Adaption and National Validation of a Tool for Predicting Mortality from Other Causes Among Men with Nonmetastatic Prostate Cancer.

BACKGROUND: An electronic health record-based tool could improve accuracy and eliminate bias in provider estimation of the risk of death from other causes among men with nonmetastatic cancer. OBJECTIVE: To recalibrate and validate the Veterans Aging Cohort Study Charlson Comorbidity Index (VACS-CCI) to predict non-prostate cancer mortality (non-PCM) and to compare it with a tool predicting prostate cancer mortality (PCM). DESIGN, SETTING, AND PARTICIPANTS: An observational cohort of men with biopsy-confirmed nonmetastatic prostate cancer, enrolled from 2001 to 2018 in the national US Veterans Health Administration (VA), was divided by the year of diagnosis into the development (2001-2006 and 2008-2018) and validation (2007) sets. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Mortality (all cause, non-PCM, and PCM) was evaluated. Accuracy was assessed using calibration curves and C statistic in the development, validation, and combined sets; overall; and by age (<65 and 65+ yr), race (White and Black), Hispanic ethnicity, and treatment groups. RESULTS AND LIMITATIONS: Among 107 370 individuals, we observed 24 977 deaths (86% non-PCM). The median age was 65 yr, 4947 were Black, and 5010 were Hispanic. Compared with CCI and age alone (C statistic 0.67, 95% confidence interval [CI] 0.67-0.68), VACS-CCI demonstrated improved validated discrimination (C statistic 0.75, 95% CI 0.74-0.75 for non-PCM). The prostate cancer mortality tool also discriminated well in validation (C statistic 0.81, 95% CI 0.78-0.83). Both were well calibrated overall and within subgroups. Owing to missing data, 18 009/125 379 (14%) were excluded, and VACS-CCI should be validated outside the VA prior to outside application. CONCLUSIONS: VACS-CCI is ready for implementation within the VA. Electronic health record-assisted calculation is feasible, improves accuracy over age and CCI alone, and could mitigate inaccuracy and bias in provider estimation. PATIENT SUMMARY: Veterans Aging Cohort Study Charlson Comorbidity Index is ready for application within the Veterans Health Administration. Electronic health record-assisted calculation is feasible, improves accuracy over age and Charlson Comorbidity Index alone, and might help mitigate inaccuracy and bias in provider estimation of the risk of non-prostate cancer mortality.

TP53 Mutation-driven Stratified Mucin-producing Carcinoma Coexisting With Squamous Cell Carcinoma of the Vulva: A Case Study.

Associated with high-risk human papillomavirus infection, invasive stratified mucin-producing carcinoma is a recently characterized adenocarcinoma of the cervix. It often occurs in association with adjacent stratified mucin-producing intraepithelial lesion. Differentiated vulvar intraepithelial neoplasia and related invasive squamous cell carcinoma often arise in background vulvar lichen sclerosus with TP53 mutation as the underlying molecular signature. We present a unique case of vulvar invasive stratified mucin-producing carcinoma-like component coexisting with invasive squamous cell carcinoma in a 64-year-old woman. Both neoplastic components were proven TP53 -driven processes arising in the background of differentiated vulvar intraepithelial neoplasia and lichen sclerosus. The invasive stratified mucin-producing carcinoma-like component behaved aggressively in this case, evidenced by the presence of lymphovascular invasion and inguinal lymph node metastasis.

Pulmonary artery angiomatoid fibrous histiocytoma mimicking pulmonary embolism.

A young man presented to the emergency department with pleuritic chest pain and shortness of breath. Of note, he recently went on a long-distance flight of about 9 hours. Given his recent long-distance travel and clinical symptoms, a pulmonary embolism was suspected. However, pathological examination of the excised pulmonary artery intraluminal mass demonstrated an angiomatoid fibrous histiocytoma. This case describes the clinicopathological and immunohistochemical features and molecular profile of a rare type of pulmonary artery tumour, a pulmonary artery angiomatoid fibrous histiocytoma.

