A photochemical dehydrogenative strategy for aniline synthesis.

Chemical reactions that reliably join two molecular fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochemicals1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho versus meta versus para) is currently achievable only in transition-metal-catalysed processes and requires halogen- or boron-containing substrates3-6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C-H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs in nature and is often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon-nitrogen (C-N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using the well established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chemistry. We demonstrate the utility of this C-N coupling protocol by preparing commercial medicines and by the late-stage amination-aromatization of natural products, steroids and terpene feedstocks.

Patient-derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn's Disease.

OBJECTIVE: Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis. DESIGN: We generated 312 intestinal epithelial organoids (IEOs) from mucosal biopsies of 168 patients with CD (n=72), UC (n=23) and healthy controls (n=73). We performed genome-wide molecular profiling including DNAm, bulk as well as single-cell RNA sequencing. Organoids were subjected to gene editing and the functional consequences of DNAm changes evaluated using an organoid-lymphocyte coculture and a nucleotide-binding oligomerisation domain, leucine-rich repeat and CARD domain containing 5 (NLRC5) dextran sulphate sodium (DSS) colitis knock-out mouse model. RESULTS: We identified highly stable, CD-associated loss of DNAm at major histocompatibility complex (MHC) class 1 loci including NLRC5 and cognate gene upregulation. Single-cell RNA sequencing of primary mucosal tissue and IEOs confirmed the role of NLRC5 as transcriptional transactivator in the intestinal epithelium. Increased mucosal MHC-I and NLRC5 expression in adult and paediatric patients with CD was validated in additional cohorts and the functional role of MHC-I highlighted by demonstrating a relative protection from DSS-mediated mucosal inflammation in NLRC5-deficient mice. MHC-I DNAm in IEOs showed a significant correlation with CD disease phenotype and outcomes. Application of machine learning approaches enabled the development of a disease prognostic epigenetic molecular signature. CONCLUSIONS: Our study has identified epigenetically regulated intestinal epithelial MHC-I as a novel mechanism in CD pathogenesis.

Photocatalysis in the Life Science Industry.

In the pursuit of new pharmaceuticals and agrochemicals, chemists in the life science industry require access to mild and robust synthetic methodologies to systematically modify chemical structures, explore novel chemical space, and enable efficient synthesis. In this context, photocatalysis has emerged as a powerful technology for the synthesis of complex and often highly functionalized molecules. This Review aims to summarize the published contributions to the field from the life science industry, including research from industrial-academic partnerships. An overview of the synthetic methodologies developed and strategic applications in chemical synthesis, including peptide functionalization, isotope labeling, and both DNA-encoded and traditional library synthesis, is provided, along with a summary of the state-of-the-art in photoreactor technology and the effective upscaling of photocatalytic reactions.

In Situ Sputtering From the Micromanipulator to Enable Cryogenic Preparation of Specimens for Atom Probe Tomography by Focused-Ion Beam.

Workflows have been developed in the past decade to enable atom probe tomography analysis at cryogenic temperatures. The inability to control the local deposition of the metallic precursor from the gas-injection system (GIS) at cryogenic temperatures makes the preparation of site-specific specimens by using lift-out extremely challenging in the focused-ion beam. Schreiber et al. exploited redeposition to weld the lifted-out sample to a support. Here, we build on their approach to attach the region-of-interest and additionally strengthen the interface with locally sputtered metal from the micromanipulator. Following standard focused-ion beam annular milling, we demonstrate atom probe analysis of Si in both laser pulsing and voltage mode, with comparable analytical performance as a presharpened microtip coupon. Our welding approach is versatile, as various metals could be used for sputtering, and allows similar flexibility as the GIS in principle.

A Versatile and Reproducible Cryo-sample Preparation Methodology for Atom Probe Studies.

Repeatable and reliable site-specific preparation of specimens for atom probe tomography (APT) at cryogenic temperatures has proven challenging. A generalized workflow is required for cryogenic specimen preparation including lift-out via focused ion beam and in situ deposition of capping layers, to strengthen specimens that will be exposed to high electric field and stresses during field evaporation in APT and protect them from environment during transfer into the atom probe. Here, we build on existing protocols and showcase preparation and analysis of a variety of metals, oxides, and supported frozen liquids and battery materials. We demonstrate reliable in situ deposition of a metallic capping layer that significantly improves the atom probe data quality for challenging material systems, particularly battery cathode materials which are subjected to delithiation during the atom probe analysis itself. Our workflow design is versatile and transferable widely to other instruments.

Effects of chronic and binge ethanol administration on mouse cerebellar and hippocampal neuroinflammation.

