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"Quinn, Timothy"
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Molecular Profiling of Syringocystadenocarcinoma Papilliferum Reveals RAS -Activating Mutations
by
Googe, Paul B.
,
Shalin, Sara C.
,
O’Donnell, Patrick
in
Adenocarcinoma
,
Analysis
,
Antineoplastic drugs
2024
Syringocystadenocarcinoma papilliferum (SCACP) is a rare adnexal carcinoma and the malignant counterpart of syringocystadenoma papilliferum (SCAP), which is commonly located on the head and neck and may arise in association with a nevus sebaceus. RAS mutations have been identified in both SCAP and nevus sebaceus.
To evaluate the clinicopathologic and molecular features of SCACPs, which have not been previously explored.
We obtained 11 SCACPs from 6 institutions and reviewed the clinicopathologic features. We also performed molecular profiling using next-generation sequencing.
The cohort comprised 6 women and 5 men with ages ranging from 29 to 96 years (mean, 73.6 years). The neoplasms occurred on the head and neck (n = 8; 73%) and extremities (n = 3; 27%). Three tumors possibly arose in a nevus sebaceus. A total of 4 cases showed at least carcinoma in situ (adenocarcinoma, n = 3; squamous cell carcinoma [SCC], n = 1), and 7 cases were invasive (SCC, n = 5; mixed adenocarcinoma + SCC, n = 2). A total of 8 of 11 cases (73%) had hot spot mutations consisting of HRAS (n = 4), KRAS (n = 1), BRAF (n = 1), TP53 (n = 4), ATM (n = 2), FLT3 (n = 1), CDKN2A (n = 1), and PTEN (n = 1). All 4 cases with HRAS mutations occurred on the head and neck, whereas the KRAS mutation occurred on the extremity.
RAS-activating mutations were detected in 50% of the cases, of which most (80%) involved HRAS and occurred on the head and neck, which shows overlapping features with SCAP, supporting that a subset may arise as a result of malignant transformation and likely an early oncogenic event.
Journal Article
Factors associated with an increased risk of perioperative cardiac arrest in emergent and elective craniotomy and spine surgery
2017
•ASA class 4 and 5, totally dependent and Black and Asian patients had a greater likelihood of cardiac arrest.•18% of cardiac arrests for craniotomy and 25% of cardiac arrests for spine surgery occurred intraop through postop day 0.•Cardiac arrest associated with emergent craniotomy was 36.5% and with emergent spine surgery was only 17.3%.•Our results may lead to initiatives to reduce morbidity and mortality for neurosurgical patients.
Cardiac arrest following neurosurgery is a devastating complication associated with significant postoperative morbidity and mortality. There are no published studies that have used a large and robust multicenter database to specifically examine demographic and surgical risk factors associated with cardiac arrests following craniotomy and spine surgeries, respectively.
We retrospectively analyzed data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for the period between January 1, 2007 and December 31, 2013, focusing on cardiac arrest associated with craniotomy and spine surgery from the intraoperative period to 30days after surgery. A total of 73,584 neurosurgical patients were analyzed (59,609 spine surgeries and 13,975 craniotomies).
There was an increased risk of cardiac arrest for both craniotomy and spine surgeries in patients with American Society of Anesthesiologists (ASA) Physical Status class 4 or 5, Black and Asian patients compared to White patients and patients totally dependent versus independent based on the ACS-NSQIP risk calculator. The risk of cardiac arrest for craniotomy was 66.5 per 10,000 anesthetics and for spine surgery was 21.3 per 10,000 anesthetics. Cardiac arrest associated with emergent non-traumatic craniotomy was 36.5% and with emergent non-traumatic spine surgery was only 17.3%. We found that 18% of cardiac arrests for craniotomy and 25% of cardiac arrests for spine surgery occurred from the intraoperative period through postoperative day (POD) 0. Both craniotomy and spine surgery patients who had a cardiac arrest were more likely to have acute kidney injury (AKI), failure to wean from the ventilator, postoperative dialysis, myocardial infarction (MI), venous thromboembolism (VTE) and sepsis in the postoperative period. The overall mortality rate for both craniotomy and spine surgeries who had a cardiac arrest from the intraoperative period to 30days postoperative was 61.8% versus 1.2% in the no cardiac arrest control group.
