Bulbar Research Articles

Patient-Tailored Therapy for Complex Aortic Arch Anatomy: An Evolving Research Field with Custom-Made Solutions.

The treatment of complex aortic pathologies requires specialized techniques and tailored approaches due to each patient's unique anatomical and clinical challenges. The European Association for Cardiothoracic Surgery (EACTS) and the Society of Thoracic Surgeons (STS) new guidelines identify the aorta as the body's 24th organ and reiterate that multidisciplinary aortic teams are recommended for shared decision-making to determine optimal treatment strategies. Patients treated for conditions such as aneurysms, dissections, intramural hematomas, or penetrating aortic ulcers may develop complex forms over time, necessitating careful follow-up and timely corrective actions. Endovascular solutions can be favorable for older patients with complex anatomies and multiple comorbidities. However, when endovascular treatment is not feasible, hybrid treatments or open surgery must be considered if the patient's condition allows it. The risk-benefit ratio of each procedure must be carefully evaluated; choosing the best intervention or deciding not to intervene becomes a critical and challenging decision. At our Cardiac Surgery Center in Verona, a multidisciplinary team with over 20 years of experience in treating complex aortic arch pathologies extensively discussed different cases of complex aortic pathologies treated with endovascular, hybrid, or surgical approaches, emphasizing the importance of considering both anatomical and patient-specific characteristics. The decisions and treatments were often challenging, and unanimity was not always achieved, reflecting the complexity of finding the best solutions.

Stereotactic radio-neurosurgery for jugular foramen schwannomas

BackgroundStereotactic radiosurgery (SRS) represents a minimally invasive and valuable alternative for jugular foramen schwannomas (JFS), both as upfront and/or adjuvant treatment (in hybrid approaches).MethodsWe conducted a retrospective review of our cases treated at the Lausanne University Hospital (CHUV) from June 2010 to October 2023. Eleven patients underwent SRS, among whom three had prior surgery, two in our center in the frame of a planned combined approach and one in another center. Two patients received "volume-staged" SRS. The mean age at SRS was 60 years (median 68; range 29–83). Cranial nerve (CN) symptoms were present in six patients, while five were asymptomatic. The mean tumor volume at SRS was 2.1 cc (median 1.2; range 0.068–7.3 cc), with a 12 Gy marginal dose prescribed in all cases.ResultsThe mean follow-up period was 3.9 years (median 2, range 1–7). Cranial nerve function improved after SRS in six patients, while five remained stable. At the last follow-up, all tumors showed a decrease in volume, except for one patient, who underwent surgery at 18 months after SRS, for volumetric increase at 6 and 12 months, with further XII−th CN palsy and medulla oblongata compression. Although tumor decreased at 18 months, such patient needed microsurgical resection for symptom persistence and was further controlled. The mean tumor volume at 1 year post-SRS was 1.6 cc (median 0.55; range 0.028–7.77 cc), at 2 years was 1.31 cc (median 0.76; range 0.19–5), and at 3 years was 1.32 cc (median 0.59; range 0.23–4.8). No adverse radiation events were observed.ConclusionsStereotactic radiosurgery is considered a safe and effective treatment for jugular foramen schwannomas, ensuring high rates of tumor control in all patients over the long term. The cranial nerve function improved after SRS in the 6 patients who had deficits and the other 5 patients who had no deficits remained asymptomatic. For larger tumors, combined/hybrid approaches can be a valuable alternative, to obtain tumor control and to preserve neurological function.

Decision Support in Cardiac Surgery: Early Exploration of Requirements with Cardiac Anesthetists and Surgeons.

Successful implementation of clinical decision support tools is rare, the key barrier being the lack of user involvement during development. Following the idea, development, exploration, assessment, long-term follow-up (IDEAL) framework, this study aims to provide early insights into the current challenges, clinical processes, and priorities when developing new decision support tools in cardiac surgery. Using a qualitative approach, semi-structured interviews were conducted with cardiac anesthetists and surgeons from three Scottish cardiac centers. Thematic analysis identified adverse postoperative outcomes, ageing cardiac patient population and changing surgical procedures to be the main challenges in cardiac surgery. Existing risk prediction tools were largely not used due to a perceived lack of utility and validation. This study underscores the need to shift focus towards predicting postoperative complications, instead of mortality. It emphasizes the importance of early collaboration with clinical experts and stakeholders in developing decision support systems that are fit for purpose. By identifying the priorities of cardiac clinicians, the study lays the groundwork for developing clinically meaningful prediction models.

