A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors.

BACKGROUND: This study aimed to evaluate the safety, pharmacokinetics (PKs), and preliminary activity of LY3405105, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), in patients with advanced solid tumors. MATERIALS AND METHODS: LY3405105 monotherapy was given once daily (QD; part A1) or thrice weekly (TIW; part A2) starting at 1 and 2 mg orally, respectively, and escalated per a Bayesian design in adult patients. The primary endpoint was safety, and secondary endpoints included PKs and antitumor activity. RESULTS: Fifty-four patients were enrolled: 43 in part A1 and 11 in part A2. Seven patients had dose-limiting toxicities, all in part A1 (45 mg: n = 3; 35 mg: n = 3; 25 mg: n = 1). Thirty-five patients (64.8%) reported at least one treatment-related adverse event (TRAE). TRAEs (≥10%) were diarrhea, nausea, fatigue, vomiting, abdominal pain, anemia, asthenia, and decreased platelet count. QD dosing showed sustained exposure with less peak-trough fluctuation compared to TIW dosing. Median time to maximum concentration was 1-2 hours and half-life was 15-19 hours. CDK7-target occupancy in skin and peripheral blood on day 15 was dose-dependent and reached near maximal occupancy of 75% at ≥15 mg QD. The maximum tolerated dose (MTD) was 20 mg QD. Twelve patients in part A1 (27.9%) and 5 patients in part A2 (45.5%) had a best overall response of stable disease. No complete response or partial response was observed. CONCLUSION: The MTD of LY3405105 monotherapy was 20 mg QD. The most common toxicities were gastrointestinal adverse events, myelosuppression, fatigue, and asthenia. Limited clinical activity was observed in this phase I trial, and there are no plans for further development. CLINICALTRIALS.GOV IDENTIFIER: NCT03770494.

Assessing cardiac resynchronization therapy response in heart failure patients: a comparative analysis of efficacy and outcomes between transvenous and epicardial leads.

Cardiac resynchronization therapy (CRT) is an effective treatment for selected heart failure (HF) patients. Although transvenous implantation is the standard method, it is not feasible in some patients, so the epicardial lead emerges as an alternative. We aim to compare CRT response, procedure-related complications, and the occurrence of clinical outcomes between patients with transvenous and epicardial leads. In a single-center retrospective study, we enrolled consecutive HF patients submitted to CRT implantation with a defibrillator between 2013 and 2022. Clinical response was defined as an improvement of at least one of the New York Heart Association classes with no occurrence of cardiovascular death or HF hospitalization in the first year of follow-up. Echocardiographic response was attained with an increase in left ventricular ejection fraction 10% or a reduction of left ventricular end-diastolic volume >15% at 6-12 months after CRT implantation. Major adverse cardiovascular events (MACE) (cardiovascular mortality and HF hospitalization) and all-cause mortality were evaluated. From a total of 149 patients, 38% (n=57) received an epicardial lead. Clinical (63% versus 60%, p=0.679) and echocardiographic (63% versus 60%, p=0.679) responses were similar between the transvenous and epicardial groups. Patients in the transvenous group had a shorter hospital stay (2 versus 7 days, p<0.001). Procedure-related complications were comparable between groups (24% versus 28%, p=0.572), but left ventricular lead-related complications were more frequent in the transvenous group (14% versus 2%). During a median follow-up of 4.7 years, the rate of MACE was 30% (n=44), with no differences in both groups (p=0.591), neither regarding HF hospitalization (p=0.917) nor cardiovascular mortality (p=0.060). Nevertheless, the epicardial group had a higher rate of all-cause mortality (35% versus 20%, p=0.005), the majority occurring during long-term follow-up (>12 months), with no deaths in the postoperative period. Considering the comparable rates of CRT response, procedure-related complications, and MACE between groups, we conclude that epicardial lead is a feasible alternative for CRT when transvenous lead implantation is not possible. The occurrence of a higher number of all-cause deaths in epicardial patients in the long-term follow-up was mainly due to infectious complications (unrelated to the lead) and the progression of oncological/chronic diseases.

