A joint normal-ordinal (probit) model for ordinal and continuous longitudinal data.

In biomedical studies, continuous and ordinal longitudinal variables are frequently encountered. In many of these studies it is of interest to estimate the effect of one of these longitudinal variables on the other. Time-dependent covariates have, however, several limitations; they can, for example, not be included when the data is not collected at fixed intervals. The issues can be circumvented by implementing joint models, where two or more longitudinal variables are treated as a response and modeled with a correlated random effect. Next, by conditioning on these response(s), we can study the effect of one or more longitudinal variables on another. We propose a normal-ordinal(probit) joint model. First, we derive closed-form formulas to estimate the model-based correlations between the responses on their original scale. In addition, we derive the marginal model, where the interpretation is no longer conditional on the random effects. As a consequence, we can make predictions for a subvector of one response conditional on the other response and potentially a subvector of the history of the response. Next, we extend the approach to a high-dimensional case with more than two ordinal and/or continuous longitudinal variables. The methodology is applied to a case study where, among others, a longitudinal ordinal response is predicted with a longitudinal continuous variable.

Rectal organoid morphology analysis (ROMA) as a novel physiological assay for diagnostic classification in cystic fibrosis.

BACKGROUND: Diagnosing cystic fibrosis (CF) is not always straightforward, in particular when sweat chloride concentration (SCC) is intermediate and <2 CF-causing CFTR variants are identified. The physiological CFTR assays proposed in the guidelines, nasal potential difference and intestinal current measurement, are not readily available nor feasible at all ages. Rectal organoid morphology analysis (ROMA) was previously shown to discriminate between organoids from subjects with and without CF based on a distinct phenotypical difference: compared with non-CF organoids, CF organoids have an irregular shape and lack a visible lumen. The current study serves to further explore the role of ROMA when a CF diagnosis is inconclusive. METHODS: Organoid morphology was analysed using the previously established ROMA protocol. Two indices were calculated: the circularity index to quantify the roundness of organoids and the intensity ratio as a measure of the presence of a central lumen. RESULTS: Rectal organoids from 116 subjects were cultured and analysed together with the 189 subjects from the previous study. ROMA almost completely discriminated between CF and non-CF. ROMA indices correlated with SCC, pancreatic status and genetics, demonstrating convergent validity. For cases with an inconclusive diagnosis according to current guidelines, ROMA provided additional diagnostic information, with a diagnostic ROMA classification for 18 of 24 (75%). DISCUSSION: ROMA provides additional information to support a CF diagnosis when SCC and genetics are insufficient for diagnostic classification. ROMA is standardised and can be centralised, allowing future inclusion in the diagnostic work-up as first-choice physiological assay in case of an unclear diagnosis.

Incidence and risk factors of metachronous contralateral inguinal hernia development up to 25 years after unilateral inguinal hernia repair: a single-centre retrospective cohort study.

BACKGROUND: Patients undergoing unilateral inguinal hernia repair (IHR) are at risk of metachronous contralateral inguinal hernia (MCIH) development. We evaluated incidence and risk factors of MCIH development up to 25 years after unilateral IHR to determine possible indications for concomitant prophylactic surgery of the contralateral groin at the time of primary surgery. METHODS: Patients between 18 and 70 years of age undergoing elective unilateral IHR in the University Hospital of Leuven from 1995 to 1999 were studied retrospectively using the electronic health records and prospectively via phone calls. Study aims were MCIH incidence and risk factor determination. Kaplan-Meier curves were constructed and univariable and multivariable Cox regressions were performed. RESULTS: 758 patients were included (91% male, median age 53 years). Median follow-up time was 21.75 years. The incidence of operated MCIH after 5 years was 5.6%, after 15 years 16.1%, and after 25 years 24.7%. The incidence of both operated and non-operated MCIH after 5 years was 5.9%, after 15 years 16.7%, and after 25 years 29.0%. MCIH risk increased with older age and decreased in primary right-sided IHR and higher BMI at primary surgery. CONCLUSION: The overall incidence of MCIH after 25-year follow-up is 29.0%. Potential risk factors for the development of a MCIH are primary left-sided inguinal hernia repair, lower BMI, and older age. When considering prophylactic repair, we suggest a patient-specific approach taking into account these risk factors, the surgical approach and the risk factors for chronic postoperative inguinal pain.

