Utilizing multimodal analgesia to evaluate postoperative analgesic requirements in kidney transplant recipients.

The use of non-opioid analgesics following surgery has proven beneficial in managing pain and decreasing adverse outcomes following surgery. Data assessing outcomes related to opioid use is limited in kidney transplant recipients (KTRs). We evaluated the effectiveness of implementing a reduced to no opioid use protocol in KTRs. This retrospective cohort study included adult KTRs between January 2017 and July 2019 with a multimodal analgesic protocol (MAP), focused on limiting opioids, implemented in August 2018. We compared analgesic requirements in morphine milligram equivalents (MME) during transplant admissions between the MAP cohort and traditional cohort. There were 217 KTRs who met the criteria. Inpatient opioid use was significantly reduced in the MAP cohort (16.5 ± 19.2 MME/day vs 24.7 ± 19.7 MME/day; P <.05) with no significant difference in pain scores. No use of opioids within six months of discharge was significantly increased in the MAP cohort (50% vs 7%; P <.001), and there were no reported deaths at six months in either cohort. The use of multimodal analgesia is beneficial in KTRs to provide adequate pain control with limited to no exposure of opioids during admission or at discharge.

Analysis of the Proton Transfer Bands in the Infrared Spectra of Linear N2H+···OC and N2D+···OC Complexes Using Electric Field-Driven Classical Trajectories.

In this work, we describe ab initio calculations and assignment of infrared (IR) spectra of hydrogen-bonded ion-molecular complexes that involve a fluxional proton: the linear N2H+···OC and N2D+···OC complexes. Given the challenges of describing fluxional proton dynamics and especially its IR activity, we use electric field-driven classical trajectories, i.e., the driven molecular dynamics (DMD) method that was developed by us in recent years and for similar applications, in conjunction with high-level electronic structure theory. Namely, we present a modified and a numerically efficient implementation of DMD specifically for direct (or "on the fly") calculations, which we carry out at the MP2-F12/AVDZ level of theory for the potential energy surface (PES) and MP2/AVDZ for the dipole moment surfaces (DMSs). Detailed analysis of the PES, DMS, and the time-dependence of the first derivative of the DMS, referred to as the driving force, for the highly fluxional vibrations involving H+/D+ revealed that the strongly non-harmonic PES and non-linear DMS yield remarkably complex vibrational spectra. Interestingly, the classical trajectories reveal a doublet in the proton transfer part of the spectrum with the two peaks at 1800 and 1980 cm-1. We find that their shared intensity is due to a Fermi-like resonance interaction, within the classical limit, of the H+ parallel stretch fundamental and an H+ perpendicular bending overtone. This doublet is also observed in the deuterated species at 1360 and 1460 cm-1.

Reducing liver transplant length of stay: a Lean Six Sigma approach.

CONTEXT: Organ transplant centers are under increasing scrutiny to maintain outcomes while controlling cost in a challenging population of patients. Throughout health care and transplant specifically, length of stay is used as a benchmark for both quality and resource utilization. OBJECTIVE: To decrease our length of stay for liver transplant by using Lean Six Sigma methods. DESIGN: The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) method was used to systematically analyze our process from transplant listing to hospital discharge after transplant, identifying many factors affecting length of stay. PATIENTS OR OTHER PARTICIPANTS: Adult, single-organ, primary liver transplant recipients between July 2008 and June 2012 were included in the study. Recipients with living donors or fulminant liver failure were excluded. INTERVENTION(S): Multiple interventions, including a clinical pathway and enhanced communication, were implemented. MAIN OUTCOME MEASURE(S): Length of stay after liver transplant and readmission after liver transplant.R ESULTS: Median length of stay decreased significantly from 11 days before the intervention to 8 days after the intervention. Readmission rate did not change throughout the study. The improved length of stay was maintained for 24 months after the study. CONCLUSION: Using a Lean Six Sigma approach, we were able to significantly decrease the length of stay of liver transplant patients. These results brought our center's outcomes in accordance with our goal and industry benchmark of 8 days. Clear expectations, improved teamwork, and a multidisciplinary clinical pathway were key elements in achieving and maintaining these gains.

Long-Term Safety, Efficacy, Indications, and Criteria of Arteriovenous Fistula Ligation Following Kidney Transplant: A Patient-Driven Approach.

