How Will Genetics Inform the Clinical Care of Atrial Fibrillation?

Susceptibility to atrial fibrillation (AF) is determined by well-recognized risk factors such as diabetes mellitus or hypertension, emerging risk factors such as sleep apnea or inflammation, and increasingly well-defined genetic variants. As discussed in detail in a companion article in this series, studies in families and in large populations have identified multiple genetic loci, specific genes, and specific variants increasing susceptibility to AF. Since it is becoming increasingly inexpensive to obtain genotype data and indeed whole genome sequence data, the question then becomes to define whether using emerging new genetics knowledge can improve care for patients both before and after development of AF. Examples of improvements in care could include identifying patients at increased risk for AF (and thus deploying increased surveillance or even low-risk preventive therapies should these be available), identifying patient subsets in whom specific therapies are likely to be effective or ineffective or in whom the driving biology could motivate the development of new mechanism-based therapies or identifying an underlying susceptibility to comorbid cardiovascular disease. While current guidelines for the care of patients with AF do not recommend routine genetic testing, this rapidly increasing knowledge base suggests that testing may now or soon have a place in the management of select patients. The opportunity is to generate, validate, and deploy clinical predictors (including family history) of AF risk, to assess the utility of incorporating genomic variants into those predictors, and to identify and validate interventions such as wearable or implantable device-based monitoring ultimately to intervene in patients with AF before they present with catastrophic complications like heart failure or stroke.

The impact of socioeconomic status on stage at presentation, receipt of diagnostic imaging, receipt of treatment and overall survival in colorectal cancer patients.

Socioeconomic factors influence patterns of care in colorectal cancer. Our study investigates the impact of socioeconomic status (SES) on stage at presentation, receipt of diagnostic imaging, receipt of treatment and overall survival (OS) in a universal healthcare system. The Ontario Cancer Registry (OCR) was accessed to identify a cohort of patients diagnosed with colorectal adenocarcinoma from 2007 to 2016 in Ontario, Canada. SES was measured using median neighborhood income divided into quintiles (Q1-Q5; Q1 = lowest income). Logistic regression analyses were used to evaluate stage, imaging and treatment. Cox proportional hazards models were used to evaluate OS. All endpoints were adjusted for demographics and comorbidities with OS models also adjusting for stage, imaging and treatment. In total, 39 802 colon and 13 164 rectal patients were identified. Lower SES was associated with advanced stage at presentation in both cohorts (Q1 vs Q5: Colon odds ratio [OR] = 1.08, P = .046, rectal OR = 1.25, P < .0001). Lower SES colon patients were less likely to receive adjuvant oxaliplatin (Q1 vs Q5: OR = 0.78, P < .001) and all palliative chemotherapies studied including oxaliplatin (Q1 vs Q5: OR = 0.60, P < 0.0001), irinotecan (Q1 vs Q5: OR = 0.65, P < .0001), bevacizumab (Q1 vs Q5: OR = 0.70, P < .001), cetuximab (Q1 vs Q5: OR = 0.40, P = .0053) and panitumumab (Q1 vs Q5: OR = 0.54, P = .0036). In rectal patients, lower SES was associated with decreased receipt of rectal cancer resection for stages I-III (Q1 vs Q5: OR = 0.78, P < .001), adjuvant oxaliplatin (Q1 vs Q5: OR = 0.72, P = .0020) and palliative chemotherapies including oxaliplatin (Q1 vs Q5: OR = 0.59, P < .001), irinotecan (Q1 vs Q5: OR = 0.53, P < .001) and bevacizumab (Q1 vs Q5: OR = 0.71, P = .046). All survival models identified poorer OS for lower SES patients (total colorectal; Q1 vs Q5: Hazard ratio [HR] = 1.25, P < .0001). These findings suggest disparities persist even within universal healthcare.

Cranio-spinal Rosai Dorfman disease: case series and literature review.

