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Background: The underrepresentation of women in leadership remains a pervasive issue, prompting a critical examination of support mechanisms within professional settings. Previous studies have identified challenges women face, ranging from limited visibility to barriers to career advancement. This survey aims to investigate perceptions regarding the effectiveness of women's leadership programs, mentoring initiatives, and a specialized communication course. Particularly it specifically targets addressing the challenges encountered by professional women., Methods: This multi-center, observational, international online survey was developed in partnership between ESICM NEXT and the ESICM Diversity and Inclusiveness Monitoring Group for Healthcare. Invitations to participate were distributed to both females and men through emails and social networks. Data were collected from April 1, 2023, through October 1, 2023., Results: Out of 354 respondents, 90 were men (25.42%) and 264 were women (74.58%). Among them, 251 completed the survey, shedding light on the persistent challenges faced by women in leadership roles, with 10%-50% of respondents holding such positions. Women's assertiveness is viewed differently, with 65% recognizing barriers such as harassment. Nearly half of the respondent's experience interruptions in meetings. Only 47.4% receiving conference invitations, with just over half accepting them. A mere 12% spoke at ESICM conferences in the last three years, receiving limited support from directors and colleagues, indicating varied obstacles for female professionals. Encouraging family participation, reducing fees, providing childcare, and offering economic support can enhance conference involvement. Despite 55% applying for ESICM positions, barriers like mobbing, harassment, lack of financial support, childcare, and language barriers were reported. Only 14% had access to paid family leave, while 32% benefited from subsidized childcare. Participation in the Effective Communication Course on Career Advancement Goals and engagement in women's leadership and mentoring programs could offer valuable insights and growth opportunities. Collaborating with Human Resources and leadership allies is crucial for overcoming barriers and promoting women's career growth., Conclusions: The urgency of addressing identified barriers to female leadership in intensive care medicine is underscored by the survey's comprehensive insights. A multifaceted and intersectional approach, considering sexism, structural barriers, and targeted strategies, is essential., (© 2024. The Author(s).)

Background: Artificial intelligence, through improved data management and automated summarisation, has the potential to enhance intensive care unit (ICU) care. Large language models (LLMs) can interrogate and summarise large volumes of medical notes to create succinct discharge summaries. In this study, we aim to investigate the potential of LLMs to accurately and concisely synthesise ICU discharge summaries., Methods: Anonymised clinical notes from ICU admissions were used to train and validate a prompting structure in three separate LLMs (ChatGPT, GPT-4 API and Llama 2) to generate concise clinical summaries. Summaries were adjudicated by staff intensivists on ability to identify and appropriately order a pre-defined list of important clinical events as well as readability, organisation, succinctness, and overall rank., Results: In the development phase, text from five ICU episodes was used to develop a series of prompts to best capture clinical summaries. In the testing phase, a summary produced by each LLM from an additional six ICU episodes was utilised for evaluation. Overall ability to identify a pre-defined list of important clinical events in the summary was 41.5 ± 15.2% for GPT-4 API, 19.2 ± 20.9% for ChatGPT and 16.5 ± 14.1% for Llama2 (p = 0.002). GPT-4 API followed by ChatGPT had the highest score to appropriately order a pre-defined list of important clinical events in the summary as well as readability, organisation, succinctness, and overall rank, whilst Llama2 scored lowest for all. GPT-4 API produced minor hallucinations, which were not present in the other models., Conclusion: Differences exist in large language model performance in readability, organisation, succinctness, and sequencing of clinical events compared to others. All encountered issues with narrative coherence and omitted key clinical data and only moderately captured all clinically meaningful data in the correct order. However, these technologies suggest future potential for creating succinct discharge summaries., (© 2024. The Author(s).)

