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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11–2.46), p = 0.013), but not in influenza (1.74 (0.99–3.06), p = 0.052), or no viral infection groups (1.13 (0.68–1.86), p = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.

International audience; BackgroundThe outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear.ObjectivesTo study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus.MethodsThis observational study was conducted during 9–16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included.ResultsHistological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic–natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL.ConclusionsOur findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

International audience; No abstract available

Objectives In the context of improved medication management of older patients, we wished to evaluate the overprescription of potentially inappropriate drugs [α1-blockers and 5α-reductase inhibitors (5-ARI)] for benign prostate hyperplasia (BPH). These drugs are considered by geriatricians to increase the risk of falls and pharmacodynamic interactions, but these properties have not yet been proven. Design This was a descriptive study of drug prescriptions in a geriatric academic center. Setting and Participants We included all patients older than 75 years who received a prescription for α1-blockers or 5-ARIs for 2 weeks in our hospital. Methods We evaluated the prevalence of the potentially inappropriate prescription of α1-blockers and 5-ARI in older people during hospitalization using a new tool consisting of an 8-item list of explicit indicators developed using the most recent summary of product characteristics (SmPC) and latest European Association of Urology (EAU) guidelines. Results: A population of 117 patients (≥75 years) was included in the study. The median age was 84.5 (±6.3) years. The average time since urological medication prescription was 1.2 ± 1.6 years. According to explicit criteria, 84 patients (71.8%) received at least 1 potentially inappropriate urologic medication, 77 (91.7%) related to α1-blockers. Patients with a potentially inappropriate prescription for α1-blockers and/or 5-ARIs more frequently had urological assessments (P = .026), more frequently showed pharmacological interactions, with the risk of orthostatic hypotension (P = .005) or arrhythmia (P = .028), and experienced more falls in their history (P = .043). The misuse group was associated with an increased risk of falls, with an odds ratio of 3.22 (P = .039, 95% confidence interval 1.08–10.2). Conclusions and Implications In our study, potentially inappropriate prescriptions for older individuals for BPH was close to 72% and mainly involved α1-blockers. Potentially inappropriate prescriptions for BPH were associated with a threefold higher frequency of falls.

Data on the incidence and severity of radiation-induced toxicity in patients with systemic and/or cutaneous lupus erythematosus (SLE/CLE) are very limited. After reporting the case of a patient who experienced major toxicity and CLE flare in the irradiated area following breast irradiation, we conducted a comprehensive literature review of available data in this setting. The few retrospectives studies which have evaluated both the risk of toxicity in SLE/CLE patients and/or the potential induction or reactivation of SLE/CLE with radiotherapy have not shown differences between SLE/CLE patients and controls. Several other factors such as concurrent chemotherapy, a particular genetic background, or lupus treatments (essentially hydroxychloroquine) can explain severe radiation-induced toxicity. Therefore, patients with SLE/CLE should be irradiated like patients without SLE/CLE, with close monitoring during radiotherapy if other risk factors exist. Further studies examining a larger number of patients would probably allow a better understanding of the radiosensitivity of these patients.

While Severe Acute Respiratory Syndrome Coronavirus-2 vaccine breakthrough infections are expected, reporting on breakthrough infections requiring hospitalization remains limited. This observational case series report reviewed 10 individuals hospitalized with vaccine breakthrough infections to identify patient risk factors and serologic responses upon admission.Electronic medical records of BNT162b2 (Pfizer-BioNTech) or mRNA-1732 (Moderna) vaccinated patients admitted to Veterans Affairs Ann Arbor Healthcare System with newly diagnosed Coronavirus Infectious Disease 2019 (COVID-19) between March 15, 2021 and April 15, 2021 were reviewed. Patient variables, COVID-19 lab testing including anti-S IgM, anti-N IgG antibodies, and hospital course were recorded. Based on lab testing, infections were defined as acute infection or resolving/resolved infection.Of the 10 patients admitted with breakthrough infections, all were70 years of age with multiple comorbidities. Mean time between second vaccine dose and COVID-19 diagnosis was 49 days. In the 7 individuals with acute infection, none had observed serologic response to mRNA vaccination, 5 developed severe disease, and 1 died. Three individuals had anti-N IgG antibodies and a high polymerase chain reaction cycle threshold value, suggesting resolving/resolved infection.Given the variability of vaccine breakthrough infections requiring hospitalization, serologic testing may impart clarity on timing of infection and disease prognosis. Individuals at risk of diminished response to vaccines and severe COVID-19 may also benefit from selective serologic testing after vaccination to guide risk mitigation strategies in a post-pandemic environment.

