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.

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.

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.

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.

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.

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.

Allopurinol in renal ischemia.

Allopurinol is a xanthine oxidase inhibitor and antioxidant free radical scavenger which facilitates the protection of ischemic organs in part via this mechanism of action. The accumulation of free radicals during ischemia and reperfusion is in great manner overcome by inhibitors of xanthine oxidase and by the development of endogenous antioxidants. The ischemic lesion generates a well-established inflammatory response with the subsequent production of inflammatory molecules characteristically present at the first stages of the injury. Inflammatory cytokines, chemokines, adhesion molecules, and other cellular and molecular compounds are consequently produced as the lesion sets in. Under these conditions, allopurinol diminishes the effect of inflammatory mediators during the ischemic inflammatory response. This study reviews the literature associated with allopurinol and renal ischemia making special emphasis on the best dose and time of administration of allopurinol regarding its protective effect. It also defines the most accepted mechanism of protection on ischemichally damaged kidneys.

Pentoxifylline in liver ischemia and reperfusion.

Pentoxifylline is a methylxanthine compound which was first filed in 1973 and registered in 1974 in the United States by Sanofi-Aventis Deustchland Gmbh for the treatment of intermittent claudication for chronic occlusive arterial disease. This methylxanthine was later discovered to be a phosphodiesterase inhibitor. Furthermore, its hemorheological properties and its function as an inhibitor of inflammatory cytokines, like TNF-α, allowed researchers to study its effects in organ ischemia and reperfusion and transplantation. Although this drug has demonstrated beneficial effects, the mechanisms by which Pentoxifylline exerts a protective effect are not fully understood. This paper focuses on reviewing the literature to define the effect of Pentoxifylline when used in liver ischemia and reperfusion injury. Our research shows different animal models in which Pentoxifylline has been used as well as different doses and time of administration, as the ideal dose and timing have not yet been ascertained in liver ischemia and reperfusion. In conclusion, Pentoxifylline has shown positive effects in liver ischemia and reperfusion injury, and the main mechanism seems to be associated with the inhibition of TNF-α.

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.

Historical development of modern anesthesia.

Of all milestones and achievements in medicine, conquering pain must be one of the very few that has potentially affected every human being in the world. It was in 1846 that one of mankind's greatest fears, the pain of surgery, was eliminated. This historical review article describes how the various elements of anesthesiology (gasses, laryngoscopes, endotracheal tubes, intravenous medications, masks, and delivery systems) were discovered and how some brilliant entrepreneurs and physicians of the past two centuries have delivered them to humanity. One name stands out amongst all others when the founder of modern anesthesia is discussed, William T.G. Morton (1819-1868). A young Boston Dentist, Dr. Morton had been in the search for a better agent than what had been used by many dentists: nitrous oxide. With Dr. Morton's tenacity driven by enthusiasm and discovery, he and renowned surgeon at Massachusetts General Hospital, John Collins Warren (1778-1856) made history on October 16, 1846 with the first successful surgical procedure performed with anesthesia. Dr. Morton had single-handedly proven to the world that ether is a gas that when inhaled in the proper dose, provided safe and effective anesthesia. One of the first accounts of an endotracheal tube being used for an airway comes from the pediatrician Joseph O'Dwyer (1841-1898). He used the metal "O'dwyer" tubes in diphtheria cases and passed them into the trachea blindly. Adding a cuff to the tube is credited to Arthur Guedel (1883-1956) and Ralph M. Waters (1883-1979) in 1932. This addition suddenly gave the practitioner the ability to provide positive pressure ventilation. The anesthesiologist Chevalier Jackson (1865-1958) promoted his handheld laryngoscope for the insertion of endotracheal tubes and its popularity quickly caught hold. Sir Robert Reynolds Macintosh's (1897-1989) breakthrough technique of direct laryngoscopy came after being appointed Nuffield professor of anesthetics at the University of Oxford in 1937. He was the first to describe the routinely placing of the tip of his newly re-designed laryngoscope in the epiglottic vallecula which is attached to the base of the tongue, thus when lifted exposed the entire larynx. Macintosh was genuinely astonished at what a great view he could achieve with his new blade and technique. The use of barbiturates as an intravenous anesthetic began in 1932. Sodium thiopental gained popularity after its use was described in detail by a Dr. John Lundy (1894-1973) of the Mayo Clinic. Other I.V. medications were tried over the past seventy years, but the newest induction drug which provided for a substantially shorter recovery period and seemed to actually suppress laryngeal reflexes has brought with it many benefits. Propofol, introduced clinically in 1977, demonstrated many positive effects even as an anti-emetic compound. Before October of 1846, surgery and pain were synonymous but not thereafter. As we entered the information age where the infrastructure of evidence based medicine and newer fields of genetics, transplantation, imaging radiology and even stem cells became quickly integrated into mainstream medicine, we can predict an excellent future on the progress to be made in anesthesia.

