Real-life experience of chronic hepatitis C treatment in Switzerland: a retrospective analysis.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C. We analysed the use of different generations of DAAs over time in Switzerland and investigated factors predictive of treatment failure. METHODS: This retrospective study was conducted within the framework of the Swiss Association for the Study of the Liver and the Swiss Hepatitis C Cohort Study; it included all patients with chronic hepatitis C treated with DAAs between January 2015 and December 2019 at eight Swiss referral centres. RESULTS: A total of 3088 patients were included; 57.3% were male, and the median age was 54 years. Liver cirrhosis was present in 23.9% of the cohort, 87.8% of whom were compensated. The overall sustained virological response (SVR) rate (defined as undetectable HCV RNA at week 12 after the first course of DAA-based treatment) was 96.2%, with an increase over time. The rate of treatment failure dropped from 8.3% in 2015 to 2.5% in 2019. Multivariable analysis revealed that female sex, the use of the latest generation of pangenotypic DAA regimens, Caucasian origin, and genotype (gt) 1 were associated with SVR, whereas the presence of active hepatocellular carcinoma (HCC), gt 3, and increasing liver stiffness were associated with treatment failure. Notably, the presence of active HCC during treatment increased the risk of DAA failure by a factor of almost thirteen. CONCLUSIONS: SVR rates increased over time, and the highest success rates were identified after the introduction of the latest generation of pangenotypic DAA regimens. Active HCC, gt 3 and increasing liver stiffness were associated with DAA failure.

Paediatric-onset lymphomatoid papulosis: results of a multicentre retrospective cohort study on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population are scarce. OBJECTIVES: To characterize the epidemiological, clinical, histopathological and prognostic features of paediatric LyP. METHODS: This was a retrospective multicentre international cohort study that included 87 children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years at disease onset were included. LyP diagnosis was made in each centre, based on clinicopathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. Mean age at disease onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2 : 1. Mean time between the onset of the first cutaneous lesions and diagnosis was 1.3 years (range 0-14). Initial misdiagnosis concerned 26% of patients. LyP was most often misdiagnosed as pityriasis lichenoides et varioliformis acuta, insect bites or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned in 21% of patients. The main histological subtype was type A in 55% of cases. When analysed, monoclonal T-cell receptor rearrangement was found in 77% of skin biopsies. The overall survival rate was 100%, with follow-up at 5 years available for 33 patients and at 15 years for 8 patients. Associated haematological malignancy (HM) occurred in 10% of cases (n = 7/73), including four patients with mycosis fungoides, one with primary cutaneous anaplastic large cell lymphoma (ALCL), one with systemic ALCL and one with acute myeloid leukaemia. If we compared incidence rates of cancer with the world population aged 0-19 years from 2001 to 2010, we estimated a significantly higher risk of associated malignancy in general, occurring before the age of 19 years (incidence rate ratio 87.49, 95% confidence interval 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall, the disease prognosis is good, with excellent survival rates for all patients. Owing to an increased risk of associated HM, long-term follow-up should be recommended for patients with LyP.

Lymphomatoid papulosis is a very rare skin condition caused by an abnormal increase in white blood cells (called 'lymphocytes') in the skin. The condition rarely affects children, so most of the scientific data published about this disease focuses on adults. This study involved 12 academic dermatology centres in Europe, the Middle East and North America, and gathered data from about 87 children who presented with symptoms of lymphomatoid papulosis before the age of 19 years. The aim of this study was to better describe this disease in the paediatric population and discuss its treatment options and evolution. We found that the presentation of the disease in children is roughly the same as in adults. Safe and effective treatment options exist. The disease is not life threatening, but it requires investigation by a dermatologist, both to make a careful diagnosis and to monitor it as sometimes associated cancers that originate from blood cells can occur, mostly on the skin.

High-risk coronary plaque of sudden cardiac death victims: postmortem CT angiographic features and histopathologic findings.

