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Surgical treatment of infrabony defects may result in gingival recession of the neighboring teeth. The aim of this clinical report is to describe a surgical technique to promote gingival margin stability in the treatment of infrabony defects at sites with a thin or medium gingival phenotype. A coronally advanced entire papilla preservation (CA-EPP) flap with a connective tissue graft (CTG) was executed in two different clinical cases. This technique substantially improved interproximal clinical attachment level and pocket closure, with no gingival recession. A CA-EPP flap using a CTG may promote gingival margin stability and can be recommended in regenerative periodontal procedures. [ABSTRACT FROM AUTHOR]

Tooth loss or extraction is associated with significant reduction in alveolar ridge volume, extensively expressed in the anterior zone, and immediate implant placement is insufficient to overcome this problem. The proposed approach combined immediate implant placement with buccal tissue enhancement by applying a crosslinked collagen matrix hydrated with crosslinked hyaluronic acid (xHyA). All 10 cases presented with a retained but narrow buccal socket wall, so immediate implant placement with the "tunneled sandwich" technique was performed after tooth extraction. The tunneled sandwich technique helped create a subperiosteal pouch for insertion of the collagen matrix buccal to the alveolar bone crest. The implants healed transmucosally by receiving either a gingiva former or an immediate temporary restoration. Ten sites in 10 patients demonstrated stable, noninflamed peri-implant conditions and suitable ridge volume at the implant neck and achieved high pink esthetic scores 6 months after implant loading. The tunneled sandwich technique is a suitable method to preserve buccal volume, which biologically and esthetically contributes to favorable long-term results. [ABSTRACT FROM AUTHOR]

Xenogeneic-derived biomaterials are among the most routinely employed bone substitutes for immediate grafting of extraction sites as a modality of alveolar ridge preservation (ARP). The deproteinized bovine bone material is widely used and documented around the world. The present pilot clinical trial evaluated and compared the clinical and morphologic alterations of extraction sites after ARP using two commercially available yet differently processed bovine bone grafts. A total of 20 adjacent extraction sites in 10 patients were included. All sites received the exact same ARP therapy except for the type of bovine bone graft, which was randomly assigned between two adjacent extraction sockets in 10 patients (Group A received Bio-Oss particles and Group B received Cerabone particles). At all sites, healing was monitored at the time of surgery and at 1, 2, 3, and 4 months postoperative. All of the augmented extraction sites achieved successful implant therapy regardless of the bone graft material used for ARP. Six weeks after implant placement, second-stage/uncovering procedures were performed without complications. Intergroup comparisons of the crestal gingival healing process (CGHP), mean transversal crestal ridge resorption (MTRR), and mean implant primary stability (MIPS) were in favor of Group A sites (treatment with Bio-Oss particles). [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Paediatric cancers are rare, and most children requiring radiation therapy receive external beam radiation (EBRT). Although EBRT may offer organ preservation compared to surgery, it can be associated with significant late effects. Image‐guided brachytherapy is a highly specialised technique offering both organ preservation and dose conformity to minimise late toxicity.This is a retrospective mono‐institutional review of paediatric brachytherapy in one of the largest paediatric centres in Australia. Outcomes and toxicities are presented as well as brachytherapy versus proton plan comparison in four patients.A total of 14 patients were treated with adjuvant brachytherapy between 2012 and 2022. The predominant histology was rhabdomyosarcoma, and all patients had pelvic tumours. High‐dose rate (HDR) brachytherapy was given for 13 patients with one patient receiving low‐dose rate (LDR) brachytherapy. Only one grade three late toxicity was reported and two patients developed metastatic disease within one year of completion of treatment. The brachytherapy plan was superior to protons in two of four patients and equivocal in one patient.This is the first Australian publication of a paediatric brachytherapy series from a single institution. This retrospective series demonstrates the feasibility and safety of brachytherapy in paediatric pelvic tumours. The initial work presented here demonstrates the value of a comprehensive radiation plan review in selecting the optimal modality for an individual paediatric patient. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion As non‐operative management of rectal cancer proliferates, re‐staging and surveillance methods are critical in selecting appropriate patients for organ preservation versus proctectomy. In previous work, the authors have shown that transrectal acoustic resolution photoacoustic microscopy (ARPAM) co‐registered with ultrasound can differentiate residual cancer from complete tumoural response to neoadjuvant therapy. We hypothesize that these findings are due to changes in microvascular density (MVD).Patients with rectal adenocarcinoma who underwent neoadjuvant therapy, transrectal photoacoustic imaging and resection were included. We first compared immunohistochemical staining with erythroblast transformation‐specific‐related gene (ERG) immunostain to standard CD31 to confirm adequate identification of endothelium. Tissue sections from identical blocks were stained with CD31 and ERG, and then a correlation was calculated between manually labelled CD31‐stained vessels and ERG nuclei density. Second, representative tissue blocks from responders, partial responders and non‐responders were stained with ERG. ERG nuclei density was quantified as a proxy for MVD.CD31 MVD and ERG nuclei density were strongly correlated (R2 = 0.87; P < 0.01). In the tumour bed of patients after neoadjuvant therapy, MVD of complete responders (599 nuclei/mm2; 95% CI 434–764) is significantly higher (P < 0.01) than that of partial responders (185 nuclei/mm2; 95% CI 64–306) and non‐responders (117 nuclei/mm2; 95% CI 42–192). No significant difference was found between the partial responders and non‐responders (P = 0.60).Microvascular density appears highest in cases of complete tumour response to neoadjuvant therapy, similar to normal rectal tissue. The histological microvascular patterns seen in treated tissue may explain the imaging patterns seen in photoacoustic microscopy. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions To evaluate the effectiveness of the Paragonix SherpaPak cardiac transport system (PSP) compared to the standard ice‐cold storage (ICS) in extended‐criteria donor grafts implanted in high‐risk recipients.Data of all HTx at the University Centers of Udine and Bologna, between January 2020 and December 2023, employing extended‐criteria donors in high‐risk HTx conditions were retrospectively analyzed. Patient outcomes and complications after HTx were assessed. Endomyocardial biopsies were performed in donor hearts immediately after retrieval (T0), before implantation (T1) and at reperfusion (T2) to evaluate signs of myocardial damage.Overall, 90 patients who had heart transplantation (HTx) with a donor graft preserved with either ICS (n = 60) or PSP (n = 30) were included in the study. The 30‐day mortality was 3% in both groups (p = 0.99), and 1‐year survival 90% and 88% (p = 0.89) for recipients transplanted with PSP and ICS preserved grafts. Rates of moderate‐to‐severe graft dysfunction and bradi‐arrhythmias for PSP and ICS groups were 7% versus 20% (p = 0.08), and 3% versus 15% (p = 0.09). Histologically, severe degrees of cellular and endothelial damage were absent in all PSP grafts while severe degree of contraction bands were higher in ICS hearts at T2.In high‐risk donor–recipient matching, donor heart preservation with PSP seems to show a tendency toward better graft protection. [ABSTRACT FROM AUTHOR]

