Genetic variations in immune mediators and prostate cancer risk: A field synopsis with Bayesian calculations.

OBJECTIVE: Our study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches. METHODS: We performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein-protein networks were designed for the genes and products enrolled in the results. RESULTS: As results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein-protein networks reinforced the findings on IL1B and IL18 genes. CONCLUSION: In conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.

Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

Heart rate score in remote monitoring: An additional tool for predicting outcomes in heart failure with reduced ejection fraction.

BACKGROUND: Heart rate score (HRS) ≥ 70% has been associated with arrhythmic events and mortality but these studies were not specific for heart failure (HF) patients. We hypothesized that HRS ≥ 70% obtained from remote monitoring (RM) is associated with HF hospitalizations and arrhythmic events in HF with reduced ejection fraction (HFrEF). METHODS: HRS was calculated from RM in patients with HFrEF and ICD or CRT-D. Two groups were defined: HRS ≥ 70% (G1, n = 55) and HRS < 70% (G2, n = 48) RESULTS: A total of 103 patients were included (64.4 ± 13.04 years, 69.9% male, mean left ventricular ejection fraction (LVEF) 33.62 ± 11.97% and FUP 61.7 ± 38.87 months). The device was CRT-D in 59.2% and ICD in 40.8% and the majority (90.3%) had the device implanted in primary prevention. G1 patients were more frequently male (p = .017) and had more coronary disease (p = .035). HRS ≥70% was an independent predictor for unplanned HF hospitalizations (OR: 1.905 (95% CI: 1.328-3.649), p < .001)). The indication for device implantation (primary vs. secondary prevention), type of device, NYHA class, age, gender and LVEF were not independent predictors of the outcome. VF (4.9 ± 20.0 G1 vs. 1.1 ± 5.47 G2, p = .046) and VT episodes were more prevalent in G1 (3.1 ± 8.93 G1 vs. 0.3 ± 1.59 G2, p = .026), as well as appropriate device shocks (4.3 ± 12.06 G1 vs. 0.3 ± 1.49 G2, p = .023). There was no difference in inappropriate shocks or mortality outcomes between groups. CONCLUSION: HRS ≥70% obtained from RM was an independent predictor of HF hospitalizations and was associated with arrhythmic events with VT and VF episodes and appropriate device shocks in HFrEF patients.

Cardiac disturbances and changes in tissue cytokine levels in mice fed with a high-refined carbohydrate diet.

AIMS: The consumption of highly refined carbohydrates increases systemic inflammatory markers, but its potential to exert direct myocardial inflammation is uncertain. Herein, we addressed the impact of a high-refined carbohydrate (HC) diet on mice heart and local inflammation over time. MAIN METHODS: BALB/c mice were fed with a standard chow (control) or an isocaloric HC diet for 2, 4, or 8 weeks (HC groups), in which the morphometry of heart sections and contractile analyses by invasive catheterization and Langendorff-perfused hearts were assessed. Cytokines levels by ELISA, matrix metalloproteinase (MMP) activity by zymography, in situ reactive oxygen species (ROS) staining and lipid peroxidation-induced TBARS levels, were also determined. KEY FINDINGS: HC diet fed mice displayed left ventricular hypertrophy and interstitial fibrosis in all times analyzed, which was confirmed by echocardiographic analyses of 8HC group. Impaired contractility indices of HC groups were observed by left ventricular catheterization, whereas ex vivo and in vitro indices of contraction under isoprenaline-stimulation were higher in HC-fed mice compared with controls. Peak levels of TNF-α, TGF-ß, ROS, TBARS, and MMP-2 occur independently of HC diet time. However, a long-lasting local reduction of the anti-inflammatory cytokine IL-10 was found, which was linearly correlated to the decline of systolic function in vivo. SIGNIFICANCE: Altogether, the results indicate that short-term consumption of HC diet negatively impacts the balance of anti-inflammatory defenses and proinflammatory/profibrotic mediators in the heart, which can contribute to HC diet-induced morphofunctional cardiac alterations.

