Novel potassium binders to optimize RAASi therapy in heart failure: A systematic review and meta-analysis.

AIMS: Hyperkalemia often occurs among heart failure (HF) patients, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest potassium levels variations raise the risk of mortality and prompt patients to discontinue disease-modifying treatment, as RAASi. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are effective in reducing potassium levels and are approved for the treatment of hyperkalemia in HF, but whether their use results in a real optimization of HF treatment remains to be seen. The aim of the present meta-analysis was to assess the efficacy of NPB on the optimization of RAASi therapy in HF patients. METHODS AND RESULTS: PubMed, Web of Science and Clinicaltrial.gov were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified primary outcome was the optimization of RAASi therapy in HF patients, defined as the proportion of patients on RAASi at the end of follow-up. Secondary outcomes were hyperkalemia events, reduction in potassium levels, and adverse drugs reactions. Six studies with a total of 1390 patients were included. NPB improved RAASi therapy optimization in HF by 14% (95% CI: 4-26%), decreased hyperkalemia events by 29% (95% CI: 55-92%), and reduced potassium levels by 0.31 mEq/L (95% CI: 0.18-0.44) compared to placebo, maintaining a good safety profile. CONCLUSION: NPB are effective in allowing RAASi therapy optimization in patients affected by HF, in reducing hyperkalemia events and potassium levels. SYSTEMATIC REVIEW REGISTRATION: CRD42022351811 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351811.

Effects of COVID-19 pandemic on pediatric tuberculosis: decrease in notification rates and increase in clinical severity.

The outbreak of COVID-19 resulted in a decrease in tuberculosis notification rates globally. We compared tuberculosis incidence rates and disease severity in children seen in our centre prior and during COVID-19 pandemic.We performed a cohort study enrolling children aged under 18 years who received a diagnosis of tuberculosis (January 1st, 2010-December 31st, 2021) at our Pediatric Infectious Diseases Unit. Disease severity was evaluated based on: the classification proposed by Wiseman et al., smear positivity, presence of symptoms at presentation, lung cavitation, extrapulmonary disease, respiratory failure and need for intensive care support. Overall, 168 children (50.6% female, median age 69 months, IQR 95.4) received a diagnosis of tuberculosis, 156 (92.8%) between 2010-2019, before COVID-19 outbreak, and 12 (7.2%) between 2020-2021, during the pandemic. The annual tuberculosis notification rate dropped by 73% in 2021 (0.38/100000, 95%CI 0.1-0.96) compared with 2019 (1.46/100000, 95%CI 0.84-2.37). Compared to the pre-pandemic period, the proportion of children classified as severe was higher in 2020-2021 (5, 41.6% vs 23, 15.7%, p = 0.006) with a higher rate of respiratory failure (2, 16.7%, vs 4, 2.6%, p = 0.01) and an increased need for intensive care support (1, 8.3% vs 1, 0.6%, p = 0.01).   Conclusion: During COVID-19 pandemic we observed a reduction in tuberculosis notification rate in pediatric population and a significant increase in disease severity. This scenario may be the consequence of a delay in diagnosis and an underreporting of cases, rather than the effect of a reduced transmission of tuberculosis. Children reached health-care services only in the need of urgent medical attention. What is Known: • COVID-19 pandemic had a huge impact on national health care systems, resulting in a reduction of access to medical care. What is New: • In Campania Region, Italy, a low tuberculosis incidence country, we witnessed a 75% reduction in tuberculosis notification rate during pandemic. In parallel we demonstrated a significant increase in disease severity, suggesting that the reduction in notification rate may be attributed to an underreporting of cases and consequential diagnostic delay, rather than a reduced transmission of infection.

Pilot label comprehension study for an over-the-counter combined oral contraceptive pill in the United States.

