Eigen-entropy based time series signatures to support multivariate time series classification.

Most current algorithms for multivariate time series classification tend to overlook the correlations between time series of different variables. In this research, we propose a framework that leverages Eigen-entropy along with a cumulative moving window to derive time series signatures to support the classification task. These signatures are enumerations of correlations among different time series considering the temporal nature of the dataset. To manage dataset's dynamic nature, we employ preprocessing with dense multi scale entropy. Consequently, the proposed framework, Eigen-entropy-based Time Series Signatures, captures correlations among multivariate time series without losing its temporal and dynamic aspects. The efficacy of our algorithm is assessed using six binary datasets sourced from the University of East Anglia, in addition to a publicly available gait dataset and an institutional sepsis dataset from the Mayo Clinic. We use recall as the evaluation metric to compare our approach against baseline algorithms, including dependent dynamic time warping with 1 nearest neighbor and multivariate multi-scale permutation entropy. Our method demonstrates superior performance in terms of recall for seven out of the eight datasets.

Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia.

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.

Threshold-Responsive Colorimetric Sensing System for the Continuous Monitoring of Gases.

Colorimetric sensors are widely used because of their inherent advantages including accuracy, rapid response, ease-of-use, and low costs; however, they usually lack reusability, which precludes the continuous use of a single sensor. We have developed a threshold-responsive colorimetric system that enables repeated analyte measurements by a single colorimetric sensor. The threshold responsive algorithm automatically adjusts the sensor exposure time to the analyte and measurement frequency according to the sensor response. The system registers the colorimetric sensor signal change rate, prevents the colorimetric sensor from reaching saturation, and allows the sensor to fully regenerate before the next measurement is started. The system also addresses issues common to colorimetric sensors, including the response time and range of detection. We demonstrate the benefits and feasibility of this novel system, using colorimetric sensors for ammonia and carbon dioxide gases for continuous monitoring of up to (at least) 60 detection cycles without signs of analytical performance degradation of the sensors.

Quality Improvement Initiative in the NICU for Improved Practice of Cuff Blood Pressure Measurements.

BACKGROUND: Extreme preterm infants face lengthy hospitalizations and are often subjected to painful stimuli. These stimuli may be related to routine caregiving that may negatively impact long-term developmental outcomes. Frequently obtained cuff blood pressure (BP) measurements are an example of a potentially noxious stimulus to preterm infants that may have a cumulating impact on development. PURPOSE: The primary aim was to explore the frequency of cuff BP measurements obtained in hemodynamically stable extreme preterm infants in the neonatal intensive care unit (NICU). Our secondary aim was to reduce the number of cuff BP measurements obtained in hemodynamically stable extreme preterm infants in the NICU. METHODS: Quality improvement methodologies per the Institute for Healthcare Improvement were used combined with a multidisciplinary approach. Participants were infants born less than 27 weeks of gestation and discharged home. The baseline period was 2015 through Q2-2018 and the intervention period was Q3-2018 through Q1-2020. The electronic medical record was used to collect data and Minitab Statistical Software was used for data analysis. FINDINGS/RESULTS: A baseline of 5.0% of eligible patients received the desired number of cuff BP measurements and increased to 63.2% after the intervention period. IMPLICATIONS FOR PRACTICE: Findings demonstrate that using quality improvement methodology can improve clinical care. Findings suggest the feasibility and safety of reducing the number of cuff BP measurements obtained on hemodynamically stable infants in the NICU. IMPLICATIONS FOR RESEARCH: Future endeavors should aim to reduce the quantity of painful stimuli in the NICU. Long-term developmental outcomes should be correlated in these patients.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

RATIONALE & OBJECTIVE: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States. PREDICTOR(S): Presence (vs absence) of pre-existing kidney disease. OUTCOME(S): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary). ANALYTICAL APPROACH: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations. RESULTS: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]). LIMITATIONS: Potential residual confounding. CONCLUSIONS: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.

Perioperative population management for primary hip arthroplasty reduces hospital and postacute care utilization while maintaining or improving care quality.