Evaluating a 3D deep learning pipeline for cerebral vessel and intracranial aneurysm segmentation from computed tomography angiography-digital subtraction angiography image pairs.

OBJECTIVE: Computed tomography angiography (CTA) is the most widely used imaging modality for intracranial aneurysm (IA) management, yet it remains inferior to digital subtraction angiography (DSA) for IA detection, particularly of small IAs in the cavernous carotid region. The authors evaluated a deep learning pipeline for segmentation of vessels and IAs from CTA using coregistered, segmented DSA images as ground truth. METHODS: Using 50 paired CTA-DSA images, the authors trained (n = 27), validated (n = 3), and tested (n = 20) a deep learning model (3D DeepMedic) for cerebrovasculature segmentation from CTA. A landmark-based coregistration algorithm was used for registration and upsampling of CTA images to paired DSA images. Segmented vessels from the DSA were used as the ground truth. Accuracy of the model for vessel segmentation was evaluated using conventional metrics (dice similarity coefficient [DSC]) and vessel segmentation-specific metrics, like connectivity-area-length (CAL). On the test cases (20 IAs), 3 expert raters attempted to detect and segment IAs. For each rater, the authors recorded the rate of IA detection, and for detected IAs, raters segmented and calculated important IA morphology parameters to quantify the differences in IA segmentation by raters to segmentations by DeepMedic. The agreement between raters, DeepMedic, and ground truth was assessed using Krippendorf's alpha. RESULTS: In testing, the DeepMedic model yielded a CAL of 0.971 ± 0.007 and a DSC of 0.868 ± 0.008. The model prediction delineated all IAs and resulted in average error rates of < 10% for all IA morphometrics. Conversely, average IA detection accuracy by the raters was 0.653 (undetected IAs were present to a significantly greater degree on the ICA, likely due to those in the cavernous region, and were significantly smaller). Error rates for IA morphometrics in rater-segmented cases were significantly higher than in DeepMedic-segmented cases, particularly for neck (p = 0.003) and surface area (p = 0.04). For IA morphology, agreement between the raters was acceptable for most metrics, except for the undulation index (α = 0.36) and the nonsphericity index (α = 0.69). Agreement between DeepMedic and ground truth was consistently higher compared with that between expert raters and ground truth. CONCLUSIONS: This CTA segmentation network (DeepMedic trained on DSA-segmented vessels) provides a high-fidelity solution for CTA vessel segmentation, particularly for vessels and IAs in the carotid cavernous region.

The first decade of flow diversion for intracranial aneurysms with the Pipeline embolization device.

OBJECTIVE: Flow diverter devices have revolutionized the treatment of intracranial aneurysms (IAs) since their approval in 2011 and have continued to evolve. The devices have been widely adopted across institutions and centers over the past decade; however, long-term follow-up after treatment with the Pipeline embolization device (PED) is not well described in the literature. The authors' institution was among the first to begin using PEDs, allowing them to report their series of patients treated with flow diverters ≥ 10 years ago. In this study, the authors aimed to evaluate the long-term angiographic and clinical outcomes of these patients and review lessons learned along the way. METHODS: The authors performed a retrospective review of their institution's IA database from January 2007 to July 2012. All patients with IAs treated with a PED prior to July 2012 were included. Clinical and angiographic characteristics were extracted. Available angiographic follow-up at 1, 3, 5, and 10 years was reported. RESULTS: A total of 83 patients with 92 aneurysms treated with a PED ≥ 10 years ago were identified and included in the study. The mean aneurysm dome diameter was 9.2 (SD 5.7) mm, the mean aneurysm height was 10.4 (SD 6.8) mm, and the mean neck width was 4.1 (SD 2.4) mm. Only 1 (1.1%) aneurysm was ruptured at presentation. Eight (8.7%) aneurysms were recurrences of previous treatment modalities. The morphology was saccular in 77 (83.7%) aneurysms, fusiform in 14 (15.2%), and blister-like in 1 (1.1%). Among saccular aneurysms, 60 (77.9%) were wide-necked. Seventy-five (81.5%) aneurysms were in the internal carotid artery, 12 (13.0%) were vertebrobasilar, 3 (3.3%) were in the middle cerebral artery, and 2 (2.2%) were in the posterior cerebral artery. Angiographic follow-up at 1, 3, 5, and 10 years was available for 75, 59, 50, and 15 patients, respectively. The complete occlusion rates at 1, 3, 5, and 10 years were 94.7%, 96.6%, 96.0%, and 100%, respectively. The retreatment rates at 1, 3, 5, and 10 years were 8.0%, 6.8%, 8.0%, and 6.7%, respectively. CONCLUSIONS: The authors provide their single-institution series of IA patients treated with a PED ≥ 10 years ago, with the first report of 10-year follow-up for the available patients.