CONTEXT: A growing body of evidence supports over-the-counter access to oral contraceptives in the United States. An important consideration for over-the-counter approval is consumers' ability to understand key package label messages related to safety and effectiveness without clinician involvement. We developed a prototype over-the-counter Drug Facts Label for a combined oral contraceptive pill and conducted a pilot label comprehension study to evaluate consumer understanding of key messages for use. METHODS: In November-December 2020, we conducted interviews with 163 adults and teens in the United States who were aged 12-49 years and identified as female or another gender but had a uterus and the ability to become pregnant. We developed 11 primary endpoints based on assessment of clinical risks that could occur if consumers fail to heed them, including messages about contraindications and directions for use; 11 secondary endpoints represented additional important information but with lower potential for clinical consequences if not understood. We evaluated endpoint comprehension by computing frequencies, percentages, and 2-sided Exact (Clopper-Pearson) 95% confidence intervals for observed proportions. RESULTS: Ten of the 11 primary endpoints and 10 of the 11 secondary endpoints were each understood by ≥95% of participants. The remaining primary endpoint on use with prior blood clots was understood by 89% of participants. The remaining secondary endpoint on the product being designed for "people who have the ability to become pregnant" was understood by 83% of participants. CONCLUSION: Participants understood the key label information required for safe and effective combined oral contraceptive use without clinician involvement.

Increasing Tuberculosis Rates and Association With Migration in Children Living in Campania Region, Southern Italy: A 10-Year Cohort Study.

BACKGROUND: Italy is classified as a low tuberculosis (TB) incidence country (rate 6.5/100,000 inhabitants). However, the Campania Region Pediatric Reference Centre (CRRC) observed an increase in TB, contemporarily with a rise in migration.Our aim was to investigate trends in TB notification rates, association with migration, and changes in clinical outcomes of children living in Campania. METHODS: We conducted a prospective cohort study (January 1, 2009-December 31, 2018), including children <18 years who received diagnosis of TB at the CRRC. Yearly crude TB incidence rates and relative confidence interval (95% CI) were calculated. Two main outcome measures were considered: loss to follow-up and poor clinical outcome, including prolonged or second-line treatment, sequelae, or death. RESULTS: Overall 146 children (52.1% male; median age, 50 months; interquartile range, 96.33) received a diagnosis of TB. TB incidence rates increased from 0.44 cases (95% CI: 0.16-0.97) per 100,000 inhabitants <18 years of age in 2009 to 1.84 cases (95% CI: 1.15-2.79) in 2018 (P < 0.05) and linearly correlated with the rate of migrants (R = 0.9272; P < 0.0001). Ziehl-Neelsen-positive children had an increased likelihood of poor clinical outcomes (odds ratio, 4.83; 95% CI: 1.28-18.2; P = 0.020). Compared with Italians, foreign children showed a lower likelihood of cure without sequelae (49.3% versus 67.9%; P < 0.001; odds ratio, 0.45; 95% CI: 0.23-0.89; P = 0.02). They accounted for all fatal cases and loss to follow-up. CONCLUSION: Pediatric TB rate in Campania increased in the last 10 years in association with the increase in migration. Emphasizing national TB rates may disregard important differences in local infection trends and limit medical awareness about TB. Foreign children may need tailored management programs.

Acute Aortic Syndromes: Diagnostic and Therapeutic Pathways.

Acute aortic syndromes are life-threatening medical conditions that include classic acute aortic dissection (AAD), aortic intramural hematoma, penetrating aortic ulcer, and even aortic pseudoaneurysm and traumatic aortic injury. The European Society of Cardiology has designed a multiparametric diagnostic algorithm to provide stepwise diagnosis. All patients with AAD should receive aggressive medical therapy to control blood pressure and heart rate. Urgent surgical repair is recommended for type A AAD. Uncomplicated type B AAD requires aggressive medical therapy. In contrast thoracic endovascular repair is recommended for complicated type B. AAD should be considered a lifelong disease that affects the entire aorta.

A panel of jitter/shimmer may identify functional dysphonia at risk of failure after speech therapy.