Lung Transplant Outcome From Selected Older Donors (≥70 Years) Equals Younger Donors (<70 Years): A Propensity-matched Analysis.

OBJECTIVE: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years. BACKGROUND: Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited. METHODS: All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed. RESULTS: Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70-84 years) versus 49 years (range: 12-69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients ( P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications ( P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% ( P = 0.72) and 51.5% versus 59.2% ( P = 0.41), respectively. CONCLUSIONS: LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years).

The Effect of Continuous Liver Normothermic Machine Perfusion on the Severity of Histological Bile Duct Injury.

Static Cold Storage (SCS) injures the bile duct, while the effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study of the COPE trial on liver NMP, we investigated the impact of preservation type on histological bile duct injury score (BDIS). Transplants with at least one bile duct biopsy, either at end of preservation or 1 h post-reperfusion, were considered. BDIS was determined by assessing peribiliary glands injury, stromal and mural loss, haemorrhage, and thrombosis. A bivariate linear model compared BDIS (estimate, CI) between groups. Sixty-five transplants and 85 biopsies were analysed. Twenty-three grafts were preserved with SCS and 42 with NMP, with comparable baseline characteristics except for a shorter cold ischemic time in NMP. The BDIS increased over time regardless of preservation type (p = 0.04). The BDIS estimate was higher in NMP [8.02 (7.40-8.65)] than in SCS [5.39 (4.52-6.26), p < 0.0001] regardless of time. One patient in each group developed ischemic cholangiopathy, with a BDIS of 6 for the NMP-preserved liver. In six other NMP grafts, BDIS ranged 7-12 without development of ischemic cholangiopathy. In conclusion, BDIS increases over time, and the higher BDIS in NMP did not increase ischemic cholangiopathy. Thus, BDIS may overestimate this risk after liver NMP.

The perioperative use of inhaled prostacyclins in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Perioperative pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality in cardiac surgery. While inhaled prostacyclins (iPGI2s) are an established treatment of chronic PH, data on the efficacy of iPGI2s in perioperative PH are scarce. METHODS: We searched PubMed, Embase, the Web of Science, CENTRAL, and the grey literature from inception until April 2021. We included randomized controlled trials investigating the use of iPGI2s in adult and pediatric patients undergoing cardiac surgery with an increased risk of perioperative right ventricle failure. We assessed the efficacy and safety of iPGI2s compared with placebo and other inhaled or intravenous vasodilators with random-effect meta-analyses. The primary outcome was mean pulmonary artery pressure (MPAP). Secondary outcomes included other hemodynamic parameters and mortality. RESULTS: Thirteen studies were included, comprising 734 patients. Inhaled prostacyclins significantly decreased MPAP compared with placebo (standardized effect size, 0.46; 95% confidence interval [CI], 0.11 to 0.87; P = 0.01) and to intravenous vasodilators (1.26; 95% CI, 0.03 to 2.49; P = 0.045). Inhaled prostacyclins significantly improved the cardiac index compared with intravenous vasodilators (1.53; 95% CI, 0.50 to 2.57; P = 0.004). In contrast, mean arterial pressure was significantly lower in patients treated with iPGI2s vs placebo (-0.39; 95% CI, -0.62 to 0.16; P = 0.001), but higher than in patients treated with intravenous vasodilators (0.81; 95% CI, 0.29 to 1.33; P = 0.002). With respect to hemodynamics, iPGI2s had similar effects as other inhaled vasodilators. Mortality was not affected by iPGI2s. CONCLUSION: The results of this systematic review and meta-analysis show that iPGI2s improved pulmonary hemodynamics with similar efficacy as other inhaled vasodilators, but caused a significant small decrease in arterial pressure when compared with placebo, indicating spill-over into the systemic circulation. These effects did not affect clinical outcomes. STUDY REGISTRATION DATE: PROSPERO (CRD42021237991); registered 26 May 2021.

