Search

The entry-inhibitor Bulevirtide (BLV) received conditional approval by EMA in July 2020 for the treatment of adult patients with compensated chronic hepatitis Delta. However, the effectiveness and safety of BLV administered as monotherapy beyond 48 weeks in difficult to treat HDV cirrhotic patients is presently unknown. Here we describe the first patients with HDV-related compensated cirrhosis who were treated with BLV (10 mg/day as a starting dose) for up to three years as compassionate use. Patients were also monitored for HBcrAg and HBV-RNA levels and HDV and HBV specific T-cells markers. In the patient who stopped BLV at week 48 after achieving a virological and biochemical response, the initial virological and biochemical rebound was followed by ALT normalization coupled with low HDV-RNA and HBsAg levels. In the two patients treated continuously for 3 years, virological and biochemical responses were maintained throughout the treatment period even after dose reduction. In a patient with advanced compensated cirrhosis, liver function tests significantly improved, esophageal varices disappeared, and histological/lab features of autoimmune hepatitis resolved. Overall, no safety issues were recorded, as bile salt increase was asymptomatic. While serum HBV-RNA levels remained undetectable in all patients, HBcrAg levels showed a progressive, yet modest decline during long-term BLV-treatment. No HDV-specific Interferon-γ producing T-cells were detected, neither after HDV reactivation (after BLV withdrawn in Patient 1) nor during 3 years of BLV treatment. In conclusion, this report shows that continuous administration of BLV monotherapy for three years provides excellent virological and clinical response in HDV cirrhotic patients who had contraindications to IFN-based therapies. LAY SUMMARY: HDV-RNA levels became undetectable, and ALT normalized in all three patients treated with Bulevirtide (BLV). Virological and biochemical responses were maintained even after dose reduction.- Improvement of liver function tests, regression of esophageal varices and recovery of HDV-related autoimmune disease were documented in the male cirrhotic patient long-term treated with BLV.- An asymptomatic increase of bile acids was the only drug-related clinical adverse event.

Background: Hypertension is a complex disease and is the major cause of cardiovascular complications. In the vast majority of individuals, the aetiology of elevated blood pressure (BP) cannot be determined, thus impairing optimized therapies and prognosis for individual patients. A more precise understanding of the molecular pathogenesis of hypertension remains a pressing priority for both basic and translational research. Here we investigated the effect of salt on naive hypertensive patients in order to better understand the salt intake-blood pressure relationship. Methods: Patients underwent an acute saline infusion and were defined as salt-sensitive or salt-resistant according to mean blood pressure changes. Urinary proteome changes during the salt load test were analysed by a label-free quantitative proteomics approach. Results: Our data show that salt-sensitive patients display equal sodium reabsorption as salt-resistant patients, as major sodium transporters show the same behaviour during the salt load. However, salt-sensitive patients regulate the renin angiotensin system (RAS) differently from salt-resistant patients, and upregulate proteins, as epidermal growth factor (EGF) and plasminogen activator, urokinase (PLAU), involved in the regulation of epithelial sodium channel ENaC activity. Conclusions: Salt-sensitive and salt-resistant subjects have similar response to a saline/volume infusion as detected by urinary proteome. However, we identified glutamyl aminopeptidase (ENPEP), PLAU, EGF and Xaa-Pro aminopeptidase 2 precursor XPNPEP2 as key molecules of salt-sensitivity, through modulation of ENaC-dependent sodium reabsorption along the distal tubule. Graphic abstract: [Figure not available: see fulltext.].

PurposeThe aim of this work was to retrospectively analyze the clinical, subjective, and radiological results of medial closing-wedge distal femur osteotomy (MCW-DFO) for the treatment of osteoarthritis (OA) in valgus knee at medium- to long-term follow-up.Materials and methodsA total of 57 patients (62 knees) treated with MCW-DFO between 1984 and 2018 were included in the study. Patient age at the time of the surgery ranged between 28 and 61 years (average: 48 years). All patients with a minimum follow-up of 4 years were contacted to request for them to undergo clinical, subjective, and radiological evaluation. Preoperative hip–knee–ankle (HKA) angle (i.e., preoperative valgus malalignment) was 8.6° ± 2°. Patients were evaluated using the following scales: the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Knee Society Score (KSS), the International Knee Documentation Committee (IKDC), the Visual Analog Scale (VAS), and the Numeric Rating Scale 11 (NRS-11).ResultsMean follow-up was 11.6 ± 4.9 years, and a total of 17 patients (20 knees) were available for the last examination. At maximum follow-up, 4 patients underwent conversion to a total knee replacement (20%); their survival rate was 100% at 10 years and 66.7% at 15 years, as estimated using the Kaplan–Meier curve. The subjective Knee Society Score improved on average from 37.7 ± 10 to 63.9 ± 15.4. The objective Knee Society Score improved on average from 42.2 ± 11.7 to 75 ± 22.5. The pain detected through the VAS and NRS-11 scales improved from 56.7 ± 12.9 to 42 ± 17.1 and from 5.8 ± 1.1 to 4.4 ± 1.7, respectively. Thirteen patients (70%) required hardware removal at an average time of 19 ± 4 months due to a local nuisance.ConclusionsMCW-DFO can improve symptoms in patients with osteoarthritis in a valgus knee at medium- to long-term follow-up, reducing the progression of osteoarthritis in properly selected patients.

