End-of-life care needs in cancer patients: a qualitative study of patient and family experiences.

BACKGROUND: Cancer is a disease that transcends what is purely medical, profoundly affecting the day-to-day life of both patients and family members. Previous research has shown that the consequences of cancer are greatly aggravated in patients at the end of life, at a time when they must also grapple with numerous unmet needs. The main objective of this study was to obtain more in-depth insight into these needs, primarily in patients with end-stage cancer nearing death. METHODS: Semi-structured interviews were conducted in Spain with cancer patients at the end of life (n = 3) and their family members (n = 12). The findings from the interviews were analyzed using qualitative thematic analysis and a grounded theory approach. RESULTS: Four major themes emerged from the interviews that explored the needs and concerns of patients with cancer at the end of life: (1) physical well-being (2) emotional well-being (3) social well-being and (4), needs relating to information and autonomous decision-making. The interviews also shed light on the specific needs of family members during this period, namely the difficulties of managing increased caregiver burden and maintaining a healthy work-life balance. CONCLUSIONS: A lack of support, information and transparency during a period of immense vulnerability makes the end-of-life experience even more difficult for patients with cancer. Our findings highlight the importance of developing a more in-depth understanding of the needs of this population, so that informed efforts can be made to improve palliative healthcare and implement more comprehensive care and support at the end of life.

Fulminant hepatitis due to spontaneous reactivation of virus B in an immunocompetent patient.

We present the case of a 52-year-old woman with a history of HBeAg-negative chronic hepatitis B virus (HBV) infection, viral load (VL) Z+<20,000U.l/ml with no evidence of liver fibrosis and, therefore, untreated. She presented to the emergency department with jaundice, epigastric pain, nausea, and vomiting. On admission, blood analysis revealed ALT 3982U/l, AST 3221U/l, Gamma-GT 80U/l, alkaline phosphatase 252U/l, LDH 960U/l, bilirrubin12.5mg/dl; no elevation of acute phase reactants, 141,000 platelets and coagulopathy with a prothrombin activity of 29%. Abdominal ultrasound showed no relevant findings. The serological profile revealed AgHBs+, anti-HBe+ y anti-HBc IgM+ and VL VHB>100 mills. Ul/ml, the remaining serology was negative and other causes of liver disease were ruled out. With the diagnosis of severe acute hepatitis (SAH) due to HBV reactivation (HBVR) treatment with entecavir was initiated. Given the analytical evolution (Table 1) and the appearance of encephalopathy grade I-II/IV, an urgent liver transplant was performed. The histological result of the explant was conclusive with intense interphase and lobular hepatitis with extensive areas of massive necrosis in both lobes, without hepatic fibrosis compatible with fulminant hepatitis (FH).

Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. METHODS: 135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. RESULTS: 125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver-kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. CONCLUSIONS: Long-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function.

Electrophysiological resting-state hyperconnectivity and poorer behavioural regulation as predisposing profiles of adolescent binge drinking.

Adolescent Binge Drinking (BD) has become an increasing health and social concern, with detrimental consequences for brain development and functional integrity. However, research on neurophysiological and neuropsychological traits predisposing to BD are limited at this time. In this work, we conducted a 2-year longitudinal magnetoencephalography (MEG) study over a cohort of initially alcohol-naïve adolescents with the purpose of exploring anomalies in resting-state electrophysiological networks, impulsivity, sensation-seeking, and dysexecutive behaviour able to predict future BD patterns. In a sample of 67 alcohol-naïve adolescents (age = 14.5 ± 0.9), we measured resting-state activity using MEG. Additionally, we evaluated their neuropsychological traits using self-report ecological scales (BIS-11, SSS-V, BDEFS, BRIEF-SR and DEX). In a second evaluation, 2 years later, we measured participant's alcohol consumption, sub-dividing the original sample in two groups: future binge drinkers (22 individuals, age 14.6 ± 0.8; eight females) and future light/no drinkers (17 individuals, age 14.5 ± 0.8; eight females). Then, we searched for differences predating alcohol BD intake. We found abnormalities in MEG resting state, in a form of gamma band hyperconnectivity, in those adolescents who transitioned into BD years later. Furthermore, they showed higher impulsivity, dysexecutive behaviours and sensation seeking, positively correlated with functional connectivity (FC). Sensation seeking and impulsivity mainly predicted BD severity in the future, while the relationship between dysexecutive trait and FC with future BD was mediated by sensation seeking. These findings shed light to electrophysiological and neuropsychological traits of vulnerability towards alcohol consumption. We hypothesise that these differences may rely on divergent neurobiological development of inhibitory neurotransmission pathways and executive prefrontal circuits.