ObjectivesWe examined the associations of history and duration in high occupational physical activity (OPA) with long-term total and cause-specific mortality.MethodsThe sample included 322 126 participants (135 254 women) from the National Institutes of Health–AARP Diet and Health Study, established in 1995–1996. History and duration in high OPA were reported by participants. All-cause, cardiovascular, cancer and other cause mortality records available through 31 December 2011.ResultsThe prevalence of high OPA was 52.1% in men and 16.1% in women. During 13.6 years (SD, 3.3) of follow-up, 73 563 participants (25 219 women) died. In age-adjusted models, the risk of death was higher among men (HR 1.14, 95% CI 1.12 to 1.16) and women (HR 1.22, 95% CI 1.18 to 1.26) with a history of high OPA. However, these associations were substantially attenuated in women (HR 1.04, 95% CI 1.00 to 1.07, an 81.8% attenuation) and eliminated in men (HR 1.02, 95% CI 0.99 to 1.04, 85.7% attenuation) after multivariable adjustments. Similar important attenuation results were found when examining duration in high OPA, as well as using cause-specific deaths as the outcomes. Educational attainment and smoking patterns were the main contributors in the excess mortality among people working in highly physically active jobs in both men and women.ConclusionParticipating in high OPA was not consistently associated with a higher mortality risk, after adjustments for education and smoking factors. Workers in high OPA should be aware that they might not be getting all well-known health benefits of being physically active if they are only very active at work.

Resume La chirurgie fœtale des myelomeningoceles a ete introduite en France en 2014. Les developpements du diagnostic prenatal des anomalies de fermeture du tube neural ont accompagne les developpements du diagnostic prenatal. Cette chirurgie represente l’un des trois parcours de soins possibles pour les femmes enceintes confrontees a ce diagnostic prenatal. Les enjeux ethiques de cette chirurgie fœtale sont discutes et notamment l’information prenatale et l’autonomie de choix des patientes

BACKGROUND AND PURPOSE Opioids and benzodiazepines are frequently combined in medical as well as in non-medical contexts. At high doses, such combinations often result in serious health complications attributed to pharmacodynamics interactions. Here, we investigate the contribution of the metabolic interactions between oxycodone, diazepam and diclazepam (a designer benzodiazepine) in abuse/overdose conditions through ex vivo, in vivo and in silico approaches. EXPERIMENTAL APPROACH A preparation of pooled human liver microsomes was used to study oxycodone metabolism in the presence or absence of diazepam or diclazepam. In mice, diazepam or diclazepam were concomitantly administered with oxycodone to mimic acute intoxication. Diclazepam was introduced on day 10 in mice continuously infused with oxycodone for 15 days to mimic chronic intoxication. In silico modelling was used to study the molecular interactions of the three drugs with CYP3A4 and 2D6. KEY RESULTS In mice, in acute conditions, both diazepam and diclazepam inhibited the metabolism of oxycodone. In chronic conditions and at pharmacologically equivalent doses, diclazepam drastically enhanced the production of oxymorphone. In silico, the affinity of benzodiazepines for CYP3A4 was higher than oxycodone, inhibiting oxycodone metabolism through CYP3A4. Oxycodone metabolism is likely to be diverted towards CYP2D6. CONCLUSION AND IMPLICATIONS Acute doses of diazepam or diclazepam results in the accumulation of oxycodone, whereas chronic administration induces the accumulation of oxymorphone, the toxic metabolite. This suggests that overdoses of opioids in the presence of benzodiazepines are partly due to metabolic interactions, which in turn rationalize the patterns of toxicity dependent on usage.

PARP inhibitors are effective in different types of tumors such as ovarian, breast, prostate and pancreatic cancer. Many studies are in progress and may lead to prescription evolution. PARP inhibitors prescription is almost reserved to patients with a constitutional BRCA mutation or a somatic BRCA alteration or a tumor with a deficiency in homologous recombination. Nowadays, the diagnosis of homologous recombination deficit, HRD, is possible with the prescription of a myChoice CDx (Myriad) test. PARP inhibitors are studied in association with chemotherapy and targeted therapies but also with radiotherapy and with immune checkpoint inhibitors. Access to PARP inhibitors is challenged with the emergence of resistance mechanism. Various trials are now studying the possibility of reversing these resistance mechanisms.

Despite the high commitments of the European Union (EU) member countries toward achieving the sustainable development goals (SDGs), on average, the region has reportedly under-performed in the area of ensuring sustainable production and consumption. This paper uses the Generalized Method of Moments (GMM) estimation of panel vector autoregressive (PVAR) with impulse response functions (IMFs) to assess the effects of domestic material consumption, renewable energy, financial development, and greenhouse gas emissions on environmental quality in the EU-28 countries based on the panel data for the period 2000:Q1–2017:Q4. The empirical results reveal that the shock to domestic material consumption, renewable energy, economic growth, financial development, and greenhouse gas emissions affect the drives towards sustainable environment. Particularly, the shocks to renewable energy and financial development improve environmental quality, while the shocks to domestic material consumption and greenhouse gas emission deteriorate environment quality. The shock to economic growth improves environmental quality up to the 4th horizon after which it begins to deteriorate environment quality. Furthermore, the panel causality results indicate bidirectional causality between greenhouse gas emissions and the rest of the variables except renewable energy, which is unidirectional. The causality between Economic growth and renewable energy, economic growth and financial development, and financial development and renewable energy has a feedback effect while a unidirectional causality flows from economic growth to domestic material consumption. These findings have implications for sustainable production and consumption.