Aims: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. Materials and methods: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. Results: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50–17.75, P = 0.009 and HR 4.75, 95% CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. Conclusions: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO

© The Author(s), under exclusive licence to Springer Nature Limited 2021, corrected publication 2022, The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world., This project was supported by funds from: the Amazon Web Services (AWS) Imagine Grant (to E.M.B.); the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI; 16h03079, 17h00875, 18k12015, and 20h04581 to Y.Y.); the research programme Dipartimenti di Eccellenza from the Ministry of Education University and Research (MIUR to N. Cellini and G.M. and the Department of General Psychology of the University of Padua); statutory funds of the University of Wroclaw (to A. Sorokowska); the Charles University Research Programme PROGRES (Q18 to M. Vranka); the Knut and Alice Wallenberg Foundation (2016:0229 to J.K.O.); the Rubicon Grant (019.183sg.007 to K.v.S.) from the Netherlands Organisation for Scientific Research; the Australian Research Council (dp180102384 to R.M.R.); the US National Institutes of Health (NIMH111640 to M.N.-D.), the Huo Family Foundation to N.J.; the NSF Directorate for Social, Behavioral and Economic Sciences, Division of Social and Economic Sciences (1559511 to J.S.L.); the US National Institutes of Health (RO1-CA-224545 to J.S.L.); Eesti Teadusagentuur–Estonian Research Council (PSG525 to A. Uusberg); the J. William Fulbright Program (to F. Azevedo); the HSE Basic Research Program (to D. Dubrov); Dominican University (a Faculty Development Grant to A. Krafnick); and the French National Research Agency Investissements d’avenir supporting PSF (ANR-15-IDEX-02 to H.I.); the Slovak Research and Development Agency (project no. APVV-20-0319 to M. Adamkovič); the programme FUTURE LEADER of Lorraine Université d’Excellence within the French National Research Agency Investissements d’avenir (ANR-15-IDEX-04-LUE to S.M.). Computation for this research was assisted by: the Harvard Business School compute cluster (HBSGrid); and the Open Science Grid. The Open Science Grid is supported by the National Science Foundation award 1148698 and the US Department of Energy’s Office of Science, as well as by the compute resources and assistance of the UW-Madison Center For High Throughput Computing (CHTC) in the Department of Computer Sciences. The CHTC is supported by UW-Madison, the Advanced Computing Initiative, the Wisconsin Alumni Research Foundation, the Wisconsin Institutes for Discovery, and the National Science Foundation, and is an active member of the Open Science Grid, which is supported by the National Science Foundation and the U.S. Department of Energy’s Office of Science.

Hypertension and obesity in the young population are major risk factors for renal and cardiovascular events, which could arise in adulthood. A candidate-gene approach was applied in a cohort observational study, in which we collected data from 2638 high school adolescent students. Participants underwent anthropometric and blood pressure (BP) measurements, as well as saliva and urine sample collection for genomic DNA extraction and renal function evaluation, respectively. We tested whether candidate genes previously implicated in salt-sensitive hypertension in adults impact BP also among adolescents. Since inflammatory mechanisms may be involved in pathophysiology of hypertension and in endothelial dysfunction and atherosclerosis through reactive oxygen species, the baseline urinary excretion of inflammatory and oxidative stress markers in a subgroup of adolescents stratified according to ADD1 (alpha adducin) rs4961 genotypes was assessed. Regression analysis of BP values with genetic polymorphisms, highlighted an association with a missense variant of LSS (lanosterol synthase, rs2254524), a gene coding for an enzyme involved in endogenous ouabain synthesis. Higher diastolic and systolic BP were associated with LSS A allele ( P =0.011 and P =0.023, respectively). BP resulted associated with 5 more SNPs. The KL (klotho) rs9536314 missense variant was associated with 24 hour urinary Na + excretion ( P =0.0083). Urinary protein tests showed a greater excretion of IL1β (interleukin 1β) and interleukin 10 ( P ADD1 rs4961 T allele. In conclusion, 3 missense gene variants already implicated in adult hypertension impact BP or Na + excretion among adolescents, and, together with activated pro-inflammatory pathways, might predispose to early cardiovascular damage.

Patients with systemic lupus erythematosus (SLE) carrying a TT genotype for the rs7925662 single nucleotide polymorphism (SNP) in the transient receptor potential canonical channel 6 (TRPC6) gene are more likely to develop neuropsychiatric manifestations (NPSLE). We functionally characterised the effects of TRPC6 on peripheral blood mononuclear cells from 18 patients with SLE and 8 healthy controls with a known genotype. TRPC6 influenced calcium currents, apoptosis rates and cytokine secretion in a disease- and genotype-dependent manner. Cells from TT patients with NPSLE were more dependent on TRPC6 for the generation of calcium currents.

