Patients with a high defibrillation threshold: Approaches to management.

Implantable cardioverter-defibrillators (ICDs) have revolutionized the prognosis for patients at elevated risk of ventricular tachyarrhythmias. For safety, defibrillation should be effective with a minimum of 10 J below the device's maximum energy. While modern ICDs rarely deliver ineffective shocks in primary prevention, the surge in managing severe heart failure patients has led to an increased number of patients with high defibrillation thresholds (DFTs). This article elucidates the potential causes of high DFT, including clinical factors, lead and device placement, the presence of a Left Ventricular Assist Device (LVAD), prolonged ventricular arrhythmias, shock vectors, waveform tilt, medications, and manufacturer-specific options. We also detail management strategies, highlighting alternative shock coil placements, practical recommendations, and case studies from our institution. Our management algorithm suggests addressing preventable causes, re-evaluating coil positions, considering non-invasive system modifications, upgrading to a higher-capacity device, and adding extra coil(s).

A case of combined pulmonary vein isolation (PVI) and watchman implant through hepatic vein in a patient with interrupted inferior vena cava (IVC).

This case report describes a successful procedure involving pulmonary vein isolation (PVI) and left atrial appendage (LAA) closure with a watchman device in a 78-year-old male with atrial fibrillation and an interrupted inferior vena cava. Due to the vascular anomaly, a transhepatic approach was used, which proved successful.

Safety and effectiveness of the first contact force ablation catheter with a flexible tip.

Background: Catheter ablation is an established therapy for paroxysmal atrial fibrillation (PAF). The TactiFlex Ablation Catheter, Sensor Enabled (TactiFlex SE) is a next-generation radiofrequency ablation catheter incorporating fiber optics-based contact force-sensing technology with a flexible, laser-cut tip. Objective: The study sought to evaluate the safety and effectiveness of the TactiFlex SE ablation catheter for treatment of drug-refractory PAF. Methods: The TactiFlex AF investigational device exemption was a prospective, nonrandomized, multicenter clinical study. Enrollment began on June 26, 2020 and completed June 18, 2021. Subjects with PAF underwent de novo pulmonary vein isolation and, if indicated, ablation for typical atrial flutter. Subjects were followed for 12 months. Results: Of the 355 subjects enrolled at 37 sites worldwide, 334 underwent ablation with the TactiFlex SE catheter. The Kaplan-Meier estimate of 12-month freedom from AF/atrial flutter (AFL)/atrial tachycardia recurrence was 72.9% (95% confidence interval [CI] 95% CI 67.2%-77.8%) and clinical success was 83.6% (95% CI 95% CI 78.1%-87.2%). As-treated analyses compared subjects treated at high power (left atrium time-averaged power setting 40-50 W; n = 222) vs low power (<40 W; n = 97). The Kaplan-Meier estimate of 12-month freedom from AF/AFL/atrial tachycardia recurrence was 76.4% (95% CI 69.3%-82.0%) and clinical success was 83.9% (95% CI 77.5%-88.6%) in the high-power group compared with 66.8% (95% CI 56.1%-75.5%) and 80.7% (95% CI 70.8%- 87.5%), respectively, in the low-power group. The primary safety event rate in all treated subjects was 4.3%; 4.1% in the HP group and 5.2% in the LP group (P = .7671). Conclusion: TactiFlex SE is safe and effective for treatment of drug-refractory PAF and concomitant AFL and enables more efficient procedures than previous generation catheters.

Correlation between sinus rhythm deceleration zones and critical sites for localized reentrant atrial flutter: A retrospective multicenter analysis.