Adaptation and validation of the Spanish version of the everyday cognition battery for assessing everyday cognition in older adults.

INTRODUCTION: Ageing entails a series of neuroanatomical and neurophysiological changes in some cognitive processes that directly affect the daily life and autonomy of a person. We believe it is necessary to have tools that assess the cognitive functions that are essential for carrying out daily activities in an independent manner. The aim of this study was to translate the Everyday Cognition Battery (ECB) into Spanish, adapt it to the sociocultural context of Spain, and validate it by testing the psychometric properties, i.e., the reliability and validity of the translated version. METHODS: The translation and adaptation of the ECB into Spanish was carried out following the method recommended by Beaton et al., the process concluding with a pilot test to ensure that subjects were able to understand the scale correctly. Between March and October 2019, the study population voluntarily completed the translated version of each of the four subscales that make up the battery of tests. The translated version was validated by analysing its psychometric properties, using reliability or internal consistency tests assessed with Cronbach's alpha coefficient and validity tests analysed using correlation tables and Spearman's correlation coefficient. The scale considered to represent the gold standard in the assessment of cognition was the Rapid Assessment of Cognitive Functions (RACF), and to assess Instrumental Activities of Daily Living (IADL) this was the Lawton and Brody Index. RESULTS: The total study population included 226 subjects, of which 52 participants were excluded, resulting in a study sample size of 174 older adults. The recognition, inductive reasoning and computation span tests showed good reliability (Cronbach's alpha coefficient of > 0.827, > 0.836, and > 0.823, respectively), while the knowledge test showed questionable reliability with a Cronbach's alpha coefficient of > 0.615. The validity analysis demonstrated that all the combinations of correlations of the different scales were significantly and positively related to one another. CONCLUSIONS: The Spanish version of the ECB tool is socially and culturally equivalent to the original version, and both its validity and reliability for assessing everyday cognition in older adults have been demonstrated.

SARS-CoV-2 vaccine, a new autoimmune hepatitis trigger?

SARS-CoV2 infection and vaccination against this virus have been related to the development of autoimmune diseases. We report a case of autoimmune hepatitis (AIH) after SARS-COV2 vaccine. Male, 76 years old, with a history of hepatic cirrhosis secondary to primary biliary cholangitis (PBC), compensated, treated with ursodeoxycholic acid and obeticholic acid. The patient received the third dose of the SARS-CoV2 vaccine (BioNTech/Pfizer) in December 2021. In subsequent analytical control, the patient presented altered liver test, with elevation of ALT and AST. Ultrasound was performed, without alterations, and viral causes were ruled out. IgG elevation and positive antinuclear antibodies were observed. A liver biopsy was performed, with findings of intense interface and lobular hepatitis and areas of centrilobular necrosis. The inflammation was predominantly lymphoplasmacytic. The patient was diagnosed with AIH and initiated therapy with steroids and azathioprine, currently with an adequate response. AIH is an immune-mediated disease of uncertain etiology. Cases of AIH with SARS-CoV2 vaccination as a possible trigger have recently been published, with characteristics similar to ours. Some of them had a history of autoimmune pathology, such as this case (PBC). Therefore, it is suggested that vaccination can induce the development of autoimmune pathology in patients at risk. Our reported case reinforces the hypothesis of an association between AIH and the SARS-CoV2 vaccine.