AIMS To report the long-term functional outcomes of artificial urinary sphincter (AUS) implantation in female patients with spinal dysraphism and stress urinary incontinence (SUI) related to intrinsic sphincter deficiency (ISD). METHODS The charts of all spina bifida female patients with SUI due to ISD who underwent AUS (AMS 800) implantation between 2005 and 2019 at three academic departments of urology were retrospectively reviewed. Reoperation was defined as either revision or explantation of the AUS device. Reoperation-free survival of the AUS device was estimated using the Kaplan-Meier method. Continence status as per patients' subjective assessment was categorized as follows: complete continence (no pads), improved continence, unchanged SUI or worsened SUI. RESULTS Twenty-three patients were included, 69.6% were self-catheterizing. The median follow-up was 14 years. Median time to first reoperation was 10 years. Survival rates without reoperation were 85.9%, 41.8%, 34.6%, and 20.9% at 5, 10, 15, 20 years, respectively. Survival rates without AUS explantation were 90.7%, 66.3%, 55.2%, and 41.4% at 5, 10, 15, 20 years, respectively. None of the patients who underwent device explantation had a new AUS implanted. The only predictive factor of reoperation-free survival was the type of spinal dysraphism (hazards ratio = 3.60 for closed vs. open dysraphism; p = .04). At last follow-up, 17 of the 23 patients were fully continent (73.9%). CONCLUSION AUS in female patients with spina bifida may be associated with satisfactory long-term functional outcomes and a high reoperation rate. The median time to first reoperation was similar to what is reported in the male AUS literature (10 years).

Objectives The objectives of this study were to test: (1) the repeatability of ultrasonographic examination of the optic nerve sheath diameter (ONSD) in the cat; (2) the association between the ONSD and age, sex and body weight in healthy cats; and (3) the difference in the ONSD between healthy cats and those suffering from presumed intracranial hypertension (ICH). Methods This study had a prospective, blinded, observational cross-sectional study design. Two groups of animals were considered: healthy cats (group A) and cats with a diagnosis of presumed ICH (group B). The ONSD was evaluated, measured and compared between the two groups via an ultrasonographic transpalpebral approach. Repeatability of the procedure was evaluated through the intraclass correlation coefficient (ICC). Data were statistically compared using the Student’s t-test and linear regression analysis. Results A strong inter- and intraobserver ICC indicating good repeatability was observed. The interobserver ICC was 0.965 ( P Conclusions and relevance The transpalpebral ultrasonographic technique is a non-invasive, feasible and reproducible method to measure ONSD both in healthy cats and in cats suffering from suspected ICH.

International audience; Despite widespread hearing problems among older adults, only a minority uses hearing aids. The stigma associated with such aids represents a key factor modulated by language. The purpose of this study is to analyze the impact of different forms of media communication on both implicit and explicit attitudes toward hearing aids. A preliminary analysis highlighted an over-representation of “technical” and “medical” terms in the corpus linguistic commonly used by the press. These results were used to design an online experimental study. The results suggested that the exposure to a language that includes informal words—as opposed to the technical terms commonly used by the press—favors positive implicit and explicit attitudes toward hearing aids, particularly among people who have direct contact with older adults. Overall, the use of an informal language in the press could generate a style of communication that positively influences people’s attitudes toward hearing aids.

Coronavirus disease of 2019 (COVID-19) is associated with severe acute respiratory failure. Early identification of high-risk COVID-19 patients is crucial. We aimed to derive and validate a simple score for the prediction of severe outcomes. A retrospective cohort study of patients hospitalized for COVID-19 was carried out by the Italian Society of Internal Medicine. Epidemiological, clinical, laboratory, and treatment variables were collected at hospital admission at five hospitals. Three algorithm selection models were used to construct a predictive risk score: backward Selection, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest. Severe outcome was defined as the composite of need for non-invasive ventilation, need for orotracheal intubation, or death. A total of 610 patients were included in the analysis, 313 had a severe outcome. The subset for the derivation analysis included 335 patients, the subset for the validation analysis 275 patients. The LASSO selection identified 6 variables (age, history of coronary heart disease, CRP, AST, D-dimer, and neutrophil/lymphocyte ratio) and resulted in the best performing score with an area under the curve of 0.79 in the derivation cohort and 0.80 in the validation cohort. Using a cut-off of 7 out of 13 points, sensitivity was 0.93, specificity 0.34, positive predictive value 0.59, and negative predictive value 0.82. The proposed score can identify patients at low risk for severe outcome who can be safely managed in a low-intensity setting after hospital admission for COVID-19.

The SARS-CoV2 pandemic forced an abrupt interruption of social contacts and interpersonal affective relationships all over the world, according to national directives. Many considerable inconveniences occurred with important repercussions also on the emotional state of people and their pets. We carried out a national survey to evaluate the human-dog relationship in a social isolation context using an adapted version of Monash Dog Owner Relationship Scale, the perception of the dogs’ discomfort by their human owners, and the resilience of the dog through the quantification of symptoms, in time of the first lockdown of the COVID-19 pandemic. The results highlighted that the human-dog interaction was similar during quarantine, however, there was lower owner’s perception of a dog’s cost during the quarantine than before it.

We compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10–11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6–19.0), P = 0.038 and 13.4 (25.4–2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10–11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.