Looking at the urine for diagnostic purposes, once performed by ancient Egyptians, can still provide some valuable clues in modern medicine. Several diseases have been named after their associated urine color and this underlines the clinical value of visual urine inspection: blue diaper disease, purple urine bag syndrome, black urine disease or porphyria. Abnormal urine color could be challenging for the clinician: it may reveal neoplastic disease (urologic cancer; melanoma), cell lysis (rhabdomyolysis; hemolysis), infection (lymphatic filariasis; malaria), enzyme deficiency (porphyria; alkaptonuria), medication or food intake. In this article, we present the diagnostic approach, the mechanisms involved and the main causes of abnormal urine color.

Currently, the main method of treatment for hemophilia A is replacement therapy with drugs of blood coagulation factors VIII (FVIII). As a result of the development of new production technologies, recombinant FVIII are increasingly used for the treatment of hemophilia A. The justification for the use of new drugs in pediatric clinical practice requires careful preparation and clinical research studies of their efficacy and safety. The aim of this study was to evaluate the efficacy, safety and pharmacokinetics (PK) of domestic B-domain deleted recombinant factor VIII of Moroctocog alpha (Octofactor, GENERIUM JSC) in a cohort of children with hemophilia A aged 6 to 12 years in the framework of phase III clinical study of moroktocoga alpha in children 2 to 12 years old with hemophilia A. Materials and methods of the research: the age cohort of 6 to 12 years olds of an open multicenter prospective noncomparative study included 27 male children with severe hemophilia A (mean age 8,3±1,9 years). The study was carried out sequentially in 2 stages. Stage I included the study of PK parameters in 22 patients after a single study drug dose of 50 IU/kg. At stage II, the efficacy and safety of the drug was assessed in patients of stage I, as well as in additionally included 5 patients who received the study drug dose of 30±10 IU/kg per day every 2–3 days for 22±1 weeks of treatment. To assess the efficacy, we analyzed the incidence of spontaneous bleeding that occurred within 48–72 h after drug administration; the number of injections and the dose of FVIII used for prophylaxis, as well as for treatment on demand of one episode of bleeding, taking into account its severity; number of patients with severe hemophilia A with residual FVIII activity >/=1% 48–72 h after drug administration; the investigator's overall assessment of response to therapy on the acute hemarthrosis response scale. The main indicators for the analysis of PK properties were the area under the «concentration-time» curve, the half-life, the elimination constant, the increase in activity, and the degree of recovery of activity. To assess safety, the frequency of formation of an inhibitor to FVIII, the dynamics of vital and laboratory parameters, the frequency and characteristics of adverse events (AEs) associated with the administration of the drug were taken into account. Results: the area under the FVIII-time activity curve in the region of 0–48 h (AUC0-48) and with exponential extrapolation to infinity (AUC0-inf) was 731,82±264,94%*h and 756,11±270,16%*h, respectively. The half-life (T1/2) was 10,32±2,27 hours. In the examined age group, 78 bleeding were recorded, of which only 27 (35%) were spontaneous, including 24 (30%) episodes that occurred during 48–72 hours after the administration of drug under investigation. Haemorrhage within 48–72 hours after administration of the Octofactor drug was absent or was observed rarely (1–3 times) against the background of prophylactic treatment in most patients (88%), the median number of bleeding within 48–72 hours after administration of the study drug was 2 episodes per observation period. The proportion of spontaneous bleeding was the smallest in patients receiving a single prophylactic doses of the study drug 2000–3000 IU (7% of all bleeding), the largest proportion of spontaneous bleeding was observed in patients receiving a single prophylactic doses of the study drug 1000–2000 IU (70% of bleeding). The average single dose of Octofactor for preventive treatment was 1290,4±458,6 IU or 39,12±7,79 IU/kg, for on-demand treatment – 1641,7±722,4 IU per single injection. Of the 78 reported bleeding episodes, 68 (87%) required the study drug administration for relief, while the remaining 10 bleedings were selfcontained. On average, to stop bleeding, it took 1,5±0,8 injections of the drug on demand, median doses were 1 [1; 2], and average doses were 2434,3±1501,7 IU. During the study, 37 AEs were recorded in 15 (56%) patients. At the same time, 36 AEs (97%) were not associated with the drug under investigation, and one AE (allergic reaction), according to the researchers, was associated with the use of the drug. Thus, the analysis of data indicates the efficacy and safety of the Octofactor drug both the prophylactic treatment and treatment of on-demand bleeding in 6 to 12 year old patients with severe hemophilia A.

