Prescription, Compliance, and Burden Associated with Salt-Restricted Diets in Heart Failure Patients: Results from the French National OFICSel Observatory

(1) Background: There is much debate about the use of salt-restricted diet for managing heart failure (HF). Dietary guidelines are inconsistent and lack evidence. (2) Method: The OFICSel observatory collected data about adults hospitalised for HF. The data, collected using study-specific surveys, were used to describe HF management, including diets, from the cardiologists’ and patients’ perspectives. Cardiologists provided the patients’ clinical, biological, echocardiography, and treatment data, while the patients provided dietary, medical history, sociodemographic, morphometric, quality of life, and burden data (burden scale in restricted diets (BIRD) questionnaire). The differences between the diet recommended by the cardiologist, understood by the patient, and the estimated salt intake (by the patient) and diet burden were assessed. (3) Results: Between March and June 2017, 300 cardiologists enrolled 2822 patients. Most patients (90%) were recommended diets with <6 g of salt/day. Mean daily salt consumption was 4.7 g (standard deviation (SD): 2.4). Only 33% of patients complied with their recommended diet, 34% over-complied, and 19% under-complied (14% unknown). Dietary restrictions in HF patients were associated with increased burden (mean BIRD score of 8.1/48 [SD: 8.8]). (4) Conclusion: Healthcare professionals do not always follow dietary recommendations, and their patients do not always understand and comply with diets recommended. Restrictive diets in HF patients are associated with increased burden. An evidence-based approach to developing and recommending HF-specific diets is required.

Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) vs CRS alone for treatment of endometrial cancer with peritoneal metastases: a multi-institutional study from PSOGI and BIG RENAPE groups

Objective To investigate the benefit of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of endometrial peritoneal carcinomatosis compared to CRS alone. Methods We conducted a retrospective multicentre study of patients from experienced centres in treating peritoneal malignancies from 2002 to 2015. Patients who underwent surgery for peritoneal evolution of endometrial cancer (EC) were included. Two groups of 30 women were matched and compared: “CRS + HIPEC” which used HIPEC after CRS, and “CRS only” which did not use HIPEC. We analysed clinical, pathologic and treatment data for patients with peritoneal metastases from EC. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS). Results In “CRS plus HIPEC” group, 96.7% of women were treated for recurrence, while in “CRS only” 83.3 were treated for primary disease. There was no significant difference between Peritoneal Carcinomatosis Index at laparotomy or Completeness of Cytoreduction score. Grade III and IV complications rates did not significantly differ between “CRS plus HIPEC” group and “CRS only” group (20.7% vs 20.7%, p = 0.739). Survival analysis showed no statistical difference between both groups. Median OS time was 19.2 months in “CRS plus HIPEC” group and 29.7 months in “CRS only” group (p = 0.606). Median PFS survival time was 10.7 months in “CRS plus HIPEC” group and 13.1 months in “CRS only” group (p = 0.511). Conclusion The use of HIPEC combined to CRS did not have any significance as regard the DFS and OS over CRS alone in patients with primary or recurrent peritoneal metastasis of endometrial cancer.

Clinicians’ perspectives on supporting individuals with severe anorexia nervosa in specialist eating disorder intensive treatment settings

Background Admissions to intensive treatment (i.e., inpatient [IP] and/or day patient [DP]) for individuals with severe anorexia nervosa (AN) are common. Growing literature indicates potential risks and benefits of each intensive treatment approach; however, existing research has focused on patient and carer perspectives of these treatments. Also, there is scant empirical evidence available for guiding the parameters of intensive treatments for AN. We therefore explored clinicians’ perspectives and experience of supporting adults with severe AN in intensive settings. Methods We conducted twenty one semi-structured interviews with clinicians who deliver intensive treatments (i.e., IP and/or DP) for individuals with severe AN across four specialist Eating Disorder Services in the United Kingdom between May 2020 and June 2021. We asked clinicians about their views and experiences of supporting individuals with severe AN in intensive treatment settings and the challenges and opportunities associated with IP and DP treatment. Data were analysed using reflexive thematic analysis supported by NVivo software. Results Five broad and interrelated themes were identified: (1) Intensive Support; (2) The Severity of Patients’ Illnesses; (3) Hope and Recovery; (4) Which Treatment When; (5) Limited Resources; and (6) Carer Burden. We identified various similarities between the two intensive treatment approaches, including the value of intensive and multidisciplinary support and carer involvement, and the challenge of managing complex and unique needs in resource-limited intensive settings. We also found differences in the relationship of treatment to patients’ home environments, the necessity of patient motivation, and the management of risk. Conclusions Both intensive treatment settings are valued by clinicians; however, there are unique challenges and opportunities for supporting individuals with severe AN within each. Our findings suggest DP treatment may be used as an alternative to IP treatment for individuals with severe AN. However, clear questions remain over which intensive treatment setting is best suited to which patient when and should be the focus of future research.