A 37-year old man had suffered palmar hyperhidrosis since he was fifteen years old. In the last year, he has been treated with tolvaptan for autosomic polycystic kidney disease (ADPKD). The start of tolvaptan therapy was associated with a complete resolution of palmar hyperhidrosis and a sensation of relaxation. During the year on which the patient took tolvaptan, he had to suspend the drug twice. The suspension of tolvaptan was associated with the reappearance of palmar hyperhidrosis followed by sudden remission after the drug reintroduction. Palmar sweating also known as 'emotional sweating' is not related to thermoregulation but allows an adequate adjustment of the frictional force to perform fine hand movements. Palmar hyperhidrosis is a chronic neurologic disorder characterized by excessive sweating of eccrine glands due to overactivity of the sympathetic nervous system. Palmar sweating and emotional processing are controlled by the limbic system. In this case report reduction of palmar sweating was associated with a sense of well-being. Corticotropin releasing factor (CRF) and adrenocorticotropic hormone (ACTH) are the two main hypothalamic hormones that interact with both the limbic system and the peripheral sympathetic nervous system. Tolvaptan is an arginine vasopressin (AVP) antagonist. AVP has effects on the sympathetic nervous system through both central and peripheral actions. Centrally AVP is a well-known ACTH secretagogue. Remission of palmar hyperhidrosis is probably mediated by tolvaptan acting on central ACTH secretion.

Local and remote complications can be observed in hip prosthesis failures associated with metallosis. Structural changes in the periprosthetic bone and soft tissues may not always be precisely assessed preoperatively due to metal artifacts. The unpredictability of the damage extension, potentially leading to complex and insidious surgeries, requires the availability of alternative surgical plan(s) for the reconstruction of the joint. The aim of the study is to present and analyze, with the literature data support, practical tips for the revision of the prosthetic components, the management of ARMD and of intraoperative complications in the unusual scenario of metallosis.

ObjectivesTo evaluate an algorithm developed for identifying non-small cell lung cancer (NSCLC) candidates among patients with lung cancer with a diagnosis International Classification of Diseases: ninth revision (ICD-9) 162.x code in administrative databases. Algorithm could then be applied for identifying the NSCLC population in order to assess the appropriateness and quality of care of the NSCLC care pathway.DesignAlgorithm discrimination capacity to select both NSCLC or non-NSCLC was carried out on a sample for which electronic health record (EHR) diagnosis was available. A bivariate frequency distribution and other measures were used to evaluate algorithm’s performances. Associations between possible factors potentially affecting algorithm accuracy were investigated.SettingAdministrative databases used in a specific geographical area of Emilia-Romagna region, Italy.ParticipantsAlgorithm was carried out on patients aged >18 years, with a lung cancer diagnosis from January to December 2017 and resident in Emilia-Romagna region who have been hospitalised at IRST or in one of the hospitals placed in the Forlì-Cesena area and for which EHR diagnosis data were available.Outcome measuresOverall accuracy, positive (PPV) and negative (NPV) predictive values, sensitivity and specificity, positive and negative likelihood ratios and diagnostic OR were calculated.ResultsA total of 430 patients were identified as lung cancer cases based on ICD-9 diagnosis. Focusing on the total incident cases (n=314), the algorithm had an overall accuracy of 82.8% with a sensitivity of 88.8%. The analysis confirmed a high level of PPV (90.2%), but lower specificity (53.7%) and NPV (50%). Higher length of stay seemed to be associated with a correct classification. Hospitalisation regimen and a supply of antiblastic therapy seemed to increase the level of PPV.ConclusionThe algorithm demonstrated a strong validity for identifying NSCLC among patients with lung cancer in hospital administrative databases and can be used to investigate the quality of cancer care for this population.Trial registration numberNCT04676321.

INTRODUCTION AND OBJECTIVE:Female urethral stricture is a rare condition. Distal stricture have usually been managed using meatoplasty. Advancement urethroplasty might be an interesting surgical al...

INTRODUCTION AND OBJECTIVE:Several studies have suggested that spina bifida patients may have a poorer response to intradetrusor botulinum toxin A (BTX-A) injections than other neurological populat...

Background In February 2020 the corona virus disease 2019 (COVID-19) infection started spreading throughout Italy, hitting the Lombardy region very hard. Despite the high diffusion, only a subset of patients developed severe COVID-19: around 25% of them developed acute kidney injury (AKI) and one-third of them died. Elderly patients and patients with high comorbidities were identified as being at higher risk of severe COVID-19. Methods Our prospective observational cohort study includes 392 consecutive patients hospitalized for COVID-19 in Milan (median age 67 years, 75% male). We evaluated the relationship between blood pressure at presentation, presence of AKI at Emergency Department admission and during hospitalization, and total in-hospital mortality (24%). Results Although 58% of our study patients reported a history of hypertension (HYP) (86% on treatment), 30% presented with low blood pressure levels. Only 5.5% were diagnosed with AKI on admission; 75% of hypertensive patients discontinued therapy during hospitalization (only 20% were on treatment at discharge). Gender and hypertension were strongly associated with AKI at admission (odds ratio 11). Blood pressure was inversely correlated with increased risk of AKI upon admission, regardless of the severity of respiratory distress. Age over 65, history of hypertension, and severity of respiratory distress were the main predictors of AKI, which developed in 34.7% of cases during hospitalization. AKI was associated with increased in-hospital mortality. Hypertension and low blood pressure at presentation were the main predictors of in-hospital mortality, together with age over 65, baseline pulmonary involvement, and severity of illness. Conclusions In patients hospitalized for COVID-19, hypertension and low blood pressure at presentation are important risk factors for AKI and mortality. Early reduction of antihypertensive therapy may improve outcomes in patients with SARS-CoV-2 infection.