Comparison of fluorescent antibody test, immunohistochemistry, and PCR testing for diagnostic confirmation of neurolisteriosis in 25 goats.

Neurolisteriosis, a common disease of small ruminants, is most often caused by Listeria monocytogenes. Here we describe 25 cases of caprine neurolisteriosis diagnosed in our laboratory over a 5-y period and compare our fluorescent antibody test (FAT) results with immunohistochemistry (IHC) and polymerase chain reaction (PCR) testing for diagnostic confirmation. Neurohistologic changes consistent with neurolisteriosis affected the pons in all cases, extending rostrally to the mesencephalon in 6 cases, caudally to the medulla oblongata in 6 cases, and/or dorsally to the cerebellum in 4 cases. Acute inflammatory changes were observed in 17 cases, and included neuroparenchymal microabscesses, neuronal necrosis and neuronophagia, axonal swelling, microgliosis and astrogliosis, and perivascular neutrophils with macrophages, lymphocytes, and plasma cells that occasionally extended to the leptomeninges. Subacute-to-chronic changes (8 cases) consisted of neuroparenchymal and perivascular clusters of macrophages with rare neutrophils, lymphocytes, and plasma cells admixed with glial nodules. Bacterial bacilli were observed within neutrophils or macrophages in H&E-stained tissue sections in 4 cases. Gram stain highlighted gram-positive bacilli in 13 cases. Neurolisteriosis was confirmed by FAT in 2 cases, by IHC in 19 cases, and by PCR in 20 cases.

Blood Investigation and Cardiac Markers: The Key Role to Rule Out Hospital Outcome of Myocardial Infraction in Tertiary Cardiac Care Centre

Blood Investigation and Cardiac Markers: The Key Role to Rule Out Hospital Outcome of Myocardial Infraction in Tertiary Cardiac Care Centre

Role of surgery in the treatment of pediatric low-grade glioma with various degrees of brain stem involvement

ObjectivePosterior fossa pediatric low-grade glioma involving the brainstem and cerebellar peduncles (BS-pLGG) are a subgroup with higher risks at surgery. We retrospectively analyzed the role of surgery in the interdisciplinary armamentarium of treatment options in our institutional series of BS-pLGG with various degrees of brainstem involvement.Material and methodsWe analyzed data of 52 children with BS-pLGG after surgical intervention for clinical/molecular characteristics, neurological outcome, factors influencing recurrence/progression pattern, and tumor volumetric analysis of exclusively surgically treated patients to calculate tumor growth velocity (TGV). Tumors were stratified according to primary tumor origin in four groups: (1) cerebellar peduncle, (2) 4th ventricle, (3) pons, (4) medulla oblongata.ResultsThe mean FU was 6.44 years. Overall survival was 98%. The mean PFS was 34.07 months. Two patients had biopsies only. Fifty-two percent of patients underwent remission or remained in stable disease (SD) after initial surgery. Patients with progression underwent further 23 resections, 15 chemotherapies, 4 targeted treatments, and 2 proton radiations. TGV decreased after the 2nd surgery compared to TGV after the 1st surgery (p < 0.05). The resection rates were significantly higher in Groups 1 and 2 and lowest in medulla oblongata tumors (Group 4) (p < 0.05). More extended resections were achieved in tumors with KIAA1549::BRAF fusion (p = 0.021), which mostly occurred in favorable locations (Groups 1 and 2). Thirty-one patients showed postoperatively new neurological deficits. A total of 27/31 improved within 12 months. At the end of FU, 6% had moderate deficits, 52% had mild deficits not affecting activities, and 36% had none. Fifty percent of patients were free of disease or showed remission, 38% were in SD, and 10% showed progression.ConclusionThe first surgical intervention in BS-pLGG can control disease alone in overall 50% of cases, with rates differing greatly according to location (Groups 1 > 2 > 3 > 4), with acceptable low morbidity. The second look surgery is warranted except in medullary tumors. With multimodality treatments almost 90% of patients can obtain remission or stable disease after > 5 years of follow-up. An integrated multimodal and multidisciplinary approach aiming at minimal safe residual disease, combining surgery, chemo-, targeted therapy, and, as an exception, radiation therapy, is mandatory.

