Tailoring the wrap: intraoperative functional lumen imaging probe (FLIP) during hiatal hernia repair.

INTRODUCTION: The introduction of the functional lumen imaging probe (FLIP) has provided objective, real-time feedback on the geometric variations with each component of a hiatal hernia repair (HHR). The utility of this technology in altering intraoperative decision-making has been scarcely reported. Herein, we report a single-center series of intraoperative FLIP during HHR. METHODS: A retrospective review of electronic medical records between 2020 and 2022 was conducted and all patients undergoing non-recurrent HHR with FLIP were queried. Patient and hernia characteristics, intraoperative FLIP values and changes in decision-making, as well as early post-operative outcomes were reported. Both diameter and distensibility index (DI) were measured at 40 ml and 50 ml balloon inflation after hiatal dissection, after hiatal closure, and after fundoplication when indicated. RESULTS: Thirty-three patients met inclusion criteria. Mean age was 62 ± 14 years and mean BMI was 28 ± 6 kg/m2. The majority (53%) were type I hiatal hernias. The largest drop in DI occurred after hiatal closure, with minimal change seen after fundoplication (mean DI of 4.3 ± 2. after completion of HH dissection, vs 2.7 ± 1.2 after hiatal closure and 2.3 ± 1 after fundoplication when performed). In 13 (39%) of cases, FLIP values directly impacted intraoperative decision-making. Fundoplication was deferred in 4/13 (31%) patients, the wrap was loosened in 2/13 (15%); the type of fundoplication was altered to achieve adequate anti-reflux values in 2/13 (15%) patients, and in 1/13 (3%) the wrap was tightened. CONCLUSION: FLIP measurements can be used intraoperatively to guide decision-making and alter management plan based on objective values. Long-term outcomes and further prospective studies are required to better delineate the value of this technology.

Effectiveness of Standard Treatment for Stage 4 Colorectal Cancer: Traditional Management with Surgery, Radiation, and Chemotherapy.

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States comprising 7.9% of all new cancer diagnoses and 8.6% of all cancer deaths. The combined 5-year relative survival rate for all stages is 65.1% but in its most aggressive form, stage 4 CRC has a 5-year relative survival rate of just 15.1%. For most with stage 4 CRC, treatment is palliative not curative, with the goal to prolong overall survival and maintain an acceptable quality of life. The identification of unique cancer genomic and biologic markers allows patient-specific treatment options. Treatment of stage 4 CRC consists of systemic therapy with chemotherapeutic agents, surgical resection if feasible, potentially including resection of metastasis, palliative radiation in select settings, and targeted therapy toward growth factors. Despite advances in surgical and medical management, metastatic CRC remains a challenging clinical problem associated with poor prognosis and low overall survival.

Contemporary Therapies and Future Directions in the Management of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by pathogenic variants in sarcomeric genes, leading to left ventricular hypertrophy and complex phenotypic heterogeneity. While HCM is the most common inherited cardiomyopathy, pharmacological treatment options have previously been limited and were predominantly directed towards symptom control owing to left ventricular outflow obstruction. These therapies, including beta blockers, calcium channel blockers, and disopyramide, have not been shown to affect the natural history of the disease, which is of particular concern for younger patients who have an increased lifetime risk of experiencing arrhythmias, heart failure, and sudden cardiac death. Increased knowledge of the genetic mechanisms underlying this disease in recent years has led to the development of targeted, potentially disease-modifying therapies for both obstructive and nonobstructive phenotypes that may help to prevent or ameliorate left ventricular hypertrophy. In this review article, we will define the etiology and clinical phenotypes of HCM, summarize the conventional therapies for obstructive HCM, discuss the emerging targeted therapies as well as novel invasive approaches for obstructive HCM, describe the therapeutic advances for nonobstructive HCM, and outline the future directions for the treatment of HCM.

Long-Term Outcomes of the Electrically Unresponsive, Anatomically Intact Facial Nerve Following Vestibular Schwannoma Surgery.