OBJECTIVES: In patients with end-stage renal disease, arteriovenous fistulas are the standard of care to ensure long-term vascular access. Recent studies suggest some long-term posttransplant cardiac benefits and quality of life improvements in kidney transplant recipients due to arteriovenous fistula ligation. However, there are no guidelines regarding arteriovenous fistula management after transplant. Our study objective was to evaluate the long-term safety of arteriovenous fistula ligation and the frequency of returning to hemodialysis after ligation. MATERIALS AND METHODS: Retrospective chart review from February 2014 to December 2020 identified 578 adult patients who underwent successful kidney transplant at our center. Of these patients, 47 underwent subsequent arteriovenous fistula ligation. Both medically driven and patient-driven cases were assessed and approved by a transplant nephrology team with regard to allograft function and ligation suitability. RESULTS: Our results showed that, of the 47 renal transplant patients, 70.2% chose to undergo arteriovenous fistula ligation due to aneurysmal formation, 44.7% due to pain, and 14.9% due to high-output heart failure. In total, 68.1% of arteriovenous fistula ligations performed were primarily patient driven. There was an average follow-up of 2.9 years after ligation, with 1 unrelated reoperation and no returns to dialysis for all patients who underwent arteriovenous fistula ligation. CONCLUSIONS: In our study, the long-term risks of surgical complications and allograft impairment after ligation were negligible. As a result of our current findings and known positive cardiovascular benefit, patient-driven arteriovenous fistula ligation after kidney transplant should be routinely considered in patients with stable allograft function.

Improvement of gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients.

As many as 50% of liver transplant patients suffer gastrointestinal (GI) disturbances post-transplant. Conversion from mycophenolate mofetil (MMF) to mycophenolate sodium (EC-MPS) alleviates GI symptom burden in renal transplant recipients. We employed a validated patient and physician-reported assessment to evaluate the impact of conversion to EC-MPS in liver transplant patients. This is a prospective, longitudinal, single-center, open-label pilot study. Thirty-one MMF-treated liver transplant patients with GI symptoms were converted to equimolar EC-MPS. Gastrointestinal Symptom Rating Scale (GSRS), GI Quality of Life, SF-12v2 and physician-reported assessments were used to evaluate GI symptom burden and severity. A significant improvement in overall GSRS score was noted from baseline (2.57; 95% CI 2.12-3.10) to one month (1.90; 1.68-2.12; p = 0.0007) and three months (1.82; 1.60-2.04; p = 0.0002) post-conversion with significant reductions in all subgroups except Reflux. The overall Gastrointestinal Quality of Life Index (GIQLI) score also showed significant increase in health-related quality of life between one month (90.89; 84.04-97.75) and three months (100.04; 94.57-105.51; p = 0.0009), with all subgroups except social functioning (p = 0.0861) and medical treatment (p = 0.3156) demonstrating significant improvements. This pilot study demonstrates improvement in GI symptom burden when converting from equimolar doses of MMF to EC-MPS. This benefit persisted for three months without evidence of rejection.

Using the Resected Kidney for Transplantation After Nephrectomy for Nutcracker Syndrome.

Nutcracker syndrome (NCS) is the clinical manifestation of unilateral renal venous hypertension. It develops secondary to the nutcracker phenomenon caused by compression of the left renal vein between the superior mesenteric artery and the aorta. We present the case of a 43-year-old female with a history of left flank pain, pelvic congestion, and hematuria secondary to NCS. The patient frequently required high-dose non-steroidal anti-inflammatory medications with minimal relief. She initiated a kidney donor evaluation after electing to undergo a nephrectomy for the possible long-term resolution of NCS symptoms. If diagnosed early, NCS does not generate pathology within the kidney. This finding allows an individual with medically refractory NCS to avoid the morbidity of a complex surgical procedure by instead donating their kidney. Attention to this treatment modality could provide individuals with NCS resolution of symptoms while providing someone with end-stage renal disease with a life-saving organ.

Evaluating Potentially Inappropriate Medications in Older Kidney Transplant Recipients.

