Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older.

INTRODUCTION AND OBJECTIVES: Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies (OT-0401, REVERSE, CONFIRM). PATIENTS AND METHODS: The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal-defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 µmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death-and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events. RESULTS: Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data. CONCLUSIONS: Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome. CLINICAL TRIAL NUMBERS: OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT02770716.

Prevalence of anxiety and depression in medical students of a public sector medical college in Islamabad and coping mechanisms adopted.

The objectives of this study were to find out the frequency of anxiety and depression in medical students and various coping mechanisms adopted by them to identify the coping trends and to stress the need of equipping these students with positive coping tools to deal with anxiety and depression. A cross-sectional, questionnaire-based observational study was conducted on a population of 500 medical students of Federal Medical and Dental College, Islamabad. The duration of the study was three months. By using the WHO sample size calculator, taking the confidence level 95%, anticipated population proportion 70% and absolute precision required 7%, the sample size was calculated at 165. The samples were collected by non-probability consecutive sampling via a questionnaire. In the study, two instruments were used: 1) Aga Khan University Anxiety and Depression Scale (AKUADS), and 2) Brief Cope Inventory. Self-administered questionnaires were filled by the students and the data collected from these questionnaires was analysed on SPSS version 19. Out of the sample size of 165 (98 female, 67 male) students, excluding 12 students with previous history of mental and physical illness, the prevalence of depressed students found after calculating their scores according to the Aga Khan Anxiety and Depression Scale (AKUADS score ≥19) was 95 (57.57%). The most used positive coping mechanisms by these students were religion (5.55±1.91), acceptance (5.28±1.56), planning (5.27±1.58) and active coping (4.85±1.45). The most used negative coping mechanisms were self-blame (5.52±1.83), self-distraction (5.29±1.56), and venting (4.67±1.49). The high presence of negative coping mechanisms indicates the urgency of the need for proper counselling and guidance of medical students about dealing correctly with anxiety and depression.

Evaluation of wound healing potential and biochemical estimation of sage oil nanoemulsion on animal model.

The study was aimed to design a nano emulsion formulations of Sage oil and to determine its effectiveness in healing the wound using rats as a model. Sage oil nanoemulsion (o/w) was formulated by a spontaneous emulsification method and tested for physicochemical parameters. The wound creation methods namely; circular excision and linear incision were utilized in the present study. Many specifications like tensile strength, DNA, total protein, Hexosamine and Uronic acid, were estimated from the tissues collected from incised wounds. The antioxidant and antimicrobial activity of the oil was estimated from the wound tissue homogenate. Finally epithelialization period and concentration of TNF-α were also measured. A Significant rise in collagen content by 77.52% and tensile strength by 56.20% were noticed in comparison to control. Reduction in period of epithelialization was noticed by 42.85% in comparison to control. The treatment groups confirmed significant antimicrobial activity in comparison to control. It was evident from the results that Sage oil nano emulsion could be the accelerator in wound healing process and it may be devoid of other drawbacks which would be possible with synthetic drug.

C-peptide levels do not correlate with pancreas allograft failure: Multicenter retrospective analysis and discussion of the new OPT definition of pancreas allograft failure.

The OPTN Pancreas Transplantation Committee performed a multicenter retrospective study to determine if undetectable serum C-peptide levels correspond to center-reported pancreas graft failures. C-peptide data from seven participating centers (n = 415 graft failures for transplants performed from 2002 to 2012) were analyzed pretransplant, at graft failure, and at return to insulin. One hundred forty-nine C-peptide values were submitted at pretransplant, 94 at return to insulin, and 233 at graft failure. There were 77 transplants with two available values (at pretransplant and at graft failure). For recipients in the study with pretransplant C-peptide <0.75 ng/mL who had a posttransplant C-peptide value available (n = 61), graft failure was declared at varying levels of C-peptide. High C-peptide values at graft failure were not explained by nonfasting testing or by individual center bias. Transplant centers declare pancreas graft failure at varying levels of C-peptide and do not consistently report C-peptide data. Until February 28, 2018, OPTN did not require reporting of posttransplant C-peptide levels and it appears that C-peptide levels are not consistently used for evaluating graft function. C-peptide levels should not be used as the sole criterion for the definition of pancreas graft failure.