Angiosarcoma of the aorta diagnosed via endoscopic ultrasound.

A 54-year-old man consulted for low back pain of 5 weeks of evolution, refractory to regular analgesics, and significant weight loss. The PET-CT revealed a retroperitoneal mass in contact with the anterior wall of the abdominal aorta. After consulting with the Endoscopy Unit, an endoscopic ultrasound-guided FNAP was performed due to the accessibility of the lesion and the less invasive nature of these procedures. The anatomopathological result was angiosarcoma of the aorta.

A protocol for a randomized trial measuring flowmetry in risk areas for pressure ulcer: Hyperoxygenated fatty acids vs olive oil.

BACKGROUND: Pressure ulcers are a common adverse event in healthcare. To date, no flowmetry studies have been conducted to compare hyperoxygenated fatty acids (HFA) vs. extra-virgin olive oil (EVOO) in alleviating this condition. AIMS: To determine and evaluate the effect of the application of HFA vs. EVOO on tissue oxygenation and perfusion in heels under pressure, in healthy persons and in hospitalised patients. DESIGN: Two-phase experimental study. METHODS: Phase 1 will be conducted with healthy subjects, using a randomised, open study design, evaluating an intrasubject control group. Phase 2 will focus on hospitalised subjects, with a randomised, open study group vs. a control group. DISCUSSION: This Project is undertaken to identify the mechanisms that intervene in the genesis of pressure ulcers and to determine whether there are differences in outcomes between the application of HFA vs. EVOO as a preventive measure The results of this study are of economic importance (due to the price difference between the products used) and will also impact on usual clinical practice for patients with impaired mobility and liable to suffer from pressure ulcers, by considering an alternative to established preventive measures.

Participation of glutamatergic and nitrergic systems in the striatal dopamine release induced by isatin, a MAO inhibitor.

Isatin is a biofactor with different biochemical and pharmacological properties whose effects attract much attention because it is an endogenous inhibitor of the monoamine oxidase in the brain. When exogenously administrated, isatin increases dopamine levels in intact and denervated striatum of rats, an effect that could indicate its potential as a therapeutic agent in Parkinson disease. However, the neurochemical mechanisms by which isatin increases dopamine in the striatum are poorly understood. In the present study, we evaluate the role of the glutamatergic and nitrergic systems in the isatin-induced dopamine release from rat striatum. Our findings show that the intrastriatal administration of 10 mM isatin significantly increases the in vivo release of dopamine (1,104.7% ± 97.1%), and the amino acids glutamate (428.7% ± 127%) and taurine (221% ± 22%) from rat striatum measured by brain microdialysis. The pretreatment with MK-801 (500 µM) or AP5 (650 µM) (glutamatergic NMDA receptors antagonists) significantly reduces the effect of isatin on dopamine release by 52% and 70.5%, respectively. The administration of the nitric oxide synthase inhibitors, L-NAME (100 µM) or 7-NI (100 µM) also decreases the isatin-induced dopamine release by 77% and 42%, respectively. These results show that isatin, in addition to increasing dopamine release, also increases glutamate levels, and possibly activates NMDA receptors and nitric oxide production, which can promote a further increase in the dopamine release.

Antimicrobial Susceptibility of Urogenital and Extragenital Neisseria gonorrhoeae Isolates Among Men Who Have Sex With Men: Strengthening the US Response to Resistant Gonorrhea and Enhanced Gonococcal Isolate Surveillance Project, 2018 to 2019.