Impact of Renin-Angiotensin Aldosterone System Inhibition on Serum Potassium Levels among Peritoneal Dialysis Patients.

BACKGROUND: The chronic use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker has been associated with hyperkalemia in patients with reduced renal function even after the initiation of hemodialysis. Whether such medications may cause a similar effect in peritoneal dialysis patients is not well established. So, the aim of our study was to analyze the impact of renin-angiotensin-aldosterone inhibitors on the serum levels of potassium in a national cohort of peritoneal dialysis patients. METHOD: A prospective, observational, nationwide cohort study was conducted. We identified all incident patients on peritoneal dialysis that had angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) prescribed for at least 3 months and a similar period of time without these medications. Patients were divided into 4 groups: Groups I and III correspond to patients using, respectively, an ACEi or ARB and then got the drug suspended; Groups II and IV started peritoneal dialysis without the use of any renin-angiotensin aldosterone system inhibitor and then got, respectively, an ACEi or ARB introduced. Changes in potassium serum levels were compared using 2 statistical approaches: (1) the non-parametric Wilcoxon test for repeated measures and (2) a crossover analysis. RESULTS: Mean potassium serum levels at the first phase of the study for Groups I, II, III, and IV were, respectively, 4.46 ± 0.79, 4.33 ± 0.78, 4.41 ± 0.63, and 4.44 ± 0.56. Changes in mean potassium serum levels for Groups I, II, III, and IV were -0.10 ± 0.60, 0.02 ± 0.56, -0.06 ± 0.46, and 0.03 ± 0.50, respectively. CONCLUSION: The use of ACEi and ARB was not associated with a greater risk for hyperkalemia in stable peritoneal dialysis patients independently of residual renal function.

Toxicity screening of diclofenac, propranolol, sertraline and simvastatin using Danio rerio and Paracentrotus lividus embryo bioassays.

Early life-stage bioassays have been used as an alternative to short-term adult toxicity tests since they are cost-effective. A single couple can produce hundreds or thousands of embryos and hence can be used as a simple high-throughput approach in toxicity studies. In the present study, zebrafish and sea urchin embryo bioassays were used to test the toxicity of four pharmaceuticals belonging to different therapeutic classes: diclofenac, propranolol, simvastatin and sertraline. Simvastatin was the most toxic tested compound for zebrafish embryo, followed by diclofenac. Sertraline was the most toxic drug to sea urchin embryos, inducing development abnormalities at the ng/L range. Overall, our results highlight the potential of sea urchin embryo bioassay as a promising and sensitive approach for the high-throughput methods to test the toxicity of new chemicals, including pharmaceuticals, and identify several drugs that should go through more detailed toxicity assays.

Mitral annular disjunction: Beyond mitral valve prolapse.

Mitral annular disjunction (MAD) is an easily identifiable entity on transthoracic echocardiography, but is still poorly recognized or ignored. It is often associated with mitral valve prolapse and is itself a risk marker for ventricular arrhythmias and sudden cardiac death, but the management and risk stratification of these patients is not systematized. Two clinical cases of MAD associated with mitral valve prolapse and ventricular arrhythmias are presented. The first case is of a patient with a history of surgical intervention on the mitral valve due to Barlow's disease. He presented to the emergency department with sustained monomorphic ventricular tachycardia requiring emergent electrical cardioversion. MAD with transmural fibrosis at the level of the inferolateral wall was documented. The second report is of a young woman with palpitations and frequent premature ventricular contractions on Holter with documentation of valvular prolapse and MAD, and focuses on the risk stratification approach. The present article offers a review of the literature regarding the arrhythmic risk of MAD and mitral valve prolapse, as well as a review of risk stratification in these patients.

Cardioneuroablation for severe neurocardiogenic syncope.