Background: Hippocampal and cerebellar neuropathology occurs in individuals with alcohol use disorders (AUD), resulting in impaired cognitive and motor function.Objectives: Evaluate the effects of ethanol on the expression of pro- and anti-inflammatory molecules, as well as the effects of the anti-inflammatory PPAR-γ agonist pioglitazone in suppressing ethanol-induced neuroinflammation.Methods: Adult male and female mice were treated chronically with ethanol for just under a month followed by a single acute binge dose of ethanol. Animals were provided liquid diet in the absence of ethanol (Control; n = 18, 9 M/9F), liquid diet containing ethanol (ethanol; n = 22, 11 M/11F), or liquid diet containing ethanol plus gavage administration of 30.0 mg/kg pioglitazone (ethanol + pioglitazone; n = 20, 10 M/10F). The hippocampus and cerebellum were isolated 24 h following the binge dose of ethanol, mRNA was isolated, and pro- and anti-inflammatory molecules were quantified by qRT-PCR.Results: Ethanol significantly (p < .05) increased the expression of pro-inflammatory molecules IL-1ß, TNF-α, CCL2, and COX2; increased the expression of inflammasome-related molecules NLRP3 and Casp1 but decreased IL-18; and altered the expression of anti-inflammatory molecules including TGFßR1 in the hippocampus and cerebellum, though some differences were observed between males and females and the two brain regions. The anti-inflammatory pioglitazone inhibited ethanol-induced alterations in the expression of most, but not all, inflammation-related molecules.Conclusion: Chronic plus binge administration of ethanol induced the expression of inflammatory molecules in adult mice and pioglitazone suppressed ethanol-induced neuroinflammation.

Diabetes mellitus, glycaemic control, and severe COVID-19 in the Australian critical care setting: A nested cohort study.

BACKGROUND: Internationally, diabetes mellitus is recognised as a risk factor for severe COVID-19. The relationship between diabetes mellitus and severe COVID-19 has not been reported in the Australian population. OBJECTIVE: The objective of this study was to determine the prevalence of and outcomes for patients with diabetes admitted to Australian intensive care units (ICUs) with COVID-19. METHODS: This is a nested cohort study of four ICUs in Melbourne participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project. All adult patients admitted to the ICU with COVID-19 from 20 February 2020 to 27 February 2021 were included. Blood glucose and glycated haemoglobin (HbA1c) data were retrospectively collected. Diabetes was diagnosed from medical history or an HbA1c ≥6.5% (48 mmol/mol). Hospital mortality was assessed using logistic regression. RESULTS: There were 136 patients with median age 58 years [48-68] and median Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 14 [11-19]. Fifty-eight patients had diabetes (43%), 46 patients had stress-induced hyperglycaemia (34%), and 32 patients had normoglycaemia (23%). Patients with diabetes were older, were with higher APACHE II scores, had greater glycaemic variability than patients with normoglycaemia, and had longer hospital length of stay. Overall hospital mortality was 16% (22/136), including nine patients with diabetes, nine patients with stress-induced hyperglycaemia, and two patients with normoglycaemia. CONCLUSION: Diabetes is prevalent in patients admitted to Australian ICUs with severe COVID-19, highlighting the need for prevention strategies in this vulnerable population.

Critical analysis of quality of life and cost-effectiveness of enhanced recovery after surgery (ERAS) for patient's undergoing urologic oncology surgery: a systematic review.

PURPOSE: Enhanced recovery after surgery (ERAS) protocols have been implemented across a variety of disciplines to improve outcomes. Herein we describe the impact of ERAS on quality of life (QOL) and cost for patients undergoing urologic oncology surgery. METHODS: A systematic literature search using the MEDLINE, Scopus, Clinictrials.gov, and Cochrane Review databases for studies published between 1946 and 2020 was conducted. Articles were reviewed and assigned a risk of bias by two authors and were included if they addressed ERAS and either QOL or cost-effectiveness for patients undergoing urologic oncology surgery. RESULTS: The literature search yielded a total of 682 studies after removing duplicates, of which 10 (1.5%) were included in the review. Nine articles addressed radical cystectomy, while one addressed ERAS and QOL for laparoscopic nephrectomy. Six publications assessed the impact of ERAS on QOL domains. Questionnaires used for assessment of QOL varied across studies, and timing of administration was heterogeneous. Overall, ERAS improved patient QOL during early phases of recovery within the realms of bowel function, physical/social/cognitive functioning, sleep and pain control. Costs were assessed in 4 retrospective studies including 3 conducted in the United States and one from China all addressing radical cystectomy. Studies demonstrated either decreased costs associated with ERAS as a result of decreased length of stay or no change in cost based on ERAS implementation. CONCLUSION: While limited studies are published on the subject, ERAS implementation for radical cystectomy and laparoscopic nephrectomy improved patient-reported QOL during early phases of recovery. For radical cystectomy, there was a decreased or neutral overall financial cost associated with ERAS. Further studies assessing QOL and cost-effectiveness over the entire global period of care in a variety of urologic oncology surgeries are warranted.