RéSUMé: OBJECTIF: L'hypertension pulmonaire (HTAP) périopératoire est un facteur de risque indépendant de morbidité et de mortalité en chirurgie cardiaque. Bien que l'inhalation de prostacyclines (iPGI2) constitue un traitement établi de l'HTAP chronique, les données sur l'efficacité de ce traitement en cas d'HTAP périopératoire sont rares. MéTHODE: Nous avons effectué des recherches dans les bases de données PubMed, Embase, Web of Science, CENTRAL et dans la littérature grise depuis leur création jusqu'en avril 2021. Nous avons inclus des études randomisées contrôlées portant sur l'utilisation de l'iPGI2 chez la patientèle adulte et pédiatrique bénéficiant d'une chirurgie cardiaque avec un risque accru d'insuffisance ventriculaire droite périopératoire. Nous avons évalué l'efficacité et l'innocuité des iPGI2 par rapport à un placebo et à d'autres vasodilatateurs inhalés ou intraveineux avec des méta-analyses à effets aléatoires. Le critère d'évaluation principal était la pression artérielle pulmonaire moyenne (PAPm). Les critères d'évaluation secondaires incluaient d'autres paramètres hémodynamiques et la mortalité. RéSULTATS: Treize études portant sur 734 patient·es ont été incluses. Les prostacyclines inhalées ont diminué de manière significative la PAPm par rapport au placebo (taille d'effet standardisée, 0,46; intervalle de confiance [IC] à 95 %, 0,11 à 0,87; P = 0,01) et aux vasodilatateurs intraveineux (1,26; IC 95 %, 0,03 à 2,49; P = 0,045). Les prostacyclines inhalées ont significativement amélioré l'index cardiaque par rapport aux vasodilatateurs intraveineux (1,53; IC 95 %, 0,50 à 2,57; P = 0,004). En revanche, la pression artérielle moyenne était significativement plus faible chez les patient·es traité·es par iPGI2 vs placebo (−0,39; IC 95 %, −0,62 à 0,16; P = 0,001), mais plus élevée que chez les personnes traitées par vasodilatateurs intraveineux (0,81; IC 95 %, 0,29 à 1,33; P = 0,002). En ce qui concerne l'hémodynamie, les iPGI2 ont eu des effets similaires à ceux des autres vasodilatateurs inhalés. La mortalité n'a pas été affectée par les iPGI2. CONCLUSION: Les résultats de cette revue systématique et méta-analyse montrent que les iPGI2 ont amélioré l'hémodynamie pulmonaire avec une efficacité similaire à celle des autres vasodilatateurs inhalés, mais ont entraîné une diminution légère mais significative de la pression artérielle par rapport au placebo, indiquant un débordement dans la circulation systémique. Ces effets n'ont pas affecté les résultats cliniques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021237991); enregistrée le 26 mai 2021.

Returning to Work After Breast Cancer Surgery: A Randomised Controlled Trial on the Effect of Pain Neuroscience Education.

PURPOSE: The aim of this study was to investigate the effect of pain neuroscience education compared to biomedical pain education after breast cancer surgery on (1) work status, (2) time until work resumption, and (3) change in return-to-work expectations up to 18 months post-surgery. METHODS: Participants were randomly assigned to either pain neuroscience education (intervention group) or biomedical pain education (control group) in addition to a standard physical therapy program after surgery for breast cancer. The first four months following surgery, one to two physiotherapy sessions and three educational sessions were scheduled. After, two educational sessions and two physiotherapy sessions were held at six and eight months postoperatively. All outcomes were assessed at four, six, eight, 12 and 18 months postoperatively. RESULTS: At 12 months, in the intervention group, 71% of the women returned to work compared to 53% in the control group (18% points difference, 95%CI:-0.1 to 35;p = 0.07). At 18 months, the differences decreased to 9% points, 95%CI:-26 to 7;p = 0.35). Neither time until work resumption (p = 0.46) nor change in estimation of own ability to return to work up to 18 months postoperatively (p = 0.21) significantly differed between both groups. CONCLUSION: No significant differences were found regarding return to work outcomes between women receiving pain neuroscience education versus biomedical pain education after breast cancer surgery. Further research is warranted to explore the potential role of pain neuroscience education in return-to-work interventions following breast cancer surgery.

