SARS CoV2 Omicron Infections Among Vaccinated Maintenance Hemodialysis Patients- outcomes and comparison to Delta variant.

Background Infections with B.1.1.529 (Omicron) variants of SARS-CoV-2 became predominant worldwide since late 2021, replacing the previously dominant B.1.617.2 variant (Delta). While those variants are highly transmissible and can evade vaccine protection, population studies suggested that outcomes from infection with Omicron variants are better compared with Delta. Data regarding prognosis of maintenance hemodialysis (MHD) patients infected with Omicron vs. Delta variants, however, is scarce. Methods This retrospective cohort study includes all patients with end-stage kidney disease treated with MHD in Meir Medical Center, Kfar-Saba, Israel that were diagnosed with SARS-CoV-2 infection between June 2021 and May 2022. Results Twenty-six subjects were diagnosed with the Delta variant and 71 with Omicron. Despite comparable age between groups and higher mean vaccine doses prior to the infection among Omicron group (p<0.001), SARS-CoV-2 infection severity was significantly worse among MHD infected with the Delta variant: 50% developed severe or critical COVID-19 vs. 5% in the Omicron group (p<0.001). Over half of MHD infected with Omicron (57%) were asymptomatic during their illness. 30-day mortality rate for the whole cohort was 5.2%. It was significantly higher among MHD in the Delta group than in the Omicron group (5/26, 19.2% vs. 0/71, p<0.001), as was 90-day mortality rate (5/26, 19.2% vs. 3/71, 4.2%, p=0.02). Conclusions Infection with the SARS-CoV-2 Delta variant was associated with worse outcomes compared with Omicron, among subjects on MHD. However, despite mild disease among vaccinated MHD patients, infection with Omicron variant was still associated with significant 90-day mortality rate.

Assessing Health-Related Quality of Life in Non-Directed Versus Directed Kidney Donors: Implications for the Promotion of Non-Directed Donation.

Living kidney donation has increased significantly, but little is known about the post-donation health-related quality of life (HRQoL) of non-directed donors (NDs) vs. directed donors (DDs). We thus examined the outcomes of 112 living kidney donors (82 NDs, 30 DDs). For the primary outcomes-namely, the mean physical component summary (PCS) and mental component summary (MCS) scores of the 12-item Short Form Survey (SF-12) questionnaire-scores were significantly higher for the NDs vs. the DDs (PCS: +2.69, MCS: +4.43). For secondary outcomes, NDs had shorter hospital stays (3.4 vs. 4.4 days), returned to physical activity earlier (45 vs. 60 days), exercised more before and after donation, and continued physical activity post-donation. Regression analyses revealed that donor type and white blood cell count were predictive of the PCS-12 score, and donor type was predictive of the MCS-12 score. Non-directed donation was predictive of a shorter hospital stay (by 0.78 days, p < 0.001) and the odds of having PCS-12 and MCS-12 scores above 50 were almost 10 and 16 times higher for NDs, respectively (p < 0.05). These findings indicate the safety and potential benefits of promoting non-directed donation. However, careful selection processes must be maintained to prevent harm and exploitation.

Comparison of clinical remission criteria for severe asthma patients receiving biologic therapy.

BACKGROUND: The concept of remission on biological treatment has been suggested as a therapeutic target for patients with severe asthma, composed of 1. no chronic use of systemic steroids, 2. no exacerbations, 3. minimal symptoms, and 4. optimized lung function, for a significant time. However, the criteria for remission are not clearly defined. OBJECTIVE: Our objective was to compare different criteria for remission in subjects receiving biologicals for severe asthma. METHODS: A cross-sectional study of adult subjects who receive a stable regimen of a biological for severe asthma for at least 6-months. We compared the proportion of subjects who fulfilled different specific criteria in the four domains, as well as those who achieved different composite outcome measures of clinical remission. RESULTS: Of 39 subjects, 28 were females (71.8%), mean age 60.4. Twelve were current or past smokers (30.8%). Twelve had prior different biological treatment (30.8%), and 3/39 had more than one previous treatment (7.7%). Current biological included mepolizumab 12/39 (30.8%), dupilumab 11/39 (28.2%), benralizumab 10/39 (25.6%), omalizumab 5/39 (12.8%), reslizumab 1/39 (2.6%). Different specific criteria were achieved in 39-80% of subjects, being highest for no chronic steroid use and lowest for symptoms control and lung function. Overall remission was obtained by 20-41%, depending on definition, with significant variability in agreement between different sets of remission criteria (Cohen's kappa 0.33-0.89). CONCLUSION: Clinical remission is achievable in real-world severe asthmatics on biological therapies. The core criteria for remission should be better defined.