INTRODUCTION AND OBJECTIVES: Cardioneuroablation (CNA), a technique based on radiofrequency ablation of cardiac vagal ganglia, was developed to treat recurrent vasovagal syncope (VVS) with a predominant cardioinhibitory component, as an alternative to pacemaker implantation. The aim of our study was to evaluate the safety and success rate of CNA guided by extracardiac vagal stimulation in patients with highly symptomatic cardioinhibitory VVS. METHODS: Prospective study of patients who underwent anatomically guided CNA at two cardiology centers. All patients had a history of recurrent syncope with a predominant cardioinhibitory component and refractory to conventional measures. Acute success was determined by the absence or significant reduction of cardiac parasympathetic response to extracardiac vagal stimulation. The primary endpoint was the recurrence of syncope during follow-up. RESULTS: In total, 19 patients (13 males; mean age 37.8±12.9 years) were included. Ablation was acutely successful in all patients. One patient had a convulsive episode after the procedure, which was deemed unrelated to the ablation, requiring admission to intensive care but without sequelae. No other complications occurred. At a mean follow-up of 21.0±13.2 months (range 3-42 months), 17 patients remained free of syncope. The remaining two patients had recurrence of syncope and, despite undergoing a new ablation procedure, required pacemaker implantation during follow-up. CONCLUSION: Cardioneuroablation, confirmed by extracardiac vagal stimulation, appears to be an effective and safe treatment option for highly symptomatic patients with refractory VVS with a predominant cardioinhibitory component, providing a new potential approach as an alternative to pacemaker implantation.

Complete genome sequence of the first Andean strain of potato virus S from Brazil and evidence of recombination between PVS strains.

An isolate of the Andean strain of potato virus S (PVS), named BB-AND, was detected for the first time in a Brazilian potato crop, fully sequenced and analyzed. A comparison of BB-AND with other PVS isolates (Andean and Ordinary) showed that BB-AND is quite distinct. The lowest amino acid sequence identity to the only other fully sequenced Andean isolate was found in ORF 1 (82%) and ORF 6 (87%). Recombination analysis showed that the isolate Vltava (AJ863510), from Germany, is a recombinant between PVS(O) and PVS(A) isolates, with the recombination event located between nucleotides 6125 and 8324.

Caseous calcification of the mitral annulus: a multi-modality imaging perspective.

Mitral annulus calcification is a common echocardiographic finding, particularly in the elderly and in end-stage renal disease patients under chronic dialysis. Caseous calcification or liquefaction necrosis of mitral annulus calcification is a rare evolution of mitral annular calcification. Early recognition of this entity avoids an invasive diagnostic approach, since it is benign and, unlike intracardiac tumors and abscesses, has a favorable prognosis. The authors present the case of an 84-year-old woman with a suspicious large, echodense mass at the level of the posterior mitral leaflet with associated severe mitral regurgitation. Cardiac magnetic resonance imaging demonstrated a hypoperfused mass with strong peripheral enhancement 10 minutes after gadolinium administration. Multislice computed tomography showed the calcified nature of the mass. A multi-modality imaging approach confirmed the diagnosis of caseous calcification of the posterior mitral annulus. The patient refused surgical treatment.

[Fungal endocarditis with central and peripheral embolization: case report]. / Endocardite fúngica corn embolização central e periférica: um caso clínico.

A 50-year-old man with a history of drug addiction was admitted to the cardiology department for aortic valve fungal endocarditis complicated by severe aortic regurgitation, cerebral infarcts and right common iliac artery pseudoaneurysm. While awaiting transfer to the cardiothoracic surgery department, the patient presented acute arterial ischemia of the left leg, and distal left patellofemoral embolectomy was successfully performed. The patient was then transferred to the cardiothoracic center and the aortic valve was replaced by a bioprosthetic valve. After fourteen days he was referred for vascular surgery, where the four-month hospitalization was complicated by left leg amputation. Four months after discharge, the patient was admitted to the emergency department for recurrent fungal endocarditis complicated by multiple renal and splenic infarcts and celiac trunk embolization. He was transferred to the cardiothoracic surgery department, but suffered cardiac arrest before surgical intervention.

