A single-center review of outcomes between COVID-19 vaccinated and unvaccinated liver transplant recipients.

BACKGROUND: With the availability of vaccines against SARS-COV-2, recommendations for vaccination of transplant candidates are widespread. At our institution, patients may receive liver transplant (LTx) regardless of vaccine status. The purpose of this study is to compare post-LTx outcomes between vaccinated (VAX) and unvaccinated (UNVAX) LTx recipients. METHODS: This is a retrospective, single-center study of LTx from January 1, 2021-March 30, 2022. The primary outcome is incidence of post-LTx COVID-19. Secondary outcomes include graft function, mortality, graft loss, and COVID-19 treatment. RESULTS: One hundred and seventy-seven LTx recipients were included, 57% [101/177] VAX and 43% [76/177] UNVAX. Baseline characteristics were similar between groups. Overall, 28 (36.8%) UNVAX and 34 (33.7%) VAX tested COVID-19 positive during the study period (p = .193) at a mean of 312.6 [255.4-369.8] days for UNVAX versus 254.6 [215.2-293.9] days for VAX (p = .084). COVID-19 treatment was administered in 15 (53.6%) of the UNVAX compared to 22 (64.7%) in the VAX (p = .374), although eight (28.6%) of UNVAX required hospital admission for treatment compared with two (5.9%) of VAX (p = .016). There were no statistically significant differences in death, and no COVID-19 related death or graft loss. There were no statistically significant differences in liver function tests at 3- and 12-months post LTx. CONCLUSION: In a series with a large percentage of UNVAX patients, LTx appears to be safe, with no difference in the rate of COVID-19 or transplant-related outcomes compared to VAX. While we encourage vaccination to prevent severe COVID, based on our results, vaccine status should not be reason to deny lifesaving transplant.

Comparison of outcomes in vaccinated versus unvaccinated COVID-19 kidney transplant recipients, a single center retrospective study-Is the taboo justified?

INTRODUCTION: We assessed differences in the post-transplant outcomes between COVID-19 vaccinated and unvaccinated Kidney transplant (KTx) recipients. METHODS: We conducted a retrospective, single-center study of 400 KTx from 2/1/2021 to 4/30/2022 with 6-21 months follow-up. Primary outcomes included differences in the incidence of post-transplant COVID-19, ICU admission for COVID-19, death, and graft failure between the two groups. Secondary outcomes were inpatient floor admission, outpatient-management, length of hospital stay during COVID-19 admission. We also reported rejection, DGF, CMV needing treatment, and BK PCR >10 000 in baseline characteristics. RESULT: 70.5% (282/400) were fully vaccinated, and 29.5% (118/400) were unvaccinated. 33% (92/282) of vaccinated and 39% (46/118) of unvaccinated patients developed COVID-19 (p-value .03). In both groups, 16% received outpatient treatments for COVID-19. 3% (12/282) of the vaccinated and 8% (11/118) unvaccinated were admitted to the general floors (p-value .06), and 1% (3/282) of the vaccinated and 3.3% (4/118) of the unvaccinated patients needed admission to the ICU (p-value .2). The length of stay was 12 days in both groups. 13/282 (4.6%) vaccinated patients and 7/118 (5.93%) unvaccinated patients died during the follow-up period (p-value = .3). COVID-19 was deemed the etiology of death in 5/13 cases in the vaccinated and 3/7 in the unvaccinated. DGF, rejection, CMV requiring treatment, and BK PCR >10 000 were comparable between groups. CONCLUSION: The incidence of COVID-19 was higher in unvaccinated than in vaccinated KTx. The two groups were not statistically different for other primary outcomes, including the need for hospital admissions (outpatient, general floor, ICU), length of hospital stay, death, and graft failure.