High-risk coronary plaques (HRP) are characterized in clinical radiological imaging by the presence of low plaque attenuation, a napkin-ring sign (NRS), spotty calcifications (SC) and a positive remodeling index (RI). To evaluate if these signs are detectable in postmortem imaging by a multi-phase postmortem CT angiography (MPMCTA), a retrospective study of a series of autopsy well-documented coronary plaques related to sudden cardiac death (SCD) was performed. Then correlations between histological and radiological findings were described. Fourty SCD cases due to acute coronary syndrome based on clinical history and confirmed at autopsy were selected (28 men and 12 women, age 53.3 ± 10.9). The culprit lesion was mainly situated in the proximal segments of coronary arteries, in the right coronary artery in 23 cases (57.5%), the left anterior descending artery in 13 cases (32.5%), the circumflex artery in 3 cases (7.5%) and in one case in the left main stem. MPMCTA showed a positive RI (≥ 1.1) in 75% of cases with a mean RI 1.39 ± 0.71. RI values were lower in cases with fibrotic plaques. NRS was observed in 40% of cases, low attenuation plaque in 46.3%, and SC in 48.7% of cases. There were significant correlations of the radiological presence of NRS for fibrolipid composition of the plaque (p-value 0.007), severe intraplaque inflammation (p-value 0.017), severe adventitial inflammation (p-value 0.021) and an increased vasa vasorum (p-value 0.012). A significant correlation (p-value 0.002) was observed between the presence of SC at radiological examination and the presence of punctuate/fragmented calcification at histology. In addition, in 58.3% of cases, plaque enhancement was observed, which correlated with plaque inflammation and the fibrolipid composition of the plaque. The coronary artery calcium score was 314 (± 455). There was a poor agreement between stenosis of the lumen at histology versus radiology. Our study shows that the various radiological signs of HRP can be detected in all plaques by MPMCTA, but individually only to a variable extent; plaque enhancement appeared as a new sign of vulnerability. In the postmortem approach, these radiological markers of HRP, should always be applied in combination, which can be useful for developing a predictive model for diagnosing coronary SCD.

Impact of the Mean Cochlear Biologically Effective Dose on Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannoma: A Retrospective Longitudinal Analysis.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is a useful alternative for small- to medium-sized vestibular schwannoma. To evaluate whether biologically effective dose (BED Gy2.47 ), calculated for mean (BED Gy2.47 mean) and maximal (BED Gy2.47 max) cochlear dose, is relevant for hearing preservation. METHODS: This is a retrospective longitudinal single-center study. Were analyzed 213 patients with useful baseline hearing. Risk of hearing decline was assessed for Gardner-Robertson classes and pure tone average (PTA) loss. The mean follow-up period was 39 months (median 36, 6-84). RESULTS: Hearing decline (Gardner-Robertson class) 3 years after SRS was associated with higher cochlear BED Gy2.47 mean (odds ratio [OR] 1.39, P = .009). Moreover, BED Gy2.47 mean was more relevant as compared with BED Gy2.47 max (OR 1.13, P = .04). Risk of PTA loss (continuous outcome, follow-up minus baseline) was significantly corelated with BED Gy2.47 mean at 24 (beta coefficient 1.55, P = .002) and 36 (beta coefficient 2.01, P = .004) months after SRS. Risk of PTA loss (>20 dB vs ≤) was associated with higher BED Gy2.47 mean at 6 (OR 1.36, P = .002), 12 (OR 1.36, P = .007), and 36 (OR 1.37, P = .02) months. Risk of hearing decline at 36 months for the BED Gy2.47 mean of 7-8, 10, and 12 Gy 2.47 was 28%, 57%, and 85%, respectively. CONCLUSION: Cochlear BED Gy2.47 mean is relevant for hearing decline after SRS and more relevant as compared with BED Gy2.47 max. Three years after SRS, this was sustained for all hearing decline evaluation modalities. Our data suggest the BED Gy2.47 mean cut-off of ≤8 Gy 2.47 for better hearing preservation rates .

Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 study.

BACKGROUND: Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. METHODS: In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18-45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. FINDINGS: 26 participants were enrolled (August-September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088-0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/105 CD8+, 95% CI: 0.19-5.13, p = 0.014 and +1.34/105 CD8+, 95% CI: 0.1-7.34, p = 0.024, respectively). INTERPRETATION: Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. FUNDING: Emergex Vaccines Holding Limited.

Kinetics of small and middle molecule clearance during continuous hemodialysis.

Regional citrate anticoagulation (RCA) enables prolonged continuous kidney replacement therapy (CKRT) filter lifespan. However, membrane diffusive performance might progressively decrease and remain unnoticed. We prospectively evaluated the kinetics of solute clearance and factors associated with decreased membrane performance in 135 consecutive CKRT-RCA circuits (35 patients). We recorded baseline patients' characteristics and clinical signs of decreased membrane performance. We calculated effluent/serum ratios (ESR) as well as respective clearances for urea, creatinine and ß2-microglobuline at 12, 24, 48 and 72 h after circuit initiation. Using mixed-effects logistic regression model analyses, we assessed the effect of time on those values and determined independent predictors of decreased membrane performance as defined by an ESR for urea < 0.81. We observed a minor but statistically significant decrease in both ESR and solute clearance across the duration of therapy for all three solutes. We observed decreased membrane performance in 31 (23%) circuits while clinical signs were present in 19 (14.1%). The risk of decreased membrane performance significantly increased over time: 1.8% at T1 (p = 0.16); 7.3% at T2 (p = 0.01); 15.7% at T3 (p = 0.001) and 16.4% at T4 (p < 0.003). Four factors present within 24 h of circuit initiation were independently associated with decreased membrane performance: arterial blood bicarbonate level (OR 1.50; p < 0.001), activated partial thromboplastin time (aPTT; OR = 0.93; p = 0.02), fibrinogen level (OR 6.40; p = 0.03) and Charlson score (OR 0.10; p < 0.01). COVID-19 infection was not associated with increased risk of decreased membrane performance. Regular monitoring of ESR might be appropriate in selected patients undergoing CKRT.

Proton beam radiation therapy for vestibular schwannomas-tumor control and hearing preservation rates: a systematic review and meta-analysis.

OBJECTIVE: Proton beam therapy is considered, by some authors, as having the advantage of delivering dose distributions more conformal to target compared with stereotactic radiosurgery (SRS). Here, we performed a systematic review and meta-analysis of proton beam for VSs, evaluating tumor control and cranial nerve preservation rates, particularly with regard to facial and hearing preservation. METHODS: We reviewed, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) articles published between 1968 and September 30, 2022. We retained 8 studies reporting 587 patients. RESULTS: Overall rate of tumor control (both stability and decrease in volume) was 95.4% (range 93.5-97.2%, p heterogeneity= 0.77, p<0.001). Overall rate of tumor progression was 4.6% (range 2.8-6.5%, p heterogeneity < 0.77, p<0.001). Overall rate of trigeminal nerve preservation (absence of numbness) was 95.6% (range 93.5-97.7%, I2 = 11.44%, p heterogeneity= 0.34, p<0.001). Overall rate of facial nerve preservation was 93.7% (range 89.6-97.7%, I2 = 76.27%, p heterogeneity<0.001, p<0.001). Overall rate of hearing preservation was 40.6% (range 29.4-51.8%, I2 = 43.36%, p heterogeneity= 0.1, p<0.001). CONCLUSION: Proton beam therapy for VSs achieves high tumor control rates, as high as 95.4%. Facial rate preservation overall rates are 93%, which is lower compared to the most SRS series. Compared with most currently reported SRS techniques, proton beam radiation therapy for VSs does not offer an advantage for facial and hearing preservation compared to most of the currently reported SRS series.