STUDY OBJECTIVE: Physician-led multidisciplinary care coordination decreases hospital-associated care needs. We aimed to determine whether such care coordination can show benefits through the posthospital discharge period for elective hip surgery. DESIGN: Time Series of prospectively recorded and historical data. SETTING: Academic tertiary care medical center and health system. PATIENTS: 449 patients undergoing elective primary hip surgery. INTERVENTIONS: For the intervention group we redesigned care with a comprehensive 14-16 week multidisciplinary standardized clinical pathway, the Ochsner hip arthroplasty perioperative surgical home (PSH). Essential pathway components were preoperative medical risk assessment, frailty scoring, home assessment, education and expectation setting. Collaborative team-based care, rigorous application of perioperative milestones, and proactive postoperative care coordination were key elements. MEASUREMENTS: The intervention group was compared to historical controls with regard to demographics, risk factors, quality metrics, resource utilization and discharge disposition, the primary outcomes were hospital length of stay and postacute facility utilization. MAIN RESULTS: Compared to historical controls, the intervention group had similar risk factors and the same or better quality outcomes. It had less combined skilled nursing facility (SNF) and inpatient rehabilitation facility (IRF) utilization compared to controls (16.5% vs. 27.5%). More intervention patients were discharged with home self-care compared to historical controls (10.7% vs 5.3%). During the intervention period combined SNF/IRF utilization decreased substantially from 19.8% early on, to 13.2% during a later phase. Intervention patients had fewer hospital days compared to historical controls (1.86 vs 3.34 days, respectively; P < 0.0001). CONCLUSIONS: A perioperative population management oriented care model redesign was effective in decreasing hospital days and postacute facility-based care utilization, while quality metrics were maintained or improved.

The Effect of the IPACK Block on Pain After Primary TKA: A Double-Blinded, Prospective, Randomized Trial.

BACKGROUND: The purpose of this study was to determine if infiltration of local anesthetic between the interspace between the popliteal artery and capsule of the knee (IPACK) provides benefit in total knee arthroplasty. METHODS: Patients were randomized into continuous adductor canal block with IPACK block or continuous adductor canal block with sham subcutaneous saline injection. Only the anesthesiologist performing the block was aware of randomization status. After surgery, a blinded assessor recorded opioid consumption, pain scores, and gait distance. RESULTS: There were 35 patients in the IPACK group and 34 in the NO IPACK group. There was no difference demographically between the groups. In the postanesthesia care unit (PACU), the average (P = .0122) and worst (P = .0168) pain scores at rest were statistically lower in the IPACK group. There was no difference in the pain scores during physical therapy (P = .2080). There was no difference in opioid consumption in the PACU (P = .7928), or at 24 hours (P = .7456). There was no difference in pain scores on POD 1 in the AM (P = .4597) or PM (P = .6273), or in the walking distance (P = .5197). There was also no difference in length of stay in the PACU (P = .9426) or hospital (P = .2141). CONCLUSION: The IPACK group had lower pain scores at rest in the PACU, but this is likely not clinically significant. The routine use of the IPACK is not supported by the results of this study. There may be indications for the use of the IPACK block as a rescue block or in patients who have contraindications to our standard multimodal treatment regimen or in patients with chronic pain or opioid dependence.

A Quality Improvement Approach to Reduce Unplanned Extubation in the NICU While Avoiding Sedation and Restraints.

