Preservation Time Research Articles

COMPARATIVE STUDY ON OUTCOME OF OPEN FISTULECTOMY VERSUS LIFT PROCEDURE FOR UNCOMPLICATED PERIANAL FISTULAS

Perianal fistulas, particularly trans sphincteric types, pose a significant challenge in terms of management, often requiring surgical intervention. Traditional open fistulotomy has been a common procedure, but newer techniques like the ligation of the intersphincteric fistula tract (LIFT) procedure are being explored for improved outcomes, particularly in terms of preserving continence. This study aims to compare the outcomes of open fistulotomy versus the LIFT procedure in patients with trans sphincteric perianal fistulas. Objective: To compare the clinical outcomes, healing times, recurrence rates, and continence status between patients undergoing open fistulotomy and those treated with the LIFT procedure for trans sphincteric perianal fistulas. Methods: A prospective comparative study was conducted in the General Surgery Department of Nishtar Medical Hospital, Multan, from May 2024 to August 2024. A total of 150 adult patients with trans sphincteric perianal fistulas were enrolled using consecutive sampling. The patients were randomly divided into two groups: Group A (n = 75) underwent the LIFT procedure, and Group B (n = 75) underwent fistulectomy. Postoperative follow-up was conducted weekly until wound healing and at three months after healing to assess pain scores, recurrence rates, healing time, and continence status. Statistical analysis was conducted using SPSS Version 25, with a significance level set at p < 0.05. Results: Among the participants, 6 patients (8%) in Group A and 8 patients (10.7%) in Group B experienced recurrent fistulas, showing no significant difference between the groups. Postoperative pain scores were similar between both groups. However, the healing time was significantly shorter in Group A (27.2 days) compared to Group B (48.1 days) (p < 0.05). Recurrence rates were higher in Group A (16%) compared to Group B (2.7%) (p < 0.05). Incontinence was observed in 10.7% of patients in Group B, while no incontinence was reported in Group A (p < 0.05). Conclusion: The LIFT procedure offers better outcomes in terms of continence preservation and shorter healing time compared to open fistulotomy in the management of trans sphincteric perianal fistulas. However, open fistulotomy showed lower recurrence rates. These findings suggest that the LIFT procedure may be preferable in patients for whom preserving continence is a priority, while open fistulotomy may be a better option in cases where recurrence prevention is the main concern.

A reproducible extended ex-vivo normothermic machine liver perfusion protocol utilising improved nutrition and targeted vascular flows

BackgroundNormothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements. We set out to develop a reproducible protocol for the extended normothermic machine perfusion of whole human livers.MethodsHuman livers declined for transplantation were perfused using a blood-based perfusate at 36 °C using the Liver Assist device (XVIVO, Sweden), with continuous veno-venous haemofiltration in-parallel. We developed the protocol in a stepwise fashion.ResultsPerfusion techniques utilised included: targeted physiological vascular flows, phosphate replacement (to prevent hypophosphataemia), N-acetylcysteine (to prevent methaemoglobin accumulation), and the utilisation of sodium lactate as both a nutritional source and real-time measure of hepatocyte function. All five human livers perfused with the developed protocol showed preserved function with a median perfusion time of 168 h (range 120–184 h), with preserved viability throughout.ConclusionsLivers can be reproducibly perfused in excess of 120 (range 121–184) hours with evidence of preserved hepatocyte and cholangiocyte function.

Descemet Membrane Endothelial Keratoplasty Graft Preparation Using the Liquid Bubble Technique with Subtrabecular Hydrodissection: A Retrospective Real-Life Study

Background: Techniques for the preparation of grafts for Descemet membrane endothelial keratoplasty (DMEK) can be classified into those that involve the manual dissection of the Descemet membrane (DM) and those that use an injection of a liquid or a gas to achieve a separation of the DM from the posterior corneal stroma. The purpose of this study was to evaluate the efficiency of the liquid bubble technique. Methods: The success rate of the technique was calculated retrospectively using the operating reports. Video files for each graft preparation were retrieved and the time, number of injections, and number of injections sites required for the hydrodissection were measured. The number of cases in which a manual dissection of the Descemet membrane was necessary was recorded. Information on donor age and graft preservation time were retrieved from the eye bank file. Results: In 58 cases, the success rate was 98.3%. In the 28 procedures where a video was available, the median time for hydrodissection was 4.4 min. The median number of injection sites was 2, with a median number of injections of 3.5. Manual dissection as a rescue technique was performed in 25% of cases, with one case resulting in graft tears. The mean graft diameter was 7.6 mm. The mean donor age was 66 years, and the mean graft storage time was 22 days. Conclusions: The liquid bubble technique can be a fast and valuable choice for DMEK graft preparation, especially in centers where the tissue is prepared in the operating theater.