Predictive value of malnutrition markers for mortality in peritoneal dialysis patients.

INTRODUCTION: Alterations in nutritional status have been described as important predictors of mortality in patients with chronic kidney disease (CKD). However, the association between multiple markers for nutritional status and the mortality rates of patients with CKD on peritoneal dialysis (PD) has not yet been illustrated in previously published data, particularly by using the new definition of protein energy wasting (PEW). OBJECTIVE: To evaluate the predictive value of malnutrition markers for mortality rates, on the basis of the PEW definition, of PD patients. MATERIALS AND METHODS: At the start of PD treatment, the nutritional status of 199 patients (mean age, 56 ± 13.3 years; 53% females) was evaluated. Body mass index (BMI), arm circumference, mid-arm muscle circumference, protein and caloric intake (by using a 3-day food record), and serum albumin were all recorded, as well as a subjective global assessment (SGA) and presence of PEW. Cut-off points were defined on the basis of the consensus of the International Society for Renal Nutrition and Metabolism (albumin, <3.8 g/dL; BMI, <23 kg/m(2); mid-arm muscle circumference, >10% in comparison with the 50th percentile for the reference population; protein intake, <0.8 g/kg/daily; caloric intake, <25 kcal/kg/daily). The data were obtained retrospectively between the years 2001 and 2008 on the basis of routine nutritional evaluation. Patients were monitored for fatal events from all possible causes. RESULT: The mean BMI for the population was 26.6 ± 5.0 kg/m(2). A median protein intake of 0.94 (0.18 to 4.57) g/kg/daily was reported and 60.3% of the patients reported a protein intake of <0.8 g/kg/daily. With respect to caloric intake, 38.7% of the patients consumed <25 kcal/kg/daily. A median of 3.5 (1.4 to 5.3) g/dL for serum albumin was observed and 29.3% of the patients presented values of <3.8 g/dL. PEW was diagnosed in 17.5% of patients. In the univariate model, being of age >65 years (P = .002), cardiovascular disease (P < .001), diabetes mellitus (P = .02), SGA (P = .02), and albumin (P = .002), were all significant markers for mortality. The presence of patients aged >65 years (P = .02), with diabetes mellitus (P = .057), cardiovascular disease (P = .005), and albumin were considered as independent factors for mortality in this study. CONCLUSION: SGA, albumin, and PEW were the only nutritional markers found to be associated with mortality in this cohort of PD patients. In the multivariate analysis, after adjusting for classic mortality risk factors, only patients with hypoalbuminemia were found to be at a high risk for mortality at follow-up. These results may be limited by the number of observations and a necessity for confirmation in larger prospective studies.

Brugada syndrome: Eligibility for subcutaneous implantable cardioverter-defibrillator after exercise stress test.

INTRODUCTION: Brugada syndrome (BrS) is a channelopathy associated with ventricular arrhythmias and sudden cardiac death. In patients at high risk of sudden death, an implantable cardioverter-defibrillator is indicated. Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are an alternative to transvenous systems, with reduced risk of infection and complications associated with system extraction or explantation. OBJECTIVE: To test electrocardiographic eligibility for S-ICD placement after exercise stress testing (EST) in patients with BrS. METHODS: The sample included 35 consecutive patients with BrS. Electrocardiographic eligibility was assessed using the Boston Scientific model 2889 EMBLEM™ S-ICD automated screening tool, in four phases: decubitus and orthostatism, and before and after EST. Those who had at least one acceptable vector in the four measurements were considered eligible. RESULTS: In this study, 71.4% of patients were male and mean age was 53.86±12 years. In screening prior to EST, 14.3% of patients (n=5) were not eligible for an S-ICD. There was a statistically significant association between ineligibility and presence of complete right bundle branch block and history of syncope. After EST, 16.7% of initially eligible patients no longer had eligible vectors (n=5). CONCLUSION: In this study, 16.7% of patients previously eligible for an S-ICD were no longer eligible after EST. This result demonstrates the importance of screening after EST in all patients with BrS and with indication for an S-ICD, and may influence decisions concerning which ICD to implant or whether to institute pharmacological measures that avoid inappropriate therapies.

Peritoneal dialysis modality transition and impact on phosphate and potassium serum levels.

Peritoneal dialysis (PD) modalities affect solute removal differently. However, the impacts of switching PD modalities on serum levels of biomarkers of different sizes are not known. Our objective was to analyze whether a change in the PD modality associates with the levels of two routine biochemical laboratories. In this multicentric prospective cohort study. we selected all patients who remained on a PD modality for at least 6 months and switched PD modality. Patients were also required to be treated with the same PD modality for at least 3 months before and after the modality change. The primary outcome was change in potassium and phosphate serum levels. We identified 737 eligible patients who switched their PD modality during the study. We found mean serum phosphate levels increased during the 3 months after switching from CAPD to APD and conversely decreased after switching to from APD to CAPD. In contrast, for potassium the difference in the mean serum levels was comparable between groups switching from CAPD to APD, and vice versa. In conclusion, CAPD seems to be as efficient as APD for the control of potassium serum levels, but more effective for the control of phosphate serum levels. The effect of a higher removal of middle size molecules as result of PD modalities in terms of clinical and patient-reported outcomes should be further explored.

Penile necrosis and calciphylaxis.

Penile necrosis is an uncommon condition associated, in most cases, with calciphylaxis, also known as calcific uremic arteriolopathy. It is a progressive disease found in approximately 1%-4% of patients with end stage renal disease. Patients with penile calciphylaxis present a mortality rate of up to 70%, with life expectancy of two-and a half months following the diagnosis. We report a severe calciphylaxis case that had to be submitted to a penectomy but survived the penile event.

Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome.

INTRODUCTION: Clopidogrel is an antiplatelet agent converted to its active metabolite by cytochrome P-450 isoenzymes. Numerous drugs are known to inhibit P-450 isoenzymes, including proton pump inhibitors (PPIs), which are often associated with aspirin and clopidogrel to prevent adverse gastrointestinal effects. In vitro studies first showed that PPIs reduced the antiplatelet effect of clopidogrel, while recent clinical studies have raised concerns that the addition of a PPI to clopidogrel in acute coronary syndrome (ACS) patients could actually increase the risk of recurrent cardiovascular events. OBJECTIVE: The aim of this study was to evaluate whether the prescription of a PPI conferred a worse prognosis in patients discharged with aspirin and clopidogrel treatment after ACS. METHODS: A total of 876 patients admitted with ACS and discharged with aspirin and clopidogrel, with a planned duration of at least six months, from January 2004 to March 2008, were reviewed. Patients were classified in two groups according to whether or not a PPI was prescribed at discharge. The PPIs considered were those mainly metabolized by cytochrome P-450 2C19. We excluded patients with insufficient information available on either prescription or clinical records that could allow clearly confirm or exclude exposure to a PPI. Primary end points were six-month all-cause mortality and the composite of death, myocardial infarction and unstable angina at six months. RESULTS: Of the 802 patients considered for further analysis, 274 (34.2%) individuals were medicated with a PPI in addition to dual antiplatelet therapy. Patients taking PPIs were older, more often had renal insufficiency and less often had a history of coronary revascularization and smoking. They more often presented with Killip class >I and lower hemoglobin concentration on admission. There were no significant differences between the two groups in terms of medical treatment (during hospital stay and at discharge) or invasive procedures. By multivariate analysis, independent and positive predictors of PPI prescription were older age and lower hemoglobin concentration on admission. Patients taking PPIs had a slightly higher prevalence of six-month mortality (6.5% vs. 3.9%) and of the composite end point (12.9% vs. 9.2%), although without statistical significance. By multivariate analysis including potential confounding variables, the prescription of a PPI on top of aspirin and clopidogrel was still n ot associated with a worse prognosis. CONCLUSIONS: In the present study, PPI precription in addition to aspirin and clopidogrel after ACS was not associated with a worse six-month prognosis.