The unplanned extubation (UE), a common adverse event in the neonatal intensive care unit (NICU), may result in airway trauma, cardiopulmonary resuscitation, and, in extreme cases, death. As part of the Nationwide Children's Hospital NICU's effort to optimize NICU graduates' neurodevelopmental outcomes, skin-to-skin care of intubated infants is encouraged, while sedation and restraints to prevent UE are strongly discouraged. This project aimed to decrease the UE rate from 1.85 to 1.5 per 100 endotracheal tube (ETT) days. METHODS: The project occurred in a 114-bed, level-IV NICU with approximately 850 admissions per year and 100% outborn infants. A multidisciplinary team began biweekly meetings to review all UE events, later separating these into preventable and nonpreventable. Important ongoing tests of change included assigning a single process owner for UE reporting, ensuring proper ETT securement, and using 2 clinical staff during patient and/or ETT manipulation. RESULTS: Early in the project, enhanced detection led to an increased rate from 1.85 to 3.26 per 100 ETT days. However, identifying preventable events empowered staff to decrease the frequency to 2.03 per 100 ETT days. In August 2017, an ETT taping method change produced an increase in special causes due to decreased compliance. However, when securement methods were enhanced, noncompliance reversed and is now trending favorably. CONCLUSIONS: Decreasing UE in a neurodevelopmentally friendly unit, which avoids sedation and restraints, is challenging. Using a multidisciplinary quality improvement approach and after appropriately capturing events, we reduced UE, with the highest impact of intervention being ETT securement standardization.

The Effects of Peri-Operative Dexamethasone on Patients Undergoing Total Hip or Knee Arthroplasty: Is It Safe for Diabetics?

BACKGROUND: Peri-operative dexamethasone has been shown to effectively reduce post-operative nausea and vomiting and aide in analgesia after total joint arthroplasty (TJA); however, systemic glucocorticoid therapy has many adverse effects. The purpose of this study is to determine the effects of dexamethasone on prosthetic joint infection (PJI) and blood glucose levels in patients undergoing TJA. METHODS: A retrospective chart review of all patients receiving primary TJA from 2011 to 2015 (n = 2317) was conducted. Patients were divided into 2 cohorts: dexamethasone (n = 1426) and no dexamethasone (n = 891); these groups were subdivided into diabetic and non-diabetic patients. The primary outcome was PJI; secondary measures included glucose levels and pre-operative hemoglobin A1c (A1c) values. Statistics were carried out using logistic and regression models. RESULTS: Of the 2317 joints, 1.12% developed PJI; this was not affected by dexamethasone (P = .166). Diabetics were found to have higher rate of infection (P < .001); however, diabetics who received dexamethasone were not found to have a significantly higher infection rate that non-diabetics (P = .646). Blood glucose levels were found to increase post-operatively, and dexamethasone did not increase this change (P = .537). Diabetes (P < .001) and increasing hemoglobin A1c (P < .001) were also associated with increased serum glucose levels; however, this was not influenced by dexamethasone (P = .595). CONCLUSION: Although diabetic patients were found to have a higher infection rate overall, this was not affected by administration of intravenous dexamethasone, nor was the post-operative elevation in serum glucose levels. In this study population, peri-operative intravenous dexamethasone did not increase the rate of PJI and was safe to administer in patients undergoing TJA.

A Handheld, Colorimetric Optoelectronic Dynamics Analyzer for Measuring Total Ammonia of Biological Samples.

This paper introduces a wireless, solid-state, portable, and automated device capable of measuring the total ammonia [ammonia (NH3) and ammonium (NH4+)] levels of fluids, including biological samples. This device reliably measures the total ammonia of biological samples (e.g., urine) faster than the current ammonia quantification techniques. Medical professionals typically estimate NH4+ levels using error-prone indirect measurement techniques (i.e., urine anion gap), which are time-consuming and are seldom suitable for periodic measurements. Several instantaneous measurements of total ammonia levels in a patient urine could be utilized as an early warning for both acid-base and/or potassium disturbances. Given the device's operation mechanism, it is able to quantify the total ammonia concentration within a biological sample in only 5 s and can simultaneously transmit data to other devices via Bluetooth. The analytical operation demonstrated high sensitivity, high specificity, fast reversibility, rapid response time, and has enabled the accurate determination of total ammonia concentration in urine samples produced by subjects who had consumed diets of variable protein compositions.

A Case Report of Cronkhite-Canada Syndrome Complicated by Membranous Nephropathy.