Evolution of Pancreas Transplantation At A Single Institution-50+ Years and 2500 Transplants.

To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades. The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era. All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year death-censored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

Improve anti-biofilm efficacy of ultrasound by modulating the phase transition of exopolysaccharides

This study focused on the adverse sonochemical effect of ultrasound on biofilm extracellular polysaccharide and the adaptive biofilm responses for ultrasound resistance. Results showed ultrasound triggered phase transition of polysaccharides within biofilm from solation to gelation, which induced following biofilm viscoelasticity enhancement, consequential failure of biofilm removal and bacteria killing. Introducing additional cationic polysaccharide, 1.25 % chitosan, inhibited the ultrasound responsive polysaccharides gelation and biofilm viscoelasticity enhancement, exerted synergistic antibacterial (97.40 %) and antibiofilm (96.38 %) effects with 120 W ultrasound combined on S. aureus biofilm, prolonged the preservation time of milk 2.45 times longer compared with ultrasound alone. These findings indicated the possible mechanism and solution to improve ultrasound efficacy on biofilm control and bacteria suppression, exhibit the promising prospect of ultrasound combined strategy in hygiene issues of food and medical industry

Research on Leaching Cesium from Medium and Low Pollucite Concentrates by the Sulfuric Acid Process

Abstract With the sharp decrease in high-grade pollucite resources, medium and low grade pollucite concentrate will become the main raw material for extracting cesium in the future. The main process conditions for leaching cesium from medium- and low grade pollucite concentrate by the sulfuric acid process were studied, and the effects of the ratio of leaching liquid to solid, leaching time, leaching temperature and of leaching liquid on the leaching rate of cesium were investigated. The results show that CsAl(SO4)2·3H2O is formed from 2Cs2O·2Al2O3·9SiO2·H2O after the medium and low grade pollucite concentrates are leached by sulfuric acid. The optimum conditions for the leaching process were as follows: the concentration of sulfuric acid was approximately 3.5 mol/L, L/S≈2, the leaching temperature was 120 °C, the heat preservation time was 2.0 h, and the leaching rate of cesium exceeded 93%. The leaching residue was washed and discarded, and the leaching solution was recycled three times and then concentrated to precipitate alum. The [Cs] in the mother liquor resulting from CsAl(SO4)2·3H2O crystallization ranged from 1 g/L to 1.28 g/L, and the [Al] ranged from 0.29 g/L to 0.33 g/L, which could be recycled for leaching.

Are there any benefits of prolonged hypothermic oxygenated perfusion? - Results from a national retrospective study.

Dual hypothermic oxygenated perfusion (DHOPE) is increasingly being used to extend liver preservation to improve transplant logistics. However, little is known about its benefits in high-risk liver grafts. This study aimed to investigate whether prolonged DHOPE provides benefits other than improved logistics in all liver types. We performed a national retrospective cohort study of 177 liver transplants from 12 Italian centers preserved with DHOPE for ≥4h between 2015 and 2022. A control group of 177 DHOPEs of <4h during the same period was created using 1:1 propensity score matching. The impact of risk profiles and preservation times on the outcomes was assessed using univariable and multivariable regression models. No significant differences in post-transplant outcomes were found between prolonged and short DHOPEs. However, the prolonged group had a significantly lower incidence of post-transplant acute kidney injury (AKI) compared to the short group (30.5% vs. 44.6%, p=0.008). Among prolonged DHOPEs, no differences in transplant outcomes were observed according to donor risk index (DRI), Eurotransplant definition for marginal grafts, and balance of risk (BAR) score. DHOPE duration was associated with a lower risk of AKI in multivariable models adjusted for DRI, Eutrotransplant marginal grafts, and BAR score. Prolonged HOPE confirmed its protective effect against AKI in a multivariable model adjusted for donor and recipient risk factors [OR: 0.412, 95%CI: 0.200-0.850, p=0.016]. Prolonged DHOPE is widely used to improve transplant logistics, provides good results with high-risk grafts, and appears to be associated with a lower risk of post-transplant AKI. These results provide further insight into the important role of DHOPE in preventing post-transplant complications.