Massive Air Embolism Following Necrotizing Pancreatitis and COVID-19 Infection-The Role of Postmortem Computed Tomography.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the COVID-19 pandemic raised important questions about workplace exposures to the virus, including postmortem exposures. The complexity of COVID-19 disease and its numerous unanticipated complications made autopsy even more vital in determining the pathophysiology of the disease. Performing traditional autopsy, however, carries risk of exposure. The following report describes an unusual case in which a patient diagnosed with COVID-19 and necrotizing pancreatitis underwent postmortem computed tomography (PMCT) prior to limited traditional autopsy and was unexpectedly found via PMCT to have large and diffuse venous air emboli and a new peripancreatic hematoma. In this case, not only did PMCT play a crucial role in determining the cause of death but also it allowed for a limited autopsy, thereby reducing the exposure to SARS-CoV-2 and associated risk to the autopsy staff and pathologists.

Prostate Cancer Screening and Incidence among Aging Persons Living with HIV.

PURPOSE: The risk of prostate cancer among persons living with human immunodeficiency virus (PWH) is not well understood and may be obscured by different opportunities for detection. MATERIALS AND METHODS: We identified 123,472 (37,819 PWH and 85,653 comparators) men enrolled in the Veterans Aging Cohort Study, a prospective national cohort of PWH and demographically matched, uninfected comparators in 2000-2015. We calculated rates of prostate specific antigen (PSA) testing by human immunodeficiency virus (HIV) status and fit multivariable Poisson models comparing the rates of PSA testing, prostate biopsy, and cancer incidence. RESULTS: The mean age at enrollment was 52 years. Rates of PSA testing were lower in PWH versus uninfected comparators (0.58 versus 0.63 tests per person-year). Adjusted rates of PSA screening and prostate biopsy were lower among PWH (incidence rate ratio [IRR] 0.87, 95% CI 0.75-0.84 and IRR 0.79 95% CI 0.74-0.83, respectively). The crude IRR for prostate cancer was lower in PWH versus controls (IRR 0.90, 95% CI 0.83-0.97). However, in a multivariable model adjusting for PSA testing, cancer incidence was similar by HIV status (IRR=0.93, 95% CI 0.86-1.01, p=0.08). Among patients who received a prostate biopsy, incidence of prostate cancer did not differ significantly by HIV status (IRR 1.06, 95% CI 0.98-1.15, p=0.15). Among incident cancers, there were significant differences in the distributions of Gleason grade (p=0.05), but not cancer stage (p=0.14) by HIV status. CONCLUSIONS: When accounting for less PSA testing among PWH, the incidence of prostate cancer was similar by HIV status. These findings suggest that less screening contributed to lower observed incidence of prostate cancer in PWH.

Impact of Hematology Electronic Consultations on Utilization of Referrals and Patient Outcomes in an Integrated Health Care System.

INTRODUCTION: Electronic consultations (e-consults) may be a valuable tool in the current era of increased demand for hematologists. Despite the increasing use of e-consults in hematology, their optimal utilization and impact on patient outcomes and workload are largely unknown. METHODS: In this retrospective cohort study, we studied the hematology consult experience at Veterans Affairs Connecticut from 2006 to 2018. We included 7,664 hematology consults (3,240 e-consults and 4,424 face-to-face [FTF] consults) requested by 1,089 unique clinicians. RESULTS: We found that e-consults were rapidly adopted and used equally among physicians of different degrees of experience. The number of FTF consults did not decrease after the introduction of e-consult services. E-consults were preferentially used for milder laboratory abnormalities that had been less likely to result in a consult before their availability. Referring clinicians used e-consults preferentially for periprocedural management, anemia, leukopenia, and anticoagulation questions. Eighty-three percent of e-consults were resolved without needing an FTF visit in the year after the consult. Consults for pancytopenia, gammopathy, leukocytosis, and for patients with known malignancy were less likely to be resolved by e-consult. Among patients who were diagnosed with a new hematologic malignancy after their consult, having an e-consult before an FTF visit did not adversely affect survival. CONCLUSION: In summary, e-consults safely expanded delivery of hematology services in our health care system but increased total consult volume. We report novel data on what types of consults may be best suited to the electronic modality, the impact of e-consults on workload, and their optimal use and implementation.

Risks of Opportunistic Infections in People With Human Immunodeficiency Virus With Cancers Treated With Chemotherapy.

