Cardiac Resynchronization Therapy and Left Atrial Remodeling: A Novel Insight?

Cardiac resynchronization therapy (CRT) restores ventricular dyssynchrony, improving left ventricle (LV) systolic function, symptoms, and outcome in patients with heart failure, systolic dysfunction, and prolonged QRS interval. The left atrium (LA) plays tremendous roles in maintaining cardiac function, being often inflicted in various cardiovascular diseases. LA remodeling implies structural-dilation, functional-altered phasic functions, and strain and electrical-atrial fibrillation remodeling. Until now, several important studies have approached the relationship between LA and CRT. LA volumes can predict responsiveness to CRT, being also associated with improved outcome in these patients. LA function and strain parameters have been shown to improve after CRT, especially in those who were positive responders to it. Further studies still need to be conducted to comprehensively characterize the impact of CRT on LA phasic function and strain, and, also, in conjunction with its impact on functional mitral regurgitation and LV diastolic dysfunction. The aim of this review was to provide an overview of current available data regarding the relation between CRT and LA remodeling.

Cardiac Resynchronization Therapy and Hypertrophic Cardiomyopathy: A Comprehensive Review.

Hypertrophic cardiomyopathy (HCM) is an inherited primary myocardial disease characterized by asymmetrical/symmetrical left ventricle (LV) hypertrophy, with or without LV outflow tract (LVOT) dynamic obstruction, and poor prognosis. Cardiac resynchronization therapy (CRT) has emerged as a minimally invasive tool for patients with heart failure (HF) with decreased LV ejection fraction (LVEF) and prolonged QRS duration of over 120 ms with or without left bundle branch block (LBBB). Several HCM patients are at risk of developing LBBB because of disease progression or secondary to septal myomectomy, while others might develop HF with decreased LVEF, alleged end-stage/dilated HCM, especially those with thin myofilament mutations. Several studies have shown that patients with myectomy-induced LBBB might benefit from left bundle branch pacing or CRT to relieve symptoms, improve exercise capacity, and increase LVEF. Otherwise, patients with end-stage/dilated HCM and prolonged QRS interval could gain from CRT in terms of NYHA class improvement, LV systolic performance increase and, to some degree, LV reverse remodeling. Moreover, several electrical and imaging parameters might aid proper selection and stratification of HCM patients to benefit from CRT. Nonetheless, current available data are scarce and further studies are still required to accurately clarify the view. This review reassesses the importance of CRT in patients with HCM based on current research by contrasting and contextualizing data from various published studies.

Longitudinal developmental profile of newborns and toddlers treated for spinal muscular atrophy.

Background: Spinal muscular atrophy (SMA) results from a loss-of-function mutation in the SMN1 gene. SMA patients suffer progressive motor disability, although no intellectual impairments have been described. Three drugs have been recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). These drugs result in longer life expectancy for SMA type 1 (SMA1) patients. Objective: The objective of the study was to assess longitudinally the psychomotor development of patients with SMA1 treated after the symptom onset and of patients treated presymptomatically. Design: Longitudinal, monocentric, noninterventional, prospective study. Methods: Our study included 11 SMA1 patients and seven presymptomatic SMA patients. The SMA1 patients were treated with an approved drug beginning after onset of symptoms; treatment for the presymptomatic patients was begun before symptom onset. They were longitudinally evaluated between September 2018 and January 2022 using the Bayley Scales of Infant and Toddler Development™ - Third Edition. Results: At each time point, all patients treated presymptomatically scored above those treated postsymptomatically on the motor scale. The cognitive scores of six of the seven patients treated presymptomatically were average; one patient was in the low average range. In the 11 postsymptomatically treated patients, four scored either in the low average or the abnormal range on the cognitive scale, but a positive trend was observed during the follow-up. Conclusion: A significant proportion of patients treated postsymptomatically scored below average on cognitive and communicative scales, with most significant concerns raised about the age of 1 year. Our study indicates that intellectual development should be considered as an important outcome in treated SMA1 patients. Cognitive and communicative evaluations should be performed as part of standard of care, and guidance should be provided to parents for optimal stimulation.

New Score for Predicting Results after Catheter Ablation for Atrial Fibrillation: VAT-DHF.