Matched pair analysis of the effect of longer hypothermic machine perfusion time on kidney transplant outcomes.

Hypothermic machine perfusion (HMP) has demonstrated benefits in terms of early kidney transplant function compared to static cold storage. While longer preservation times have shown detrimental effects, a previous paired study indicated that longer pump times (the second kidney in a pair) might lead to improved outcomes. To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience. A total of 61 pairs of transplant recipients who received kidneys from the same donor (2012-2021) were analyzed. Patients were divided into two groups depending on whether they were transplanted first (K1) or second (K2). Therefore, the patients in each pair had identical donor characteristics, except for time on the pump. Statistical analyses included Kaplan-Meyer analysis and paired tests, including McNemar's test, student's paired t-test, or Wilcoxon's test, as appropriate. The two groups of recipients had similar demographics (age, body mass index, diabetes, time on dialysis, sensitization and retransplants). Cold ischemic times for K1 and K2 were 8.9 (95%CI: 7.9, 9.8) and 14.7 hours (13.7, 15.8) (P < 0.0001), respectively. Overall, K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year (P = 0.015). Delayed graft function was less common in K2, 12/61 (20%) than in K1, 20/61 (33%) (P = 0.046). Finally, K2 showed a higher graft survival than K1 (P = 0.023). Our results agree with a previous study that suggested possible advantages to longer pump times. Both studies should encourage further research into HMP's potential anti-inflammatory effect.

The Rationale for Combining Normothermic Liver Machine Perfusion with Continuous Renal Replacement Therapy to Maintain Physiological Perfusate during Ex Vivo Organ Perfusion.

Background: The possibility of keeping liver grafts viable and functioning until transplantation has been explored since the 1950s. However, the current modalities of Normothermic Machine Perfusion (NMP) have shown several limitations, such as the inability to correct electrolytes and pH derangements efficiently. Combining NMP with continuous kidney replacement therapy (CKRT) might provide a promising new model to overcome these issues. Methods: An NMP that covers the organ perfusion, oxygenation, carbon dioxide removal, and thermal balance was connected to a CKRT circuit to ensure physiological hydro-electrolytes, acid-base balance, and catabolite removal from the perfusate. Results: The integration of NMP and CKRT maintains a neoplastic liver in a perfusion system with physiological perfusate for 100 h. CKRT re-established and maintained the hydro-electrolyte and acid-base status throughout the 100 h of perfusion. Significant limitations were the need for frequent monitoring of electrolytes and acid-base disorders and the loss of low molecular weight nutrients, which have to be replenished by manual infusion into the system. Conclusions: This novel CKRT-NMP integrated system may represent a practical and versatile model to support organs' perfusion and extend preservation times. Further experiments are needed to fix monitoring and adjusting processes.

Effects of Storage Time and Temperature on the Fermentation Characteristics of Rumen Fluid from a High-Forage Diet

The objective of this experiment was to investigate the effects of storage temperature and preservation time on the fermentation characteristics of rumen fluid collected from six Hu sheep fed a high-forage diet. The storage temperatures were set at −80 °C and −20 °C, and the preservation times were labelled as follows: 0 d (fresh rumen fluid, D0), 7 d (D7), 14 d (D14), 30 d (D30), 60 d (D60), 120 d (D120), and 240 d (D240). A repeated-measures design was applied to analyze the fermentation characteristics of rumen fluid across each preservation time point and storage temperature. The results showed that storage temperature had no significant effects on pH value, ammonia nitrogen (NH3-N), microbial protein (MCP), and volatile fatty acid (VFA) concentration and proportion (p &gt; 0.05). Specifically, the pH value increased on D7, D14, and D60 (p &lt; 0.05), while the MCP concentration decreased on D7, D14, D30, D120, and D240 but increased on D60 (p &lt; 0.05), and the concentration of NH3-N decreased on D14 (p &lt; 0.05). The acetate concentration increased on D30, while the concentrations of propionate, butyrate, valerate, and total VFA increased on D60 (p &lt; 0.05). The concentration of isovalerate decreased on D60, and isobutyrate and branched-chain VFA concentrations decreased on D120 (p &lt; 0.05). The proportion of acetate increased on D30, while the butyrate and valerate proportions increased on D60, and the proportions of isovalerate, isobutyrate, and branched-chain VFA decreased on D60 (p &lt; 0.05). For rumen fluid from a high-forage diet, the storage temperature (−80 °C and −20 °C) did not affect its fermentation characteristics, suggesting that rumen fluid could be preserved at −80 °C or −20 °C without altering its fermentation characteristics. The fermentation parameters of rumen fluid changed significantly after 7 days of preservation; hence, it is recommended to finish determining the fermentation parameters of rumen fluid within 7 days of collection. The concentrations and proportions of most VFA changed after 30 days of preservation; therefore, it is recommended that VFA determination should be completed within 30 days of rumen fluid collection.