Insights into early postoperative acute kidney injury following lung transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication after lung transplantation (LT) and is associated with higher cost and mortality. We sought to evaluate the incidence of postoperative AKI, defined as AKI within 14 days of transplant, and identify associated perioperative factors. METHODS: We conducted a single-center, retrospective review of 153 lung transplant recipients. Postoperative AKI was determined using the RIFLE (Risk, Injury, Failure, Loss, End Stage) criteria. Perioperative covariates and their association with postoperative AKI were analyzed using Cox proportional hazards. Kaplan-Meier survival curves were constructed to evaluate patient survival at 1 year and data finalization. A sub-analysis was performed evaluating factors associated with early AKI (within 48 h of transplant) and late AKI. RESULTS: Postoperative AKI occurred in 36.6% of patients with 51.8% of cases occurring within 48 h of LT. Recipient race, transplant type, cardiopulmonary support, and red blood cell administration were associated with postoperative AKI. Survival was significantly lower in patients with postoperative AKI following LT. CONCLUSIONS: Postoperative AKI within 2 weeks of lung transplant is associated with lower short- and long-term survival. Perioperative factors associated with postoperative AKI may be potential points of intervention to minimize AKI development in the future.

Kidney transplant from hepatitis C viremic donors into aviremic recipients and risk for post-transplant BK and cytomegalovirus infection.

BACKGROUND: kidney transplantation from Hepatitis C virus (HCV) viremic donors to uninfected recipients is associated with excellent short-term outcomes. However, HCV viremia might be associated with an increased risk for post-transplant viral complications. METHODS: We designed a retrospective study of HCV-negative kidney-only transplant recipients between 2018 and 2020. Recipients were grouped into group 1; HCV-negative donors, and group 2; HCV-viremic donors. Patients were matched 1:1 using propensity score. The primary objectives were to compare the incidence of cytomegalovirus (CMV) viremia ≥ 200 ml/IU, and BK viremia ≥1000 copies/ml between the groups. Secondary outcomes included group comparison of CMV disease, BK viremia ≥10 000 copies/ml, and 1-year patient and allograft survival. RESULTS: The study included 634 patients in group 1, and 71 patients in group 2. Sixty-five pairs of patients were matched. Incidence of CMV viremia (33.3% vs. 40.0%, p = .4675), and BK viremia (15.9% vs. 27.7%, p = .1353) did not differ significantly between groups in the matched cohort. Incidence of CMV disease (81.0% vs. 76.9%, p = 1.000), and BK viremia ≥10 000 copies/ml (9.5% vs. 16.9%, p = .2987) were comparable between groups. There was no difference in the 1-year patient or allograft survival between groups. CONCLUSION: kidney transplant from HCV-viremic donors is not associated with increased risk for BK or CMV viremia.

Modification in induction immunosuppression regimens to safely perform kidney transplants amid the COVID-19 pandemic: A single-center retrospective study.

BACKGROUND: The COVID-19 pandemic has negatively impacted organ donation and transplantation across the globe. METHODS: This study analyzed transplant outcomes during the pre-pandemic [PPE, 1/2019-2/2020] and pandemic era [PE, 3/2020-8/2020] based on changes in induction immunosuppression. During PPE, high immunological risk patients received 4-6 mg/kg, moderate risk 2-4 mg/kg, and low risk 1-2 mg/kg of ATG. During PE, ATG doses were reduced to 3-4 mg/kg for high risk, 1-2 mg/kg for moderate, and low changed to basiliximab. Primary outcomes are as follows: biopsy-proven rejection [BPAR], de-novo donor-specific antibody [DSA], delayed graft function [DGF], infection rates, graft loss, and all-cause of mortality. RESULTS: During PPE, 224 kidney transplants [KTx] and 14 kidney/pancreas transplants [KP] were included, while 180 KTx and 5 KP were included for PE. Basiliximab use increased by 30% in the PE. The odds of DGF were statistically significant between PE vs PPE, OR 1.7 [1.05, 2.8, p-value = .042]. The odds of developing DSAs and BPAR during the PE vs. PPE were 0.34 [0.16, 0.71, p-value = .004] and OR 0.34 (0.1 to 1.1, p-value, .104)], respectively. Cytomegalovirus [19% in PE, 37% in PPE] and BK virus [5.4% PE vs. 16% PPE] incidence reduced during PE vs. PPE. COVID-19, graft loss, and mortality were comparable between groups. CONCLUSION: KTx and KP transplants were performed safely during the COVID-19 pandemic with a reduction of induction immunosuppression.