Analysis of craniectomy bone flaps stored in a neurosurgical cryopreservation freezer: microorganism culture results and reimplantation rates.

BACKGROUND: Cryopreservation of bone flaps after decompressive craniectomies is a common practice. A frequent complication after bone flap reimplantation is postoperative infection, so culturing of frozen craniectomy bone flaps is a crucial practice that can prevent patient morbidity and mortality. Although many studies report on infection rates after cranioplasty, no study reports on the results of bone flaps stored in a cryopreservation freezer, reimplanted or otherwise. We sought to analyze the flaps in our medical center's bone bank freezer, including microorganism culture results and reimplantation rates of cryopreserved bone flaps. METHODS: Patients who underwent craniectomy and had bone flaps cryopreserved between January 1, 2016, and July 1, 2022, were included in this retrospective study. Information about bone flap cultures and reimplantation or discard was obtained from a prospectively maintained cryopreservation database. Information including infection rates and mortality was acquired from a retrospective review of patient records. Culture results were obtained for all flaps immediately before cryopreservation and again at the time of reimplantation at the operator's discretion. RESULTS: There were 148 bone flaps obtained from 145 patients (3 craniectomies were bilateral) stored in our center's freezer. Positive culture results were seen in 79 (53.4%) flaps. The most common microorganism genus was Propionibacterium with 47 positive flaps, 46 (97.9%) of which were P. acnes. Staphylococcus was the second most common with 23 positive flaps, of which 8 (34.8%) tested positive for S. epidermidis. Of the 148 flaps, 25 (16.9%) were reimplanted, 116 (78.4%) were discarded, and 7 (4.7%) are still being stored in the freezer. Postcranioplasty infections were seen in 3 (12%) patients who had flap reimplantation. CONCLUSIONS: Considering the substantial number of positive cultures and limited reimplantation rate, we have reservations about the logistical efficiency of cryopreservation for flap storage. Future multicenter studies analyzing reimplantation predictors could help to reduce unnecessary freezing and culturing.

Contact allergy to a subcutaneous implantable cardiac defibrillator - A rare problem with a golden solution.

Contact allergy to implantable cardiac defibrillators (ICD) is an uncommon and underdiagnosed complication. We report a case of a 20-years-old man patient that was resuscitated from sudden cardiac death. Workup imaging study was unremarkable, but genetic testing identified a mutation in the KCNH2 gene of uncertain significance. The patient underwent a subcutaneous implantable cardiac defibrillator (S-ICD) implantation, with no complications. The patient suffered two hospital re-admissions due to a device-related inflammatory reaction, leading to two device re-implantations. At the first time, it was considered a bacterial infection and the S-ICD was replaced by an endovascular device. At the second time, a tissue-device interaction, with hypersensitivity reaction and device rejection was suspected. The skin patch-tests were inconclusive, but it was decided to implant a custom-made gold-coated endovascular ICD. Indeed, the tendency is an initial misdiagnosis as an infection and a high clinical suspicion is essential to an early diagnosis.

