Citations

Purpose Identifying actionable oncogenic mutations have changed the therapeutic landscape in different types of tumors. This study investigated the utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) assay, in clinical practice in a developing country. Methods In this retrospective cohort study, CGP was performed on clinical samples from patients with different solid tumors recruited between December 2016 and November 2020, using hybrid capture-based genomic profiling, at the individual treating physicians’ request in the clinical care for therapy decisions. Kaplan–Meier survival curves were estimated to characterize the time-to-event variables. Results Patients median age was 61 years (range: 14–87 years), and 64.7% were female. The most common histological diagnosis was lung primary tumors, with 90 patients corresponding to 52.9% of the samples (95% CI 45.4-60.4%). Actionable mutations with FDA-approved medications for specific alterations correspondent to tumoral histology were identified in 58 cases (46.4%), whereas other alterations were detected in 47 different samples (37.6%). The median overall survival was 15.5 months (95% CI 11.7 months-NR). Patients who were subjected to genomic evaluation at diagnosis reached a median overall survival of 18.3 months (95% CI 14.9 months-NR) compared to 14.1 months (95% CI 11.1 months-NR) in patients who obtained genomic evaluation after tumor progression and during standard treatment ( P = .7). Conclusion CGP of different types of tumors identifies clinically relevant genomic alterations that have benefited from targeted therapy and improve cancer care in a developing country to guide personalized treatment to beneficial outcomes of cancer patients.

Gastrointestinal (GI) amyloidosis can be acquired or genetic and is commonly caused by chronic inflammatory illnesses (AA amyloidosis), haematological malignancies (AL amyloidosis) and end-stage renal disease (beta-2 microglobulin amyloidosis). The accumulation of these aberrant proteins disrupts the structures and functions of many organs; the least common of which is the GI tract. GI presentations depend on the type, location and amount of amyloid deposition. Symptoms can range from nausea and vomiting to fatal GI bleeds. Pathological examination of the involved tissue with characteristic green birefringence under polarised light is used to confirm the diagnosis. Patients should be considered for further evaluation to rule out additional organ involvement, notably cardiac and renal. We present a patient with amyloidosis-induced gastroparesis, an under-recognised presentation of systemic amyloidosis in the gastroenterology system.

Laryngeal high-speed videoendoscopy (HSV) is a powerful tool to study the detailed vibratory characteristics of the vocal folds. The use of HSV in connected speech enables us to study the transitory behaviors of the vocal folds during different vocalizations. The onset and offset of voicing contain critical information about the health and function of the vocal folds. In this work, HSV is used to study how the voicing begins/ends at the laryngeal level at the onset/offset of phonation. HSV data were obtained during production of connected speech from participants with non-pathological voices and patients with different neurogenic voice disorders. The data collection was performed using a Photron FASTCAM mini AX200 high-speed camera coupled with a flexible nasolaryngoscope. The glottal attack time and glottal offset time were measured at the onset and offset of different vocalizations, respectively, from the HSV data. The findings show differences in the onset and offset measures between the two groups of participants. The vocal fold vibratory behaviors will be discussed qualitatively and quantitatively using these measures. The use of HSV in connected speech could help us develop accurate voice assessment procedures to assess the vocal folds function during connected speech.

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.

Introduction Arteriovenous fistulas at the craniocervical junction (CCAVFs) are challenging to treat due to variation in angioarchitecture and shunting sites. No consensus exists as to whether open surgery or endovascular approaches are better in regards to outcomes, complications, and need for reintervention. As such, weexplore the efficacy, outcomes, and complications of endovascular versus open surgery for dural arteriovenous fistulas at the craniocervical junction. Methods A systematic review was performed using the EMBASE, PubMed,and Cochrane databases in April 2022. MeSH search terms included (craniocervical) AND (arteriovenous OR fistula OR AVF). Inclusion criteria were defined as patients with CCAVFs who were treated with open surgery or endovascular therapy with reported clinical outcomes at 6 months or later. Results A total of 357 studies were screened; of which 75 were included. A total of 416 patients (309 males, 91 females) were included with an average age of 61.9 years. A total of 236 patients underwent surgery (mean age: 61.5), 71 patients underwent embolization (mean age: 62.6), and 25 patients underwent a combination (mean age: 54.7). Outcomes were reported in 39 surgery cases (mean follow up time: 31.4 months), and 54 endovascular cases (mean follow up time: 24.2 months). Within the open surgery group 47 (57.3%) had complete symptom resolution, 23 (28%) had symptom improvement or stabilization, 11 (13.4%) permanent deficit, and 1 (1.2%) resulted in death. Within the endovascular group 26 (56.5%) had complete symptom resolution, 5 (10.9%) had symptom improvement or stabilization, 15 (32.6%) permanent deficit, and 0 (0%) resulted in death. Conclusions Open surgery and embolization yield comparable symptomatic improvement and stabilization. However, the rate of permanent deficits is higher withembolization, while mortality is higher with open surgery. Further studies are required to better associate these outcomes to baseline parameters including treatment decision making, size of the lesion, patient age, and co‐morbidities.

Introduction While neurovascular surgeries have largely been performed by neurosurgeons, the advent of endovascular procedures has produced increasing involvement of other specialists in this arena (i.e. neurologists and radiologists).This study aims to analyzethe involvement of different specialties within theneuroendovascular workforce by characterizingthem by their primary specialty. Methods The Medicare Provider Utilization Database was queried from 2013 to 2019 for all primary Current Procedural Terminology (CPT) codes identified by the American Medical Association as pertaining to endovascular procedures of the nervous system (61623, 61624, 61630, 61635, 61626, 61645, and 61650). We counted the number of unique providers in respective fields (neurology, neurosurgery, and radiology) who performed these procedures. Statistical analyses, including data aggregation, exploratory analysis, and propensity adjustment, were performed using R, version 4.0.1 (The R Foundation, Vienna, Austria). The two‐sided Mann‐Kendall trend test, a non‐parametric statistical test that assesses for monotonic trends in either an upward or downward trend, was utilized to assess for trends over time. Within each year analyzed, a Chi‐squared test for trend in proportions was used. A significance level of 0.05 was used. Results In 2013, neurosurgeons comprised 45% of the workforce performing these procedures, neurologists were 9%, and radiologists were 47%. By 2019, neurosurgeons decreased to 34.5% of the workforce, while neurologists increased to 21.5%, and radiologists decreased slightly to 44%. Neurologists were the only field in which the proportional shift in providers was noted to have a significant change in trajectory (p:0.04), an upward trajectory. Overall proportional differences between respective specialists were statistically significant each year (p< 0.01). Conclusions Neurologists are increasingly performing endovascular procedures. Increased communication and coordination between specialties can improve disparities in care to ensure adequate access to neurovascular care across the US.