Kidney allograft survival outcomes in combined intestinal-kidney transplant: An analysis of the UNOS/OPTN database 2000-2014.

BACKGROUND AND OBJECTIVES: Intestinal transplants carry a high morbidity/mortality. Kidney allograft outcomes after combined intestinal (IT) with kidney transplant (CIKT) remain largely uninvestigated. MATERIALS AND METHODS: The UNOS STAR database was queried to identify all such combined organ transplants from 2000 to 2015. RESULTS: Out of a total 2215 (51.4% peds vs 48.6% adults) intestinal transplants, 111 (5.0%) CIKT were identified (32.4% peds vs 67.6% adults). Over the study period of CIKT, a total of 45.9% of these cases died with a functioning kidney graft. DGF rate was 9.0%. The 1-year reported kidney acute rejection rate was 6.3%. For the entire CIKT population over the entire study era, the 1-, 3-, and 5-year unadjusted kidney graft survival was 57%, 39%, and 34%, while death-censored kidney graft survival was 93%, 90%, and 86%, respectively. Overall conditional 5-year kidney graft survival (defined as 1-year kidney graft survival) was 58%. Overall, patient survival was significantly lower in recipients of CIKT compared to intestinal transplant (IT) (P < .005); However, the 5-year conditional (1 year kidney graft) patient survival in adults was not significantly different between IT and CIKT overall (P = .194). CONCLUSIONS: Kidney allograft survival is primarily dependent on 1-year patient survival. Guidelines regarding allocation of kidney allografts in CIKT need to take into consideration utility and urgency.

The Multifunctional Role of Chitosan in Horticultural Crops; A Review.

Chitosan is a naturally occurring compound and is commercially produced from seafood shells. It has been utilized in the induction of the defense system in both pre and post-harvest fruits and vegetables against fungi, bacteria, viruses, and other abiotic stresses. In addition to that, chitosan effectively improves the physiological properties of plants and also enhances the shelf life of post-harvest produces. Moreover, chitosan treatment regulates several genes in plants, particularly the activation of plant defense signaling pathways. That includes the elicitation of phytoalexins and pathogenesis-related (PR) protein. Besides that, chitosan has been employed in soil as a plant nutrient and has shown great efficacy in combination with other industrial fertilizers without affecting the soil's beneficial microbes. Furthermore, it is helpful in reducing the fertilizer losses due to its coating ability, which is important in keeping the environmental pollution under check. Based on exhibiting such excellent properties, there is a striking interest in using chitosan biopolymers in agriculture systems. Therefore, our current review has been centered upon the multiple roles of chitosan in horticultural crops that could be useful in future crop improvement programs.

Trends and outcomes in right vs. left living donor nephrectomy: an analysis of the OPTN/UNOS database of donor and recipient outcomes--should we be doing more right-sided nephrectomies?

BACKGROUND: Discussion continues about right vs. left donor nephrectomy (LDN). Left side is preferred due to longer renal vein while right side has been associated with renal vein thrombosis and shorter vessels. METHODS: A retrospective analysis of UNOS database for adult living donor transplants between 1 January 2000 and 31 December 2009. RESULTS: We identified 58 599 living donor transplants, of which 86.1% were LDN. There were no significant differences between the recipients or donors demographics. There were higher rates of delayed graft function in right donor nephrectomy (RDN) recipients with a hazard risk of 1.38 (95% CI 1.24-1.53; p < 0.0001). Primary failure rates were similar. In the RDN group, graft thrombosis as cause of graft failure was statistically higher with a hazard ratio of 1.48 (95% CI 1.18-1.86, p = 0.0004), and graft survival was significantly inferior (p = 0.006 log-rank test). For living donors outcomes, the conversion from laparoscopic to open was higher in the RDN group with an odds ratio of 2.02 (95% CI 1.61-2.52; p < 0.00001). There was no significant difference in vascular complications or re-operation required due to bleeding. Re-operations and re-admissions were higher in the LDN group. CONCLUSION: There are statistical differences between left and right kidney donor nephrectomies on recipient outcomes, but the difference is extremely small. The choice and laterality should be based on center and surgeon preference and experience.