CDK4/6 inhibitors (CDK4/6i) are recommended in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC). Up to now, no prognostic biomarkers have been identified in this setting. We retrospectively analyzed the expression of progesterone receptor (PR) and Ki67, assessed by immunohistochemistry, in 71 ABC patients treated with CDK4/6i and analyzed the impact of these markers on progression-free survival (PFS). The majority of patients 63/71 (88.7%) received palbociclib, 4 (5.6%) received ribociclib, and 4 (5.6%) received abemaciclib. A higher median value of Ki67 was observed in cases undergoing second-line treatment (p = 0.047), whereas the luminal B subtype was more prevalent (p = 0.005). In the univariate analysis of the first-line setting, luminal A subtype showed a trend towards a correlation with a longer PFS (p = 0.053). A higher continuous Ki67 value led to a significantly shorter PFS. When the interaction between pathological characteristics and line of treatment was considered, luminal B subtype showed a significantly (p = 0.043) worse outcome (Hazard Ratio (HR) 2.84, 1.03&ndash, 7.82 95% Confidence Interval (CI)). PFS in patients undergoing endocrine therapy plus CDK4/6i was inversely correlated with Ki67 expression but not with PR, suggesting that tumor proliferation has a greater impact on cell cycle inhibitors combined with endocrine therapy than PR expression.

Liquid biopsy analytes such as cell-free DNA (cfDNA) and circulating tumor cells (CTCs) exhibit great potential for personalized treatment. Since cfDNA and CTCs are considered to give additive information and blood specimens are limited, isolation of cfDNA and CTC in an "all from one tube" format is desired. We investigated whether cfDNA variant sequencing from CTC-depleted blood (CTC-depl. B; obtained after positive immunomagnetic isolation of CTCs (AdnaTest EMT-2/Stem Cell Select, QIAGEN)) impacts the results compared to cfDNA variant sequencing from matched whole blood (WB). Cell-free DNA was isolated using matched WB and CTC-depl. B from 17 hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer patients (QIAamp MinElute ccfDNA Kit, QIAGEN). Cell-free DNA libraries were constructed (customized QIAseq Targeted DNA Panel for Illumina, QIAGEN) with integrated unique molecular indices. Sequencing (on the NextSeq 550 platform, Illumina) and data analysis (Ingenuity Variant Analysis) were performed. RNA expression in CTCs was analyzed by multimarker quantitative PCR. Cell-free DNA concentration and size distribution in the matched plasma samples were not significantly different. Seventy percent of all variants were identical in matched WB and CTC-depl. B, but 115/125 variants were exclusively found in WB/CTC-depl. B. The number of detected variants per patient and the number of exclusively detected variants per patient in only one cfDNA source did not differ between the two matched cfDNA sources. Even the characteristics of the exclusively detected cfDNA variants in either WB or CTC-depl. B were comparable. Thus, cfDNA variants from matched WB and CTC-depl. B exhibited no relevant differences, and parallel isolation of cfDNA and CTCs from only 10 mL of blood in an "all from one tube" format was feasible. Matched cfDNA mutational and CTC transcriptional analyses might empower a comprehensive liquid biopsy analysis to enhance the identification of actionable targets for individual therapy strategies.

In late December 2019, some patients were hospitalized with an initial diagnosis of pneumonia of unknown etiology. These patients were epidemiologically linked to a wholesale market of seafood, wild animals and meat located in Wuhan, Hubei province, China. Acute respiratory disease caused by a new Coronavirus SARS-CoV-2, formerly known as 2019-nCoV, afterwards as Coronavirus disease 2019 (COVID-19), spread throughout China and received the attention of the entire world. Analysis of the genomic sequence of COVID-19 showed 88% of identity with two bat-derived severe acute respiratory syndrome-like Coronaviruses. Illegal and sustainable wildlife trade is the second largest direct threat to species after habitat destruction. Each year, hundreds of millions of plants and animals are captured or collected in the wild to be sold as food, pets, medicines, ornaments and for a variety of other reasons. Even the climate crisis could offer dangerous scenarios in addition to another fundamental chapter of the environmental pillar which is the one concerning air quality. There is a solid scientific literature which correlates the incidence of viral infection cases with concentrations of atmospheric particulate matter (e.g. PM10 and PM2.5). Despite the current regulations, which limit the levels of certain atmospheric pollutants, there are still numerous negative health effects deriving from exposure to these agents. However, it can be said that chronic air pollution, such as peaks of concentration of fine dust and other pollutants, acts as a pejorative factor in cases of epidemics. (GCND_planet)

BACKGROUND: Pathological complete response (pCR) is rare in hormone receptor-positive (HR+) HER2-negative breast cancer (BC) treated with either endocrine therapy (ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures. The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced pCR after treatment with palbociclib. CASE SUMMARY: We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a pCR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified as endocrine-sensitive, a condition associated with high sensitivity to palbociclib. CONCLUSION: This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.

