Global Leadership Initiative on Malnutrition-Diagnosed Malnutrition in Lung Transplant Candidates.

BACKGROUND AND AIMS: Malnutrition in lung transplantation (LT) candidates increases postoperative morbidity and mortality. Early diagnosis of malnutrition could attenuate adverse prognostic factors. This study aimed to assess the prevalence of nutritional risk and malnutrition using GLIM criteria in LT candidates and clinically characterize those with malnutrition. METHODS: A prospective longitudinal study was conducted from 2000 to 2020 of LT candidates who underwent complete nutritional assessment (nutritional screening, anthropometry, bioelectrical impedance, blood laboratory tests and malnutrition diagnosis using GLIM criteria). RESULTS: Obstructive diseases (45.6%), interstitial diseases (36.6%) and cystic fibrosis/non-cystic fibrosis bronchiectasis (15.4%) were the main conditions assessed for LT. Of the 1060 candidates evaluated, 10.6% were underweight according to BMI, 29% were at risk of malnutrition and 47% were diagnosed with malnutrition using GLIM criteria. Reduced muscle mass was the most frequent GLIM phenotypic criterion. Malnutrition was more prevalent in patients with cystic fibrosis/non-cystic fibrosis bronchiectasis (84.5%) and obstructive (45.4%) and interstitial (31.3%) diseases. GLIM criteria detected some degree of malnutrition in all diseases requiring LT and identified patients with higher CRP levels and worse respiratory function, anthropometric measurements and visceral protein and lipid profiles. CONCLUSIONS: LT candidates present a high prevalence of malnutrition using the GLIM algorithm. GLIM criteria detected malnutrition in all diseases requiring LT and defined patients with worse clinical-analytical profiles.

Peri-operative and long-term outcomes of kidney transplantation in patients with cystic fibrosis.

INTRODUCTION: There is a lack of data regarding the peri-operative and long-term outcomes of kidney transplantation in cystic fibrosis (CF) patients. Herein, we report the peri-operative and long-term outcomes of kidney transplantation in CF patients. MATERIALS AND METHODS: All CF patients who received a kidney transplant at the national kidney transplant center between 1993 and 2022 were identified. Recipients of the contralateral donor kidney were selected as a control group. Primary outcomes included 1-, 5-, and 10- year death-censored graft survival and overall survival. Secondary outcomes included peri-operative morbidity, acute graft rejection, delayed graft function (DGF), and length of stay (LOS). RESULTS: Fourteen patients received a kidney transplant over the study period. Median age at transplantation was 35 (IQR 31, 40) years. The 1-, 5-, and 10-year death-censored graft survival was 92, 74, and 74% in the CF group compared to 100, 92, and 92% in the control group (p = .44). The 1-, 5-, and 10-year overall survival in the CF group was 85, 66, and 57% compared to 100, 92, and 82% in the control group (p = .036). There was no significant difference in peri-operative outcomes including LOS (10 vs. 11 days, p = .84), ICU admission (1 vs. 0 patients, p > .99), acute rejection episodes (2 vs. 1 patients, p > .99), and DGF (1 vs. 2 patients, p = .60). CONCLUSION: CF patients have good long-term graft survival, however, overall survival was worse compared to a matched cohort. These data provide important information for transplant surgeons when considering suitable donor allografts in this unique patient population.

Patients With Cystic Fibrosis Undergoing Total Hip and Total Knee Arthroplasty Are at Increased Risk for Perioperative Complications.

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.

Pre-emptive transjugular intrahepatic portosystemic shunt in pediatric cystic fibrosis-related liver disease and portal hypertension: prospective long-term results.