A real-world, single-center experience of the utilization of hepatitis C-viremic kidneys for hepatitis C-negative recipients.

The advent of direct-acting antiviral (DAA) therapies has allowed kidney transplantation from hepatitis C (HCV)-viremic donors into negative recipients. We evaluated the safety and feasibility of such practice when utilizing a patient's health plan to cover the cost for DAAs. MATERIALS AND METHODS: This was a prospective, non-randomized, pilot clinical study. 30 HCV-negative participants received kidney transplant from HCV-viremic deceased donors. HCV polymerase chain reaction (PCR) was checked on day 3 post transplant, and a request for pan-genotypic DAA therapy was sent once viremia was confirmed. Primary outcomes were the percentage of patients achieving sustained virologic response defined as undetectable HCV PCR 12 weeks after therapy completion, and the percentage of patients receiving DAAs via patient's health plan. RESULTS: HCV viremia occurred in all 30 recipients. Sustained viral response was achieved in 93% of the patients. Two patients failed first-line DAAs, 1 patient due to non-compliance with the prescribed regimen while the other due to NS5A mutation. DAA therapy was successfully obtained via patient's health plan in 28/30 patients. There was no significant liver-related complication, patient death, or graft loss. CONCLUSION: Kidney transplantation from HCV-viremic donors appears to be safe. However, challenges with obtaining DAA coverage in the United States persist.

Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility.

PURPOSE: To identify the contribution of mutations in the Desert Hedgehog (DHH) gene to the disorders of sexual differentiation (DSD) and male infertility. METHODS: The study included a total 430 subjects, including 47 gonadal dysgenesis cases, 6 patients with undescended testis and infertility characterized by azoospermia, 125 infertile male patients characterized by oligoasthenozoospermia, 24 patients with oligoasthenoteratozoospermia, and 200 ethnically matched normozoospermic fertile men who had fathered a child in the last two years. Sequencing of the complete coding region of the DHH gene was undertaken to find its contribution to the DSD and male infertility. RESULTS: We observed four novel mutations in the DHH gene in the cases with different reproductive anomalies. A synonymous substitution, c. 543C>T (p.His181His) was observed in 6.6% oligoasthenozoospermic infertile males and 1.5% normozoospermic fertile control samples (RR = 4.4077, 95%CI 1.19-16.29). Another synonymous substitution, c.990G>A (p.Ala330Ala) was observed in an infertile patient with unilateral undescended testis (case #12). Insertion of G at c.1156insG (p.Arg385fs) was observed in a case with bilateral undescended testis and azoospermia (case #23). In gonadal dysgenesis category, two mutations, insertion of G at c.1156insG (p.Arg385fs) and c.997A>G (p.Thr333Ala) substitution were observed in one case (case #34). These mutations were completely absent in control samples. CONCLUSION: Mutations in the DHH gene impact reproduction with mild mutations affecting fertility, and severe or multiple mutations resulting in gonadal dysgenesis.

Comparison of the glucagon-like-peptide-1 receptor agonists dulaglutide and liraglutide for the management of diabetes in solid organ transplant: A retrospective study.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining popularity in the management of diabetes in solid organ transplant (SOT) recipients. There are no studies available comparing the two GLP-1RAs dulaglutide and liraglutide in SOT. We performed a retrospective chart review to assess the safety and effectiveness of these agents in adult SOT with diabetes at 6, 12 and 24 months. There were 63 and 25 recipients on dulaglutide and liraglutide, respectively. There was a sustained reduction in primary endpoints of weight, BMI and insulin requirement with dulaglutide when compared to liraglutide. Decrease in weight was 2%, 4% and 5.2% with dulaglutide and 0.09%, 0.87% and 0.89% with liraglutide at 6, 12 and 24 months respectively. BMI reduction followed the same trend in the two groups. The percentage reduction for insulin was 26% with dulaglutide and 3.6% with liraglutide. There was a 10% reduction in creatinine and a 15% increase in estimated glomerular filtration rate (eGFR) at the end of 24 months with dulaglutide. However, there was an increase in creatinine by 7% and an 8% decrease in eGFR at the end of 24 months with liraglutide.