INTRODUCTION: Catheter ablation (CA) for atrial fibrillation (AF) has been proven to have the highest efficacy in maintaining sinus rhythm. Several studies have proposed different scores for predicting post-procedural success, but most have not been validated in prospective cohorts. Further research is required to determine the optimal formulae. PURPOSE: This study aimed to identify independent predictors of AF recurrence after CA and develop a composite score. METHODS: Consecutive patients with persistent and paroxysmal AF who underwent CA were retrospectively analyzed. The independent predictors of recurrence were used to create a new predictive score. RESULTS: The cohort included 263 patients with a follow-up of 37.6 ± 23.4 months. Persistent AF, f-waves < 0.1 mV, indexed left atrium volume, the presence of type 2 diabetes, and smaller height were independent predictors of recurrence and were used to create a new scoring model, VAT-DHF (V = Volume, AT = AF Type, D = Diabetes, H = Height, F = f waves). The ROC curve for this new score showed an AUC of 0.869, p < 0.0001, 95% CI [0.802-0.936], while those for APPLE and CHA2DS2-VASc showed an AUC of 0.765, 95% CI [0.637-0.893] and an AUC of 0.655, 95% CI [0.580-0.730], respectively. Patients who had a VAT-DHF score between 0 and 3.25, 3.25 and 6, and ≥6, had success rates of 95.7%, 76.3%, and 25% (p < 0.0001), respectively. CONCLUSIONS: The novel VAT-DHF score is easy to calculate and may be a useful clinical tool for identifying patients with a low, intermediate, or high risk of AF recurrence after CA.

Anti-chloride Intracellular Channel Protein 1 (CLIC1) Antibodies Induce Tumour Necrosis and Angiogenesis Inhibition on In Vivo Experimental Models of Human Renal Cancer.

BACKGROUND/AIM: Chloride intracellular channel protein 1 (CLIC1) is known as a promoter of cancer progression, metastasis, and angiogenesis. Thus, CLIC1 could be a future therapeutic target. This study aimed to evaluate the effect of anti-CLIC1 antibodies on tumour cells and vessels of human renal cell carcinoma (RCC) in rabbit cornea and chick embryo chorioallantoic membrane (CAM) models. MATERIALS AND METHODS: Human cc-RCC xenografts on rabbit cornea and CAM surface were performed. Anti-CLIC1 antibodies were applied for 5 consecutive days on both tumor models. We comparatively evaluated treated and untreated tumors by combining ultrasonography with microscopic techniques. RESULTS: RCC implants rapidly recruited blood vessels and had an exponential growth rate on both tumor models. Anti-CLIC1 antibodies suppressed tumor growth by inducing tumor cell necrosis. Tumor vessels regressed rapidly but not completely during anti-CLIC1 antibodies based therapy. CONCLUSION: Anti-CLIC1 antibodies induced tumor necrosis and tumor vasculature regression in human cc-RCC xenografts in both in vivo experimental models.

Surgical treatment for patent ductus arteriosus in adult patients: a single center experience.

In contemporary practice, percutaneous closure of the patent ductus arteriosus (PDA) has become the procedure of choice. While the surgical ligation of ductus arteriosus ensures an immediate and definitive obliteration of the ductus, this therapeutic option is rarely used and reserved for situations when percutaneous solution is unsuitable. In this manuscript, we summarize the clinical and intraoperative findings of consecutive adult patients referred to our Institution in an interval of 10 years for surgical treatment of PDA. A total of five cases of surgical closure for PDA were performed in our Center. Four subjects were not suitable for percutaneous closure, and one was discovered intraoperatively, during surgery for another cardiac condition. In all patients, the closure of the PDA was carried out by means of a suture with reinforced patch threads, in a double layer. The intervention was performed in total cardiopulmonary bypass and mild or moderate hypothermia, through a transpulmonary approach. Total circulatory arrest was not required, in any of the cases. The occlusive balloon technique was applied to all patients. All patients survived the intervention and did not suffer perioperative complications. Postoperative follow-up at 36 months did not show repermeabilization of the arterial duct or aneurysmal dilation of the adjacent aorta. Moreover, all patients showed postoperative improvement in the performance of the left ventricle. In adult patients with PDA and contraindication to percutaneous closure or in those who require surgical sanction for other cardiac diseases, surgical closure of the duct is safe and associated with favorable clinical evolution.

Experimental Study on the Corrosion of Carbon Steel and Aluminum Alloy in Firefighting Protein Foam Concentrates.