Prediction of pan-solid tumor pembrolizumab benefit by integrating tumor mutation and gene expression profiling

Pembrolizumab is approved in many advanced solid tumor types, however predictive biomarkers and the proportion of pembrolizumab-benefiting patients vary. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability (MSI) status, and tumor mutation burden (TMB) may improve benefit prediction. Here, leveraging treatment data (time to next treatment [TTNT]) and comprehensive genomic and quantitative transcriptomic profiling on routine tumor tissue from 708 patients (24 tumor types) collected in an ongoing observational trial (NCT03061305), we report a multivariate, integrative predictor of pan-solid tumor pembrolizumab benefit. The Immune Response Score (IRS) model, which includes TMB and quantitative PD-1, PD-L2, ADAM12 and CD4 RNA expression, was confirmed as predictive through comparison of pembrolizumab TTNT with previous chemotherapy TTNT in a subset of 166 patients treated with both. Applying IRS to the entire NCT03061305 cohort (n=25,770 patients), 13.2-30.7% of patients (2.2-9.6% of patients outside of pembrolizumab approved tumor types [including TMB-High and MSI-High]) are predicted to benefit substantially from pembrolizumab. Hence, if prospectively validated, the IRS model may improve pembrolizumab benefit prediction across approved tumor types including patients outside of currently approved indications.

Immunogenicity of BNT162b2 mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis on TNF inhibitors

BackgroundScanty data on the immunogenicity of the BNT162b2 vaccine in patients with psoriatic arthritis (PsA) on Tumor Necrosis Factor inhibitors (TNFi) have been published.ObjectiveTo investigate the humoral response to BNT162b2 vaccination patients with PsA on TNFi, comparing immunogenicity with healthy controls.MethodsForty patients with classified PsA on TNFi undergoing vaccination with the BNT162b2 mRNA SARS-CoV-2 vaccine (BioNTech/Pfizer) were enrolled. Fifteen days after the second shot, serum IgG levels against SARS-CoV-2 (Abbott ARCHITECT i2000SR, positivity cut-off 50 AU/mL) were assayed in all patients. Clinimetrics and treatment data were gathered. TNFi treatment was not discontinued throughout the whole period, whereas methotrexate (MTX) was discontinued for 1 week after each shot in those on combination therapy. Sera from healthcare professionals were considered as healthy controls for 1:1 propensity score matching; any of them was taking medication.Student’s t-test and logistic regression were used for investigating differences in immunogenicity between groups and predictors of antibody response.ResultsClinical Disease Activity Index did not change before and after vaccination (7.06±5.23 to 7.10±5.27, p=0.92).Patients with PsA achieved a positive anti-SARS-CoV-2 IgG level with a mean (±SD) of 13794.44±15 815.42 AU/mL. Although lower, the antibody level was not significantly different from matched controls (19227.4±11.8460.45 AU/mL, p=0.08). In the overall sample, those on MTX (12/80, 15%) had a trend toward lower immune response (p=0.07); glucocorticoid therapy (11/80, 13.8%) predicted lower antibody levels (p=0.04).ConclusionsContinuing TNFi in patients with PsA throughout the vaccination did not hamper immunogenicity.