Intra-Cranial Arterial Calcifications in Hemodialysis Patients.

Background and objectives: Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods: The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results: A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group (p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population.

The Long-Term Outcome of Kidney Transplant Recipients in the Eighth Decade Compared With Recipients in the Seventh Decade of Life.

BACKGROUND: With the aging of the population, more older patients are being considered for kidney transplantation; therefore, it is crucial to evaluate the risks and benefits of transplantation in this population. This study aimed to assess long-term outcomes of kidney transplantation in a cohort of patients who underwent kidney transplantation at age >70 years, compared with patients aged 60 to 69 years at transplantation. METHODS: Included in the study were 261 consecutive kidney transplant recipients: 52 were aged >70 years, and 209 were aged 60 to 69 years at transplantation. Data were collected retrospectively and analyzed using multivariate logistic regression to identify potential outcome risk factors. RESULTS: The number of transplants in both groups increased during the study period. Mortality after transplantation was strongly correlated to age (hazard ratio [HR] = 1.11; 95% CI, 1.05-1.18; P < .001), deceased donor (HR = 2.0; 95% CI, 1.1-3.8; P = .034), and pretransplant diabetes (HR = 2.9; 95% CI, 1.7-4.9; P = .001). Recipients aged >70 years had an increased risk of death censored graft failure (HR = 2.98; 95% CI, 1.56-5.74; P = .001). In living donor transplants, 3-year survival was 80% in recipients age >70 years, compared with 98% in the 60- to 69-year group. Five-year survival was 71% and 92%, respectively. In deceased donor transplants, 3-year survival was 63% and 78%, and 5-year survival was 58% and 72%, respectively. The risk of malignancy (excluding nonmelanotic skin cancer) was nearly triple in the age >70 years group (HR = 2.96; 95% CI, 1.3-6.8; P = .01). CONCLUSIONS: Patient and graft survival in kidney recipients in the eighth decade is worse compared with recipients in the seventh decade of life. However, it is improved with living kidney donation.

Acute Kidney Injury and Rehabilitation Outcomes among Elderly Patients with Chronic Kidney Disease.

INTRODUCTION: The incidence of chronic kidney disease (CKD) is growing rapidly, along with the increasing geriatric population. CKD patients have higher incidence of fractures, stroke, and hospitalizations requiring rehabilitation. This is accompanied with the need for suitable rehabilitation programs to decrease disability and improve functionality to help elderly CKD patients maintain independence in activities of daily living. Considering that survivors of acute kidney injury (AKI) tend to experience decreased quality of life with increased frailty, rehabilitation in the elderly with kidney injury becomes even more complex. The aim of this study was to examine the impact of AKI on the outcomes of rehabilitation among elderly patients with CKD. METHODS: For this retrospective, observational study, the electronic medical records of all patients who were hospitalized in the rehabilitation department were reviewed. We assessed functional status at the beginning and end of rehabilitation, renal outcome, and all-cause mortality among elderly patients with CKD who experienced an AKI and compared them to those who did not have an AKI. RESULTS: The study cohort included 183 elderly patients with non-dialysis-dependent CKD. Patients with AKI (23% of study cohort) had a higher prevalence of heart failure and lower baseline estimated glomerular filtration rate, as compared with patients who did not have AKI. They were admitted to rehabilitation at a poorer functional capacity and were also discharged with lower functional independence measure scores. Overall odds ratio for all-cause death among patients with AKI versus without AKI was 3.2 (95% CI: 1.6-6.5; p = 0.001). CONCLUSION: AKI and CKD are interrelated syndromes. AKI was prevalent among elderly CKD patients and was associated with worse rehabilitation outcomes and higher mortality compared to similar patients without AKI.

The Clinical Significance of LDL-Cholesterol on the Outcomes of Hemodialysis Patients with Acute Coronary Syndrome.