What every nephrologist needs to know about hydroxychloroquine toxicity
.

Hydroxychloroquine (HCQ) has become the rheumatologists's "Swiss army knife" when it comes to managing the rheumatologic manifestations of SLE and other auto-immune disorders. By contrast, nephrologists are much less comfortable in managing the multifaceted effect of HCQ. As a result, nephrologists are inclined to abdicate their responsibility for HCQ management, if this therapy was initiated by a rheumatologist. This report describes such a situation, which had devastating consequences for the patient. On this basis we suggest that this report is a story worth telling, and should encourage the nephrologist to be more involved in their patients' HCQ management.

Largest single-centre experience of dulaglutide for management of diabetes mellitus in solid organ transplant recipients.

Published data regarding the approach to management of diabetes mellitus in solid organ transplant (SOT) recipients are limited. We performed a retrospective chart review of SOT recipients with diabetes, above 18 years of age, who were usisng dulaglutide. There was a sustained, statistically significant reduction in the primary endpoints of weight, body mass index (BMI) and insulin requirement in 63 SOT recipients at 6, 12 and 24 months, respectively. A total of 59, 50 and 13 recipients were followed during 6, 12 and 24 months, with a mean paired difference for weight reduction of 2.07 (P value <0.003), 4.007 (P value <0.001) and 5.23 (P value <0.034) kgs and a BMI reduction of 0.80 (P value <0.001), 1.35 (P value <0.005) and 2.015 (P value <0.045) kg/m2 , respectively. The mean paired difference for insulin reduction before and after dulaglutide treatment was 5.94 units (P value <0.0002). There was no increased risk of malignancy, cardiovascular morbidity, graft-failure or all-cause mortality. Gastrointestinal manifestations were rare, even in patients with advanced chronic kidney disease (CKD), and required no change in immunosuppressive agents. Thus, dulaglutide may be considered an important option for diabetes management in SOT.

Structural Features of Carbon Dots and Their Agricultural Potential.

Carbon dots (CDs) have drawn attention due to their enticing physical, chemical, and surface properties. Besides, good conductivity, low toxicity, environmental friendliness, simple synthetic routes, and comparable optical properties are advantageous features of CDs. Further, recently, CDs have been explored for biological systems, including plants. Among biological systems, only plants form the basis for sustainability and life on Earth. In this Review, we reviewed suitable properties and applications of CDs, such as promoting the growth of agricultural plants, disease resistance, stress tolerance, and target transportation. Summing up the available studies, we believe that the applications of CDs are yet to be explored significantly for innovation and technology-based agriculture.

Phenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activity.