Nucleus of the solitary tract neuronal degeneration and impaired hypoxia response in a model of Parkinson's disease

Parkinson's disease (PD) involves the degeneration of dopaminergic neurons in the substantia nigra (SNpc) and manifests with both classic and non-classic motor symptoms, including respiratory failure. Our study aims to investigate the involvement of the commissural and intermediate nucleus of the solitary tract (cNTS and iNTS) in the attenuated respiratory response to hypoxia in PD. Using a PD rat model induced by bilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum of male Wistar rats, we explored potential alterations in the population of Phox2b neurons or hypoxia-activated neurons in the NTS projecting to the retrotrapezoid nucleus (RTN). Additionally, we explored neuronal connectivity between SNpc and cNTS. Projections pathways were assessed using unilateral injection of the retrograde tracer Fluorogold (FG) in the cNTS and RTN. Neuronal activation was evaluated by analyzing fos expression in rats exposed to hypoxia. In the PD model, the ventilatory response, measured through whole-body plethysmography, was impaired at both baseline and in response to hypoxia. A reduction in Phox2b-expressing neurons or hypoxia-activated neurons projecting to the RTN was observed. Additionally, we identified an indirect pathway linking the SNpc and cNTS, which passes through the periaqueductal gray (PAG). In conclusion, our findings suggest impairment in the SNpc-PAG-cNTS pathway in the PD model, explaining the loss of Phox2b-expressing neurons or hypoxia-activated neurons in the cNTS and subsequent respiratory impairment during hypoxic stimulation. We propose that the reduced population of Phox2b-expressing neurons in the NTS may include the same neurons activated by hypoxia and projecting to the RTN.

Clinical Impact of Intracoronary Imaging in the Management of Stent Thrombosis.

Objectives: Use of intracoronary imaging (ICI) in cases of stent thrombosis (ST) is recommended and tailored treatment appears reasonable. Nevertheless, data supporting such a strategy are lacking. The aim of this study was to evaluate the clinical impact of ICI in the management of ST. Methods: The unadjusted study population was consecutive patients with definite ST presenting in a single tertiary cardiac centre and undergoing percutaneous coronary intervention (PCI). The presumed major mechanism of ST was assigned according to the real-time ICI interpretation by the PCI operator. Propensity score matching was performed with regard to ICI use to form the adjusted population and Kaplan-Meier analysis was applied to compare survival free of cardiac death (CD) or target lesion revascularization (TLR). Results: The unadjusted population included 130 ST patients, with the majority presenting with ST-elevation myocardial infarction (STEMI) (88%) and very late ST (86%). ICI was performed in 45 patients, of whom optical coherence tomography (OCT) was performed in 30 cases. When the individual ST mechanisms were viewed as groups, there was an interaction observed between type of treatment (stent vs. non-stent) and ST mechanism, with non-stent treatment being more prevalent in cases of underexpansion, malapposition, in-stent restenosis and mechanism uncertainty. After application of matching, two groups of 30 patients were formed. ICI-guided management resulted in better survival free of CD-TLR at 2 years (93% vs. 73%, p = 0.037). Conclusions: Intracoronary imaging guidance during PCI for ST had a direct impact on management (stent vs. non-stent) and resulted in a lower event rate at mid-term follow-up when propensity matched analysis was applied.

Impact of Routine Case Volume on Door-to-Device Time for Primary PCI Patients: The Concept of a Designated Primary PCI Cath Lab at a Large Volume Cardiac Center

Impact of Routine Case Volume on Door-to-Device Time for Primary PCI Patients: The Concept of a Designated Primary PCI Cath Lab at a Large Volume Cardiac Center

Understanding subcortical projections to the lateral posterior thalamic nucleus and its subregions using retrograde neural tracing.