Objective The study aimed to determine long-term outcomes in patients with intraoperative electrical conduction block in an anatomically intact facial nerve (FN). Methods Single center retrospective review of prospectively collected database of all vestibular schwannoma surgeries between January 1, 2008 and August 25, 2015. Operative notes were reviewed and patients with anatomically intact FNs, but complete conduction block at the end of surgery were included for analysis. Results In total, 371 patients had vestibular schwannoma surgery of which 18 met inclusion criteria. Mean follow-up was 34.28 months and average tumor size was 28.00 mm. Seventeen patients had House-Brackmann Grade VI facial palsy immediately postoperatively and one patient was grade V. At 1 year, three patients remained grade VI (17%), two improved to grade V (11%), seven to grade IV (39%), six to grade III (33%), and one patient to grade II (6%). On extended follow-up, five patients (28%) had additional 1 to 2 score improvement in facial function. Subset analysis revealed no correlation of tumor size, vascularity, adherence to nerve, operative approach, extent of resection, splaying of FN, and recurrent tumor or sporadic tumors to the extent of FN recovery. Conclusion Intraoperative conduction block does not condemn a patient to permanent FN palsy. There is potential for a degree of recovery comparable with those undergoing nerve grafting. Our data do not clearly support a policy of same-surgery or early-postoperative primary nerve grafting in the event of a complete conduction block, and instead we favor monitoring for recovery in an anatomically intact nerve.

Cardiovascular Characteristics of Patients with Genetic Variation in Desmoplakin (DSP).

BACKGROUND: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding the cardiac phenotypes associated with genetic variation in DSP have been largely accumulated from phenotype-first studies of ARVC. METHODS: We aimed to evaluate the clinical manifestations of cardiac disease associated with variants in DSP through a genotype-first approach employed in the University of Pennsylvania Center for Inherited Cardiovascular Disease registry. We performed a retrospective study of 19 individuals with "pathogenic" or "likely pathogenic" variants in DSP identified by clinical genetic testing. Demographics and clinical characteristics were collected. RESULTS: Among individuals with disease-causing variants in DSP, nearly 40% had left ventricular enlargement at initial assessment. Malignant arrhythmias were prevalent in this cohort (42%) with a high proportion of individuals undergoing primary and secondary prevention implantable cardioverter defibrillator implantation (68%) and ablation of ventricular arrhythmias (16%). Probands also experienced end-stage heart failure requiring heart transplantation (11%). CONCLUSIONS: Our data suggest DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. Targeted strategies for diagnosis and risk stratification for DSP cardiomyopathy should be investigated.

Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy in Adult Solid Organ Transplant Recipients.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) in pediatric solid organ transplant recipients has been reported in association with use of calcineurin inhibitors. However, data on the incidence and prevalence of HCM in adult posttransplant patients are limited. We sought to describe the clinical characteristics of solid organ transplant recipients who were diagnosed with HCM from 2011 to 2021 at a single center. METHODS: Patients who had undergone solid organ transplant and exhibited left ventricular hypertrophy with left ventricular wall thickness ≥13 mm on transthoracic echocardiography were included. Clinical history, pedigree analysis, clinical genetic testing, transthoracic echocardiography, cardiac magnetic resonance imaging, treatment, and follow-up testing results were collected. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges and compared using the Wilcoxon rank-sum and Kruskal-Wallis tests. A 2-sided P < 0.05 was considered statistically significant. RESULTS: Three lung, 5 kidney, and 4 liver transplant recipients from 12 different families were included. Seven patients (58%) did not carry a preexisting diagnosis of hypertension, and none had a history of aortic or subaortic stenosis. A majority of patients exhibited asymmetric septal hypertrophy (67%; medial septal thickness versus left ventricular posterior wall thickness 17 versus 13 mm; P < 0.001) and dynamic left ventricular outflow tract (LVOT) obstruction (58%). All patients were managed long term with calcineurin inhibitors. Clinical genetic testing in 6 patients identified 2 with disease-causing variants in 2 sarcomere genes, myosin binding protein-C and myosin heavy chain 7. Four patients (33%) underwent successful septal reduction therapy for treatment of symptomatic LVOT obstruction. CONCLUSIONS: Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients, and genetic testing can identify individuals with sarcomeric HCM. Medical management and septal reduction therapies are treatment options for severe symptomatic disease.