Re-transplants compared to primary kidney transplants recipients: a mate kidney paired analysis of the OPTN/UNOS database.

Outcomes of kidney re-transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre-emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death-censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.

GENDER INFLUENCES DIFFERENTIATION OF CHITIN AMONG BODY PARTS.

Earlier reports have established that chitin isolates from each body part of an insect cuticle can exhibit diverse physicochemical properties. But it is still unknown if the gender of the insect can influence characteristics of chitin isolates from different body parts. The present study addresses this question. As a result, important physicochemical differences in the chitin samples from different body parts of Melolontha sp. were recorded on the basis of sex. The chitin samples were extracted from eight different body parts (antennae, head, eyes, thorax, abdomen, elytra, hindwings, and legs) of female and male. The most remarkable variations in the chitin isolates from female and male body parts were recorded in chitin content, crystallinity, thermal stability, and surface morphology. And also it was wondered these chitin isolates from different body parts of female and male could find different applications. To check this hypothesis, the chitin samples from female and male were interacted with bovine serum albumin (BSA) protein and important variations were observed.

Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.

Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p < 0.0001), 12 months (p < 0.0001), and from post-6 to post-12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.

Long-term outcomes of transplant recipients referred for angiography for suspected transplant renal artery stenosis.

Our aim was to study the long-term outcomes of all transplant recipients who underwent angiography for suspected TRAS at our institution. The patients were divided into TRAS+ve and TRAS-ve groups based upon angiographically confirmed results. TRAS was confirmed in 58.1% of 74 patients with median time of 8.9 months. Primary angioplasty alone was performed in 56% of patients with TRAS, while the remaining had PTA with stent (PTAS). There was reduction in systolic and diastolic BP (165 ± 19-136 ± 15 mmHg and 82 ± 14 mmHg to 68 ± 12 mmHg; p < 0.05) and number of antihypertensive drugs (3.5 ± 0.9-2.7 ± 1.0; p < 0.05). Overall, graft survival and patient survival from time of transplant were similar in both groups. Graft function was similar for the patients with treated TRAS+ve as compared to TRAS-ve over time. Graft survival and patient survival when compared to an age- and year of transplant-matched cohort control group were also similar. In conclusion, angiography for suspected TRAS is more likely to yield a confirmatory result early in the transplant course as compared to late. Treatment of TRAS in these patients had sustained long-term graft function. Alternative etiologies of HTN and graft dysfunction should be sought for recipients further out from transplant.

Late pancreas retransplantation.

Pancreas retransplantation, excluding immediate retransplantation for graft thrombosis, is a technically treacherous operation with the added challenges of adhesions from the prior transplant and difficulties identifying usable recipient vessels. The goal of this study was to review our single-center experience with late pancreas retransplantation. Charts for all pancreas transplant recipients between 01/2003 and 04/2013 were reviewed for demographics, graft and patient survival, length of stay (LOS), readmissions, and technical complications. Of 473 pancreas transplants, there were 20 late pancreas retransplants compared to 441 first transplants. There were no significant differences in donor or recipient demographics. There was no significant difference in graft or patient survival. The mean and median lengths of stay were 22 and nine d, respectively (range 5-175 d), and 11 recipients required readmission within the first three months post-transplant. Five patients were reexplored in the early postoperative period for an enteric leak at the site of the primary allograft (n = 1), complications of percutaneous gastrostomy tube placement (n = 1), hemorrhage (n = 1), and negative laparotomy for hyperglycemia (n = 2). Pancreas retransplantation is technically challenging but can be safely performed with graft and recipient survival comparable to primary transplants.