The rat lateral posterior thalamic nucleus (LP) is composed of the rostromedial (LPrm), lateral (LPl), and caudomedial parts, with LPrm and LPl being areas involved in information processing within the visual cortex. Nevertheless, the specific differences in the subcortical projections to the LPrm and LPl remain elusive. In this study, we aimed to reveal the subcortical regions that project axon fibers to the LPl and LPrm using a retrograde neural tracer, Fluorogold (FG). After FG injection into the LPrm or LPl, the area was visualized immunohistochemically. Retrogradely labeled neurons from the LPrm were distributed in the retina and the region from the diencephalon to the medulla oblongata. Diencephalic labeling was found in the reticular thalamic nucleus (Rt), zona incerta (ZI), ventral lateral geniculate nucleus (LGv), intergeniculate leaflet (IGL), and hypothalamus. In the midbrain, prominent labeling was found in the periaqueductal gray (PAG) and deep layers of the superior colliculus. Additionally, retrograde labeling was observed in the cerebellar and trigeminal nuclei. When injected into the LPl, several cell bodies were labeled in the visual-related regions, including the retina, LGv, IGL, and olivary pretectal nucleus (OPT), as well as in the Rt and anterior pretectal nucleus (APT). Less labeling was found in the cerebellum and medulla oblongata. When the number of retrogradely labeled neurons from the LPrm or LPl was compared as a percentage of total subcortical labeling, a larger percentage of subcortical inputs to the LPl included projections from the APT, OPT, and Rt, whereas a large proportion of subcortical inputs to the LPrm originated from the ZI, reticular formation, and PAG. These results suggest that LPrm not only has visual but also multiple sensory-and motor-related functions, whereas the LPl takes part in a more visual-specific role. This study enhances our understanding of subcortical neural circuits in the thalamus and may contribute to our exploration of the mechanisms and disorders related to sensory perception and sensory-motor integration.

Intrinsic molecular proton sensitivity underlies GPR4 effects on retrotrapezoid nucleus (RTN) neuronal activation and CO2-stimulated breathing.

An interoceptive homeostatic reflex monitors levels of CO2/H+ to maintain blood gas homeostasis and rapidly regulate tissue acid-base balance by driving lung ventilation and CO2 excretion - this CO2-evoked increase in respiration is the hypercapnic ventilatory reflex (HCVR). Retrotrapezoid nucleus (RTN) neurons provide crucial excitatory drive to downstream respiratory rhythm/pattern-generating circuits, and their activity is directly modulated by changes in CO2/H+ RTN neurons express GPR4 and TASK-2, global deletion of which abrogates CO2/H+ activation of RTN neurons and the HCVR. It has not been determined if the intrinsic pH sensitivity of these proton detectors is required for these effects. We used CRISPR/Cas9 genome editing to generate mice with mutations in either of two pH-sensing histidine residues in GPR4 to determine effects on RTN neuronal CO2/H+ sensitivity and the HCVR. In global GPR4(H81F) and GPR4(H167F) mice, CO2-stimulated breathing and CO2-induced RTN neuronal activation were strongly blunted, with no effect on hypoxia-stimulated breathing. In brainstem slices from GPR4(H81F) mice, peak firing of RTN neurons during bath acidification was significantly reduced compared to GPR4 wild type mice, and a subpopulation of RTN neurons was rendered pH-insensitive, phenocopying previous results from GPR4-deleted mice. These effects were independent of changes in RTN number/distribution, neuronal excitability or transcript levels for GPR4 and TASK-2. CO2-stimulated breathing was reduced to a similar extent in GPR4(H81F) and TASK-2-deleted mice, with combined mutation yielding no additional deficit in the HCVR. Together, these data demonstrate that the intrinsic pH sensitivity of GPR4 is necessary for full elaboration of the HCVR.Significance Statement Among the critical mechanisms for whole-body homeostasis, the hypercapnic ventilatory reflex (HCVR) regulates lung ventilation in order to maintain physiological levels of arterial PCO2 and acid-base balance. GPR4 is a proton-activated receptor and putative molecular proton sensor in retrotrapezoid nucleus (RTN) neurons, which are a crucial neural component of this respiratory reflex. In this work, we developed multiple lines of mice in which the intrinsic pH sensitivity of GPR4 was globally disabled by mutations in key histidine residues; in those mice, CO2/H+-sensitivity of RTN neurons and the HCVR were strongly blunted. These data support a role for GPR4 as a direct molecular sensor for CO2/H+ in support of this important homeostatic reflex.