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.

Principles of statistics in surgery.

Surgery, like any other scientific discipline, requires a systematic analysis of all its different variables in order to prove the real significance of research findings. Statistics, the science of numerical evaluation, can thoroughly help to determine the real value of surgical treatment. In this work, we study the statistical tests and principles needed to demonstrate their role in surgical research. Without a strong statistical background, a researcher may feel overwhelmed when deciding what statistical methods to utilize in research. Determining what type of data to collect and what hypothesis test to run can alter the entire way a surgical study is conducted. The relationship between power, sample size and effect size is discussed as well as the components necessary for a power analysis. Selecting an appropriate sample size is of utmost importance in any type of research since an undersized sample can invalidate an entire study. Categorical surgical data, numerical data, and the appropriate statistical procedures needed for analysis are reviewed. Methods discussed include the 2-Sample t-test, Mann Whitney U test, Kruskal-Wallis, ANOVA, Chi-Square test and Fisher's exact test.

Developing the research hypothesis.

The research hypothesis is needed for a sound and well-developed research study. The research hypothesis contributes to the solution of the research problem. Types of research hypotheses include inductive and deductive, directional and non-directional, and null and alternative hypotheses. Rejecting the null hypothesis and accepting the alternative hypothesis is the basis for building a good research study. This work reviews the most important aspects of organizing and establishing an efficient and complete hypothesis.

Tumor necrosis factor-α in liver ischemia/reperfusion injury.

The pathophysiology of hepatic ischemia/reperfusion injury (IRI) includes a number of complex and diverse mechanisms involving interactions between hepatocytes, Kupffer cells, neutrophils, macrophages, sinusoidal endothelial cells, and platelets. Tumor Necrosis Factor-α (TNF-α), a cytokine produced by numerous cell types in response to inflammatory stimuli, is a well-known mediator during ischemia/reperfusion (IR) that plays a central role in injury to hepatocytes. TNF-α has a multifactorial effect in hepatic IRI because of the many interactions between TNF-α and reactive oxygen species, nitric oxide, adhesion molecules, and various cytokines and chemokines. The intracellular cascades that TNF-α triggers and their downstream effects are clearly presented throughout this manuscript. With these mechanisms in mind, ischemic preconditioning and pharmacological interventions with potential clinical application to prevent or attenuate IRI will be emphasized.

Allopurinol and xanthine oxidase inhibition in liver ischemia reperfusion.

INTRODUCTION: Allopurinol was first introduced, in 1963, as a xanthine oxidase inhibitor when it was investigated for concomitant use with cancer chemotherapy drugs. Today it is used in gout and hyperuricemia. Due to its additive benefit in preventing oxidative damage, attention has shifted towards the use of allopurinol in organ ischemia and reperfusion. CURRENT STATUS: Currently, the mechanism by which allopurinol exerts a protective benefit in ischemia reperfusion related events is not fully understood. There are various theories: it may act by inhibiting the irreversible breakdown of purine substrates, and/or by inhibiting the formation of reactive oxygen species, and/or by protecting against damage to the mitochondrial membrane. AIM: This work focuses on liver ischemia and reperfusion injury in an effort to better understand the mechanisms associated with allopurinol and with this pathological entity. REVIEW OF LITERATURE: The current research, mainly in animal models, points to allopurinol having a protective benefit, particularly if used pre-ischemically in liver ischemia reperfusion injury. Furthermore, after reviewing allopurinol dosing and administration, it was found that 50 mg/kg is statistically the most effective dose in attenuating liver ischemia reperfusion injury. Owing to the limited number of samples, the time of administration did not show statistical difference, but allopurinol was often beneficial when given around 1 h before ischemia. CONCLUSION: In conclusion, allopurinol, through its known xanthine oxidase inhibitory effect, as only one of the potential mechanisms, has demonstrated its potential application in protecting the liver during ischemia and reperfusion.