Bronchial asthma (BA) is a multifactorial disease, genetic factors play an important role in its etiopathogenesis. At the same time, data on associations of polymorphic variants of the estrogen receptor gene with BA are quite contradictory. Objective of this research was to study the peculiarities of allele polymorphism frequencies of ER1 and TNF-α genes and their combinations in patients with atopic BA depending on the disease severity. Materials and methods: in the course of a retrospective single-center comparative pilot study by PCR/RFLP analysis, the frequencies of alleles and genotypes for the ER1 and TNF-α genes were determined in 78 prepubertal children (9 [6–13] years) with atopic BA. The population comparison group included 115 people. Results: the study revealed that in BA patients with moderate severity, genotypes Xx (48% and 14%; OR=6,067 CI=[1,653–22,268]), and Pp (94% and 47%, respectively; OR=18,074 CI=[2,319–140,854]) of the ER1 gene were statistically significantly more common than in the comparison group. A statistically significant difference was found in the distribution of genotype combinations for the XbaI and PvuII polymorphisms of the ER1 and –308A genes>G of TNF-α gene polymorphism in patients with BA and in the comparison group (2=31,761, p=0,0043). The frequency of the combined a-PpXx genotype in BA patients was higher than in the comparison group (22% and 3%, OR=11,09, p

International audience; BackgroundST‐elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) are associated with a worse prognosis. However, few comparisons are available according to coronary status in the era of modern reperfusion and optimized secondary prevention.HypothesisWe hypothesized that the difference in prognosis according to number of vessel disease in STEMI patients has reduced.MethodsAll consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI) within 24 h of symptoms onset between January 1, 2014 and June 30, 2016 enrolled in the CRAC (Club Régional des Angioplasticiens de la région Centre) France PCI registry were analyzed. Baseline characteristics, management, and outcomes at 1‐year were analyzed according to coronary status (one‐, two‐, and three‐VD).ResultsA total of 1886 patients (mean age 62.2 ± 14.0 year; 74% of male) were included. Patients with MVD (two or three‐VD) represented 53.7%. They were older with higher cardiovascular risk factor profile. At 1 year, the rate of major adverse cardiovascular events (MACE, defined as all‐cause death, stroke or re‐MI) was 10%, 12%, and 12% in one‐, two, and three‐VD respectively (p = .28). In multivariable adjusted Cox proportional hazard regression model, two‐ and three‐VD were not associated with higher rate of MACE compared to patients with single VD (HR, 1.09; 95%CI 0.76–1.56 for two‐VD; HR, 0.74; 95%CI 0.48–1.14 for three‐VD).ConclusionsMVD still represents an important proportion of STEMI patients but their prognoses were not associated with worse clinical outcomes at 1‐year compared with one‐VD patients in a modern reperfusion area and secondary medication prevention.

The external auditory canal is not only a part of the external ear, but also an integral part of the human auditory system, which conducts and amplifies the sound wave. In the field of otosurgery, it is often the priority access to the tympanic cavity, and therefore it is necessary to clearly understand the features of its anatomy. The dimensions and anatomy of the external auditory canal are extremely variable: the length is 2–3,5 cm, the diameter ranges from 5-9 mm, it is somewhat curved in the horizontal and frontal planes and consists of a membranous cartilaginous part and a bony part, between which there is the most the bottleneck – the isthmus. The ear canal is covered with skin, the thickness and structure of which depends on the section of the ear canal. The membranous cartilaginous section contains sebaceous and sulfur glands. Studies identify several forms of the bony part of the ear canal: conical, hourglass-shaped, ovoid, reverse conical, and cylindrical. The endoscopic scale (CES) for the visibility of the tympanic membrane was also proposed for the convenience of assessment. It has been suggested that the shape of the external auditory canal is an etiological factor in chronic otitis externa. Unambiguous interpretations of the relationship between ear diseases and the shape of the external auditory canal have not yet been obtained, but modern developments tend to consider its importance in the development of ear diseases. Clinical observations show that certain anatomical forms of it may be involved in the pathogenesis of chronic inflammation, since they interfere with proper self-cleaning.

The analysis of tendencies related to provision of measurement trustworthiness has made it possible to propose a methodology for automatic checking metrological health of measuring instruments and multichannel measuring systems in the course of their operation. This methodology is called «metrological selfcheck ». The selfcheck enables calibration/verification intervals to be significantly increased. In case of virtual test and artificial intelligent application, automation of the trustworthiness provision becomes possible for traditional measurements. It has been shown that the problem of trustworthiness related to soft measurements taking into consideration the growing interest in them, also becomes actual.

The article provides information about the discussion panel of the ARCI’ 2021 conference.