Cronkhite-Canada syndrome (CCS) is a very rare disorder with less than 500 reported cases. It is characterized by extensive gastrointestinal polyposis and ectodermal anomalies including alopecia, cutaneous hyperpigmentation, and onychodystrophy. Only 3 cases of associated kidney disease (membranous nephropathy [MN]) have been reported. A 71-year-old male with CCS was referred for further evaluation of proteinuria. The patient initially presented with abdominal discomfort, weight loss, dysgeusia, skin hyperpigmentation, alopecia, and dystrophic nails. Endoscopic evaluation showed widespread gastrointestinal nodular inflammation and polyps. Histopathology was consistent with CCS. Initial treatment was with prednisone, azathioprine, and ranitidine. He had moderate clinical improvement but developed nephrotic-range proteinuria. Renal biopsy showed MN, and cyclosporine was started. The patient had significant improvement in his CCS manifestations; however, his proteinuria and renal function worsened. Rituximab was added to his regimen of cyclosporine and azathioprine, which resulted in remission of his MN, marked improvement in his polyposis, and near resolution of his cutaneous symptoms. This case represents a unique presentation of CCS associated with MN treated with rituximab. The excellent clinical response observed for both CCS and MN advocates consideration of this treatment, especially for refractory disease.

Novel Regional Techniques for Total Knee Arthroplasty Promote Reduced Hospital Length of Stay: An Analysis of 106 Patients.

BACKGROUND: Novel regional techniques, including the adductor canal block (ACB) and the local anesthetic infiltration between the popliteal artery and capsule of the knee (IPACK) block, provide an alternative approach for controlling pain following total knee arthroplasty (TKA). This study compared 3 regional techniques (femoral nerve catheter [FNC] block alone, FNC block with IPACK, and ACB with IPACK) on pain scores, opioid consumption, performance during physical therapy, and hospital length of stay in patients undergoing TKA. METHODS: All patients had a continuous perineural infusion, either FNC block or ACB. Patients in the IPACK block groups also received a single injection 30-mL IPACK block of 0.25% ropivacaine. Pain scores and opioid consumption were recorded at postanesthesia care unit discharge and again at 8-hour intervals for 48 hours. Physical therapy performance was measured on postoperative days (POD) 1 and 2, and hospital length of stay was recorded. RESULTS: We found no significant differences in the 3 groups with regard to baseline patient demographics. Although we observed no differences in pain scores between the 3 groups, opioid consumption was significantly reduced in the FNC with IPACK group. Physical therapy performance was significantly better on POD 1 in the ACB with IPACK group compared to the other 2 groups. Hospital length of stay was significantly shorter in the ACB with IPACK group. CONCLUSION: This study demonstrated that an IPACK block reduced opioid consumption by providing effective supplemental analgesia following TKA compared to the FNC-only technique. ACB with IPACK provided equivalent analgesia and improved physical therapy performance, allowing earlier hospital discharge.

The Perioperative Surgical Home: Improving the Value and Quality of Care in Total Joint Replacement.

PURPOSE OF REVIEW: The perioperative surgical home (PSH) is a patient-centered, physician-led, multidisciplinary care pathway developed to deliver value-based care based on shared decision-making. Physician and hospital reimbursement will be tied to providing quality care at lower cost, and the PSH model has been used in providing care to patients undergoing lower extremity arthroplasty. The purpose of this review is to discuss the rationale, definition, development, current state, and future direction of the PSH. RECENT FINDINGS: The PSH model guides the patient throughout the pre and perioperative process and into the postoperative phase. It has been shown in multiple studies to decrease length of stay, improve functional outcomes, allow more home discharges, and lower costs. There is no increase in complications or readmission rates. The PSH pathway is a safe and effective method of providing value-based care to patients undergoing hip and knee arthroplasty.

[Small cell lung cancer associated with multiple paraneoplastic syndromes].

We report the case of a patient presenting with multiple severe electrolyte disturbances who was subsequently found to have small cell lung cancer. Upon further evaluation, she demonstrated three distinct paraneoplastic processes, including the syndrome of inappropriate antidiuretic hormone, Fanconi syndrome, and an inappropriate elevation in fibroblast growth factor-23 (FGF23). The patient underwent one round of chemotherapy, but she was found to have progressive disease. After 36 days of hospitalization, the patient made the decision to enter hospice care and later she expired.