Pharmacophores such as hydroxyethylamine (HEA) and phthalimide (PHT) have been identified as potential synthons for the development of compounds against various parasitic infections. In order to further advance our progress, we conducted an experiment utilising a collection of PHT and HEA derivatives through phenotypic screening against a diverse set of protist parasites. This approach led to the identification of a number of compounds that exhibited significant effects on the survival of Entamoeba histolytica, Trypanosoma brucei, and multiple life-cycle stages of Leishmania spp. The Leishmania hits were pursued due to the pressing necessity to expand our repertoire of reliable, cost-effective, and efficient medications for the treatment of leishmaniases. Antileishmanials must possess the essential capability to efficiently penetrate the host cells and their compartments in the disease context, to effectively eliminate the intracellular parasite. Hence, we performed a study to assess the effectiveness of eradicating L. infantum intracellular amastigotes in a model of macrophage infection. Among eleven L. infantum growth inhibitors with low-micromolar potency, PHT-39, which carries a trifluoromethyl substitution, demonstrated the highest efficacy in the intramacrophage assay, with an EC50 of 1.2 +/- 3.2 µM. Cytotoxicity testing of PHT-39 in HepG2 cells indicated a promising selectivity of over 90-fold. A chemogenomic profiling approach was conducted using an orthology-based method to elucidate the mode of action of PHT-39. This genome-wide RNA interference library of T. brucei identified sensitivity determinants for PHT-39, which included a P-type ATPase that is crucial for the uptake of miltefosine and amphotericin, strongly indicating a shared route for cellular entry. Notwithstanding the favourable properties and demonstrated efficacy in the Plasmodium berghei infection model, PHT-39 was unable to eradicate L. major infection in a murine infection model of cutaneous leishmaniasis. Currently, PHT-39 is undergoing derivatization to optimize its pharmacological characteristics.

Current advances in drug development in spinal muscular atrophy.

PURPOSE OF REVIEW: Spinal muscular atrophy (SMA) is a pediatric neuromuscular condition characterized by progressive proximal muscle weakness. It is one of the most common genetic causes of infant mortality across different races and is caused by mutation of the survival of motor neuron 1 (SMN1) gene on chromosome 5q13. RECENT FINDINGS: To date, there have been many therapeutics developments for SMA targeting various potential pathways such as increasing SMN gene expression, enhancing SMN2 exon 7 inclusion, neuroprotection, cell replacement, and gene therapy. SUMMARY: Although SMA remains an incurable disease to date, recent advances in the field of basic and translational research have enhanced our understanding of the pathogenesis of the disease and opened new possibilities for therapeutic intervention. This article reviews and highlights past and current translational research on SMA therapeutics.

Is there a need for "triple therapy"? Role of anticoagulation with dual antiplatelet therapy in acute coronary syndromes (ATLAS Study & TRAP Study).

In the past two decades there has been a succession of advances in the development of anticoagulant and antiplatelet therapies to be used in the treatment of ACS. Despite optimal dual antiplatelet therapy, nearly 10-12 % of patients still face a risk of death or myocardial infarction one year following PCI. This large residual risk provides the impetus for the development of more effective strategies. Dual pathway regimens that combine antiplatelets (aspirin and a thienopyridine), along with an anticoagulant such as rivaroxaban may prove to be a therapeutic option in patients with ACS.

A Single-Center Case Series of Successful Abdominal Organ Transplantation From SARS-CoV-2-infected Donors to Uninfected Recipients-Do We Need Rigorous Monitoring?

There is limited documentation of hematogenous transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in non-lung transplants from infected donors to uninfected recipients. Methods: We analyzed 16 recipients (7 liver, 9 kidney) transplanted from SARS-CoV-2 nucleic acid test+ deceased donors from December 25, 2021, to February 28, 2022, who were followed-up for at least 90 d. Primary outcomes included coronavirus disease 2019-positivity, allograft loss, and all-cause mortality. Secondary outcomes included biopsy-proven rejection (BPAR), donor-specific antibodies, delayed graft function, and opportunistic infections. Unlike previous studies, we followed the recipients clinically with the intent to treat if they developed SARS-CoV-2 symptoms. Results: All donors were SARS-CoV-2 polymerase chain reaction-positive 72 h before donation. No recipients developed SARS-CoV-2 infection. The nadir serum creatinine and estimated glomerular filtration rate were 1.33 mg/dL and 64 mL/min/1.732 m2 for kidney transplantation (KTx) respectively. The median alanine transaminase was 14.5 IU/L, aspartate aminotransferase 13 IU/L, and alkaline phosphatase 74 IU/L. Two KTx patients lost allograft, and 1 liver transplantation patient died with a failed allograft. However, this was unrelated to their SARS-CoV-2-positive donor status. One BPAR in the liver transplantation was treated with steroids. No donor-specific antibodies or BPAR were reported in the KTx. Six KTx patients experienced delayed graft function, and 4 are off dialysis. Two KTx patients developed cytomegalovirus infection because of an error in reporting the cytomegalovirus serostatus by the donor center. We did not do serial testing for SARS-CoV-2 by polymerase chain reaction, imaging, or cycle threshold score pre- or posttransplant for donor/recipient and had comparable outcomes with previous studies. Conclusions: Because of the low risk of transmission, serial testing might not be necessary and, thus, could be reciprocated at small-volume transplant centers.