Purpose: Ischemia reperfusion injury represents a significant yet difficult to assess risk factor for short- and long-term graft impairment in human liver transplantation (LT). As a non-invasive, non-ionizing tool, hyperspectral imaging (HSI) is capable of correlating optical properties with organ microperfusion. Hence, we here performed a study of human liver allografts assessed by HSI for microperfusion and prediction of initial graft function. Methods: Images of liver parenchyma of 37 human liver allografts were acquired at bench preparation, during normothermic machine perfusion (NMP), if applicable, and after reperfusion in the recipient. A specialized HSI acquisition software computed oxygen saturation (StO2), tissue hemoglobin indices (THI), near infrared perfusion indices (NIR), and tissue water indices (TWI). HSI parameters were analyzed for differences with regard to preservation technique, reperfusion sequence and presence of early allograft dysfunction (EAD). Results: Organ preservation was performed by means of NMP (n = 31) or static cold storage (SCS; n = 6). Patients' demographics, donor characteristics, presence of EAD (NMP 36.7% vs. SCS 50%, p = 0.6582), and HSI parameters were comparable between both groups of preservation method. In organs developing EAD, NIR at 1, 2, and 4 h NMP and after reperfusion in the recipient was significantly lower (1 h NMP: 18.6 [8.6–27.6] vs. 28.3 [22.5–39.4], p = 0.0468; 2 h NMP: 19.4 [8.7–30.4] vs. 37.1 [27.5–44.6], p = 0.0011; 4 h NMP: 26.0 [6.8–37.1] vs. 40.3 [32.3–49.9], p = 0.0080; reperfusion: 13.0 [11.5–34.3] vs. 30.6 [19.3–44.0], p = 0.0212). Conclusion: HSI assessment of human liver allografts is feasible during organ preservation and in the recipient. NIR during NMP and after reperfusion might predict the onset of EAD. Larger trials are warranted for assessment of this novel technique in human LT. [ABSTRACT FROM AUTHOR]

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial. [ABSTRACT FROM AUTHOR]

This study investigates the potential improvement of polyhemoglobin's protective properties by the addition of 3 synthetic enzymes (neo-carbonic anhydrase, neo-catalase and neo-superoxide dismutase) to polyhemoglobin after 90 and 180 min of warm in-vitro ischemia (100% Nitrogen at 37 °C). Following the warm ischemic shock, cell cultures were subjected to various treatment solutions: Controls; PolyHb; 3 neoenzymes; PolyHb + 3 neoenzymes; PolyHb + 2 neoenzymes. The cultures were then incubated (Oxygen, 5% CO2 at 37 °C) for 24 h followed by several analyses. Compared to polyhemoglobin alone, this novel solution containing polyhemoglobin + 3 neoeznymes significantly increased the viability, cell growth, albumin production, protection against oxidative stress and cellular injury of human hepatocytes. Moreover, this also protects the viability of human cardiomyocytes. These findings suggest that it could be useful as a pre-transplant cell/organ preservation solution which, in the long-term, could contribute to the development of blood substitutes. [ABSTRACT FROM AUTHOR]

Background: Transgender and non-binary individuals face unique challenges when it comes to fertility preservation (FP). Objective: Despite the growing prevalence of gender dysphoria (GD) and gender transitioning, there is a lack of clear guidelines and consensus on the management of these patients in the FP setting. Clinicians and institutions providing FP services should ensure that they are aware of the needs and circumstances of this underrepresented group of patients and offer them accurate and evidence-based information when counseling and tailoring their FP treatment. Materials and methods: For this scoping review, three major search engines were used. Including Embase, Epistemonikos, Google Scholar, MEDLINE and PubMed. Sources of grey literature were also explored (ResearchGate and Web of Science). The combination of only two keywords [transgender] AND [fertility preservation] was used up to May 2023. Results: The available evidence on clinical management and FP outcomes in transgender patients is limited and mainly originates from case reports or small case series. The main limitation of current FP services for transgender and non-binary individuals is the lack of scientific evidence regarding their care. Discussion: Overall, FP in transgender patients requires individualized and realistic plans, and psychological counseling should be offered. This review aims to provide the latest evidence coming from original studies to facilitate proper counseling and fertility management for these individuals. Conclusions: Inclusive health systems that provide comprehensive reproductive health care to transgender individuals can help them make informed decisions about FP and improve their quality of life. Future research is needed to establish more robust evidence-based guidelines for the management of transgender and non-binary individuals in the FP setting. [ABSTRACT FROM AUTHOR]

The major prognostic factor in head-neck squamous cell carcinoma is the status of lymph nodes. Though there are studies addressing the role of neck dissection in organ preservation protocol, a lacuna still exists as far as the question of upfront neck dissection arises. Despite the potential benefits of upfront neck dissection; the benefits have not been well researched and thus its place in management of head-neck cancers undergoing organ preservation protocol is still questionable. We conducted an observational study in 22 patients with T1 − 2N2 − 3a biopsy proven squamous cell carcinoma of hypopharynx, oropharynx and laryngopharynx which were eligible for organ preservation protocol for their primary site. The primary outcome was to calculate their overall survival rate at 5 years. Overall 5 year survival rate was 68.12%, 5-year Disease free survival rate was 77.2%. The time to start for the primary site, after neck dissection however had a significant effect on overall survival. Those who had a delay of 21 days or less had 80.1% survival at 5 years compared to those who started at 30 days (61.3%) and drastically reduced in those who started at 39 days (20.4%). Log-rank test for the effect of nodal status showed a significant difference in terms of 5 year survival between the groups(p =.027). The 5 year survival rates for N2A, N3A and N2B nodal status were 88.8%, 50% ,and 54.5% ,respectively. We strongly favour upfront neck dissections in a subset of head-neck squamous cell carcinoma cases with T1 − 2N2 − 3a eligible for organ preservation regimen. [ABSTRACT FROM AUTHOR]