The Relevance of Biologically Effective Dose for Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannomas: A Retrospective Longitudinal Study.

BACKGROUND: Stereotactic radiosurgery has become a common treatment approach for small-to-medium size vestibular schwannomas. OBJECTIVE: To evaluate relationship between time (beam-on and treatment) and risk of hearing decline after stereotactic radiosurgery for vestibular schwannomas in patients with Gardner-Robertson (GR) baseline classes I and II. METHODS: This retrospective longitudinal single-center study included 213 patients with GR I and II treated between June 2010 and December 2019. Risk of passing from GR classes I and II (coded 0) to other classes III, IV, and V (coded 1) and the increase in pure tone average (continuous outcome) were evaluated using a mixed-effect regression model. Biologically effective dose (BED) was further assessed for an alpha/beta ratio of 2.47 (Gy 2.47 ). RESULTS: Binary outcome analysis revealed sex, dose rate, integral dose, time [beam-on time odds ratio 1.03, P = .03, 95% CI 1.00-1.06; treatment time ( P = .02) and BED ( P = .001) as relevant. Fitted multivariable model included the sex, dose rate, and BED. Pure tone average analysis revealed age, integral dose received by tumor, isocenter number, time (beam-on time odds ratio 0.20, P = .001, 95% CI 0.083-0.33) and BED ( P = .005) as relevant. CONCLUSION: Our analysis showed that risk of hearing decline was associated with male sex, higher radiation dose rate (cutoff 2.5 Gy/minute), higher integral dose received by the tumor, higher beam-on time ≥20 minutes, and lower BED. A BED between 55 and 61 was considered as optimal for hearing preservation.

Combining default choices and an encounter decision aid to improve tobacco cessation in primary care patients: protocol for a cluster-randomized trial.

BACKGROUND: While quitting smoking dramatically decreases overall mortality, general practitioners (GPs) are less likely to prescribe medications for smoking cessation than other cardiovascular risk factors. Guidelines recommend providers first assess patients' "readiness" to quit, an "opt-in" strategy, but only a minority of tobacco users are ready to quit on a given day. An "opt-out" strategy offering treatment as the default choice increased quit attempts in hospital and with pregnant women, but has not been tested in primary care. We will assess the efficacy of training GPs to offer treatment as the default choice using an encounter decision aid with current smokers seen in primary care. METHODS: This is a pragmatic cluster-randomized controlled superiority trial with block randomization at the GP level in private practice in French-speaking Switzerland. GPs will be blinded to the arm allocation. The intervention is a half-day training course teaching an 'opt-out' approach to smoking cessation using an encounter decision aid (paper or electronic). GPs in the enhanced usual care group receives a brief refresher training about smoking cessation without changing their behaviour. GPs in both arms will recruit 23 patients each prior to routine primary care visits. The primary outcome is the effect of consulting a GP who received the intervention on the 7-day, point prevalence, smoking abstinence 6 months after the baseline appointment. Secondary outcomes include continuous abstinence; number of quit attempts; use of smoking cessation aids; patient-perceived involvement in discussions; and changes in GP behaviour. Patient outcomes will be collected using paper and telephone questionnaires. Assuming 15% drop-out, recruiting 46 GPs with 23 patients each will give us 80% power to detect an increase in smoking cessation from 4% (control) to 10.5% (intervention), with an alpha < 0.05. DISCUSSION: GP visits are an opportunity to administer proven smoking cessation treatments. We hypothesize GPs offering smoking cessation treatment as the default choice using an encounter decision aid will increase the number of patients who quit. This study could significantly change our approach to smoking cessation in primary care. Default choices and the electronic decision aid are low-cost, easily diffusible interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04868474, First Posted May 3, 2021, Last Update Posted October 6, 2021.