Background and objectives: Dyslipidemia is one of the most important modifiable risk factors in the pathogenesis of cardiovascular disease in the general population, but its importance in the hemodialysis (HD) population is uncertain. Materials and Methods: This retrospective cohort study includes HD patients hospitalized due to acute coronary syndrome (ACS) in the period 2015-2020 with lipid profile data during ACS. A control group with preserved kidney function was matched. Risk factors for 30-day and 1-year mortality were assessed. Results: Among 349 patients included in the analysis, 246 were HD-dependent ("HD group"). HD group patients had higher prevalence of diabetes, hypertension, and heart disease than the control group. At ACS hospitalization, lipid profile and chronic statin treatment were comparable between groups. Odds ratios for 30-day mortality in HD vs. control group was 5.2 (95% CI 1.8-15; p = 0.002) and for 1-year, 3.4 (95% CI 1.9-6.1; p <0.001). LDL and LDL < 70 did not change 30-day and 1-year mortality rates in the HD group (p = 0.995, 0.823, respectively). However, survival after ACS in HD patients correlated positively with nutritional parameters such as serum albumin (r = 0.368, p < 0.001) and total cholesterol (r = 0.185, p < 0.001), and inversely with the inflammatory markers C-reactive protein (CRP; r = -0.348, p < 0.001) and neutrophils-to-lymphocytes ratio (NLR; r = -0.181, p = 0.019). Multivariate analysis demonstrated that heart failure was the only significant predictor of 1-year mortality (OR 2.8, p = 0.002). LDL < 70 mg/dL at ACS hospitalization did not predict 1-year mortality in the HD group. Conclusions: Despite comparable lipid profiles and statin treatment before and after ACS hospitalization, mortality rates were significantly higher among HD group. While malnutrition-inflammation markers were associated with survival of dialysis patients after ACS, LDL cholesterol was not. Thus, our study results emphasize that better nutritional status and less inflammation are associated with improved survival among HD patients.

Neutrophil reactive oxygen formation, bacterial infections and mortality in malnourished hemodialysis patients: Evaluation of clinical outcomes.

INTRODUCTION: Patients with end stage kidney disease undergoing maintenance hemodialysis (MHD) are prone to malnutrition and infections. OBJECTIVE: The objective of this study was to evaluate the effect of polymorphonuclear (PMN) cell dysfunction on clinical outcomes of MHD patients, in association with nutritional status. METHODS: This prospective study investigated 39 MHD patients by evaluating the oxidative activity of their PMN cells using Phorbol 12-Myristate-13-Acetate (PMA) stimulation. Blood samples were taken from each participant at dialysis initiation. Demographics, laboratory data, and clinical outcomes during a 24-month follow-up period were obtained from electronic medical records. RESULTS: Phagocytic activity was described in percentiles of mean fluorescence intensity (MFI) of PMA levels. There were no differences in comorbidities between patients with low or high MFI-PMA percentiles. Patients in the lowest (25th) MFI-PMA percentile (N = 10) had poorer nutritional status and more frequent severe infections compared to the other 29 patients (4.3 ± 3.4 events versus 2 ± 2.2 events, p = 0.017). Furthermore, they had more frequent hospitalizations (>3) due to infections (70% versus 41%, p = 0.073) and their mortality rate was higher (80% versus 31%, p = 0.007). The odds ratio for all-cause mortality was 8.85. In multivariate analysis, the MFI-PMA percentile and ischemic heart disease were the strongest predictors of all-cause mortality (p = 0.02 and p = 0.005, respectively). CONCLUSIONS: Low MFI-PMA levels were associated with poor nutritional status and adverse clinical outcomes and might serve as a prognostic biomarker, predicting severe infections and mortality among malnourished MHD patients.

Clinical efficacy of the fourth dose of the BNT162b2 vaccine in maintenance dialysis patients.