The corrosion of mild steel and Al alloy in Fomtec P 6% and 6% P Profoam 806 protein-based foam concentrates was investigated. Weight-loss data for steel showed corrosion penetration of 0.745 mipy in Fomtec and 2.269 mipy in Profoam, whereas for Al alloy the penetration levels were 0.474 and 1.093 mipy, respectively. Scanning electron microscopy and energy dispersive X-ray spectroscopy allowed characterization of the metallic surface covered or free from corrosion products. Values of corrosion potential, corrosion current density and corrosion penetration were calculated by using potentiodynamic polarization curves. Electrochemical impedance spectra illustrated the change in polarization resistance during anodic polarization. Data obtained by accelerated electrochemical methods confirm the greater aggressiveness of the Profoam concentrate compared to Fomtec concentrate.

Ratio between Right Ventricular Longitudinal Strain and Pulmonary Arterial Systolic Pressure: Novel Prognostic Parameter in Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND: We aimed to evaluate whether right ventricle (RV) longitudinal strain indexed to pulmonary arterial systolic pressure (PASP) has prognostic significance in patients undergoing cardiac resynchronization therapy (CRT). METHODS: Patients undergoing CRT were prospectively included. The primary endpoint was adverse cardiovascular events (death and HF-related hospitalizations). RV global longitudinal strain (RVGLS) and RV free wall strain (RVfwS) were measured by speckle tracking and indexed to echocardiographic estimated PASP. RESULTS: A total of 54 patients (64.0 ± 13.8 years; 58% male) were included. After 33 ± 12.9 months, the primary endpoint occurred in 18 patients. Baseline RVGLS/PASP and RVfwS/PASP showed good discriminative ability for response to CRT (AUC = 0.88, 95% CI (0.74-1) and AUC = 0.87, 95% CI (0.77-1)). RVGLS/PASP and RVfwS/PASP were significantly associated with high risk of events at univariate analysis (HR 0.039, 95% CI (0.001-0.8) p < 0.05, respectively HR = 0.049, 95% CI (0.0033-0.72), p < 0.05). Upon multivariate Cox regression analysis, RVGLS/PASP and RVfwS/PASP remained associated with high risk of events (HR 0.018, 95% CI (0.0005-0.64), p = 0.02 and HR 0.015, 95% CI (0.0004-0.524), p = 0.01) after correction for gender, etiology, QRS duration and morphology. Conclusions: Indexing RV longitudinal strain (global and free wall) by PASP provides a parameter, which independently identifies patients with high risk of cardiovascular events and predicts non-response to CRT.

Ce/Sm/Sr-Incorporating Ceramic Scaffolds Obtained via Sol-Gel Route.

Three different inorganic scaffolds were obtained starting from the oxide system SiO2‒P2O5‒CaO‒MgO, to which Ce4+/Sm3+/Sr2+ cations were added in order to propose novel materials with potential application in the field of hard tissue engineering. Knowing the beneficial effects of each element, improved features in terms of mechanical properties, antibacterial activity and cellular response are expected. The compositions were processed in the form of scaffolds by a common sol-gel method, followed by a thermal treatment at 1000 and 1200 °C. The obtained samples were characterized from thermal, compositional, morphological and mechanical point of view. It was shown that each supplementary component triggers the modification of the crystalline phase composition, as well as microstructural details. Moreover, the shrinkage behavior is well correlated with the attained compression strength values. Sm was proven to be the best choice, since in addition to a superior mechanical resistance, a clear beneficial influence on the viability of 3T3 fibroblast cell line was observed.

Paraneoplastic cerebellar degeneration associated with anti-Yo antibodies in an ovarian cancer case: A case report.

Paraneoplastic neurologic syndromes (PNS) are a rare heterogeneous group of disorders associated with malignancy that can result in significant functional impairment. One syndrome in particular, paraneoplastic cerebellar degeneration (PCD), may be severely disabling. PCD is a rare neurological syndrome, associated with active or subclinical cancer, characterized by acute or subacute onset cerebellar ataxia due to tumor-induced autoimmunity against cerebellar antigens. Treatment of paraneoplastic syndromes is generally unsatisfactory, but early diagnosis and treatment of PCD, which includes neurological treatment, immunotherapy and oncological treatment of associated malignancy, may improve the neurological prognosis. We reported the case of a 59-year-old woman who presented PCD as the first sign of ovarian cancer. Laboratory investigations showed the presence of anti-Yo antibodies in the serum. The brain MRI revealed specific modifications for PCD. After oncological treatment, intravenous immunoglobulin therapy and corticosteroid therapy, the oncological response was satisfactory, but no improvement of the neurologic symptoms was achieved.