Study on the involvement of microglial S100A8 in neuroinflammation and microglia activation during migraine attacks

BackgroundMicroglia is the primary source of inflammatory factors during migraine attacks. This study aims to investigate the role of microglia related genes (MRGs) in migraine attacks. MethodsThe RNA sequencing results of migraineurs and the panglaodb database were used to obtain differentially expressed genes (DEGs) in migraine related to microglia. A migraine rat model was established for validating and localizing of the MRGs, and subsequent screening for target genes was conducted. A shRNA was designed to interference the expression of target genes and administered into the trigeminal ganglion (TG) of rats. Pain sensitivity in rats was evaluated via the hot water tail-flick (HWTF) and formalin-induced pain (FIP) experiments. ELISA was used to quantify the levels of inflammatory cytokines and CGRP. WB and immunofluorescence assays were applied to detect the activation of microglia. ResultsA total of five DEGs in migraine related to microglia were obtained from RNA sequencing and panglaodb database. Animal experiments showed that these genes expression were heightened in the TG and medulla oblongata (MO) of migraine rats. The gene S100A8 co-localized with microglia in both TG and MO. The HWTF and FIP experiments demonstrated that interference with S100A8 alleviated the sense of pain in migraine rats. Moreover, the levels of TNFα, IL-1β, IL-6, and CGRP in the TG and MO of rats in the model rats were increased, and the expression of microglia markers IBA-1, M1 polarization markers CD86 and iNOS was upregulated. Significantly, interference with S100A8 reversed these indicators. ConclusionInterference with S100A8 in microglia increased the pain threshold during migraine attacks, and inhibited neuroinflammation and microglia activation.

Tracheoplasty should be proactively considered within the surgical strategy for treating the ring-sling complex

To examine the safety and effectiveness of proactive tracheoplasty for pediatric ring-sling complex. We retrospectively collected data from 304 children who were diagnosed with a ring-sling complex and underwent surgery at 3 cardiac centers in China between January 2010 and June 2023. The children were categorized into 3 surgical groups: concurrent sling and tracheal surgery (group A; n=258), staged sling and tracheal surgery (group B; n=25), and sling-only surgery (group C; n=21). We compared perioperative clinical characteristics, tracheal morphology changes, and outcomes across the 3 groups. The median age of the children was 1.2years (interquartile range, [IQR], 0.7-1.9years). The anomalous tracheobronchial arborization rates were higher in group A (52.5%) and group B (60.0%) compared to group C (15.0%). The preoperative narrow-wide ratio (NWR) was lower in groups A and B than in group C, with values of 0.44 (IQR, 0.35-0.52), 0.44 (IQR, 0.33-0.59), and 0.68 (IQR, 0.54-0.72), respectively (P<.001). Preoperative subcarina angles were similar among the groups (P=.54). After specific surgeries, the NWR and subcarina angle were improved significantly in groups A and B but not in group C. There were 7 in-hospital deaths and 2 postdischarge deaths. Respiratory symptoms improved in groups A and B, but 7 children in group C remained in respiratory dysfunction. Six children presented with residual stenosis of the left pulmonary artery. Concurrent sling and tracheal surgeries for children with the ring-sling complex are safe and effective and are especially preferable for those with NWR ≤0.6, long-segment or diffuse tracheal stenosis, anomalous tracheobronchial arborization, and pronounced respiratory symptoms.

The Effectiveness of Leadership Interventions on Cardiologists' Performance Using Benchmarking as a Tool.

Aligned with the Health Sector Transformation Strategy of Saudi Vision 2030, the study analyzed the attitudes and behaviors of cardiologists toward change and identified factors that could either facilitate or hinder the success of leadership interventions. At our cardiac center, the cath lab department is at the forefront of operations, accounting for 80% of the procedures. Our team members may not be fully equipped with the necessary attitudes and behaviors to drive successful improvement projects. Therefore, our top priority is ensuring they remain productive and engaged throughout the process. This is especially crucial because 60% of our budget is allocated to the cath lab department. The study aimed to assess the effectiveness of a leadership intervention on cardiologists' performance in terms of safety, speed, and cost. The research analyzed the behavior and attitude of cardiologists towards change and encouraged progress and collaborative learning between doctors, using benchmarking as a tool. Besides, the study sought to determine the contribution of the interventions used to overall efficiency in performing interventions. This case study focuses on four main aspects of the program. First, it aims to explore an innovative approach to improving the PSCCQ cath lab for patients. Second, it assesses the collective effort of all participants involved in the program. Third, it analyzes the program results and compares them with those of international experiences. And finally, it examines the program's potential benefits for our patients. The study's objectives were evaluated through qualitative analysis of in-depth interviews and quantitative data analysis of three variables in the cath lab: radiation dose, time, and inventory. The reason for using mixed methods was to comprehensively understand the same concept from different angles. According to the study, participants improved the safety and effectiveness of our cath lab by reducing the radiation dose and its cost. The study revealed a 52% decrease in the radiation dose for diagnostic cases and an 11% decrease for interventional cases. Similarly, the cost of the radiation dose decreased by 28% for diagnostic cases and 11% for interventional cases. During the observation, it was noted that the participants were highly engaged and willing to adapt to the situation. Some even viewed it as an opportunity for personal growth and improvement in the cath lab. However, they stressed the significance of awareness as a crucial element in improving their behavior and reinforcing it as the foundation for maintaining progress. Furthermore, the study revealed that collaborative work among the participants could have been more optimal. The study concludes that implementing innovative improvements to the cath lab was a necessary yet complex undertaking. Participants were more inclined to embrace the changes when they were easily understandable and motivating. The study recommends the appointment of a change agent, the establishment of benchmarks, and the creation of a collaborative working environment between leaders and staff. Above all, the leader should support and sponsor the change to facilitate the transition at various levels.