Defining dysmorphic facial features in congenital Zika syndrome.

Congenital Zika syndrome (CZS) constitutes a recently identified malformation caused by Zika virus infection during pregnancy. Limited data is available to date on the facial dysmorphic features of these patients. This study evaluated the facial dysmorphisms of children with CZS, compared with clinically healthy children, using clinical examination and standardized photographic images. Sixty-three children with CZS (9.70 ± 3.2 months-age), and 31 Controls (8.67 ± 6.2 months-age) joined the study. Seven out of 15 indices differed between groups: midfacial height (MFH)/horizontal facial reference (HFR) (p = .0003), interalar distance/HFR (p = .0027), nasal root depth/MFH (p = .0030), posterior nasal length/MFH (p = .0002), vertical position of the ear/MFH (p <.0001), ear length/MFH (p = .0005), chin height/total facial height (CH/TFH) (p <.0001). A CH/TFH of 0.229 showed 93.9% sensitivity and 80.6% specificity in diagnosing CZS. Children with CZS had broad, short faces, decreased intercanthal distance, short posterior nasal length, prominent nasal root, broad nasal wings, and high-set and long ears. Increased chin height index provided the most accurate diagnostic potential.

The use of cangrelor in neurovascular interventions: a multicenter experience.

PURPOSE: Thromboembolic events represent the most common procedure-related complication associated with neurointerventions. Cangrelor is a potent, intravenous (IV), P2Y12-receptor antagonist with a rapid onset and offset presented as an alternative antiplatelet agent. We aim to evaluate the safety and effectiveness of IV cangrelor in neurovascular intervention. METHODS: This is a retrospective analysis of data from four cerebrovascular interventional centers. We identified patients who underwent acute neurovascular intervention and received cangrelor as part of their optimum care. Patients were divided into 2 groups: ischemic and aneurysm. Periprocedural thromboembolic events, hemorrhagic complications, and outcomes were analyzed. RESULTS: Sixty-six patients were included, 42 allocated into the ischemic group (IG), and 24 into aneurysm group (AG). The IG periprocedural symptomatic complication rate was 9.5%, represented by 3 postoperative intracranial hemorrhages and 1 retroperitoneal hematoma. At discharge, 47.6% had a favorable outcome and the mortality rate was 2.4%, related to clinical deterioration of a large infarct. In the AG, 4.2% had a periprocedural complication during or after cangrelor infusion, represented by an intracranial hemorrhage in an initially ruptured aneurysm. Favorable clinical outcome was seen in 56.2% and 87.7% of ruptured and unruptured aneurysms, respectively, upon discharge. CONCLUSIONS: Cangrelor may be a feasible alternative for patients requiring immediate intervention with the use of endoluminal devices. It allows the possibility for a secure transition to long-term ticagrelor and progression to surgery in the setting of unexpected complications.

Morbidity and mortality of rheumatic heart disease and acute rheumatic fever in the inpatient setting in Timor-Leste.

AIM: To describe the clinical features, treatment and outcomes of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children admitted to the national referral hospital in Dili, Timor-Leste. METHODS: This prospective study documented cases of ARF and RHD in children aged 14 years and under who were admitted between June 2017 and May 2019. ARF was diagnosed using an adapted version of the 2015 Jones criteria and presumed (rather than proven) exposure to group A Streptococcus. Clinical and echocardiographic findings, comorbidities and discharge outcomes are reported. RESULTS: A total of 63 patients were admitted with ARF or RHD; 54 were diagnosed with RHD for the first time. Median age was 11 years (range 3-14); 48% were female. Of those with echocardiograms, 56/58 had RHD, 55/56 (98%) had mitral regurgitation (37/55 (67%) severe), 11/56 (20%) had mitral stenosis and 43/56 (77%) had aortic regurgitation. Left ventricular dysfunction (55%), pulmonary hypertension (64%) and cardiac failure (78%) were common. Four (6%) patients died in hospital, and 30/59 (51%) of surviving patients were lost to follow up. CONCLUSIONS: Community echocardiography screening has reported a high prevalence of undetected mild to moderate cases of RHD in Timor-Leste, whereas this hospital study documents mostly severe disease among hospitalised patients with a high case fatality rate and loss to follow up. RHD is a significant health problem in Timor-Leste and improved recognition and diagnosis, as well as effective delivery of treatment and follow-up are imperative.