Pharyngocutaneous fistula (PCF) is a common postoperative complication in patients undergoing laryngectomy. Many studies have focused on the predisposing factors and their treatment, but there is still controversy on how to identify high-risk patients.PCF is associated with delay in adjuvant treatment, prolonged hospital stay, and the requirement for additional surgical procedures. The increased incidence of post-laryngectomy PCF in the modern era of organ preservation therapy has driven considerable efforts to develop techniques to avoid and treat this complication. The study aims to analyze the incidence, predisposing factors, management, and outcome of PCF in post laryngectomy patients. We reviewed retrospectively the medical records of 72 patients who underwent total laryngectomy during the period from 2013 to 2022 at our institute. Details regarding age, gender, tumor site, comorbidities, radiotherapy, chemotherapy, duration of nasogastric tube feeding, the incidence of PCF and its management, and length of hospital stay. In our analysis of 72 patients, with 38 undergoing upfront laryngectomy and 34 salvage laryngectomy post-chemoradiation, we observed a 23% incidence of Pharyngocutaneous Fistula (PCF). Our univariate analysis revealed that low pre-op albumin levels and advanced stage significantly increased the risk of PCF. Specifically, PCF occurred in 16% of upfront laryngectomy patients and increased to 32% in salvage laryngectomy patients, though there was no significant association with pre-operative radiotherapy (RT).Among PCF cases, those from upfront laryngectomy had a mean onset time of 12 days, while salvage laryngectomy cases had a mean onset time of 8 days. The majority of PCF cases (64%) were managed conservatively, with 11% resolving through secondary suturing and 25% requiring surgical repair using local flaps. Notably, 80% of upfront laryngectomy PCF cases were managed conservatively, compared to 54% in salvage laryngectomy cases.The average hospitalization time for PCF patients was significantly longer at 35.6 days, compared to 12 days for non-PCF patients. Importantly, there were no fatal complications related to PCF in either group. Our study found that Pharyngocutaneous Fistula (PCF) occurs in both irradiated and non-irradiated patients, with T staging and pre-op albumin levels being significant risk factors. While PCF in non-irradiated patients can be treated conservatively, those in chemoradiation patients often require surgical intervention. Postoperative nutritional support like Feeding jejunostomy or Peg tube insertion aids in patient recovery from PCF. [ABSTRACT FROM AUTHOR]

Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients. • This is the first phase III trial comparing SCRT followed by immunochemotherapy to LCRT followed by chemotherapy in LARC. • Neoadjuvant SCRT followed by CAPOX and camrelizumab significantly improved pCR versus neoadjuvant LCRT followed by CAPOX. • Neoadjuvant SCRT followed by CAPOX and camrelizumab demonstrated promising efficacy in LARC patients with pMMR/MSS. • The treatment arm provides LARC patients with the opportunity for organ preservation and a watch-and-wait strategy. • No unexpected toxicities were observed, and the safety profile of the treatment arm was manageable. [ABSTRACT FROM AUTHOR]

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Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia- reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combi- nation with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low- resource locations. [ABSTRACT FROM AUTHOR]

When faced with the prospect of death, some people would prefer a form of long-term preservation that may allow them to be restored to healthy life in the future, if technology ever develops to the point that this is feasible and humane. Some believe that we may have the capacity to perform this type of experimental preservation today--although it has never been proven--using contemporary methods to preserve the structure of the brain. The idea is that the morphomolecular organization of the brain encodes the information required for psychological properties such as personality and long-term memories. If these structures in the brain can be maintained intact over time, this could theoretically provide a bridge to access restorative technologies in the future. To consider this hypothesis, we first describe possible metrics that can be used to assess structural brain preservation quality. We next explore several possible methods to preserve structural information in the brain, including the traditional cryonics method of cryopreservation, as well as aldehyde-stabilized cryopreservation and fluid preservation. We focus in-depth on fluid preservation, which relies on aldehyde fixation to induce chemical gel formation in a wide set of biomolecules and appears to be a cost-effective method. We describe two theoretical recovery technologies, alongside several of the ethical and legal complexities of brain preservation, all of which will require a prudent approach. We believe contemporary structural brain preservation methods have a non-negligible chance of allowing successful restoration in the future and that this deserves serious research efforts by the scientific community. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate outcomes of organ preservation by local excision (LE) compared to proctectomy following neoadjuvant therapy for rectal cancer. Methods: This retrospective observational study using the National Cancer Database (NCDB) included patients with locally advanced non-metastatic rectal cancer (ypT0–1 tumors) treated with neoadjuvant therapy between 2004 and 2019. Outcomes of patients who underwent LE or proctectomy were compared. 1:1 propensity score matching including patient demographics, clinical and therapeutic factors was used to minimize selection bias. Main outcome was overall survival (OS). Results: 11,256 of 318,548 patients were included, 526 (4.6%) of whom underwent LE. After matching, mean 5-year OS was similar between the groups (54.1 vs. 54.2 months; p = 0.881). Positive resection margins (1.2% vs. 0.6%; p = 0.45), pathologic T stage (p = 0.07), 30-day mortality (0.6% vs. 0.6%; p = 1), and 90-day mortality (1.5% vs. 1.2%; p = 0.75) were comparable between the groups. Length of stay (1 vs. 6 days; p < 0.001) and 30-day readmission rate (5.3% vs. 10.3%; p = 0.02) were lower in LE patients. Multivariate analysis of predictors of OS demonstrated male sex (HR 1.38, 95% CI 1.08–1.77; p = 0.009), higher Charlson score (HR 1.52, 95% CI 1.29–1.79; p < 0.001), poorly differentiated carcinoma (HR 1.61, 95% CI 1.08–2.39; p = 0.02), mucinous carcinoma (HR 3.53, 95% CI 1.72–7.24; p < 0.001), and pathological T1 (HR 1.45, 95% CI 1.14–1.84; p = 0.002) were independent predictors of increased mortality. LE did not correlate with worse OS (HR 0.91, 95% CI 0.42–1.97; p = 0.82). Conclusion: Our findings show no overall significant survival difference between LE and total mesorectal excision, including ypT1 tumors. Moreover, patients with poorly differentiated or mucinous adenocarcinomas generally had poorer outcomes, regardless of surgical method. [ABSTRACT FROM AUTHOR]

We previously reported that normothermic ex vivo kidney perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS). Mitochondrial respiration and ATP levels were further enhanced when AP39, a mitochondria-targeted hydrogen sulfide donor, was administered during warm perfusion. Correspondingly, the combination of NEVKP and AP39 was associated with decreased oxidative stress and inflammation, and with improved graft function after transplantation. In conclusion, our findings suggest that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by AP39 administration. Activation of mitochondrial function through the combination of AP39 and normothermic perfusion could represent a new therapeutic strategy for long-term renal preservation. The authors previously reported that normothermic ex vivo kidney perfusion is superior to static cold storage in terms of organ protection, but the detailed mechanism was unclear. Here the authors show that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by administration of AP39, a mitochondria-targeted hydrogen sulfide donor. [ABSTRACT FROM AUTHOR]

