Nevin Manimala

Nephrol Dial Transplant. 2022 Feb 23:gfac010. doi: 10.1093/ndt/gfac010. Online ahead of print.

ABSTRACT

BACKGROUND: Non-dialytic conservative care (CC) has been proposed as a treatment option for patients with kidney failure. This systematic review and meta-analysis aims to compare survival outcomes between dialysis and CC in studies where patients made an explicit treatment choice.

METHODS: Five databases were systematically searched from origin up to February 25th, 2021 for studies comparing survival outcomes among patients choosing dialysis versus CC. Adjusted and unadjusted survival rates were extracted and meta-analysis performed where applicable. Risk of bias analysis was performed according to the Cochrane Risk Of Bias In Non-randomised Studies – of Interventions (ROBINS-I).

RESULTS: Twenty-two cohort studies were included covering 21,344 patients. Most studies were prone to selection bias and confounding. Patients opting for dialysis were generally younger, had less comorbid conditions, functional impairments and frailty than patients who chose CC. Unadjusted median survival from treatment decision or eGFR <15mL/min/1.73m2 ranged between 20-67 months for dialysis and 6-31 months for CC. Meta-analysis of twelve studies that provided adjusted hazard ratios (HRs) for mortality showed a pooled adjusted HR of 0.47 (95% CI 0.39-0.57) for patients choosing dialysis compared to CC. In subgroups of patients with higher age or severe comorbidities, the reduction of mortality risk remained statistically significant, although analyses were unadjusted.

CONCLUSIONS: Patients opting for dialysis have an overall lower mortality risk compared to patients opting for CC. However, high risk of bias and heterogeneous reporting preclude definitive conclusions and results cannot be translated to an individual level.

PMID:35195249 | DOI:10.1093/ndt/gfac010

Biol Open. 2022 Feb 15;11(2):bio059016. doi: 10.1242/bio.059016. Epub 2022 Feb 23.

ABSTRACT

Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) offer an attractive platform for cardiovascular research. Patient-specific iPSC-CMs are very useful for studying disease development, and bear potential for disease diagnostics, prognosis evaluation and development of personalized treatment. Several monolayer-based serum-free protocols have been described for the differentiation of iPSCs into cardiomyocytes, but data on their performance are scarce. In this study, we evaluated two protocols that are based on temporal modulation of the Wnt/β-catenin pathway for iPSC-CM differentiation from four iPSC lines, including two control individuals and two patients carrying an SCN5A mutation. The SCN5A gene encodes the cardiac voltage-gated sodium channel (Nav1.5) and loss-of-function mutations can cause the cardiac arrhythmia Brugada syndrome. We performed molecular characterization of the obtained iPSC-CMs by immunostaining for cardiac specific markers and by expression analysis of selected cardiac structural and ionic channel protein-encoding genes with qPCR. We also investigated cell growth morphology, contractility and survival of the iPSC-CMs after dissociation. Finally, we performed electrophysiological characterization of the cells, focusing on the action potential (AP) and calcium transient (CT) characteristics using patch-clamping and optical imaging, respectively. Based on our comprehensive morpho-functional analysis, we concluded that both tested protocols result in a high percentage of contracting CMs. Moreover, they showed acceptable survival and cell quality after dissociation (>50% of cells with a smooth cell membrane, possible to seal during patch-clamping). Both protocols generated cells presenting with typical iPSC-CM AP and CT characteristics, although one protocol (that involves sequential addition of CHIR99021 and Wnt-C59) rendered iPSC-CMs, which were more accessible for patch-clamp and calcium transient experiments and showed an expression pattern of cardiac-specific markers more similar to this observed in human heart left ventricle samples.

PMID:35195246 | DOI:10.1242/bio.059016

Arq Neuropsiquiatr. 2022 Feb 21:S0004-282X2022005003207. doi: 10.1590/0004-282X-ANP-2021-0034. Online ahead of print.

ABSTRACT

BACKGROUND: Although facial muscle weakness is common in patients with Facioscapulohumeral Muscular Dystrophy (FSHD), the literature is scarce on the speech and swallowing aspects.

OBJECTIVE: To investigate speech and swallowing patterns in FSHD and assess the correlation with clinical data.

METHODS: A cross-sectional study was conducted. Patients with clinical confirmation of FSHD and aged above 18 years were included and paired with healthy control individuals by age and gender. Individuals who had neurological conditions that could interfere with test results were excluded. The following assessments were applied: speech tests (acoustic and auditory-perceptual analysis); swallowing tests with the Northwestern Dysphagia Patient Check Sheet (NDPCS), the Eat Assessment Tool (EAT-10), the Speech Therapy Protocol for Dysphagia Risk (PARD), and the Functional Oral Intake Scale (FOIS); disease staging using the modified Gardner-Medwin-Walton scale (GMWS); and quality of life with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The correlation between test results and clinical data was verified by non-parametric statistics.