Profiles of differential expression of miRNAs in the late stage of red blood cell preservation and their potential roles

ObjectiveTo detect the differentially expressed regulatory miRNAs in the late stage of red blood cell (RBC) preservation and predict their roles. MethodsSuspended RBCs with different storage periods of 35 day, 42 day, and 50 day were collected for routine blood tests, RNA extraction, and preparation of small RNA sequencing libraries. The constructed libraries were sequenced and the biological functions of differential miRNAs in RBCs in the late storage were analyzed by bioinformatics. ResultsRoutine indicators of RBCs in the late stage were not significantly affected by preservation time. The Pearson correlation analysis performing on RBC miRNAs with different storage days revealed that RBC miRNAs changed with the increase of storage days. RBC miRNAs from day 35 (D35), day 42 (D42) and day 50 (D50) showed significant differences (P < 0.05). Compared RBC miRNAs from D42 with these from D35, there were 690 up-regulated miRNAs and 82 down-regulated miRNAs; compared RBC miRNAs from D50 with these from D35, there were 638 up-regulated miRNAs and 123 down-regulated miRNAs; compared RBC miRNAs from D42 with these from D50, there were 271 up-regulated miRNAs and 515 down-regulated miRNAs. GO enrichment analysis of target genes of differential miRNAs were mainly involved in cell metabolism, biosynthesis, protein modification, gene expression and transcriptional regulation of biological processes. KEGG pathway enrichment analysis of miRNA target genes showed that differential miRNA target genes were closely related to pathways in cancer. ConclusionMiRNAs were differentially expressed in the late stage of RBC preservation, and may be involved in various biological processes, especially cancer.

Trends in infectious adverse events after elective optical keratoplasty (PK, EK, and ALK) - Ten years' analysis from an eye bank.

To report the clinical profile and donor characteristics of post-optical keratoplasty adverse events notified at an eye bank. Between January 2013 and December 2022, 37,041 donor corneas were utilized for keratoplasty, of which 16,531 were used for penetrating keratoplasty (PK), 12,171 for endothelial keratoplasty (EK), and 1356 for anterior lamellar keratoplasty (ALK). EK included 10,956 Descemet stripping automated endothelial keratoplasty (DSAEK) and 1215 Descemet membrane endothelial keratoplasty (DMEK). The adverse events reported within the first 6 weeks of optical keratoplasty were analyzed for donor-related parameters. A total of 41 (0.11%) recipients had post-keratoplasty infections. Of these, 33 occurred after EK (29 after DSAEK, and four after DMEK), two after ALK, and six after PK. The clinical presentation was keratitis alone in 16 eyes and associated with endophthalmitis in 25 eyes. The organisms isolated were gram-negative bacteria in 26 eyes, fungus in eight eyes, gram-positive bacteria in four eyes, mixed infection in five eyes, and microbiology inconclusive in seven eyes. The majority (78%) of the gram-negative infections were due to multidrug-resistant organisms. Most (88%) donor corneas were harvested from hospital premises. The most common cause of donor mortality was trauma. The median duration of presentation from surgery was 4.46 (range: 1-30) days. The death to preservation time was 4.18 (1.5-7.65) hours. The death to utilization time was 3 (2-4.7) days. The overall risk of infectious adverse events after keratoplasty was 0.11%, ranging from 0.08% to 0.36%. Most (80.4%) of the adverse events occurred after EK. The majority (78.9%) of the adverse events were of bacterial etiology, of which gram-negative infections (68.4%) were the most common. The trends and microbiological spectrum of organisms associated with infections should be thoroughly documented in eye banks to gain insights and formulate guidelines on the management of adverse events.