Mechanical thrombectomy versus intravenous thrombolysis for distal large-vessel occlusion: a systematic review and meta-analysis of observational studies.

OBJECTIVE: While several studies have compared the feasibility and safety of mechanical thrombectomy (MT) for distal large-vessel occlusion (LVO) strokes in patients, few studies have compared MT with intravenous thrombolysis (IVT) alone. The purpose of this systematic review was to compare the effectiveness and safety between MT and standard medical management with IVT alone for patients with distal LVOs. METHODS: PubMed, Google Scholar, Embase, Scopus, Web of Science, Ovid Medline, and Cochrane Library were searched in order to identify studies that directly compared MT with IVT for distal LVOs (anterior cerebral artery A2, middle cerebral artery M3-4, and posterior cerebral artery P2-4). Primary outcomes of interest included a modified Rankin Scale (mRS) score of 0 to 2 at 90 days posttreatment, occurrence of symptomatic intracerebral hemorrhage (sICH), and all-cause mortality at 90 days posttreatment. RESULTS: Four studies representing a total of 381 patients were included in this meta-analysis. The pooled results indicated that the proportion of patients with an mRS score of 0 to 2 at 90 days (OR 1.16, 95% CI 0.23-5.93; p = 0.861), the occurrence of sICH (OR 2.45, 95% CI 0.75-8.03; p = 0.140), and the mortality rate at 90 days (OR 1.73, 95% CI 0.66-4.55; p = 0.263) did not differ between patients who underwent MT and those who received IVT alone. CONCLUSIONS: The meta-analysis did not demonstrate a significant difference between MT and standard medical management with regard to favorable outcome, occurrence of sICH, or 90-day mortality. Prospective clinical trials are needed to further compare the efficacy of MT with IVT alone for distal vessel occlusion.

Comparison of effectiveness and outcomes among different thrombectomy techniques in acute basilar artery occlusion: a dual-center experience.