Relationship of left ventricular diastolic dysfunction with quality of life in heart failure patients with reduced ejection fraction (HFrEF).

Heart failure is a complex clinical manifestation due to diastolic dysfunction and systolic dysfunction of the left ventricle (LV). Diastolic dysfunction of the LV plays an important role in worsening the quality of life (QoL) in heart failure patients. The aim of this study was to assess the relationship between the severity or grade of LV diastolic dysfunction and QoL in heart failure with reduced ejection fraction (HFrEF) patients. A retrospective cohort study was conducted at the Cardiac Center of H. Adam Malik Hospital, Medan, Indonesia, from January 2022 to December 2022. This study included inpatients and outpatients aged above 18 years who were diagnosed with HFrEF, identified by echocardiography with an ejection fraction of ≤40%. Echocardiography was performed to evaluate left ventricular diastolic dysfunction, and QoL was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) 6-12 months after the severity of LV diastolic dysfunction was confirmed. The MLHFQ was classified into good and poor QoL. The severity of LV diastolic function was measured using the E/A ratio, mean E/e' ratio, tricuspid regurgitation velocity (TR Vmax), and left atrial volume index (LAVI), and was classified into grades I, II, and III. The relationships between the severity of diastolic dysfunction and other factors with QoL were measured using Chi-squared, Fisher's exact test, or Mann-Whitney test, as appropriate. A total of 96 patients were included in the study, of which 56 (58.3%) patients had grade I, 12 (12.5%) had grade II, and 28 (29.2%) patients had grade III of LV diastolic dysfunction. There were 77 (80.2%) and 19 (19.8%) patients with good and poor QoL, respectively. This study revealed a significant relationship between the severity of LV diastolic dysfunction and QoL in HFrEF patients with p=0.040. In conclusion, the degree of LV diastolic dysfunction is related to the QoL of HFrEF patients and therefore better comprehensive management strategies should be considered in HFrEF cases to address the impact of LV diastolic dysfunction on QoL.

Clonal haematopoiesis is associated with major adverse cardiovascular events in patients with hypertrophic cardiomyopathy.

The heterogeneous phenotype of hypertrophic cardiomyopathy (HCM) is still not fully understood. Clonal haematopoiesis (CH) is emerging as a cardiovascular risk factor potentially associated with adverse clinical events. The prevalence, phenotype and outcomes related to CH in HCM patients were evaluated. Patients with HCM and available biospecimens from the Peter Munk Cardiac Centre Cardiovascular Biobank were subjected to targeted sequencing for 35 myeloid genes associated with CH. CH prevalence, clinical characteristics, morphological phenotypes assessed by echocardiogram and cardiac magnetic resonance and outcomes were assessed. All patients were evaluated for a 71-plex cytokines/chemokines, troponin I and B-type natriuretic peptide analysis. Major adverse cardiovascular events (MACE) were defined as appropriate implantable cardioverter-defibrillator shock, stroke, cardiac arrest, orthotopic heart transplant and death. Among the 799 patients, CH was found in 183 (22.9%) HCM patients with sarcomeric germline mutations. HCM patients with CH were more symptomatic and with a higher burden of fibrosis than those without CH. CH was associated with MACE in those HCM patients with sarcomeric germline mutations (adjusted hazard ratio [HR] 6.89, 95% confidence interval [CI] 1.78-26.6; p = 0.005), with the highest risk among those that had DNMT3A, TET2 and ASXL1 mutations (adjusted HR 5.76, 95% CI 1.51-21.94; p = 0.010). Several cytokines (IL-1ra, IL-6, IL-17F, TGFα, CCL21, CCL1, CCL8, and CCL17), and troponin I were upregulated in gene-positive HCM patients with CH. These results indicate that CH in patients with HCM is associated with worse clinical outcomes. In the absence of CH, gene-positive patients with HCM have lower rates of MACE.