PURPOSE: Portal hypertension (PHT) and its sequelae are the most clinically important manifestations in cystic fibrosis-related liver disease (CFLD). This paper aimed to evaluate the safety and efficacy of a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) to prevent PHT-related complications in pediatric patients with CFLD. METHODS: This was a prospective single-arm study on pediatric patients with CFLD, signs of PHT, and preserved liver function who underwent a pre-emptive TIPS in a single tertiary CF center between 2007 and 2012. The long-term safety and clinical efficacy were assessed. RESULTS: A pre-emptive TIPS was performed on seven patients with a mean age of 9.2 years (± standard deviation: 2.2). The procedure was technically successful in all patients, with an estimated median primary patency of 10.7 years [interquartile range (IQR) 0.5-10.7)]. No variceal bleeding was observed during the median follow-up of 9 years (IQR 8.1-12.9). In two patients with advanced PHT and rapidly progressive liver disease, severe thrombocytopenia could not be stopped. Subsequent liver transplantation revealed biliary cirrhosis in both patients. In the remaining patients with early PHT and milder porto-sinusoidal vascular disease, symptomatic hypersplenism did not occur, and liver function remained stable until the end of the follow-up. Inclusion for pre-emptive TIPS was discontinued in 2013 following an episode of severe hepatic encephalopathy. CONCLUSION: TIPS is a feasible treatment with encouraging long-term primary patency to avoid variceal bleeding in selected patients with CF and PHT. However, as the progression of liver fibrosis, thrombocytopenia, and splenomegaly is inevitable, the clinical benefits due to pre-emptive placement appear to be minor.

Lung Allocation Score Exceptions in Persons with Cystic Fibrosis Undergoing Lung Transplant.

Rationale: Lung transplantation can extend the lives of individuals with advanced cystic fibrosis (CF). Until March 2023, the Lung Allocation Score (LAS) was used in the United States to determine transplant priority. Certain clinical events or attributes ("risk events") that are not included in the LAS (e.g., massive hemoptysis) are relatively common and prognostically important in CF and may prompt an exception request to increase priority for donor lungs. The new Lung Composite Allocation Score (CAS) also allows for exceptions based on the same principles. Objectives: To evaluate the frequency of LAS exceptions in persons with CF (PwCFs) listed for lung transplantation and assess whether LAS exceptions are associated with improved waitlist outcomes for PwCFs compared with similarly "at-risk" individuals without LAS exceptions. Methods: A merged dataset combining data from the CF Foundation Patient Registry and the Organ Procurement and Transplantation Network (2005-2019) was used to identify PwCFs listed for lung transplantation. We compared waitlist outcomes between PwCFs with a LAS exception versus those without an exception despite having a risk event. Risk events were defined as an episode of massive hemoptysis, pneumothorax, at least three moderate/severe pulmonary exacerbations, and/or a decrease in forced expiratory volume in 1 second by ⩾30% predicted (absolute) in the prior 12 months. Analyses were performed using competing risk regression with time to transplantation as the primary outcome and death without a transplant as a competing risk. Results: Of 3,538 listings from 3,309 candidates, 2% of listings (n = 81) had at least one exception. Candidates with an exception and those with a risk event but no exception received lung transplants more slowly than people without an exception or risk event (subdistribution hazard ratio [95% confidence interval]: LAS exception cohort, 0.66 [0.52-0.85]; risk event cohort without exceptions, 0.79 [0.72-0.86]). There was no difference between those with LAS exceptions and those at risk without LAS exceptions: subdistribution hazard ratio, 0.84 (0.66-1.08). Conclusions: LAS exceptions are rare in PwCFs listed for lung transplantation. LAS exceptions resulted in a similar time to transplantation for PwCFs compared with similarly at-risk individuals. As we enter the CAS era, these LAS-based results are pertinent to improve risk stratification among PwCFs being considered for lung transplantation.

How Would We Treat Our Own Cystic Fibrosis With Lung Transplantation?

Lung transplantation is the only therapy for patients with end-stage lung disease. In advanced lung diseases such as cystic fibrosis (CF), life expectancy increases, and it is important to recognize extrapulmonary comorbidities. Cardiovascular involvement, including pulmonary hypertension, right-heart failure, and myocardial dysfunction, are manifest in the late stages of CF disease. Besides right-heart failure, left-heart dysfunction seems to be underestimated. Therefore, an optimal anesthesia and surgical management risk evaluation in this high-risk patient population is mandatory, especially concerning the perioperative use of mechanical circulatory support. The use of an index case of an older patient with the diagnosis of cystic fibrosis demonstrates the importance of early risk stratification and strategy planning in a multidisciplinary team approach to guarantee successful lung transplantation.