OBJECTIVES: Beers Criteria and the Screening Tool of Older Persons' Prescriptions (STOPP) Criteria/Screening Tool to Alert to Right Treatment Criteria are used to assess potentially inappropriate prescribing and medications, which could pose a harm to those of older age. The purpose of this study was to assess and compare the use of Beers and STOPP Criteria in older kidney transplant recipients. METHODS: This was a dual-center, retrospective chart review from May 1, 2014, to March 1, 2018, including kidney transplant recipients 65 years and older. Those who underwent a dual transplant or had incomplete medical records were excluded. Outcomes included number of potentially inappropriate medications (PIMs) comparing Beers and STOPP Criteria on transplant admission, number of PIMs on admission compared with discharge, and readmissions within 3 months related to these medications. RESULTS: A total of 121 recipients were evaluated. On admission, 60 medications were listed on the STOPP Criteria compared with 106 medications on the Beers Criteria. When comparing PIMs on admission to discharge, there was a 38% decrease in the number of medications on discharge using the STOPP Criteria, whereas there was a 9% increase using the Beers Criteria. CONCLUSIONS: Older recipients were more likely to be on a medication listed in the Beers Criteria on admission and have a new medication listed in the Beers Criteria upon discharge compared with the STOPP Criteria.

Early Use of Tacrolimus Extended-Release in a Pediatric Kidney Transplant Recipient.

Tacrolimus extended-release pharmacokinetics and its once-daily formulation provide beneficial properties, and its use has been evaluated in the adult kidney transplant population. Here, we report a case of successful conversion from tacrolimus immediate-release capsules to tacrolimus extended-release tablets in a pediatric kidney transplant recipient.

Graft Nephrectomy as Rescue Therapy for Posttransplant Rhizopus Pyelonephritis in a Pediatric Patient.

Rhizopus infection is an often-fatal complication after transplant. We present a 3-year-old pediatric patient with end-stage renal disease due to congenital hypoplastic kidneys who underwent deceased donor renal transplant. Approximately 3 months after transplant, the patient underwent renal biopsy for a presentation of fevers, acute kidney injury, and imaging evidence of hydronephrosis. The patient was found to have a Rhizopus infection of the transplanted kidney and underwent transplant nephrectomy. In addition to surgical debridement of the infection, the patient was treated with long-term antifungal therapy for complete eradication. After intervention, the patient has had no clinical or imaging evidence of residual or recurrent disease and has been reactivated on the transplant wait list. The positive outcome in this case highlights the importance of rapid diagnosis and treatment of a lethal complication.

Alemtuzumab in Renal Retransplantation - Transplant Outcomes and Associated Infections.

Renal retransplant patients have decreased graft survival compared with primary renal transplant patients. Alemtuzumab induction is often used at the time of retransplant; however, the literature surrounding alemtuzumab induction in renal retransplant patients is limited. In this single-center, retrospective, observational study, we aimed to determine the 1-year incidence of infections and transplant outcomes in renal retransplant patients who received alemtuzumab induction. Thirty-four patients who received alemtuzumab met inclusion criteria and were included in the final analysis. Twenty-two (64.7%) of these patients acquired infections. Of these, 7 patients (31.8%) acquired infections that resulted in hospitalization or intravenous antibiotics. The most common infections were urinary tract infections (n = 10; 29.4%), cytomegalovirus DNAemia (n = 7; 20.6%), and BK virus (n = 6; 17.6%). The use of steroid maintenance therapy after alemtuzumab induction did not increase the number of infections compared with patients with a steroid-free interval after alemtuzumab induction. The number of patients who developed de novo donor-specific antibodies (DSA) was 11 (32.4%) with only 1 of these patients having DSA before retransplantation. The incidence of acute cellular rejection was 2.9% (n = 1). There was no graft loss, and patient survival was 97% (n = 33). There were no significant differences in infection rate or DSA development between alemtuzumab and the other induction agents, antithymocyte globulin and basiliximab, among retransplanted patients. Alemtuzumab induction in renal retransplant patients resulted in similar bacterial and viral infection rates as previously reported in the literature and did not negatively impact graft and patient survival.

Mixed Purpuric and Maculopapular Lesions in a Patient with COVID-19: A Case Report.