Pathogen producing aflatoxin in contaminated sandwich: Identification and preservation

The toxicity of the contaminated powder contributed to toxic aflatoxins has been well-known in the literature. However, before this study, the specific fungal strain behind aflatoxin production remained unidentified. Our research aimed to isolate and identify fungi from the tainted sandwiches while also assessing the preservation of sandwiches in ambient conditions. The study pinpointed Aspergillus flavus as the fungus responsible for aflatoxin production. Analysis revealed that the sandwich samples contaminated with pure A. flavus exhibited a significant Aflatoxin B1 (AFB1) concentration of 55.2 ± 0.21 ng/g, accompanied by a spore count of 2 × 106 Colony-Forming Unit (CFU)/g after ten days. In contrast, sandwich samples contaminated with the unspecified fungi displayed a lower AFB1 content of 16.21 ± 0.42 ng/g, with a spore count of 2.2 × 102 CFU/g after the same duration. In the prevention study, the efficacy of the ethanol spray method for inhibiting aflatoxin from A. flavus was investigated. Results demonstrated that a 70 % ethanol concentration at a ratio of 2.0 % total weight of the sandwich proved highly effective, significantly impeding fungal growth. This method extended the preservation time by sevenfold compared to the control. Importantly, tests at 2.0 % ethanol of the sandwich weight did not detect aflatoxin presence.

Fabrication and characterization of a chitosan/cyclodextrin/TiO2-NPs composite for preservation of avocados.

In this study, a TiO2 material with nanoparticle size of about 10-20 nm, surface area of 109 m2 g-1 was synthesized using the microwave-assisted hydrothermal method. The chitosan/TiO2 film combined with cyclodextrin (chitosan-cyclodextrin/TiO2, CS-CD/TiO2NPs) helps significantly improve the mechanical properties and enhance the antibacterial activity of the polymer film. Furthermore, the content of TiO2 nanoparticles in CS-CD/TiO2NPs also affects the tensile strength, antibacterial activity, ripening rate, ethylene production rate, and water vapor permeability during food preservation of the CS-CD film that has been studied. The CS-CD/TiO2NPs film is effective against Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aereus) reaching over 99.5% after 15 min of contact. The preservation ability of avocados coated with CS-CD/TiO2NPs was evaluated through some physiological parameters of the avocados, such as sensory evaluation, weight loss, and hardness. The results show that the use of CS-CD/TiO2NPs films extends the preservation time of avocados up to 7 days under conditions of 30 °C and 80% relative humidity.

Innovations in transplant techniques for complex anomalies.

With advances in the field of congenital cardiac surgery and in the management of congenital heart defects in early life, the population of adult congenital heart disease (ACHD) patients is increasing. End-stage heart failure is currently the main cause of cardiovascular mortality and is expected to increase in the coming years. This review summarizes recent innovations in transplant techniques, with special attention to what is known in the population of ACHD recipients. The use of machine perfusion for heart preservation enables longer preservation times. Normothermic (organ care system - OCS) and hypothermic (hypothermic oxygenated perfusion - HOPE) machine perfusion will alleviate the time pressure associated with heart transplantation in the ACHD population, may allow for expansion of the geographical range in which donors can be matched and may improve graft quality. Donation after circulatory death (DCD) heart transplantation, either through direct procurement-machine perfusion (DP-MP) or thoraco-abdominal normothermic regional perfusion (TA-NRP) is a viable strategy to further expand the donor pool. The use of machine perfusion and DCD donors in ACHD is feasible and shows promise. Time pressure and shortage of donors is even more critical in ACHD than in other patient populations, making these innovations particularly relevant. Further clinical experience and research is needed to elucidate their impact.

Zwitterionic-hydrogel-based sensing system enables real-time ROS monitoring for ultra-long hypothermic cell preservation