BACKGROUND AND OBJECTIVES: Highly effective vaccines against severe acute respiratory syndrome virus 2 have been developed and administered worldwide. However, protection from coronavirus disease 2019 is not absolute and an optimal vaccination regimen needs to be established. This study assessed the clinical efficacy of the coronavirus disease 2019 vaccine among dialysis patients receiving 3 or 4 doses of vaccine. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This retrospective study was conducted using the electronic database of Clalit Health Maintenance Organization in Israel. Chronic dialysis patients treated with either hemodialysis or peritoneal dialysis during the coronavirus disease 2019 pandemic were included. We compared clinical outcomes of patients who had received three or four doses of the severe acute respiratory syndrome virus 2 vaccine. RESULTS: This study included 1,030 patients on chronic dialysis, with a mean age of 68 ± 13 years. Among them, 502 patients had received 3 doses of the vaccine and 528 received 4 doses. Severe acute respiratory syndrome virus 2 infection rates, severe COVID-19 that resulted in hospitalizations, COVID-19-related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after controlling for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, the fourth dose was significantly associated with reduced COVID-19-related mortality (1.7% vs. 3.8%, p = 0.04). Odds ratio for COVID-19-related mortality was 0.44 with 95% CI 0.2-0.98. CONCLUSIONS: As seen in the general population and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19-related hospitalization and mortality among chronic dialysis patients. Further studies are needed to establish the optimal regimens of vaccination for patients on chronic dialysis.

The Clinical Manifestation of Immunosuppressive Therapy as a Tool to Improve Immune Monitoring in Renal Transplant Recipients.

INTRODUCTION: Metrics for posttransplant immune monitoring to prevent over or under immunosuppression in renal transplant recipients (RTRs) are lacking. METHODS: We surveyed 132 RTRs, 38 in the first year posttransplant and 94 >1-year posttransplant, to study the clinical expression of immunosuppressive therapy. A questionnaire administered to these RTRs was divided into physical (Q physical) and mental (Q mental) symptoms. RESULTS: In multivariable models for the association between the calculated Q physical and Q mental scores and different clinical and biochemical variables in the 38 RTRs who filled out the questionnaire 130 times during the first year posttransplant, it was found that mycophenolic acid (MPA) and prednisone use increased the mean Q physical score by 0.59 (95% CI: 0.21-0.98, p = 0.002) and 0.53 (95% CI: 0.26-0.81, p = 0.00), respectively, while MPA use increased the mean Q mental score by 0.72 (95% CI: 0.31-1.12, p = 0.001). Among the 94 RTRs who each completed the questionnaire only once, the odds for the mean Q mental score to be above the median value were more than 3 times higher for RTRs treated versus non-treated with MPA (OR 3.38, 95% CI: 1.1-10.3, p = 0.03). MPA-treated RTRs had higher mean scores for questions related to sleep disorders (1.83 ± 1.06 vs. 1.32 ± 0.67 for not treated, p = 0.037), to difficulty falling asleep (1.72 ± 1.11 vs. 1.16 ± 0.5, p = 0.02), and to depression and anxiety. CONCLUSION: We concluded that prednisone and MPA use are associated with an increased Q physical and Q mental scores in RTRs. Routine monitoring of physical and mental status of RTRs should be implemented to improve the diagnosis of overimmunosuppression. Dose reduction or discontinuation of MPA should be considered in RTRs who report sleep disorders, depression, and anxiety.

Hemodialysis Serum Stimulates the TXNIP-eNOS-STAT3 Inflammatory Pathway In Vitro.

BACKGROUND: Endothelial dysfunction, vascular inflammation and accelerated atherosclerosis have been investigated extensively in patients with chronic kidney disease (CKD). These conditions, as well as protein-energy malnutrition and oxidative stress, impair kidney function and contribute to increased morbidity and mortality among patients with end-stage kidney disease undergoing hemodialysis (HD). TXNIP, a key regulator of oxidative stress, has been linked to inflammation and suppresses eNOS activity. STAT3 activation adds to endothelial cell dysfunction, macrophage polarization, immunity and inflammation. Therefore, it is critically involved in atherosclerosis. This study evaluated the effect of sera from HD patients on the TXNIP-eNOS-STAT3 pathway using an in vitro model of human umbilical vein endothelial cells (HUVECs). METHODS: Thirty HD patients with end-stage kidney disease and ten healthy volunteers were recruited. Serum samples were taken at dialysis initiation. HUVECs were treated with HD or healthy serum (10% v/v) for 24 h. Then, cells were collected for mRNA and protein analysis. RESULTS: TXNIP mRNA and protein expression were significantly increased in HUVECs treated with HD serum compared to healthy controls (fold changes: 2.41 ± 1.84 vs. 1.41 ± 0.5 and 2.04 ± 1.16 vs. 0.92 ± 0.29, respectively), as were IL-8 mRNA (fold changes: 2.22 ± 1.09 vs. 0.98 ± 0.64) and STAT3 protein expression (fold changes: 1.31 ± 0.75 vs. 0.57 ± 0.43). The expression of eNOS mRNA and protein (fold changes: 0.64 ± 0.11 vs. 0.95 ± 0.24; 0.56 ± 0.28 vs. 4.35 ± 1.77, respectively) and that of SOCS3 and SIRT1 proteins were decreased. Patients' nutritional status, reflected by their malnutrition-inflammation scores, did not affect these inflammatory markers. CONCLUSIONS: This study showed that sera from HD patients stimulated a novel inflammatory pathway, regardless of their nutritional status.