Predictors of pre-hospital delay in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Early reperfusion therapy in ST-elevation myocardial infarction (STEMI) correlates with its success. The aim of our study was to characterize patients admitted with a diagnosis of STEMI with longer prehospital delay and to analyze its impact on the choice of treatment and on in-hospital prognosis. METHODS: We performed a retrospective cohort study of 797 patients consecutively admitted with a diagnosis of STEMI from January 2002 to December 2007. The cutoff for longer pre-hospital delay was defined as three hours. We analyzed demographic, clinical and echocardiographic data and determined the predictors of pre-hospital delay of > or = 3 h. RESULTS: Of the 797 patients, 77% were male and mean age was 62 +/- 13.64 years. Patients with longer pre-hospital delay were older (p < 0.001), with a higher proportion of female (p = 0.001), hypertensive (p = 0.002), diabetic (p < 0.001), and surgically revascularized patients (p = 0.007), and those with symptom onset between 10 pm and 8 am (p = 0.001). The group with shorter pre-hospital delay included more men (p = 0.001), patients with prior myocardial infarction (p = 0.025) and smokers (p = 0.009). Independent predictors of pre-hospital delay of 3 h included female gender (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.03-2.16), diabetes (OR 1.78, 95% CI 1.23-2.56), systemic arterial hypertension (OR 1.41, 95% CI 1.04-1.93), and symptom onset between 10 pm and 8 am (OR 1.76, 95% CI 1.31-2.38). Independent predictors of pre-hospital delay of > or = 3 h included male gender (OR 0.67, 95% CI 0.46-0.97) and prior myocardial infarction (OR 0.48, 95% CI 0.27-0.84). Reperfusion therapy was performed in 72%, 52% and 12% of patients with pre-hospital delay of <3 h, 3-12 h and >12 h, respectively (p for trend <0.001). Patients with longer delay more often had severely reduced left ventricular ejection fraction (LVEF) (p = 0.004). A non-significant trend was observed towards increased in-hospital mortality with longer delay (8.3% vs. 6.6%, p for trend = 0.342). CONCLUSIONS: A significant proportion of patients continue to have long pre-hospital delay. Female patients and those with diabetes, systemic arterial hypertension and symptom onset between 10 pm and 8 am made up the majority of this group. Longer pre-hospital delay was associated with a lower probability of being treated with reperfusion therapy, a higher frequency of severely depressed LVEF and a non-significant increase in in-hospital mortality. It is essential to develop mechanisms to reduce pre-hospital delay.

Insulin resistance and glucose homeostasis in peritoneal dialysis.

Cardiovascular disease (CVD) is the main cause of death in peritoneal dialysis (PD) patients, a situation that can be explained by a combination of traditional and nontraditional risk factors for CVD in these patients. Glucose and insulin homeostasis are altered in chronic kidney disease (CKD) patients even in the early stages of CKD, leading to insulin resistance by various pathways. Several factors have been implicated in the pathogenesis of insulin resistance, including anemia, dyslipidemia, uremia, malnutrition, excess of parathyroid hormone, vitamin D deficiency, metabolic acidosis, and increase in plasma free fatty acids and proinflammatory cytokines. Insulin resistance and dyslipidemia are observed and increase with the progression of CKD, playing an important role in the pathogenesis of hypertension and atherosclerosis. Particularly in PD patients, exposure to glucose from dialysis fluid accentuates the foregoing metabolic abnormalities. In conclusion, insulin resistance and altered glucose metabolism are frequently observed in CKD, and although dialysis partly corrects those disturbances, the use of glucose PD solutions intensifies a series of harmful metabolic consequences. New therapeutic measures aimed at reducing metabolic disorders are urgently needed and perhaps will improve PD patient survival.

