Robotic living donor nephrectomy is associated with reduced post-operative opioid use compared to hand-assisted laparoscopic approach.

BACKGROUND: Robotic donor nephrectomy (RDN) has emerged as a safe alternative to laparoscopic donor nephrectomy (LDN). Having previously demonstrated comparable efficacy, this study aims to examine postoperative analgesia use (opioid and non-opioid) in the two groups. METHODS: We conducted a retrospective review of 300 living donor nephrectomies performed at our center, comparing 150 RDN's with a contemporary cohort of 150 hand-assisted LDN's. In addition to clinical and demographic information, data on postoperative inpatient opioid and non-opioid analgesia (from patient's arrival to the surgical floor after surgery till the time of discharge) was collected. Opioid dosages were standardized by conversion to morphine milligram equivalents (MME). All patients were managed post-operatively under a standardized ERAS pathway for living donor nephrectomy patients. RESULTS: There were no significant differences in donor age, gender, and BMI between RDN and LDN groups. Total post-operative opioid use (MME's) was significantly lower in RDN patients (RDN 27.1 vs. LDN 46.3; P < 0.0001). Breakdown of opioid use with post-operative (POD) day demonstrated significantly lower use in RDN group on POD1 (RDN 8.6 vs. LDN 17.0; P < 0.05), and POD2 (RDN 3.9 vs LDN 10; P < 0.05). RDN patients had a shorter post-operative length of stay (LOS) (RDN 1.69 days vs. LDN 1.98; P = 0.0003). There were no differences between groups in non-opioid medication use, complications, and readmission rates. CONCLUSION: RDN has comparable safety to hand-assist LDN and offers additional benefits of lower postoperative opioid requirement and a shorter hospital LOS.

Utilization of older deceased donors for pediatric liver transplant may negatively impact long-term survival.

BACKGROUND: Multiple adult studies have investigated the role of older donors (ODs) in expanding the donor pool. However, the impact of donor age on pediatric liver transplantation (LT) has not been fully elucidated. METHODS: UNOS database was used to identify pediatric (≤18 years) LTs performed in the United States during 2002-22. Donors ≥40 years at donation were classified as older donors (ODs). Propensity analysis was performed with 1:1 matching for potentially confounding variables. RESULTS: A total of 10,024 pediatric liver transplantation (PLT) patients met inclusion criteria; 669 received liver grafts from ODs. Candidates receiving OD liver grafts were more likely to be transplanted for acute liver failure, have higher Model End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) scores at LT, listed as Status 1/1A at LT, and be in the intensive care unit (ICU) at time of LT (all p < 0.001). Kaplan-Meier (KM) analyses showed that recipients of OD grafts had worse patient and graft survival (p < 0.001) compared to recipients of younger donor (YD) grafts. KM analyses performed on candidates matched for acuity at LT revealed inferior patient and graft survival in recipients of deceased donor grafts (p < 0.001), but not living donor grafts (p > 0.1) from ODs. Cox regression analysis demonstrated that living donor LT, diagnosis of biliary atresia and first liver transplant were favorable predictors of recipient outcomes, whereas ICU stay before LT and transplantation during 2002-12 were unfavorable. CONCLUSION: Livers from ODs were used for candidates with higher acuity. Pediatric recipients of livers from ODs had worse outcome compared to YDs; however, living donor LT from ODs had the least negative impact on recipient outcomes.

Global liver transplantation: emerging trends and ethical challenges.

PURPOSE: Liver transplant (LT) is the only definitive treatment for end-stage liver disease (ESLD). This review aims to explore current global LT practices, with an emphasis on challenges and disparities that limit access to LT in different regions of the world. METHODS: A detailed analysis was performed of present-day liver transplant practices throughout the world, including the etiology of liver disease, patient access to transplantation, surgical costs, and ongoing ethical concerns. RESULTS: Annually, only 10% of the patients needing a liver transplant receive an organ. Currently, the USA performs the highest volume of liver transplants worldwide, followed by China and Brazil. In both North America and Europe, nonalcoholic fatty liver disease is becoming the most common indication for LT, compared to hepatitis B and C in most Asian, South American, and African countries. While deceased donor liver transplant remains the most performed type of LT, living donor liver transplant is becoming increasingly popular in some parts of the world where it is often the only option due to a lack of well-developed infrastructure for deceased organ donation. Ethical concerns in liver transplantation fundamentally revolve around the definition of a deceased donor and the exploitation of living donor liver donation systems. CONCLUSION: Globally, liver transplant practices and outcomes are varied, with differences driven by healthcare policies, inequities in healthcare access, and ethical concerns.