OBJECTIVE: Acute basilar artery occlusion (BAO) is a rare large-vessel occlusion associated with high morbidity and mortality. Modern thrombectomy with stent retrievers and large-bore aspiration catheters is highly effective in achieving recanalization, but a direct comparison of different techniques for acute BAO has not been performed. Therefore, the authors sought to compare the technical effectiveness and clinical outcomes of stent retriever-assisted aspiration (SRA), aspiration alone (AA), and a stent retriever with or without manual aspiration (SR) for treatment of patients presenting with acute BAO and to evaluate predictors of clinical outcome in their cohort. METHODS: A retrospective analysis of databases of large-vessel occlusion treated with endovascular intervention at two US endovascular neurosurgery centers was conducted. Patients ≥ 18 years of age with acute BAO treated between January 2013 and December 2020 with stent retrievers or large-bore aspiration catheters were included in the study. Demographic information, procedural details, angiographic results, and clinical outcomes were extracted for analysis. RESULTS: Eighty-three patients (median age 67 years [IQR 58-76 years]) were included in the study; 33 patients (39.8%) were female. The median admission National Institutes of Health Stroke Scale (NIHSS) score was 16 (IQR 10-21). Intravenous alteplase was administered to 26 patients (31.3%). The median time from symptom onset to groin or wrist puncture was 256 minutes (IQR 157.5-363.0 minutes). Overall, successful recanalization was achieved in 74 patients (89.2%). The SRA technique had a significantly higher rate of modified first-pass effect (mFPE; 55% vs 31.8%, p = 0.032) but not true first-pass effect (FPE; 45% vs 34.9%, p = 0.346) than non-SRA techniques. Good outcome (modified Rankin Scale [mRS] score 0-2) was not significantly different among the three techniques. Poor outcome (mRS score 3-6) was associated with a higher median admission NIHSS score (12.5 vs 19, p = 0.007), a higher rate of adjunctive therapy usage (9% vs 0%, p < 0.001), and a higher rate of intraprocedural complications (10.7% vs 14.5%, p = 0.006). The admission NIHSS score significantly predicted good outcome (OR 0.98, 95% CI 0.97-0.099; p = 0.032). Incomplete recanalization after thrombectomy significantly predicted mortality (OR 1.68, 95% CI 1.18-2.39; p = 0.005). CONCLUSIONS: The evaluated techniques resulted in high recanalization rates. The SRA technique was associated with a higher rate of mFPE than AA and SR, but the clinical outcomes were similar. A lower admission NIHSS score predicted a better prognosis for patients, whereas incomplete recanalization after thrombectomy predicted mortality.

Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII.

Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca2+ dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca2+ spark rate and enhanced Ca2+ reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca2+ transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII.

Taking the pulse of Timor-Leste's cardiac needs: a 10-year descriptive time-trend analysis.

BACKGROUND: Timor-Leste is one of the poorest countries in the world. The East Timor Hearts Fund is a charitable organisation involving Australian cardiologists providing outreach screening and access to cardiac interventions. AIMS: To assess ten years of clinical volume, demographics and patient outcomes. Our intention was to identify existing limitations to facilitate planning for further capacity building over the next decade. METHODS: The East Timor Hearts Fund database was sectioned into 2-year intervals (2009/2010, 2011/2012, 2013/2014, 2015/2016 and 2017/2018). Demographics and clinical outcomes of patients were compared, with subgroup analysis of adult (>18 years old), paediatric and interventional patients. RESULTS: Over 10 years, 2050 patient encounters have occurred; 1119 (54.6%) encounters occurred in 2017/2018; 73.6% of patients were assessed in the capital Dili. Rheumatic and congenital cardiac diseases remain very common (39.1% of adult new patients and 74.2% of paediatric new patients), with 1.4% of new patients exhibiting both pathologies. The number of new patients with rheumatic or congenital heart disease tripled in 2017/2018 compared to 2009/2010 (99 vs 34 patients, P < 0.0001). Paediatric case volume increased over 10-fold over 10 years (288 new patients in 2017/2018 vs 24 in 2009/2010, P < 0.0001), with corresponding increase in proportion of paediatric interventions (59.4% in 2017/2018 vs 25.0% in 2009/2010, P = 0.027). For patients undergoing intervention (n = 87), post-procedural complications and mortality are extremely low (3.4% and 1.1%, respectively), with all eligible patients attending at least one post-procedure appointment. CONCLUSION: Demand for cardiac services in Timor-Leste is rising exponentially, with inequitable geographic coverage. Rheumatic and congenital cardiac diseases remain priorities for assessment, and paediatric case volume is increasing. Patients undergoing intervention experience good medical outcomes.

Adult and Paediatric Cardiac Intervention in Timor-Leste: Disease Burden, Demographics and Clinical Outcomes.