Objective. To assess the efficacy and safety of low molecular weight sugar solution as a hepatoprotector in the first trimester of pregnancy in patients with liver functional disorders against the background of early toxicosis and / or hepatotoxicity. Patients and methods. The study included 70 patients: the main group (n = 30) – pregnant women with functional hepatopathies who received therapy with drug Heptrong; the control group (n = 30) – pregnant women who received standard treatment, of which 15 patients had hepatotoxicity (essential phospholipid therapy) and 15 patients with early toxicosis (intravenous saline fluid therapy, Cerucal), as well as 10 pregnant women with early toxicosis who were treated without drugs (the placebo group). Results. Pregnant women with early toxicosis noted a decrease in its clinical manifestations against the use of the drug Heptrong after 2.3 ± 0.8 days from the onset of therapy; by the end of therapy, all patients had no vomiting, and nausea stopped in 80%, which was not observed in comparison groups. The normalization of alanine aminotransferase (≤40 U/L) occurred in 80% of pregnant women in the main group (p < 0.01) and in 66% (p < 0.01) when treating with essential phospholipids. The normalization of alanine aminotransferase (≤40 U/L) occurred in 90% (p < 0.01) and 33.3% (p = 0.03), respectively. A significant decrease in the level of bile acids (from 8.49 ± 2.1 μmol/L to 2.74 ± 1.1 μmol/L; p < 0.05) and improvement in the indicators of the antioxidant system – an increase in total antiradical activity (from 804.0.0 ± 10.5 μmol/L to 839.0 ± 11.0 μmol/L; p < 0.05) and a decrease in the level of conjugated dienes (from 3.77 ± 0.2 μmol/L to 3.26 ± ± 0.1 μmol/L; p < 0.05) – were observed only in the main group. A number of other indicators of the “liver panel” tended to improve only in the main group. Conclusion. Heptrong is an effective hepatoprotective drug, which considerably improves the state of pregnant women during early toxicosis and helps to reduce liver transaminases and bile acids in pregnant women with hepatotoxicity. Due to the antiinflammatory and pronounced antioxidant effect, which is not observed in standard pharmacological treatment, Heptrong can be used to prevent late obstetric complications. Key words: Heptrong, drug-induced hepatopathies, “liver panel” indicators, early toxicosis

Goal The aim of the study is to assess the incidence, risk factors and prognosis of definite stent thrombosis (ST) at 1 year in the France PCI multicenter prospective registry. Patients and methods Only patients who underwent coronary angioplasty with at least one stent implantation between 1st January 2014 and 31 December 2019 were included. The population was separated into 2 groups: the "ST" group with stent thrombosis and the "control" group without stent thrombosis. Results 35,435 patients were included. 256 patients (0.72%) presented a ST at 1 year. The rate of ST decreased significantly in acute coronary syndrome (1.5% in 2014 vs. 0.73% in 2019; p = 0.05) but not in chronic coronary syndrome (0.46% in 2014 vs 0.40%; p = 0.98). The risk factors are young age (65.8 years vs 68.2; p = 0.002), clinical context (35.27% vs 16.68%; p = 0.0001), diabetes (35.2 % vs 26.4%; p = 0.002), renal failure (11.7% vs 8%; p = 0.009) and history of coronary angioplasty (28.63% vs 21.86%; p = 0.009) and peripheral arterial disease (14.5% vs 10.1%; p = 0.021), LV dysfunction (37% vs 27.5%; p = 0.003), mean length (39.6 mm vs 31, 7mm; p Conclusion Since 2014, the incidence of ST at 1 year has been decreasing but remains stuck at a floor level of 0.54% in 2019. The battle for ST seems to have been partly won and its risk factors well identified, but its mortality is still high.

OBJECTIVE Intracranial dural arteriovenous fistula (DAVF) is mainly treated with an endovascular approach. Two major treatment advances include transvenous embolization (TVE) with coils in 1989 and, more recently, transarterial embolization with Onyx. The aim of this study was to present a large monocentric series of patients with DAVF treated with TVE. This series reports more than 20 years of experience and describes the evolution of the medical management of these patients, as well as current indications for this treatment at the authors’ center. METHODS Consecutive patients treated for intracranial DAVFs with TVE from 1995 to 2018 were included. Clinical and imaging data were systematically collected. Univariate and multivariate analyses were performed to identify factors that were significantly associated with adverse clinical course or complications. RESULTS In this study of 136 patients with 142 DAVFs treated with TVE, the occlusion rate was 90%. The median length of follow-up was 11 months. The rate of permanent complications was 5.1%, and the procedure-related mortality rate was 1.5%. Procedure-related mortality was associated with extension of thrombosis that was observed early in our experience. The introduction of a postoperative anticoagulation regimen has drastically decreased the occurrence of this complication. Other minor complications included cochleovestibular syndrome after embolization of lateral sinus DAVF and oculomotor nerve damage after embolization of cavernous sinus DAVF. CONCLUSIONS TVE allows efficient occlusion of DAVF. It remains a valid option for DAVF located on a sinus that does not participate in normal venous drainage of the brain.