Awake prone positioning (APP) of patients with acute hypoxaemic respiratory failure gained considerable attention during the early phases of the coronavirus disease 2019 (COVID-19) pandemic. Prior to the pandemic, reports of APP were limited to case series in patients with influenza and in immunocompromised patients, with encouraging results in terms of tolerance and oxygenation improvement. Prone positioning of awake patients with acute hypoxaemic respiratory failure appears to result in many of the same physiological changes improving oxygenation seen in invasively ventilated patients with moderate-severe acute respiratory distress syndrome. A number of randomised controlled studies published on patients with varying severity of COVID-19 have reported apparently contrasting outcomes. However, there is consistent evidence that more hypoxaemic patients requiring advanced respiratory support, who are managed in higher care environments and who can be prone for several hours, benefit most from APP use. We review the physiological basis by which prone positioning results in changes in lung mechanics and gas exchange and summarise the latest evidence base for APP primarily in COVID-19. We examine the key factors that influence the success of APP, the optimal target populations for APP and the key unknowns that will shape future research., Competing Interests: Conflicts of interest: M. Ibarra-Estrada, A. Kharat, D. Cosgrave and C. Guerin report no conflicts of interest. B.A. McNicholas reports consulting fees received personally from Teleflex. Y. Perez reports grants to institution and personal support for attending medical congress from Fisher & Paykel. J. Li reports grants to institution from Fisher & Paykel, Aerogen, Rice Foundation and American Association for Respiratory Care; personal honoraria for lectures from Fisher & Paykel, Aerogen, Heyer lts, and American Association for Respiratory Care. I. Pavlov reports grants to institution from Open AI inc and Fisher & Paykel. D.L. Vines reports grants to institution from Teleflex Medical and Rice Foundation; personal honoraria from Theravance Biopharma; unpaid role as President, National board for Respiratory Care. O. Roca reports grants to institution from Hamilton Medical AG and Fisher & Paykel; personal consulting fees from Aerogen, and honoraria received from Hamilton Medical AG, Fisher & Paykel, Aerogen and Ambu Ltd; unpaid role as chair of Acute Respiratory Failure group of Spanish Society of Intensive Care Medicine; non-funded research support from Timpel Ltd. S. Ehrmann reports grants to institution from Aerogen Ltd and Fisher & Paykel; personal consulting fees from Aerogen Ltd; personal honoraria and support for attending meetings from Aerogen Ltd and Fisher & Paykel; participation on Data Safety Monitoring Board for Aerogen Ltd; receipt of equipment/materials from Aerogen Ltd and Fisher & Paykel. J.G. Laffey reports funding to institution from Science Foundation Ireland; personal consulting fees from Baxter Healthcare; unpaid participation in Data Safety Monitoring Board (investigator trials); unpaid role as chair of Translational Biology Section of European Society of Intensive Care Medicine., (Copyright ©The authors 2023.)

Background: Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic., Methods: The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort., Results: Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups [no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001]. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population., Conclusion: AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes., (© 2023. The Author(s).)

Background: The impact of underlying comorbidities on the clinical presentation, management and outcomes in patients with ARDS is poorly understood and deserves further investigation., Objectives: We examined these issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study., Methods: In this secondary analysis of the patient cohort enrolled in the LUNG SAFE study, our primary objective was to determine the frequency, and impact of comorbidities on the management and ICU survival of patients with ARDS. Secondary outcomes relating to comorbidities included their impact on ventilatory management, the development of organ failures, and on end-of-life care., Results: Of 2813 patients in the study population, 1692 (60%) had 1 or more comorbidities, of whom 631 (22.4%) had chronic respiratory impairment, 290 (10.3%) had congestive heart failure, 286 (10.2%) had chronic renal failure, 112 (4%) had chronic liver failure, 584 (20.8%) had immune incompetence, and 613 (21.8%) had diabetes. Multiple comorbidities were frequently present, with 423 (25%) having 2 and 182 (11%) having at least 3 or more comorbidities. The use of invasive ventilation (1379 versus 998, 82 versus 89%), neuromuscular blockade (301 versus 249, 18 versus 22%), prone positioning (97 versus 104, 6 versus 9%) and ECMO (32 versus 46, 2 versus 4%) were each significantly reduced in patients with comorbidities as compared to patients with no comorbidity (1692 versus 1121, 60 versus 40%). ICU mortality increased from 27% (n = 303) in patients with no comorbidity to 39% (n = 661) in patients with any comorbidity. Congestive heart failure, chronic liver failure and immune incompetence were each independently associated with increased ICU mortality. Chronic liver failure and immune incompetence were independently associated with more decisions to limitation of life supporting measures., Conclusions: Most patients with ARDS have significant comorbidities, they receive less aggressive care, and have worse outcomes. Enhancing the care of these patients must be a priority for future clinical studies. Trial registration LUNG-SAFE is registered with ClinicalTrials.gov, number NCT02010073., (© 2022. The Author(s).)