RESULTS: Thirteen individuals with FSHD and 10 healthy controls were evaluated. The groups presented significant differences in the motor bases of phonation and breathing. Regarding swallowing, two (15%) individuals presented mild dysphagia and seven (53.8%) showed reduced facial muscles strength. These results were not correlated with duration of the disease, age at symptoms onset, and quality of life. Dysphagia was related to worsening disease severity.

CONCLUSIONS: FSHD patients presented mild dysarthria and dysphagia. Frequent monitoring of these symptoms could be an important way to provide early rehabilitation and better quality of life.

PMID:35195226 | DOI:10.1590/0004-282X-ANP-2021-0034

Arq Bras Cardiol. 2022 Jan;118(1):115-373. doi: 10.36660/abc.20211012.

NO ABSTRACT

PMID:35195219 | DOI:10.36660/abc.20211012

Arq Bras Cardiol. 2022 Jan;118(1):88-94. doi: 10.36660/abc.20200921.

ABSTRACT

BACKGROUND: Atrial fibrillation is a public health problem associated with a fivefold increased risk of stroke or death. Analyzing costs is important when introducing new therapies and must be reconsidered in special situations, such as the novel coronavirus pandemic of 2020.

OBJECTIVE: This study aimed to evaluate the costs related to anticoagulant therapy in a one-year period, and the quality of life of atrial fibrillation patients treated in a public university hospital.

METHODS: Patient costs were those related to the anticoagulation and calculated by the average monthly costs of warfarin or direct oral anticoagulants (DOACs). Patient non-medical costs (eg., food and transportation) were calculated from data obtained by questionnaires. The Brazilian SF-6D was used to measure the quality of life. P-values < 0.05 were considered statistically significant.

RESULTS: The study population consisted of 90 patients, 45 in each arm (warfarin vs direct oral anticoagulants). Costs were 20% higher in the DOAC group ($55,532.62 vs $46,385.88), and mainly related to drug price ($23,497.16 vs $1,903.27). Hospital costs were higher in the warfarin group ($31,088.41 vs $24,604.74) and related to outpatient visits. Additionally, non-medical costs were almost twice higher in the warfarin group ($13,394.20 vs $7,430.72). Equivalence of price between the two drugs could be achieved by a 39% reduction in the price of DOACs. There were no significant group differences regarding quality of life.

CONCLUSIONS: Total costs were higher in the group of patients taking DOACs than those taking warfarin. However, a nearly 40% reduction in the price of DOACs could make it feasible to incorporate these drugs into the Brazilian public health system.

PMID:35195214 | DOI:10.36660/abc.20200921

Arq Bras Cardiol. 2022 Jan;118(1):77-87. doi: 10.36660/abc.20200890.

ABSTRACT

BACKGROUND: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities.

OBJECTIVES: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients.

METHODS: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05.

RESULTS: Mean LV ejection fraction was not different between the groups. The E/e’ ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027).

CONCLUSIONS: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

PMID:35195213 | DOI:10.36660/abc.20200890

Arq Bras Cardiol. 2022 Jan;118(1):68-74. doi: 10.36660/abc.20201060.

ABSTRACT

BACKGROUND: Despite the high proportion of octogenarians with acute pulmonary embolism, there is little information indicating the optimal management strategy, mainly therapeutic measures, such as lytic therapy.

OBJECTIVES: The number of elderly patients diagnosed with acute pulmonary embolism increases constantly. However, the role of thrombolytic treatment is not clearly defined among octogenarians. Our objective is to evaluate the effectiveness of lytic therapy in octogenarian patients diagnosed with pulmonary embolism.

METHODS: One hundred and forty eight subjects (70.3% women, n=104) aged more than eighty years were included in the study. The patients were divided in two groups: thrombolytic versus non-thrombolytic treatment. In-hospital mortality rates and bleeding events were defined as study outcomes. P-value <0.05 was considered as statistical significance.

RESULTS: In-hospital mortality decreased significantly in the thrombolytic group compared to the non-thrombolytic group (10.5% vs. 24.2% p=0.03). Minor bleeding events were more common in the arm that received thrombolytic treatment, but major hemorrhage did not differ between the groups (35.1% vs. 13.2%, p<0.01; 7% vs. 5.5% p=0.71, respectively). High PESI score (OR: 1.03 95%CI; 1.01-1.04 p<0.01), thrombolytic therapy (OR: 0.15 95%CI; 0.01-0.25, p< 0.01) and high troponin levels (OR: 1.20 95%CI; 1.01-1.43, p=0.03) were independently associated with in-hospital mortality rates in the multivariate regression analysis.