Rosai-Dorfman disease (RDD) is a rare condition similar to lymphomas, presenting with cervical lymphadenopathy in young adults. Extra-nodal involvement is relatively common but involvement of the central nervous system (CNS) is rare. Cranial RDD presents with symptoms of raised intracranial pressure, focal or generalised seizures, while spinal RDD presents with pain, peripheral neurological deficits and radiculopathy. In contrast to other similar neoplastic or degenerative conditions affecting the CNS, RDD is a benign, non-infective, granulomatous disorder. Radiologically cranio-spinal RDD often mimics commoner dural-based lesions like meningioma, with only subtle radiological differentiating findings on Magnetic Resonance Imaging (MRI). The histopathology of RDD is diagnostic. Surgical excision is preferred modality of treatment. However, adjuvant therapies like steroids and radiation may help controlling residual or recurrent disease. There are multiple sporadic reports and short case publications in the literature, often focusing on a particular aspect of RDD. In this study, authors aim to present five cases of craniospinal RDD, and comprehensive review of literature and highlight neurological complications of systemic RDD.

Phrenic Relocation by Endoscopy, Intentional Pneumothorax Using Carbon Dioxide, and Single Lung Ventilation (PHRENICS) Technique.

Strategies to prevent right phrenic nerve (PN) injury during catheter ablation can be difficult to employ, ineffective, and risky. A novel PN-sparing technique involving single lung ventilation followed by "intentional pneumothorax" was prospectively evaluated in patients with multidrug refractory periphrenic atrial tachycardia (AT). This hybrid technique, termed PHRENICS (Phrenic Relocation by Endoscopy & Intentional Pneumothorax using Carbon Dioxide & Single Lung Ventilation), resulted in effective PN relocation away from the target site in all cases, allowing successful catheter ablation of AT without procedural complication or arrhythmia recurrence. The PHRENICS hybrid ablation technique can effectively mobilize the PN, avoiding unnecessary invasion of the pericardium, and can expand the safety of catheter ablation for periphrenic AT.

Hybrid Ablation for Atrial Fibrillation: Safety & Efficacy of Unilateral Epicardial Access.

Hybrid ablation combines thoracoscopic epicardial ablation with percutaneous catheter based endocardial ablation for the treatment of AF. The purpose of this study was to evaluate the safety and efficacy of hybrid ablation surgery for the treatment of atrial fibrillation (AF), and to compare outcomes of unilateral vs bilateral thoracoscopic epicardial ablation. Patients with documented AF who underwent hybrid ablation were followed post-operatively for major events. Major events were classified into 2 categories consisting of (1) safety, comprising all-cause mortality and major morbidities, and (2) efficacy, which included recurrence of atrial arrhythmia, cessation of antiarrhythmic drugs (AAD), and completeness of lesion set. A total of 84 consecutive patients were consented for hybrid ablation. Patients presented with an average AF duration of 85.9 months before hybrid ablation. 80 patients underwent successful thoracoscopic epicardial ablation. At 1-year, 87% (60/69) of patients were free from AF and 73% (50/69) were free from AF and off AAD. 63 patients completed both epicardial and endocardial hybrid ablation with posterior wall isolation achieved in 89% (56/63) of patients. Unilateral epicardial ablation was associated with significantly shorter hospital length of stay compared to bilateral surgical approached (3.9 vs 6.7 days, p = 0.002) with no difference in freedom from AF between groups at 1 year. Hybrid ablation for atrial fibrillation is effective for patients at high risk for recurrence after catheter ablation. The unilateral surgical approach may be associated with shorter hospital stay with no appreciable effect on procedure success rates.

Non-malignant gall bladder perforation: Our experience from an institution-based retrospective analysis of 25 cases.

Gallbladder perforation still continues to perplex surgeons; 25 such patients diagnosed either pre- or intra-operatively and managed at our institute over the last 10 years period were analysed. Only eight were diagnosed pre-operatively, while a large majority (17) had a wrong initial working diagnosis. Symptoms and signs were variable. No blood investigation was specific. A computed tomography scan was generally better than ultrasound in detecting the perforation. All our cases were managed operatively with no mortality and a mean duration of hospital stay of 6.8 days. Most perforations were extra-hepatic (84%) and those of Niemeier's type I (52.2%). Because of its varied clinical presentation, gallbladder perforation is often an intra-operative diagnosis, but early intervention carries a good outcome.