BACKGROUND: We ascertained incidence of opportunistic infections (OIs) in people with human immunodeficiency virus (PWH) with cancer undergoing chemotherapy with non-human immunodeficiency virus (HIV) comparators. METHODS: We identified 2106 PWH and 2981 uninfected Veterans with cancer who received at least 1 dose of chemotherapy between 1996 and 2017 from the Veterans Aging Cohort Study. We ascertained incident OIs within 6 months of chemotherapy amongst zoster, cytomegalovirus, tuberculosis, Candida esophagitis, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, Cryptococcosis, atypical Mycobacterium infection, Salmonella bacteremia, histoplasmosis, coccidioidomycosis, or progressive multifocal leukoencephalopathy. We used Poisson methods to calculate OI incidence rates by HIV status, stratifying for hematological and nonhematological tumors. We compared OI rates by HIV status, using inverse probability weights of HIV status, further adjusting for PCP prophylaxis. RESULTS: We confirmed 106 OIs in 101 persons. Adjusted OI incidence rate ratios (IRRs) indicated higher risk in PWH for all cancers (IRR, 4.8; 95% confidence interval [CI], 2.8-8.2), hematological cancers (IRR, 8.2; 95% CI, 2.4-27.3), and nonhematological cancers (IRR, 3.9; 95% CI, 2.1-7.2). Incidence rate ratios were not significantly higher in those with CD4 >200 cells/mm3 and viral load <500 copies/mL (IRR, 1.8; 95% CI, 0.9-3.2). All PCP cases (n = 11) occurred in PWH, with 2 microbiologically unconfirmed cases among 1467 PWH with nonhematological cancers, no PCP prophylaxis, and CD4 counts >200/mm3. CONCLUSIONS: Veterans with HIV undergoing chemotherapy had higher rates of OIs than uninfected Veterans, particularly those with hematological cancers, but not in PWH with HIV controlled disease. Our study does not support systematic PCP prophylaxis in solid tumors in PWH with HIV controlled disease.

A Machine Learning Model to Successfully Predict Future Diagnosis of Chronic Myelogenous Leukemia With Retrospective Electronic Health Records Data.

BACKGROUND: Chronic myelogenous leukemia (CML) is a clonal stem cell disorder accounting for 15% of adult leukemias. We aimed to determine if machine learning models could predict CML using blood cell counts prior to diagnosis. METHODS: We identified patients with a diagnostic test for CML (BCR-ABL1) and at least 6 consecutive prior years of differential blood cell counts between 1999 and 2020 in the largest integrated health care system in the United States. Blood cell counts from different time periods prior to CML diagnostic testing were used to train, validate, and test machine learning models. RESULTS: The sample included 1,623 patients with BCR-ABL1 positivity rate 6.2%. The predictive ability of machine learning models improved when trained with blood cell counts closer to time of diagnosis: 2 to 5 years area under the curve (AUC), 0.59 to 0.67, 0.5 to 1 years AUC, 0.75 to 0.80, at diagnosis AUC, 0.87 to 0.92. CONCLUSIONS: Blood cell counts collected up to 5 years prior to diagnostic workup of CML successfully predicted the BCR-ABL1 test result. These findings suggest a machine learning model trained with blood cell counts could lead to diagnosis of CML earlier in the disease course compared to usual medical care.

Short-term outcomes for lung cancer resection surgery in HIV infection.

OBJECTIVE: Lung cancer is the leading cause of cancer death in people living with HIV (PWH). Surgical resection is a key component of potentially curative treatment regimens for early-stage lung cancers, but its safety is unclear in the setting of HIV. From a national cohort, we assessed potential differences in the risk of major lung cancer surgery complications by HIV status. DESIGN: We linked clinical and cancer data from the Veterans Aging Cohort Study (VACS) and Veterans Affairs Corporate Data Warehouse to outcomes from the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and identified 8371 patients (137 PWH, 8234 uninfected) who underwent lung cancer surgeries between 2000 and 2016. METHODS: We compared rates of 15 major short-term surgical complications by HIV status. RESULTS: Use of surgical resection for early-stage lung cancer did not differ by HIV status. Lung cancer surgery postoperative (30-day) mortality was 2.0% for PWH and did not differ by HIV status (P = 0.9). Pneumonia was the most common complication for both PWH and uninfected veterans, but did not differ significantly in prevalence between groups (11.0% for PWH versus 9.4%; P = 0.5). The frequency of complications did not differ by HIV status for any complication (all P > 0.3). There were no significant predictors of postoperative complications for PWH. CONCLUSIONS: In a national antiretroviral-era cohort of lung cancer patients undergoing surgical lung resection, short-term outcomes after surgery did not differ significantly by HIV status. Concerns regarding short-term surgical complications should have limited influence on treatment decisions for PWH with lung cancer.