Hypothermic preservation (HP) is highly desired for the maintenance of the viability of living cell specimens, e.g. rare cells in whole-blood samples or therapeutic cells, in an unfrozen state. However, the extension of the viable preservation time is a challenge because of the multiple injuries suffered by hypothermically preserved cells. Here, based on a dynamic bond crosslinked zwitterionic hydrogel, we established a sensing preservation system that could monitor the levels of reactive oxygen species (ROS) via real-time electronic signals and intelligent control of antioxidant addition, to completely prevent an excess of ROS in the whole-cell specimen. Furthermore, the hydrogel-based system can counter the extracellular-matrix-loss-induced anoikis of living cells. Based on the design aimed at affording protection against two primary HP injuries (i.e. ROS overproduction and anoikis) to cells, this system extended the preservation time of cell specimens under refrigerated conditions to 24 days. After preservation, the use of a mild cell retrieval process guaranteed the activity of the preserved living cells. This work not only possesses the potential to facilitate intelligent cell-based clinical applications, but also paves the way for the preparation of living materials that can host programmed cells with long-term survival. Statement of significanceAn intelligent system based on a zwitterionic sensing hydrogel is established, which can afford ultra-long hypothermic cell-preservation times of up to 24 days. The system enables the real-time monitoring of ROS overproduction and intelligent antioxidant addition, because of the merging of the smart hydrogel with a computer intelligent detection and control system. Furthermore, the automatic addition of an antioxidant according to the ROS-signal changes produced by the ZBA hydrogel effectively prevented HP lesions, including ROS over-production and ECM loss, in the preserved living cells. Subsequently, the system could also be gently dissociated, to retrieve the preserved cells. This work provides a solution for the real-time monitoring and long-term HP of living specimens, which holds the promise of benefiting cell-based medicine and the development of genetically programmed cell-based living materials.

Effect of Post-Weld heat treatment on residual stress in deck-rib double-side welded joints and process optimization

Post-weld heat treatment (PWHT) is expected to release the welding residual stress (WRS) of deck-rib double-side welded joints in orthotropic steel decks (OSDs). In this paper, the WRS distribution of deck-rib double-side welded joints before and after PWHT is evaluated by hole drilling method and numerical simulation, and the effect of PWHT parameters on WRS relaxation is further compared, and reasonable parameters are suggested. Based on the principle of WRS relaxation by PWHT, the feasibility of secondary continuous PWHT was explored. The results show that PWHT can effectively release the WRS and make the distribution more uniform. Extending the heat preservation time and increasing the temperature can release more WRS, and the heating and cooling rate has little influence on the WRS, so it is recommended to use the specified maximum value. The effect of secondary continuous PWHT is slight, and it is not recommended for use.

Cardiac Loading using Passive Left Atrial Pressurization and Passive Afterload for Graft Assessment.

Ex vivo machine perfusion or normothermic machine perfusion is a preservation method that has gained great importance in the transplantation field. Despite the immense opportunity for assessment due to the beating state of the heart, current clinical practice depends on limited metabolic trends for graft evaluation. Hemodynamic measurements obtained from left ventricular loading have garnered significant attention within the field due to their potential as objective assessment parameters. In effect, this protocol provides an easy and effective manner of incorporating loading capabilities to established Langendorff perfusion systems through the simple addition of an extra reservoir. Furthermore, it demonstrates the feasibility of employing passive left atrial pressurization for loading, an approach that, to our knowledge, has not been previously demonstrated. This approach is complemented by a passive Windkessel base afterload, which acts as a compliance chamber to maximize myocardial perfusion during diastole. Lastly, it highlights the capability of capturing functional metrics during cardiac loading, including left ventricular pulse pressure, contractility, and relaxation, to uncover deficiencies in cardiac graft function after extended periods of preservation times (˃6 h).

Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer

BackgroundRecent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes.MethodsIn this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0–4; 4–8; 8–12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3–4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8–12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org.DiscussionBuilding on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer.Trial registrationClinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Kato-Katz slide preservation technique: Extension of viability and the benefits for schistosomiasis control programs

The World Health Organization recommends the use of the Kato-Katz method in the procedures of schistosomiasis control programs. Studies show the importance of a fast reading of the slides due to the decline of their viability, with the appearance of fungi or desiccation of the sample, which hinders diagnosis. It is necessary to establish a procedure to improve the long-term preservation of these Kato-Katz slides in order to accomplish the following: (1) preserve the slides for future quality control procedures and readings; (2) allow for the production of durable materials for training; and (3) train health professionals involved in diagnosing schistosomiasis. Therefore, this study aims to test a slide preservation methodology for these purposes. The results showed that the modifications made to the experimental slides demonstrated that egg loss was within the expected range and the limit accepted by quality control standards, as well as improved the diagnostic durability of the slides during the preservation times tested. We concluded that the application of the preservation technique to the slides promoted stabilization and permanence for long-term storage.