Small cell lung cancer associated with multiple paraneoplastic syndromes / Cáncer de pulmón de células pequeñas asociado a múltiples síndromes paraneoplásicos

Abstracts We report the case of a patient presenting with multiple severe electrolyte disturbances who was subsequently found to have small cell lung cancer. Upon further evaluation, she demonstrated three distinct paraneoplastic processes, including the syndrome of inappropriate antidiuretic hormone, Fanconi syndrome, and an inappropriate elevation in fibroblast growth factor-23 (FGF23). The patient underwent one round of chemotherapy, but she was found to have progressive disease. After 36 days of hospitalization, the patient made the decision to enter hospice care and later she expired.

Resumen Se reporta el caso de una paciente que ingresó al hospital para evaluación de múltiples trastornos electrolíticos y, posteriormente, se le hizo el diagnóstico de cáncer de pulmón de células pequeñas. Tras la evaluación médica, se detectaron tres síndromes paraneoplásicos: síndrome de secreción inadecuada de hormona antidiurética, síndrome de Fanconi y elevación inapropiada del factor 23 de crecimiento de fibroblastos. Se le administró quimioterapia sin éxito, por lo cual se decidió darle tratamiento paliativo y, un tiempo después, falleció.

Challenging the knowledge base and skillset for providing surgical consent by orthopedic and plastic surgeons in the Netherlands: an identified area of improvement in patient safety.

BACKGROUND: Successfully completing a surgical informed consent process is an important element of the preoperative consult. A previous study of Dutch general surgeons demonstrated that the implementation of SIC did not meet acceptable standards. However, the quality of the SIC process in the orthopedic surgical or plastic surgical arena is unknown. METHODS: Following ethical approval, an online survey investigating specifics of surgical informed consent was performed among members of the Dutch Scientific Association of Orthopedic Surgeons and the Dutch Society for Plastic Surgery. RESULTS: A total of 335 responses from a majority of departments of orthopedic (86 %) and plastic surgery (78 %) were eligible for analysis. Scores on knowledge were poor as only 50 % recognized the three basic elements of surgical informed consent (competence, exchange of information and consent). The orthopedic group used more tools in the surgical informed consent process, such as instruction movies and websites or specialized nursing staff, compared to plastic surgery (orthopedic: 31-50 % vs. plastic: 6-30 %, p = 0.05- < 0.001). In contrast, surgical informed consent forms were used more frequently by the plastic surgical group (orthopedic 21 % vs. plastic:42 % p < 0.001). Control of the efficacy of the surgical informed consent process was low, 36 % in both groups. One in every seven orthopedic or plastic surgeons was faced with an official surgical informed consent-related complaint in the previous five years. CONCLUSIONS: Similar to general surgeons, Dutch orthopedic and plastic surgeons demonstrate poor knowledge and skills regarding surgical informed consent. Increased awareness, better training and use of modern tools including standard forms and online software programs will improve the SIC process and will optimize patient care.

A novel dextran polymer hydrogel local antimicrobial therapy in dogs: A pilot study.

Our purpose was to evaluate physical, laboratory, and/or radiographic abnormalities associated with a novel dextran polymer hydrogel local antimicrobial agent impregnated with amikacin and clindamycin in dogs having tibial plateau leveling osteotomy implants removed due to suspected surgical site infection. A total of 28 client-owned dogs were enrolled and 20 completed the study. Routine plate explantation and bacterial cultures were performed and the polymer hydrogel was applied to the surgery site. No systemic antimicrobials were used after surgery. Serum biochemistry, hematology, urinalysis, physical examinations, and radiographs were monitored before surgery and up to 12 wk after surgery. Sixteen of the 20 dogs (80%) had a positive bacterial culture, 44% of which were methicillin resistant. There were no significant alterations of laboratory values, physical examination, or radiographs to indicate adverse reactions to the polymer hydrogel. There were no signs of inflammation or infection in any patient at the 12-week postoperative recheck.