CONCLUSION: Thrombolytic therapy was associated with reduced in-hospital mortality at the expense of increased overall bleeding complications in octogenarians.

PMID:35195211 | DOI:10.36660/abc.20201060

Arq Bras Cardiol. 2022 Jan;118(1):52-58. doi: 10.36660/abc.20200669.

ABSTRACT

BACKGROUND: Serum Complement C1q/tumor necrosis factor-related protein-3 (CTRP3) levels and the relationship with atrial fibrillation (AF) in stable coronary artery disease (CAD) are not clearly known.

OBJECTIVE: The aim of this study was to investigate the change in serum CTRP3 levels and its relationship with paroxysmal AF in stable CAD.

METHOD: The study included 252 patients with CAD and 50 age-sex matched healthy control subjects. Serum CTRP3 levels were measured in addition to routine anamnesis, physical examination, laboratory and echocardiography examinations. The patients were divided into groups with and without CAD and CAD patients with and without paroxysmal AF. Statistical significance was accepted as p<0.05.

RESULTS: Serum CTRP3 levels were found to be significantly lower in patients with CAD than in the control group (p<0.001). AF was detected in 38 patients (15.08%) in the CAD group. The frequency of hypertension and female gender, hs-CRP, blood urea nitrogen, creatinine levels and left atrial end-diastolic (LAd) diameter were higher (p<0.05 for each one), and CTRP3 levels were lower in patients with AF (p <0.001). In the logistic regression analysis, serum CTRP3 levels and LAd diameters were independently determined the patients with AF (p<0.01 for each one). In this analysis, we found that every 1 ng/mL reduction in CTRP3 levels increased the risk of AF by 10.7%. In the ROC analysis of CTRP3 values for detecting patients with AF, the area under the ROC curve for CTRP3 was 0.971 (0.951-991) and was statistically significant (p<0.001). When the CTRP3 cut-off value was taken as 300 ng/mL, it was found to predict the presence of AF with 87.9% sensitivity and 86.8% specificity.

CONCLUSION: Serum CTRP3 levels were significantly reduced in patients with stable CAD and decreased CTRP3 levels were closely related to the presence of paroxysmal AF in these patients.

PMID:35195208 | DOI:10.36660/abc.20200669

Arq Bras Cardiol. 2022 Jan;118(1):24-32. doi: 10.36660/abc.20201036.

ABSTRACT

BACKGROUND: The smoking paradox has been a matter of debate for acute myocardial infarction patients for more than two decades. Although there is huge evidence claiming that is no real paradox, publications supporting better outcomes in post-MI smokers are still being released.

OBJECTIVE: To explore the effect of smoking on very long-term mortality after ST Elevation myocardial infarction (STEMI).

METHODS: This study included STEMI patients who were diagnosed between the years of 2004-2006 at three tertiary centers. Patients were categorized according to tobacco exposure (Group 1: non-smokers; Group 2: <20 package*years users, Group 3: 20-40 package*years users, Group 4: >40 package*years users). A Cox regression model was used to estimate the relative risks for very long-term mortality. P value <0.05 was considered as statistically significant.

RESULTS: There were 313 patients (201 smokers, 112 non-smokers) who were followed-up for a median period of 174 months. Smokers were younger (54±9 vs. 62±11, p: <0.001), and the presence of cardiometabolic risk factors were more prevalent in non-smokers. A univariate analysis of the impact of the smoking habit on mortality revealed a better survival curve in Group 2 than in Group 1. However, after adjustment for confounders, it was observed that smokers had a significantly increased risk of death. The relative risk became higher with increased exposure (Group 2 vs. Group 1; HR: 1.141; 95% CI: 0.599 to 2.171, Group 3 vs Group 1; HR: 2.130; 95% CI: 1.236 to 3.670, Group 4 vs Group 1; HR: 2.602; 95% CI: 1.461 to 4.634).

CONCLUSION: Smoking gradually increases the risk of all-cause mortality after STEMI.

PMID:35195205 | DOI:10.36660/abc.20201036

Arq Bras Cardiol. 2022 Jan;118(1):14-21. doi: 10.36660/abc.20201057.

ABSTRACT

BACKGROUND: Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial.

OBJECTIVES: The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI).

METHODS: One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant.

RESULTS: During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality.

CONCLUSIONS: Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

PMID:35195203 | DOI:10.36660/abc.20201057