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.

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.

Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective.

Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx®) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx®. Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively (p = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all p = 0.01), however, no difference was found for SCr and proteinuria (p > 0.05). The AUC was 0.80 (95% CI: 0.69-0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx® was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx®, and histology has aided in early diagnosis and timely individualized intervention.

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.

Antibody Therapeutics as Interfering Agents in Flow Cytometry Crossmatch for Organ Transplantation.

Donor-recipient matching is a highly individualized and complex component of solid organ transplantation. Flowcytometry crossmatching (FC-XM) is an integral step in the matching process that is used to detect pre-formed deleterious anti-donor immunoglobulin. Despite high sensitivity in detecting cell-bound immunoglobulin, FC-XM is not able to determine the source or function of immunoglobulins detected. Monoclonal antibody therapeutic agents used in a clinic can interfere with the interpretation of FC-XM. We combined data from the prospectively maintained Antibody Society database and Human Protein Atlas with a comprehensive literature review of PubMed to summarize known FC-XM-interfering antibody therapeutics and identify potential interferers. We identified eight unique FC-XM-interfering antibody therapeutics. Rituximab (anti-CD20) was the most-cited agent. Daratumuab (anti-CD38) was the newest reported agent. We identified 43 unreported antibody therapeutics that may interfere with FC-XM. As antibody therapeutic agents become more common, identifying and mitigating FC-XM interference will likely become an increased focus for transplant centers.

Understanding the effects of chitosan, chia mucilage, levan based composite coatings on the shelf life of sweet cherry.

Sweet cherry (Prunus avium L.) fruits are prone to quality and quantity loss in shelf-life conditions and cold storage due to their short post-harvest life. Until now efforts have been made to extend the shelf life of the sweet cherry. However, an efficient and commercially scalable process remains elusive. To contribute to this challenge, here in this study, biobased composite coatings consisting of chitosan, mucilage, and levan, were applied on sweet cherry fruits and tested for postharvest parameters in both market and cold storage conditions. Results demonstrated that the shelf life of sweet cherries can be extended until the 30th day while retaining important post-harvest properties like decreased weight loss, fungal deterioration, increased stem removal force, total flavonoid, l-ascorbic acid, and oxalic acid. Given the cost-effectiveness of the polymers used, the findings of this study indicate the feasibility of extending the shelf-life of sweet cherries on a larger scale.

Intra-Peritoneal Pseudocyst as a Rare Complication After Peritoneal Dialysis: The Use of a Staged Surgical Approach in Management.

Despite its numerous benefits, peritoneal dialysis (PD) can rarely result in dangerous and even life-threatening complications, including peritonitis, hernias, encapsulating peritoneal sclerosis (EPS), and rarely peritoneal pseudocysts. Herein, we present a rare case of a giant intra-peritoneal pseudocyst that presented four months following the discontinuation of a 5-year course of complicated PD. Despite the initially successful drainages, the patient's symptoms continued to recur, and the imaging findings were concerning for underlying neoplastic processes. As such, a staged surgical approach was performed, starting with a diagnostic laparoscopy and was subsequently followed with cyst excision and marsupialization to the peritoneal cavity. While previous reports of such rare pseudocyst have been documented in the literature as a complication of PD, to our knowledge, this is the second case of pseudocyst formation to occur months after the discontinuation of PD therapy. This case emphasizes the importance of close follow-up in PD patients and showcases how a staged surgical approach can be utilized to accurately diagnose and manage such complicated cases.

The Current State of Donor-Derived Cell-Free DNA Use in Allograft Monitoring in Kidney Transplantation.

Renal transplantation is the definitive therapy for patients suffering from end-stage renal disease. Though there have been significant advances in immunosuppression in these patients, there is still up to 30% acute and subclinical rejection. Current standards employ lab markers of renal function and biopsy results for accurate diagnosis. However, donor derived cell-free DNA has been identified as a measurable lab test that may be able to adequately diagnose rejection at early stages, precluding the need for invasive procedures like biopsy. We obtained published data directly from companies that offer ddcfDNA assay tests and additionally conducted a literature review using databases like PUBMED and NIH U.S. National Library of Medicine. We comprehensively compare the most used ddcfDNA assays, delineate their respective limitations, and further explore future directions in the utility of ddcfDNA in renal transplant patients.