BACKGROUND AND OBJECTIVES Claudin-16 and -19 are proteins forming pores for the paracellular reabsorption of divalent cations in the ascending limb of Henle loop; conversely, claudin-14 decreases ion permeability of these pores. Single-nucleotide polymorphisms in gene coding for claudin-14 were associated with kidney stones and calcium excretion. This study aimed to explore the association of claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms with calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective observational study of 393 patients with hypertension who were naive to antihypertensive drugs, in whom we measured 24-hour urine calcium excretion; history of kidney stones was ascertained by interview; 370 of these patients underwent an intravenous 0.9% sodium chloride infusion (2 L in 2 hours) to evaluate the response of calcium excretion in three different 2-hour urine samples collected before, during, and after saline infusion. Genotypes of claudin-14, claudin-16, and claudin-19 were obtained from data of a previous genome-wide association study in the same patients. RESULTS Thirty-one single-nucleotide polymorphisms of the 3' region of the claudin-14 gene were significantly associated with 24-hour calcium excretion and calcium excretion after saline infusion. The most significant associated single-nucleotide polymorphism was rs219755 (24-hour calcium excretion in GG, 225±124 mg/24 hours; 24-hour calcium excretion in GA, 194±100 mg/24 hours; 24-hour calcium excretion in AA, 124±73 mg/24 hours; P

BACKGROUND: Vitamin K (VK)-dependent γ-glutamate carboxylation and serine phosphorylation activate matrix Gla protein (MGP) to a potent locally acting inhibitor of calcification. Nephrolithiasis represents a process of unwanted calcification associated with substantial mortality and high recurrence rates. We hypothesized that the risk of nephrolithiasis increases with VK shortage, as exemplified by higher plasma levels of desphospho-uncarboxylated MGP (dp-ucMGP). METHODS: In 1748 randomly recruited Flemish individuals (51.1% women; mean age 46.8 years), we determined dp-ucMGP and the prevalence of nephrolithiasis at baseline (April 1996-February 2015) and its incidence during follow-up until March 2016. We estimated the multivariable-adjusted relative risk associated with the doubling of dp-ucMGP, using logistic or Cox regression. We did a Mendelian randomization analysis using four MGP genotypes as instrumental variables. RESULTS: With adjustments applied for sex, age and 24-h urinary volume and calcium excretion, the odds of having prevalent nephrolithiasis [n = 144 (8.2%)] associated with dp-ucMGP was 1.31 [95% confidence interval (CI) 1.04-1.64; P = 0.022]. dp-ucMGP levels were associated (P ≤ 0.001) with MGP variants rs2098435, rs4236 and rs2430692. In the Mendelian analysis, the causal odds ratio was 3.82 (95% CI 1.15-12.7; P = 0.029). The incidence of nephrolithiasis over 12.0 years (median) was 37 cases (0.2%). With similar adjustments as before, the hazard ratio in relation to dp-ucMGP was 2.48 (95% CI 1.71-3.61; P

Metabolic dysfunction and fatty liver disease (FLD) are epidemiologically associated with increased risk of severe COVID-19 requiring hospitalization (1, 2). The mechanism may encompass promotion of inflammation by facilitation of liver injury, which is a frequent feature of severe COVID-19 (3). However, metabolic dysfunction rather than FLD itself may induce disease progression (2). Indeed, we previously showed that a genetic FLD-risk score does not predispose to severe COVID-19 in UK Biobank population-based cohort (UKBB) (4).

Berzuini et al report the observation that nearly half of patients with COVID-19 tested at their blood center had a positive direct antiglobulin test (DAT). However, eluates did not react with any test cells but did react with red cells from other patients with COVID-19 that were DAT negative. This suggests that COVID-19 may modulate the red cell membrane and present novel antigenic epitopes.

The aim of this study was to investigate the disease-specific urinary levels variations of neurotrophins (NGF, BDNF), mediators of inflammation (TGFβ-1, PGE-2) and markers of extracellular matrix alterations (TIMP-2) in patients with multiple sclerosis (MS) spinal cord injury (SCI), or spina bifida (SB), and neurogenic detrusor overactivity (NDO). A prospective single-center study was conducted between March 2015 and March 2017. Patients aged over 18 years old, with neurological disease, with a urodynamic diagnosis of NDO were included. The urinary levels of NGF, BDNF, TIMP-2, PGE 2, and TGF-β1 were measured using dedicated ELISA kits. Forty-one patients were included: 6 with MS, 20 with SCI, and 15 with spina bifida. The average urinary level of NGF/Cr was significantly higher in MS patients compared to other neurologic populations (8 vs. 0.56 vs. 1.25 pg/mg of creatinine; p = 0.001) as well for the average urinary level of BDNF (88.3 vs. 5 vs. 4.8 pg/mg of creatinine; p

A 7-year-old mixed breed spayed bitch (body weight: 10.6 kg) was presented with a history of intermittent episodes of seizures and untreated limb fracture. Appetite loss, nervousness, lateral recumbency, fasciculations, ataxia and poor nutritional condition were found. Venous blood gas analysis highlighted normal acid-base balance and severe low ionized calcium (0.58 mEq/L [range 1.13-1.32 mEq/L]). Marked total hypocalcaemia (6.4 mg/dL [range 8-10] or 1.6 mM [range: 2-2.5]) associated with hyperphosphoraemia (9.3 mg/dl [range 3.5-6.5 mg/dl]) displayed inverted ratio between minerals. ECG showed sinus arrhythmias. Circulating levels of Mg and Cu were within physiological range (1.97 mg/dl and 128 μg/dl respectively) and effects from interactions were excluded. Oral administration of calcitriol at 40 ng/kg/day led to clinical improvement within 48 hours, but circulating iCa levels were still below the lower limit of the reference range. Baseline levels of circulating parathormone (PTH) were 3 pg/ml, along with normal values of circulating vitamin D. Primary hypoparathyroidism was diagnosed as a chronic underlying condition triggered by pelvic fracture.

