Small Donors, Big Impact: Optimizing Organ Utilization in Simultaneous Pancreas and Kidney Transplantation From Extra Small Pediatric Donors.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis. METHODS: This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain-dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20 kg. RESULTS: All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re-exploration. During a 5-27-month follow-up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%-5.2%), with 100% graft and patient survival. CONCLUSION: This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk-benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates.

Scedosporium Infection in Recipients of Kidney Transplants from Deceased Near-Drowning Donor.

Scedosporium aurianticum infection developed in 2 recipients of kidney transplants in India, acquired from the same deceased near-drowning donor. Given the substantial risk for death associated with Scedosporium infection among solid-organ transplant recipients, safety protocols for organ transplantation from nearly drowned donors should be thoroughly revaluated and refined.

A Split Face Comparative Interventional Study to Evaluate the Efficacy of Fractional Carbon Dioxide Laser against Combined use of Fractional Carbon Dioxide Laser and Platelet-Rich Plasma in the Treatment of Acne Scars.

Background: Fractional carbon dioxide laser (FCL) is an established treatment option for acne scars, but use of platelet-rich plasma (PRP) as an adjuvant still requires elaborate studies. Aim: To compare the efficacy and safety of FCL alone and combined use of FCL with PRP in the treatment of acne scars. Materials and Methods: This was a split-face (right-left) comparative study including 32 patients with moderate to severe acne scars. The patients underwent three sessions of FCL along with PRP and FCL alone on right and left sides of the face, respectively, at an interval of 6 weeks. Goodman and Baron qualitative and quantitative scores were used for the evaluation of results along with visual analog scale (VAS) for patient satisfaction and physician assessment of scars. Adverse effects following the procedure were also evaluated and compared. Results: There was significant improvement of scars over both sides of the face, but the difference between right and left sides was not statistically significant according to Goodman and Baron qualitative (p 0.9115) and quantitative score (p 0.6957). On assessing VAS score, patients were more satisfied with the right side, but the values were not statistically significant (p 0.8571). Physician assessment grading showed comparable results over both the sides (p 1). There was no difference in adverse effects between both sides of the face. Conclusions: Inclusion of intradermal PRP to FCL did not produce any statistically significant synergistic effects in the treatment of acne scars.

Risk factors for pulmonary mucormycosis in subjects with diabetes mellitus-A case-control study.

BACKGROUND: Factors associated with pulmonary mucormycosis (PM) among subjects with diabetes mellitus (DM) remain unclear. Following the coronavirus disease (COVID-19)-associated mucormycosis outbreak in India, specific environmental exposures (especially cattle dung exposure) were proposed as possible aetiology. We hypothesized that environmental factors are associated with PM. We compared subjects with DM with (cases) and without PM (controls). METHODS: In this case-control study, for each PM case, we included five unmatched diabetic controls (hospital [n = 2], community [n = 3]) without PM. We collected information on demography, COVID-19 infection, glycated haemoglobin% (HbA1c), the type of house (pucca vs. kutcha) where the participants reside, and other environmental factors. The primary exposure tested was cattle dung exposure (CDE; using cattle dung cakes as fuel or cattle handling). We performed a multivariate logistic regression to explore factors associated with PM and report the association as an adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: We enrolled 39 PM cases and 199 controls (hospital [n = 80], community [n = 119]). CDE (OR 0.68, 95% CI [0.14-3.31]; p = 0.63) was not associated with increased PM in DM. We found male sex (OR 4.07, 95% CI [1.16-14.31]), higher HbA1c (OR 1.51, 95% CI [1.18-16.32]), COVID-19 (OR 28.25, 95% CI [7.02-113.6]) and residence at kutcha house (OR 4.84, 95% CI [1.33-17.52]) associated with PM. CONCLUSION: Cattle dung exposure was not associated with PM in subjects with DM. Instead, male sex, poor glycaemic control, COVID-19 and the type of housing were associated with pulmonary mucormycosis.

Bridging the Gap With Clinical Pharmacology in Innovative Rare Disease Treatment Modalities: Targeting DNA to RNA to Protein.