A case series of perioperative anaphylaxis to cefazolin during kidney transplant and review of literature.

BACKGROUND: Intraoperative anaphylaxis is a life threatening and multiorgan system hypersensitivity reaction that frequently leads to cessation of operations. Despite the incidence of Cefazolin allergy being on the rise, the cases of anaphylaxis to Cefazolin during surgeries and its management are seldom reported. CASE PRESENTATION: We present two patients with no known beta-lactam allergy and end stage kidney disease who received perioperative intravenous Cefazolin for planned deceased kidney transplant surgery at our academic medical center. Both patients developed anaphylaxes approximately three minutes following the administration of the antibiotic and experienced severe, refractory hypotension that required the use of vasopressors. The severity of the anaphylactic reactions resulted in the cessation of the transplant operation and multiple days of intensive care unit admission. CONCLUSION: Peri-or intraoperative anaphylaxis to Cefazolin is on the rise and its consequences in transplant candidates are even more dire given the pre-existing end organ failure, financial burden for health care system, potential loss of donor organs, and emotional burden for recipients and their families. These are the first two cases of reported Cefazolin-induced anaphylaxis that actually resulted in aborting the kidney transplant operation. In addition, cases of previously reported Type 1 hypersensitivity to Cefazolin as prophylaxis for operations were reviewed and the allergy workups were discussed.

Trends and challenges in the development of bio-based barrier coating materials for paper/cardboard food packaging; a review.

Currently, petroleum-based synthetic plastics are used as a key barrier material in the paper-based packaging of several food and nonfood goods. This widespread usage of plastic as a barrier lining is not only harmful to human and marine health, but it is also polluting the ecosystem. Researchers and food manufacturers are focused on biobased alternatives because of its numerous advantages, including biodegradability, biocompatibility, non-toxicity, and structural flexibility. When used alone or in composites/multilayers, these biobased alternatives provide strong barrier qualities against grease, oxygen, microbes, air, and water. According to the most recent literature reports, biobased polymers for barrier coatings are having difficulty breaking into the business. Technological breakthroughs in the field of bioplastic production and application are rapidly evolving, proffering new options for academics and industry to collaborate and develop sustainable packaging solutions. Existing techniques, such as multilayer coating of nanocomposites, can be improved further by designing them in a more systematic manner to attain the best barrier qualities. Modified nanocellulose, lignin nanoparticles, and bio-polyester are among the most promising future candidates for nanocomposite-based packaging films with high barrier qualities. In this review, the state-of-art and research advancements made in biobased polymeric alternatives such as paper and board barrier coating are summarized. Finally, the existing limitations and potential future development prospects for these biobased polymers as barrier materials are reviewed.

Donor-directed immunologic safety of COVID-19 vaccination in renal transplant recipients.

Infection risk and COVID-19 outcomes make SARS-CoV-2 vaccination essential forsolid-organ transplant recipients. Reports of immune activation after vaccination causing graft failure raise concerns, but data are limited. Here, we document graft function, donor-derived-cell-free-DNA(dd-cfDNA), and donor-specific antibodies (DSA) in solid-organ renal transplant recipients after vaccination. Retrospective demographics, graft function, and immunologic parameters were collected in 96 renal transplant patients one month after their second vaccine dose. For-cause biopsies were performed based on clinician judgment. Similar proportions of subjects experienced increases (39.6 %) and decreases (44.8 %) in serum creatinine in the post-vaccination period, p = 0.56. Similar proportions of subjects experienced increases (23 %) and decreases (25 %) in serum ddcfDNA in the post-vaccination period, p = 0.87. Post-vaccination changes in serum creatinine and ddcfDNA (r(95) = -0.04, p = 0.71), serum creatinine and cumulative DSA MFI (r(95) = 0.07, p = 0.56), and ddcfDNA and cumulative DSA MFI(r(95) = 0.13, p = 0.21) were not significantly correlated. Five subjects had increased cumulativeDSA MFI, but there were no de novo cases. Biopsies on three subjects confirmed pre-existing diagnoses. Our study found minimal evidence ofdonor-directed immunologic activity post-vaccination, and all immunologic changesdid not correlate to graft dysfunction. We believe these findings do not amount to evidence ofpost-vaccination deleterious donor-directed activation. SARS-CoV-2 vaccination is immunologically safe and should continue for renal transplant recipients.