Seroprevalence of SARS-CoV-2 antibodies and associated risk factors in children less than 6 years of age in the canton of Fribourg, Switzerland (COVPED study): a population-based cross-sectional study.

BACKGROUND: To date, few data are available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in young children and the role of early-life childcare arrangements in transmission of the virus. In this study, we assessed the SARS-CoV-2 seroprevalence in children less than 6 years of age in the canton of Fribourg and identified risk factors associated with seropositivity. METHODS: The COVPED study is a population-based cross-sectional study in children less than 6 years of age living in the canton of Fribourg, Switzerland, who presented to a private paediatrician or the paediatric emergency department of the Fribourg Hospital during a 9-week period between 11 January and 14 March 2021. Immunoglobulin G antibodies against SARS-CoV-2 trimeric spike protein were measured in capillary blood samples using an in-house Luminex assay. A mean fluorescence intensity ratio of above 6 was considered as positive. Metadata was collected through electronic questionnaires. Logistic regression analysis was performed to assess the risk of seropositivity and associated factors. RESULTS: A total of 871 children, with a median age of 33 months (range 6 days to 5 years 11 months) were included; 412 (47%) were female. Overall, 180 (21%, 95% confidence interval [CI] 18-24%) children were seropositive. Age as continuous variable was not associated with seropositivity risk, apart from a higher rate in children less than 3 months of age. Univariable analysis showed that female sex was associated with a lower seropositivity risk (unadjusted odds ratio [OR] 0.69, 95% CI 0.49-0.96; p = 0.03). Day-care attendance was also associated with a lower seropositivity risk (OR 0.67, 95% CI 0.47-0.95; p = 0.03), whereas all other childcare arrangements were not associated with seropositivity. No association was found between the number of children and adults present in extra-familial care and seropositivity. Multivariable analysis identified the number of household members above the age of 12 years being positive for SARS-CoV-2 as the main risk factor for seropositivity in children (adjusted odds ratio [aOR] 7.80, 95% CI 4.65-13.07; p <0.001 for one household member, aOR 22.07, 95% CI 13.49-36.11; p <0.001 for two household members and aOR 32.20, 95% CI 9.30-111.55; p <0.001 for three or more household members). CONCLUSION: The number of household members tested positive for SARS-CoV-2 (PCR test) is the main exposure risk to seropositivity for children less than 6 years of age. But the family size is not associated with an increased risk of infection. In young children, extra-familial care does not increase the risk of becoming SARS-CoV-2 seropositive, neither does the number of contacts present in extra-familial care. As adults and children will be vaccinated and new virus variants will be circulating the risk of exposure for young children will likely change and needs further monitoring.

Tumor control and radiobiological fingerprint after Gamma Knife radiosurgery for posterior fossa meningiomas: A series of 46 consecutive cases.

INTRODUCTION: Gamma Knife radiosurgery (GKR) can be a valuable treatment option for posterior cranial fossa meningiomas (PCFM). We retrospectively analyzed outcomes of GKR for PCFM. METHODS: Were included forty-six patients with 47 PCFM. Primary endpoint was tumor control. Secondary endpoint was clinical improvement. Biologically effective dose (BED) was evaluated in relationship to primary and secondary outcomes. Mean marginal dose was 12.4 Gy (median 12, 12-14). Mean BED was 63.6 Gy (median 65, 49.1-88.3). Mean target volume (TV) was 2.21 cc (range 0.3-8.9 cc). RESULTS: Overall tumor control rate was 93.6% (44/47) after mean follow-up of 47.8 months ± 28.46 months (median 45.5, range 6-108). Radiological progression-free survival at 5 years was 94%. Higher pretherapeutic TVs were predictive for higher likelihood of tumor progression (Odds ratio, OR 1.448, 95% confidence interval - CI 1.001-2.093, p = 0.049). At last clinical follow-up, 28 patients (71.8%) remained stable, 10 (25.6%) improved and 1 patient (2.6%) worsened. Using logistic regression, the relationship between BED and clinical improvement was assessed (OR 0.903, standard error 0.59, coefficient 0.79-1.027, CI -0.10; 0.01; p = 0.14). The highest probability of clinical improvement corresponded to a range of BED values between 56 and 61 Gy. CONCLUSION: Primary GKR for PCFM is safe and effective. Higher pretherapeutic TV was predictor of volumetric progression. Highest probability of clinical improvement might correspond to a range of BED values between 56 and 61 Gy, although this was not statistically significant. The importance of BED should be further validated in larger cohorts, other anatomical locations and other pathologies.