Identification of patient and surgery specific characteristics from ACS-NSQIP data associated with cardiac arrest following craniotomy and spine surgery may lead to initiatives to reduce morbidity and mortality in the neurosurgical patient population.
Journal Article
Localised chronic fibrosing vasculitis versus erythema elevatum diutinum
by
Chen, Steven T
,
Goldstein, Jay
,
Lin, William M
in
Case Reports: Rare disease
,
Dapsone - therapeutic use
,
Erythema - diagnosis
2023
A woman in her 70s was referred for a painless plaque on the shin, present for 2 years and progressing in thickness. Examination revealed a large erythematous to violaceous indurated plaque with cobblestone appearance. Biopsy revealed an inflammatory infiltrate of neutrophils with scattered histiocytes, lymphocytes, eosinophils and plasma cells interspersed with areas of lamellar fibrosis and focal areas of vascular damage, suggestive of a localised chronic fibrosing vasculitis of the skin. Localised chronic fibrosing vasculitis is a rare dermatosis, typically presenting as ulcerated violet-red nodules, which can appear histologically similar to erythema elevatum diutinum (EED), which typically presents as red-brown annular plaques. EED may have a predominance of neutrophils and granulomas, while chronic fibrosing vasculitis may have a sparse infiltrate of mixed inflammatory cells without granulomas. While dapsone is a first-line treatment for EED, there are no formal guidelines on the treatment of localised chronic fibrosing vasculitis. Given the neutrophils in this sample and similarities with EED, this patient was treated with oral dapsone, resulting in plaque improvement.
Journal Article
Negative effects of forest harvest on coastal tailed frog (Ascaphus truei) emerge after a decade‐long experiment
by
Jones, Jay E.
,
Quinn, Timothy
,
Ojala‐Barbour, Reed
in
amphibian density
,
Amphibians
,
Ascaphus
2025
Perennial, low‐order headwater streams provide critical ecosystem functions, including habitat for specialized aquatic species. Anthropogenic disturbances can degrade biological and physical conditions in headwater streams, with potentially corresponding negative effects on stream biodiversity. Headwater streams comprise most of the stream length in forested watersheds in the Pacific Northwest, the United States, including those that are globally important sources of wood biomass. To conserve stream biota, water quality, and related public resources, riparian buffers are retained as a management tool expected to ameliorate effects of anthropogenic disturbances, including timber harvests. From 2006 to 2015, we used a replicated Before‐After Control‐Impact (BACI) experiment to evaluate how coastal tailed frog (Ascaphus truei) density varied in three alternative riparian buffer configurations (continuous buffer, patchy buffer, and clearcut riparian area) and unharvested reference basins, in western Washington, the United States. We used count data to estimate tailed frog density for three years pre‐harvest, the first two years post‐harvest, and years seven and eight post‐harvest. We compared relative change in density for each buffer configuration between pre‐ and post‐harvest after controlling for temporal changes in the reference. We found no evidence of a decline in tailed frog density in the first two years post‐harvest but saw evidence of substantial declines in larval and post‐metamorphic coastal tailed frog densities in years seven and eight post‐harvest. Specifically, we estimated a 65%, 93%, and 84% decline in average larval tailed frog density in basins with a continuous buffer, patchy buffer, and clearcut riparian area, respectively. We estimated 71% and 97% declines in post‐metamorphic tailed frog densities in the continuous and patchy buffers. Because evidence of tailed frog declines became apparent only after eight years post‐harvest, our results underscore the need for longer term studies to address lag effects in population responses to human land use and to understand how effectiveness of conservation practices can vary spatially and temporally.
Journal Article
General Anesthetics in CAncer REsection Surgery (GA-CARES) randomized multicenter trial of propofol vs volatile inhalational anesthesia: protocol description
by
Nadler, Jacob W.
,
Romeiser, Jamie L.
