Enhancing Vascularized Composite Allograft Supercooling Preservation: A Multifaceted Approach with CPA Optimization, Thermal Tracking, and Stepwise Loading Techniques.

Vascularized composite allografts (VCAs) present unique challenges in transplant medicine, owing to their complex structure and vulnerability to ischemic injury. Innovative preservation techniques are crucial for extending the viability of these grafts, from procurement to transplantation. This study addresses these challenges by integrating cryoprotectant agent (CPA) optimization, advanced thermal tracking, and stepwise CPA loading strategies within an ex vivo rodent model. CPA optimization focused on various combinations, identifying those that effectively suppress ice nucleation while mitigating cytotoxicity. Thermal dynamics were monitored using invasive thermocouples and non-invasive FLIR imaging, yielding detailed temperature profiles crucial for managing warm ischemia time and optimizing cooling rates. The efficacy of stepwise CPA loading versus conventional flush protocols demonstrated that stepwise (un)loading significantly improved arterial resistance and weight change outcomes. In summary, this study presents comprehensive advancements in VCA preservation strategies, combining CPA optimization, precise thermal monitoring, and stepwise loading techniques. These findings hold potential implications for refining transplantation protocols and improving graft viability in VCA transplantation.

"Long term speech outcomes after using the Sommerlad technique for primary palatoplasty: a retrospective study in the Wilhelmina Children's Hospital, Utrecht."

OBJECTIVES: After cleft lip and/or palate (CL/P) repair, children may develop velopharyngeal insufficiency (VPI) leading to speech imperfections, necessitating additional speech correcting surgery. This study examines the incidence of VPI and speech correcting surgery after Sommerlad's palatoplasty for CL/P, and its association with various clinical features. MATERIALS AND METHODS: A retrospective cohort study was performed in the Wilhelmina Children's Hospital in Utrecht and child records from 380 individuals with CL/P registered from 2008 to 2017 were retrospectively reviewed. Inclusion criteria comprised the diagnosis of CL/P, primary palatoplasty according to Sommerlad's technique, and speech assessment at five years or older. Association between cleft type and width, presence of additional genetic disorders and postoperative complications (palatal dehiscence, fistula) were assessed using odds ratios and chi squared tests. RESULTS: A total of 239 patients were included. The VPI rate was 52.7% (n = 126) and in 119 patients (49.8%) a speech correcting surgery was performed. Severe cleft type, as indicated by a higher Veau classification, was associated with a significant higher rate of speech correcting surgeries (p = 0.033). Significantly more speech correcting surgeries were performed in patients with a cleft width >10 mm, compared to patients with a cleft width ≤10 mm (p < 0.001). Patients with oronasal fistula underwent significantly more speech correcting surgeries than those without fistula (p = 0.004). No statistically significant difference was found in the incidence of speech correcting surgery between patients with and without genetic disorders (p = 0.890). CONCLUSIONS/CLINICAL RELEVANCE: Variations in cleft morphology, cleft width and complications like oronasal fistula are associated with different speech outcomes. Future research should focus on creating a multivariable prediction model for speech correcting surgery in CL/P patients.

VCA supercooling in a swine partial hindlimb model.

Vascularized composite allotransplantations are complex procedures with substantial functional impact on patients. Extended preservation of VCAs is of major importance in advancing this field. It would result in improved donor-recipient matching as well as the potential for ex vivo manipulation with gene and cell therapies. Moreover, it would make logistically feasible immune tolerance induction protocols through mixed chimerism. Supercooling techniques have shown promising results in multi-day liver preservation. It consists of reaching sub-zero temperatures while preventing ice formation within the graft by using various cryoprotective agents. By drastically decreasing the cell metabolism and need for oxygen and nutrients, supercooling allows extended preservation and recovery with lower ischemia-reperfusion injuries. This study is the first to demonstrate the supercooling of a large animal model of VCA. Porcine hindlimbs underwent 48 h of preservation at - 5 °C followed by recovery and normothermic machine perfusion assessment, with no issues in ice formation and favorable levels of injury markers. Our findings provide valuable preliminary results, suggesting a promising future for extended VCA preservation.

The Development of a European Multidisciplinary Cleft Lip and Palate Registry by the European Reference Network CRANIO: Experiences, Barriers, And Facilitators.