INTRODUCTION: The coronavirus disease of 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 is a global pandemic that expresses itself with a wide variety of presenting symptoms in patients. There is a paucity of literature describing the dermatologic manifestations of the virus, particularly in the United States. CASE REPORT: Here we present a case of COVID-19 that manifested with a purpuric rash on the lower extremities and a maculopapular eruption on the abdomen in a patient in acute diabetic ketoacidosis and normal platelet count. DISCUSSION: The reported presenting symptoms of patients with COVID-19 vary greatly. This is the first documented case of COVID-19 presenting with mixed cutaneous manifestations of a purpuric as well as maculopapular rash. CONCLUSION: The cutaneous lesions associated with the COVID-19 infection may mimic or appear similar to other well-known conditions. We illustrate a case of COVID-19 infection presenting with purpuric rash on the lower extremities and a maculopapular rash on the abdomen.

Role of p38 and JNK in liver ischemia and reperfusion.

BACKGROUND/PURPOSE: The signal transduction of mitogen-activated protein kinases (MAPKs) has appeared to be an important mediator of ischemic-related events. Because of this, we analyzed the participation of p38 and JNK in liver ischemia and reperfusion, as two individual members of the MAPK family of proteins. METHODS: All papers referred to in PubMed for the past 15 years were analyzed to determine how and when these MAPKs were considered to be an intricate part of the ischemic event. References were cross-studied to ascertain whether other papers could be found in the literature. RESULTS: The role of p38 and JNK in liver ischemia was confirmed in the literature. The activation of these mediators was associated with the induction of apoptosis and necrosis. Inhibitors of p38 and JNK reduced the liver ischemia and reperfusion damage, probably through the mechanisms mentioned before. CONCLUSIONS: The development of effective inhibitors of p38 and JNK protein mediators is important for minimizing the harmful effects associated with liver ischemia and reperfusion.

Inflammatory mediators of liver ischemia-reperfusion injury.

Liver ischemia and reperfusion--which cause liver damage that is significant in a variety of diseases, injuries, and procedures (including but not limited to trauma and transplant)--have been the focus of many investigations in recent years. Although the mechanisms of ischemia-reperfusion injury are numerous and complex, many advances in treatment have been made. The following review considers recent advances in the understanding of hepatic ischemia-reperfusion injury and focuses on inflammatory mediators of significance. To provide a unique analysis and evaluation, we emphasized the most recent pertinent investigations of the last decade. Specific topics addressed include reactive oxygen species, nitric oxide, toll-like receptors, ischemic preconditioning, T cells, heme oxygenase-1, heat shock proteins, erythropoietin, selectins, protein kinases, matrix metalloproteinases, and cytokines.

Evaluation of a novel cold storage solution (HBs) in a rat kidney transplant model.

We developed an improved solution for hypothermic storage (0-4 degrees C) of kidneys. The cold storage solution (HBS) was composed of macromolecules, high-energy cellular substrates, and a mixture of antiproteolytic amino acids, antioxidants, and anti-inflammatory compounds. The objectives in developing this solution were to achieve superior metabolic support of the kidney during cold storage and to protect against ischemic injury. Inbred Brown Norway rats, weighing 225-250 g, were subjected to orthotopic ultrarapid technique for kidney isotransplantation to minimize warm ischemia and to test the preservation process. The kidney was transplanted after 12 h of preservation. The animals were divided into three groups based upon the preservation solution utilized: HBS solution, HTK solution (Custodiol), and UW solution (UWS)(ViaSpan). Among the recipients, each group had two subsets. The first subset of animals was used to assess survival at 7 days as well as the reperfusion damage index (RDI) based on the macroscopic physical characteristics of the kidney at the time of transplantation. The second subset in each group was utilized to measure serum creatinine and blood urea nitrogen at 4 and 7 days, and histology at death or sacrifice. Mean +/- standard deviation (M +/- SD) was used for all parameters studied. The HBS solution showed significantly better protection at 12 h when compared to HTK and UW solutions. The reperfusion damage index (RDI) showed excellent preservation in the HBS (14 +/- 1), good preservation in UWS (13 +/- 1.5), and moderate preservation in the HTK (11 +/- 2) group. Histology was in concordance with the RDI, showing better histological findings with HBS and UW solutions than with the HTK group. Serum creatinine was significantly better in the HBS group when compared to HTK and UWS. Survival was statistically different, with 80% survival at 7 days in the HBS group, 20% survival in the HTK group, and 50% survival in the UWS group (p < .05). The HBS solution offered a new alternative for kidney cold storage with significantly better results when compared to the current gold standards of HTK and UW solutions in Brown Norway rats. This solution warrants further testing in other mammals.