Is women's sexual function impaired by an abnormal pap smear?

OBJECTIVE: Although the stressful psychological impact on women of an abnormal Pap smear is well documented, little research has been undertaken on its sexual impact. Our objective was to assess the impact of an abnormal Pap smear on the sexual function of affected women. METHODS: A prospective study compared the sexual function of 48 women with an abnormal Pap smear (case group) with that of 48 women with a normal Pap smear (control group). Sexual function was assessed using the Female Sexual Function Index and the Hospital Anxiety Depression Scale. The questionnaires were mailed to the participants. RESULTS: Surprisingly, the risk of sexual dysfunction was comparable between women with and without an abnormal Pap smear (odds ratio [OR] 0.7; p = 0.4). The OR remained statistically non-significant after adjustment for risk factors. Multivariable analysis showed that only older age at first intercourse, depression and anxiety were identified as factors significantly associated with sexual dysfunction. CONCLUSION: Contrary to our clinical experience, female sexual function is not impaired by an abnormal Pap smear. Further research is needed to better understand how sexuality in women with abnormal Pap smears may be affected.

Virtually Augmented Self-Hypnosis applied to endovascular interventions (VA-HYPO): Randomized Controlled Trial Protocol.

Endovascular interventions (EVI) are increasingly performed as minimally-invasive alternatives to surgery and have many advantages, including a decreased need for general anesthesia. However, EVI can be stressful for patients and often lead to anxiety and pain related to the procedure. The use of local anesthetics, anxiolytics, and analgesic drugs can help avoid general anesthesia. Nevertheless, these drugs have potential side effects. Alternative nonpharmacological therapies can improve patients' experience during conscious interventions and reduce the need for additional medications. The added value of virtually augmented self-hypnosis (VA-HYPO) and its potential to reduce pain and anxiety during peripheral and visceral arterial and venous EVI is unknown. This is a prospective two-arm trial designed to randomize 100 patients in two groups according to the use or not of VA-HYPO during peripheral EVI as a complementary nonpharmacological technique to improve patient comfort. The main objective is to compare per-procedural anxiety, and the secondary aim is to compare the rated per-procedural pain in both groups. The potential significance is that VA-HYPO may improve patients' experience during peripheral and visceral arterial and venous EVI and other minimally invasive interventions performed under local anesthesia. Trial registration: Our study is registered on clinicaltrials.gov, with trial registration number: NCT04561596.

Association of Oliguria With Acute Kidney Injury Diagnosis, Severity Assessment, and Mortality Among Patients With Critical Illness.