Background: Atypical left atrial flutter (AFL) may be macroreentrant or spatially localized. The relationship between the critical isthmus (CI) for localized reentry with sinus rhythm (SR) conduction slowing has not been systematically examined. Objective: To examine the correlation between CI sites for localized AFL (L-AFL) and deceleration zones (DZ) identified by isochronal late activation mapping (ILAM) during baseline rhythm. Methods: Patients with localized AFL who underwent high-density activation mapping of both SR and AFL were retrospectively analyzed. L-AFL was defined as reentry restricted to 2 wall segments of the left atrium. CI was defined by activation mapping and sites of successful termination during ablation. DZ, defined as >3 isochrones within 1 cm radius during baseline rhythm, were correlated to the locations of the CI. Results: Thirty-one consecutive patients that underwent detailed sinus rhythm and AFL high-density activation maps were analyzed at 3 centers. A mean 4060 ± 3275 and 6209 ± 8656 points were collected in ILAM and AFL activation maps, respectively. At least 1 DZ (1.7 ± 0.77) was identified in all patients. ILAM showed 3.27 ± 0.52 isochrones per DZ (168 ± 32 ms), and co-localized to CI sites at a distance of 6.7 ± 3 mm. A total of 34% ± 14% of the AFL cycle length was contained within 0.5 cm of the DZ. Conclusions: In patients with L-AFL, CI co-localized with DZ during baseline rhythm, suggesting that DZ mapping during SR may yield candidate targets for ablation as an adjunct to pulmonary vein isolation to prevent a subtype of AFL.

Performance and outcomes of transvenous rotational lead extraction: Results from a prospective, monitored, international clinical study.

BACKGROUND: Transvenous lead extraction (TLE) plays a critical role in managing patients with cardiovascular implantable electronic devices. Mechanical TLE tools, including rotational sheaths, are used to overcome fibrosis and calcification surrounding leads. Prospective clinical data are limited regarding the safety and effectiveness of use of mechanical TLE devices, especially rotational tools. OBJECTIVE: To prospectively investigate the safety and effectiveness of mechanical TLE in real-world usage. METHODS: Patients were enrolled at 10 sites in the United States and Europe to evaluate the use of mechanical TLE devices. Clinical success, complete procedural success, and complications were evaluated through follow-up (median, 29 days). Patient data were source verified and complications were adjudicated by an independent clinical events committee (CEC). RESULTS: Between October 2018 and January 2020, mechanical TLE tools, including rotational sheaths, were used to extract 460 leads with a median indwell time of 7.4 years from 230 patients (mean age 64.3 ± 14.4 years). Noninfectious indications for TLE were more common than infectious indications (61.5% vs 38.5%, respectively). The extracted leads included 305 pacemaker leads (66.3%) and 155 implantable cardioverter-defibrillator leads (33.7%), including 85 leads with passive fixation (18.5%). A bidirectional rotational sheath was needed for 368 leads (88.0%). Clinical success was obtained in 98.7% of procedures; complete procedural success was achieved for 96.3% of leads. CEC-adjudicated device-related major complications occurred in 6 of 230 (2.6%) procedures. No isolated superior vena cava injury or procedural death occurred. CONCLUSION: This prospective clinical study demonstrates that use of mechanical TLE tools, especially bidirectional rotational sheaths, are effective and safe.

Determining Cost-Optimal Next-Generation Sequencing Panels for Rare Disease and Pharmacogenomics Testing.

BACKGROUND: Multi-gene panel sequencing using next-generation sequencing (NGS) methods is a key tool for genomic medicine. However, with an estimated 140 000 genomic tests available, current system inefficiencies result in high genetic-testing costs. Reduced testing costs are needed to expand the availability of genomic medicine. One solution to improve efficiency and lower costs is to calculate the most cost-effective set of panels for a typical pattern of test requests. METHODS: We compiled rare diseases, associated genes, point prevalence, and test-order frequencies from a representative laboratory. We then modeled the costs of the relevant steps in the NGS process in detail. Using a simulated annealing-based optimization procedure, we determined panel sets that were more cost-optimal than whole exome sequencing (WES) or clinical exome sequencing (CES). Finally, we repeated this methodology to cost-optimize pharmacogenomics (PGx) testing. RESULTS: For rare disease testing, we show that an optimal choice of 4-6 panels, uniquely covering genes that comprise 95% of the total prevalence of monogenic diseases, saves $257-304 per sample compared with WES, and $66-135 per sample compared with CES. For PGx, we show that the optimal multipanel solution saves $6-7 (27%-40%) over a single panel covering all relevant gene-drug associations. CONCLUSIONS: Laboratories can reduce costs using the proposed method to obtain and run a cost-optimal set of panels for specific test requests. In addition, payers can use this method to inform reimbursement policy.