BACKGROUND: We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through the Centers for Disease Control and Prevention's enhanced Gonococcal Isolate Surveillance Project and Strengthening the US Response to Resistant Gonorrhea. METHODS: During the period January 1, 2018-December 31, 2019, 12 enhanced Gonococcal Isolate Surveillance Project and 8 Strengthening the US Response to Resistant Gonorrhea sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in sexually transmitted disease clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs), and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. RESULTS: Participating clinics collected 3974 urethral, 1553 rectal, and 1049 pharyngeal isolates from 5456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared with anogenital isolates (P < 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥0.125 µg/mL) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (P < 0.05). CONCLUSIONS: Based on data collected from multijurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of Neisseria gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time.

Tissue temperature, flux and oxygen of sacral and trochanteric area under pressure of healthy subjects: A quasi-experimental study.

AIM: To evaluate the changes that take place in the perfusion, oxygenation and local temperature of the skin of the sacrum and trochanter when subjected to direct pressure for 2 h. METHODS: Quasi-experimental study in the preclinical phase with healthy subjects acting as their own controls (intrasubject control). The outcome variables were measured with a laser Doppler system (local temperature and oxygenation) and by near-infrared spectroscopy (perfusion). The pressure exerted was measured with a capacitive pressure sensor. No more than one week elapsed between the sacrum and trochanter measurements. RESULTS: The study sample consisted of 18 persons. The comparative analysis of the fluctuations in the parameters measured on the skin of the trochanters and sacrum, according to the time elapsed, revealed a statistically significant increase in temperature and in the pressure exerted. On the other hand, the changes in capillary blood flow and in SaO2 were not statistically significant. CONCLUSION: Our study results show that changes found in terms of temperature and pressure should be taking into account when planning personalised repositioning to patients according to biomechanical and biological situations that vary between anatomical areas. In future research, the changes reported could be evaluated in patients with risk factors for the development of pressure ulcers, thus facilitating the introduction of more personalised planning in the care and prevention of these injuries.

Lime is a new protein linking immunity and metabolism in Drosophila.

The proliferation, differentiation and function of immune cells in vertebrates, as well as in the invertebrates, is regulated by distinct signalling pathways and crosstalk with systemic and cellular metabolism. We have identified the Lime gene (Linking Immunity and Metabolism, CG18446) as one such connecting factor, linking hemocyte development with systemic metabolism in Drosophila. Lime is expressed in larval plasmatocytes and the fat body and regulates immune cell type and number by influencing the size of hemocyte progenitor populations in the lymph gland and in circulation. Lime mutant larvae exhibit low levels of glycogen and trehalose energy reserves and they develop low number of hemocytes. The low number of hemocytes in Lime mutants can be rescued by Lime overexpression in the fat body. It is well known that immune cell metabolism is tightly regulated with the progress of infection and it must be supported by systemic metabolic changes. Here we demonstrate that Lime mutants fails to induce such systemic metabolic changes essential for the larval immune response. Indeed, Lime mutants are not able to sustain high numbers of circulating hemocytes and are compromised in the number of lamellocytes produced during immune system challenge, using a parasitic wasp infection model. We therefore propose the Lime gene as a novel functional link between systemic metabolism and Drosophila immunity.

Perfusion, tissue oxygenation and peripheral temperature in the skin of heels of healthy participants exposed to pressure: a quasi-experimental study.