BACKGROUND: The East Timor Hearts Fund (ETHF) is a charitable organisation of Australian cardiologists providing outreach screening in Timor-Leste. For patients requiring intervention, ETHF arranges logistics, procedures, and postoperative care. The aim of this project is to evaluate outcomes of patients requiring intervention. METHODS: The ETHF database of all patients was utilised to identify patients with disease warranting surgical or percutaneous intervention. Both patients who underwent intervention and those who did not proceed to intervention were included in this study. Patients who had intervention arranged by other organisations but have then had follow-up with ETHF were also included. Overall demographics and pre and postoperative factors were assessed, with sub-group analysis of adult and paediatric patients to identify any differences in care. RESULTS: Of 221 patients requiring intervention, 101 patients underwent intervention, receiving 22 different operations or procedures. Patients were predominantly young (median age 17.5 years) and female (64.7%), with rheumatic heart disease (63.8%). Twenty-four (24) (33.3%) women aged 15-45 years old with cardiac disease warranting intervention were documented as pregnant or breastfeeding at time of clinic assessment. Of patients who did not proceed to intervention, adults were more likely to be lost to follow-up (42.4% vs 18.5%) while paediatric patients were more likely to experience progression of disease (18.5% vs 7.5%, p=0.005). Median waitlist time was 5 months, with no significant difference between adults and children, correlating with a preoperative mortality rate of 5.4%. For patients who underwent intervention, post-procedure mortality was extremely low (0.9%) and attendance of at least one post-procedure review was excellent (99.0%). Eleven (11) (10.9%) patients have required repeat intervention, with no difference in rates between adult and paediatric patients. Length of follow-up extends up to 20 years for some patients. CONCLUSION: The Timor-Leste interventional cohort was predominantly a young female population with rheumatic and congenital cardiac disease. There were also high rates of pregnancy amongst female patients with severe cardiac disease. Delayed access to intervention may result in preoperative adverse events and mortality, and is a key target for improvement. Patients who undergo intervention have very low post-procedural mortality, good adherence to early medical follow-up and good long-term outcomes.

Prognostic power of anaerobic threshold parameters in patients with transposition of the great arteries and systemic right ventricle.

INTRODUCTION: Both transposition of the great arteries (TGA) previously submitted to a Senning/Mustard procedure and congenitally corrected TGA (cc-TGA) have the systemic circulation supported by the morphological right ventricle, thereby rendering these patients to heart failure events risk. The aim of this study was to evaluate cardiopulmonary exercise test parameters for stratifying the risk of heart failure events in TGA patients. METHODS: Retrospective evaluation of adult TGA patients with systemic circulation supported by the morphological right ventricle submitted to cardiopulmonary exercise test in a tertiary centre. Patients were followed up for at least 1 year for the primary endpoint of cardiac death or heart failure hospitalisation. Several cardiopulmonary exercise test parameters were analysed as potential predictors of the combined endpoint and their predictive power were compared (area under the curve). RESULTS: Cardiopulmonary exercise test was performed in 44 TGA patients (8 cc-TGA), with a mean age of 35.1 ± 8.4 years. The primary endpoint was reached by 10 (22.7%) patients, with a mean follow-up of 36.7 ± 26.8 months. Heart rate at anaerobic threshold had the highest area under the curve value (0.864), followed by peak oxygen consumption (pVO2) (0.838). Heart rate at anaerobic threshold ≤95 bpm and pVO2 ≤20 ml/kg/min had a sensitivity of 87.5 and 80.0% and a specificity of 82.4 and 76.5%, respectively, for the primary outcome. CONCLUSION: Heart rate at anaerobic threshold ≤95 bpm had the highest predictive power of all cardiopulmonary exercise test parameters analysed for heart failure events in TGA patients with systemic circulation supported by the morphological right ventricle.

A New Structural Health Monitoring Strategy Based on PZT Sensors and Convolutional Neural Network.