Rare diseases are frequently caused by inherited 'monogenic' defects. Treatment interventions that target a specific genetic location or that replaces a specific protein provide rational therapeutic approaches. The current review discusses innovative targeted therapies that act or modulate at the level of DNA, RNA, or protein. They include DNA gene editing, small interference RNA (siRNA), antisense oligonucleotide (ASO), small molecule RNA splicing modifier, and bispecific antibody. With limited numbers of patients, testing multiple dose levels and regimens prior to making an informed dose decision remains one of the major challenges in rare disease drug development. Clinical pharmacology strategically bridges the gap to support drug development and regulatory approvals. Pharmacokinetic drug exposures are driven by absorption, distribution, metabolism, elimination, and in some cases immunogenicity. Drug responses are measured by pharmacodynamic biomarkers that are linked to either short- or long-term clinical outcomes. Understanding the drug exposure-response relationship lies at the heart of bridging the gap that enables a dose decision by balancing effectiveness and safety. Furthermore, and importantly, understanding the influence of intrinsic and extrinsic factors on drug pharmacokinetics enables dose adjustment decisions based on drug exposures. Case examples include the identification of doses and regimens without a formal dose-finding study, the support of new doses and regimens without conducting additional studies, and the extrapolation of adult drug-drug interaction (DDI) studies to pediatrics without performing a pediatric DDI study. With increasing discoveries of innovative treatment modalities, the responsibility of clinical pharmacologists is expected to grow and enhance the development of novel treatments for rare diseases.

Application of Ex Vivo Normothermic Machine Perfusion in Deceased Donors With Acute Kidney Injury With Successful Renal Transplantation: A Preliminary Experience.

Ex vivo normothermic machine perfusion (NMP) has improved organ preservation and viability assessment among heart, liver, and lung transplantation. However, literature regarding the application of NMP in human clinical kidney transplantation remains limited. Numerous kidneys, especially from donors with stage 3 acute kidney injury (AKI), are not utilized concerning the high rate of delayed graft function (DGF) and primary nonfunction. The present study investigated the impact of NMP (135-150 min) on short-term outcomes after kidney transplantation from deceased donors with AKI. Methods: Graft outcomes of NMP kidneys were compared with contralateral kidneys stored in static cold storage (SCS) from the same donor with AKI during December 2019-June 2021. The study's primary aim is to assess the safety and feasibility of NMP in deceased donors with AKI. The primary outcome was DGF. Secondary outcomes were duration of DGF, biopsy-proven rejection, postoperative intrarenal resistive index, postoperative infections, hospital stay duration, primary nonfunction, and kidney function estimated glomerular filtrate rate at discharge, 3 mo, and 1 y. Results: Five pairs of AKI kidneys (NMP versus SCS) were included in the final analysis. The results show no statistically significant differences in clinical outcomes between NMP versus SCS kidneys; however, NMP kidneys demonstrated slightly improved estimated glomerular filtrate rate at 3 mo (59.8 ± 5.93 [59] versus 75.20 ± 14.94 [74]) mL/min/1.73 m2 (P < 0.065) and at the last follow-up (12-29 mo) (72.80 ± 10.71 [75]) versus (94 ± 22.67 [82]) mL/min/1.73 m2 (P < 0.059) as compared with SCS kidneys. A higher proportion of NMP kidneys had normal intrarenal resistive index (0.5-0.7) and mild acute tubular injury on protocol biopsy, suggesting NMP is safe and feasible in deceased donors with acute kidney injury. Conclusions: NMPs of AKI donor kidneys are safe and feasible. A larger cohort is required to explore the reconditioning effect of NMP on AKI kidneys.

Outcomes after lung resection in renal transplant patients with pulmonary mucormycosis.

BACKGROUND: Pulmonary mucormycosis has been associated with high mortality (reported up to 100%) in renal transplant recipients. METHODS: This was a retrospective analysis of renal transplant patients with pulmonary mucormycosis between April 2014 and March 2020, who underwent surgical resection of the affected lung along with liposomal amphotericin therapy. Patients with lower respiratory illness features underwent chest X-ray, high-resolution computed tomography of the chest, and those with suspicious findings underwent analysis of bronchioloalveolar fluid and transbronchial lung biopsy. Patients with histological or microbiological evidence of mucormycosis were started on liposomal Amphotericin B. Tacrolimus and mycophenolate mofetil were stopped at the time of diagnosis. RESULT: Ten patients underwent combined management, while five patients were managed medically. At last follow up, seven out of ten patients (70%) who underwent combined management and two of the five patients (40%) who were managed medically, had a mean survival of 28.86 months (sd = 15.71, median = 25) and 14.17 months (sd = 12.21, median = 18), respectively, post-diagnosis of pulmonary mucormycosis. CONCLUSION: Surgical resection combined with antifungals in the perioperative period and decreased immunosuppression may improve the outcomes in renal transplant patients with pulmonary mucormycosis.