Giant left atrial myxoma - literature review and case presentation.

Primary cardiac tumors are an extremely rare pathology, representing only 5-10% of cardiac neoplasms, but among them, the most common are cardiac myxomas, that appear to originate from multipotent mesenchymal cells of the subendocardial and endocardial stroma. The incidence of cardiac myxomas is higher in females and they are usually diagnosed between the fourth and sixth decade of life. Most often, they are located in the left atrium, having the site of attachment at the level of the interatrial septum, especially at the level of the fossa ovalis and the adjacent limbus. Due to the increased risk of systemic embolization and intracardiac obstruction, cardiac myxomas have a definite indication for emergency surgical treatment. Cardiac myxomas are a very rare cause of transient ischemic attacks and stroke. We present the case of a 38-year-old patient who experienced four recurrent transient ischemic attacks and strokes. At the fourth cerebrovascular event, echocardiography was performed and it revealed a giant tumor located in the left atrium that was surgically removed. Pathological examination confirmed the diagnosis of cardiac myxoma. The postoperative evolution was favorable, both from a neurological and cardiac point of view. Although cardiac myxomas represent a rare cause of transient ischemic attacks and stroke, they must be considered as part of the assessment protocol for cerebrovascular events.

Early Laparoscopic Ileostomy Reversal After Rectal Cancer Surgery - Technique and Outcomes.

Background: A temporary diverting ileostomy (TDI) is performed in a significant number of patients undergoing colorectal surgery. The best timing for ileostomy reversal (IR), early or late after its formation and the proper technique used for its closure are controversial.The objective of the present study is to describe the particular aspects of the laparoscopic technique of ileostomy reversal and to analyze the outcomes of its early closure. Methods: A retrospective analysis on all the patients who underwent laparoscopic ileostomy reversal (LIR) after MIS rectal surgery between 2015 and 2018 in Ponderas Academic Hospital was performed. No patient was excluded from the study. The outcomes of the early laparoscopic closure of the diverting ileostomy (less than 30 days) were analyzed and compared with the standard closure ones. Results: Twenty-one patients, (10 males), average age and BMI of 57 years (range 33-77) and 21.6 kg/m2 (range 14.4-34) were included into the study. All the procedures were completed laparoscopically. No patient was lost from follow-up. The laparoscopic ileostomy reversal was performed at 50.4 days (range 7-150) from the open (1 patient) or laparoscopic (20 patients) rectal cancer resection. Twelve patients had preoperative RCT (48%), 17 low colorectal anastomosis and the coloanal one was performed in three patients with TDI. Eleven patients (52%) had an early ileostomy reversal after 23.6 days (7-30 days). A very early LIR (7-10 days) was necessary in 3 patients with complicated evolution after TDI. No significant intra-operative or postoperative complications between the two subgroups of early or late LIR was encountered. The hospital stay (LOS) after LIR was 3.9 days (2-5) with no difference between the two subgroups. We encountered one postoperative complication (5%), - enteral bleeding conservatively treated. Conclusions: Laparoscopic ileostomy reversal may be considered as a primary option for temporary diverting ileostomy after colorectal resection. The early ileostomy reversal is safe and improved postoperative outcomes in are demonstrated selected patients. Careful investigation and rigorous selection of the patients for EIR is mandatory.

Deep vein thrombosis following the treatment of lower limb pathologic bone fractures - a comparative study.