Outcomes After Deceased Donor Kidney Transplantation Using Kidney Allografts With Marginal Perfusion Parameters.

BACKGROUND: This study examines outcomes of deceased donor kidney transplantation (DDKT) in recipients of kidney allografts with marginal perfusion parameters. METHODS: Allografts with marginal perfusion parameters (resistance index [RI] >0.4 and pump flow rate [F] <70 mL/min; MP group) were compared with those with good parameters (RI <0.4 and F >70 mL/min; GP group) for DDKT recipients between January 1996 and November 2017 after hypothermic pulsatile perfusion. Demographics, creatinine, cold ischemia times (CIT), delayed graft function (DGF), and recipient glomerular filtration rate at pre- and post-transplant were noted. The primary outcome was graft survival post-transplant. RESULTS: In the MP (n = 31) versus GP (n = 1281) group, the median recipient was aged 57 years versus 51 years; the median donor was aged 47 versus 37 years; terminal creatinine was 0.9 versus 0.9 mg/dL; CIT was 10.2 versus 13 hours, and the RI and flow were 0.46 and 60 mL/min versus 0.21 and 120 mL/min. The DGF rate was 19% (MP) versus 8% (GP). The graft survival in the MP versus GP group was 81% versus 90% (1 year), 65% versus 79% (3 years), 65% versus 73% (4 years), and 45% versus 68% (5 years). CONCLUSION: Carefully selected kidney allografts after comprehensive donor and recipient evaluation may allow for the use of these routinely discarded kidneys with marginal perfusion parameters.

Looking Beyond the Allograft Survival: Long-Term, 5-Year Renal Outcome in Lung Transplant Recipients.

With the increased incidence and survival of lung transplant (LTx) recipients, the risk for chronic sequelae such as chronic kidney disease (CKD) is on the rise. Data on the long-term renal outcome are scarce. We performed a retrospective chart review of 171 adults with LTx from January 1, 2014, to January 1, 2019. Primary outcomes were prevalence of CKD/end-stage renal disease, acute kidney injury (AKI) as a risk factor for future CKD, and all-cause mortality in recipients with CKD compared with the non-CKD group. Secondary outcomes were frequency of utilization of modalities for CKD (urinalysis, imaging, biopsy, nephrology consultations). Baseline median creatinine and estimated glomerular filtration rate (eGFR) were 0.8 mg/dL and 90 mL/min/1.73 m2, respectively. Of the participants, 60% (96 of 161), 67% (102 of 153), 79% (37 of 47), 86% (10 of 12) had CKD at the end of 6, 12, 36, and 60 months, respectively, and 16% were on dialysis at the end of the study period; 3% received a subsequent renal transplant, and 27% mortality was noted over a 5-year follow-up period. The odds of CKD development in patients with an AKI during index hospitalization vs no AKI was 6.22 (2.87 to 13.06, P < .0001). The odds ratio of all-cause mortality in patients with CKD compared with non-CKD was 3.36 (95% confidence interval, 1.44-8.64, P = .005). Measurement of hematuria/proteinuria, imaging, and renal biopsy were infrequently used. Given the high prevalence of AKI and CKD in this population, a multidisciplinary team approach with an early nephrology consultation will be key to improve the overall and renal outcomes in LTx recipients.