Applying Shared Decision Making to Sports Participation for a Patient With Hypertrophic Cardiomyopathy.

A patient with hypertrophic cardiomyopathy and a cardio-defibrillator implanted for primary prevention would like to compete on the ski team at his school. This case illustrates how a shared decision-making approach can be applied when counseling patients with hypertrophic cardiomyopathy about exercise and sports participation. (Level of Difficulty: Intermediate.).

Incremental prognostic value of visually estimated coronary artery calcium in patients undergoing positron emission tomography imaging.

OBJECTIVE: Visually estimated coronary artery calcium (VECAC) from chest CT or attenuation correction (AC)/CT obtained during positron emission tomography (PET)-myocardial perfusion imaging (MPI) is feasible. Our aim was to determine the prognostic value of VECAC beyond conventional risk factors and PET imaging parameters, including coronary flow reserve (CFR). METHODS: We analysed 608 patients without known coronary artery disease who underwent PET-MPI between 2012 and 2016 and had AC/CT and/or chest CT images. We used Cox regression to estimate the association of VECAC categories (≤10, 11-400, >400 Agatston units (AU)) with the primary outcome of all-cause death, acute coronary syndrome or stroke (mean follow-up 4.3±1.8 years). C-statistics assessed the relationship between PET parameters and VECAC with the primary outcome. RESULTS: Mean age was 58±11 years, 65% were women and 67% were black. VECAC ≤10, 11-400 and >400 AU was observed in 68%, 12% and 20% of subjects, respectively. Compared with VECAC ≤10, VECAC categories 11-400 (HR 2.25, 95% CI 1.24 to 4.08) and >400 AU (HR 3.05, 95% CI 1.87 to 4.98) were associated with the primary outcome after adjusting for traditional risk factors, MPI findings and CFR. Adding VECAC to a model that included PET-MPI, CFR and clinical risk factors improved the prognostic value for the primary outcomes (c-statistic 0.71 to 0.75 with VECAC, p=0.01). CONCLUSIONS: VECAC is a potent predictor of events beyond traditional risk factors and PET imaging markers, including CFR. These data further support the importance for routine VECAC implementation.

Sarcomere mutation negative hypertrophic cardiomyopathy is associated with ageing and obesity.

BACKGROUND: Despite advances in our understanding of the genetic causes of hypertrophic cardiomyopathy (HCM), a large portion of this patient population do not carry sarcomere gene mutations when screened. It remains largely unknown why patients without sarcomere mutations develop asymmetric myocardial hypertrophy. METHODS: We performed a retrospective analysis of probands with HCM who underwent genetic testing to determine if clinical phenotypes were different depending on sarcomere mutation status. A medical history, three generation family history and clinical phenotyping were performed on 127 probands with HCM. Genetic screening was performed using clinically available HCM genetic testing panels. RESULTS: We found that probands with HCM with pathogenic sarcomere mutations were over three times more likely to have a family history of HCM (66% vs 17%, p<0.0001) and were diagnosed with HCM at a much younger age (32 vs 51 years old, p<0.0001). In contrast, probands with HCM without sarcomere mutations were significantly more obese (body surface area p=0.003, body mass index p=0.04 adjusted for age) and were more likely to present with left ventricular outflow tract obstruction (p=0.0483). CONCLUSION: Patients with sarcomere mutation negative HCM present at an older age and are more obese compared with patients with sarcomere mutation positive HCM. The role of ageing and obesity in asymmetric myocardial hypertrophy warrants further investigation.

Ruptured temporal horn aneurysm associated with Moyamoya collateral vessel coexisting with contralateral arteriovenous malformation - technical note with clinical vignette.

The co-occurrence of a brain arteriovenous malformation, Moyamoya Disease, and intracranial aneurysm is exceedingly rare. We report the third case of this disease constellation, and the first where the aneurysm arises from the Moyamoya collateral vessel. We review the relevant literature and discuss proposed pathophysiological mechanisms and clinical implications.

Outcomes and Complications of Endovascular Mechanical Thrombectomy in the Treatment of Acute Posterior Circulation Occlusions: A Systematic Review.

BACKGROUND: The use of thrombectomy in the treatment for acute ischemic stroke (AIS) affecting the anterior circulation is well established. Comparatively, fewer data exist on the effectiveness of these techniques in treating posterior circulation occlusions. This review analyzes and reports on the usefulness and outcomes of emergent thrombectomy in large-vessel occlusions affecting the posterior circulation. METHODS: A literature review was performed to identify all studies of patients with AIS in the posterior circulation who underwent endovascular mechanical thrombectomy (EMT) with stent retrievers and/or aspiration devices that were reported between January 1, 2015 and February 12, 2019. Favorable outcomes were defined as a modified Rankin Scale (mRS) score 0-2 at 3 months follow-up. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b-3. RESULTS: Twenty-five studies, comprising 1612 EMT-treated patients with posterior circulation AIS, were included in this analysis. The median presenting National Institutes of Health Stroke Scale score was 20.9 (range, 10.5-34). Favorable outcomes at 3 months follow-up were observed in 38% of patients (range, 16%-75%) and a mortality of 30% (range, 4%-64%). Successful reperfusion was achieved in 86% of cases (range, 62%-100%). CONCLUSIONS: In patients with AIS caused by large-vessel occlusion of the posterior circulation, successful reperfusion can be achieved via EMT, with approximately a third of these patients achieving a good functional outcome. However, with similar proportions of treated patients experiencing significant morbidity or mortality, respectively, there is urgent need for additional studies to identify predictive or modifiable factors for a positive outcome.

False Localizing Trigeminal V2 Sensory Loss in Vestibular Schwannoma.

False localizing signs involving cranial nerves are rare, even more so when involving the trigeminal nerve. Here we present the first case of trigeminal V2 sensory loss as a false localizing sign. The sensory dysfunction was caused by a large contralateral cystic vestibular schwannoma and subsequently improved after tumor resection. The clinical and radiographic features are described, and proposed mechanisms for this false localizing sign are discussed.

Recurrent Left Pleural Effusion Following Left Atrial Appendage Closure With the Watchman Device.

A 75-year-old woman with recent left atrial appendage closure with the Watchman device (Boston Scientific, Natick, Massachusetts) presented with recurrent left pleural effusion. The constellation of chest pain, pericardial effusion, and exudative pleural effusion were suggestive of an inflammatory process precipitated by microperforation of the fixation anchors during the Watchman placement. (Level of Difficulty: Intermediate.).

Alterations in sarcomere function modify the hyperplastic to hypertrophic transition phase of mammalian cardiomyocyte development.

It remains unclear how perturbations in cardiomyocyte sarcomere function alter postnatal heart development. We utilized murine models that allowed manipulation of cardiac myosin-binding protein C (MYBPC3) expression at critical stages of cardiac ontogeny to study the response of the postnatal heart to disrupted sarcomere function. We discovered that the hyperplastic to hypertrophic transition phase of mammalian heart development was altered in mice lacking MYBPC3 and this was the critical period for subsequent development of cardiomyopathy. Specifically, MYBPC3-null hearts developed evidence of increased cardiomyocyte endoreplication, which was accompanied by enhanced expression of cell cycle stimulatory cyclins and increased phosphorylation of retinoblastoma protein. Interestingly, this response was self-limited at later developmental time points by an upregulation of the cyclin-dependent kinase inhibitor p21. These results provide valuable insights into how alterations in sarcomere protein function modify postnatal heart development and highlight the potential for targeting cell cycle regulatory pathways to counteract cardiomyopathic stimuli.