Outcome of tibio-saphanous arteriovenous fistula in patients with failed upper extremity dialysis access: A report of two cases.

Arteriovenous fistulas (AVF) are the preferred access for hemodialysis in patient with end stage renal disease. Usually, distal vessels of upper limb are preferred. There are situations in which the upper limb cannot be a site for AVFs or graft as in cases of bilateral central venous stenosis or with exhausted sites in upper limb. In these cases, lower limb AVF can be considered. Tibial-saphanous (ankle) fistula should be the preferred site over femoral AVF/graft following the principle of distal to proximal. Also, femoral AVFs are associated with more ischemic and infective complications. The present report describes successful hemodialysis in two patients with tibial-saphanous fistula a site rarely used as an option for HD access. Hemodialysis for over 1 year in one patient and 6 months in the other portrays the success of this approach.

Impact of a trained vascular access coordinator on a vascular access program in India.

BACKGROUND: Native AV fistulas are the ideal access for hemodialysis but require monitoring and multiple interventions in some patients to keep them functioning. The aim of the study was to assess the impact of the appointment of a trained vascular access coordinator (VAC) for fistula monitoring, on the evolution of the vascular access program at our institute. METHOD: Data was retrieved from the departmental database for the baseline year 2014 and compared with the data from 2018. Initial review showed that appointment of the VAC in 2015 resulted in a steady increase in the number of AV fistula interventions over 2 years to a plateau in 2018 which was chosen as the comparison year. The number of AVF's created, number of salvage procedures performed, and follow-up data were compared. Other parameters like number of operation theatre hours, surgeons, and nursing staff remained constant during this period. RESULT: Total numbers of AVFs increased from 511 to 713 (39.3%). The number of follow-up visits to surgeons reduced from an average of 4-0.25 visits per patient during this period. Follow up Doppler examinations increased from 761 to 1296 (70%) indicating improved follow up. The salvage procedures increased from 44 to 161 (272%) with early detection of fistula dysfunction. Primary and secondary patency rates of 86% and 92% at 3 months could be achieved whereas limited follow-up data was available for 2014. CONCLUSION: Appointment of trained VAC increased the number of vascular access procedures, improved follow-up care, and led to early detection and intervention for access dysfunction while reducing the workload of surgeons.

Analysis of Organ Utilization From Deceased Organ Donation in India.

OBJECTIVES: This report presents an audit of utilization of various organs from deceased donors in different states of India over a 3-year period METHODS: Data released by the various regions on their official website was analyzed from 2015 to 2017.Regions with less than 25 donations per year were excluded while calculating utilization rates. RESULTS: Total organ donation in India had increased from 570 to 843 donations from 2015 to 2017 (47.8% increase) with southern states performing exceedingly well compared with northern states. Total organs retrieved during the 3-year period were 6659 with a 54.7% increase in organ retrieval in 2017 compared with 2015 (2592 vs 1675 respectively). The net utilization rate of kidneys was 87.35%. Total liver transplants done during this period were 1894. Net liver utilization rate was 86.81% over 3 years. Total Heart transplants during this period were 641 with net utilization rate of 28.98%. An increase in utilization rates was observed from 2015 to 2017 (19.33%-34.46%). A total of 217 lung transplants were done with net utilization rate of 8.86% with an increase in yearly utilization rate from 6.5% in 2015 to 11.97% in 2017. Total pancreas transplants remained low with 48 transplants over 3 year duration with net utilization rate of 2.25% but an increase in utilization rate was observed. (0.92% in 2015 to 2.1% in 2017). CONCLUSION: There is a significant regional variability in organ utilization in India. Evaluating and addressing the cause of high variability can further increase the transplant activity.