Preliminaries convolutional neural network (CNN) applications have recently emerged in structural health monitoring (SHM) systems focusing mostly on vibration analysis. However, the SHM literature shows clearly that there is a lack of application regarding the combination of PZT-(lead zirconate titanate) based method and CNN. Likewise, applications using CNN along with the electromechanical impedance (EMI) technique applied to SHM systems are rare. To encourage this combination, an innovative SHM solution through the combination of the EMI-PZT and CNN is presented here. To accomplish this, the EMI signature is split into several parts followed by computing the Euclidean distances among them to form a RGB (red, green and blue) frame. As a result, we introduce a dataset formed from the EMI-PZT signals of 720 frames, encompassing a total of four types of structural conditions for each PZT. In a case study, the CNN-based method was experimentally evaluated using three PZTs glued onto an aluminum plate. The results reveal an effective pattern classification; yielding a 100% hit rate which outperforms other SHM approaches. Furthermore, the method needs only a small dataset for training the CNN, providing several advantages for industrial applications.

RoPE Score as a Predictor of Recurrent Ischemic Events After Percutaneous Patent Foramen Ovale Closure.

The benefits of patent foramen ovale (PFO) closure for cryptogenic stroke secondary prevention are still debated. The Risk of Paradoxical Embolism (RoPE) study developed a score to improve patient selection for this procedure. We proposed to assess the validity of this score to assess the prognostic impact of PFO closure.From 2000 to 2014, all consecutive patients submitted to PFO closure were included in a prospective registry in a university center. The primary endpoint was recurrent ischemic cerebrovascular events and the secondary endpoints were all-cause, neurological, and cardiac mortality rates and new-onset atrial fibrillation (NOAF) rates. In total, 403 patients were included in the study (women: 52.1%; mean age: 44.7 ± 10.9 years). The mean follow-up period was 6.4 ± 3.7 years. Immediate success was achieved in 97% patients. There were 23 (5.8%) ischemic cerebrovascular events, 8 (2.0%) deaths, and 17 (4.3%) NOAFs. The mean RoPE score was 6.10 ± 1.79. Smoker status, coronary artery disease, lower RoPE score, and higher left atrial dimensions were predictors of the primary endpoint. However, a lower RoPE score and coronary artery disease remained independent predictors in multivariate analysis.RoPE score was shown to be an independent predictor of recurrent ischemic cerebrovascular events, and a score of ≤ 6 was shown to identify patients with significantly higher risk of mortality and recurrent ischemic events.

Lingual Frenulum Phenotypes in Brazilian Infants With Congenital Zika Syndrome.

OBJECTIVE: The present study aimed to evaluate lingual frenulum in children affected by congenital Zika syndrome (CZS) and to analyze the association of lingual frenulum phenotypes with other variables. DESIGN: This present work had a cross-sectional, descriptive study design. SETTING: This study was carried out in Fortaleza (Brazil). The health professionals provided tertiary level of care. Data collection occurred during a multidisciplinary task force for evaluating infants affected by CZS in December 2 to 3, 2016. PATIENTS: Fifty-four patients with CZS (1-12 months old; 32 girls and 22 boys) were recruited from a population of 70 infants. INTERVENTIONS: A multidisciplinary group comprised of speech-language pathologist/audiologists and pediatric dentists evaluated all patients through an intraoral examination and a specific tongue maneuver protocol for infants. MAIN OUTCOME MEASURES: Lingual frenulum visibility was the primary outcome measure. Before initiating the study, we hypothesized that children with CZS had an absent lingual frenulum. RESULTS: Lingual frenula were visible in 34 (63%) infants, whereas in 20 (37%) infants lingual frenula visibility required a specific maneuver to retract the tongue. Six of 20 infants presented posteriorly positioned lingual frenula that were visible after maneuver. Lingual frenula were covered by mucous tissue in 14 infants. Presence of posterior frenulum was associated with dysphagia ( P = 0.038). However, the presence of dysphagia in a multivariate model did not associate with the presence of a posterior lingual frenulum ( P = .069) or neurologic symptoms ( P = .056). CONCLUSION: Children with CZS showed predominance of a posterior lingual frenula covered by an overlapping curtain-like mucous membrane.