Importance: The current definition and staging of acute kidney injury (AKI) considers alterations in serum creatinine (sCr) level and urinary output (UO). However, the relevance of oliguria-based criteria is disputed. Objective: To determine the contribution of oliguria, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, to AKI diagnosis, severity assessment, and short- and long-term outcomes. Design, Setting, and Participants: This cohort study included adult patients admitted to a multidisciplinary intensive care unit from January 1, 2010, to June 15, 2020. Patients receiving long-term dialysis and those who declined consent were excluded. Daily sCr level and hourly UO measurements along with sociodemographic characteristics and severity scores were extracted from electronic medical records. Long-term mortality was assessed by cross-referencing the database with the Swiss national death registry. The onset and severity of AKI according to the KDIGO classification was determined using UO and sCr criteria separately, and their agreement was assessed. Main Outcomes and Measures: Using a multivariable model accounting for baseline characteristics, severity scores, and sCr stages, the association of UO criteria with 90-day mortality was evaluated. Sensitivity analyses were conducted to assess how missing sCr, body weight, and UO values, as well as different sCr baseline definitions and imputations methods, would affect the main results. Results: Among the 15 620 patients included in the study (10 330 men [66.1%] with a median age of 65 [IQR, 53-75] years, a median Simplified Acute Physiology Score II score of 40.0 [IQR, 30.0-53.0], and a median follow-up of 67.0 [IQR, 34.0-100.0] months), 12 143 (77.7%) fulfilled AKI criteria. Serum creatinine and UO criteria had poor agreement on AKI diagnosis and staging (Cohen weighted κ, 0.36; 95% CI, 0.35-0.37; P < .001). Compared with the isolated use of sCr criteria, consideration of UO criteria enabled identification of AKI in 5630 patients (36.0%). Those patients had a higher 90-day mortality than patients without AKI (724 of 5608 [12.9%] vs 288 of 3462 [8.3%]; P < .001). On multivariable analysis accounting for sCr stage, comorbidities, and illness severity, UO stages 2 and 3 were associated with a higher 90-day mortality (odds ratios, 2.4 [95% CI, 1.6-3.8; P < .001] and 6.2 [95% CI, 3.7-10.5; P < .001], respectively). These results remained significant in all sensitivity analyses. Conclusions and Relevance: The findings of this cohort study suggest that oliguria lasting more than 12 hours (KDIGO stage 2 or 3) has major AKI diagnostic implications and is associated with outcomes irrespective of sCr elevations.

Bariatric Surgery Induces a Differential Effect on Plasma Aldosterone in Comparison to Dietary Advice Alone.

Background and Objectives: The pathophysiological mechanisms linking weight loss to blood pressure (BP) reduction are not completely understood. The objective of this study was to compare the effect of weight loss after Roux-en-Y gastric bypass (RYGB) on BP, renin-angiotensin-aldosterone system (RAAS), and urinary electrolytes excretion to those of dietary advice. Methods: This was a case-control prospective study including obese patients referred for RYGB (cases) and obese receiving diet advice only (controls). Ambulatory BP, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary electrolytes were measured before (M0) and after intervention (M3: 3 months and M12: 12 months). Results: Twenty-five patients were included in the RYGB group and twelve patients in the control group. After 12 months, weight loss (-42 ± 11.5 vs -12.3 ± 6.3 kg in the control group, p=0.001) and decrease in PAC were more pronounced in the RYGB group (-34 ± 76 vs +14 ± 45 pg/ml in the control group, p=0.002). There was no difference in PRA between both groups (-0.08 ± 1.68 vs 0.01 ± 0.37 ng/ml/h, p=0.31). Sodium excretion was more marked in the RYGB group after 3 months only (-89 ± 14.9 vs -9.9 ± 27.9 mmol/day, p=0.009). The decrease in SBP was similar between both groups (-6.9 ± 9.9 vs -7.1 ± 11.9 mmHg in the control group, p=0.96). Conclusions: Bariatric-induced weight loss induces a progressive decrease in PAC independently of PRA and sodium excretion. Whether this decrease in PAC affects target organ damage in the long term remains to be determined. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02218112.

The fate of orally administered sialic acid: First insights from patients with N-acetylneuraminic acid synthase deficiency and control subjects.