,
Quinn, Timothy D.
in
Cancer surgery
,
Critical Care Medicine
,
Emergency Medicine
2023
Background
Studies indicate that patients can be “seeded” with their own cancer cells during oncologic surgery and that the immune response to these circulating cancer cells might influence the risk of cancer recurrence. Preliminary data from animal studies and some retrospective analyses suggest that anesthetic technique might affect the immune response during surgery and hence the risk of cancer recurrence. In 2015, experts called for prospective scientific inquiry into whether anesthetic technique used in cancer resection surgeries affects cancer-related outcomes such as recurrence and mortality. Therefore, we designed a pragmatic phase 3 multicenter randomized controlled trial (RCT) called General Anesthetics in Cancer Resection (GA-CARES).
Methods
After clinical trial registration and institutional review board approval, patients providing written informed consent were enrolled at five sites in New York (NY) State. Eligible patients were adults with known or suspected cancer undergoing one of eight oncologic surgeries having a high risk of cancer recurrence. Exclusion criteria included known or suspected history of malignant hyperthermia or hypersensitivity to either propofol or volatile anesthetic agents. Patients were randomized (1:1) stratified by center and surgery type using REDCap to receive either propofol or volatile agent for maintenance of general anesthesia (GA). This pragmatic trial, which seeks to assess the potential impact of anesthetic type in “real world practice”, did not standardize any aspect of patient care. However, potential confounders, e.g., use of neuroaxial anesthesia, were recorded to confirm the balance between study arms. Assuming a 5% absolute difference in 2-year overall survival rates (85% vs 90%) between study arms (primary endpoint, minimum 2-year follow-up), power using a two-sided log-rank test with type I error of 0.05 (no planned interim analyses) was calculated to be 97.4% based on a target enrollment of 1800 subjects. Data sources include the National Death Index (gold standard for vital status in the USA), NY Cancer Registry, and electronic harvesting of data from electronic medical records (EMR), with minimal manual data abstraction/data entry.
Discussion
Enrollment has been completed (
n
= 1804) and the study is in the follow-up phase. This unfunded, pragmatic trial, uses a novel approach for data collection focusing on electronic sources.
Trial registration
Registered (NCT03034096) on January 27, 2017, prior to consent of the first patient on January 31, 2017.
Journal Article
Threat assessment for Pacific sand lance (Ammodytes personatus) in the Salish Sea
by
Koval, Brian A.
,
Houtman, Nicola R.
,
Bruce, Ian
in
conservation
,
ecological risk assessment
,
expert elicitation
2024
Like many forage fish species, Pacific sand lance ( Ammodytes personatus ) play a key role in nearshore marine ecosystems as an important prey source for a diverse array of predators in the northeastern Pacific. However, the primary threats to Pacific sand lance and their habitat are poorly defined due to a lack of systematic data. Crucial information needed to assess their population status is also lacking including basic knowledge of their local and regional abundance and distribution. Sand lance are currently listed as ‘not evaluated’ under the IUCN red list and they have not been assessed by US and Canadian agencies. This hampers management and policy efforts focused on their conservation. To address this knowledge gap, we conducted a three-part, structured expert elicitation to assess the vulnerability of Salish Sea sand lance populations. Experts were asked to list and rank key threats to Salish Sea sand lance and/or their habitat, to further quantify the vulnerability of sand lance to identified threats using a vulnerability matrix, and to predict the population trajectory in 25 years from today. Impacts associated with climate change (e.g. sea level rise, sea temperature rise, ocean acidification, and extreme weather) consistently ranked high as threats of concern in the ranking exercise and quantified vulnerability scores. Nearly every expert predicted the population will have declined from current levels in 25 years. These results suggest sand lance face numerous threats and may be in decline under current conditions. This research provides vital information about which threats pose the greatest risk to the long-term health of sand lance populations and their habitat. Managers can use this information to prioritize which threats to address. Future research to reliably quantify population size, better understand the roles of natural and anthropogenic impacts, and to identify the most cost-effective actions to mitigate multiple threats, is recommended.
Journal Article