Validation of whole genome sequencing from dried blood spots.

BACKGROUND: Dried blood spots (DBS) are a relatively inexpensive source of nucleic acids and are easy to collect, transport, and store in large-scale field surveys, especially in resource-limited settings. However, their performance in whole-genome sequencing (WGS) relative to that of venous blood DNA has not been analyzed for various downstream applications. METHODS: This study compares the WGS performance of DBS paired with venous blood samples collected from 12 subjects. RESULTS: Results of standard quality checks of coverage, base quality, and mapping quality were found to be near identical between DBS and venous blood. Concordance for single-nucleotide variants, insertions and deletions, and copy number variants was high between these two sample types. Additionally, downstream analyses typical of population-based studies were performed, such as mitochondrial heteroplasmy detection, haplotype analysis, mitochondrial copy number changes, and determination of telomere lengths. The absolute mitochondrial copy number values were higher for DBS than for venous blood, though the trend in sample-to-sample variation was similar between DBS and blood. Telomere length estimates in most DBS samples were on par with those from venous blood. CONCLUSION: DBS samples can serve as a robust and feasible alternative to venous blood for studies requiring WGS analysis.

Ultrasensitive detection of tumor-specific mutations in saliva of patients with oral cavity squamous cell carcinoma.

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck malignancy. Although the survival rate of patients with advanced-stage disease remains approximately 20% to 60%, when detected at an early stage, the survival rate approaches 80%, posing a pressing need for a well validated profiling method to assess patients who have a high risk of developing OCSCC. Tumor DNA detection in saliva may provide a robust biomarker platform that overcomes the limitations of current diagnostic tests. However, there is no routine saliva-based screening method for patients with OCSCC. METHODS: The authors designed a custom next-generation sequencing panel with unique molecular identifiers that covers coding regions of 7 frequently mutated genes in OCSCC and applied it on DNA extracted from 121 treatment-naive OCSCC tumors and matched preoperative saliva specimens. RESULTS: By using stringent variant-calling criteria, mutations were detected in 106 tumors, consistent with a predicted detection rate ≥88%. Moreover, mutations identified in primary malignancies were also detected in 93% of saliva samples. To ensure that variants are not errors resulting in false-positive calls, a multistep analytical validation of this approach was performed: 1) re-sequencing of 46 saliva samples confirmed 88% of somatic variants; 2) no functionally relevant mutations were detected in saliva samples from 11 healthy individuals without a history of tobacco or alcohol; and 3) using a panel of 7 synthetic loci across 8 sequencing runs, it was confirmed that the platform developed is reproducible and provides sensitivity on par with droplet digital polymerase chain reaction. CONCLUSIONS: The current data highlight the feasibility of somatic mutation identification in driver genes in saliva collected at the time of OCSCC diagnosis.

Long-term safety and effectiveness of paroxysmal atrial fibrillation ablation using a porous tip contact force-sensing catheter from the SMART SF trial.