Thérapie antimicrobienne innovatrice locale à l'hydrogel de polymère de dextrane chez les chiens : étude pilote. Notre but consistait à évaluer les anomalies physiques, de laboratoire et/ou radiographiques associées à un nouvel agent antimicrobien local d'hydrogel de polymère de dextrane imprégné d'amikacine et de clindamycine chez les chiens dont les implants d'ostéotomie de nivellement du plateau tibial avaient été enlevés en raison d'une infection suspectée du site de la chirurgie. Un total de 28 chiens appartenant à des clients ont été recrutés et 20 ont fait partie de l'étude. Une explantation de routine de la plaque et des cultures bactériennes ont été réalisées et l'hydrogel de polymère a été appliqué au site de la chirurgie. Aucun antimicrobien systémique n'a été utilisé après la chirurgie. Une biochimie sérique, l'hématologie, l'analyse d'urine, des examens physiques et des radiographies ont été réalisés avant la chirurgie et jusqu'à 12 semaines après la chirurgie. Seize des 20 chiens (80 %) avaient une culture bactérienne positive dont 44 % était résistante à la méthicilline. Il n'y avait aucune altération importante des valeurs de laboratoire, de l'examen physique ou des radiographies pour indiquer des réactions indésirables à l'hydrogel de polymère. Il n'y a eu aucun signe d'inflammation ou d'infection chez aucun patient lors d'un examen postopératoire à 12 semaines.(Traduit par Isabelle Vallières).

Obesity Correlates With Glomerulomegaly But Is Not Associated With Kidney Dysfunction Early After Donation.

BACKGROUND: Body mass index (BMI) is a convenient measure used to assess obesity and is used to select candidates for kidney donation. Glomerulomegaly is an early indicator of obesity-related kidney disease. Whether obesity assessment by BMI best reflects underlying glomerulomegaly and is predictive of adverse changes in renal function postdonation is unclear. METHODS: We performed a retrospective study on a cohort of 1065 living donors at the Mayo Clinic in Rochester; obesity measures by BMI and by computed tomography were compared between 20 donors with largest to 20 donors with the smallest glomerular volumes (on implantation biopsy). In addition, the change in kidney function postdonation (mean 7 months) was compared across BMI groups (<25, 25-29, 30-34, ≥35 kg/m2) in about 500 donors. RESULTS: We observed that larger glomerular volume was more strongly associated with BMI per standard deviation (SD) (odds ratio [OR] =5.0, P = 0.002) than waist circumference/height2 per SD (OR = 3.9, P = 0.02), visceral fat/height2 per SD (OR = 2.4, P = 0.02), subcutaneous fat/height2 per SD (OR = 2.0, P = 0.06), renal hilar fat/height2 per SD (OR = 1.6, P = 0.19), or peri/pararenal fat/height2 per SD (OR = 1.5, P = 0.23). Postdonation changes in glomerular filtration rate, blood pressure, and albuminuria were similar across BMI categories. CONCLUSIONS: The BMI outperforms various computed tomography measures of abdominal fat in detecting obesity-related glomerulomegaly. Despite this strong association with glomerulomegaly, short-term renal function outcomes are similar across BMI categories. Long-term follow-up is required to definitively define the impact of obesity on kidney function after donation.

A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

BACKGROUND: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. METHODS AND DESIGN: Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. DISCUSSION: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.

Smart Program Design Through a Common Information Model.

Although much information is already available publically from information-sharing initiatives such as ClinicalTrials.gov, information about clinical programs is unstructured, inconsistent, and incomplete. Clinical research within bioscience companies, health care, academia, and governmental agencies could benefit from easier access to best practices, historical information, and improved information sharing. Facilitating information sharing requires a standardized information model. Information standards today focus on individual clinical trials and the representation of clinical trial data. Although work is ongoing to expand standards to cover the protocol, these are insufficient to capture the objectives, rationale, and design thinking behind clinical programs. An information model is proposed to cover the rationalization and decision-making aspects of designing a clinical program and its associated trials. This paper is the output of a newly formed multicompany working group that examines the merits of a clinical program-level information standard. An example information model is presented to explain the concept.