Allopurinol protection in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: Through the evaluation of randomized clinical trials using a statistical methodology consisting of comparative assessment, we sought to determine the conditions under which allopurinol was a protective agent for patients undergoing coronary artery bypass grafting (CABG). METHODS: The medical literature was searched for all human clinical trials from 1966 to 2008 examining the use of allopurinol in CABG. The final articles were divided into two groups based on the effectiveness of allopurinol, as determined by the requirement of postoperative inotropic/mechanical LV support. In four of the studies patients had high risk factors for CABG and this group was considered the high-risk (HR) group. The other four studies found that allopurinol-treated patients did as well as their own controls. This group had few risk factors and was considered the low-risk (LR) group. RESULTS: This study demonstrated that HR patients who received allopurinol during CABG had significantly better results than the HR patients without allopurinol treatment. Patients receiving allopurinol in the group with LR factors had no significant differences compared with the LR controls. HR allopurinol patients did significantly better (p <. 05) than LR allopurinol patients undergoing CABG. CONCLUSIONS: It was observed that patients with HR factors benefited more from allopurinol than patients with LR factors. Our findings lead us to believe that it is possible that allopurinol is efficacious in patients with a potentially higher oxidant buildup as a result of increased cardiovascular risk. This hypothesis needs to be confirmed.

Effects of dantrolene on ischemia-reperfusion injury in animal models: a review of outcomes in heart, brain, liver, and kidney.

BACKGROUND/OBJECTIVES: Ischemia-reperfusion (IR) is the restoration of blood flow to a tissue that was formerly deficient of blood flow. Tissue damage after IR is considered an IR injury (IRI). During IR, there is an increased level of cytosolic calcium ([Ca(2+)]i) due to the release of calcium from mitochondrial, sarcoendoplasmic reticulum, and nuclear organelles. Dantrolene sodium (dantrolene) is a 1-[[[5-(4-nitrophenol)-2-furanyl]methylene]amino]-2, 4-imidazolidinedione sodium salt with a nonspecific mechanism, inhibiting organelle release of Ca(2+) into the cytosol. This work reviews the outcomes of administering dantrolene in brain, heart, liver, and kidney animal models of IRI. METHODS: An extensive PubMed, MEDLINE, and MEDLAR literature review during the last 30 years on the effect of dantrolene in IRI in animal models was analyzed to determine the clinical implications of this important study. Particular attention was given to dantrolene in heart, brain, liver, and kidney IRI. RESULTS: Heart: Nine studies of heart IRI were reviewed and include an in vivo dog model (n = 1), in vivo rabbit model (n = 1), isolated dog myocardial fibers (n = 1), and isolated rat hearts (n = 6). Four studies showed decreased infarct size and increased cardiac function after IRI. One in vivo rabbit study found no difference in infarct size or cardiac function after IRI versus controls. Dantrolene may be protective or inductive of post-IRI arrhythmias depending on preestablished myocyte cycling times. Brain: Nine studies of brain IRI were reviewed and include an in vivo dog model (n = 1), in vivo gerbil model (n = 2), and in vivo rat models (n = 6). Dantrolene shows protective decreases in apoptotic markers in 6 studies, but it shows no effect on the necrotic core and mixed effects on reduction of infarct volume. One study found increased mortality in the dantrolene group. Liver: One study of in vivo rat liver IRI found that dantrolene decreased liver function tests, tissue necrosis factor α, tissue necrosis, and increased interleukin 10. Kidney: One study of in vivo rat kidney IRI showed that dantrolene had no effect. CONCLUSIONS: Dantrolene shows protective effects in animal models of heart, brain, and potentially liver IRI, reinforcing the importance of calcium homeostasis during IRI. Variations of dose, timing of administration, route of administration, and outcomes between studies make definitive conclusions difficult. The nonspecific mechanism of action of dantrolene may also account for the variation among studies. Lack of studies in the liver and kidney makes any consensus in these organs premature, and thus, emphasis for this review was put on studies of the heart and brain.

Allopurinol, xanthine oxidase, and cardiac ischemia.

Allopurinol as an effective inhibitor of the enzyme xanthine oxidase (XO) has been used for several decades for the treatment of patients with gout and hyperuricemia. Because the inhibition of XO limits the formation of radical oxygen species as well as uric acid (UA) production, allopurinol has been used experimentally for the treatment of conditions associated with ischemia and reperfusion (I/R) injury.Although there have been many ischemic organs treated in the laboratory with allopurinol, the heart has been of particular interest. Therefore, we emphasize our attention to the administration of XO inhibitors such as allopurinol on cardiac I/R as well as cardiac failure. Experimental data also support allopurinol as a possible consideration for biochemical support after acute myocardial infarction. Anker and associates (Circulation. 2003;107:1991-1997) have observed a direct correlation between uric acid levels and mortality in treated heart failure patients. Anker and associates showed a 100% mortality rate in patients with UA levels 800 micromol/L or less over a period of 3 years. Comparing this to a 27% mortality rate in patients with UA levels 400 micromol/L or less over a period of 10 years, it seems that the suppression of XO activity ameliorates myocardial inefficiency, and poor vascular flow may present innovative contributions to the future treatment of I/R heart failure patients. Our review focuses on the role of allopurinol on ischemic hearts as well as those with added chronic heart failure.