Drawing from basic knowledge of stem-cell biology, embryonic development, wound healing, and aging, regenerative medicine seeks to develop therapeutic strategies that complement or replace conventional treatments by actively repairing diseased tissue or generating new organs and tissues. Among the various clinical-translational strategies within the field of regenerative medicine, several can be broadly described as promoting disease resolution indirectly through local or systemic interactions with a patient's cells, without permanently integrating or directly forming new primary tissue. In this review, we focus on such therapies, which we term disease-modulating regenerative therapies (DMRT), and on the extent to which they have been translated into the clinical arena in four distinct areas of nephrology: renovascular disease (RVD), sepsis-associated AKI (SA-AKI), diabetic kidney disease (DKD), and kidney transplantation (KTx). As we describe, the DMRT that has most consistently progressed to human clinical trials for these indications is mesenchymal stem/stromal cells (MSCs), which potently modulate ischemic, inflammatory, profibrotic, and immune-mediated tissue injury through diverse paracrine mechanisms. In KTx, several early-phase clinical trials have also tested the potential for ex vivo -expanded regulatory immune cell therapies to promote donor-specific tolerance and prevent or resolve allograft injury. Other promising DMRT, including adult stem/progenitor cells, stem cell-derived extracellular vesicles, and implantable hydrogels/biomaterials remain at varying preclinical stages of translation for these renal conditions. To date (2021), no DMRT has gained market approval for use in patients with RVD, SA-AKI, DKD, or KTx, and clinical trials demonstrating definitive, cost-effective patient benefits are needed. Nonetheless, exciting progress in understanding the disease-specific mechanisms of action of MSCs and other DMRT, coupled with increasing knowledge of the pathophysiologic basis for renal-tissue injury and the experience gained from pioneering early-phase clinical trials provide optimism that influential, regenerative treatments for diverse kidney diseases will emerge in the years ahead.