PURPOSE: The prospective, multicenter SMART SF trial demonstrated the acute safety and effectiveness of the 56-hole porous tip irrigated contact force (CF) catheter for drug-refractory paroxysmal atrial fibrillation (PAF) ablation with a low primary adverse event rate (2.5%), leading to FDA approval of the catheter. Here, we are reporting the long-term effectiveness and safety results that have not yet been reported. METHODS: Ablations were performed using the 56-hole porous tip irrigated CF catheter guided by the 3D mapping system stability module. The primary effectiveness endpoint was freedom from atrial tachyarrhythmia (including atrial fibrillation, atrial tachycardia, and/or atrial flutter), based on electrocardiographic data at 12 months. Atrial tachyarrhythmia recurrence occurring 3 months post procedure, acute procedural failures such as lack of entrance block confirmation of all PVs, and undergoing repeat procedure for atrial fibrillation in the evaluation period (91 to 365 days post the initial ablation procedure) were considered to be effectiveness failures. RESULTS: Seventy-eight patients (age 64.8 ± 9.7 years; male 52.6%; Caucasian 96.2%) participated in the 12-month effectiveness evaluation. Mean follow-up time was 373.5 ± 45.4 days. The Kaplan-Meier estimate of freedom from 12-month atrial tachyarrhythmia was 74.9%. Two procedure-related pericardial effusion events were reported at 92 and 180 days post procedure. There were no pulmonary vein stenosis complications or deaths reported through the 12-month follow-up period. CONCLUSIONS: The SMART SF 12-month follow-up evaluation corroborates the early safety and effectiveness success previously reported for PAF ablation with STSF.

Voluntary perioperative colorectal cancer registry from Kerala-An initial overview.

BACKGROUND: Although colorectal cancer (CRC) may not be uncommon in India, accurate data regarding its demographics and surgical outcomes is sparse. METHODS: With an aim to assess demographics and perioperative outcomes of CRC in Kerala, all members of Association of Surgical Gastroenterologists of Kerala (ASGK) were invited to participate in a registry. Data of operated cases of CRC were entered on a web-based questionnaire by participating members from January 2016. Analysis of accrued data until March 2018 was performed. RESULTS: From 25 gastrointestinal surgical centers in Kerala, 15 ASGK member hospitals contributed 1018 CRC cases to the database (M:F 621:397; median age-63.5 years [15-95 years]). Rectum (39.88%) and rectosigmoid (20.33%) cancers comprised the majority of the patients. Among them, preoperative bowel preparation was given to 37.68%, minimally invasive surgery (MIS) was performed in 73%, covering stoma in 47% and had an overall leak rate of 3.58%. In colonic malignancies, MIS was performed in 56.74%, covering stoma created in 13% and had a leak rate of 2.71%. Of 406 patients with rectal cancers, neo-adjuvant radiotherapy/chemoradiotherapy was given to 51.23%. The mean hospital stay for MIS in both rectal and colonic cancer patients was significantly shorter than open approach (10.46 ± 5.08 vs. 12.26 ± 6.03 days; p = 0.001and 10.29 ± 4.58 vs. 12.46 ± 6.014 days; p = <0.001). Mortality occurred in 2.2% patients. CONCLUSION: A voluntary non-funded registry for CRC surgery was successfully created. Initial data suggest that MIS was performed in majority, which was associated with shorter hospital stay than open approach. Overall mortality and leak rate appeared to be low.

Ambulatory Monitoring of Heart Sounds via an Implanted Device Is Superior to Auscultation for Prediction of Heart Failure Events.

BACKGROUND: We compared the relationship between the third heart sound (S3) measured by an implantable cardiac device (devS3) and auscultation (ausS3) and evaluated their prognostic powers for predicting heart failure events (HFEs). METHODS AND RESULTS: In the MultiSENSE study, devS3 was measured daily with continuous values, whereas ausS3 was assessed at study visits with discrete grades. They were compared among patients with and without HFEs at baseline and against each other directly. Cox proportional hazard models were developed between follow-up visits and over the whole study. Simulations were performed on devS3 to match the limitations of auscultation. We studied 900 patients, of whom 106 patients experienced 192 HFEs. Two S3 sensing modalities correlated with each other, but at baseline, only devS3 differentiated patients with or without HFEs (P < 0.0001). The prognostic power of devS3 was superior to that of ausS3 both between follow-up visits (HR = 5.7, P < 0.0001, and 1.7, P = 0.047, respectively) and over the whole study (HR = 2.9, P < 0.0001, and 1.4, P = 0.216, respectively). Simulation results suggested this superiority may be attributed to continuous monitoring and to subaudible measuring capability. CONCLUSIONS: S3 measured by implantable cardiac devices has stronger prognostic power to predict episodes of future HFEs than that of auscultation.

Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients.

BACKGROUND: Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. METHODS: We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. CONCLUSION: In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.

Analysis of solid tumor mutation profiles in liquid biopsy.

Liquid biopsy is increasingly gaining traction as an alternative to invasive solid tumor biopsies for prognosis, treatment decisions, and disease monitoring. Matched tumor-plasma samples were collected from 180 patients across different cancers with >90% of the samples below Stage IIIB. Tumors were profiled using next-generation sequencing (NGS) or quantitative PCR (qPCR), and the mutation status was queried in the matched plasma using digital platforms such as droplet digital PCR (ddCPR) or NGS for concordance. Tumor-plasma concordance of 82% and 32% was observed in advanced (Stage IIB and above) and early (Stage I to Stage IIA) stage samples, respectively. Interestingly, the overall survival outcomes correlated to presurgical/at-biopsy ctDNA levels. Baseline ctDNA stratified patients into three categories: (a) high ctDNA correlated with poor survival outcome, (b) undetectable ctDNA with good outcome, and (c) low ctDNA whose outcome was ambiguous. ctDNA could be a powerful tool for therapy decisions and patient management in a large number of cancers across a variety of stages.

Safety and Efficacy of Transvenous Lead Extraction Utilizing the Evolution Mechanical Lead Extraction System: A Single-Center Experience.

OBJECTIVES: The goal of this study is to assess the safety and efficacy of mechanical lead extraction utilizing the Evolution system. BACKGROUND: Compared with other techniques commonly used for lead extraction, data regarding the safety and efficacy of mechanical lead extraction using the Evolution system is limited and needs further evaluation. METHODS: Between June 1, 2009 and September 30, 2016, we retrospectively analyzed 400 consecutive patients who exclusively underwent mechanical lead extraction utilizing the Evolution system. RESULTS: A total of 400 patients underwent mechanical lead extraction of 683 leads. Mean age of extracted leads was 6.77 ± 4.42 years (range 1 to 31 years). The extracted device system was an implantable cardioverter-defibrillator in 274 patients (68.5%) and a pacemaker system in 126 patients (31.5%). Complete lead removal rate was 97% with a clinical success rate of 99.75%. Incomplete lead removal with <4-cm remnant was associated with older leads (lead age >8 years). Failure to achieve clinical success was noted in 1 patient (0.25%). Cardiac papillary avulsion, system-related infection, and cardiac tamponade were the major complications noted in 6 patients (1.5%). Minor complications were encountered in 24 patients (6%), of which hematoma requiring evacuation was the most common minor complication. There were no patient deaths. CONCLUSIONS: In our single-center study, lead extractions utilizing the Evolution mechanical lead extraction system were safe and effective and resulted in high clinical and procedural success, with low complication rates and no fatalities.

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. METHODS: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. CONCLUSION: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.

StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.

Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.

A Multisensor Algorithm Predicts Heart Failure Events in Patients With Implanted Devices: Results From the MultiSENSE Study.

OBJECTIVES: The aim of this study was to develop and validate a device-based diagnostic algorithm to predict heart failure (HF) events. BACKGROUND: HF involves costly hospitalizations with adverse impact on patient outcomes. The authors hypothesized that an algorithm combining a diverse set of implanted device-based sensors chosen to target HF pathophysiology could detect worsening HF. METHODS: The MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) study enrolled patients with investigational chronic ambulatory data collection via implanted cardiac resynchronization therapy defibrillators. HF events (HFEs), defined as HF admissions or unscheduled visits with intravenous treatment, were independently adjudicated. The development cohort of patients was used to construct a composite index and alert algorithm (HeartLogic) combining heart sounds, respiration, thoracic impedance, heart rate, and activity; the test cohort was sequestered for independent validation. The 2 coprimary endpoints were sensitivity to detect HFE >40% and unexplained alert rate <2 alerts per patient-year. RESULTS: Overall, 900 patients (development cohort, n = 500; test cohort, n = 400) were followed for up to 1 year. Coprimary endpoints were evaluated using 320 patient-years of follow-up data and 50 HFEs in the test cohort (72% men; mean age 66.8 ± 10.3 years; New York Heart Association functional class at enrollment: 69% in class II, 25% in class III; mean left ventricular ejection fraction 30.0 ± 11.4%). Both endpoints were significantly exceeded, with sensitivity of 70% (95% confidence interval [CI]: 55.4% to 82.1%) and an unexplained alert rate of 1.47 per patient-year (95% CI: 1.32 to 1.65). The median lead time before HFE was 34.0 days (interquartile range: 19.0 to 66.3 days). CONCLUSIONS: The HeartLogic multisensor index and alert algorithm provides a sensitive and timely predictor of impending HF decompensation. (Evaluation of Multisensor Data in Heart Failure Patients With Implanted Devices [MultiSENSE]; NCT01128166).