Risk for Delayed Graft Function in Deceased Donor Renal Transplant Patients: A Single-Center Experience From North India.

OBJECTIVES: Delayed graft function (DGF) in renal allograft transplantation refers to the need for dialysis in the first week after renal transplantation. This study analyzed the causes of DGF in deceased donor transplantation. METHODS: Data from January 2018 to July 2019 was reviewed with regard to donor and recipient characteristics such as demographics, biochemical parameters, organ dysfunction, and preterminal management. The recipients were divided into 2 groups: group I: patients without DGF and group II: patients with DGF. RESULTS: Kidneys were retrieved from 49 deceased donors (male:female = 41:8) and transplanted to 95 recipients (male:female = 60:35). Mean age of the donors and recipients was 35.34 ± 18.2 and 40.72 ± 13.30 years, respectively. The most common cause of brain death was central nervous system trauma (45 out of 49, 91%). In total, 20/95 (21%) recipients had DGF. Twelve recipients had received kidneys from donors who had circulatory arrest. Two patients were re-explored on postoperative day 1 for bleeding from renal artery anastomosis. The mean age in group I and group II was 28.65 ± 10.2 and 37.38 ± 12.28 years, respectively. The mean cold ischemia time in group I and group II was 398.73 ± 187.19 and 333.24 ± 115.49 minutes, respectively. The mean hospital stay of donor before donation in group I and group II was 4.34 ± 1.27 and 6 ± 2.95 days, respectively. The terminal donor creatinine in group I and group II was 0.88 ± 0.47 and 2.33 ± 1.73 mg/dL, respectively. CONCLUSION: DGF in deceased donor transplantation may be attributed to donation after circulatory death, prolonged donor hospital stay, high donor leukocyte count, and high terminal creatinine.

Reasons for Low Utilization of Pancreas for Transplantation From Deceased Donors: Analysis of Data From a Single Center in India.

OBJECTIVES: Although pancreas transplants were started at our center in 2014, the number of pancreases procured have remained low. This report presents an audit of donors over the past 18 months with the aim to identify factors preventing pancreas utilization. METHODS: This was a retrospective study. All deceased donors from January 2018 to July 2019 were included in this study. The medical records of deceased donors were reviewed with regard to donor characteristics such as demographics, biochemical parameters, and preterminal management. RESULTS: Organs were retrieved from 49 deceased donors over the duration of the study. Mean age of the donors was 35.34 ± 18.2 years (11 months to 72 years). Most donors were men (M:F 41:8). In total, 45/49 (92%) donors had central nervous system trauma as a cause of brain death. Out of 49, multiple abdominal organs were retrieved from 21 donors (42.8%), whereas kidneys alone were retrieved from the rest. Pancreases were retrieved from 8 donors (16.3%). Pancreases were rejected in 21 donors (42.8%) because of age limit criteria. Other reasons for refusal included donor sepsis (n = 12, 24.5%), severe hemodynamic instability (n = 5, 10.2%), donation after cardiac death (DCD) (n = 2, 4.1%), and ischemic hepatitis (n = 7, 14.3%) while 3 (6.1%) donations happened while awaiting license renewal. A suitable recipient was not available for 1 donor (2.0%). CONCLUSION: Pancreas retrieval rates remain low because of donor-related factors. Expansion of age limits and better donor management could improve pancreas transplant activity.

Experience With 15 Years of Laparoscopic Donor Nephrectomy: Review of 2500 Cases.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) is considered the gold standard for live donor nephrectomies owing to lesser pain, shorter hospitalization, and earlier return to normal activities, yet it remains a technically challenging surgery. Repetition of a highly skilled task such as LDN should lead to improved performance reflected in shorter surgery times and a decrease in adverse events. METHODS: The records of over 2524 LDNs from February 2004 to June 2019 were evaluated for duration of surgery (from incision time to clamping of the renal artery) and occurrence of complications. RESULTS: The mean duration of surgery ± SD from incision to clamp time for the first 100 cases at the inception of LDN was 166.13 ± 33.28 minutes whereas it was 124.59 ± 35.91 minutes for the best 100 consecutive cases in 2015 with a decrease of 41 minutes duration of surgery from incision to artery clamping. The adverse events were accessory renal artery injury (n = 10), splenic laceration (n = 2), bowel and mesocolon injuries (n = 12), venous or arterial clip slippage (n = 4), inferior vena cava tear (n = 2) pneumothorax (during stapler application, n = 1), missing gauze counts (n = 1), chylous ascites (n = 1), ureteric thermal injury (n = 2), and renal parenchyma injury (n = 3). CONCLUSIONS: LDN is a technically demanding surgery where surgeon experience appears to affect operative metrics such as operative time. The occurrence of intraoperative complications appears to be acceptably low, although serious complications are a possibility.