Antimicrobial Selection for the Treatment of Clinical Mastitis and the Efficacy of Penicillin Treatment Protocols in Large Estonian Dairy Herds

Clinical mastitis (CM) is the most common microbial disease treated in dairy cows. We analyzed the antimicrobial usage in cows with CM (n = 11,420) in large dairy herds (n = 43) in Estonia. CM treatment data were collected during a 12-month study period. The antimicrobial usage was observed during the 21 days from the initiation of treatment, and the incidence of antimicrobial-treated CM was calculated for each study herd. The effect of intramammary (IMM), systemic, and combined (systemic and IMM) penicillin treatment of CM on the post-treatment somatic cell count (SCC) was analyzed using the treatment records of 2222 cows from 24 herds with a mixed multivariable linear regression model. The median incidence of antimicrobial-treated CM was 35.8 per 100 cow-years. Procaine benzylpenicillin and marbofloxacin were used in 6103 (35.5%, 95% CI 34.8–36.2) and 2839 (16.5%, 95% CI 16.0–17.1) CM treatments, respectively. Post-treatment SCC was higher after IMM penicillin therapy compared to systemic or combination therapy. Treatment of CM usually included first-choice antimicrobials, but different antimicrobial combinations were also widely used. The effect of procaine benzylpenicillin to post-treatment SCC was dependent on the administration route, cow parity, and days in milk. Further studies should evaluate the factors affecting veterinarians’ choice of antimicrobial used in the treatment of CM.

Anti-inflammatory activity of the topical formulation of Drymoglossum piloselloides (L) Presl. extract on mice

Background: Chronic inflammation of the joints that occur in the condition of gout or osteoarthritis and rheumatoid arthritis often causes repeated inflammation which requires patients to take a long-term pain medication, leading to serious side effects. Alternative treatment especially from herbal ingredients in a topical form is needed. Objective: This study aims to evaluate the anti-inflammatory activity of the leaves extract of Drymoglossum piloselloides (L) Presl. in mice to prove their potential as an anti-inflammatory agent. Methods: Mice were divided into four groups (n=7), namely positive control (sodium diclofenac emulgel), negative control (placebo), P1 (emulgel extract 2.5%), and P2 (emulgel extract 5%). The anti-inflammatory activity test was carried out on mice with carrageenan-induced paw edema by measuring the relative changes in the volume of inflammation at 0 and 3 hours after treatment. Data were analyzed using the Kruskal-Wallis and Mann-Whitney tests with a confidence level of 95%. Results: The emulgel contained flavonoids, triterpenoids, steroids, tannins, and quinones. The anti-inflammatory test showed a significant inhibition of inflammation (p <0.05) at concentrations of 2.5% and 5%. This anti-inflammatory activity could be influenced by the phytochemical compounds contained in the emulgel. Conclusion:Drymoglossum piloselloides (L) Presl. emulgel at concentrations of 2.5% and 5% had an anti-inflammatory activity on mice with carrageenan-induced paw edema. Keywords: inflammation, Drymoglossum piloselloides (L) Presl., emulgel

Differences in Baseline Characteristics and Access to Treatment of Newly Diagnosed Patients With IPF in the EMPIRE Countries

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with poor prognosis. The diagnosis and treatment possibilities are dependent on the health systems of countries. Hence, comparison among countries is difficult due to data heterogeneity. Our aim was to analyse patients with IPF in Central and Eastern Europe using the uniform data from the European Multipartner IPF registry (EMPIRE), which at the time of analysis involved 10 countries. Newly diagnosed IPF patients (N = 2,492, between March 6, 2012 and May 12, 2020) from Czech Republic (N = 971, 39.0%), Turkey (N = 505, 20.3%), Poland (N = 285, 11.4%), Hungary (N = 216, 8.7%), Slovakia (N = 149, 6.0%), Israel (N = 120, 4.8%), Serbia (N = 95, 3.8%), Croatia (N = 87, 3.5%), Austria (N = 55, 2.2%), and Bulgaria (N = 9, 0.4%) were included, and Macedonia, while a member of the registry, was excluded from this analysis due to low number of cases (N = 5) at this timepoint. Baseline characteristics, smoking habit, comorbidities, lung function values, CO diffusion capacity, high-resolution CT (HRCT) pattern, and treatment data were analysed. Patients were significantly older in Austria than in the Czech Republic, Turkey, Hungary, Slovakia, Israel, and Serbia. Ever smokers were most common in Croatia (84.1%) and least frequent in Serbia (39.2%) and Slovakia (42.6%). The baseline forced vital capacity (FVC) was &gt;80% in 44.6% of the patients, between 50 and 80% in 49.3%, and &lt;50% in 6.1%. Most IPF patients with FVC &gt;80% were registered in Poland (63%), while the least in Israel (25%). A typical usual interstitial pneumonia (UIP) pattern was present in 67.6% of all patients, ranging from 43.5% (Austria) to 77.2% (Poland). The majority of patients received antifibrotic therapy (64.5%); 37.4% used pirfenidone (range 7.4–39.8% between countries); and 34.9% nintedanib (range 12.6–56.0% between countries) treatment. In 6.8% of the cases, a therapy switch was initiated between the 2 antifibrotic agents. Significant differences in IPF patient characteristics and access to antifibrotic therapies exist in EMPIRE countries, which needs further investigation and strategies to improve and harmonize patient care and therapy availability in this region.

