Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy

Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy. Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out. The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P=0.008, P<0.001, P=0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P< 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P<0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P<0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons-Smith classification) in patients on conservative therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P=0.016) and theta band (P= 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D. In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological, and cognitive disorders, might enable a better quality of life and a major compliance with a probable reduction in the healthcare costs

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study

Introduction In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and &gt;= 3 (late add-on) prior antiseizure medications. Results A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p &lt; 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p &lt; 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p &lt; 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively. Conclusion Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy

The Importance of Microcirculation and the Pathophysiological Role of Endothelin-1 in Liver Surgery and Transplantation

The complex functions of the liver in metabolism, biosynthesis, and clearance, are all dependent on microcirculation. Despite growing data demonstrating the role of microcirculation in regulating liver function, this knowledge has not been translated into clinical practice. The aim of this study is to quantify hepatic microcirculation in-vivo using Side-stream dark field (SDF) imaging in order to predict the risk of early allograft dysfunction (EAD) or postoperative liver failure after liver resection and transplantation. Microcirculation parameters were correlated with hepatic blood flow, hemodynamic parameters, and soluble mediators. The study investigates also the role of endothelin-1 (ET-1), a modulator of the microcirculation, as marker of hepatic and renal functions. Materials and Methods Study 1 describes the use of SDF in 35 patients undergoing liver resection. Study 2 describes the use of SDF in 28 patients undergoing LT and the relationship between microcirculation with hemodynamics. Study 3 describes the impact of technique of reperfusion on microcirculation, and its correlation with gene expression, and serum markers. Seventy patients undergoing LT were randomized in two groups, sequential versus simultaneous reperfusion. Study 4 investigates the importance of ET-1 axis in predicting the risk of acute kidney injury in LT. Microcirculation measurement by SDF included functional sinusoidal density, sinusoidal diameter, red blood cell velocity, volumetric blood flow, and flow heterogeneity. The serum concentrations of ET-1, and 4 cytokines were analyzed with Luminex. Gene expression was assessed with qPCR. Results Study 1 demonstrates that low residual volume is associated with microcirculation dysfunction which is predictive of liver function. ET-1 and sRAGE level were also correlated to post-operative liver dysfunction. Study 2: SDF assessment post reperfusion was predictive of the risk of developing EAD. Study 3: demonstrates that ET-1 level is an independent predictor of EAD and AKI post-LT. Study 4: Despite longer warm ischemic time, simultaneous reperfusion caused less microcirculatory disturbance and superior primary function. Conclusions Assessment of the microcirculation in real time can be used to identify patients at risk of EAD or postoperative liver dysfunction who may benefit from surgical or pharmacological intervention. Despite longer warm ischemic time, simultaneous reperfusion causes less microcirculatory disturbance and improved functions in marginal grafts

Anti-LGI1 encephalitis: A family affair

Here we describe the second ever-reported case of familial anti-leucine-rich glioma-inactivated protein 1 (LGI1) limbic encephalitis (LE). Two elderly Caucasian sisters presented with psychiatric symptoms and cognitive impairment, followed by faciobrachial dystonic seizures. Anti-LGI1 antibodies were detected in their serum. Considering they had been living in distant regions for decades, environmental factors could be ruled out. Human leukocyte antigen (HLA) genotyping revealed that both carried HLA-DRB1*07, found in 90% of anti-LGI1 en-cephalitis patients, HLA-DQA1*02:01 and HLA-DQB1*03:03, commonly associated with DRB1*07:01. Consid-ering the exceptional nature of familial cases, as-yet-unknown genetic contributors other than HLA might play a role in our siblings

Acute hepatitis associated with lamotrigine and managed with the molecular adsorbents recirculating system (MARS)

Lamotrigine (LTG) has been associated with serious idiosyncratic reactions, including fulminant hepatic failure in children and adults (1–4). Recently Sen et al. (5) proposed treating hepatotoxicity induced by phenytoin (PHT), a drug that is 90% protein bound, by detoxification with the molecular adsorbents recirculating system (MARS). Because this blood-purification system is based on the principle of albumin dialysis, it is especially useful in cases of toxicity induced by highly protein bound drugs. LTG is eliminated primarily by glucuronide conjugation, and its plasma protein binding is 55

Impact of Intensive Care Unit Discharge Delay on Liver Transplantation Outcomes

Background: For general intensive care unit (ICU) patients, ICU discharge delay (ICUDD) has been associated with an increased hospital length of stay (LOS) and the acquisition of multi-resistant organism (MRO) infections. The impact of ICUDD on liver transplant (LT) recipients is unknown. Methods: We retrospectively studied consecutive adult LT between 2011 and 2019. ICUDD was defined as &gt;8 h between a patient being cleared for discharge to ward and the patient leaving the ICU. Results: 550 patients received LT and the majority (68.5%) experienced ICUDD. The median time between clearance for ward and the patient leaving the ICU was 25.6 h. No donor or recipient variables were associated with ICUDD. Patients cleared for discharge early in the week (Sunday-Tuesday) and those discharged outside routine work hours were more likely to experience ICUDD (p = 0.001 and p &lt; 0.001, respectively). The median hospital LOS was identical (18 days, p = 0.96) and there were no differences in other patient outcomes. Patients who became colonized with MRO in the ICU spent a longer time there compared to those who remained MRO-free (9 vs. 6 days, p &lt; 0.001); however, this was not due to ICUDD. Conclusion: ICUDD post-LT is common and does not prolong hospital LOS. ICUDD is not associated with adverse patient outcomes or MRO colonization