AIM: To evaluate the relationship between the pressure exerted on the heel of one foot resting directly on a mattress, versus that exerted on the other heel, protected by a pillow beneath the Achilles tendon area and the changes thus produced in perfusion, oxygenation and temperature in the skin of heels of healthy volunteers lying in a supine position. DESIGN: Experimental study in a pre-clinical phase, with healthy volunteer participants and intrapeople control. METHODS: The study was carried out from November 2017 - May 2018. A pressure measurement surface was placed between the participant and the constant low-pressure support surface. Doppler laser devices were used to measure local temperature and perfusion. The degree of oxygenation was determined using an infrared beam close to the pressure zone in each heel. Both feet rested immobile on the bed, in a natural position, for 2 hr. To ensure intrapeople control, in every case the left heel was raised slightly, compared with the right. RESULTS: Eighteen participants took part in this study. Analysis of the results obtained showed that capillary blood flow was significantly reduced in the heel subjected to pressure, compared with the other heel, while no significant effects on oxygen saturation or temperature were observed. The variables associated with greater oxygen saturation were capillary blood flow, local temperature and pressure exerted. Fat-free mass, fat mass and duration of exposure to pressure were all significantly associated with reduced oxygen saturation. CONCLUSIONS: In healthy participants, when the heel is subjected to constant pressure against a constant low-pressure support surface, there is a significant reduction in blood flow, compared with the heel where pressure is relieved. However, there are no significant differences in temperature or tissue oxygenation. IMPACT: Significant reductions in vascular flow were observed; however, the oxygenation and temperature of the heel tissues remained unchanged. These findings, corroborated in real patients, would advance our understanding and facilitate decision-making on measures to prevent pressure ulcers, such as repositioning or tissue protection. TRIAL REGISTRATION: The protocol is registered in ClinicalTrials.gov (NCT02736838).

Pressure levels in the trochanter area according to repositioning at different degrees of inclination in healthy subjects.

OBJECTIVES: Patient repositioning is a recommended intervention to prevent or treat pressure ulcers (PUs). One option under consideration is the tailored repositioning according to patient characteristics, but more knowledge is needed on how different repositioning patterns influence on skin pressure. To determine what degree of inclination of the body in bed generates more pressure in the trochanteric region. Additionally, to analyze the influence of factors such as gender, age and anthropometric characteristics in the variations of this pressure. METHODS: Analytical cross-sectional study. Body Mass Index (BMI), lean mass and fat mass were measured in healthy volunteers subject to different inclinations (90°, 60° and 30°) in right lateral decubitus. Pressure was measured with a capacitive surface. RESULTS: In total, 146 subjects were included, of which 45 were men and 101 women. The results showed pressure differences due to the inclination according to gender and anthropometric values, being statistically significant in men at 90° and 60°, and in women at 30°. (hombres 90° p = 0,026, 60° p = 0,049; mujeres 30° p = 0,036) según prueba Brown-Forsythe. CONCLUSIONS: There are differences in the pressures of the trochanteric zone depending on anthropometric factors and by gender, in different body positions. Obese people exerted a higher pressure in the trochanter area at 30° of body inclination than overweight, normal weight and underweight people, respectively. From the clinical point of view, these findings invite to consider a possible differentiation in the repositioning interventions of the patients, according to gender and BMI, as a preventive strategy for PUs.

Healing of autoimmune hepatitis associated with hepatitis C virus infection treated with direct-acting antivirals.

The use of direct-acting antivirals (DAA) for the hepatitis C virus (HCV) has yielded a significant improvement in the treatment of autoimmune hepatitis (AIH) associated with HCV infection. Interferon was the cornerstone of HCV therapy before the introduction of these agents into the clinical practice. Herein, we report the case of an HCV-infected patient who developed an interferon-induced AIH and since then, has received immunosuppressive therapy. Administration of DAA resulted in a sustained virologic response (SVR) and clinical AIH remission which allowed a discontinuation of immunosuppressive treatment.

Hepatitis B virus in patients with chronic hepatitis C treated with direct antiviral agents.