Surgery for nasal polyposis in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in paranasal sinuses determines chronic rhinosinusitis (CRS) and nasal polyposis. Endoscopic sinus surgery is used to open the sinuses and allow medical treatment to work properly. OBJECTIVES: To determine the effects of sinus surgery alone or in combination with medical treatment (non-surgical) compared to medical treatment (non-surgical) alone on both nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis. Further, to evaluate the impact of sinus surgery (with or without medical treatment) on hospitalization rates, use of antibiotics and pulmonary exacerbation rates. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched other databases (Pubmed, Embase, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Virtual Health Library and ClinicalTrials.gov). Date of last search: 18 September 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing groups who underwent endoscopic sinus surgery and groups with medical treatment alone. DATA COLLECTION AND ANALYSIS: The review authors independently selected studies, extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE. They contacted the authors of the included study for additional information. MAIN RESULTS: We identified 66 publications relating to 50 studies from electronic searches. Only one study fulfilled the inclusion criteria, and only limited information was available. In this study, 28 participants aged 19 to 28 years were randomized in equal numbers to either nasal irrigation alone or nasal irrigation with surgery (endoscopic polypectomy with extended sinusotomy). The certainty of the evidence was very low according to the GRADE approach. We are uncertain whether, compared to medical treatment alone, the addition of surgical intervention improves nasal symptoms, or reduces bacterial colonization, the use of antibiotics and pulmonary exacerbations. We are also uncertain whether the addition of surgery to medical treatment leads to changes in pulmonary function. There was one episode of bleeding during surgery that was corrected during the procedure with no further consequences. The study did not report on survival. AUTHORS' CONCLUSIONS: Very low-certainty evidence means we are not certain if endoscopic sinus surgery to treat chronic rhinosinusitis with nasal polyposis in cystic fibrosis is effective. Future research should be multicentric to increase the number of participants and increase statistical power. Adequate randomization and allocation concealment are important to guarantee that the groups are similar. Blinding, however, may not be possible in an ethical trial; even without blinding, results can achieve high-level evidence if the outcomes used are objective parameters. Future research should follow participants of all ages for at least 12 months to evaluate the evolution of nasal polyposis, its recurrence and how symptoms may return. We also consider mortality an important outcome to be assessed. Future clinical research should consider the effects of cystic fibrosis transmembrane conductance regulators, a new group of drugs that may affect the development of nasal polyps.

Self-reported engagement in everyday activities following bilateral lung transplantation in paediatric cystic fibrosis: a single centre study.

INTRODUCTION: Following lung transplantation, it is unknown how children/adolescents self-assess their performance in everyday activities, importance of these activities, and whether resumption of everyday activities influences self-reported quality of life. The aim was to examine the effect of bilateral lung transplantation on children's/adolescent's perception of engagement in everyday activities over the first 18 months post-transplant. METHODS: A multiple-single-case-study pre-post test design was conducted at a National Paediatric Lung Transplant Service. Participants were aged under 18 years and were 3 months post first bilateral lung transplant at the time of recruitment. Outcomes were self-reported quality of life (Paediatric Quality of Life Inventory (PedsQL), Transplant Module and engagement in meaningful life roles (Child Occupational Self-Assessment (COSA) Scale) measured at 3 months and 18 months post-transplant from participants, and their parent(s) (PedsQL). Analysis included paired between-time differences and descriptive analysis. RESULTS: Seven participants were recruited to the trial with a mean age of 13 (SD 4) years and a diagnosis of cystic fibrosis. The total mean scores on PedsQL remained stable between 3 months and 18 months for both participants and parents. The PedsQL transplant module total mean scores of participants significantly increased from 3 months (M=66.58, SD=11.83) to 18 months (M=80.25, SD=11.56), t(5) = 2.91, p=0.03 whereas parents' scores remained stable. COSA responses reported 'big problems' with self-care tasks, family engagement and coping with worries at 3 months. At 18 months, the 'big problem' activities shifted to community engagement and independence. CONCLUSION: Time influences self-reported quality of life and engagement in meaningful life roles for children/adolescents and their parents 3 months to 18 months post-lung transplant. Our findings highlight the importance of focusing on occupational roles and occupational performance of children and adolescents when designing post-transplant interventions, suggesting a key role for occupational therapy after transplantation.

The prevalence of vascular and metabolic complications after lung transplant in people with cystic fibrosis in a Dutch cohort.