Background: Considerable variability exists regarding CO 2 management in early ARDS, with the impact of arterial CO 2 tension on management and outcomes poorly understood., Research Question: To determine the prevalence and impact of hypocapnia and hypercapnia on the management and outcomes of patients with early ARDS enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study, an international multicenter observational study., Study Design and Methods: Our primary objective was to examine the prevalence of day 1 and sustained (day 1 and 2) hypocapnia (Paco 2  < 35 mm Hg), normocapnia (Paco 2 35-45 mm Hg), and hypercapnia (Paco 2 > 45 mm Hg) in patients with ARDS. Secondary objectives included elucidating the effect of CO 2 tension on ventilatory management and examining the relationship with ARDS outcome., Results: Of 2,813 patients analyzed, 551 (19.6%; 95%CI, 18.1-21.1) were hypocapnic, 1,018 (36.2%; 95% CI, 34.4-38.0) were normocapnic, and 1,214 (43.2%; 95% CI, 41.3-45.0) were hypercapnic, on day 1. Sustained hypocapnia was seen in 252 (9.3%; 95% CI, 8.2-10.4), sustained normocapnia in 544 (19.3%; 95% CI, 17.9-20.8), and sustained hypercapnia in 654 (24.1%; 95% CI, 22.5-25.7) patients. Hypocapnia was more frequent and severe in patients receiving noninvasive ventilation but also was observed in patients on controlled mechanical ventilation. Sustained hypocapnia was more frequent in middle-income countries, whereas sustained hypercapnia was more frequent in Europe. ARDS severity profile was highest in sustained hypercapnia, and these patients received more protective ventilation. No independent association was seen between arterial CO 2 and outcome. In propensity-matched analyses, the hospital mortality rate was 36% in both sustained normocapnic and hypercapnic patients (P = 1.0). ICU mortality was higher in patients with mild to moderate ARDS receiving sustained hypocapnia (38.1%) compared with normocapnia (27.1%)., Interpretation: No evidence was found for benefit or harm with hypercapnia. Of concern, ICU mortality was higher with sustained hypocapnia in mild to moderate ARDS., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Adjunctive strategies are an important part of the management of ARDS. However, their application in clinical practice remains inconsistent., Research Question: We wished to determine the frequency and patterns of use of adjunctive strategies in patients with moderate to severe ARDS (Pao 2 /Fio 2 [P/F ratio] < 150) enrolled into the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study., Study Design and Methods: The LUNG SAFE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in 2014 in 459 ICUs from 50 countries. The primary objective of this substudy was to determine the frequency of use of widely available (neuromuscular blockade, prone position) adjuncts vs adjuncts requiring specialized equipment (extracorporeal membrane oxygenation, inhaled vasodilators, high-frequency ventilation) in patients in the first 48 h of moderate to severe ARDS (P/F ratio < 150)., Results: Of 1,146 patients on invasive ventilation with moderate to severe ARDS, 811 patients (71%) received no adjunct within 48 h of ARDS onset. Of 335 (29%) that received adjunctive strategies, 252 (75%) received a single strategy, and 83 (25%) receiving more than one adjunct. Of ARDS nonsurvivors, 67% did not receive any adjunctive strategy in the first 48 h. Most patients (67%) receiving specialized adjuncts did not receive prone positioning or neuromuscular blockade. Patients that received adjuncts were more likely to have their ARDS recognized, be younger and sicker, have pneumonia, be more difficult to ventilate, and be in a European high-income country than those that did not receive adjuncts., Interpretation: Three in 10 patients with moderate to severe ARDS, and only one-third of nonsurvivors, received adjunctive strategies over the first 48 h of ARDS. A more consistent and evidence-driven approach to adjunct use may reduce costs and improve outcomes in patients with moderate to severe ARDS., Trial Registry: ClinicalTrials.gov; No.: NCT02010073; URL: www.clinicaltrials.gov., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Rationale: We wished to determine the influence of sex on the management and outcomes in acute respiratory distress syndrome (ARDS) patients in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE)., Methods: We assessed the effect of sex on mortality, intensive care unit and hospital length of stay, and duration of invasive mechanical ventilation (IMV) in patients with ARDS who underwent IMV, adjusting for plausible clinical and geographic confounders., Findings: Of 2377 patients with ARDS, 905 (38%) were female and 1472 (62%) were male. There were no sex differences in clinician recognition of ARDS or critical illness severity profile. Females received higher tidal volumes (8.2±2.1 versus 7.2±1.6 mL·kg -1 ; p<0.0001) and higher plateau and driving pressures compared with males. Lower tidal volume ventilation was received by 50% of females compared with 74% of males (p<0.0001). In shorter patients (height ≤1.69 m), females were significantly less likely to receive lower tidal volumes. Surviving females had a shorter duration of IMV and reduced length of stay compared with males. Overall hospital mortality was similar in females (40.2%) versus males (40.2%). However, female sex was associated with higher mortality in patients with severe confirmed ARDS (OR for sex (male versus female) 0.35, 95% CI 0.14-0.83)., Conclusions: Shorter females with ARDS are less likely to receive lower tidal volume ventilation, while females with severe confirmed ARDS have a higher mortality risk. These data highlight the need for better ventilatory management in females to improve their outcomes from ARDS., Competing Interests: Conflict of interest: B.A. McNicholas has nothing to disclose. Conflict of interest: F. Madotto has nothing to disclose. Conflict of interest: T. Pham has nothing to disclose. Conflict of interest: E. Rezoagli has nothing to disclose. Conflict of interest: C.H. Masterson has nothing to disclose. Conflict of interest: S. Horie has nothing to disclose. Conflict of interest: G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Hamilton, Getinge and Dimar SRL, outside the submitted work. Conflict of interest: L. Brochard reports grants from Covidien, grants and nonfinancial support from Fisher Paykel, Air Liquide and General Electric, nonfinancial support from Philips and Sentec, outside the submitted work. Conflict of interest: J.G. Laffey has nothing to disclose., (Copyright ©ERS 2019.)