Total Arterial Multivessel Minimally Invasive Coronary Artery Bypass Surgery: 5-Year Outcomes

BackgroundTotal arterial revascularization is associated with superior outcomes to conventional coronary artery bypass graft (CABG) surgery performed with the left internal thoracic artery (ITA) and veins. It is often performed with bilateral ITAs that increase risk of sternal wound infection. Minimally invasive multivessel CABG through a left anterior minithoracotomy eliminates sternal wound complications. However, being performed only in a few specialized centers, there is a paucity in follow-up outcome data. We, therefore, describe our 5-year single-center experience with such operations. MethodsBetween 2015 and 2021, 186 patients underwent elective, total arterial minimally invasive CABG in our institution. Patient data were prospectively collected in the institutional database and retrospectively analyzed. Primary end points were in-hospital mortality and 5-year survival. The secondary end points included freedom from major adverse cerebrovascular and cardiac events. ResultsPatients were a mean age of 66 ± 9 years, and 23 (12%) were women. The mean number of bypass grafts performed was 2.4 ± 0.5 (range, 2-4 grafts). Bilateral ITAs were used in 163 patients (88%) and left ITA and radial arteries in 22 (12%). The mean procedure time was 277 ± 58 minutes. There was 1 hospital death. Perioperative myocardial infarction, repeat thoracotomy, and conversion to sternotomy was observed in 6 (3%), 12 (6.5%), and 2 patients (1.1%), respectively. The mean 5-year survival was 93.3% ± 2.2%, and freedom from major adverse cardiac and cerebrovascular events was 83.8% ± 4.1%. ConclusionsTotal arterial minimally invasive CABG is a feasible surgical approach yielding excellent short- and midterm results when performed in selected patients in specialized high-volume cardiac centers.

Predictors of complications and mortality among patients undergoing pacemaker implantation in resource-limited settings: a 10-year retrospective follow-up study

IntroductionPacemakers (PMs) are used to treat patients with severe bradycardia symptoms. They do, however, pose several complications. Even with these risks, there are only a few studies assessing PM implantation outcomes in resource-limited settings like Ethiopia and other sub-Saharan countries in general. Therefore, this study aims to assess the mid-term outcome of PM implantation in patients who have undergone PM implantation in the Cardiac Center of Ethiopia by identifying the rate and predictors of complications and death.MethodologyThis retrospective study was conducted at the Cardiac Center of Ethiopia from October 2023 to January 2024 on patients who had PM implantation from September 2012 to August 2023 to assess the midterm outcome of the patients. Complication rate and all-cause mortality rate were the outcomes of our study. Multivariable logistic regression was used to identify factors associated with complications and death. To analyze survival times, a Kaplan–Meier analysis was performed.ResultsThis retrospective follow-up study included 182 patients who underwent PM implantation between September 2012 and August 2023 and were at least 18 years old. The patients' median follow-up duration was 72 months (Interquartile range (IQR): 36–96 months). At the end of the study, 26.4% of patients experienced complications. The three most frequent complications were lead dislodgement, which affected 6.6% of patients, PM-induced tachycardia, which affected 5.5% of patients, and early battery depletion, which affected 5.5% of patients. Older age (Adjusted Odds Ratio (AOR) 1.1, 95% CI 1.04–1.1, p value < 0.001), being female (AOR 4.5, 95%CI 2–9.9, p value < 0.001), having dual chamber PM (AOR 2.95, 95%CI 1.14–7.6, p value = 0.006) were predictors of complications. Thirty-one (17%) patients died during the follow-up period. The survival rates of our patients at 3, 5, and 10 years were 94.4%, 92.1%, and 65.5% respectively with a median survival time of 11 years. Patients with a higher Charlson comorbidity index before PM implantation (AOR 1.2, 95% CI 1.1–1.8, p = 0.04), presence of complications (AOR 3.5, 95% CI 1.2–10.6, p < 0.03), and New York Heart Association (NYHA) class III or IV (AOR 3.3, 95% CI 1.05–10.1, p = 0.04) were associated with mortality.ConclusionMany complications were experienced by patients who had PMs implanted, and several factors affected their prognosis. Thus, it is essential to identify predictors of both complications and mortality to prioritize and address the manageable factors associated with both mortality and complications.