BACKGROUND: With improvements in care for people with Cystic Fibrosis (pwCF), total survival after Lung Transplantation (LTx) will be longer. Therefore, this population's up-to-date analysis of late-onset post-transplant metabolic and vascular complications will be more relevant in current clinical practice. METHODS: We studied 100 pwCF who underwent an LTx between 2001 and 2020 at the University Medical Centre Utrecht, the Netherlands. The median age at transplant was 31 years and 55 percent was male. We assessed survival, the prevalence of metabolic complications (diabetes, renal damage, dyslipidemia, and metabolic syndrome), and vascular complications (hypertension, heart rhythm disease, micro-, and macrovascular disease). In addition, differences in risks for developing complications based on sex and overall survival were analyzed. RESULTS: The prevalence of macrovascular disease raised to 15.9 percent 15 years post-LTx. The prevalence of diabetes increased from 63 percent at LTx to over 90 percent 15 years post-LTx and the prevalence of dyslipidemia increased from 21 percent to over 80 percent. Survival 1-, 2-, 5-, and 10 years post-transplant were 84, 80, 76, and 58 percent respectively. No significant differences were found based on sex. CONCLUSION: This study shows that the prevalence of cardiovascular risk factors increases after LTx for CF, potentially leading to major complications. These data emphasize the necessity of regular check-ups for metabolic and vascular complications after LTx with specific attention to renal damage. Early recognition of these complications is crucial and will lead to earlier intervention, which could lead to improved prognosis after lung transplantation.

The Weariness of Hoping: Synchronizing Affect While Awaiting Organ Transplantation for Cystic Fibrosis in Germany.

We describe the challenges in synchronizing affect during the lengthy lead-up to organ transplantation. Our analysis draws on ethnographic fieldwork in Eastern Germany among medical staff caring for patients with cystic fibrosis, a progressive, genetic illness. Patient and practitioners must together endure an uncertain wait for a donor organ, while simultaneously living and working toward living as well as possible. The organizing affective principle in this setting is hoping, which is a socio-material practice that must be continuously and interactively re-produced. Too little or too much hoping must be managed by adjusting affective intensities. A failure to strike this balance can lead to what we designate as the weariness of hoping.

Esophageal squamous cell carcinoma at the site of tracheo-esophageal fistula repair in a patient with cystic fibrosis.

With increasing survival in patients with cystic fibrosis (CF), complications such as gastrointestinal (GI) malignancies are becoming more apparent, especially in transplanted patients. In patients with CF, these malignancies are most commonly found in the small bowel, colon, biliary tract and pancreas. We describe a patient with esophageal squamous cell cancer at the site of trachea-esophageal fistula repair in the setting of long-standing CF. Many factors such as low expression of CF transmembrane conductance regulator gene, inflammation and resulting metaplasia, bacterial dysbiosis, dysregulation of Wnt/ß-catenin signalling, immune cell infiltration, disruption of intestinal stem cell homeostasis and intestinal barrier integrity have all been implicated in the causation of GI malignancy in patients with CF. Based on shared decision-making in high-risk transplanted individuals, esophagogastroduodenoscopy can be considered alongside colon cancer screening which is currently recommended starting at age 30-35 years.

Cystic fibrosis survival outcomes following second lung transplant: The north American experience.

INTRODUCTION: Re-transplant is an option for those who develop end-stage lung disease due to rejection; however, little data exist following re-transplantation in cystic fibrosis (CF). METHODS: Data from the Canadian CF Registry and US CF Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. Individuals who underwent a 2nd lung transplant between 2005 and 2019 were included. The Kaplan-Meier method was used to estimate the probability of survival post-second transplant at 1, 3, and 5-years. RESULTS: Of those people who were waitlisted for a second transplant (N = 818), a total of 254 (31%) died waiting, 395 (48%) were transplanted and 169 (21%) people were alive on the waitlist. Median survival time after 2nd lung transplant was 3.3 years (95% CI: 2.8-4.1). The 1-, 3- and 5-year survival rates were 77.4% (95% CI: 73.1-82%), 52% (95% CI: 46.7-58%) and 39.4% (95% CI: 34.1-45.6%). CONCLUSIONS: Survival following second lung transplant in CF patients is lower than estimates following the first transplant. Over half of subjects who are potentially eligible for a second transplant die without receiving a second organ. This warrants further investigation.

Results of Lung Transplantation for Cystic Fibrosis With Selected Donors Over 65 Years Old.

