowledgeable about cystic fibrosis-related impacts on their fertility, with high-rated self-confidence. A fraction of patients still desire to conceive but have not been provided with assisted reproductive services. We recommend the establishment of active partnerships between cystic fibrosis care teams and fertility specialists to maximize their chances of conception.

PMID:37877879 | DOI:10.5152/tud.2023.23061

Pediatr Pulmonol. 2023 Oct 25. doi: 10.1002/ppul.26737. Online ahead of print.

NO ABSTRACT

PMID:37877709 | DOI:10.1002/ppul.26737

Microbiol Spectr. 2023 Oct 25:e0177323. doi: 10.1128/spectrum.01773-23. Online ahead of print.

ABSTRACT

Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF) lungs contribute to increasing morbidity and mortality. Pseudomonas aeruginosa, a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance (AMR). These bacterial populations display genetic and phenotypic diversity, but it is unclear how this diversity affects susceptibility to bacteriocins. R-pyocins, i.e., bacteriocins produced by P. aeruginosa, are phage-tail-like antimicrobials. R-pyocins have potential as antimicrobials, however, recent research suggests the diversity of P. aeruginosa variants within CF lung infections leads to varying susceptibility to R-pyocins. This variation may be linked to changes in lipopolysaccharide (LPS), acting as the R-pyocin receptor. Currently, it is unknown how frequently R-pyocin-susceptible strains are in chronic CF lung infection, particularly when considering the heterogeneity within these strains. In this study, we tested the R2-pyocin susceptibility of 139 P. aeruginosa variants from 17 sputum samples of 7 CF patients and analyzed LPS phenotypes. We found that 83% of sputum samples did not have R2-pyocin-resistant variants, while nearly all samples contained susceptible variants. There was no correlation between LPS phenotype and R2-pyocin susceptibility, though we estimate that about 76% of sputum-derived variants lack an O-specific antigen, 40% lack a common antigen, and 24% have altered LPS cores. The absence of a correlation between LPS phenotype and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Our research supports the potential of R-pyocins as therapeutic agents, as many infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations. IMPORTANCE Cystic fibrosis (CF) patients often experience chronic, debilitating lung infections caused by antibiotic-resistant Pseudomonas aeruginosa, contributing to antimicrobial resistance (AMR). The genetic and phenotypic diversity of P. aeruginosa populations in CF lungs raises questions about their susceptibility to non-traditional antimicrobials, like bacteriocins. In this study, we focused on R-pyocins, a type of bacteriocin with high potency and a narrow killing spectrum. Our findings indicate that a large number of infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations, supporting their potential use as therapeutic agents. The absence of a clear correlation between lipopolysaccharide (LPS) phenotypes and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Understanding the relationship between LPS phenotypes and R-pyocin susceptibility is crucial for developing effective treatments for these chronic infections.

PMID:37877708 | DOI:10.1128/spectrum.01773-23