Mapping Atrial Fibrillation After Surgical Therapy to Guide Endocardial Ablation.

BACKGROUND: Surgical ablation for atrial fibrillation (AF) can be effective, yet has mixed results. It is unclear which endocardial lesions delivered as part of hybrid therapy' will best augment surgical lesion sets in individual patients. We addressed this question by systematically mapping AF endocardially after surgical ablation and relating findings to early recurrence, then performing tailored endocardial ablation as part of hybrid therapy. METHODS: We studied 81 consecutive patients undergoing epicardial surgical ablation (stage 1 hybrid), of whom 64 proceeded to endocardial catheter mapping and ablation (stage 2). Stage 2 comprised high-density mapping of pulmonary vein (PV) or posterior wall (PW) reconnections, low-voltage zones (LVZs), and potential localized AF drivers. We related findings to postsurgical recurrence of AF. RESULTS: Mapping at stage 2 revealed PW isolation reconnection in 59.4%, PV isolation reconnection in 28.1%, and LVZ in 42.2% of patients. Postsurgical recurrence of AF occurred in 36 patients (56.3%), particularly those with long-standing persistent AF (P=0.017), but had no relationship to reconnection of PVs (P=0.53) or PW isolation (P=0.75) when compared with those without postsurgical recurrence of AF. LVZs were more common in patients with postsurgical recurrence of AF (P=0.002), long-standing persistent AF (P=0.002), advanced age (P=0.03), and elevated CHA2DS2-VASc (P=0.046). AF mapping revealed 4.4±2.7 localized focal/rotational sites near and also remote from PV or PW reconnection. After ablation at patient-specific targets, arrhythmia freedom at 1 year was 81.0% including and 73.0% excluding previously ineffective antiarrhythmic medications. CONCLUSIONS: After surgical ablation, AF may recur by several modes particularly related to localized mechanisms near low voltage zones, recovery of posterior wall or pulmonary vein isolation, or other sustaining mechanisms. LVZs are more common in patients at high clinical risk for recurrence. Patient-specific targeting of these mechanisms yields excellent long-term outcomes from hybrid ablation.

Angioma serpiginosum in zosteriform distribution on abdomen: A rare presentation.

Angioma serpiginosum is a rare benign nevoid disorder affecting the small vessels of the upper dermis. We are presenting a case of this rare disease in an 11-year-old girl who presented with this condition on abdomen in zosteriform pattern which is rare presentation and is the first of its type.

Rate of COVID-19 Infection in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) in patients with ST-segment elevation myocardial infarction (STEMI) has not been fully described. METHODS: All patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in Ontario, Canada between March 1 and September 30, 2020 were included. Rates of positive COVID-19 tests from January 1, 2020 to the date of STEMI presentation were ascertained. For comparison, COVID-19 results were also evaluated in the adult Ontario population between January 1, 2020 and September 30, 2020, using provincial laboratory testing data. RESULTS: There were 3606 unique patients presenting with STEMI and receiving PCI in Ontario, Canada during the study period. Sixteen patients (0.44%) tested positive for COVID-19. The background infection rate among all 12,448,541 Ontario residents was similar, at 0.34%. CONCLUSIONS: The results of this population-based analysis suggest that proceeding with primary PCI with appropriate infection control practices is reasonable when community infection rates are low.