Lung transplantation is limited by the shortage of suitable donors. Many programs have begun to use extended criteria donors. Donors over 65 years old are rarely reported, especially for young cystic fibrosis recipients. This monocentric study was conducted for cystic fibrosis recipients from January 2005 to December 2019, comparing two cohorts according to lung donor age (<65 years or ≥65 years). The primary objective was to assess the survival rate at 3 years using a Cox multivariable model. Of the 356 lung recipients, 326 had donors under 65 years, and 30 had donors over 65 years. Donors' characteristics did not differ significantly in terms of sex, time on mechanical ventilation before retrieval, and partial pressure of arterial oxygen/fraction of inspired oxygen ratio. There were no significant differences in post-operative mechanical ventilation duration and incidence of grade 3 primary graft dysfunction between the two groups. At 1, 3, and 5 years, the percentage of predicted forced expiratory volume in 1 s (p = 0.767) and survival rate did not differ between groups (p = 0.924). The use of lungs from donors over 65 years for cystic fibrosis recipients allows extension of the donor pool without compromising results. Longer follow-up is needed to assess the long-term effects of this practice.

The centripetal endoscopic sinus surgery in patients with cystic fibrosis: A preliminary study.

OBJECTIVES: The main aim of this study is to analyze the possible differences between clinical, demographic or genetic characteristics, in Cystic Fibrosis (CF) patients with chronic rhinosinusitis (CRS) with different phenotype. The secondary objective is to describe the possible benefit of surgery with Centripetal Endoscopic Sinus Surgery (CESS). METHODS: The study includes 56 who performed CT scan of the paranasal sinuses. They were divided in 3 group according to phenotype: CRS without Nasal Polyps (NP); CRS with NP; CRS complicated with Mucocele. The clinical symptoms, age, gender, genotype, microbial colonization and pulmonary disease stage were collected and analyzed to assess possible statistically significant differences. Regarding the 7 patients who performed CESS surgery, the number of hospitalizations, intravenous (iv) antibiotic courses, respiratory exacerbations, the FEV1, the Lund-Mackay Score (LMS) and the SNOT 22 were evaluated before and 1 year after surgery. RESULTS: No statistically significant differences regarding clinical symptoms between the 3 groups were identified (p > 0.05). Furthermore, there were no differences in age, gender, genotype, microbial colonization and pulmonary disease stage (p > 0.05). Regarding the patients who performed CESS, no significative difference in FEV1 progression was found. A reduction in hospitalization, pulmonary exacerbation and in the number of iv antibiotic courses resulted statistically significant different (p = 0.004; <0.001 and <0.001 respectively). A significant improvement in SNOT-22 and LMS (p < 0.001) was obtained. CONCLUSION: Radiological monitoring of the rhinosinus disease is necessary regardless of the clinical expression of the disease. The presence of CRS with NP complicated by mucocele is frequent and independent of the patient's age and clinical manifestations. An extensive surgical approach could represent the gold standard for patients with CF in consideration of the potential important advantages to perform a total toilet of all the sinuses and nasal cavities and at the same time eliminating a potential microbiological reservoir.

Impact of extended sinus surgery on allograft infection, allograft function and overall survival in cystic fibrosis lung transplant recipients.

BACKGROUND: Studies investigating the impact of sinus surgery for cystic fibrosis (CF) patients performed early after lung transplantation (Ltx) are scarce. Recent studies evaluating frequency of respiratory infections and graft outcomes are not available. OBJECTIVES/HYPOTHESIS: To determine whether there is a difference in allograft infection, allograft function and overall survival among CF lung transplant recipients with and without concomitant sinus surgery. STUDY DESIGN: Retrospective single-center study. METHODS: We examined 71 CF patients who underwent Ltx between 2009 and 2019 at our center. Fifty-nine patients had sinus surgery before or/and after transplantation and twelve did not undergo sinus surgery. We assessed the survival, the diagnosis of chronic allograft dysfunction (CLAD) and all elevated (> 5 mg/l) c-reactive protein episodes during the observed period. The infectious events of the upper and lower airways were categorized in mild infections (5-15 mg/l CRP) and severe infections (> 15 mg/l CRP). RESULTS: There was no difference in the long-time overall survival (p = 0.87) and no benefit in the short-term survival at 4 year post-transplant (p = 0.29) in both groups. There was no difference in both groups concerning CLAD diagnosis (p = 0.92). The incidence of severe upper and lower airway infections (CRP > 15 mg/l) was significantly decreased in the sinus surgery group (p = 0.015), whereas in mild infections there was a trend to decreased infections in the sinus surgery group (p = 0.056). CONCLUSIONS: CF patients undergoing Ltx benefit from extended endoscopic sinus surgery (eESS) in terms of frequency of severe infectious events of the upper and lower airways. There was no difference in overall survival and frequency of CLAD in the two groups.