Dialysis modality, humoral response to vaccine, and SARS-CoV-2 infection risk: Comparative prospective evaluation.

BACKGROUND: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection. METHODS: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection. RESULTS: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality. CONCLUSION: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.

Predictors and Adverse Outcomes of Acute Kidney Injury in Hospitalized Renal Transplant Recipients.

Data about in-hospital AKI in RTRs is lacking. We conducted a retrospective study of 292 RTRs, with 807 hospital admissions, to reveal predictors and outcomes of AKI during admission. In-hospital AKI developed in 149 patients (51%). AKI in a previous admission was associated with a more than twofold increased risk of AKI in subsequent admissions (OR 2.13, p < 0.001). Other major significant predictors for in-hospital AKI included an infection as the major admission diagnosis (OR 2.93, p = 0.015), a medical history of hypertension (OR 1.91, p = 0.027), minimum systolic blood pressure (OR 0.98, p = 0.002), maximum tacrolimus trough level (OR 1.08, p = 0.005), hemoglobin level (OR 0.9, p = 0.016) and albumin level (OR 0.51, p = 0.025) during admission. Compared to admissions with no AKI, admissions with AKI were associated with longer length of stay (median time of 3.83 vs. 7.01 days, p < 0.001). In-hospital AKI was associated with higher rates of mortality during admission, almost doubled odds for rehospitalization within 90 days from discharge and increased the risk of overall mortality in multivariable mixed effect models. In-hospital AKI is common and is associated with poor short- and long-term outcomes. Strategies to prevent AKI during admission in RTRs should be implemented to reduce re-admission rates and improve patient survival.

Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

One-year dynamics of antibody titers after three doses of SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: A third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination. METHODS: A prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4-6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded. RESULTS: Seventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months. CONCLUSIONS: A third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months.

Negative impact of high-performance flights on aviators with mitral valve prolapse.

BACKGROUND: While it appears not to affect healthy aviators' hearts, there are scarce data regarding the impact of high-performance flights on aviators with mitral valve prolapse (MVP). METHODS: A retrospective, comparative cohort study of military aviators with MVP. Subjects were categorized to either high-performance (jet fighter) or low-performance (transport and helicopter) aviators. The primary outcomes were the rates of mitral interventions and of adverse cardiovascular events since being an aircrew candidate and up to the end of flying career. Additional outcomes were echocardiographic measurements and the cumulative proportion of mitral valve interventions over time. RESULTS: Of 33 male aviators with MVP, 18 were high-performance aviators. On average, follow-up started at age 18.5 years and lasted 27.8 ±â€¯10.1 years. Baseline characteristics were similar between the study groups. Aviators of high-performance aircraft had increased rates of mitral valve surgery (33 % vs. 0, p = 0.021), MVP-related complications (39 % vs. 6.7 %, p = 0.046), and a higher incidence of mitral valve repair over time (p = 0.02). High-performance flight was associated with increased intraventricular septum thickness (IVS, 9.7 mm vs 8.9 mm, p = 0.015) and IVS index (p = 0.026) at the last echocardiographic assessment. High-performance aviators tended to develop worsening severity of mitral regurgitation. CONCLUSIONS: High-performance flight may be associated with an increased risk for valvular deterioration and need for mitral surgery in aviators with MVP.