The European Reference Network for Rare Craniofacial Aanomalies and Ear-Nose-Throat disorders aims to improve care for patients with such afflictions, including cleft lip and palate (CL/P) across Europe. Cleft treatment remains varied throughout European centers, inhibiting meaningful comparison of treatment outcomes. To overcome these issues, a European-wide common CL/P dataset and registry was developed, facilitating standardized treatment endpoints and outcome measures for international comparison and benchmarking of CL/P centers. Questionnaires and semi-structured interviews were used to determine the set-up of the registry. Previous CL/P initiatives were analyzed to create an initial dataset, refined through consensus meetings. In total, 87 cleft specialists working in specialized CL/P centers from 16 European nations participated. Consensus on a common dataset was reached. A "Level 1" dataset, with mandatory clinical and patient-reported outcome measures, and "Level 2" dataset with additional outcome measures. Finally, 2 dashboards were developed for data dissemination. The development of the European CL/P common dataset and registry tackled challenges with resource disparities, variations in specialists within CL/P teams, regulatory differences in patient data usage, patient-reported outcome measures availability in European languages, and use of assessment tools. This study described the successful development of the European Reference Network for Rare Craniofacial Aanomalies and Ear-Nose-Throat disorders CL/P common dataset and registry. This achievement will help improve patient care and outcomes for patients with CL/P in Europe. Furthermore, this study provides useful information for initiatives with similar aims.

Effect of Subnormothermic Machine Perfusion on the Preservation of Vascularized Composite Allografts After Prolonged Warm Ischemia.

BACKGROUND: Warm ischemia time (WIT) and ischemia-reperfusion injury are limiting factors for vascularized composite allograft (VCA) transplantation. Subnormothermic machine perfusion (SNMP) has demonstrated the potential to extend WIT in organ transplantation. This study evaluates the effect of SNMP on VCA viability after prolonged WIT. METHODS: Rat hindlimbs underwent WIT for 30, 45, 60, 120, 150, or 210 min, followed by 3-h SNMP. Monitoring of perfusion parameters and outflow determined the maximum WIT compatible with limb viability after SNMP. Thereafter, 2 groups were assessed: a control group with inbred transplantation (Txp) after 120 min of WIT and an experimental group that underwent WIT + SNMP + Txp. Graft appearance, blood gas, cytokine levels, and histology were assessed for 21 d. RESULTS: Based on potassium levels, the limit of WIT compatible with limb viability after SNMP is 120 min. Before this limit, SNMP reduces potassium and lactate levels of WIT grafts to the same level as fresh grafts. In vivo, the control group presented 80% graft necrosis, whereas the experimental group showed no necrosis, had better healing (P = 0.0004), and reduced histological muscle injury (P = 0.012). Results of blood analysis revealed lower lactate, potassium levels, and calcium levels (P = 0.048) in the experimental group. Both groups presented an increase in interleukin (IL)-10 and IL-1b/IL-1F2 with a return to baseline after 7 to 14 d. CONCLUSIONS: Our study establishes the limit of WIT compatible with VCA viability and demonstrates the effectiveness of SNMP in restoring a graft after WIT ex vivo and in vivo, locally and systemically.

Body Contouring Surgery After Bariatric Surgery Improves Long-Term Health-Related Quality of Life and Satisfaction With Appearance: An International Longitudinal Cohort Study Using the BODY-Q.

OBJECTIVE: To examine health-related quality of life (HRQL) and satisfaction with appearance in patients who have undergone bariatric surgery (BS) with or without subsequent body contouring surgery (BCS) in relation to the general population normative for the BODY-Q. BACKGROUND: The long-term impact of BS with or without BCS has not been established using rigorously developed and validated patient-reported outcome measures. The BODY-Q is a patient-reported outcome measure developed to measure changes in HRQL and satisfaction with appearance in patients with BS and BCS. METHODS: Prospective BODY-Q data were collected from 6 European countries (Denmark, the Netherlands, Finland, Germany, Italy, and Poland) from June 2015 to February 2022 in a cohort of patients who underwent BS. Mixed-effects regression models were used to analyze changes in HRQL and appearance over time between patients who did and did not receive BCS and to examine the impact of patient-level covariates on outcomes. RESULTS: This study included 24,604 assessments from 5620 patients. BS initially led to improved HRQL and appearance scores throughout the first postbariatric year, followed by a gradual decrease. Patients who underwent subsequent BCS after BS experienced a sustained improvement in HRQL and appearance or remained relatively stable for up to 10 years postoperatively. CONCLUSIONS: Patients who underwent BCS maintained an improvement in HRQL and satisfaction with appearance in contrast to patients who only underwent BS, who reported a decline in scores 1 to 2 years postoperatively. Our results emphasize the pivotal role that BCS plays in the completion of the weight loss trajectory.

What is the optimal assessment of speech? A multicentre, international evaluation of speech assessment in 2500 patients with a cleft.

