Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Kliničke praktične smjernice za perioperacijsku i poslijeoperacijsku skrb o arterijsko-venskim fistulama i umetcima za hemodijalizu u odraslih

Krvožilni pristup omogućuje hemodijalizu koja spašava život. Stoga je nužna dobra funkcija krvožilnog pristupa koja omogućuje prikladan krvni protok radi uklanjanja tvari koje se u uremiji zadržavaju u krvi bolesnika, uz istodobno sniženje rizika od sustavne infekcije na najmanju moguću mjeru. Godine 2007. Europske smjernice najbolje prakse (engl. European Best Practice Guidelines – EBPG), prethodnice trenutačne Europske najbolje bubrežne prakse (engl. European Renal Best Practice – ERBP), donijele su nacrt skupine preporuka – vodiča pri donošenju odluka o upućivanju na pregled radi krvožilnog pristupa, o procjeni i nadzoru izbora pristupa te o postupcima kod komplikacija. (1) Otad su se znatno razvili ne samo dokazi na kojima se temelje ove preporuke nego i procesi nastajanja smjernica. (2) Kao odgovor na to, ERBP je ažurirao prethodno djelo u suradnji s raznim stručnjacima iz tog područja uključujući i predstavnike Društva za krvožilni pristup (engl. Vascular Access Society – VAS), kirurge za krvožilni pristup, radiologe, medicinske sestre za dijalizu, znanstvenike, bolesnike i one koji se za njih brinu. Nastojanje da se pridržavaju sve strože metodike izrade smjernica nalagalo je određena odricanja u pogledu područja obuhvata ovih smjernica. Posljedično, one ne „pokrivaju” baš sve iste teme kao njihova prethodna verzija. Neka su područja zajednička, a neka su arhivirana da bi ustupila mjesto novim pitanjima kojima su prednost dali i pružatelji zdravstvene skrbi i oni za koje se skrbi. Odvojeno su objavljene pojedinosti postupka izbora djelokruga problematike koju su smjernice obuhvatile. (3) Nastajanje ovih smjernica slijedilo je strog proces pregleda i procjene dokaza koji se temeljio na sustavnim pregledima rezultata kliničkih istraživanja te opservacijskih podataka gdje je to bilo potrebno. Strukturirani pristup slijedio je model sustava GRADE (hrv. stupanj), koji svakoj preporuci pripisuje stupanj s obzirom na sigurnost sveukupnih dokaza te snagu. (4) Gdje je to bilo primjereno skupina za izradu smjernica unijela je nestupnjevan savjet za kliničku praksu, a koji nije proistekao iz pregleda sustavnih dokaza. Kliničke praktične smjernice iz 2019. godine specifično pokrivaju peritransplantacijske i poslijetransplantacijske aspekte arterijsko-venskih (AV) fistula i umetaka (graftova). Drugi dio, koji je bio u nastajanju kada su ove smjernice išle u tisak, pokrit će aspekte izbora krvožilnog pristupa, prijeoperacijske procjene krvnih žila i središnje venske katetere. Unatoč nedostatku dokaza velike sigurnosti za većinu područja krvožilnih pristupa, ERBP se posvetio izradi smjernica velike kakvoće, dajući smjernicu gdje god je moguće, a popis preporuka za istraživanje ondje gdje se nije moglo uputiti smjernicom. Nadamo se da će ove smjernice i one planirane pomoći stručnoj zajednici pri donošenju odluka o postupcima, postupnicima i skrbi vezanima s krvožilnim pristupima, pomoći bolesnicima i onima koji se za njih brinu da steknu uvid u problematiku te olakšati zajedničko donošenje odluka u tom području

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Literary studies and the academy

In 1885 the University of Oxford invited applications for the newly created Merton Professorship of English Language and Literature. The holder of the chair was, according to the statutes, to ‘lecture and give instruction on the broad history and criticism of English Language and Literature, and on the works of approved English authors’. This was not in itself a particularly innovatory move, as the study of English vernacular literature had played some part in higher education in Britain for over a century. Oxford University had put English as a subject into its pass degree in 1873, had been participating since 1878 in extension teaching, of which literary study formed a significant part, and had since 1881 been setting special examinations in the subject for its non-graduating women students. What was new was the fact that this ancient university appeared to be on the verge of granting the solid academic legitimacy of an established chair to an institutionally marginal and often contentious intellectual pursuit, acknowledging the study of literary texts in English to be a fit subject not just for women and the educationally disadvantaged but also for university men

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma

BackgroundImmune checkpoint inhibitors (ICIs) have expanded treatment options for metastatic renal cell carcinoma (mRCC); however, there are limited predictive biomarkers for response to ICIs in this indication, with programmed death-ligand 1 (PD-L1) status demonstrating little predictive utility in mRCC. While predictive of ICI response in other tumor types, the utility of tumor mutation burden (TMB) in mRCC is unclear. Here, we assess TMB, loss of antigen presentation genes and PD-L1 status correlated with outcomes to ICI treatment in mRCC.MethodsTumor samples from 34 patients with mRCC treated with ICI therapy at Duke Cancer Institute were retrospectively evaluated using Personal Genome Diagnostics elio tissue complete (RUO version), a tumor genomic profiling assay for somatic variants, TMB, microsatellite status and genomic status of antigen presentation genes. Tumor samples were also analyzed with the Dako 28-8 PD-L1 immunohistochemistry assay. Deidentified clinical information was extracted from the medical record, and tumor response was evaluated based on the Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1 criteria.ResultsPatients were stratified by overall response following ICI therapy and designated as progressive disease (PD; n=18) or disease control groups (DC; n=16). TMB scores ranged from 0.36 to 12.24 mutations/Mb (mean 2.83 mutations/Mb) with no significant difference between the PD and DC groups (3.01 vs 2.63 mutations/Mb, respectively; p=0.7682). Interestingly, 33% of PD patients displayed loss of heterozygosity of major histocompatibility complex class I genes (LOH-MHC) vs 6% of DC patients. Nine of 34 samples were PD-L1-positive (4 in the PD group; 5 in the DC group), suggesting no correlation between PD-L1 expression and response to ICI therapy. Notably, the DC group displayed an enrichment of mutations in DNA repair genes (p=0.04), with 68.8% exhibiting at least one mutated homologous recombination repair (HRR)-related gene compared with only 38.9% of the PD group (p=0.03).ConclusionsOverall, neither TMB nor PD-L1 correlated with ICI response and TMB was not significantly associated with PD-L1 expression. The higher incidence of LOH-MHC in PD group suggests that loss of antigen presentation may restrict response to ICIs. Separately, enrichment of HRR gene mutations in the DC group suggests potential utility in predicting ICI response and a potential therapeutic target, warranting future studies