To evaluate the determinants and prognostic value of post-operative maximum urethral closure pressure (MUCP) after AUS implantation in male patients. The charts of all male patients who had an AUS implantation between 2008 and 2018 at a single center were reviewed retrospectively for an exploratory study. A post-operative urethral profilometry was performed systematically as part of routine daily practice over the study period to assess the post-operative MUCP with the AUS consecutively closed (c-MUCP) and opened (o-MUCP). The difference between c-MUCP and the manufacturer’s theoretical pressure objective determined by the pressure regulating balloon (PRB) was calculated (diff-th-MUCP). The primary endpoint was social continence at 3 months defined as 0–1 protection/day. Ninety patients were included. The median age was 71 years, and the median follow-up was 50 months. The etiology of incontinence was radical prostatectomy in 84% of cases, and endoscopic prostate surgery in 6.6% of patients. There were 74.4% of patients who were socially continent at 3 months. The c-MCUP was significantly higher in the continent group (53 [42.2, 60.2] vs 62 [58, 70] p = 0.02). The diff-th-MUCP did not differ significantly between the two groups (18 [0, 23] vs 1 [− 2, 7.7] p = 0.29). The c-MUCP was not statistically associated with the risk of revision and/or explantation. The MUCP after AUS implantation in male patients often differs from the manufacturer’s pressure objective. The postoperative c-MUCP might be significantly associated with functional outcomes suggesting that it might be a valuable tool for treatment decision-making. This should be confirmed by larger studies.

Objective To evaluate the clinical efficacy, urodynamic effect and safety of Botulinum Toxin A (BTXA) injections after failure of augmentation enterocystoplasty (AE) performed for neurogenic detrusor overactivity. Patients and Methods We performed a multicenter retrospective study that included patients who had AE and at least one injection of BTXA after AE in 15 GENULF (French Speaking Neuro-Urology Study Group) centers. Clinical and urodynamic data were collected from medical files according to a standardized questionnaire and colligated in an anonymous database. Results Thirty-three patients with an injection of BTXA after AC in 9 out of 15 centers were included. Mean age at the time of AE was 24 ± 15 years. Overall efficacy (defined by clinical efficacy associated with a request by the patient for reinjection) was observed in 58% of the patients. Mean maximum cystomanometric capacity increased by 28% (333 ± 145 vs 426 ± 131 mL; P = .007) and maximum detrusor pressure (Pdet max) decreased by 43% (44 ± 37 vs 25 ± 18 cm H2O; P = .02) after BTXA. Only one side effect was recorded out of the 152 procedures (transient generalized muscle weakness without respiratory distress). Conclusion In patients with failure after AE performed for neurogenic detrusor overactivity, injection of BTXA in the enlarged bladder was effective in over half of the cases with low morbidity. If this therapeutic approach were confirmed, it could be proposed as an alternative to AE surgical revision.

Objectifs La cystectomie chez les sujets neurologiques reste une intervention peu pratiquee, dont les indications sont limitees. La plupart des donnees sur les complications peri-operatoires dont nous disposons concernent les patients ayant eu une cystectomie avec derivation ileale pour cancer. L’objectif de cette etude etait d’evaluer les complications de la cystectomie avec derivation non continente par conduit ileal pour vessie neurologique et leurs facteurs de risque. Methodes Tous les patients ayant eu une cystectomie avec derivation cutanee trans-ileale non continente de type Bricker pour vessie neurologique entre octobre 2004 et novembre 2020 dans un centre ont ete inclus dans une etude retrospective. La voie d’abord etait ouverte, laparoscopique ou robot-assistee selon la periode. La derivation etait realisee en extra-corporel ou en intra-corporel. La survenue d’une complication precoce ( Resultats Apres exclusion de 10 patients traites pour une pathologie non neurologique, 126 patients ont ete inclus sur la periode d’etude. Les pathologies neurologiques les plus frequentes etaient la SEP (36,5 %) et la lesion medullaire traumatique (25,4 %). La voie d’abord etait ouverte, laparoscopique et robotique dans 31 (24,6 %), 26 (20,6 %) et 69 cas (54,7 %) respectivement. Soixante-douze patients ont presente une complication precoce (57,1 %) dont 21 une complication majeure (16,7 %) comprenant un deces (0,8 %). Apres un suivi median de 23 mois, 22 patients ont presente des complications tardives (17,6 %) essentiellement des eventrations (5 ; 4 %) et des stenoses uretero-ileales (9 ; 7,2 %). L’utilisation de la voie robotique etait le seul facteur associe a un risque significativement reduit de complication majeure (OR = 0,30 ; CI95 % = 0,09-0,87 ; p = 0,027) ( Tableau 1 , Tableau 2 ). Conclusion La cystectomie avec derivation ileale non continente pour vessie neurologique est associee a une morbidite peri-operatoire importante, similaire a celle retrouvee pour la cystectomie totale oncologique. L’utilisation de la voie robotique pourrait diminuer le risque de complications majeures pour cette population.