Background: It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size. Methods: Patients treated with LARC from 2014 to 2021 with cT2–3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version 20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270). Results: The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3 cm to 20% in cT3N+ > 4 cm. Organ preservation without recurrence at 2 years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+. Conclusion: There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The Organ Care System (OCS) (Transmedics, Andover, MA) reduces cold ischemic time of donor hearts by producing a normothermic beating state during ex vivo perfusion, enabling extended ex situ intervals, which potentially increases donor pool. We aimed to compare outcomes in utilization of OCS and conventional cold storage technique.Consecutive heart transplants following brain death at our institution between May 2022 and July 2023 were analyzed. Recipients were divided into those receiving hearts preserved with OCS [N = 15] and those with conventional cold storage (Control, N = 27), with OCS utilization when anticipated ischemic time was more than 4 h. Pre‐transplant characteristics and transplant outcomes were compared.OCS utilization allowed a significant increase in distance traveled for heart retrieval (OCS, 624 ± 269 vs. Control, 153 ± 128 miles, p < 0.001), with longer mean total preservation times (6.2 ± 1.1 vs 2.6 ± 0.6 h, p < 0.001). All but one patient displayed a general decrease or plateau in lactate throughout perfusion time by OCS. Both groups experienced similar rates of severe primary graft dysfunction (OCS, 6.7% [N = 1] vs. Control, 11.1% [N = 3], p = 0.63), with 100% in‐hospital survival in the OCS group compared to 96.3% in the Control group (p = 0.34). Kaplan–Meier survival analysis showed that estimated one‐year survival were comparable (OCS, 93.3 ± 6.4% vs. Control, 88.9 ± 6.0%, p = 0.61).With a mean preservation time of around 6 h and distance covered of over 600 miles, our results using OCS indicate a potential to safely increase the quantity and viability of accessible organs, thus broadening the donor pool without negatively affecting outcomes. [ABSTRACT FROM AUTHOR]

The European Larynx Organ Preservation Study (ELOS; NCT06137378) is a prospective, randomized, open-label, two-armed parallel group controlled, phase II multicenter larynx organ preservation (LOP) trial in locoregionally advanced (LA) stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHSCC) amenable for total laryngectomy (TL) with PD-L1 expression within tumor tissue biopsy, calculated as CPS = 1. Induction chemotherapy (IC) with docetaxel and cisplatin (TP) followed by radiation will be compared to TP plus PD-1 inhibition by pembrolizumab (MK-3475; 200 mg i.v. starting day 1 q3w for 17 cycles). After a short induction early response evaluation (ERE) 21 ± 3 days after the first cycle of IC (IC-1), responders achieving endoscopic estimated tumor surface shrinkage (ETSS) =30% will get an additional two cycles of IC followed by intensity-modulated radiotherapy 70-72 Gy (EQD2/a/b = 10) aiming at LOP. Nonresponders (ETSS < 30% or progressing disease) will receive TL and bilateral neck dissection followed by postoperative radiation or chemoradiation as recommended by the clinic's multidisciplinary tumor board. Pembrolizumab treatment will be continued in the intervention arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent of subsequent decisions on adjuvant therapy after TL. [ABSTRACT FROM AUTHOR]

Background: Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/β-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. Methods: The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/β-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. Results: The mean resorption rate in the HA/β-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/β-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/β-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. Conclusion: The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/β-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning. [ABSTRACT FROM AUTHOR]

Background: Prospective randomized trials have not yet identified baseline features predictive of organ preservation in locally advanced rectal cancers treated with total neoadjuvant therapy and a selective watch-and-wait strategy. Methods: This was a secondary analysis of the OPRA trial, which randomized patients with stage II–III rectal adenocarcinoma to receive either induction or consolidation total neoadjuvant therapy. Patients were recommended for total mesorectal excision, or watch and wait based on clinical response at 8 ± 4 weeks after completing treatment. Standardized baseline clinical and radiological variables were collected prospectively. Survival outcomes, including total mesorectal excision-free survival, disease-free survival, and overall survival, were assessed by intention-to-treat analysis. Cox proportional hazards models were used to evaluate associations between baseline variables and survival outcomes. Results: Of the 324 patients randomized for the OPRA trial, 38 (11.7%) had cT4 tumours, 230 (71.0%) cN-positive disease, 101 (32.5%) mesorectal fascia involvement, and 64 (19.8%) extramural venous invasion. Several baseline features were independently associated with recommendation for total mesorectal excision on multivariable analysis: nodal disease (HR 1.66, 95% c.i. 1.12 to 2.48), extramural venous invasion (HR 1.57, 1.07 to 2.29), mesorectal fascia involvement (HR 1.45, 1.01 to 2.09), and tumour length (HR 1.11, 1.00 to 1.22). Of these, nodal disease (HR 2.02, 1.15 to 3.53) and mesorectal fascia involvement (HR 2.02, 1.26 to 3.26) also predicted worse disease-free survival. Age (HR 1.03, 1.00 to 1.06) was associated with overall survival. Conclusion: Baseline MRI features, including nodal disease, extramural venous invasion, mesorectal fascia involvement, and tumour length, independently predict the likelihood of organ preservation after completion of total neoadjuvant therapy. Mesorectal fascia involvement and nodal disease are associated with disease-free survival. Prospective randomized studies have not yet evaluated baseline features that predict organ preservation in locally advanced rectal cancer treated with total neoadjuvant therapy and a selective watch-and-wait strategy. This secondary analysis of the OPRA trial demonstrated that baseline MRI features, including nodal status, extramural venous invasion, mesorectal fascia involvement, and tumour length, independently predict total mesorectal excision-free survival. Nodal status and mesorectal fascia involvement are associated with disease-free survival. [ABSTRACT FROM AUTHOR]

The African clawed frog (Xenopus laevis) endures prolonged periods of dehydration while estivating underground during the dry season. Epigenetic modifications play crucial roles in regulating gene expression in response to environmental changes. The elucidation of epigenetic changes relevant to survival could serve as a basis for further studies on organ preservation under extreme stress. The current study examined the relative protein levels of key enzymes involved in the arginine methylation of histones in the liver and kidney tissues of control versus dehydrated (35 ± 1%) X. laevis through immunoblotting. Protein arginine methyltransferases (PRMT) 4, 5, and 6 showed significant protein level decreases of 35 ± 3%, 71 ± 7%, and 25 ± 5%, respectively, in the liver tissues of the dehydrated frogs relative to controls. In contrast, PRMT7 exhibited an increase of 36 ± 4%. Similarly, the methylated histone markers H3R2m2a, H3R8m2a, and H3R8m2s were downregulated by 34 ± 11%, 15 ± 4%, and 42 ± 12%, respectively, in the livers of dehydrated frogs compared to controls. By contrast, the kidneys of dehydrated frogs showed an upregulation of histone markers. H3R2m2a, H3R8m2a, H3R8m2s, and H4R3m2a were significantly increased by 126 ± 12%, 112 ± 7%, 47 ± 13%, and 13 ± 3%, respectively. These changes can play vital roles in the metabolic reorganization of X. laevis during dehydration, and are likely to increase the chances of survival. In turn, the tissue-specific regulation of the histone arginine methylation mechanism suggests the importance of epigenetic regulation in the adaptation of X. laevis for whole-body dehydration. [ABSTRACT FROM AUTHOR]

Background: The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change. Methods: The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021. Transplant centers were grouped by average donor heart travel distance based on whether they received more or less than 50% of organs from >250 miles away. Descriptive statistics were provided for waitlisted and transplanted patients. Regression analyses modeled waitlist mortality, incidence of transplant, overall survival, and graft survival. Results: Centers with a longer average travel distance had a higher mean annual transplant volume with a reduction in total days on a waitlist (86.6 vs. 149.2 days), an increased cold ischemic time (3.6 vs. 3.2 h), with no significant difference in post‐transplant overall survival or graft survival. Conclusions: The benefits of reducing waitlist time while preserving post‐transplant outcomes extend broadly. The trends observed in this investigation will be useful as we revise organ transplant policy in the era of new organ procurement and preservation techniques. [ABSTRACT FROM AUTHOR]

We recently reported in a rat model of kidney transplantation that the addition of sodium thiosulfate (STS) to organ preservation solution improved renal graft quality and prolonged recipient survival. The present study investigates whether STS pre-treatment would produce a similar effect. In vitro, rat kidney epithelial cells were treated with 150 μM STS before and/or during exposure to hypoxia followed by reoxygenation. In vivo, donor rats were treated with PBS or 2.4 mg/kg STS 30 min before donor kidneys were procured and stored in UW or UW+150 μM STS solution at 4 °C for 24 h. Renal grafts were then transplanted into bilaterally nephrectomised recipient rats which were then sacrificed on post-operative day 3. STS pre-treatment significantly reduced cell death compared to untreated and other treated cells in vitro (p < 0.05), which corresponded with our in vivo result (p < 0.05). However, no significant differences were observed in other parameters of tissue injury. Our results suggest that STS pre-treatment may improve renal graft function after transplantation. [ABSTRACT FROM AUTHOR]

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine–Tryptophan–Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP. NEW & NOTEWORTHY: We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile. [ABSTRACT FROM AUTHOR]

A systematic evaluation of vascular access device (VAD) selection incorporates patient, device, and infusate characteristics to ensure optimal device placement. This article explores VAD selection from the perspective of vessel health and preservation and describes VAD selection options and indications, VAD-related complications, and strategies to reduce those complications. [ABSTRACT FROM AUTHOR]

Background: Normothermic machine perfusion (NMP) allows for the assessment and resuscitation of ex‐vivo human livers prior to transplantation. Commercially available NMP systems are closed circuits that accumulate metabolic waste and cytokines over time, potentially limiting organ preservation times. Dialysis has been proposed as a method to remove waste and excess fluid from such systems. This study aimed to demonstrate the utility of integrating dialysis into a commercially available system by quantifying solute removal. Methods: A dialysis filter was attached in parallel to a commercially available liver perfusion system. Three livers declined for transplantation were split before undergoing long‐term NMP with blood using the modified system. During perfusion, dialysate flow rates were set in the range of 100–600 mL/h for short periods of time. At each flow rate, perfusate and spent dialysate samples were collected and analyzed for solute clearance. Results: The addition of dialysis to a commercial NMP system removed water‐soluble waste and helped regulate electrolyte concentrations. Interleukin‐6 was successfully removed from the perfusate. Solute clearance was proportional to dialysate flow rate. A guide for our perfusion setup was created for the appropriate selection of dialysis flow rates and duration based on real‐time perfusate composition. Conclusions: Dialysis circuits can efficiently remove waste and regulate perfusate composition, and can be easily incorporated to improve the performance of commercially available systems. Quantification of the effect of dialysis on perfusate composition enables refined dialysis control to optimize electrolyte profiles and avoid the over‐ or under‐correction of key solutes. [ABSTRACT FROM AUTHOR]

Safely expanding the use of extended-criteria organ donors is critical to increase access to kidney transplantation and reduce wait list mortality. We performed a retrospective analysis of 24 pediatric en-bloc (PEB) compared to 13 dual-kidney transplantations (DKT) and 39 living donor kidney transplants (LDKT) at the University of Virginia hospital, performed between 2011 and 2019. All living donor kidney transplants were performed in 2017. This year was chosen so that 5-year outcomes data would be available. Primary outcomes were glomerular filtration rate and serum creatinine at 12 and 24 months postoperatively. Secondary outcomes were patient and graft survival. The 1-year creatinine levels (mL/min/1.73 m2) were lower in the PEB group (median 0.9, IQR 0.8–1.4) when compared to the DKT (median 1.4, IQR 1.2–1.5) and LDKT (median 1.3, IQR 1.1–1.5) groups (p < 0.001). The 2-year creatinine levels (mL/min/1.73 m2) were also lower in the PEB group (median 0.8, IQR 0.7–1.08) compared to the DKT (median 1.3, IQR 1.1–1.5) and LDKT (median 1.3, IQR 1.0–1.5) groups (p < 0.001). The glomerular filtration rates demonstrated similar results. Graft survival at 1, 3, and 5 years was 100/100/90, 100/92/69, and 96/96/91 for LDKT, DKT, and PEB, respectively (p = 0.27). Patient survival at 1, 3, and 5 years was 100/100/90, 100/100/88 and 100/100/95 for LDKT, DKT, and PEB, respectively (p = 0.78). Dual KT and PEB transplantation are two alternative techniques to safely expand the donor pool. PEB kidney transplantation, though technically more demanding, provides the best long-term graft function. [ABSTRACT FROM AUTHOR]