Background Cabazitaxel was shown to improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after abiraterone/enzalutamine and docetaxel failure, though benefit by the presence of DNA damage repair (DDR) defects is unknown. With the advent of poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi) in partially overlapping indications with cabazitaxel, we aimed to determine cabazitaxel activity in men with mCRPC according to their DDR status. Methods This is a retrospective multicenter study that enrolled patients with mCRPC treated with cabazitaxel who had undergone DDR tumour tissue profiling. Patients with at least one deleterious germline or somatic alterations were considered DDR positive (DDR+). Each DDR + patient has been matched with a DDR negative (DDR-) from the same institution who underwent the same test. An exploratory cohort of patients found to be DDR + by liquid biopsy was also included. Prostate specific antigen (PSA) decline≥50% (PSA50), PSA progression-free survival (PFS, PSA-PFS), radiographic PFS (rPFS), clinical PFS or radiographic PFS (c/rPFS) and OS were evaluated. Results Among 190 men (95 DDR+, 95 DDR-) with tissue sequencing, PSA50 was achieved with cabazitaxel in 29/92 (32%) and 33/92 (36%) in patients with DDR+ and DDR- (P = 0.64). The median rPFS was 5.33 months [95%CI 4.34–7.04] versus 5.75 months [95%CI 4.67–7.27] (P = 0.55). The median OS was 15.4 months [95%CI 12.16–26.6] and 11.5 months [95%CI 9.76–14.4] (P = 0.036), respectively. No PSA50 responses on cabazitaxel were observed in BRCA1/2 patients previously treated with PARPi (n = 10). Similar outcomes with cabazitaxel were observed in the liquid biopsy cohort (n = 63 DDR+). Conclusions Our study suggests that cabazitaxel is active in patients with mCRPC regardless of their DDR status, although its activity in men pretreated with a PARPi may be lower.

The paper highlights a modern spectral device for measuring the optical parameters of solid-state materials in liquid-phase. The development of these devices is promising for optical instrumentation and science in general, since these devices are informative, highly accurate and provide reliable information. In the paper the appearance, block diagram and lighting system of the spectrometer are presented. The spectral dependences of the transmission on the wavelength in the visible range of the spectrum for disinfectants Like, Grand, Aqualite (1% solutions) are obtained. For the analysis of the studied substances, specialized cuvettes with a working length from 0.1 to 0.5 mm and leucosapfir optical pads were used. The cuvettes were 0.05 mm thick. The spectrometer provided measurement of the transmission of disinfectants in the wavelength range of 380–760 nm with an error not worse than ΔТ ≤ 2%.

International audience; OBJECTIVE: This initial study aimed to investigate the feasibility of simultaneously measuring perfusion and diffusion including kurtosis features in acute ischemic stroke with the combined intravoxel incoherent motion and non-Gaussian diffusional kurtosis imaging (DKI-IVIM). MATERIAL AND METHODS: Five ischemic stroke patients underwent a 4-minute diffusion weighted imaging (DWI) protocol, using 8 b values chosen with the Cramer-Rao-Lower-Bound optimization approach, in addition to conventional DWI and arterial spin labeling sequences. Regions of interest in pathological and control regions were analyzed with DKI-IVIM, and parametric maps were reconstructed. RESULTS: The IVIM diffusion coefficient (D) decreased (P < 0.0001) in the infarcted areas, whereas higher kurtosis coefficient values were found (P = 0.0002). Regarding the perfusion, the individual IVIM perfusion fraction f decreased in 3 matching cases with the cerebral blood flow estimated through arterial spin labeling and the fD* decreased only in 2 patients of those. CONCLUSIONS: When compared with conventional stroke imaging protocol, DKI-IVIM 4-minute 2-in-1 acquisition can provide diffusion results comparable with conventional DWI with complementary kurtosis estimations but a limited robustness regarding perfusion estimations for clinical purpose.

BackgroundRespiratory infection with nontuberculous mycobacteria (NTM) in children with cystic fibrosis (CF) has increased in prevalence. The condition is difficult to diagnose and treatments are complex with limited evidence to guide practice. This study describes the approaches to diagnosis, management and consequences of treatment in a multicentre cohort of children with CF in the UK.MethodsRetrospective data were collected from 11 CF specialist centres from patients less than 17 years old, treated for NTM infection between 2006 and 2017. Descriptive statistics were used to describe the clinical characteristics of children treated. Treatment regimens, adverse events and success of treatment, with respect to lung function and culture conversion, were evaluated.ResultsData from 70 patients treated for NTM pulmonary disease were collated (60 Mycobacterium abscessus complex (MABSC); 10 M. avium complex (MAC)). Older age and previous diagnosis of allergic bronchopulmonary aspergillosis were all significantly associated with NTM. There was a wide variance in drug choice and side effects were reported with all agents. NTM eradication occurred in 80% of patients with MAC and 48% with MABSC, with variable outcomes on lung function.ConclusionsDiagnosis and treatment of NTM infection in children with CF is challenging. Treatment success is not guaranteed, particularly for MABSC. Large clinical trials are urgently required to evaluate treatment regimes and their suitability and efficacy in children.