INTRODUCTION: cases of hepatitis B virus (HBV) reactivation have been reported in patients with hepatitis C virus (HCV) treated with direct antiviral agents (DAA). OBJECTIVES AND METHODS: the main objectives of the present study are: a) to determine the prevalence of HBV/HCV coinfection in HCV patients treated with DAAs in the Autonomous Community of Madrid (CM) and also to determine the incidence and clinical relevance of HBV reactivation; and b) to determine the HBV screening rates in HCV patients in our region. For that purpose, 1,337 HCV patients were consecutively treated with DAAs in two hospitals located in South CM between January 2015 and June 2017. RESULTS: nine of the 1,337 (0.67%) participants were HBsAg positive and 356 (26.6%) had previous HBV infection markers. Two of the four (50%) HBsAg positive patients with untreated HBV developed a virological reactivation, but not a biochemical reaction. Of the 356 patients with previous HBV infection markers, all had normal transaminases at the end of treatment and during follow-up. The HBV screening rate amounted to 92.9% of the cohort. CONCLUSIONS: the prevalence of HBV (HBsAg positive) infection in patients with chronic hepatitis C in the southern area of the CM is low. HBV reactivation in HBsAg positive patients treated with DAAs is common, although without clinical relevance. In our region, there is a high rate of HBV screening in patients with HCV that are likely treated with DAAs.

[The clinical psychologist in health centres. A joint work between primary care and mental health]. / El psicólogo clínico en los centros de salud. Un trabajo conjunto entre atención primaria y salud mental.

From the model of Integral Primary Care and under the principle of continuity of care, the development of channels of communication and integration between the first and second level of care in relation to mental health care is proposed. It presents the pioneering experience established in the Health Service of Lanzarote in which the figure of the clinical psychologist has been moved to the Health Centres to develop a joint community program from the Primary Care. The lines of action have focused on direct work with the patient, as well as with the staff, both individually and as a group. The objective is the sensitisation and standardisation of the treatment for mental disease in Health Centres. This work has been carried out with a positive assessment by patients and staff of the centres, which at the same time has demanded greater accessibility for a full implementation of the joint work model focused on the promotion, prevention, detection, and treatment for health mental.

Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C.

BACKGROUND & AIMS: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. METHODS: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. RESULTS: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004). CONCLUSIONS: Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy. LAY SUMMARY: Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.

The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila.

The silent information regulator 1 (Sirt1) has been shown to have negative effects on the Notch pathway in several contexts. We bring evidence that Sirt1 has a positive effect on Notch activation in Drosophila, in the context of sensory organ precursor specification and during wing development. The phenotype of Sirt1 mutant resembles weak Notch loss-of-function phenotypes, and genetic interactions of Sirt1 with the components of the Notch pathway also suggest a positive role for Sirt1 in Notch signalling. Sirt1 is necessary for the efficient activation of enhancer of split [E(spl)] genes by Notch in S2N cells. Additionally, the Notch-dependent response of several E(spl) genes is sensitive to metabolic stress caused by 2-deoxy-d-glucose treatment, in a Sirt1-dependent manner. We found Sirt1 associated with several proteins involved in Notch repression as well as activation, including the cofactor exchange factor Ebi (TBL1), the RLAF/LAF histone chaperone complex and the Tip60 acetylation complex. Moreover, Sirt1 participates in the deacetylation of the CSL transcription factor Suppressor of Hairless. The role of Sirt1 in Notch signalling is, therefore, more complex than previously recognized, and its diverse effects may be explained by a plethora of Sirt1 substrates involved in the regulation of Notch signalling.

Noninvasive ventilation for severely acidotic patients in respiratory intermediate care units : Precision medicine in intermediate care units.

BACKGROUND: Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. METHODS: We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH ≥ 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. RESULTS: We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 ± 7.2 and 19 ± 5.8 for the ACPE patients (p < 0.05), 20 ± 5.7 and 19 ± 5.1 for the COPD patients (p < 0.01) and 18 ± 5.9 and 17 ± 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 ± 22 and 70 ± 15 in the ACPE patients (p < 0.001), 87 ± 21 and 76 ± 14 in the COPD patients, and 83 ± 17 and 74 ± 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 ± 3.1 vs. 3.6 ± 2.5, NS; COPD, 5.1 ± 3 vs. 3.6 ± 2.1, p < 0.001; and OHS, 4.3 ± 2.6 vs. 3.7 ± 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. CONCLUSIONS: ACPE, COPD and OHS patients with AHRF and severe acidosis (pH ≤ 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria.