Adherence to NCCN Genetic Testing Guidelines in Pancreatic Cancer and Impact on Treatment.

INTRODUCTION: National Comprehensive Cancer Network (NCCN) 2019 Guidelines recommend universal germline (GL) testing for patients (pts) with pancreatic cancer (PC), given germline mutations (gMut) can occur at a similar rate irrespective of an individual's family history of cancer. Molecular analysis of tumors in those with metastatic disease is also recommended. We aimed to determine rates of genetic testing at our institution, factors associated with testing, and outcomes of those tested. METHODS: Frequency of GL and somatic testing was examined in pts diagnosed with non-endocrine PC, with >2 visits between June 2019 and June 2021 at the Mount Sinai Health System. The clinicopathological variables and treatment outcomes were also recorded. RESULTS: A total of 149 pts met the inclusion criteria. Sixty-six pts (44%) underwent GL testing: 42 (28%) at time of diagnosis with the remainder later in treatment. The rate of GL testing increased every year: 33% (2019), 44% (2020), and 61% (2021). A family history of cancer was the only variable associated with the decision to perform GL testing. Eight pts (12% of pts tested) had pathological gMut: BRCA1 (1), BRCA2 (1), ATM (2), PALB2 (2), NTHL1 (1), both CHEK2 and APC (1). Neither gBRCA pt received a PARP inhibitor, all except one received first-line platinum. Ninety-eight pts (65.7%) had molecular tumor testing (66.7% of patients with metastases). Two pts with BRCA2 somatic mut did not have GL testing. Three pts received targeted therapies. CONCLUSION: Genetic testing based on provider discretion results in low rates of GL testing. Early results of genetic testing can have an impact on treatment decisions and trajectory of disease. Initiatives to increase testing are needed but must be feasible in real-world clinic settings.

The Delta Delta: Gaps in screening and patient assessment for hepatitis D virus infection.

Hepatitis D virus (HDV) infection is highly prevalent in patients with chronic hepatitis B (CHB). AASLD guidelines recommend a risk-based screening approach. Our aim was to ascertain if the risk-based approach leads to appropriate HDV screening, identify targets to improve screening rates, and study HDV clinical burden. CHB patients screened for HDV from 01/2016 to 12/2021 were identified. Level of training and specialty of providers ordering HDV screening tests were determined. HDV seropositive (HDV+) patient charts were reviewed for the presence of individual risk factors per the AASLD guidelines to determine if they met screening criteria. The severity of liver disease at the time of HDV screening was compared between the HDV+ group and a matched (based on age, hepatitis B e antigen status, BMI and sex) HDV seronegative (HDV-) group. During the study period, 1444/11,190 CHB patients were screened for HDV. Most screening tests were ordered by gastroenterology (90.2%) specialists and attending physicians (80.5%). HDV+ rate was 88/1444 (6%), and 72 HDV+ patients had complete information for analysis. 18% of HDV+ patients would be missed by a risk-based screening approach due to unreported or negative risk factors (see Table). A significantly higher number of HDV+ patients had developed significant fibrosis (p = 0.001) and cirrhosis (p < 0.01) by the time of screening than HDV- (n = 67) patients. In conclusion, targeted interventions are needed towards trainees and primary care clinics to improve screening rates. Current risk-based criteria do not appropriately screen for HDV. It is time for universal screening of HDV in CHB patients.

Characteristics and Outcomes of Tracheostomized Patients With and Without COVID-19.

Outcomes of tracheostomized patients with COVID-19 are seldomly investigated with conflicting evidence from the existing literature. OBJECTIVES: To create a study evaluating the impact of COVID-19 on tracheostomized patients by comparing clinical outcomes and weaning parameters in COVID-19 positive and negative cohorts. DESIGN SETTING AND PARTICIPANTS: A retrospective observational cohort study of 604 tracheostomized patients hospitalized in 16 ICUs in New York City between March 9, 2020, and September 8, 2021. MAIN OUTCOMES AND MEASURES: Patients were stratified into two cohorts: 398 COVID-19 negative (COVID-ve) and 206 COVID-19 positive (COVID+ve) patients. Clinical characteristics, outcomes, and weaning parameters (first pressure support [PS], tracheostomy collar [TC], speech valve placement, and decannulation) were analyzed. RESULTS: COVID+ve had fewer comorbidities including coronary artery disease, congestive heart failure, malignancy, chronic kidney disease, liver disease, and HIV (p < 0.05). Higher Fio2 (53% vs 44%), positive end-expiratory pressure (PEEP) (7.15 vs 5.69), Pco2 (45.8 vs 38.2), and lower pH (7.41 vs 7.43) were observed at the time of tracheostomy in COVID+ve (p < 0.005). There was no statistical difference in post-tracheostomy complication rates. Longer time from intubation to tracheostomy (15.90 vs 13.60 d; p = 0.002), tracheostomy to first PS (2.87 vs 1.80 d; p = 0.005), and TC placement (11.07 vs 4.46 d; p < 0.001) were seen in COVID+ve. However, similar time to speech valve placement, decannulation, and significantly lower 1-year mortality (23.3% vs 36.7%; p = 0.001) with higher number of discharges to long-term acute care hospital (LTACH) (23.8% vs 13.6%; p = 0.015) were seen in COVID+ve. CONCLUSIONS AND RELEVANCE: Patients with COVID-19 required higher Fio2 and PEEP ventilatory support at the time of tracheostomy, with no observed change in complication rates. Despite longer initial weaning period with PS or TC, similar time to speech valve placement or decannulation with significantly lower mortality and higher LTACH discharges suggest favorable outcome in COVID-19 positive patients. Higher ventilatory support requirements and prolonged weaning should not be a deterrent to pursuing a tracheostomy.