The impact of a dedicated operating room team on robotic transplant program growth and fellowship training.

INTRODUCTION: Despite considerable interest in robotic surgery, successful incorporation of robotics into transplant programs has been challenging. Lack of a dedicated OR team with expertise in both robotics and transplant is felt to be a major barrier. This paper assesses the impact of a dedicated robotic transplant team (DART) on program growth and fellowship training at one of the largest robotic transplant programs in North America. METHODS: This is a single center, retrospective review of all robotic operations performed on the transplant surgery service from October 2017 to October 2022. DART was incorporated in February 2020 and included transplant first assists (RFAs), scrub technologists and circulating nurses who received robotic training. Robotic experience before and after DART was compared to assess its impact on program growth and training. RESULTS: Four hundred and two robotic cases were performed by five transplant surgeons: 63 pre-DART and 339 post-DART. 40% of cases were transplant-related and 59.5%, HPB. There was a significant increase in case volume (2.5-10.6 cases/month, p < .0001) and complexity (36.5% vs. 70.3% high complexity cases, p < .0001) post-DART. RFA case coverage increased from 17% to 95%, and participation of transplant fellows as primary surgeons increased from 17% to 95% post-DART period (both p < .05). Conversion rates (9.5% vs. 4.1%) and room turn-around-times (TAT) (58.4 vs. 40.3 min) were lower post-DART (p < .05). There were no emergent conversions, conversions in transplant patients, or robot-related complications in either group. CONCLUSION: OR teams with expertise in robotics and transplant surgery can accelerate growth of robotic transplant programs while maintaining patient safety.

Robotic donor nephrectomy: optimizing outcomes beyond the limitations of laparoscopy.

BACKGROUND: Robotic donor nephrectomy (RDN) has emerged as a safe alternate to laparoscopic donor nephrectomy (LDN), offering improved visualization, instrument dexterity and ergonomics. There is still concern about how to safely transition from LDN to RDN. METHODS: We performed a retrospective review of 150 consecutive living donor operations (75 LDN and 75 RDN) at our center, comparing the first 75 RDN's with the last 75 LDN's performed prior to the initiation of the robotic transplant program. Operative times and complications were used as surrogates of efficiency and safety, respectively, to estimate the learning curve with RDN. RESULTS: RDN was associated with a longer total operative time (RDN 182 vs LDN 144 min; P < 0.0001) but a significantly shorter post-operative length of stay (RDN 1.8 vs LDN 2.1 days; P = 0.0213). Donor complications and recipient outcomes were the same between both groups. Learning curve of RDN was estimated to be about 30 cases. CONCLUSIONS: RDN is a safe alternate to LDN with acceptable donor morbidity and no negative impact on recipient outcomes even during the early part of the RDN learning curve. Surgeon preferences for the robotic approach compared to traditional laparoscopy will require further scrutiny to improve ergonomics and operative efficiency.

Liver Transplantation After Hepatic Artery Infusion Pump Therapy: Single-Center Experience and Technical Considerations.