Pre-transplant angiotensin receptor II type 1 antibodies and risk of post-transplant focal segmental glomerulosclerosis recurrence.

Post-kidney transplant recurrence of focal segmental glomerulosclerosis (FSGS) is a major problem. AT1R is expressed on podocyte; its expression is elevated in the proteinuric state. Using an ELISA, we tested pre-transplant sera of 28 patients with history of idiopathic FSGS for anti-AT1R levels and serum soluble urokinase-type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence of FSGS. Sera from 11 patients with polycystic kidney disease (PKD) were used as controls. Twelve patients had biopsy proven post-transplant FSGS recurrence at 1.5 months. No difference was found in the pre-transplant suPAR levels of FSGS patients (5993 ± 2292 pg/mL) vs. PKD (7334 ± 4538 pg/mL) (p = 0.23). Serum suPAR levels in patients with FSGS recurrence (5786 ± 1899 pg/mL) vs. no FSGS recurrence (6149 ± 2598 pg/mL) (p = 0.69) were not different. Anti-AT1R levels in patients with FSGS were 12.66 ± 11.85 U/mL vs. 8.69 ± 6.52 U/mL in PKD (p = 0.32); however, a difference was found in patients with and without FSGS recurrence 20.41 ± 14.36 U/mL 6.84 ± 4.181 U/mL, respectively (p < 0.01). Area under curve for suPAR and anti-AT1R to predict post-transplant FSGS recurrence was 0.51 and 0.84, respectively. Pre-transplant anti-AT1R levels appear to be a helpful biomarker in identifying patients at high risk of post-transplant FSGS recurrence.

Correlation between CT-based measured renal volumes and nuclear-renography-based split renal function in living kidney donors. Clinical diagnostic utility and practice patterns.

INTRODUCTION: Living donor evaluation involves imaging to determine the choice of kidney for nephrectomy. Our aim was to study the diagnostic accuracy and correlation between CT-based volume measurements and split renal function (SRF) as measured by nuclear renography in potential living donors and its impact on kidney selection decision. METHODS: We analyzed 190 CT-based volume measurements in healthy donors, of which 65 donors had a radionuclide study performed to determine SRF. RESULTS: There were no differences in demographics, anthropometric measurements, total volumes, eGFR, creatinine clearances between those who required a nuclear scan and those who did not. There was a significant correlation between CT-volume-measurement-based SRF and nuclear-scan-based SRF (Pearson coefficient r 0.59; p < 0.001). Furthermore, selective nuclear-based SRF allowed careful selection of donor nephrectomy, leaving the donor with the higher functioning kidney in most cases. There was also a significantly higher number of right-sided nephrectomies selected after nuclear-based SRF studies. CONCLUSION: CT-based volume measurements in living donor imaging have sufficient correlation with nuclear-based SRF. Selective use of nuclear-scan-based SRF allows careful selection for donor nephrectomy.

Lignin beyond the status quo: recent and emerging composite applications.

The demand for biodegradable materials across various industries has recently surged due to environmental concerns and the need for the adoption of renewable materials. In this context, lignin has emerged as a promising alternative, garnering significant attention as a biogenic resource that endows functional properties. This is primarily ascribed to its remarkable origin and structure that explains lignin's capacity to bind other molecules, reinforce composites, act as an antioxidant, and endow antimicrobial effects. This review summarizes recent advances in lignin-based composites, with particular emphasis on innovative methods for modifying lignin into micro and nanostructures and evaluating their functional contribution. Indeed, lignin-based composites can be tailored to have superior physicomechanical characteristics, biodegradability, and surface properties, thereby making them suitable for applications beyond the typical, for instance, in ecofriendly adhesives and advanced barrier technologies. Herein, we provide a comprehensive overview of the latest progress in the field of lignin utilization in emerging composite materials.

The learning curve of COVID-19 and organ donation: Potential missed opportunities in the COVID era.