BACKGROUND: There are no reliable outcome predictors for functional dysphonia (FD) patients. OBJECTIVES: To investigate if any clinical or phoniatric characteristics could identify FD patients at risk of negative outcome after speech therapy. METHODS: We retrospectively reviewed the results of 78 FD patients treated with the proprioceptive elastic method. Before and one-month after therapy, patients underwent endoscopy, acoustic analysis with Multi-Dimensional Voice Program, and Voice Handicap Index-10 questionnaire (VHI-10). Negative outcome was the persistence of VHI-10 ≥ 13. RESULTS: 26 FD patients had negative outcome (i.e. VHI-10 ≥ 13) after speech therapy. At univariate analysis, clinical variables (i.e. sex, age, comorbidities, dysphonia duration, and professional voice use) were not associated with the outcome. Elevated Jitter% (Jitt; p = 0.03), Shimmer% (Shim; statistical trend, p = 0.06), and Noise to Harmonics Ratio (statistical trend, p = 0.06) were found in patients with poor results. At multivariate analysis, higher Jitt was an independent negative prognostic factor (p = 0.02), while a statically trend was identified for Shim (p = 0.06). A panel of Jitt >1.5 and Shim >5.1 showed an acceptable discriminatory power (AUC [ROC] = 0.76) according to Hosmer and Lemeshow scale. CONCLUSION: A panel of two acoustic analysis parameters could help in identifying FD patients at risk of speech therapy failure. Further studies in these patients are needed to evaluate the most efficient treatment protocol.

Nutritional Mushroom Treatment in Meniere's Disease with Coriolus versicolor: A Rationale for Therapeutic Intervention in Neuroinflammation and Antineurodegeneration.

Meniere's disease (MD) represents a clinical syndrome characterized by episodes of spontaneous vertigo, associated with fluctuating, low to medium frequencies sensorineural hearing loss (SNHL), tinnitus, and aural fullness affecting one or both ears. To date, the cause of MD remains substantially unknown, despite increasing evidence suggesting that oxidative stress and neuroinflammation may be central to the development of endolymphatic hydrops and consequent otholitic degeneration and displacement in the reuniting duct, thus originating the otolithic crisis from vestibular otolithic organs utricle or saccule. As a starting point to withstand pathological consequences, cellular pathways conferring protection against oxidative stress, such as vitagenes, are also induced, but at a level not sufficient to prevent full neuroprotection, which can be reinforced by exogenous nutritional approaches. One emerging strategy is supplementation with mushrooms. Mushroom preparations, used in traditional medicine for thousands of years, are endowed with various biological actions, including antioxidant, immunostimulatory, hepatoprotective, anticancer, as well as antiviral effects. For example, therapeutic polysaccharopeptides obtained from Coriolus versicolor are commercially well established. In this study, we examined the hypothesis that neurotoxic insult represents a critical primary mediator operating in MD pathogenesis, reflected by quantitative increases of markers of oxidative stress and cellular stress response in the peripheral blood of MD patients. We evaluated systemic oxidative stress and cellular stress response in MD patients in the absence and in the presence of treatment with a biomass preparation from Coriolus. Systemic oxidative stress was estimated by measuring, in plasma, protein carbonyls, hydroxynonenals (HNE), and ultraweak luminescence, as well as by lipidomics analysis of active biolipids, such as lipoxin A4 and F2-isoprostanes, whereas in lymphocytes we determined heat shock proteins 70 (Hsp72), heme oxygenase-1 (HO-1), thioredoxin (Trx), and γ-GC liase to evaluate the systemic cellular stress response. Increased levels of carbonyls, HNE, luminescence, and F2-isoprostanes were found in MD patients with respect to the MD plus Coriolus-treated group. This was paralleled by a significant (p < 0.01) induction, after Coriolus treatment, of vitagenes such as HO-1, Hsp70, Trx, sirtuin-1, and γ-GC liase in lymphocyte and by a significant (p < 0.05) increase in the plasma ratio-reduced glutathione (GSH) vs. oxidized glutathione (GSSG). In conclusion, patients affected by MD are under conditions of systemic oxidative stress, and the induction of vitagenes after mushroom supplementation indicates a maintained response to counteract intracellular pro-oxidant status. The present study also highlights the importance of investigating MD as a convenient model of cochlear neurodegenerative disease. Thus, searching innovative and more potent inducers of the vitagene system can allow the development of pharmacological strategies capable of enhancing the intrinsic reserve of vulnerable neurons, such as ganglion cells to maximize antidegenerative stress responses and thus providing neuroprotection.

Band Gap Implications on Nano-TiO2 Surface Modification with Ascorbic Acid for Visible Light-Active Polypropylene Coated Photocatalyst.

The effect of surface modification using ascorbic acid as a surface modifier of nano-TiO2 heterogeneous photocatalyst was studied. The preparation of supported photocatalyst was made by a specific paste containing ascorbic acid modified TiO2 nanoparticles used to cover Polypropylene as a support material. The obtained heterogeneous photocatalyst was thoroughly characterized (scanning electron microscope (SEM), RAMAN, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), photoluminescence (PL), and Diffuse Reflectance Spectra (DRS) and successfully applied in the visible light photodegradation of Alizarin Red S in water solutions. In particular, this new supported TiO2 photocatalyst showed a change in the adsorption mechanism of dye with respect to that of only TiO2 due to the surface properties. In addition, an improvement of photocatalytic performances in the visible light photodegration was obtained, showing a strict correlation between efficiency and energy band gap values, evidencing the favorable surface modification of TiO2 nanoparticles.

Aggregation and metal-complexation behaviour of THPP porphyrin in ethanol/water solutions as function of pH.

The effect of pH change on 5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine (THPP) with its aggregation as function of water-ethanol mixture was studied with UV-vis, fluorescence, Raman and computational analysis. In neutral pH, THPP was present as free-base and, increasing the water amount, aggregation occurred with the formation of H- and J-aggregates. The aggregation constant and the concentration of dimers were calculated, other information about the dimer aggregation were evaluated by computational study. In acidic pH, by the insertions of two hydrogens in the porphyrin rings, the porphyrin changed its geometry with a ring deformation confirmed by red-shifted spectrum and quenching in fluorescence; at this low pH, increasing the water amount, the acidic form (THPPH2)2+ resulted more stable due to a polar environment with stronger interaction by hydrogen bonding. In basic pH, reached by NH4OH, THPP porphyrin was able to react with alkali metals in order to form sitting-atop complex (M2THPP) confirmed by the typical absorption spectrum of metallo-porphyrin, Raman spectroscopy and by computational analysis.

Spectroscopic studies of porphyrin functionalized multiwalled carbon nanotubes and their interaction with TiO2 nanoparticles surface.

UV-vis and fluorescence investigations about the non-covalent interaction, in ethanolic solutions, of multi-wall carbon nanotube (MWCNT) with Coproporphyrin-I, and its Cu(II) and Zn(II) complexes (MCPIs) have been reported. Evidence of binding between MWCNTs and porphyrins was discovered from spectral adsorption decrease with respect to free porphyrins and by the exhibition of photoluminescence quenching with respect to free porphyrins demonstrating that MWCNT@MCPIs are potential donor-acceptor complexes. Equilibrium and kinetic aspects in the interactions with monolayer transparent TiO2 thin films with the obtained MWCNT@MCPIs are clarified showing their effective adsorption by porphyrin links on the TiO2 monolayer support, with respect to not only MWCNTs, according to the Langmuir model and with pseudo-first-order kinetics. Morphological description of the adsorption of MWCNT@MCPIs on TiO2 with scanning electron microscopy has been reported. The obtained experimental evidences describe therefore MWCNT@MCPIs as potential sensitizers in the DSSC (Dye-Sensitized Solar Cell) applications.