BACKGROUND: Hepatic artery infusion pump (HAIP) therapy has become increasingly commonplace in the treatment of intrahepatic tumors. When combined with standard chemotherapy, HAIP therapy demonstrates a higher response rate than chemotherapy alone. Biliary sclerosis is observed in up to 22 % of patients, for whom no treatment has been standardized. This report describes orthotopic liver transplantation (OLT) both as a treatment for HAIP-induced cholangiopathy and as a possible definitive oncologic treatment after HAIP-bridging therapy. METHODS: A retrospective study reviewed patients who had undergone HAIP placement followed by OLT at the authors' institution. Patient demographics, neoadjuvant treatment, and postoperative outcomes were reviewed. RESULTS: Seven OLTs were performed for patients with prior HAIP placement. The majority were women (n = 6), and the median age was 61 years (range, 44.5-65.5 years). Transplantation was performed for five patients due to biliary complications secondary to HAIP and two patients because of residual tumor after HAIP therapy. All the OLTs had difficult dissections due to adhesions. Because of HAIP-induced damage, atypical arterial anastomoses were required in six patients (2 patients used a recipient common hepatic artery below the gastroduodenal artery takeoff; 2 patients used recipient splenic arterial inflow; 1 patient used the junction of the celiac and splenic arteries; and 1 patient used the celiac cuff). The one patient with standard arterial reconstruction experienced an arterial thrombosis. The graft was salvaged with thrombolysis. Biliary reconstruction was duct-to-duct in five cases and Roux-en-Y in two cases. CONCLUSIONS: The OLT procedure is a feasible treatment option for end-stage liver disease after HAIP therapy. Technical considerations include a more challenging dissection and an atypical arterial anastomosis.

Circadian regulation of dentate gyrus excitability mediated by G-protein signaling.

The central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm driven by molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machinery, but whether these molecular programs generate oscillations of membrane properties is unclear. Here, we show that intrinsic excitability of mouse dentate granule neurons exhibits a 24-h oscillation that controls spiking probability. Diurnal changes in excitability are mediated by antiphase G-protein regulation of potassium and sodium currents that reduce excitability during the Light phase. Disruption of the circadian transcriptional machinery by conditional deletion of Bmal1 enhances excitability selectively during the Light phase by removing G-protein regulation. These results reveal that circadian transcriptional machinery regulates intrinsic excitability by coordinated regulation of ion channels by G-protein signaling, highlighting a potential novel mechanism of cell-autonomous oscillations.

Incidences of extrapyramidal symptoms in patients with schizophrenia after treatment with long-acting injection (depot) or oral formulations of olanzapine.

BACKGROUND: The incidence of extrapyramidal symptoms (EPS) has been shown to be generally low among patients with schizophrenia receiving oral olanzapine. A long-acting injection (LAI) of olanzapine has recently been approved for the treatment of schizophrenia in a number of countries. Accordingly, the objective of the current analyses was to compare the incidences of EPS during treatment with olanzapine LAI versus oral olanzapine. METHODS: The incidences of treatment-emergent EPS were examined in adults with schizophrenia receiving olanzapine LAI or oral olanzapine for up to 3 years. Short-term data were obtained from two double-blind studies of olanzapine LAI: one included a placebo comparator, and the other included oral olanzapine as an active comparator. Long-term data were obtained from an open-label extension study for olanzapine LAI and from an integrated database for oral olanzapine. RESULTS: The short-term incidence of EPS was 5.6% during treatment with olanzapine LAI (45-405 mg every 2-4 weeks) and 5.0% with oral olanzapine (5-20 mg/day). Akathisia (2.6% LAI, 1.2% oral), and Parkinson-like symptoms (1.8% LAI, 3.7% oral) were similar between treatment groups. The incidence of EPS for long-term treatment was 9.2% for olanzapine LAI. Incidences of EPS events were not significantly different between patients receiving olanzapine LAI or oral olanzapine for up to 3 years. CONCLUSIONS: These findings suggest that EPS profiles are similar for olanzapine LAI and oral olanzapine.

Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia.

BACKGROUND: In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al., 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes. METHODS: Outpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140), "medium" (405 mg/4 weeks; N = 318), or "high" (300 mg/2 weeks; N = 141) dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data), or the Cochran-Armitage test (categorical data). RESULTS: Safety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose), mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02]), high: +3.58 [SD = 33.78] µg/L, p = .001; ES = 0.410 high vs. low dose), fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose) and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose). Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p <.01; ES = 0.356 high vs. low dose), relapse rate (low: 16%, medium: 10%, high: 5%, p = .003; NNT = 9 high vs. low dose), all-cause discontinuation rate (low: 36%, medium: 30%, high: 24%, p = .037; NNT = 9 high vs. low dose), and rate of discontinuation due to efficacy-related reasons (low: 20%, medium: 14%, high: 6%, p <.001). Time to all-cause discontinuation (p = .035) and time to relapse (p = .005) were also significantly related to dose. CONCLUSIONS: Analyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00088491.