HMGA1 Has Predictive Value in Response to Chemotherapy in Gastric Cancer

Gastric cancer is a serious health problem worldwide. Although its incidence is decreasing, the five-year survival rate remains low. Thus, it is essential to identify new biomarkers that could promote better diagnosis and treatment of patients with gastric cancer. High-mobility group AT-hook 1 (HMGA1) is a non-histone, chromatin-binding protein that has been found overexpressed in several tumor types. It has been correlated with invasion, metastasis, and drug resistance, leading to worse patient survival. The aim of this work was to evaluate the clinical value of HMGA1 in gastric cancer. HMGA1 expression was analyzed by immunohistochemistry in a single hospital series (n = 323) of gastric adenocarcinoma cases (stages I to IV) with clinicopathological and treatment data. In this series, HMGA1 expression showed no significant relevance as a prognostic biomarker. Nevertheless, a significantly better overall survival was observed in cases with high levels of HMGA1 when they were treated with chemotherapy, compared to the nontreated ones, implying that they can benefit more from treatment than patients with low expression of HMGA1. We thereby show for the first time that HMGA1 expression has a substantial value as a biomarker of response to chemotherapy in gastric cancer.

Evaluation of a phenotypic, point-of-care solution for the detection and quantitative antibiotic susceptibility testing for lower Urinary Tract Infection

Background Urinary tract infections (UTIs) are one of the most common bacterial infections seen in primary care. The current standard for the definitive diagnosis of a UTI is culture and sensitivity testing of a mid-stream urine sample at a clinical laboratory; however, this technique is costly, labour intensive and is not directly relevant clinically - typically taking 2-3 days to yield a result. Study design and Objective This is a nonexperimental cross-sectional study. The aim of this study was to evaluate the efficacy of U-treat, a bioluminescent approach for rapid detection of bacteriuria and quantitative determination of the antimicrobial susceptibility profiles of uropathogens in clinical urine specimens - in under an hour. Method The evaluation was carried out in two UK-based Medical Centres using urine samples from patients presenting with symptoms of a UTI (n=249). The U-treat technology is a two test, two reagent process. Test 1 detects the presence of a bacterial UTI > 104 bacteria/mL (5-10 minutes). Test 2 produces quantitative antibiotic susceptibility (<50 minutes). Only urine samples testing positive for bacteria in Test 1 underwent Test 2 (n=82). U-treat results were compared retrospectively against reference laboratory culture and sensitivity findings. The influence of the technology on patient treatment outcomes was also analysed. Results Relative to reference laboratory analysis, Test 1 showed a sensitivity of 97.1% and specificity of 92.0%. (PPV: 89.3%; NPV: 97.8%). Test 2 produced an overall sensitivity (measurement of true susceptibility) of 94.1% (Predictive value: 96%) and an overall specificity (measurement of true resistance) of 90.5% (Predictive value 86.4%). Analysis of treatment data demonstrated that had the physicians had access to U-treat results at the point of care, the percentage of patients treated successfully would have risen from 68.3% to 92.7%. Conclusion U-treat represents the first technology, world-wide, capable of providing UTI treatment data to physicians at the point of care, in less than 60 minutes.