Objectives: To understand the impact of mild-moderate and severe acute kidney injury in patients with acute respiratory distress syndrome., Design: Secondary analysis of the "Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure", an international prospective cohort study of patients with severe respiratory failure., Setting: Four-hundred fifty-nine ICUs from 50 countries across five continents., Subjects: Patients with a glomerular filtration rate greater than 60 mL/min/1.73 m prior to admission who fulfilled criteria of acute respiratory distress syndrome on day 1 and day 2 of acute hypoxemic respiratory failure., Interventions: Patients were categorized based on worst serum creatinine or urine output into: 1) no acute kidney injury (serum creatinine < 132 µmol/L or urine output ≥ 0.5 mL/kg/hr), 2) mild-moderate acute kidney injury (serum creatinine 132-354 µmol/L or minimum urine output between 0.3 and 0.5mL/kg/hr), or 3) severe acute kidney injury (serum creatinine > 354 µmol/L or renal replacement therapy or minimum urine output < 0.3 mL/kg/hr)., Measurements and Main Results: The primary outcome was hospital mortality, whereas secondary outcomes included prevalence of acute kidney injury and characterization of acute respiratory distress syndrome risk factors and illness severity patterns, in patients with acute kidney injury versus no acute kidney injury. One-thousand nine-hundred seventy-four patients met inclusion criteria: 1,209 (61%) with no acute kidney injury, 468 (24%) with mild-moderate acute kidney injury, and 297 (15%) with severe acute kidney injury. The impact of acute kidney injury on the ventilatory management of patients with acute respiratory distress syndrome was relatively limited, with no differences in arterial CO2 tension or in tidal or minute ventilation between the groups. Hospital mortality increased from 31% in acute respiratory distress syndrome patients with no acute kidney injury to 50% in mild-moderate acute kidney injury (p ≤ 0.001 vs no acute kidney injury) and 58% in severe acute kidney injury (p ≤ 0.001 vs no acute kidney injury and mild-moderate acute kidney injury). In multivariate analyses, both mild-moderate (odds ratio, 1.61; 95% CI, 1.24-2.09; p < 0.001) and severe (odds ratio, 2.13; 95% CI, 1.55-2.94; p < 0.001) acute kidney injury were independently associated with mortality., Conclusions: The development of acute kidney injury, even when mild-moderate in severity, is associated with a substantial increase in mortality in patients with acute respiratory distress syndrome.

Objectives: Pancreatic lesions in autosomal dominant polycystic kidney disease (ADPKD) are primarily cysts. They are increasingly recognized, with isolated reports of intraductal papillary mucinous neoplasia (IPMN)., Methods: Retrospective study to determine prevalence, number, size, and location of pancreatic abnormalities using abdominal magnetic resonance imaging (MRI) of genotyped ADPKD patients (seen February 1998 to October 2013) and compared with age- and sex-matched non-ADPKD controls. We evaluated presentation, investigation, and management of all IPMNs among individuals with ADPKD (January 1997 to December 2016)., Results: Abdominal MRIs were examined for 271 genotyped ADPKD patients. A pancreatic cyst lesion (PCL) was detected in 52 patients (19%; 95% confidence interval, 15%-23%). Thirty-seven (71%) had a solitary PCL; 15 (28%) had multiple. Pancreatic cyst lesion prevalence did not differ by genotype. Intraductal papillary mucinous neoplasia was detected in 1% of ADPKD cases. Among 12 IPMN patients (7 branch duct; 5 main duct or mixed type) monitored for about 140 months, 2 with main duct IPMNs required Whipple resection, and 1 patient died of complications from small-bowel obstruction after declining surgical intervention., Conclusions: With MRI, PCLs were detected in 19% and IPMNs in 1% of 271 ADPKD patients with proven mutations, without difference across genotypes. Pancreatic cyst lesions were asymptomatic and remained stable in size.

Purpose of Review: Recent advances in our understanding of the epidemiology of ARDS has generated key insights into the incidence, risk factors, demographics, management and outcomes from this devastating clinical syndrome., Recent Findings: ARDS occurs in 10% of all ICU patients, in 23% of all mechanically ventilated patients, with 5.5 cases per ICU bed each year. Although some regional variation exists regarding ARDS incidence, this may be less than previously thought. Subphenotypes are increasingly identified within the ARDS cohort, with studies identifying a 'hyperinflammatory' or 'reactive' subgroup that has a higher mortality, and may respond differently to therapeutic interventions. Demographic factors, such as race, may also affect the therapeutic response. Although mortality in ARDS is decreasing in clinical trials, it remains unchanged at approximately 40% in major observational studies. Modifiable ventilatory management factors, including PEEP, airway pressures, and respiratory rate are associated with mortality in ARDS. Hospital and ICU organizational factors play a role in outcome, whereas socioeconomic status is independently associated with survival in patients with ARDS. The Kigali adaptation of the Berlin ARDS definition may provide useful insights into the burden of ARDS in the developing world., Summary: ARDS exerts a substantial disease burden, with 40% of patients dying in hospital. Diverse factors, including patient-related factors such as age and illness severity, country level socioeconomic status, and ventilator management and ICU organizational factors each contribute to outcome from ARDS. Addressing these issues provides opportunities to improve outcome in patients with ARDS.

Introduction: Complications associated with insulin treatment for hyperkalemia are serious and common. We hypothesize that, in chronic kidney disease (CKD) and end-stage renal disease (ESRD), giving 5 units instead of 10 units of i.v. regular insulin may reduce the risk of causing hypoglycemia when treating hyperkalemia., Methods: A retrospective quality improvement study on hyperkalemia management (K +  ≥ 6 mEq/l) from June 2013 through December 2013 was conducted at an urban emergency department center. Electronic medical records were reviewed, and data were extracted on presentation, management of hyperkalemia, incidence and timing of hypoglycemia, and whether treatment was ordered as a protocol through computerized physician order entry (CPOE). We evaluated whether an educational effort to encourage the use of a protocol through CPOE that suggests the use of 5 units might be beneficial for CKD/ESRD patients. A second audit of hyperkalemia management from July 2015 through January 2016 was conducted to assess the effects of intervention on hypoglycemia incidence., Results: Treatments ordered using a protocol for hyperkalemia increased following the educational intervention (58 of 78 patients [74%] vs. 62 of 99 patients [62%]), and the number of CKD/ESRD patients prescribed 5 units of insulin as per protocol increased (30 of 32 patients [93%] vs. 32 of 43 [75%], P  = .03). Associated with this, the incidence of hypoglycemia associated with insulin treatment was lower (7 of 63 patients [11%] vs. 22 of 76 patients [28%], P  = .03), and there were no cases of severe hypoglycemia compared to the 3 cases before the intervention., Conclusion: Education on the use of a protocol for hyperkalemia resulted in a reduction in the number of patients with severe hypoglycemia associated with insulin treatment.

Background: Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV) is a disease characterized by inflammation of small vessels and detectable ANCA in the circulation. Patients may develop a broad spectrum of clinical features ranging from indolent sino-nasal disease and rashes to fulminant renal failure or acute life-threatening pulmonary haemorrhage. Consequently, patients with AAV present to a variety of specialties including nephrology and rheumatology, whose training and approaches to management of such patients may differ. There is little literature comparing patients presenting to different specialties and their outcomes., Methods: We compared two cohorts of patients with ANCA-positive AAV presenting to either the rheumatology or nephrology department at Galway University Hospitals from June 2002 to July 2011. A standardized data collection form was used to collect information regarding baseline demographics, manifestations of AAV, initial management, relapses and complications., Results: Forty-five patients were included in this study (15 rheumatology/30 nephrology). The nephrology cohort was older, had a higher C-reactive protein, Birmingham Vascular Activity Score and ANCA titer at presentation compared to the rheumatology group. Induction treatment varied between the cohorts with rheumatology patients most commonly receiving a combination of oral corticosteroids (73%) and methotrexate (60%) and nephrology patients receiving a combination of intravenous corticosteroids (93%) and cyclophosphamide (90%). Fifty-three percent of the rheumatology patients who completed induction therapy relapsed compared to 30% of the nephrology patients., Conclusion: This study presents two different cohorts of patients with the same disease that were managed by two different disciplines. It highlights the heterogeneity of AAV and the importance of interdisciplinary communication and cooperation when managing these patients., (© The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Parietal epithelial cell (PEC) response to glomerular injury may underlie a common pathway driving fibrogenesis following podocyte loss that typifies several glomerular disorders. Although the mammalian target of rapamycin (mTOR) pathway is important in cell homeostasis, little is known of the biological role or impact of reducing mTOR activity on PEC response following podocyte depletion, nor in the aging kidney. The purpose of these studies was to determine the impact on PECs of reducing mTOR activity following abrupt experimental depletion in podocyte number, as well as in a model of chronic podocyte loss and sclerosis associated with aging. Podocyte depletion was induced by an anti-podocyte antibody and rapamycin started at day 5 until death at day 14 Reducing mTOR did not lead to a greater reduction in podocyte density, despite greater glomerulosclerosis. However, mTOR inhibition lead to an increase in PEC density and PEC-derived crescent formation. Additionally, markers of epithelial-to-mesenchymal transition (platelet-derived growth factor receptor-β, α-smooth muscle actin, Notch-3) and PEC activation (CD44, collagen IV) were further increased by mTOR reduction. Aged mice treated with rapamycin for 1, 2, and 10 wk before death at 26.5 mo (≈75-yr-old human age) had increased the number of glomeruli with a crescentic appearance. mTOR inhibition at either a high or low level lead to changes in PEC phenotype, indicating PEC morphology is sensitive to changes mediated by global mTOR inhibition., (Copyright © 2016 the American Physiological Society.)