Background: Early in the COVID-19 pandemic, positive COVID-19 status often disqualified potential organ donors due to perceived risks, despite limited evidence. Subsequent studies have clarified that the COVID-19 status of donors, particularly when incidental and not the cause of death, does not adversely affect non-lung transplant outcomes. This study quantifies the potential loss of eligible organ donors and the corresponding impact on organ availability during the initial phase of the pandemic. Methods: In this retrospective analysis, we examined deceased donor referrals to a major organ procurement organization from June 2020 to January 2022. Referrals were categorized as All Referrals, Medically Ruled Out (MRO), or Procured Donors (PD). We used Chi-square tests for categorical comparisons and logistic regression to model additional donors and organs, contrasting COVID-negative and positive cases within age-matched cohorts. Results: Among 9478 referrals, 23.4 % (2221) were COVID-positive. Notably, COVID-positive referrals had a substantially higher MRO rate (80.6 % vs. 29.6 %, p < 0.01) and a markedly lower PD rate (0.2 % vs. 8.2 %, p < 0.01). Potential missed donations of 103 organs from COVID-positive referrals were identified. Conclusion: This OPO-level study demonstrates a substantial impact of COVID-19 status on organ donation rates, revealing significant missed opportunities. Improved management of donor COVID-19 status could potentially increase organ donations nationwide, taking into account evolving evidence and vaccine availability changes.

Beyond prevention: Unveiling the benefits of triple vaccination on COVID-19 severity and resource utilization in solid organ transplant recipients.

OBJECTIVE: Despite the widespread reduction in COVID-19-related morbidity and mortality attributed to vaccination in the general population, vaccine efficacy in solid organ transplant recipients (SOTR) remains under-characterized. This study aimed to investigate clinically relevant outcomes on double and triple-vaccinated versus unvaccinated SOTR with COVID-19. STUDY DESIGN AND SETTING: A retrospective propensity score-matched cohort study was performed utilizing data from the US Collaborative Network Database within TriNetX (n = 117,905,631). We recruited vaccinated and unvaccinated (matched controls) SOTR with COVID-19 over two time periods to control for vaccine availability: December 2020 to October 2022 (bi-dose, double-dose vaccine effectiveness) and December 2020 to April 2023 (tri-dose, triple-dose vaccine effectiveness). A total of 42 factors associated with COVID-19 disease severity were controlled for including age, obesity, diabetes, and hypertension. We monitored 30-day outcomes including acute respiratory failure, intubation, and death following a diagnosis of COVID-19. RESULTS: Subjects were categorized into two cohorts based on the two time periods: bi-dose cohort (vaccinated, n = 462; unvaccinated, n = 20,998); tri-dose cohort (vaccinated, n = 517; unvaccinated, n = 23,061).Compared to unvaccinated SOTR, 30-day mortality was significantly lower for vaccinated subjects in both cohorts: tri-dose (2.0% vs 7.5%, HR = 0.22 [95% CI: 0.11, 0.46]); bi-dose (3.7% vs 8.2%, HR = 0.43 [95% CI: 0.24, 0.76]). Hospital admission rates were similar between bi-dose vaccinated and unvaccinated subjects (33.1% vs 28.6%, HR = 1.2 [95% CI: 0.95, 1.52]). In contrast, tri-dose vaccinated subjects had a significantly lower likelihood of hospital admission (29.4% vs 36.6%, HR = 0.74 [95% CI: 0.6, 0.91]). Intubation rates were significantly lower for triple-vaccinated- (2.3% vs 5.2%, p < 0.05), but not double-vaccinated subjects (3.0% vs 5.2%, p > 0.05). CONCLUSION: In solid organ transplant recipients with COVID-19, triple vaccination, but not double vaccination, against SARS-CoV-2 was associated with significantly less hospital resource utilization, decreased disease severity, and fewer short-term complications. These real-world data from extensively matched controls support the protective effects of COVID-19 vaccination with boosters in this vulnerable population.