A comparative assessment of age-related nicotinamide adenine dinucleotide phosphate-diaphorase positivity in the spinal cord and medulla oblongata of pigeons, rats, and mice.

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (N-d) positive neurons have been extensively studied across various animals, and N-d neurodegenerative neurites have been detected in some aged animal models. However, detailed knowledge on N-d positivity and aging-related alterations in the spinal cord and medulla oblongata of pigeons is limited. In this study, we investigated N-d positivity and age-related changes in the pigeon's spinal cord and medulla oblongata and compared them to those in rats and mice. Pigeons, had more N-d neurons in the dorsal horn, around the central canal, and in the column of Terni in the thoracic and lumbar segments, with scattered neurons found in the ventral horn of the spinal segments. N-d neurons were also present in the white matter of the spinal cord. Morphometric analysis revealed that the size of N-d soma in the lumbosacral, cervical, and thoracic regions was substantially altered in aged pigeons compared to young birds. Furthermore, the lumbar to sacral segments underwent significant morphological alterations. The main findings of this study were the presence of age-related N-d positive bodies (ANB) in aged pigeons, predominantly in the external cuneate nucleus (CuE) and occasionally in the gracilis and CuEs. ANBs were also identified in the gracile nuclei and spinal cord in the aged rats and mice, whereas in aged rats, ANBs were detected in the CuE spinal nucleus. Immunohistochemistry showed that the age-related alterations occurred in the cell types and neuropeptides in old animals. The results suggest weak inflammatory response and neuronal dysfunction in the spinal cord in aged pigeons. Our results suggested that the ANB could be a potential aging marker for the central nervous system.

Cardiac (tele)rehabilitation in routine clinical practice for patients with coronary artery disease: protocol of the REHAB + trial.

Cardiac rehabilitation programs face the challenge of suboptimal participation, despite being a level Ia recommendation. Cardiac telerehabilitation, with its potential to engage patients who might otherwise not show interest, necessitates the adaption of existing center-based cardiac rehabilitation programs to facilitate rehabilitation at home. REHAB + is a mobile cardiac telerehabilitation program cocreated with patients and rehabilitation centers, aiming to future-proof cardiac rehabilitation and improve accessibility. The REHAB + application enables users to remotely communicate with their coach, receive on-demand feedback on health goal progression, and reduces the need for frequent in-person meetings at the cardiac rehabilitation center. The REHAB + study seeks to compare patient-related outcomes and characteristics of patients between those offered the option to participate in cardiac telerehabilitation and those attending center-based cardiac rehabilitation over a twelve-month period. The REHAB + study is a multicenter, prospective, matched controlled, observational study that includes (N)STEMI patients eligible for cardiac rehabilitation. We aim to enroll 300 participants for cardiac telerehabilitation and 600 for center-based cardiac rehabilitation. Participants opting for cardiac telerehabilitation (REHAB+) will be matched with center-based cardiac rehabilitation participants. Additionally, characteristics of patients unwilling to participate in either center-based rehabilitation or telerehabilitation but are willing to share their demographics will be collected. The primary endpoint is quality of life measured with the SF-36 questionnaire at three and twelve months, with patient-related characteristics driving intervention choice as the most important secondary endpoint. Secondary endpoints include physical activity, modifiable risk factors, and digital health experience. The trial is registered at clinicaltrials.gov with registration number NCT05207072. The REHAB + trial is unique by offering patients freedom to choose between cardiac telerehabilitation and center-based rehabilitation. The integration of digital components into cardiac rehabilitation has the potential to complement behavioral change strategies for specific patient groups. Offering patients the option of cardiac telerehabilitation next to center-based rehabilitation could enhance overall cardiac rehabilitation participation rates.