CONTEXTE: L'incidence de la maladie à coronavirus 2019 (COVID-19) chez les patients présentant un infarctus du myocarde avec élévation du segment ST (STEMI) n'a pas été entièrement décrite. MÉTHODOLOGIE: Tous les patients atteints de STEMI ayant subi une intervention coronarienne percutanée (ICP) primaire en Ontario (Canada) entre le 1er mars et le 30 septembre 2020 ont été inclus. Les taux de tests positifs à la COVID entre le 1er janvier 2020 et le moment de la présentation du STEMI ont été vérifiés. Aux fins de comparaison, les résultats des tests de dépistage de la COVID-19 ont également été évalués au sein de la population adulte de l'Ontario entre le 1er janvier 2020 et le 30 septembre 2020 au moyen des données des laboratoires provinciaux. RÉSULTATS: Pendant la période d'étude, 3 606 patients présentant un STEMI et ayant subi une ICP en Ontario (Canada) ont été recensés. Seize patients (0,44 %) ont reçu un résultat positif au test de dépistage de la COVID-19. Le taux d'infection parmi les 12 448 541 résidents de l'Ontario était similaire, soit 0,34 %. CONCLUSIONS: Les résultats de cette analyse populationnelle portent à penser qu'il est raisonnable de procéder à une ICP primaire avec des mesures appropriées de contrôle des infections lorsque les taux d'infection dans la collectivité sont faibles.

Antiarrhythmic drug loading at home using remote monitoring: a virtual feasibility study during COVID-19 social distancing.

The epidemiological necessity for distancing during the COVID-19 pandemic has resulted in postponement of non-emergent hospitalizations and increase use of telemedicine. The feasibility of virtual antiarrhythmic drug (AAD) loading specifically with digital QTc electrocardiographic monitoring (EM) in conjunction with telemedicine video visits is not well established. We tested the hypothesis that existing digital health technologies and virtual communication platforms could provide EM and support medically guided AAD loading for patients with symptomatic tachyarrhythmia in the ambulatory setting, while reducing physical contact between patient and healthcare system. A prospective pilot, case series was approved by the institutional ethics committee, entailing three subjects with symptomatic arrhythmia during the COVID-19 pandemic who were enrolled for virtual AAD loading at home. Clinicians met with participants twice daily via video visits conducted after QTc analysis (Kardia 6L mobile sensor) and telemetry review (Mobile Cardiac Outpatient Telemetry of silent arrhythmias). Participants received direct instruction to either terminate the study or proceed with the next single dose of AAD. All participants completed contactless loading of five AAD doses, without untoward event. Scheduled video visits allowed dialogue and participant counselling where decision-making was guided by remote review of EM. Participant adherence with transmissions and scheduled visits was 98.3%; a single electrocardiogram was delayed beyond the 2 hours of post-dose schedule. This virtual approach reduced overall expenditures based on retrospective comparison with previous AAD load hospitalizations. We found that a 'virtual hospitalization' for AAD loading with remote EM and twice-daily virtual rounding is feasible using existing digital health technologies.

Substrate Characterization and Outcomes of Ventricular Tachycardia Ablation in TTN (Titin) Cardiomyopathy: A Multicenter Study.

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The cost of chemotherapy administration: a systematic review and meta-analysis.

PURPOSE: Cancer treatment is a significant driver of healthcare costs worldwide, however, the economic impact of treating patients with anti-neoplastic agents is poorly elucidated. We conducted a systematic review and meta-analysis to estimate the direct costs associated with administering intravenous chemotherapy in an outpatient setting. METHODS: We systematically searched four databases from 2010 to present and extracted hourly administration costs and the respective components of each estimate. Separate analyses were conducted of Canadian and United States (US) studies, respectively, to address a priori hypotheses regarding heterogeneity amongst estimates. The Drummond checklist was used to assess risk-of-bias. Data were summarized using medians with interquartile ranges and five outliers were identified; costs were presented in 2019 USD. RESULTS: Forty-four studies were analyzed, including sub-analyses of 19 US and seven Canadian studies. 26/44 studies were of moderate-high quality. When components of administration cost were evaluated, physician costs were reported most frequently (24 studies), followed by lab tests (13) and overhead costs (9). The median estimate (excluding outliers) was $142/hour (IQR = $103-166). The median administration cost in the US was $149/hour (IQR = $118-158), and was $128/hour (IQR = $102-137) in Canada. CONCLUSIONS: There is currently a paucity of literature addressing the costs of chemotherapy administration, and existing studies utilize a patchwork of reporting methodologies which renders direct comparison challenging. Our results demonstrate that the cost of administering chemotherapy is approximately $125-150/hour, globally. This value is dependent upon the region of analysis, inclusiveness of cost subcomponents as well as the methodology used to estimate unit prices, as described here.