BackgroundThe natural history of unruptured intracranial aneurysms (UIAs) in Western populations is still debated, especially for those MethodsFrom January 2011 to June 2019, 662 UIAs were followed up by yearly MR angiography. Morphologically stable UIAs were managed conservatively while unstable UIAs were offered treatment. The patients’ clinical and radiological data were analyzed retrospectively.ResultsUIAs were ≤4 mm in 60%, 4.1–7.0 mm in 33%, and >7 mm in 7%. They were located on the anterior circulation in 90% of cases. The mean follow-up duration was 51.32 months for a total of 2831 aneurysm-years. During follow-up, 37 UIAs (5.5%) were treated because of an increase in size, and 8 UIAs were treated because of patient decision. Three aneurysms ruptured during follow-up for an annual risk of rupture of 0.1% (95% CI 0% to 0.24%). No risk factors for rupture were identified. The three ruptured cases made an excellent recovery. During follow-up, annual mortality from unrelated causes was 0.8% (95% CI 0.51% to 1.18%).ConclusionsThis single-center cohort evaluated our watchful waiting policy applied in two-thirds of all incidental UIAs. Morphological change of UIAs during follow-up led to treatment in 5.5% of cases. With such a management paradigm, we found a low rupture rate in these selected UIAs and the mortality was unrelated to aneurysms.

Application of transcranial alternating current stimulation (tACS) is thought to modulate ongoing brain oscillations in a frequency-dependent manner. However, recent studies report various and sometimes inconsistent results regarding its capacity to induce changes in cortical activity beyond the stimulation period. Here, thirty healthy volunteers participated in a randomized, cross-over, sham-controlled, double-blind study using EEG to measure the offline effects of tACS on alpha and beta power. Sham and high current density tACS (1 mA; 10 Hz and 20 Hz; 0.32 mA/cm2) were applied for 20 min over bilateral sensorimotor areas and EEG was recorded at rest before and after stimulation for 20 min. Bilateral tACS was not associated with significant changes in local alpha and beta power frequencies at stimulation sites (C3 and C4 electrodes). Overall, the present results fail to provide evidence that bilateral tACS with high current density applied over sensorimotor regions at 10 and 20 Hz reliably modulates offline brain oscillation power at the stimulation site. These results may have implications for the design and implementation of future protocols aiming to induce sustained changes in brain activity, including in clinical populations.

Background Morbidity and mortality associated with prostate cancer in a given geographic area might be related to the level of socioeconomic deprivation. The Somme area (a region of northern France) is considered economically disadvantaged, with major territorial disparities. The aim of this study was to assess the impact of the socioeconomic level on prostate cancer, using data from a population-based cancer registry. Methods The source of data on cases of prostate cancer between 2006 and 2010 was the Somme cancer registry (Amiens, France). Socioeconomic status was measured according to the European Deprivation Index (EDI), which was used to classify each geographical “IRIS” unit (the smallest sub-municipal geographical entity for which French census data are available) according to its level of social deprivation. For spatial analysis, we considered a hierarchical generalized linear model. Results In the spatial analysis, prostate cancer incidence was higher in the less disadvantaged areas and treatment frequency with curative intent was lower in the most disadvantaged areas. Cancer aggressiveness and mortality were higher in the most disadvantaged areas: relative risk (RR) = 1.36; 95% CI: [1.09; 1.73] and RR=3.09 [1.70; 5.59], respectively. Conclusion Our results evidenced a significant association between socioeconomic deprivation and prostate cancer, with worse outcomes among men with the lowest socioeconomic status.

Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening form of heart failure (HF). Bromocriptine, a dopamine D2 agonist, has been used as an adjunctive treatment for PPCM with controversial benefits. A comprehensive literature search was conducted through June 2021. We included studies comparing the outcomes of PPCM with or without bromocriptine use. Pooled risk ratio (RR) with 95% confidence intervals (CI) and I2 statistics were calculated. Composite major adverse outcomes were defined by a composite of death, need for advanced HF therapies, persistent New York Heart Association (NYHA) functional class III/V, or left ventricular ejection fraction (LVEF) ≤ 35% at 6-month follow-up. LVEF recovery was defined by improvement of LVEF to more than 50%. Eight studies (two randomized-controlled, six observational) involving 593 PPCM patients were included. Bromocriptine use was associated with significantly higher survival (91.6% vs. 83.9%, RR 1.11 p = 0.02). Baseline LVEF was not significantly different between the groups. LVEF at follow-up was significantly higher in the bromocriptine group (53.3% vs. 41.8%, p < 0.001). There was no significant association between bromocriptine use and lower composite major adverse outcomes (13.7% vs. 33.3%, RR 0.60 p = 0.54) or LVEF recovery (46.9% vs. 46.8%, RR 0.94 p = 0.74). In conclusion, the addition of bromocriptine to standard HF treatment in PPCM was associated with significantly higher survival and higher LVEF improvement. No association with lower composite adverse clinical outcomes or LVEF recovery was seen. The findings, although encouraging, warrant larger randomized-controlled studies.