Exploration of a Nitromethane-Carbonylation Strategy during Route Design of an Atropisomeric KRASG12C Inhibitor.

Route design and proof of concept synthesis was conducted on a synthetically challenging atropisomeric KRASG12C inhibitor to support clinical API manufacture. Improvements to the synthesis of a chiral piperazine fragment gave reduced step count and streamlined protecting group strategy via the formation and methanol ring opening of an N-carboxy-anhydride (NCA). The complex atropisomeric nitroquinoline was accessed via an early stage salt-resolution followed by a formal two-part nitromethane-carbonylation, avoiding a high temperature Gould-Jacobs cyclization that previously led to atropisomer racemization. The substrate scope of the formal nitromethane-carbonylation strategy was further explored for a range of ortho-substituted bromo/iodo unprotected anilines.

A Desaturative Approach for Aromatic Aldehyde Synthesis via Synergistic Enamine, Photoredox and Cobalt Triple Catalysis.

Aromatic aldehydes are fundamental intermediates that are widely utilised for the synthesis of important materials across the broad spectrum of chemical industries. Accessing highly substituted derivatives can often be difficult as their functionalizations are generally performed via electrophilic aromatic substitution, SE Ar. Here we provide an alternative and mechanistically distinct approach whereby aromatic aldehydes are assembled from saturated precursors via a desaturative process. This novel strategy harnesses the high-fidelity of Diels-Alder cycloadditions to quickly construct multi-substituted cyclohexenecarbaldehyde cores which undergo desaturation via the synergistic interplay of enamine, photoredox and cobalt triple catalysis.

Ethanol modulation of cerebellar neuroinflammation in a postnatal mouse model of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) are alarmingly common, result in significant personal and societal loss, and there is no effective treatment for these disorders. Cerebellar neuropathology is common in FASD and causes aberrant cognitive and motor function. Ethanol-induced neuroinflammation is believed to contribute to neuropathological sequelae of FASD, and was previously demonstrated in the cerebellum in animal models of FASD. We now demonstrate neuroinflammation persists in the cerebellum several days following cessation of ethanol treatment in an early postnatal mouse model, with meaningful implications for timing of therapeutic intervention in FASD. We also demonstrate by Sholl analysis that ethanol decreases ramification of microglia cell processes in cells located near the Purkinje cell layer but not those near the external granule cell layer. Ethanol did not alter the expression of anti-inflammatory molecules or molecules that constitute NLRP1 and NLRP3 inflammasomes. Interestingly, ethanol decreased the expression of IL-23a (P19) and IL-12Rß1 suggesting that ethanol may suppress IL-12 and IL-23 signaling. Fractalkine-fractalkine receptor (CX3CL1-CX3CR1) signaling is believed to suppress microglial activation and our demonstration that ethanol decreases CX3CL1 expression suggests that ethanol modulation of CX3CL1-CX3CR1 signaling may contribute to cerebellar neuroinflammation and neuropathology. We demonstrate ethanol alters the expression of specific molecules in the cerebellum understudied in FASD, but crucial for immune responses. Ethanol increases the expression of NOX-2 and NGP and decreases the expression of RAG1, NOS1, CD59a, S1PR5, PTPN22, GPR37, and Serpinb1b. These molecules represent a new horizon as potential targets for development of FASD therapy.

Divergent and overlapping hippocampal and cerebellar transcriptome responses following developmental ethanol exposure during the secondary neurogenic period.