Surgical management of intracranial aneurysms previously treated with endovascular therapy.

Endovascular treatment with coils of cerebral aneurysm is being increasingly used for definitive treatment. An increasing number of patients are coming for surgical intervention either for recurrences, incomplete coil embolization or its complications. Our objective was to assess the surgical management in such patients. This was a retrospective analysis of the patients who were initially treated with endovascular embolization and later managed surgically with clipping either for unsuccessful coiling, recurrence of aneurysm or post-procedural complication, between 2003 and 2007. Anatomical results were excellent in all five patients, and all the aneurysms were totally excluded from the circulation. All patients had good recovery. None of the patients suffered any major intraoperative or postoperative complication. Neurosurgical management of intracranial aneurysms previously treated with endovascular therapy is an emerging challenge, but with proper patient selection and careful planning, this subset of aneurysms can be managed with good results.

Metastatic adenocarcinoma of bilateral cavernous sinus and optic nerve with unknown primary mimicking orbital pseudotumor.

Bilateral cavernous sinus and optic nerve metastases is extremely rare. We report an extremely rare case of metastatic adenocarcinoma of bilateral cavernous sinus and optic nerve with unknown primary presenting as orbital pseudotumor. She underwent bilateral optic nerve decompression and the diagnosis was established by biopsy.

Effect of local bee honey on dihydrofolate reductase enzyme inhibitor-induced mucositis: A histological study on albino wistar rats.

INTRODUCTION: Mucositis is a common complication in around 40% of patients receiving chemotherapy which profoundly impact the quality of life. Despite the availability of many therapeutic agents that claim to prevent or reduce the severity of oral mucositis, no intervention that is completely successful at preventing oral mucositis exists. The present study aimed to demonstrate the effect of local honey on methotrexate-induced mucositis of the tongue. MATERIALS AND METHODS: The study was done in albino rats (n = 24), divided into four groups: honey-normal saline group (H/NS), distilled water-NS group (DW/NS), DW-methotrexate group (DW/MTX), and H/MTX group. Local honey was given (2.5 g/kg) twice a daily for 8 days. NS or methotrexate (60 mg/kg) interrupted the experiment procedure on day 4. At day 8, rats were sacrificed and middle third of tongue was removed for preparation of histological slides. Slides were examined for inflammatory cell infiltration (ICI), cell vacuolization (CV), congested blood vessels (CBV), thickness of epithelium (both dorsal and ventral mucosa), and thickness keratin. RESULTS: Statistically significant association was found between the groups for ICI and CV, χ2 (3) = 11.97, P= 0.003 for ICI, and χ2 (3) = 8.307, P= 0.023 for CV. Mean number of CBV per microscopic filed was 0.445, 0.389, 1.28, and 0.5 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. Mean value of dorsal epithelial thickness (µm) was 96.78 ± 13.59, 100.50 ± 9.75, 75.53 ± 9.24, and 98.75 ± 10.92 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. Mean value of ventral epithelial thickness (µm) was 70.45 ± 13.60, 58.38 ± 14.26, 37.04 ± 5.37, and 52.80 ± 7.97 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. The thickness of epithelium of DW/MTX group was significantly different from other groups (P < 0.05). CONCLUSION: The present study demonstrated the palliative effect of local honey over the mucositis induced by the chemotherapeutic drug (methotrexate).

Three-Dimensional Printing for Planning of Structural Heart Interventions.

Three-dimensional (3D) printing is a process leading to the creation of a physical 3D model used for teaching, patient education, device evaluation, and procedural planning. 3D printed models of patient-specific anatomy can be generated from 3D transesophageal, cardiac MRI, or cardiac computed tomographic datasets. This article discusses the potential advantages of 3D printing, reviews the different modalities to acquire a 3D dataset, and highlights the application of 3D printing to enhance patient screening and procedural planning in structural heart intervention.