Multisite biologic tissue SARS-CoV-2 PCR testing in kidney transplantation from a COVID-positive donor.

With a high community transmission rate, SARS-CoV-2 has profoundly exacerbated the shortage of organs. Although the risk of donor-recipient transmission of SARS-CoV-2 is anecdotally low, an organ-specific infection analysis of procured organs from SARS-CoV-2 positive donors has yet to be established. Using a combination of clinically available and research-only polymerase chain reaction methods, organ preservation fluid and renal parenchymal tissues were tested for SARS-CoV-2 from the kidney of a SARS-CoV-2-positive donor prior to transplantation. The recipient has remained SARS-CoV-2 negative and clinically well, with excellent graft function 120 days post-transplantation.

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.

Antibiotic Stewardship and Inpatient Clostridioides difficile Testing in Solid Organ Transplant Recipients: The Need for Multilevel Checks and Balances.

BACKGROUND: Diarrhea among recipients of solid organ transplants is a commonly encountered problem and is often multifactorial in etiology. Owing to the combination of perioperative antibiotic administration and the immunosuppressed status of transplant recipients, a high degree of suspicion for Clostridioides difficile (C. difficile) colitis is prudent. The purpose of this study is to demonstrate the association of an institutional integrated stewardship program with C. difficile testing practices after abdominal solid organ transplantation. METHODS: Starting in July 2017, a diagnostic stewardship was enacted in our institution requiring the ordering provider to answer a series of questions within the electronic medical record before ordering a C. difficile toxin test. The charts were reviewed for all solid organ transplant recipients on whom a test was ordered between January 2016 and September 2019. RESULTS: Orders for C. difficile toxin per quarter significantly decreased in the postintervention era (18 vs 8.5, P = .038). Median cost of inpatient treatment and days of therapy per thousand patient days was significantly lower in the postintervention era (median cost, $2,944.55 vs $416.92; P = .01) (days of therapy per thousand patient days, 521.9 vs 300.5; P < .01). Quarterly rates of negative tests were similar between the pre- and postintervention eras (65% vs 73%, P = .38). CONCLUSIONS: Although no orders were blocked based on the responses, this multilevel intervention was associated with a 47% decrease in C. difficile testing without effecting the rate of negative testing. These results suggest that we have achieved significant cost savings, in testing and isolation, without sacrificing critical aspects of clinical care.

Escalation to Barbiturate-Induced Coma for Refractory Seizures after Liver Transplantation.

Seizures after liver transplantation were previously thought to be a reliable harbinger of catastrophe, but more recent studies have found seizure activity to be relatively common, and most cases do not result in a poor outcome. Generalized seizures are the most common, and they typically occur de novo within the first two weeks after transplantation. The underlying cause for seizure activity in these patients may be complex, with potential etiologies including metabolic, infectious, cerebrovascular, and medication-induced causes. Identification of the underlying cause and the use of antiepileptic drugs (AEDs) is crucial for minimizing risk to the patient's neurologic and overall health. In this report, we present the case of a patient with refractory seizures unresponsive to conventional treatment, requiring prolonged barbiturate burst suppression with ventilator support. Seizure activity eventually ceased, and the patient made a full recovery.