Tumor mutation profiling (MP) is often conducted on tissue from biopsies conducted for clinical purposes (diagnostic tissue). We aimed to explore the views of patients with cancer on who should own tumor biopsy tissue, pay for its storage, and decide on its future use; and determine their attitudes to and predictors of undergoing additional biopsies if required for research purposes. In this mixed methods, cross-sectional study, patients with advanced solid cancers enrolled in the Molecular Screening and Therapeutics Program (n  = 397) completed a questionnaire prior to undergoing MP (n  = 356/397). A subset (n  = 23) also completed a qualitative interview. Fifty percent of participants believed they and/or relatives should own and control access to diagnostic tissue. Most (65.5%) believed the government should pay for tissue preparation. Qualitative themes included (1) custodianship of diagnostic tissue, (2) changing value of tissue across time and between cultures, (3) equity regarding payment, and (4) cost-benefit considerations in deciding on additional biopsies. Policy and regulation should consider patient perspectives. Extension of publicly funded health care to include tissue retrieval for clinical trials should be considered. [ABSTRACT FROM AUTHOR]

Purpose: Debate persists regarding the feasibility of adopting an organ-preserving strategy as the treatment modality for clinical T2N0 rectal cancer. This study aimed to compare the outcomes of attempting organ-preserving strategies versus radical surgery in patients with clinical T2N0 mid to low rectal cancer. Methods: Patients diagnosed with clinical T2N0 rectal cancer, with lesions located within 8 cm from the anal verge as determined by pre-treatment magnetic resonance imaging between January 2010 and December 2020 were included. Results: Of 119 patients, 91 and 28 were categorized into the organ-preserving attempt group and the radical surgery group, respectively. The median follow-up duration was 48.8 months (range, 0–134 months). The organ-preserving attempt group exhibited a reduced incidence of stoma formation (44.0% vs. 75.0%; p = 0.004) and a lower occurrence of grade 3 or higher surgical complications (5.8% vs. 21.4%; p = 0.025). Univariate analyses revealed no significant association between treatment strategy and 3-year local recurrence-free survival (organ-preserving attempt 87.9% vs. radical surgery 96.2%; p = 0.129), or 3-year disease-free survival (79.6% vs. 84.9%; p = 0.429). Multivariate analysis did not identify any independent prognostic factors associated with oncologic outcomes. Conclusion: Compared with radical surgery, attempted organ preservation resulted in lower incidences of stoma formation and severe surgical complications, whereas oncological outcomes were comparable. Attempting organ preservation may be a safe alternative to radical surgery for clinical T2N0 mid to low rectal cancer. [ABSTRACT FROM AUTHOR]

Background: The aims of this narrative review were (i) to describe the current indications of SLKT, (ii) to report evolution of SLKT activity, (iii) to report the outcomes of SLKT, (iv) to explain the immune-protective effect of liver transplant on kidney transplant, (v) to explain the interest of delay kidney transplantation, using hypothermic machine perfusion (HMP), (vi) to report kidney after liver transplantation (KALT) indications and (vii) to describe the value of the increase in the use of extended criteria donors (ECD) and particular controlled donation after circulatory death (cDCD) transplant, thanks to the development of new organ preservation strategies. Method: Electronic databases were screened using the keywords "Simultaneous", "Combined", "kidney transplantation" and "liver transplantation". The methodological and clinical heterogeneity of the included studies meant that meta-analysis was inappropriate. Results: A total of 1,917 publications were identified in the literature search. Two reviewers screened all study abstracts independently and 1,107 of these were excluded. Thus, a total of 79 full text articles were assessed for eligibility. Of these, 21 were excluded. In total, 58 studies were included in this systematic review. Conclusions: Simultaneous liver-kidney transplantation has made a significant contribution for patients with dual‐organ disease. The optimization of indication and selection of SLKT patients will reduce futile transplantation. Moreover, increasing the use of transplants from extended criteria donors, in particular cDCD, should be encouraged, thanks to the development of new modalities of organ preservation. [ABSTRACT FROM AUTHOR]

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multiomics data, thereby enhancing the precision and efficacy of patient selection for LP protocols. [ABSTRACT FROM AUTHOR]

Brain death (BD) is a complex medical state that triggers systemic disturbances and a cascade of pathophysiological processes. This condition significantly impairs both kidney function and structural integrity, thereby presenting considerable challenges to graft viability and the long-term success of transplantation endeavors. Tacrolimus (FK506), an immunosuppressive drug, was used in this study to assess its impact as a pretreatment on brain deathinduced renal injury. This study aimed to investigate changes associated with brain death-induced renal injury in a 4-month-old female porcine model. The experimental groups included brain death placebo-pretreated (BD; n = 9), brain death tacrolimus-pretreated using the clinical dose of 0.25 mg/kg the day before surgery, followed by 0.05 mg/kg/day 1 hour before the procedure (BD + FK506; n = 8), and control (ctrl, n = 7) piglets, which did not undergo brain death induction. Furthermore, we aimed to assess the effect of FK506 on these renal alterations through graft preconditioning. We hypothesized that immunosuppressive properties of FK506 reduce tissue inflammation and preserve the glycocalyx. Our findings revealed a series of interconnected events triggered by BD, leading to a deterioration of renal function and increased proteinuria, increased apoptosis in the vessels, glomeruli and tubules, significant leukocyte infiltration into renal tissue, and degradation of the glycocalyx in comparison with ctrl group. Importantly, treatment with FK506 demonstrated significant efficacy in attenuating these adverse effects. FK506 helped reduce apoptosis, maintain glycocalyx integrity, regulate neutrophil infiltration, and mitigate renal injury following BD. This study offers new insights into the pathophysiology of BD-induced renal injury, emphasizing the potential of FK506 pretreatment as a promising therapeutic intervention for organ preservation, through maintaining endothelial function with the additional benefit of limiting the risk of rejection. [ABSTRACT FROM AUTHOR]

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma. Methods: A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 - 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios. Results: Of the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1 cm from the anal verge (range, 0.0 - 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 - 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p=0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival (p=0.033). Clinical response at earlier follow up points did not predict surgery-nor permanent ostomy-free survival. Conclusion: These results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy. [ABSTRACT FROM AUTHOR]

Transplantation of the liver in combination with other organs is an increasingly performed procedure. Over the years, continuous improvement in survival could be realized through careful patient selection and refined organ preservation techniques, in spite of the challenges posed by aging recipients and donors, as well as the increased use of steatotic liver grafts. Herein, we revisit the epidemiology, allocation policies in different transplant zones, indications, and outcomes with regard to simultaneous organ transplants involving the liver, that is combined heart–liver, liver–lung, liver–kidney, and multivisceral transplantation. We address challenges surrounding combined organ transplantation such as equity, utility, and logistics of dual organ implantation, but also advantages that come along with combined transplantation, thereby focusing on molecular mechanisms underlying immunoprotection provided by the liver to the other allografts. In addition, the current standing and knowledge of machine perfusion in combined organ transplantation, mostly based on center experience, will be reviewed. Notwithstanding all the technical advances, shortage of organs, and the lack of universal eligibility criteria for certain multi-organ combinations are hurdles that need to be tackled in the future. [ABSTRACT FROM AUTHOR]