BACKGROUND: Deep vein thrombosis is a well-known complication of fracture occurrence, lower limb surgery and periods of prolonged immobilisation. Its incidence can be increased even more in specific cases with metastatic bone disease and adjuvant treatment. There is a small amount of literature that addresses the incidence of DVT by comparing osteosynthesis and arthroplasty as surgical treatments. Current recommended anticoagulation protocols might be inadequate for specific groups of cancer patients undergoing osteosynthesis or arthroplasty. METHODS: The study was designed and performed in a retrospective manner and carried out on patients that presented at our Emergency Clinical County Hospital between 01.01.2008-31.12.2016. The patients' evolution was followed for a standard of 2 months. All our deep vein thrombosis events were diagnosed via venous duplex imaging. The studied lot (n = 85) was paired with a control group (n = 170) with similar baseline characteristics. RESULTS: Our lot was comprised of 85 patients that underwent 85 surgeries, on both of our hospital's Orthopaedic and Traumatology wards. When performing the student t-test and calculating OR (odds ratio) and RR (risk ratio) we encountered 11 cases of DVT in our studied group and 12 cases of DVT in our control group (p < 0.04). We found statistical significance when correlating DVT with type of implant (prosthesis), the presence of metastases over primary tumour and the choice of implant (prosthesis over intramedullary nail). There was no statistical significance found when correlating DVT events with the type of anticoagulation and the amount of blood transfusion units required. CONCLUSION: Patients who undergo surgical treatment for lower limb pathological fracture due to malignancy are at increased risk of DVT or death due to PE under current general thromboprophylaxis regimens. The risk is higher for the immediate postoperative period (10 days). The risk is increased by metastasis, arthroplasty and adjuvant therapy (radiotherapy, chemotherapy), and we think that a more aggressive prophylactic protocol should be used.

Long term results after arthroscopic resection of medial plicae of the knee-a prospective study.

PURPOSE: The medial plica (MP) is a normal anatomic structure consisting of a fold in the synovial layer of the joint. Arthroscopic resection is currently used as a gold standard procedure in patients with medial plica syndrome (MPS), but there are few prospective studies that analyze the long-term functional outcomes of plica resection. METHODS: The purpose of this prospective study was to evaluate the long-term results of arthroscopic resection of the medial plicae of the knee. Between 1999 and 2014 we included 267 patients that showed MRI evidence of MP out of the 5682 knee arthroscopies that we performed. We recorded pre and post-operative Tegner Lysholm knee scale scores (TLKSS) for up to 36 (3, 6, 12, 24, 36) months. The EQ-5D questionnaire was used to measure the patients' generic health status. RESULTS: The mean values of the TLKSS were 68 (61-82) pre-operative, 87 (81-94) at the 3-month follow-up and 94 (92-97) at the 6-month follow-up. The long term results (TLKSS at 12, 24, and 36 months post-operatively) were 94.8 (91-98), 94.8 (90-97), and 94.5 (92-97) respectively. The EQ-5D and EQ-VAS showed significant improvement between each of the first three data registering moments (pre-operative, 3 and 6 month follow-up). CONCLUSION: The quality of the treatment and the final functional result is directly influenced by the type of plica that creates the symptomatology. We have achieved good overall results for our patients, the ones with less cartilage damage having the fastest recovery time. The arthroscopic resection is a very good option for medial plicae that do not respond to conservative treatment, and it must be initiated as a first option when cartilage damage is suspected.

The utility of bone remodeling markers in the diagnosis, evolution and treatment response evaluation in bone metastases.

After the lungs and liver, the bone is the third most common site for metastatic disease, appearing frequently in breast and prostate malignancies. These pathological bone events that occur during the evolution of the metastatic disease are usually the onset of osteolysis and they lower the patient's life quality, and are sometimes the cause of death due to the required treatments (surgery, radiotherapy). Due to the nature of the bone remodeling process, the markers that control bone resorption are the main early indicators of bone malignancy. These markers can be found in excess quantities of 50-150% in patients with bone metastases. Analyzing these indicators in conjunction with traditional tumoral markers such as the prostate specific antigen (PSA) and the type I collagen cross-linked telopeptide (ICTP) can often increase the sensibility of the investigation and the chances of diagnosing bone metastases. The studies that were carried out in order to research this area of knowledge have had good and expected results. Most of the efforts are now channeled into developing a better therapeutic strategy that would allow for the early diagnosis and treatment of the pathological bone events. Until these markers can be used as standard investigation methods in all of our patients, some controlled studies must be carried out in order to statistically prove these results, which are purely observational.

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis.

INTRODUCTION: Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. METHODS: DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. RESULTS: Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1ß, IL-6, and IL-22 in the CFA/CII group and IL-1ß, tumor necrosis factor-α, transforming growth factor-ß, IL-6 and IL-23 in the IFA/CII group. CONCLUSIONS: Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.