Addictive Disorders in Adolescents.

Addictive disorders in youth represent a dynamic field characterized by shifting patterns of substance use and high rates of experimentation, while retaining the risky behaviors and negative outcomes associated with established drug classes. Youth/adolescents are also at the forefront of use of new technologies, and non-substance-related disorders are pertinent. These disorders present with similar pictures of impairment, and can be diagnosed following the same principles. An underlying mental disorder and the possibility of a dual diagnosis need to be assessed carefully, and optimal treatment includes psychosocial treatments with applicable pharmacologic management, the latter representing an expanding field.

John Collins Warren: Master educator and pioneer surgeon of ether fame.

John Collins Warren (1778-1856) represented the apex of surgery and medicine of the first half of nineteenth century Boston. Educated at Harvard College where he obtained a Bachelor of Arts in 1797, he contemplated the idea of a business career prior to setting sail for a traditional medical education at Europe's finest universities. From 1799 to 1802, he attended prestigious medical and surgical lectures in London, Edinburgh, and Paris. Warren received an honorary MD from Scotland's St. Andrews University in 1802. He then returned to Boston and joined his father's practice. In 1815, he followed his accomplished father as the Hersey Professor of Anatomy and Surgery at Harvard Medical School. He held this position with great distinction until 1847 when he retired as professor emeritus. From 1816 to 1819 he served as Harvard Medical School dean and received an honorary medical degree at the end of his term.John Collins Warren had numerous surgical accomplishments during his illustrious career. Clinically, he was active and varied in his practice, operating on strangulated hernias, tumors, and cataracts, in addition to performing vascular surgery and amputations. He published many articles and books of widespread circulation. Professor Warren also performed the first reported case of ether anesthesia administered by William T. Morton on October 16, 1846. Outside the operating theatre, Doctor Warren and his colleagues were revered for founding the Massachusetts General Hospital in 1821, and years before, in 1812, Warren and his associates established the New England Journal of Medicine and Surgery. In light of his varied contributions, John Collins Warren is remembered as a dedicated and innovative surgeon, as well as a committed medical educator, able administrator and effective leader.

The surgeon as a scientific writer.

The skills of a surgeon as a scientific writer are many and sophisticated. Recognizing the essential elements of research, learning how to plan and execute the idea, and finally assembling and reporting the data in a coherent and intelligent manner are all critical elements in successfully writing a publication. But writing a research paper is a demanding process that young surgeons are often ill-equiped to address. It consists of many complex tasks and inevitable difficulties that confront every researcher. From undergraduate programs through residency, more attention must be given to cultivate writing skills, especially within the scientific realm. In this article we specifically address these shortcomings while identifying solutions for and attributes of sound scientific writing. When we can manage the parts, we can manage the whole, and look forward to more research with greater confidence. Those who want to join communities that depend on research, such as surgical and medical communities, have to demonstrate not only that they can give good answers to hard questions, but also that they can report their results in ways that are useful to their community, and that means in ways that are apparent, accessible, and recognizable. Being a scientific writer allows him or her to clearly express and effectively convey the importance of worthwhile research. Only when someone has experienced the process of doing his or her own research can one intelligently evaluate the research of others.

1954.

1954 marked the most important year for modern transplantation. It represented the date in which the first successful live kidney transplant was performed by the devoted group of Joseph Murray, Hartwell Harrison, and their Peter Bent Brigham associates in Boston. Intense preparation and careful analysis was required for a long time to arrive at the resounding success manifested in the case of the Herrick twin brothers. Years later, only the discovery of chemical immunosuppression such as azathioprine and the use of radiation therapy permitted occasional good results in kidney transplantation. Great contributors of this period included Elion and Hitchings, Calne and Zukowski, Woodruff, Goodwin, and many others. In a few more years, the use of steroids and an antilymphocyte preparation by the committed team of Tom Starzl from Colorado improved the opportunities for patient outcome. The latter part of the 1960s witnessed the maturation of the Minnesota program with the arrival of John Najarian from California. The 1970s introduced different morbidity and mortality associated with immunosuppressive treatment, and required adjustments in patient management were necessary. New advances were to come in years ahead.