Peritoneal dialysis in Brazil: twenty-five years of experience in a single center.

OBJECTIVES: To evaluate patient and technique survival and to provide an analysis of peritoneal dialysis (PD)-related peritonitis in 25 years of experience in a single center. STUDY DESIGN: Retrospective study of incident patients on PD from July 1980 to July 2005. SETTING: Single, university based, Brazilian dialysis program. PATIENTS: 680 patients were analyzed in our study from July 1980 to July 2005, with a cumulative experience of 15 303 patient-months. All patients over 15 years of age entering the dialysis program were included in the study. Patients with less than 30 days of follow-up were excluded. Biochemical and demographic variables, peritonitis episodes, and patient and technique survival were analyzed. RESULTS: Mean age at start of PD was 53 +/- 16 years; diabetic nephropathy was the main cause of chronic kidney disease. Cardiovascular disease was the main cause of death (44%); peritonitis was responsible for 16% of fatal events. The predictors of death in our study were diabetes [relative risk (RR) 1.23, p < 0.01], advanced age (RR 1.58, p < 0.001), low serum albumin level (RR 1.25, p < 0.01), and low serum phosphate level (RR 1.39, p < 0.001) upon starting PD. There were 1048 cases of peritonitis over the 25-year period, with a significant reduction in incidence after the introduction of the double-bag system. The number of incident PD patients originating from hemodialysis increased threefold over the observation period (p < 0.001), with a similar increase in comorbidities over time. CONCLUSION: In the largest single-center report of PD experience in Latin America, we describe the overall rate and trends over time of peritonitis as well as patient and technique survival, which are similar to previous reports. Significant changes in peritonitis rates and causative organisms as well as a significant time-dependent increase in high-risk patients starting PD were observed.

Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients.

Disturbances in mineral metabolism play a central role in the development of renal bone disease. In a 54-wk, randomized, open-label study, 119 hemodialysis patients were enrolled to compare the effects of sevelamer hydrochloride and calcium carbonate on bone. Biopsy-proven adynamic bone disease was the most frequent bone abnormality at baseline (59%). Serum phosphorus, calcium, and intact parathyroid hormone were well controlled in both groups, although calcium was consistently lower and intact parathyroid hormone higher among patients who were randomly assigned to sevelamer. Compared with baseline values, there were no changes in mineralization lag time or measures of bone turnover (e.g., activation frequency) after 1 yr in either group. Osteoid thickness significantly increased in both groups, but there was no significant difference between them. Bone formation rate per bone surface, however, significantly increased from baseline only in the sevelamer group (P = 0.019). In addition, of those with abnormal microarchitecture at baseline (i.e., trabecular separation), seven of 10 in the sevelamer group normalized after 1 yr compared with zero of three in the calcium group. In summary, sevelamer resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation increased and trabecular architecture improved with sevelamer. Further studies are required to assess whether these changes affect clinical outcomes, such as rates of fracture.

Post mortem genetic test, the clinical diagnosis is not fade with the death of the patient. / Teste genético post mortem, o diagnóstico clínico não se esgota com a morte do doente.

In up to one-third of cases of sudden death, the medico-legal autopsy finding is inconclusive, and the option to perform a molecular autopsy is covered in international guidelines. The importance of postmortem genetic testing lies in its ability to identify hereditary diseases, often those with an autosomal dominant transmission pattern, and, through consultations and screening of relatives, to identify family members with a pathogenic mutation, who are often asymptomatic, providing an opportunity to change the course of their lives. The authors present three clinical cases that highlight the importance of postmortem genetic studies and family studies, as well as the integration of the data obtained in a cardiology consultation, which may be for arrhythmology, coronary disease or cardiomyopathy, depending on the specific condition. This could modify the course of the disease in many relatives.