Context: Clinical adoption of ex situ liver perfusion is growing. While hypothermic perfusion protects against ischemia–reperfusion injury in marginal grafts, normothermic perfusion enables organ viability assessment and therefore selection of borderline grafts. The combination of hypothermic and normothermic perfusion, known as "cold‐to‐warm," may be the optimal sequence for organ preservation, but is difficult to achieve with most commercial perfusion systems. We developed an adaptable customized circuit allowing uninterrupted "cold‐to‐warm" perfusion and conducted preclinical studies on healthy porcine livers and discarded human livers to demonstrate the circuit's efficacy. Methods: In collaboration with bioengineers, we developed a customized circuit that adapts to extracorporeal circulation consoles used in cardiovascular surgery and includes a proprietary reservoir enabling easy perfusate change without interrupting perfusion. This preclinical study was conducted on porcine and human livers. Perfusion parameters (pressures, flows, oxygenation) and organ viability were monitored. Results: The customized circuit was adapted to a LivaNova S5® console, and the perfusions were flow‐driven with real‐time pressure monitoring. Ten porcine liver and 12 discarded human liver perfusions were performed during 14 to 18 h and 7 to 25 h, respectively. No hyperpressure was observed (porcine and human portal pressure 2–6 and 2–8 mm Hg; arterial pressure 10–65 and 20–65 mm Hg, respectively). No severe histological tissue injury was observed (Suzuki score ≤ 3 at the end of perfusion). Seven (70%) porcine livers and five (42%) human livers met the UK viability criteria. Conclusion: The customized circuit and system design enables smooth uninterrupted "cold‐to‐warm" perfusion not present in current commercial perfusion systems. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role of formal reproductive endocrinology and infertility (REI) consultation in fertility preservation counseling in a pediatric/adolescent oncology patient population. Methods: Retrospective chart review was performed at an academic adult hospital from 2021 to 2022. Pre- and postpubertal patients admitted to the pediatric/adolescent oncology service with cancer diagnoses and imminent gonadotoxic chemotherapy plans were included. Baseline characteristics were collected, including patient age, sex, race, language, insurance, and cancer diagnosis. Primary outcomes were formal REI consultation and fertility preservation election. Results: Nineteen of 58 eligible patients received a formal REI consultation. Patients were more likely to elect fertility preservation if they received a consult. Females were more likely to receive a consult than males and more likely to elect fertility preservation. Patients of age ≥16 years were more likely to receive consultation than younger patients. However, all patients of age <16 years who received a consult elected fertility preservation. There was no difference in consultation based on race, language, or insurance. Thirteen of 19 patients who received an REI consultation elected fertility preservation. Ten of 11 female elections were ovarian suppression, an unproven method of fertility preservation. The two male elections were semen cryopreservation. Conclusion: Underutilization of formal REI consults and a relative lack of proven fertility preservation elections may shed light on a need for increased fertility preservation awareness among young oncology patients and the providers who care for them. A streamlined process that automates formal REI consultation for all eligible patients may maximize the potential for comprehensive counseling and improve patient participation in fertility preservation. [ABSTRACT FROM AUTHOR]

The standard treatment of T2–T3 rectal adenocarcinoma is radical proctectomy by total mesorectal excision often combined with some neoadjuvant treatment. To reduce morbidity of this surgery, organ preservation strategy using various combination of radiotherapy, chemotherapy and local excision is gaining interest. Some randomized trials have proven the feasibility of such approaches. The OPERA trial demonstrated, for T2 T3 < 5 cm diameter low-middle rectum, that a contact X-ray brachytherapy boost of 90 Gy in three fractions over 4 weeks was able to achieve a planned organ preservation in 81% of patients at 3 years with 97% success for tumour smaller than 3 cm treated with contact X-ray brachytherapy boost first. To try to expand organ preservation to larger tumours we set up a feasibility trial in T2–T3 tumours using total neoadjuvant treatment and a contact X-ray brachytherapy boost. The trial was approved by the institutional review board of Nice. Inclusion criteria were operable patients, 75 years or less, adenocarcinoma of the low-middle rectum staged T2c-T3N0 larger than 3.5 cm and less than 6 cm in diameter or T2-T3N1 less than 6 cm in diameter. Treatment started in all cases with neoadjuvant chemotherapy associating 5-fluoro-uracile, irinotecan and oxaliplatin ('folfirinox' regimen, four to six cycles). In case of good tumour response after four cycles, a contact X-ray brachytherapy boost (delivering 90 Gy in three fractions) was given followed by chemoradiotherapy (external beam radiotherapy delivering 50 Gy, with concurrent capecitabine). After six cycles if only a partial response (tumour still larger than 3 cm) was seen, chemoradiotherapy was given and contact X-ray brachytherapy boost was delivered after that. At the end of this total neoadjuvant treatment a watch and wait strategy was decided in case of clinical complete response or radical proctectomy by total mesorectal excision for partial response. Between July 2019 and October 2022, 14 patients were included; median age was 66 years (range: 51–77 years), there were nine male and five female, two T2 N1 tumours, seven T3N0, and five T3N1, all were M0. Median tumour diameter was 40 mm (range: 11–50 mm); three tumours had a circumferential extension greater than 50%. Seven patients received four folfirinox cycles and seven had six cycles. Contact X-ray brachytherapy boost was given during folfirinox chemotherapy before chemoradiotherapy in 11 patients (and after in three). The tolerance was good, with no grade 4–5 toxicity. The main grade 3 early toxicity was in relation with the folfirinox regimen. A clinical complete response was seen in 12 patients at the end of the total neoadjuvant treatment (85%). All these patients are alive and have preserved their rectum with a mean follow-up time of 17.8 months (range: 6–48 months) and a good bowel function (low anterior rectal resection syndrome score below 30). The main contact X-ray brachytherapy boost toxicity was radiation ulceration in three patients that usually healed within 6 months, sometimes necessitating hyperbaric oxygen. The preliminary results of this feasibility study show that early tolerance of these intensive total neoadjuvant treatment is compatible with an acceptable toxicity. The high rate of organ preservation in this intermediate group of T2–T3 tumours is encouraging and is a good argument to start the next randomized TRESOR trial that will aim at achieving a 65% of 3-year survival with organ preservation in this intermediate tumour group. [ABSTRACT FROM AUTHOR]