Neoadjuvant chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: Meta-analysis and trial sequential analysis of randomized controlled trials.

We aimed to compare resection and survival outcomes of neoadjuvant chemoradiotherapy (CRT) and immediate surgery in patients with resectable pancreatic cancer (RPC) or borderline resectable pancreatic cancer (BRPC). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards, a systematic review of randomized controlled trials (RCTs) was conducted. Random effects modeling was applied to calculate pooled outcome data. Likelihood of type 1 or 2 errors in the meta-analysis model was assessed by trial sequential analysis. A total of 400 patients from four RCTs were included. When RPC and BRPC were analyzed together, neoadjuvant CRT resulted in a higher R0 resection rate (risk ratio [RR]: 1.55, p = 0.004), longer overall survival (mean difference [MD]: 3.75 years, p = 0.009) but lower overall resection rate (RR: 0.83, p = 0.008) compared with immediate surgery. When RPC and BRPC were analyzed separately, neoadjuvant CRT improved R0 resection rate (RR: 3.72, p = 0.004) and overall survival (MD: 6.64, p = 0.004) of patients with BRPC. However, it did not improve R0 resection rate (RR: 1.18, p = 0.13) or overall survival (MD: 0.94, p = 0.57) of patients with RPC. Neoadjuvant CRT might be beneficial for patients with BRPC, but not for patients with RPC. Nevertheless, the best available evidence does not include contemporary chemotherapy regimens. Patients with RPC and those with BRPC should not be combined in the same cohort in future studies.

A novel evidence-based predictor tool for hospitalization and length of stay: insights from COVID-19 patients in New York city.

Predictive models for key outcomes of coronavirus disease 2019 (COVID-19) can optimize resource utilization and patient outcome. We aimed to design and internally validate a web-based calculator predictive of hospitalization and length of stay (LOS) in a large cohort of COVID-19-positive patients presenting to the Emergency Department (ED) in a New York City health system. The study cohort consisted of consecutive adult (> 18 years) patients presenting to the ED of Mount Sinai Health System hospitals between March 2020 and April 2020, diagnosed with COVID-19. Logistic regression was utilized to construct predictive models for hospitalization and prolonged (> 3 days) LOS. Discrimination was evaluated using area under the receiver operating curve (AUC). Internal validation with bootstrapping was performed, and a web-based calculator was implemented. From 5859 patients, 65% were hospitalized. Independent predictors of hospitalization and extended LOS included older age, chronic kidney disease, elevated maximum temperature, and low minimum oxygen saturation (p < 0.001). Additional predictors of hospitalization included male sex, chronic obstructive pulmonary disease, hypertension, and diabetes. AUCs of 0.881 and 0.770 were achieved for hospitalization and LOS, respectively. Elevated levels of CRP, creatinine, and ferritin were key determinants of hospitalization and LOS (p < 0.05). A calculator was made available under the following URL: https://covid19-outcome-prediction.shinyapps.io/COVID19_Hospitalization_Calculator/ . This study yielded internally validated models that predict hospitalization risk in COVID-19-positive patients, which can be used to optimize resource allocation. Predictors of hospitalization and extended LOS included older age, CKD, fever, oxygen desaturation, elevated C-reactive protein, creatinine, and ferritin.

Interesting case of dual pathology: Crohn's disease and Peutz-Jeghers syndrome.

An 18-year-old man presented with fever, night sweats and progressive weight loss over 2 months. He had a history of Peutz-Jeghers syndrome (PJS) complicated by previous intussusception requiring left hemicolectomy. Colonoscopy revealed deep punched out ulceration throughout the colon with multiple polyps. He was investigated for tuberculosis based on his occupation as dairy farmer. Following a negative QuantiFERON test, he was started on infliximab as emergency therapy and made a good recovery at 6 months follow-up. We describe a case of newly diagnosed Crohn's disease (CD) in an adolescent with a background diagnosis of PJS. While inflammatory bowel disease, such as CD, is common in the UK, the association with PJS is very rare, with only two existing case reports in the literature.