OBJECTIVES: Speech problems in patients with a cleft palate are often complex and multifactorial. Finding the optimal way of monitoring these problems is challenging. The International Consortium of Health Outcomes Measurement (ICHOM) has developed a set of standardised outcome measures at specific ages for patients with a cleft lip and/or palate, including measures of speech assessment. This study evaluates the type and timing of speech outcome measures currently included in this ICHOM Standard Set. Additionally, speech assessments in other cleft protocols and initiatives are discussed. DESIGN, SETTING AND PARTICIPANTS: An international, multicentre study was set up including centres from the USA and the Netherlands. Outcomes of clinical measures and Patient Reported Outcome Measures (PROMs) were collected retrospectively according to the ICHOM set. PROM data from a field test of the CLEFT-Q, a questionnaire developed and validated for patients with a cleft, were collected, including participants from countries with all sorts of income statuses, to examine the value of additional moments of measurement that are used in other cleft initiatives.Data from 2500 patients were included. Measured outcomes contained univariate regression analyses, trend analyses, t-tests, correlations and floor and ceiling effects. RESULTS: PROMs correlated low to moderate with clinical outcome measures. Clinical outcome measures correlated low to moderate with each other too. In contrast, two CLEFT-Q Scales correlated strongly with each other. All PROMs and the Percent Consonants Correct (PCC) showed an effect of age. In patients with an isolated cleft palate, a ceiling effect was found in the Intelligibility in Context Scale. CONCLUSION: Recommendations for an optimal speech outcome assessment in cleft patients are made. Measurement moments of different cleft protocols and initiatives are considered in this proposition. Concerning the type of measures, adjustment of the current PCC score outcome seems appropriate. For centres with adequate resources and specific interest in research, translation and validation of an upcoming tool, the Cleft Audit Protocol for Speech Augmented, is recommended.

Speech correcting surgery after primary palatoplasty: a systematic literature review and meta-analysis.

OBJECTIVES: In cleft palate patients, the soft palate is commonly closed using straight-line palatoplasty, Z-palatoplasty, or palatoplasty with buccal flaps. Currently, it is unknown which surgical technique is superior regarding speech outcomes. The aim of this review is to study the incidence of speech correcting surgery (SCS) per soft palatoplasty technique and to identify variables which are associated with this outcome. MATERIALS AND METHODS: A systematic literature search was carried out according to the PRISMA guidelines. Inclusion and exclusion criteria were applied to focus on the incidence of SCS after soft palatoplasty. Additional variables like surgical modification, cleft morphology, syndrome, age at palatoplasty, fistula and assessment of velopharyngeal function were reported. A modified New-Ottawa Scale (NOS) was used for quality appraisal. Pooled estimates from the meta-analysis were calculated using a random-effects model. RESULTS: One thousand twenty-nine studies were found of which 54 were included in the analysis. The pooled estimate proportion of SCS after straight-line palatoplasty was 19% (95% CI 15-24), after Z-palatoplasty 6% (95% CI 4-9), and after palatoplasty with buccal flaps 7% (95% CI 4-11). CONCLUSIONS: A lower SCS rate was found in patients receiving Z-palatoplasty when compared to straight-line palatoplasty. We propose a minimum set of outcome parameters which ideally should be included in future studies regarding speech outcomes after cleft palate repair. CLINICAL RELEVANCE: Current literature reports highly heterogenous data regarding cleft palate repair. Our recommended set of parameters may address this inconsistency and could make intercenter comparison possible and of better quality.

Supercooling: A Promising Technique for Prolonged Organ Preservation in Solid Organ Transplantation, and Early Perspectives in Vascularized Composite Allografts.

Ex-vivo preservation of transplanted organs is undergoing spectacular advances. Machine perfusion is now used in common practice for abdominal and thoracic organ transportation and preservation, and early results are in favor of substantially improved outcomes. It is based on decreasing ischemia-reperfusion phenomena by providing physiological or sub-physiological conditions until transplantation. Alternatively, supercooling techniques involving static preservation at negative temperatures while avoiding ice formation have shown encouraging results in solid organs. Here, the rationale is to decrease the organ's metabolism and need for oxygen and nutrients, allowing for extended preservation durations. The aim of this work is to review all advances of supercooling in transplantation, browsing the literature for each organ. A specific objective was also to study the initial evidence, the prospects, and potential applications of supercooling preservation in Vascularized Composite Allotransplantation (VCA). This complex entity needs a substantial effort to improve long-term outcomes, marked by chronic rejection. Improving preservation techniques is critical to ensure the favorable evolution of VCAs, and supercooling techniques could greatly participate in these advances.

Sub-Zero Non-Freezing of Vascularized Composite Allografts Preservation in Rodents.

Ischemia is a major limiting factor in Vascularized Composite Allotransplantation (VCA) as irreversible muscular injury can occur after as early as 4-6 hours of static cold storage (SCS). Organ preservation technologies have led to the development of storage protocols extending rat liver ex vivo preservation up to 4 days. Development of such a protocol for VCAs has the added challenge of inherent ice nucleating factors of the graft, therefore this study focused on developing a robust protocol for VCA supercooling. Rodent partial hindlimbs underwent subnormothermic machine perfusion (SNMP) with several loading solutions, followed by cryoprotective agent (CPA) cocktail developed for VCAs. Storage occurred in suspended animation for 24h and VCAs were recovered using SNMP with modified Steen. This study shows a robust VCA supercooling preservation protocol in a rodent model. Further optimization is expected to allow for its application in a transplantation model, which would be a breakthrough in the field of VCA preservation.