Esophagectomy and lymphadenectomy have been the standard of care for patients at high risk (HR) of lymph node metastasis following a diagnosis of early esophageal adenocarcinoma (OAC) after endoscopic resection (ER). However, recent cohorts suggest lymph node metastasis risk is lower than initially estimated, suggesting organ preservation with close endoscopic follow-up is a viable option. We report on the 3- and 5-year risk of lymph node/distant metastasis among patients diagnosed with early HR-T1 OAC undergoing endoscopic follow-up. Patients diagnosed with HR-T1a or T1b OAC following ER at a tertiary referral center were identified and retrospectively analyzed from clinical records between 2010 and 2021. Patients were included if they underwent endoscopic follow-up after resection and were divided into HR-T1a, low risk (LR)-T1b and HR-T1b cohorts. After ER, 47 patients underwent endoscopic follow-up for early HR OAC. In total, 39 patients had an R0 resection with a combined 3- and 5-year risk of LN/distant metastasis of 6.9% [95% confidence interval (CI): 1.8–25] and 10.9% (95% CI, 3.6–30.2%), respectively. There was no significant difference when stratifying by histopathological subtype (P  = 0.64). Among those without persistent luminal disease on follow-up, the 5-year risk was 4.1% (95% CI, 0.6–26.1). Two patients died secondary to OAC with an all-cause 5-year survival of 57.5% (95% CI, 39.5–71.9). The overall risk of LN/distant metastasis for early HR T1 OAC was lower than historically reported. Endoscopic surveillance can be a reasonable approach in highly selected patients with an R0 resection and complete luminal eradication, but clear, evidence-based surveillance guidelines are needed. [ABSTRACT FROM AUTHOR]

The use of machine perfusion in solid organ transplantation has developed tremendously worldwide in recent years. Although the number of randomized controlled trials in the field of organ preservation is still limited, machine perfusion has been shown to be superior to static cold storage of donor organs. Various devices for clinical use with hypothermia or normothermia are already available for most organs. Whether and which perfusion strategy is superior to the others is the subject of current clinical research. This also applies to the further evaluation of possible synergistic effects in the sequential use of the various protocols. The common goal of all dynamic perfusion technologies is to optimize organ preservation between removal and transplantation. By testing the quality of marginal donor organs prior to transplantation, it should also be possible to use these organs without exposing the patient to increased risk. This can lead to a significant expansion of the donor pool. This is particularly important in Germany, where there is an ongoing shortage of organs and restrictive legislation regarding the expansion of the donor pool. Furthermore, the perfusion technology offers the possibility to serve as a platform for other ex situ and in situ therapies on isolated organs. In addition to the conditioning of pre-damaged organs for transplantation, this could lead to further applications in the context of targeted organ therapies and also to improved transplant logistics in the future. [ABSTRACT FROM AUTHOR]

This retrospective study investigates the efficacy of the socket shield (SS) in preserving inter-implant papilla and bone in anterior adjacent implant sites. Clinical and radiographic records of 23 patients were evaluated. A total of 31 implants were placed immediately into extraction sockets with SS, resulting in 26 inter-implant sites, and 7 implants were placed without SS. After a mean follow-up of 41.5 months (range: 12 to 124 months), 30/31 (96.8%) implants with SS and 7/7 (100%) implants without SS were clinically successful. The mean changes in inter-implant papilla and bone heights were -0.40 mm and -0.46 mm, respectively. The effects of implant placement timing and the socket shield number, shape, and crestal level on interimplant tissue height changes were found to be insignificant (P > .05). Supracrestal shield level (31.6% vs 16.6% in equicrestal), U-shape shield (41.2% vs 7.1% in C-shape), and shield-to-implant contact (40.0% vs 12.5% in no contact) were associated with increased occurrence of exposures. The application of SS in adjacent anterior implant situations is a viable treatment option for maintaining inter-implant papilla. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the outcomes of a modified entire papilla preservation technique (EPPT) in the treatment of isolated intrabony defects in patients diagnosed with stage III periodontitis. A total of 18 intrabony defects were treated: 4 one-wall, 7 two-wall, and 7 three-wall. Mean probing pocket depth reductions of 4.33 mm (P < .0001), clinical attachment level gains of 4.87 mm (P < .0001), and radiographic defect depth reductions of 4.27 mm (P < .0001) were observed at 6 months. Changes in gingival recession and keratinized tissue were not statistically significant. It can be concluded that the proposed modification of the EPPT is useful in the treatment of isolated intrabony defects. [ABSTRACT FROM AUTHOR]

This pilot case series study reports the dimensional alveolar bone changes after reconstruction of severely resorbed postextraction sockets treated with a mixture of particulate bone allograft and xenograft in combination with titanium-reinforced dense polytetrafluoroethylene (Ti-d-PTFE) membranes. Ten subjects who required premolar or molar extraction were included. Bone grafts were protected with Ti-d-PTFE membranes, utilizing an open-healing environment; membranes were removed 4 to 6 weeks after extraction, and implants were placed 6.7 months mean) after extraction (T1). One patient required additional augmentation to correct an apical undercut of the alveolar process that was present preextraction. All implants integrated well and showed an implant stability quotient (ISQ) value between 71 and 83. The mean horizontal ridge width reduction from baseline extraction) to T1 was 0.8 mm. Throughout the study, the mean vertical bone gain increase ranged from 0.2 mm to 2.8 mm (mean keratinized tissue width increase: 5.8 mm). The ridge preservation/restoration technique showed good preservation and restoration of severely resorbed sockets as well as improved amounts of keratinized tissue. If implant therapy is required after tooth extraction and severely resorbed sockets are present, the use of a Ti-d-PTFE membrane is a realistic option. [ABSTRACT FROM AUTHOR]

Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation. [Display omitted] • This natural experiment uniquely compared organ preservation between patients managed with LCCRT- versus SCRT-based TNT. • LCCRT and SCRT cohorts achieved similar clinical complete response (cCR) rates and WW eligibility. • Two-year organ preservation was higher and local regrowth was lower in WW patients treated with LCCRT than SCRT-based TNT. • No differences in OS, DFS, or distant recurrence rates were observed between the WW cohorts. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation is used for treating end‐stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). Methods: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non‐oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. Results: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. Conclusion: We present a novel low‐cost device that is feasible and could represent a valuable tool in organ preservation during SCS. [ABSTRACT FROM AUTHOR]