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age., (Copyright © 2015 the American Physiological Society.)

Collapsing glomerulopathy predominantly afflicts patients of African ancestry, often first presenting after the immune system is engaged by another disorder. Nichols et al. now show that collateral induction of pathogenic APOL1 allelic variants in podocytes by the ongoing immune response may be the long-sought-after explanation for the development of collapsing glomerulopathy in these patients.

Mesenchymal stem cells (MSCs) suppress T helper (Th)17 cell differentiation and are being clinically pursued for conditions associated with aberrant Th17 responses. Whether such immunomodulatory effects are enhanced by coadministration of MSCs with other agents is not well known. In the present study, individual and combined effects of MSCs and the vitamin D receptor (VDR) agonist paricalcitol on Th17 induction were investigated in vitro and in a mouse model of sterile kidney inflammation (unilateral ureteral obstruction). In vitro, MSCs and paricalcitol additively suppressed Th17 differentiation, although only MSCs suppressed expression of Th17-associated transcriptions factors. Combined administration of MSCs and paricalcitol resulted in an early (day 3) reduction of intrarenal CD4(+) and CD8(+) T cells, CD11b(+)/lymphocyte antigen 6G(+) neutrophils, and inflammatory (lymphocyte antigen 6C(hi)) monocytes as well as reduced transcript for IL-17 compared with untreated animals. Later (day 8), obstructed kidneys of MSC/paricalcitol double-treated mice, but not mice treated with either intervention alone, had reduced tubular injury and interstitial fibrosis as well as lower numbers of neutrophils and inflammatory monocytes and an increase in the ratio between M2 (CD206(+)) and M1 (CD206(-)) macrophages compared with control mice. Adjunctive therapy with VDR agonists may enhance the immunosuppressive properties of MSCs in the setting of pathogenic Th17-type immune responses and related inflammatory responses., (Copyright © 2014 the American Physiological Society.)

Acute kidney injury triggers activation of innate immune responses and of proapoptotic programs such as the p53 pathway. Mulay et al. examine the effects of blocking murine double minute-2 (mdm2), a negative regulator of p53, using a novel chemotherapeutic agent, nutlin-3a, in mouse ischemia-reperfusion injury. Their results indicate that mdm2 promotes renal regeneration by limiting p53-mediated apoptosis but also enhances early inflammation by facilitating DNA binding of nuclear factor-κB independently of p53.

A 36-year-old gentleman presented with 6 months of poor energy, tingling in fingers and weight loss with a change in bowel habit. He appeared cachectic and had clubbing, demineralisation of teeth, pectus carinatus, kyphosis, spinal tenderness, proximal muscle weakness and generalised muscle atrophy. Chvostek's and Trosseau's signs were positive. His haemoglobin (Hb) was 8.7 g/dl, MCV 64.7 fl with low iron. Calcium corrected was 1.30 nmol/l, parathyroid hormone 440.4 ng/l, vitamin D <12.5 nmol/l; INR was 2.7 with coagulation inhibitor studies negative. Radiographs of spine and pelvis commented on osteopenia with thoracic kyphosis and mild anterior wedging of thoracic vertebrae. Antitissue transglutaminase was 145 U/ml, and antiendomysial antibodies were positive. An oesophagogastroduodenoscopy was consistent with coeliac disease. A diagnosis of osteomalacia and coagulopathy secondary to coeliac disease was made. The hypocalcaemia was treated with calcium gluconate infusions with symptomatic relief. Coagulopathy was treated with vitamin K intravenously with normalisation of INR. Following treatment with coeliac diet, calcium slowly normalised.