Objectifs L’obstruction sous-vesicale (OSV) est un probleme courant apres bandelette sous-uretrale (BSU). Elle peut aboutir a une retention aigue ou chronique d’urine, ou a des symptomes de la phase de remplissage et/ou de vidange handicapants. La prise en charge de l’OSV apres BSU n’est pour autant pas standardisee. L’objectif de cette etude etait de comparer deux strategies de prise en charge de suspicion d’OSV apres BSU. Methodes Les patientes ayant eu une reintervention pour retention aigue ou chronique d’urine et/ou symptomes du bas appareil urinaire (SBAU) attribues a une OSV apres BSU ont ete incluses dans une etude retrospective, dans 5 centres entre 2005 et 2020. Seules les patientes avec un RPM > 100 mL etaient incluses, puis divisees en 2 groupes : detente precoce (DP) ou section/excision partielle tardive (ST) de la BSU. Le choix de l’une ou l’autre de ces techniques etait laisse a la discretion du chirurgien, mais assez uniforme dans chaque centre : la DP etait le standard dans trois des centres, et la ST dans les deux autres. Resultats Soixante-dix patientes ont ete incluses : 38 dans le groupe DP et 32 dans le groupe ST. La duree moyenne entre BSU et reintervention etait significativement plus courte dans le groupe DP (5,1 vs 433,9 jours ; p Conclusion La detente precoce de BSU en cas de retention et/ou OSV est une option therapeutique interessante avec une efficacite qui parait similaire a la section ou excision partielle tardive mais un taux de recidive de l’incontinence urinaire d’effort qui pourrait etre moins important.

Literature presents several examples of surgical techniques for the treatment of carpometacarpal osteoarthritis. In our study we used a modified Ceruso’s suspended arthroplasty technique. In this study, 53 patients from 2011 to 2017 underwent arthroplasty with trapezius excision and suture suspension between abductor pollicis longus and flexor carpi radialis. The average age at surgery was 69, the participants were 43 women and 10 men. The average total operation time was 59 minutes. The modified CMC suspension arthroplasty technique provides excellent results compared with those in the literature.

International audience; Objectives: The aim of the present study was to compare the perioperative outcomes of extracorporeal (EXTRA) vs intracorporeal (INTRA) urinary diversion in patients undergoing robotic cystectomy and ileal conduit for neurogenic bladder. Methods: All consecutive patients who underwent robot-assisted cystectomy and ileal conduit for neurogenic bladder in six centers between 2011 and 2020 were included in a retrospective study. Four centers performed exclusively INTRA urinary diversion all over the study period, one center performed exclusively EXTRA urinary diversion, and the last center performed EXTRA urinary diversion during a first period and INTRA during the subsequent period. Results: Ninety-seven patients were included: 66 in the EXTRA group and 31 in the INTRA group. There were 11 major (Clavien grade >= 3) postoperative complications in the overall population (11.3%) with no statistically significant difference between both groups (EXTRA = 12.1% vs INTRA = 9.7%; p = 0.99). The mean length of stay did not differ significantly between INTRA and EXTRA (13.1 vs 14.1 days; p = 0.44). The mean times to oral feeding and to return of bowel function were similar in the two groups (3.9 vs 3.5 days; p = 0.28 and 4.1 vs 4.1 days; p = 0.51, respectively). There was no incisional hernia in the INTRA group vs five in the EXTRA group (0% vs 7.6%; p = 0.17). Conclusion: The perioperative morbidity of robotic cystectomy and ileal conduit for neurogenic bladder appears to be relatively limited compared with the historical open series. Possibly due to the relatively small sample size, no difference was found between INTRA and EXTRA urinary diversion in terms of perioperative outcomes.

Background Animal models and few clinical reports suggest the involvement of the complement system in the onset of severe manifestations of coronavirus disease-2019 (COVID-19). However, complement contribution to endotheliopathy and hypercoagulability has not been elucidated yet. Objective To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients. Methods In this single-centre cohort study, 148 patients with COVID-19 of different severity were evaluated upon hospital admission and 30 days later. Markers of complement activation (SC5b-9 and C5a) and endothelial perturbation (von Willebrand factor [vWF], tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1], soluble thrombomodulin [sTM], and soluble endothelial selectin [sE-selectin]) were measured in plasma. Results The patients had high plasma levels of SC5b-9 and C5a (p = 0.0001 for both) and vWF, t-PA and PAI-1 (p = 0.0001 for all). Their SC5b-9 levels correlated with those of vWF (r = 0.517, p = 0.0001) and paralleled disease severity (severe vs mild p = 0.0001, severe vs moderate p = 0.026 and moderate vs mild p = 0.001). The levels of sE-selectin were significantly increased only in the patients with severe disease. After 30 days, plasma SC5b-9, C5a and vWF levels had significantly decreased (p = 0.0001 for all), and 43% of the evaluated patients had normal levels. Conclusions Complement activation is boosted during the progression of COVID-19 and dampened during remission, thus indicating its role in the pathophysiology of the disease. The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy.