Same-day discharge after elective percutaneous closure of patent foramen ovale.

Percutaneous closure of the patent foramen ovale (PFO) is increasingly performed in specific patients with cryptogenic stroke or clinical evidence of a paradoxical embolism. This study was performed to determine the safety of same-day discharge (SDD) following such procedures. This is a prospective, observational study of patients undergoing elective percutaneous PFO closure in a single tertiary center in Portugal between January 2020 and July 2023. AmplatzerTM devices (St. Jude Medical, St. Paul, MN, USA) and NobblestichTM EL (HeartStitch, Inc., Fountain Valley, CA, USA) were used. After 6 months, the following events were looked at: post-procedural paroxysmal atrial fibrillation, stroke, unplanned cardiac re-hospitalization, urgent cardiac surgery, major vascular complications, pericardial effusions, device embolization, and death. We studied 122 consecutive patients (52% female, 68; 48±12 years old) who had elective percutaneous closure with success and no complications. Forty-nine (40%) had SDD. AmplatzerTM devices were used more frequently in the SDD group, while NobblestichTM EL was more common in the overnight group. During the overnight group's follow-up period, there was one non-cardiovascular death; there were no further events. SDD after elective percutaneous closure of PFO was shown to be a safe and successful patient management method, including NobblestichTM, which we describe for the first time. Our results prove the safety of this same-day discharge strategy. We hypothesize that in the near future, in selected cases, PFO closure might become an ambulatory procedure.

Wernicke encephalopathy and beriberi disease presenting as STEMI-equivalent.

Thiamine deficiency is commonly associated with malnutrition, alcoholism and bariatric surgery. Thiamine deficiency can manifest in different ways, especially in developing countries: as peripheric neuropathy, as Wernicke encephalopathy or as beriberi disease. The authors present the case of a 72-year-old male, with a hiatal hernia that led to thiamine deficiency due to malnutrition. The initial clinical manifestation was an ST-elevation myocardial infarct equivalent, an ECG with a shark-fin pattern that evolved to a Wellens type B pattern. The patient evolved with severe altered mental status. A Wernicke encephalopathy diagnosis was confirmed by MRI; the patient was medicated with high-dose thiamine, with quick recovery, both neurologic and cardiac. The clinical history and response to treatment confirm the diagnosis of Wernicke encephalopathy and beriberi disease.

Does the type of seizure influence heart rate variability changes?

OBJECTIVE: Heart rate variability (HRV), an index of the autonomic cardiac activity, is decreased in patients with epilepsy, and a low HRV is associated with a higher risk of sudden death. Generalized tonic-clonic seizures are one of the most consistent risk factors for SUDEP, but the influence (and relative risk) of each type of seizure on cardiac function is still unknown. Our objective was to assess the impact of the type of seizure (focal to bilateral tonic-clonic seizure - FBTCS - versus non-FBTCS) on periictal HRV, in a group of patients with refractory epilepsy and both types of seizures. METHODS: We performed a 48-hour Holter recording on 121 patients consecutively admitted to our Epilepsy Monitoring Unit. We only included patients with both FBTCS and non-FBTCS on the Holter recording and selected the first seizure of each type to analyze. To evaluate HRV parameters (AVNN, SDNN, RMSSD, pNN20, LF, HF, and LF/HF), we chose 5-min epochs pre- and postictally. RESULTS: We included 14 patients, with a median age of 36 (min-max, 16-55) years and 64% were female. Thirty-six percent had cardiovascular risk factors, but no previously known cardiac disease. In the preictal period, there were no statistically significant differences in HRV parameters, between FBTCS and non-FBTCS. In the postictal period, AVNN, RMSSD, pNN20, LF, and HF were significantly lower, and LF/HF and HR were significantly higher in FBTCS. From preictal to postictal periods, FBTCS elicited a statistically significant rise in HR and LF/HF, and a statistically significant fall in AVNN, RMSSD, pNN20, and HF. Non-FBTCS only caused statistically significant changes in HR (decrease) and AVNN (increase). SIGNIFICANCE/CONCLUSION: This work emphasizes the greater effect of FBTCS in autonomic cardiac function in patients with refractory epilepsy, compared to other types of seizures, with a significant reduction in vagal tonus, which may be associated with an increased risk of SUDEP.

Perioperative Extracorporeal Membrane Oxygenation for Refractory Cardiopulmonary Failure Complicating Papillary Muscle Rupture.

The prognosis of papillary muscle rupture (PMR) leading to acute mitral regurgitation, pulmonary oedema, and cardiogenic shock remains dismal, with survival dependent on prompt recognition and surgical intervention. The use of extracorporeal membrane oxygenation (ECMO) for circulatory and/or respiratory support in critically ill patients failing conventional treatment has significantly increased in the past few years, mainly owing to technology improvements that have rendered the provision of this technique simpler and safer. In this report, four cases of refractory cardiopulmonary collapse complicating ischaemic and traumatic PMR successfully managed perioperatively with ECMO are presented. In this context, a review of the potential role of perioperative ECMO support for cardiogenic shock secondary to cardiac mechanical complications is also provided.

Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics.

AIMS: To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. METHODS: Two randomized, double blind, sex-balanced, placebo-controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once-daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LB was administered. RESULTS: All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose-dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (Emax ) and extent (AUEC) of the catechol-O-methyltransferase activity in relation to placebo. The tolerability profile was favourable. CONCLUSION: Opicapone, as once-daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long-lasting and sustained catechol-O-methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo.

Atrial Fibrillation as an Ischemic Stroke Clinical and Economic Burden Modifier: A 15-Year Nationwide Study.

BACKGROUND: Atrial fibrillation (AF) is a major risk factor for ischemic stroke (IS). Patients with AF may undergo preventive therapy. Although the AF impact in the clinical burden of IS has been studied, information is lacking in Southern Europe and there are no studies about the impact in potential years of life lost. Moreover, no nationwide or long-term study analyzed the economic burden of IS stratified by AF. OBJECTIVE: To study the impact of AF in the clinical and economic burden of IS. METHODS: We conducted a retrospective study using nationwide administrative data for all public hospitalizations in mainland Portugal from 2000 to 2014. We considered IS hospitalizations stratified by the presence of AF as secondary diagnosis. RESULTS: Of the total 275,173 IS hospitalizations, 22.6% reported AF. The total number of IS hospitalizations increased from 14,836 in 2000 to 19,561 in 2014 (32% increase), with an increase of 138% in the AF group (from 2,411 to 5,727). In-hospital mortality decreased from 13.6% to 11.5% and was consistently higher in the AF group (17.3% vs. 11.1%). Mean charges were also higher in the AF group (€2297 vs. €2191). Age-adjusted potential years of life lost rate was higher in the group without AF (39.6 vs. 7.5). CONCLUSIONS: AF-associated IS hospitalizations more than doubled in the studied 15-year period. Also, AF was responsible for higher in-hospital mortality and hospitalization charges. These facts highlight the need for early detection of AF and preventive treatment to limit IS occurrence, its associated burden, and poorer health outcomes.

Effect of moderate liver impairment on the pharmacokinetics of opicapone.

PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. The purpose of this study was to evaluate the effect of moderate liver impairment on the pharmacokinetics (PK) and pharmacodynamics (PD; effect on COMT activity) of OPC. METHODS: An open-label, parallel-group study in patients (n = 8) with moderate liver impairment (Child-Pugh category B, score of 7 to 9) and matched healthy subjects (n = 8, control) with normal liver function. All subjects received a single 50-mg oral dose of OPC, with plasma and urine concentrations of opicapone and its metabolites measured up to 72 h post-dose, including soluble COMT (S-COMT) activity. A one-way analysis of variance (ANOVA) was used to compare the main PK and PD parameters between groups. Point estimates (PE) of geometric mean ratios (GMR) and corresponding 90 % confidence intervals (90%CI) for the ratio hepatic/control subjects of each parameter were calculated and compared with the reference interval (80-125 %). RESULTS: Exposure to opicapone (AUC and Cmax) increased significantly in patients with moderate hepatic impairment (PE [90%CI]: AUC0-∞, 184 % [135-250 %]; Cmax, 189 % [144-249 %]). Although apparent total clearance (CL/F) of opicapone was decreased by ∼35 %, similar elimination half-life and unbound/bound fractions of opicapone were observed between the two groups. Both rate and extent of exposure to BIA 9-1103 were higher in the hepatically impaired group, but not statistically significant compared with the control group. Similar to the parent (opicapone), the observed increase in exposure to BIA 9-1106 was statistically significant in the hepatically impaired group over the control group. BIA 9-1106 was the only metabolite detected in urine and its urine PK parameters were in accordance with plasma data. Maximum S-COMT inhibition (Emax) occurred earlier for the hepatically impaired group with values of 100 % and 91.2 % for the hepatically impaired and control groups respectively. Both Emax and AUEC for the hepatically impaired group reached statistical significance over the control group. OPC was well tolerated in both hepatically impaired and control groups. CONCLUSION: The bioavailability of an orally administered single dose of 50 mg OPC was significantly higher in patients with moderate chronic hepatic impairment, perhaps by a reduced first-pass effect. As the tolerability profile of OPC was favourable under the conditions of this study and its exposure is completely purged from systemic circulation before the subsequent dose administration, no OPC dose adjustment is needed in patients with mild to moderate chronic hepatic impairment. However, as OPC is under clinical development for use as adjunctive therapy in levodopa-treated patients with Parkinson's disease, an adjustment of levodopa and/or OPC regimens in patients should be carefully considered based on a potentially enhanced levodopa dopaminergic response and the associated tolerability.

Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations.

BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone. METHODS: A randomized, double-blind, gender-balanced, parallel-group study was performed in 4 groups of 20 healthy subjects each. Four subjects in each group received placebo during the entire study. Sixteen subjects in one group received placebo once daily for 11 days and on day 12, 200 mg entacapone concomitantly with each levodopa/carbidopa dose (three times separated by a 5-h interval). Sixteen subjects in each of the remaining three groups received respectively 25, 50, and 75 mg opicapone once daily for 11 days and on day 12, placebo concomitantly with each levodopa/carbidopa dose. RESULTS: Levodopa minimum plasma concentration (Cmin) for each levodopa/carbidopa dose and for the mean of all levodopa/carbidopa doses increased substantially with all active treatments (entacapone and opicapone) when compared to the control group (placebo), with values ranging from 1.7-fold (200 mg entacapone) to 3.3-fold (75 mg opicapone). No statistical difference was found for levodopa peak of systemic exposure (as assessed by maximum observed plasma concentration (Cmax)) between all active treatments and placebo. A significant increase in the levodopa extent of systemic exposure (as assessed by concentration-time curve (AUC)) occurred with all opicapone treatments in relation to placebo. No statistical difference was found for levodopa AUC when entacapone was compared to placebo. When compared to entacapone, both 50 and 75 mg opicapone presented a significant increase for the levodopa AUC. All active treatments significantly inhibited both peak (as assessed by Emax) and extent (as assessed by effect-time curve (AUEC)) of the COMT activity in relation to placebo. When compared to entacapone, all opicapone treatments significantly decreased the extent (AUEC) of the COMT activity due to a long-lasting and sustained effect. The tolerability profile was favorable for all active treatments. CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. The tolerability profile was favorable. On the basis of the results presented in this study and along with the earlier pharmacology studies, it is anticipated that opicapone adjunct therapy at the dosages of 25 and 50 mg will provide an enhancement in levodopa availability that will translate into clinical benefit for Parkinson's disease patients.

Morphological aspects of Clinostomidae metacercariae (Trematoda: Digenea) in Hoplerytrinus unitaeniatus and Hoplias malabaricus (Pisces: Erythrinidae) of the Neotropical region, Brazil.

Species of fish of Marajó Island, State of Pará, Brazil, were examined to identify the trematodes parasitizing 102 Hoplerytrinus unitaeniatus (gold wolf fish) and 104 Hoplias malabaricus (thraira). Metacercariae of two species of trematodes, 170 specimens of Clinostomatopsis sorbens and 10 Ithyoclinostomum dimorphum were found and identified. The parasitary indices of C. sorbens from H. unitaeniatus and H. malabaricus, were 43.14% and 30.77% for prevalence, 2.52 and 1.84 for mean intensity, 1.09 and 0.57 for mean abundance and 1 to 9 and 1 to 7 for range of infection, respectively, on both fish the site of infection was the mesentery. The parasitary indices of I. dimorphum from H. unitaeniatus were 2.94% for prevalence, 2.66 for mean intensity, 0.08 for mean abundance, 1 to 4 for range of infection, and the sites of infection were the mesentery and the muscle. Metacercariae of I. dimorphum were collected in muscles of a specimen of H. malabaricus, with 0.96% of prevalence, intensity of infection of 2 parasites and 0.02 of abundance. New morphological data of external and internal structures are presented. This is the first record of metacercariae of C. sorbens and I. dimorphum in Amazonian fish.

Loop diuretic discontinuation in chronic heart failure patients: A retrospective study.

INTRODUCTION AND OBJECTIVES: The use of loop diuretics is central in managing congestion in heart failure (HF), but their impact on prognosis remains unclear. In euvolemic patients, dose reduction is recommended, but there is no recommendation on their discontinuation. This study aims to assess the impact of loop diuretic discontinuation on the prognosis of outpatients with HF with reduced ejection fraction. METHODS: This retrospective cohort study collected data from medical records of patients followed in an outpatient HF clinic at a university hospital center. Patients were included if they had been on loop diuretics and these were discontinued. Demographic, clinical and laboratory data were collected, and number and type of congestive events during the one-year period after discontinuation were recorded. RESULTS: Among 265 patients on loop diuretics, almost half (129) discontinued them at some point. Patients had optimized medical therapy, low median age, low New York Heart Association class, low B-type natriuretic peptide values, normal blood pressure, controlled heart rate and kidney function within normal limits. Among 122 patients with one year of follow-up, 18 (14.8%) had a congestive event. Fifteen events (83.3%) were low-dose diuretic reinitiation at a scheduled visit. There were only three worsening heart failure events (2.5%) during the one-year period. A significant improvement in kidney function from discontinuation to the one-year follow-up appointment was also observed. CONCLUSIONS: In our cohort, loop diuretic discontinuation was possible and safe in a large proportion of patients. The results should be interpreted with caution and cannot be extrapolated to a broader population of HF patients.

Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects.

AIMS: The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. METHODS: This randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days. RESULTS: Opicapone was well tolerated. Its systemic exposure increased in an approximately dose-proportional manner with an apparent terminal half-life of 1.0 to 1.4 h. Sulphation was the main metabolic pathway. Opicapone metabolites recovered in urine accounted for less than 3% of the amount of opicapone administered suggesting that bile is likely the main route of excretion. Maximum S-COMT inhibition (Emax ) ranged from 69.9% to 98.0% following the last dose of opicapone. The opicapone-induced S-COMT inhibition showed a half-life in excess of 100 h, which was dose-independent and much longer than plasma drug exposure. Such a half-life translates into a putative underlying rate constant that is comparable with the estimated dissociation rate constant of the COMT-opicapone complex. CONCLUSION: Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen.

Effectiveness of Exercise-Based Cardiac Rehabilitation for Heart Transplant Recipients: A Systematic Review and Meta-Analysis.

Background: Heart Transplant (HTx) is the ultimate chance of life for end stage Heart Failure (HF). Exercise training has consistently shown the potential to improve functional capacity in various chronic heart diseases. Still, the evidence in HTx recipients is scarcer. This study aims to systematically review the literature to evaluate the effectiveness and safety of Exercise-based Cardiac Rehabilitation (EBCR) in HTx recipients and to identify possible moderators of success. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials on the effect and safety of EBCR in adult HTx recipients. The primary outcome was functional capacity, measured by Peak Oxygen Uptake (pVO2). We searched CENTRAL, MEDLINE, Embase, Scopus, and Web of Knowledge databases until December 2020, reviewed references of relevant articles and contacted experts. Usual care (UC), the different dosages of exercise regimens and alternative settings were allowed as comparators. A quantitative synthesis of evidence was performed using random-effects meta-analyses. Results: A total of 11 studies with 404 patients were included. Nine studies comprising 306 patients compared EBCR with usual care. They showed that EBCR improved pVO2 compared to usual care (Mean Difference [MD] 3.03 mL/kg/min, 95% CI [2.28-3.77]; I 2 = 32%). In the subgroup analysis, including length of intervention and timing of enrollment after HTx, no significant moderator was found. Two trials, with 98 patients total, compared High Intensity Interval Training (HIIT) and Moderate Intensity Continuous Training (MICT). HIIT attained a significant edge over MICT (MD 2.23 mL/kg/min, 95% CI [1.79-2.67]; I 2 = 0%). No major adverse events associated with EBCR were reported. Conclusion: We found moderate quality evidence suggesting EBCR has a significant benefit on functional capacity improvement HTx recipients at the short-term. HIIT showed superiority when compared to MICT. Research focusing long term outcomes and standardized protocols are needed to improve evidence on EBCR effectiveness.

An Unexpected Cause of Acute Abdomen Late After Heart Transplantation-A Case Report.

Cytomegalovirus (CMV) infection is a frequent complication after a solid organ transplant, and in 86% of the cases, CMV disease occurred during the first 6 months after transplantation. Invasive CMV infections may be present as ulcerative infections of the upper gastrointestinal tract with esophagitis, gastritis, and ulcerations of the duodenum and the small bowel; however, CMV infections of the pancreatobiliary system, especially papillitis, are rarely observed. We present a case report of a man who underwent a heart transplant 6 years before, with a clinical picture of duodenitis and a simultaneous pseudotumor of major duodenal papilla who developed signs of acute abdomen caused by gastrointestinal CMV infection, successfully treated with medical therapy with valganciclovir. There is an urgent need for developments in CMV and solid organ transplantation to stratify the risk of late-onset CMV disease.

Cutaneous Tuberculosis in Heart Transplant.

Tuberculosis is a disease with a significant global burden in terms of morbidity and mortality. It usually presents as a pulmonary disease but can occasionally have extrapulmonary presentations. Immunosuppressed people are at an increased risk of tuberculosis and more frequently have atypical manifestations of the disease. Cutaneous involvement is estimated to occur in only 2% of extrapulmonary presentations. We report a case of a heart transplant recipient with disseminated tuberculosis who initially presented with cutaneous manifestations in the form of multiple abscesses that were mistaken for a community-acquired bacterial infection. The diagnosis was made after positive nucleic acid amplification testing and cultures for Mycobacterium tuberculosis from the drainage of the abscesses. After initiating antituberculous treatment, the patient had 2 instances of immune reconstitution inflammatory syndrome. A combination of diminished immunosuppression due to discontinuation of mycophenolate mofetil in the setting of acute infection, rifampin drug interactions with cyclosporine, and the beginning of treatment of tuberculosis all contributed to this paradoxical worsening. The patient responded favorably to increased glucocorticoid therapy and showed no signs of treatment failure after 6 months of antituberculous therapy.

Total thyroidectomy in a patient awaiting heart transplant with amiodarone-induced thyrotoxicosis: A case report.

Thyroid function may have a severe impact in cardiac function. Herein, we present the case report of a 53-year-old male patient awaiting heart transplant with amiodarone induced thyrotoxicosis that presented a marked improvement of his cardiac function after total thyroidectomy.

Genetic and morphological characterisation of a new species of the genus Hysterothylacium (Nematoda) from Paralichthys isosceles Jordan, 1890 (Pisces: Teleostei) of the Neotropical Region, state of Rio de Janeiro, Brazil.

Taking into account the difficulties of taxonomic identification of larval anisakid nematodes based on morphological characters, genetic analyses were performed, together with those usually applied, in order to identify anisakid larvae found in the flounder Paralichthys isosceles from the littoral of the state of Rio de Janeiro, Brazil. The analysis of 1,820 larvae revealed a new species, similar to Hysterothylacium MD, Hysterothylacium 2, Hysterothylacium KB and Hysterothylacium sp regarding the absence of the larval tooth, an excretory pore situated below the nerve ring level, and slender lateral alae. Moreover, the new species differs from Hysterothylacium fortalezae and Hysterothylacium reliquens with regard to the number and size of spines present on the tail end and from Hysterothylacium patagonicus by the absence of interlabia. The maximum parsimony and neighbour joining tree topologies based on the 18S ribosomal DNA gene, complete internal transcribed spacer region and cytochrome oxidase 2 (COII) gene demonstrated that the Brazilian larvae belong to Raphidascarididae and represent a unique genetic entity, confirmed as a new Hysterothylacium species. Furthermore, the new species presents COII genetic signatures and shares polymorphisms with Raphidascarididae members. This is the first description of a new anisakid species from Brazil through the integration of morphological and molecular taxonomy data.

Hyperkalemia as a limiting factor of neurohormonal blockade/modulation in everyday clinical practice.

INTRODUCTION AND OBJECTIVES: Neurohormonal blockade (NB)/modulation is the combination of two renin-angiotensin-aldosterone system inhibitors (RAASi) with a beta blocker. It is the core therapy for heart failure with reduced ejection fraction (HFrEF). While improving long term prognosis, it also induces hyperkalemia (serum K+ >5.0 mEq/L) due to RAASi effects. This may cause lethal arrhythmias and increase mortality in the short term. Thus, hyperkalemia frequently leads to withholding or reducing the intensity of neurohormonal blockade/modulation, which is associated with worsening long term prognosis. We assessed the relevance of hyperkalemia as a limiting factor of neurohormonal blockade/modulation in real life clinical conditions. METHODS: We reviewed the medical records of HFrEF patients attending a HF clinic at a tertiary Portuguese hospital during 2018 (n=240). The number of patients not tolerating maximal neurohormonal blockade/modulation due to hyperkalemia was determined. The incidence and characteristics of hyperkalemia episodes were also assessed. RESULTS: Only six patients (3%) achieved maximal doses of neurohormonal blockade/modulation. Hyperkalemia was the limiting factor in 48 (20%) patients. A total of 185 hyperkalemia episodes occurred in 100 (42%) patients. Forty-five (24%) episodes were moderate or severe (serum K+ >5.5 mEq/L). In these HFrEF patients, the co-existence of hypertension, diabetes or renal failure was associated with the occurrence of hyperkalemia. CONCLUSIONS: In daily clinical practice, hyperkalemia is frequent and limits neurohormonal blockade/modulation by leading to the withholding or reducing of the intensity of RAAS inhibition. Considering the negative prognostic impact associated with sub-optimal neurohormonal blockade/modulation, addressing hyperkalemia is an important issue when treating HFrEF patients.

Evaluation of stiffness loss of reinforced concrete beams using the diffuse ultrasound method.

Flexural cracks are common in reinforced concrete (RC) beams. At service loads, the tensile stresses induced by the bending moments cause beam sections to crack, leading to loss of stiffness and a consequent increase in beam deflections. Serviceability limit states in RC beam design include maximum deflection and maximum crack widths. Cracks affect the propagation of ultrasound by disrupting its travel path, which leads to a strongly scattering of the ultrasonic waves. As a result, there is a delay in the arrival of the ultrasonic energy flux, which can be observed by the increasing formation of coda waves. This resultant incoherent wavefield can be approximated by the diffuse ultrasound method. The diffuse ultrasound method can better describe the cracking effects over a larger region of the RC element compared to the ultrasonic pulse velocity, the most used ultrasound parameter in concrete applications. Changes in the diffuse ultrasound parameters (diffusivity, dissipation and ATME) can be related to the extent of cracking in a RC element. The objective of this research was to apply the diffuse ultrasound method to evaluate the stiffness loss due to flexural cracking of RC beams. Beams with different longitudinal flexural reinforcement ratios were cast and submitted to a bending test. The deflection at mid-span, and thus beam stiffness, was monitored during the test. Ultrasound transducers were installed in the central region of the beams with ultrasound readings performed during the tests in order to acquire the waveforms at various loading stages. For each waveform, the diffuse ultrasound parameters were recovered using a time-frequency analysis. The behavior of the diffuse parameters with increasing progressive damage caused by flexural cracking was analyzed and correlated to the stiffness loss of the beams. As a result, it was observed that diffusivity and ATME were the most sensitive parameters to identify the onset of cracking and also were seen to be related to beam stiffness variation at early cracking stage. When correlated with stiffness loss values up to 70%, diffusivity and ATME presented high mean correlation coefficients, allowing to conclude that it is possible to estimate the stiffness loss through the diffuse ultrasound parameters in the interval following the beginning of the cracking process.

Translation and validation of the Portuguese version of the Keratoconus Outcomes Research Questionnaire (KORQ).

PURPOSE: The purpose of this study is to translate and validate a Portuguese version of the Keratoconus Outcomes Research Questionnaire. The Keratoconus Outcomes Research Questionnaire is a psychometrically robust and valid instrument used to assess the impact of keratoconus on activity limitations and symptoms. METHODS: We performed a translation, cross-cultural adaptation, and validation of the Portuguese version of the Keratoconus Outcomes Research Questionnaire. The initial translation of the English version to the Portuguese language was performed by two independent native speaker translators, followed by an interdisciplinary panel evaluation of the translated version. The Portuguese version was then back-translated into English by two independent native speakers, followed by evaluation and comparison with the original English version by the same interdisciplinary panel. For subsequent validation, the translated questionnaire was administered at two different times to a population of 30 subjects, and the results were compared in a concordance analysis. RESULTS: The translation into Portuguese and back-translation were determined to be correct. Thirty participants were enrolled in the study (mean age, 29.23 ± 7.56 years). Nine questions (31%) had almost perfect agreement (questions 3, 4, 5, 8, 18, 22, 27, 28, and 29), 15 questions (51.7%) had substantial agreement (questions 1, 2, 6, 7, 9, 12, 14, 15, 16, 17, 20, 21, 23, 25, and 26), 4 questions (13.8%) had moderate agreement (questions 10, 11, 19, and 24) and 1 question (3.5%) had reasonable agreement (question 13). High-correlation coefficients were obtained when comparing results of the initial application and second application of this questionnaire to a sample of 30 individuals, which indicated excellent concordance with regard to results, repeatability, and reliability. CONCLUSIONS: This translated and validated questionnaire can be applied to a larger population with the intent to assess quality of life in keratoconus patients in the overall Brazilian population as well as in distinct regions of the country.

Cardiac rehabilitation in older patients: Indication or limitation?

OBJECTIVE: To assess the clinical impact of a cardiac rehabilitation program in an older population. METHODS: This is a retrospective analysis of 731 coronary patients who attended phase 2 of a cardiac rehabilitation program between January 2009 and December 2016. We compared the response to the program of older (≥65 years) and younger (<65 years) patients, analyzing changes in metabolic profile (including body mass index, waist circumference and lipid profile), exercise capacity, cardiac autonomic regulation parameters (such as chronotropic index and resting heart rate), and health-related quality of life scores. RESULTS: Older patients represented 15.9% of our cohort. They showed significant reductions in waist circumference (male patients: 98.0±7.9 cm vs. 95.9±7.9 cm, p<0.001; female patients: 90.5±11.4 cm vs. 87.2±11.7 cm, p<0.001), LDL cholesterol (102.5 [86.3-128.0] mg/dl vs. 65.0 [55.0-86.0] mg/dl, p<0.001) and triglycerides (115.0 [87.8-148.5] mg/dl vs. 97.0 [81.8-130.0] mg/dl, p<0.001). Post-training data also showed a noticeable improvement in older patients' exercise capacity (7.6±1.8 METs vs. 9.3±1.8 METs, p<0.001), along with a higher chronotropic index and lower resting heart rate. Additionally, health-related quality of life indices improved in older subjects. However, our overall analysis found no significant differences between the groups in changes of the studied parameters. CONCLUSION: Older coronary patients benefit from cardiac rehabilitation interventions, similarly to their younger counterparts. Greater involvement of elderly patients in cardiac rehabilitation is needed to fully realize the therapeutic and secondary preventive potential of such programs.