BackgroundThe balloon-assisted sinus protection technique has been described as a sinus-preserving technique during transarterial embolization (TAE) of dural arteriovenous fistulas (DAVFs). However, some serious complications of this technique have been documented.ObjectiveTo describe our preliminary experience with a new technique called stent-assisted sinus protection (SSP).MethodsWe performed a retrospective analysis of seven consecutive patients with type I or IIa DAVFs of the lateral sinus treated by TAE with a closed-cell stent temporarily deployed in the sinus.ResultsOf the seven patients, four had type I DAVF, and three had type IIa DAVF. The patency of all involved sinuses and their tributaries (including the inferior anastomotic vein and the superior petrosal sinus) was preserved. At the end of the procedure, all stents were successfully retrieved with embolic particles trapped in their meshes. No procedural complications were noted. Clinical follow-up was satisfactory, with complete resolution or significant reduction of pulsatile tinnitus.ConclusionsSSP appears to be feasible and probably safe. However, larger studies are needed to confirm these preliminary results.

Methacholine challenge testing (MCT) is considered when asthma remains clinically suspected despite normal spirometry. Few studies have attempted to determine the predictive factors of MCT results. We aimed to establish which demographic data, clinical symptoms, pulmonary function testing results, and laboratory values were associated with abnormal MCT (provocation concentration causing a 20% decrease in FEVsub1/sub(PC20) ≤ 16 mg/mL) in subjects without airflow obstruction on spirometry.All patients who completed MCT at Montfort Hospital between January 1supst/sup, 2016 and December 31supst/sup, 2018 were identified. Subjects with a reduced FEVsub1/sub/FVC ratio were excluded. We used Pearson's chi-squared test and point-biserial correlation method to determine which variables had a significant relationship (ip/i lt; 0.05) with MCT results.23.3% of patients who underwent MCT had airflow limitation. In the 1126 subjects with a normal FEVsub1/sub/FVC ratio, PC20 ≤ 16 mg/mL was found in 13.0%. Younger age, female gender, body mass index ≥ 40, and reported wheezing were factors associated with increased probability of airway hyper responsiveness. Lower FEVsub1/sub, significant improvement of the FEVsub1/subpost-bronchodilator, reduced FEF25%-75%, greater FEF25%-75% reversibility, airway resistance measurements above the upper limit of normal, and increased blood eosinophil counts were predictive of abnormal MCT.Only 13.0% of patients referred for MCT had a PC20 ≤ 16 mg/mL when the FEVsub1/sub/FVC ratio was normal, highlighting the need to further define in which individuals this test is truly warranted. Further investigation is required to develop an easy-to-use and validated prediction model in order to better understand patients' pretest probability of abnormal MCT.

Introduction Analysis of publications on primary hip replacement shows lower survival rates in patients with acetabular injuries. With the lack of a unified system for assessing post-traumatic acetabular deformities, authors tend to use the available classifications of acute pelvic trauma (AO/ ASIF, Young & Burgess, Tile, etc.) and acetabular osteolysis (AAOS, DGOT, Gross and Saleh, Paprosky), which we think can be inappropriate with the classifying systems meant for different patterns of acetabular deficiency. Material and methods CT scans of 117 patients with posttraumatic acetabular deformities were reviewed prior to total hip replacement (THR) performed for posttraumatic grade III coxarthrosis. The displacement of acetabular walls was determined with the measurements tabulated and analyzed. Results An original "ASPID" classification of post-traumatic deformities based on the findings obtained was offered with use of three assessment criteria: localization of the deformity, extent of displacement and the integrity of the pelvic ring. The ASPID classification can be used for the localization of the deformity with anterior (A), superior (S), posterior (P) and inner acetabular walls (I) to be identified. Measurements of displacement ranging 0-5 mm suggests grade 0 displacement; 6-15 mm, grade 1 displacement and greater than 15 mm, grade 2 displacement. The integrity of the pelvic ring evaluated from the involvement side as D0 suggests maintained pelvic integrity and D1, broken pelvic integrity. An acetabular hardware would be marked with 'H'. Conclusion ASPID classification is easy to use and has shown to be practical for planning of primary THR after acetabular fracture.

Introduction Periprosthetic joint infections (PJI) are serious complications of total hip arthroplasty (THA) and affect the patient's life expectancy. The aim of the study was to identify independent factors influencing the risk of death in patients with PJI after revision THA. Materials and methods The study included 51 lethal outcomes in patients with chronic PJI of the hip. Results and discussion In our cohort of 434 patients, 13 (2.99 %) patients died within the first year after surgery (p > 0.05), which is 2.2 times less than similar published data. The result of gender analysis showed no statistically significant differences in the risk of death between men and women (OR1.05 CI 0.59–1.89, p = 0.87). It was found that in patients over 70 years old, the risk of death was significantly higher (OR 2.05 CI 1.09–3.87, p = 0.031). Additional independent risk factors of death are diseases of the cardiovascular system. It was not possible to find a statistically significant effect of the nature of infection on the risk of death: no growth (OR 2.23, CI 0.52–9.61), monomicrobial infection (OR 1.98, CI 0.45–8, 73), polymicrobial infection (OR 3.2, CI 0.71–14.45, p > 0.05). Conclusion The mortality rate during the first year after revision THA in patients with PJI was 2.99 %, which is lower than the results of other researchers. In the next 2–3 years, the rate of death increases 3.9 times. The main independent risk factors are the age of patients and concomitant diseases of the cardiovascular system.