BACKGROUND: The developing hippocampus and cerebellum, unique among brain regions, exhibit a secondary surge in neurogenesis during the third trimester of pregnancy. Ethanol (EtOH) exposure during this period is results in a loss of tissue volume and associated neurobehavioral deficits. However, mechanisms that link EtOH exposure to teratology in these regions are not well understood. We therefore analyzed transcriptomic adaptations to EtOH exposure to identify mechanistic linkages. METHODS: Hippocampi and cerebella were microdissected at postnatal day (P)10, from control C57BL/6J mouse pups, and pups treated with 4 g/kg of EtOH from P4 to P9. RNA was isolated and RNA-seq analysis was performed. We compared gene expression in EtOH- and vehicle-treated control neonates and performed biological pathway-overrepresentation analysis. RESULTS: While EtOH exposure resulted in the general induction of genes associated with the S-phase of mitosis in both cerebellum and hippocampus, overall there was little overlap in differentially regulated genes and associated biological pathways between these regions. In cerebellum, EtOH additionally induced gene expression associated with the G2/M-phases of the cell cycle and sonic hedgehog signaling, while in hippocampus, EtOH-induced the pathways for ribosome biogenesis and protein translation. Moreover, EtOH inhibited the transcriptomic identities associated with inhibitory interneuron subpopulations in the hippocampus, while in the cerebellum there was a more pronounced inhibition of transcripts across multiple oligodendrocyte maturation stages. CONCLUSIONS: These data indicate that during the delayed neurogenic period, EtOH may stimulate the cell cycle, but it otherwise results in widely divergent molecular effects in the hippocampus and cerebellum. Moreover, these data provide evidence for region- and cell-type-specific vulnerability, which may contribute to the pathogenic effects of developmental EtOH exposure.

Early Cannulation ePTFE Arteriovenous Access Grafts are Associated with a Low Incidence of Pseudoaneurysm Formation.

BACKGROUND: Pseudoaneurysm formation is common in standard thin-walled polytetrafluoroethylene (sPTFE) grafts, occurring in up to 10% of grafts, and is reported as the most common cause of graft loss for grafts more than 2 years old. The Gore® Acuseal™ graft is an early cannulation graft, needled before incorporation, and thus may be especially prone to pseudoaneurysm formation. In addition, as this is a relatively new product, there are limited data on long-term outcomes such as pseudoaneurysm. We report one center's experience of the incidence and etiological factors associated with pseudoaneurysm formation over 5 years and 265 grafts. METHODS: A total of 265 Acuseal grafts were placed in the last 5 years. All patients had prospective data entered into an electronic searchable patient record. Surveillance was performed with 3 monthly imaging (digital subtraction angiography or ultrasound), clinical examination, and hemodynamic performance. Data examined included the incidence, causative factors, and outcomes of pseudoaneurysm. RESULTS: Eleven grafts (4.15%) developed a pseudoaneurysm, with 2 patients developing significant hemorrhage. The median time to development of a pseudoaneurysm was 25 months interquartile range (IQR, 20-28 months). Several common etiological factors were identified. All but one patient had overuse of needling sites (n = 10; 90.9%). Other factors associated with pseudoaneurysm formation were inadequate surveillance (n = 9; 81.8%), venous outflow stenosis (n = 9; 81.8%), and anticoagulation/dual antiplatelet therapy (n = 7; 63.6%). Management included observation and needle rotation (n = 5; 45.5%), stent grafting (n = 3; 27.3%), or excision (n = 1; 9.1%) of the pseudoaneurysm. Surgical or endovascular augmentation of the venous outflow was required in 9 patients (81.8%). Graft ligation and explantation were required in 5 patients (45.5%) with graft preservation achieved in 6/11 patients (54.5%). CONCLUSIONS: Pseudoaneurysm formation occurs less frequently in Acuseal grafts compared with historical data for standard PTFE grafts. Pseudoaneurysm formation did not occur in any graft within the first 13 months after implantation, suggesting early cannulation before incorporation is not by itself a risk factor for pseudoaneurysm development. Poor needling, venous stenosis, inadequate surveillance, and anticoagulation/dual antiplatelet therapy are remediable factors, and graft preservation is possible. Acuseal is a robust graft with lower rates of pseudoaneurysm formation on long-term follow-up than standard PTFE grafts.

Building visualization skills through investigating the Journal of the Medical Library Association coauthorship network from 2006-2017.

OBJECTIVE: The primary objective of this study was to explore different dimensions of Journal of the Medical Library Association (JMLA) authorship from 2006-2017. Dimensions that were evaluated using coauthorship networks and affiliation data included collaboration, geographical reach, and relationship between Medical Library Association (MLA) member and nonmember authors. A secondary objective was to analyze the practice and practical application of data science skills. METHODS: A team of librarians who attended the 2017 Data Science and Visualization Institute used JMLA bibliographic metadata extracted from Scopus, together with select MLA membership data from 2006-2017. Data cleaning, anonymization, analysis, and visualization were done collaboratively by the team members to meet their learning objectives and to produce insights about the nature of collaborative authorship at JMLA. RESULTS: Sixty-nine percent of the 1,351 JMLA authors from 2006-2017 were not MLA members. MLA members were more productive and collaborative, and tended to author articles together. The majority of the authoring institutions in JMLA are based in the United States. Global reach outside of the United States and Canada shows higher authorship in English-speaking countries (e.g., Australia, United Kingdom), as well as in Western Europe and Japan. CONCLUSIONS: MLA support of JMLA may benefit a wider network of health information specialists and medical professionals than is reflected in MLA membership. Conducting coauthorship network analyses can create opportunities for health sciences librarians to practice applying emerging data science and data visualization skills.