Impact of anastomosis time during lung transplantation on primary graft dysfunction.

Primary graft dysfunction (PGD) is a major obstacle after lung transplantation (LTx), associated with increased early morbidity and mortality. Studies in liver and kidney transplantation revealed prolonged anastomosis time (AT) as an independent risk factor for impaired short- and long-term outcomes. We investigated if AT during LTx is a risk factor for PGD. In this retrospective single-center cohort study, we included all first double lung transplantations between 2008 and 2016. The association of AT with any PGD grade 3 (PGD3) within the first 72 h post-transplant was analyzed by univariable and multivariable logistic regression analysis. Data on AT and PGD was available for 427 patients of which 130 (30.2%) developed PGD3. AT was independently associated with the development of any PGD3 ≤72 h in uni- (odds ratio [OR] per 10 min 1.293, 95% confidence interval [CI 1.136-1.471], p < .0001) and multivariable (OR 1.205, 95% CI [1.022-1.421], p = .03) logistic regression analysis. There was no evidence that the relation between AT and PGD3 differed between lung recipients from donation after brain death versus donation after circulatory death donors. This study identified AT as an independent risk factor for the development of PGD3 post-LTx. We suggest that the implantation time should be kept short and the lung cooled to decrease PGD-related morbidity and mortality post-LTx.

Comparing real-time and intermittently scanned continuous glucose monitoring in adults with type 1 diabetes (ALERTT1): a 6-month, prospective, multicentre, randomised controlled trial.

BACKGROUND: People with type 1 diabetes can continuously monitor their glucose levels on demand (intermittently scanned continuous glucose monitoring [isCGM]), or in real time (real-time continuous glucose monitoring [rtCGM]). However, it is unclear whether switching from isCGM to rtCGM with alert functionality offers additional benefits. Therefore, we did a trial comparing rtCGM and isCGM in adults with type 1 diabetes (ALERTT1). METHODS: We did a prospective, double-arm, parallel-group, multicentre, randomised controlled trial in six hospitals in Belgium. Adults with type 1 diabetes who previously used isCGM were randomly assigned (1:1) to rtCGM (intervention) or isCGM (control). Randomisation was done centrally using minimisation dependent on study centre, age, gender, glycated haemoglobin (HbA1c), time in range (sensor glucose 3·9-10·0 mmol/L), insulin administration method, and hypoglycaemia awareness. Participants, investigators, and study teams were not masked to group allocation. Primary endpoint was mean between-group difference in time in range after 6 months assessed in the intention-to-treat sample. This trial is registered with ClinicalTrials.gov, NCT03772600. FINDINGS: Between Jan 29 and Jul 30, 2019, 269 participants were recruited, of whom 254 were randomly assigned to rtCGM (n=127) or isCGM (n=127); 124 and 122 participants completed the study, respectively. After 6 months, time in range was higher with rtCGM than with isCGM (59·6% vs 51·9%; mean difference 6·85 percentage points [95% CI 4·36-9·34]; p<0·0001). After 6 months HbA1c was lower (7·1% vs 7·4%; p<0·0001), as was time <3·0 mmol/L (0·47% vs 0·84%; p=0·0070), and Hypoglycaemia Fear Survey version II worry subscale score (15·4 vs 18·0; p=0·0071). Fewer participants on rtCGM experienced severe hypoglycaemia (n=3 vs n=13; p=0·0082). Skin reaction was more frequently observed with isCGM and bleeding after sensor insertion was more frequently reported by rtCGM users. INTERPRETATION: In an unselected adult type 1 diabetes population, switching from isCGM to rtCGM significantly improved time in range after 6 months of treatment, implying that clinicians should consider rtCGM instead of isCGM to improve the health and quality of life of people with type 1 diabetes. FUNDING: Dexcom.