Dose response and atypical antipsychotics in schizophrenia.

Based on information from clinical trials, both the efficacy and adverse effects of conventional antipsychotics in the treatment of schizophrenia are dose related. The overlapping nature of these dose-response profiles limits the use of these agents. Atypical antipsychotics provide greater relief across the comorbid symptom domains of schizophrenia, but dose-response studies and clinical experience have revealed that some of these drugs also have dose limitations. This article reviews the dose-response relationships of the atypical antipsychotics as presented predominantly in pivotal, randomised studies (double-blind and otherwise). Limited data indicate that clozapine shows dose-related efficacy up to 600 mg/day in patients with treatment-resistant schizophrenia. However, higher dosages of clozapine may be associated with the risk of seizures. Risperidone demonstrates dose-related adverse events that compromise efficacy. The dose-response relationships for ziprasidone, quetiapine and aripiprazole are less well established. The efficacy of olanzapine appears to be dose related within the recommended dosage range of 10-20 mg/day, but clinical trials that have explored higher dosages suggest improved efficacy. Furthermore, the higher doses are not associated with a significantly increased incidence of adverse events. Further studies are clearly needed to fully characterise the dose-response relationships of atypical antipsychotics.

Olanzapine orally disintegrating tablets in the treatment of acutely ill non-compliant patients with schizophrenia.

The objective of this study was to determine if the orally disintegrating tablet formulation of olanzapine, Zyprexa Zydis, would facilitate antipsychotic medication compliance in acutely ill, non-compliant patients. Eighty-five acutely ill patients with schizophrenia or schizoaffective disorder who met medication non-compliance criteria received open-label olanzapine orally disintegrating tablets (1020 mgd) for up to 6 wk. Improvement in medication compliance was assessed using various rating scales to measure changes in psychopathology, medication-taking and compliance attitudes, and nursing care burden. Safety variables were also measured. Significant improvement from baseline was demonstrated in the Positive and Negative Syndrome Scale total score at Week 1 and subsequently (p0.001). Significant improvement from baseline was also seen in various scales measuring medication compliance, attitude, and nursing care burden (p0.05). Olanzapine orally disintegrating tablets were well-tolerated. Olanzapine orally disintegrating tablets may benefit acutely ill, non-compliant schizophrenic patients by facilitating acceptance of active antipsychotic drug therapy.

Effectiveness of rapid initial dose escalation of up to forty milligrams per day of oral olanzapine in acute agitation.

BACKGROUND: Patients experiencing an acute decompensation of schizophrenia or bipolar disorder often present in an agitated state. Agitation presents a barrier to therapy, interrupting the typical physician-patient alliance and creating a disruptive, even hazardous, environment. Rapid assessment and effective treatment are necessary to manage agitation and, potentially, to shorten the time to recovery. METHODS: One hundred forty-eight acutely agitated patients received either: rapid initial dose escalation (RIDE) in which up to 40 mg of oral olanzapine was allowed on days 1 and 2, up to 30 mg on days 3 and 4, and 5 to 20 mg thereafter; or usual clinical practice (UCP) in which patients received 10 mg/d olanzapine plus up to 4 mg lorazepam on days 1 and 2, up to 2 mg on days 3 and 4, and olanzapine 5 to 20 mg/d thereafter. The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC: poor impulse control, tension, hostility, uncooperativeness, and excitement) measured at 24 hours was the primary measure. Secondary assessments of agitation and safety were also performed. RESULTS: Agitation improved significantly from baseline for both treatment groups; however, improvement with the RIDE strategy was superior to UCP. The RIDE group improvement was superior on the primary efficacy measure (PANSS-Excited) at 24 hours; it was superior on all agitation measures at the end of double-blind treatment. Both treatments were well tolerated, with no clinically significant differences in safety measures. Treatment was not limited by oversedation and attention improved from baseline in both groups. CONCLUSIONS: This study demonstrates the value of olanzapine in the treatment of acutely agitated patients. A new approach to olanzapine dosing that expands the initial dose range up to 40 mg/d may offer superior efficacy in rapidly and effectively controlling the symptoms of agitation.