BACKGROUND: In NANS deficiency, biallelic mutations in the N-acetylneuraminic acid synthase (NANS) gene impair the endogenous synthesis of sialic acid (N-acetylneuraminic acid) leading to accumulation of the precursor, N-acetyl mannosamine (ManNAc), and to a multisystemic disorder with intellectual disability. The aim of this study was to determine whether sialic acid supplementation might be a therapeutic avenue for NANS-deficient patients. METHODS: Four adults and two children with NANS deficiency and four adult controls received oral NeuNAc acid (150 mg/kg/d) over three days. Total NeuNAc, free NeuNAc and ManNAc were analyzed in plasma and urine at different time points. RESULTS: Upon NeuNAc administration, plasma free NeuNAc increased within hours (P < 0.001) in control and in NANS-deficient individuals. Total and free NeuNAc concentrations also increased in the urine as soon as 6 h after beginning of oral administration in both groups. NeuNAc did not affect plasma and urinary ManNAc, that remained higher in NANS deficient subjects than in controls (day 1-3; all P < 0.01). Oral NeuNAc was well tolerated with no significant side effects. DISCUSSION: Orally administered free NeuNAc was rapidly absorbed but also rapidly excreted in the urine. It did not change ManNAc levels in either patients or controls, indicating that it may not achieve enough feedback inhibition to reduce ManNAc accumulation in NANS-deficient subjects. Within the limitations of this study these results do not support a potential for oral free NeuNAc in the treatment of NANS deficiency but they provide a basis for further therapeutic approaches in this condition.

Fractures After Denosumab Discontinuation: A Retrospective Study of 797 Cases.

A rebound of osteoclast activity during the 2 years after a treatment or prevention of osteoporosis with denosumab (Dmab) leads to an increased risk of vertebral fractures (VFs). We attempted to identify the risk factors for these VF and to examine the protective role of bisphosphonates. For that, 22 specialists in Switzerland provided data of unselected patients, treated with denosumab for osteoporosis or breast cancer without metastases under aromatase inhibitors, who have received at least two injections of Dmab, with at least 1 year of follow-up after discontinuation. The questionnaire covered separately the periods before, during, and after Dmab treatment, and registered clinical, radiological, and lab data. For the analysis of the risk factors, the main outcomes were the time to the first VF after the treatment, the presence of multiple VFs (MVFs), and the number of VFs. The incidence of VF was 16.4% before, 2.2% during, and 10.3% after the treatment with Dmab. The risk of VF after Dmab discontinuation was associated with an increased risk of non-vertebral fractures. The pretreatment predictors of the post-treatment fracture risk were a parental hip fracture and previous VFs. Further risk factors appeared later, such as low total hip bone mineral density (BMD) during and after denosumab, increased bone resorption markers, and the loss of total hip BMD after the denosumab. Treatment with bisphosphonates, especially after Dmab, had a protective effect. Bisphosphonates given before Dmab did not further decrease the risk of VF in cases who got bisphosphonates after Dmab. This study shows that the risk of VF is poorly predictable before the prescription of denosumab. But during and after the treatment, bone resorption markers and BMD have a significant predictive value. Bisphosphonates after the treatment with denosumab are protective against VFs. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The influence of psychosocial factors on the intention to incorporate complementary and integrative medicine into psychiatric clinical practices.

Complementary and integrative medicine (CIM) can be of great support to individuals suffering from psychiatric conditions; however, it is still rarely incorporated into clinical practice. OBJECTIVE: To examine the influences of psychosocial and sociodemographic factors on health-care professionals' intention to use CIM in their psychiatric clinical practice. METHOD: One-hundred-and-five participants completed a questionnaire developed from an adapted version of Triandis' Theory of Interpersonal Behavior (TIB). Intentions to use CIM (yes or no) were analyzed using logistic regression models. RESULTS: The multivariate model retained three main factors: affect, perceived social norms, and conditions facilitating CIM. These predicted health-care professionals' intention to use CIM with an AUC = 94.7%. RESULTS: underlined that positive affective attitudes towards CIM, feeling that CIM was congruent with professional and institutional goals, and having sufficient skills in CIM were essential to ensuring that health-care professionals would integrate CIM into their clinical practice.