Behavioural and psychological patterns of patients with idiopathic pulmonary fibrosis: a prospective study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung condition. Currently, care models predominantly focus on acute medical and pharmacological needs. As a step towards holistic care, the aim of this prospective study was to investigate the psychological and behavioural needs of IPF patients treated with pirfenidone from diagnosis until two years of follow-up. METHODS: The following variables were selected from the literature on patients' needs and the COM-B model, a theoretical model explaining behaviour: medication adherence, barriers to adherence, importance and intentions of medication adherence, anxiety, depression, health literacy, knowledge, reported side effects, adherence to sun protection recommendations, alcohol use, physical activity, quality of life and health status. Linear and generalised linear models for longitudinal data were used to evaluate the evolution since treatment initiation. RESULTS: We included 66 outpatients: 72.7% men, mean age of 70.3 years (range 50-87), predicted mean forced vital capacity of 85.8% (SD 17.4) and predicted mean diffusing capacity for monoxide of 56.9% (SD 15.7). The participants placed considerable importance on following the treatment recommendations. We noticed difficulties regarding health literacy, alcohol use, pirfenidone adherence (decline over time) and adherence to sun protection recommendations (early in follow-up care). There were low levels of physical activity (no effect of time), high body mass indices (decline over time) and moderate levels of depression and anxiety. CONCLUSION: When providing care to IPF patients, behavioural issues, health literacy and psychological well-being should be taken into consideration. There is a need to further explore interventions and care models to tackle these difficulties. Trial registration This study was registered in the ClinicalTrials.gov database (identifier NCT03567785) on May 9th, 2018.

Quantifying the potential of morphological parameters for human dental identification: part 2-selecting the strongest identifiers in mandibular permanent teeth.

The current study aimed to select the best dental morphological identifiers for human identification. Sixty-two panoramic radiographs were collected retrospectively, in which six measurements were performed on all seven mandibular left permanent teeth: tooth length (TL), crown length (CL), root length (RL), crown width (CW), cervical width (CEJW), and root width (RW). Nine length-width ratios were then calculated using these measurements. Three groups of statistics were considered: (1) inter-observer reliability quantified by intra-class correlation (ICC); (2) mean "potential set"; and (3) Spearman correlation. A step-by-step cascade was then established based on selected parameters. In a univariate approach, the following parameters were the best identifiers: TL/CW for tooth 36 (ICC 0.82; mean potential set 13.7%), TL/CEJW for tooth 35 (ICC 0.87; mean potential set 15.2%), and TL/RW for tooth 32 (ICC 0.89; mean potential set 16.0%). The correlations between these three parameters ranged from 0.24 to 0.47. In a multivariate approach, the following parameters had the best identifying capacity: all parameters combined for tooth 31 (mean potential set 8.1%), for tooth 35 (mean potential set 11.9%), and for tooth 32 (mean potential set 16.3%). In conclusion, a single ratio in a specific tooth narrows down the potential set of matches, but the mean potential set remains relatively large. Combining all ratios of a single specific tooth increases the certainty of the match. In particular, tooth 31 was the strongest identifier.

Quantifying the potential of morphological parameters for human dental identification: part 3-selecting the strongest skeletal identifiers in the mandible.

The current study aimed to select the best mandibular morphological identifiers. One-hundred eighty-five panoramic radiographs were retrospectively collected, in which four landmarks were located on the mandible: the most superior point of the condyle right/left (CONR/L), of the coronoid right/left (CORR/L), of the mandibular lingula right/left (LINR/L), and the most mesial point of the mental foramen right/left (MMFR/L). Five linear measurements, 6 angles, and 10 ratios were measured bilaterally. Three groups of statistics were considered: (1) mean potential set; (2) inter-observer agreement quantified by intra-class correlation (ICC) and within-subject coefficient of variation (WSCV); and (3) Spearman correlation. Parameters were selected for a step-by-step cascade. In a univariate approach, the following parameters proved to have the best identifying capacity: ratio 3 right (between lines CONR - CORR and LINR - MMFR) with mean potential set 13%, ICC 0.90, and WSCV 4.8%; ratio 4 (between lines CONR/L - CORR/L and MMFR - MMFL) with mean potential set 13%, ICC 0.92, and WSCV 8.9%; and angle 4 left (between landmarks LINL, MMFL, and MMFR) with mean potential set of 18%, ICC 0.91, and WSCV 1.2%. The correlation coefficients ranged from 0.01 to 0.33. In a multivariate approach, the identifying capacity improved drastically, with all ratios combined as the strongest identifier (mean potential set 1.29%). In conclusion, a single ratio or a single angle already narrows down the set of potential matches, but the mean potential set remains relatively large. Combining all ratios drastically increases the certainty of the match.

Characteristics and Outcome of Post-Transplant Lymphoproliferative Disorders After Solid Organ Transplantation: A Single Center Experience of 196 Patients Over 30 Years.

Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication after transplantation. In this retrospective, monocentric study we aimed to collect real life data regarding PTLD and determine the role of Epstein Barr Virus (EBV) status and year of diagnosis on prognosis. We identified 196 biopsy-proven PTLD after solid organ transplantation (SOT) diagnosed at the University Hospitals Leuven (Belgium) from 1989 to 2019. EBV status was positive in 61% of PTLD. The median overall survival (OS) was 5.7 years (95% CI: 2.99-11.1). Although EBV positivity was not significantly correlated with OS in multivariate analyses (HR: 1.44 (95% CI: 0.93-2.24); p = 0.10), subgroup analysis showed a significantly better median OS for EBV negative post-transplant diffuse large B-cell lymphoma (DLBCL) compared to EBV positive post-transplant DLBCL (8.8 versus 2.5 years respectively; p = 0.0365). There was a significant relation between year of PTLD diagnosis and OS: the more recent the PTLD diagnosis, the lower the risk for death (adjusted HR: 0.962 (95% CI: 0.931-0.933); p = 0.017). In conclusion, the prognosis of PTLD after SOT has improved in the past decades. Our analysis shows a significant relation between EBV status and OS in post-transplant DLBCL.

Functional outcomes of transanal versus transabdominal restorative proctectomy with ileal pouch-anal anastomosis in ulcerative colitis-a monocentric retrospective comparative study.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) ensures satisfactory gastro-intestinal function and quality of life (QoL) in patients with refractory ulcerative colitis (UC). The transanal approach to proctectomy and IPAA (Ta-IPAA) has been developed to address the technical shortfalls of the traditional transabdominal approach (Tabd-IPAA). Ta-IPAA has proven to be safe but there is lack of reported functional outcomes. Aim of this study is to compare functional outcomes and QoL after Ta- or Tabd-IPAA for UC. METHODS: This is a retrospective study of consecutive UC patients who underwent IPAA between 2011 and 2017, operated according to a modified 2- or 3-stage approach. Close rectal dissection was performed in Ta-IPAA as opposed to total mesorectal excision in Tabd-IPAA. A propensity score weighting was performed. Functional outcomes were assessed using the pouch functional score (PFS) and the Öresland score (OS). The global quality of life scale (GQOL) was used for patients' perspective on QoL. Follow-up was scheduled at 1, 3, 6, and 12 months, postoperatively. RESULTS: One hundred and eight patients were included: 38 patients had Ta-IPAA. At 12 months follow-up, mean OS and PFS were 4.6 (CI 3.2-6.0) vs 6.2 (CI 5.0-7.3), p = 0.025 and 6.1 (CI 3.5-8.8) vs 7.4 (CI 5.4-9.5), p = 0.32, for Ta and Tabd-IPAA, respectively. Mean GQOL for Ta-IPAA was 82.5 (CI 74.8-90.1) vs 75.5 (69.4-81.7) for Tabd-IPAA (p = 0.045). CONCLUSIONS: At 12 months postoperatively, pouch function and QoL of Ta-IPAA are probably as good as those of Tabd-IPAA. Limitations include retrospectivity, differences in the surgical technique, and lack of validated scores for QoL.

Fast-Track Failure After Cardiac Surgery: Risk Factors and Outcome With Long-Term Follow-Up.

OBJECTIVES: An important cornerstone of the Enhanced Recovery After Cardiac Surgery initiative is a fast-track cardiac anesthesia management protocol. Fast-track failure has been described to have a detrimental impact on immediate postoperative outcomes. The authors here evaluated risk factors for short- and long-term effects of fast-track failure. DESIGN: A retrospective cohort study. SETTING: A single academic center. PARTICIPANTS: Adult cardiac surgery was performed on 7,064 patients between January 2013 and October 2019. INTERVENTION: The inclusion criteria for the fast-track program at the postanesthesia care unit were met by 1,097 patients. MEASUREMENTS AND MAIN RESULTS: Univariate and multivariate logistic regression analyses were used to identify independent risk factors. Fast-track failure occurred in 69 (6.3%) patients. These were associated with significant increases in the incidences of coronary revascularization, cardiac tamponade or bleeding requiring surgical intervention, new-onset atrial fibrillation, pneumonia, delirium, and sepsis. Likewise, the postoperative length of stay, and up to 5-year mortality, were significantly higher in the fast-track failure than the nonfailure group. The European System for Cardiac Operative Risk Evaluation II and transfusion of any blood product could be identified as independent risk factors for fast-track failure, with only limited discriminative ability (area under the curve = 0.676; 95% confidence interval, 0.611-0.741). CONCLUSION: Fast-track failure is associated with increases in morbidity and long-term mortality, but remains difficult to predict.

Evolution of root length throughout orthodontic treatment in maxillary incisors with previous history of dental trauma: a longitudinal controlled trial.

OBJECTIVES: To compare changes in root length of maxillary incisors with and without dental trauma throughout orthodontic treatment. MATERIALS AND METHOD: Patients younger than 18 years, with trauma on at least one maxillary incisor, undergoing orthodontic treatment between 2017 and 2021 were included, using the contralateral side as control without trauma when available. Periapical radiographs were taken pre-treatment and at 6 months intervals, and root/crown ratio was calculated. Linear mixed models were used to describe the evolution of root length at the different time points and to compare trauma and control values. Differences between central and lateral incisors and between treatment modalities were additionally explored. RESULTS: A total of 1768 measurements were performed on 499 teeth (201 with trauma) in 135 patients. Incisor root length significantly decreased during orthodontic treatment in teeth with and without trauma. Lateral incisors with trauma were more susceptible to root resorption than those without trauma and central incisors. No significant decrease in root length was observed with removable appliances, which never exceeded 15 months of treatment. Treatment with fixed appliances led to gradually increasing, significant root length shortening in teeth with and without trauma. CONCLUSION: Treatment duration directly correlated with root length shortening both in teeth with and without trauma history. Teeth with trauma showed significantly more root resorption after treatment with fixed appliances while removable appliances had no significant influence on root length. CLINICAL RELEVANCE: Previous history of dental trauma is no absolute contra-indication to start orthodontic treatment, as long as treatment duration is kept as short as possible.

The effect of IGL-1 preservation solution on outcome after kidney transplantation: A retrospective single-center analysis.

Institut Georges Lopez-1 (IGL-1) solution is increasingly used for kidney preservation, although little information on outcomes is available. Outcomes of all deceased donor kidneys preserved by IGL-1, University of Wisconsin solution (UW), or histidine-tryptophan-ketoglutarate (HTK) and transplanted in our center (2000-2018) were analyzed. Multivariable analysis for delayed graft function (DGF), functional DGF, estimated glomerular filtration rate (eGFR, CKD-EPI equation), proteinuria, acute rejection, death-censored graft loss, and patient survival were performed. A double robust approach, consisting of propensity score weighting and correction for confounders, minimized the risk of bias. In total, 1943 transplants were included: 234 with IGL-1, 1046 with UW, and 663 with HTK. As IGL-1 was only introduced in 2014, a prespecified sensitivity analysis of 917 kidneys (2010-2018) was performed using the same statistical approach. After weighting, IGL-1 retained a higher proportion of kidneys donated after circulatory death (DCD). IGL-1 was not independently associated with any of the outcomes when compared to UW or HTK. Sensitivity analysis between 2010 and 2018 showed similar results. In this retrospective analysis, using robust methodology to reduce the risk of bias, IGL-1 preservation results in equal outcomes compared to UW or HTK, despite more DCD transplants in the IGL-1 group.

Rectal organoid morphology analysis (ROMA) as a promising diagnostic tool in cystic fibrosis.

Diagnosing cystic fibrosis (CF) when sweat chloride is not in the CF range and less than 2 disease-causing CFTR mutations are found requires physiological CFTR assays, which are not always feasible or available. We developed a new physiological CFTR assay based on the morphological differences between rectal organoids from subjects with and without CF. In organoids from 167 subjects with and 22 without CF, two parameters derived from a semi-automated image analysis protocol (rectal organoid morphology analysis, ROMA) fully discriminated CF subjects with two disease-causing mutations from non-CF subjects (p<0.001). ROMA, feasible at all ages, can be centralised to improve standardisation.

Male age interferes with embryo growth in IVF treatment.

STUDY QUESTION: Does male age affect embryo growth or quality in couples undergoing IVF treatment? SUMMARY ANSWER: Advanced paternal age (APA) is negatively associated with the chance of an optimal eight-cell embryo on the third day of development. WHAT IS KNOWN ALREADY: Literature shows that APA is associated with decreased sperm quality and fecundity. However, the effect of male age on embryo growth in an IVF setting remains inconclusive. Literature concerning male influences on IVF success is scarce and approaches used to analyse embryo outcomes differ by study. STUDY DESIGN, SIZE, DURATION: This study was part of the longitudinal Epigenetic Legacy of Paternal Obesity (ELPO) study for which fathers and mothers were followed from pre-pregnancy until the birth of their child. Couples were recruited from April 2015 to September 2017. A total of 1057 embryos from 87 couples were studied. PARTICIPANTS/MATERIALS, SETTING, METHODS: Dutch-speaking couples planning to undergo an IVF treatment were recruited at the Leuven University Fertility Center in Flanders, Belgium. Anthropometrics were documented and compared to the general Flemish population. Semen characteristics, pregnancy rates and the following embryo characteristics were recorded: number of blastomeres, symmetry and percentage fragmentation. Statistical modelling was applied taking into account correlation of within-cycle outcomes and use of multiple cycles per couple. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a significant inverse association between APA and a key determinant for scoring of embryo quality: older men were less likely to produce an embryo of eight blastomeres at Day 3, compared to younger fathers; odds ratio for the effect of 1 year equals 0.960 (95% CI: 0.930-0.991; P = 0.011). Our finding remained significant after adjusting for female age and male and female BMI. Degree of fragmentation and symmetry were not significantly related to male age. LIMITATIONS, REASONS FOR CAUTION: Because of the study's small sample size and its monocentric nature, a larger study is warranted to confirm our results. In addition, distribution of BMI and level of education were not representative of the general Flemish population. Although we corrected for BMI status, we do not exclude that obesity may be one of the determinants of infertility in our study population. Furthermore, it is known from other European countries that a higher education eases access to fertility treatment. Hence, caution should be taken when interpreting our findings from a fertility setting to the general population. WIDER IMPLICATIONS OF THE FINDINGS: We suggest a heightened need for future research into male age and its potential effects on embryo growth, embryo quality and ART outcomes. Clinical decision-making and preventative public health programmes would benefit from a better understanding of the role of men, carried forward by the Paternal Origins of Health and Disease (POHaD) paradigm. We hope the current finding will encourage others to examine the role of the sperm epigenome in embryo development according to paternal age. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a research grant from KU Leuven University (OT/14/109). The authors declare no competing financial, professional or personal interests. TRIAL REGISTRATION NUMBER: KU Leuven S57378 (ML11309), B322201523225.