Successful Implantation of a Renal Allograft With Quintuple Arteries Retrieved From a Living Donor.

In renal transplant, multiple renal arteries in a donor require meticulous vascular reconstruction for successful allograft function in the recipient. Presence of more than 4 renal arteries is usually considered to be a relative contraindication for proceeding with renal donation. We report a living-donor renal transplant procedure where preoperative radiologic imaging of the donor showed 3 left renal arteries. Two additional arteries were identified intraoperatively. All 5 arteries were reconstructed during the back-table procedure, and the allograft was implanted in the recipient. At 3-month follow-up, computed tomographic imaging demonstrated patency of all 5 renal arteries, and the patient had a serum creatinine level of 0.8 mg/dL. Unidentified arteries on preoperative imaging may occasionally require complex reconstruction. A renal allograft with 5 renal arteries is usually a contraindication for renal donation. Here, we describe the first published case of successful kidney transplant after reconstruction of 5 renal arteries in the donor graft.

Ultrasound-guided angioplasty for treatment of peripheral stenosis of arteriovenous fistula - a single-center experience.

PURPOSE: In patients with end-stage renal disease, arteriovenous fistulas (AVFs) are the access of choice for hemodialysis but are often complicated by stenosis. We present single-center experience of 78 ultrasound-guided angioplasty procedures for treating peripheral stenoses of AVFs. METHODS: Between January 2013 and November 2015, 78 angioplasties were performed under ultrasound guidance in 53 patients with end-stage renal disease who were referred from dialysis centers with low flow rate, difficult cannulation, increased cannulation site bleeding, immature or thrombosed AVF. Angioplasties were carried out in the presence of a structural lesion in the AVF resulting in at least 50% reduction in vein diameter with a blood flow of <250 mL/min or a peak systolic velocity >300 cm/s. Clinical success, anatomical success and post-intervention primary and secondary patency rates at 6, 12, 18 and 24 months were studied. RESULTS: In 49/53 patients (92.4%), 74 angioplasty procedures were successfully performed, whereas 4/53 patients (7.6%) had primary failure. A total of 35/49 patients (71.4%) underwent single angioplasty procedure whereas 14/49 patients (28.6%) underwent multiple angioplasty procedures. Post-intervention primary patency rates at 6, 12, 18 and 24 months were 78.6%, 60.2%, 53.8% and 48.9%, respectively. Post-intervention secondary patency rates at 6, 12, 18 and 24 months were 100%, 100%, 95.4% and 89%, respectively. Clinical success and anatomical success was 94.8% and 89.7%, respectively. CONCLUSIONS: Ultrasound-guided angioplasty is an effective method with good long-term outcomes in selected dialysis patients with peripheral stenosis of AVF.

A novel approach in root coverage - Coronally repositioned flap with GTR membrane and frenotomy.

This case report describes a guided tissue regeneration (GTR) based root coverage procedure over maxillary central incisor using coronally advanced flap with simultaneously performed frenotomy. The patient was a 32-year-old female with chief complaint of gingival enlargement in relation to 11. Based on overall findings it was diagnosed as a case of inflammatory gingival enlargement. Vertical osseous defect along with Millers class I gingival recession was seen after initial therapy. GTR-based root coverage procedure using coronally advanced flap with simultaneously performed frenotomy was planned. Complete root coverage was achieved over the maxillary central incisor that initially presented with Miller's class I gingival recession along with radiographic bone fill of the osseous defect. This case report shows the possibility of applying GTR-based root coverage procedure using coronally advanced flap combined with frenotomy to treat Millers class I gingival recession.