Next-generation sequencing-based method shows increased mutation detection sensitivity in an Indian retinoblastoma cohort.

PURPOSE: Retinoblastoma (Rb) is the most common primary intraocular cancer of childhood and one of the major causes of blindness in children. India has the highest number of patients with Rb in the world. Mutations in the RB1 gene are the primary cause of Rb, and heterogeneous mutations are distributed throughout the entire length of the gene. Therefore, genetic testing requires screening of the entire gene, which by conventional sequencing is time consuming and expensive. METHODS: In this study, we screened the RB1 gene in the DNA isolated from blood or saliva samples of 50 unrelated patients with Rb using the TruSight Cancer panel. Next-generation sequencing (NGS) was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect germline pathogenic mutations in 66% (33/50) of the cases, 12 of which were novel. We were able to detect all types of mutations, including missense, nonsense, splice site, indel, and structural variants. When we considered bilateral Rb cases only, the mutation detection rate increased to 100% (22/22). In unilateral Rb cases, the mutation detection rate was 30% (6/20). CONCLUSIONS: Our study suggests that NGS-based approaches increase the sensitivity of mutation detection in the RB1 gene, making it fast and cost-effective compared to the conventional tests performed in a reflex-testing mode.

Perforated Gastric Gangrene without Pneumothorax in an Adult Bochdalek Hernia due to Volvulus.

Bochdalek hernia is the most frequent congenital diaphragmatic hernia which occurs due to a defect in the posterior attachment of the diaphragm when there is a failure of closure of the pleuroperitoneal membrane in utero. It rarely presents for the first time in adults. We report one such case of a 23-year-old male patient who presented with an acute abdomen. Chest X-ray showed air under diaphragm and he was taken up for an emergency laparotomy. Intraoperatively an organoaxial volvulus of the stomach was found in a bochdaleks hernia with a focal gangrene of the stomach fundus with perforation and peritonitis. However, there was no breach of pleural cavity. A sleeve resection of the gangrenous portion of the stomach was performed and the diaphragmatic defect was repaired. Patient made an uneventful postoperative recovery. Gastric gangrene with perforation as a manifestation of the adult bochdalek hernia is indeed rare. A concomitant pneumothorax occurs along with this condition which requires an intercostal drainage tube prior to the laparotomy. We report this case for its unique presentation without pneumothorax.

No Electromagnetic Interference Occurred in a Patient with a HeartMate II Left Ventricular Assist System and a Subcutaneous Implantable Cardioverter-Defibrillator.

The use of subcutaneous implantable cardioverter-defibrillators is a novel option for preventing arrhythmia-mediated cardiac death in patients who are at risk of endovascular-device infection or in whom venous access is difficult. However, the potential for electromagnetic interference between subcutaneous defibrillators and left ventricular assist devices is largely unknown. We report the case of a 24-year-old man in whom we observed no electromagnetic interference between a subcutaneous implanted cardioverter-defibrillator and a HeartMate II Left Ventricular Assist System, at 3 different pump speeds. To our knowledge, this is the first report of such findings in this circumstance.