Photoinduced decarboxylative azidation of cyclic amino acids.

The direct decarboxylative azidation of cyclic α-amino acids has been achieved via visible light-mediated organo-photoredox catalysis. This synthetic strategy allows the simple preparation of azide-contaning building blocks and has been used in the selective modification of N-terminal proline residues of two di-peptides.

The latest treatment options for bladder cancer.

Introduction: Bladder cancer carries a high healthcare burden and a poor prognosis once distant metastatic spread has occurred. Sources of data: We utilised a PubMed/MEDLINE literature search using the terms bladder cancer, chemotherapy, immunotherapy, intra-vesical therapy, surgery and radiotherapy, and current clinical management guidelines (Association of Cancer Physicians, British Association of Urological Surgeons, National Institute for Health and Care Excellence, European Association of Urology). Areas of agreement: Optimal bladder cancer management requires a multi-modal approach incorporating surgery, radiotherapy, chemotherapy and immunotherapy. Areas of controversy: Selection criteria for radical surgery, or radiotherapy as a bladder sparing option, and their relative efficacy, remains poorly defined. Growing points: Palliative immunotherapy has been recently established for advanced bladder cancer after prior chemotherapy. Earlier use is under investigation. Areas timely for developing research: Validated predictive biomarkers, potentially from easily repeatable sites ('liquid biopsies'), will be required to optimise use of molecularly targeted treatment options.

Hydroxylamine Derivatives as Nitrogen-Radical Precursors in Visible-Light Photochemistry.

In recent years, hydroxylamines derivatives have been exploited as nitrogen-radical precursors in visible-light photochemistry. Their ability to serve as electrophores in redox chemistry has propelled the development of many novel transformations. Fundamental mechanistic aspects as well as the importance in the preparation of nitrogen-containing molecules will be highlighted.

Genomic sequencing is required for identification of tuberculosis transmission in Hawaii.

BACKGROUND: Tuberculosis (TB) caused an estimated 1.4 million deaths and 10.4 million new cases globally in 2015. TB rates in the United States continue to steadily decline, yet rates in the State of Hawaii are perennially among the highest in the nation due to a continuous influx of immigrants from the Western Pacific and Asia. TB in Hawaii is composed of a unique distribution of genetic lineages, with the Beijing and Manila families of Mycobacterium tuberculosis (Mtb) comprising over two-thirds of TB cases. Standard fingerprinting methods (spoligotyping plus 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats [MIRU-VNTR] fingerprinting) perform poorly when used to identify actual transmission clusters composed of isolates from these two families. Those typing methods typically group isolates from these families into large clusters of non-linked isolates with identical fingerprints. Next-generation whole-genome sequencing (WGS) provides a new tool for molecular epidemiology that can resolve clusters of isolates with identical spoligotyping and MIRU-VNTR fingerprints. METHODS: We performed WGS and SNP analysis and evaluated epidemiological data to investigate 19 apparent TB transmission clusters in Hawaii from 2003 to 2017 in order to assess WGS' ability to resolve putative Mtb clusters from the Beijing and Manila families. This project additionally investigated MIRU-VNTR allele prevalence to determine why standard Mtb fingerprinting fails to usefully distinguish actual transmission clusters from these two Mtb families. RESULTS: WGS excluded transmission events in seven of these putative clusters, confirmed transmission in eight, and identified both transmission-linked and non-linked isolates in four. For epidemiologically identified clusters, while the sensitivity of MIRU-VNTR fingerprinting for identifying actual transmission clusters was found to be 100%, its specificity was only 28.6% relative to WGS. We identified that the Beijing and Manila families' significantly lower Shannon evenness of MIRU-VNTR allele distributions than lineage 4 was the cause of standard fingerprinting's poor performance when identifying transmission in Beijing and Manila family clusters. CONCLUSIONS: This study demonstrated that WGS is necessary for epidemiological investigation of TB in Hawaii and the Pacific.

Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease.

RATIONALE: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. OBJECTIVES: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease. METHODS: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow-up, and the urinary albumin-to-creatinine ratio was measured at study exit. MEASUREMENTS AND MAIN RESULTS: In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m2), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m2/yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (-4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between-group differences in end-of-study urinary albumin-to-creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings. CONCLUSIONS: CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).