Bullous hemorrhagic dermatosis is an under-recognized side effect of full dose low-molecular weight heparin: a case report and review of the literature.

Bullous hemorrhagic dermatosis (BHD) is a systemic side-effect of low molecular weight heparin, characterized by multiple intra-epidermal hemorrhages distant from the site of injection. There have been several small case series and literature reviews on BHD, but none have captured a complete set of reported patients. We sought to describe a case of BHD with late diagnosis and completely summarize the existing English and Spanish literature with searches of Pubmed, Scopus, Ovid Embase and Ovid Medline. After narrowing to 33 relevant reports, we describe 90 reported cases worldwide from 2004 to 2017, in addition to a new case from our institution as a means of comparison. We found that BHD was common in elderly men (mean age 72 ± 12; male:female, 1.9:1) and typically occurred within 7 days of administration of anticoagulation (median 7 days ± 6.4) usually with enoxaparin use (66% of cases). Lesions occurred primarily on the extremities only (67.9% of cases). Coagulation testing was most often normal before administration, and the majority of patients had coagulation testing in therapeutic range during treatment. Most practitioners stopped anticoagulation if continued therapeutic intervention was no longer required (57% of cases), or changed therapy to another anticoagulation if continued treatment was required (14.3% of cases). Therapy was continued outright in 23% of patients. The lesions usually resolved within 2 weeks (mean days, 13.0 ± 7.4). There was no difference in time to resolution between patients who continued the culprit anticoagulant or changed to a different anticoagulant, and those who discontinued anticoagulation altogether (13.9 days vs. 12.1, p = 0.49). Four deaths have been reported in this clinical context, two specified as intracranial hemorrhage. These deaths were unrelated to the occurrence of BHD. Continuation of low-molecular weight heparins appeared to be safe in patients with BHD.

The prevention of chemotherapy induced peripheral neuropathy by concurrent treatment with drugs used for bipolar disease: a retrospective chart analysis in human cancer patients.

Peripheral neuropathy is a major adverse effect in the use of chemotherapeutic drugs. In nearly 50% of patients, chemotherapy induced peripheral neuropathy (CIPN) has been reported as irreversible. With increasing numbers of patients surviving treatment as well as increasing duration of survival after treatment, reducing the side effects of chemotherapy and improving the quality of life has become a major focus of cancer survivorship. Multiple classes of chemotherapeutic drugs including taxanes, platinum agents and vinka alkaloids list peripheral neuropathy as the main dose-limiting side effect of treatment. We previously found that drugs that interfere with the microtubule function, including taxanes and vinca alkaloids, bind to neuronal calcium sensor 1 (NCS1), leading to aberrant calcium signaling. The altered calcium signaling can be mitigated by application of drugs used to treat bipolar disease (e.g., lithium and valproic acid) prior to initiation of chemotherapy. Because pre-treatment with these drugs prevented CIPN in mice treated with taxanes, we sought clinical evidence by performing a retrospective chart review study of the VA electronic health record to see whether or not there would be evidence to support our scientific belief that patients treated with lithium or valproic acid while receiving chemotherapy have a lower risk for development of CIPN than patients who received chemotherapy alone. Our data did provide evidence supporting the belief that treatment with lithium or valproic acid concurrently with chemotherapy was associated with a decreased incidence of developing CIPN.

Comparison of Natural Language Processing and Manual Coding for the Identification of Cross-Sectional Imaging Reports Suspicious for Lung Cancer.

PURPOSE: To compare the accuracy and reliability of a natural language processing (NLP) algorithm with manual coding by radiologists, and the combination of the two methods, for the identification of patients whose computed tomography (CT) reports raised the concern for lung cancer. METHODS: An NLP algorithm was developed using Clinical Text Analysis and Knowledge Extraction System (cTAKES) with the Yale cTAKES Extensions and trained to differentiate between language indicating benign lesions and lesions concerning for lung cancer. A random sample of 450 chest CT reports performed at Veterans Affairs Connecticut Healthcare System between January 2014 and July 2015 was selected. A reference standard was created by the manual review of reports to determine if the text stated that follow-up was needed for concern for cancer. The NLP algorithm was applied to all reports and compared with case identification using the manual coding by the radiologists. RESULTS: A total of 450 reports representing 428 patients were analyzed. NLP had higher sensitivity and lower specificity than manual coding (77.3% v 51.5% and 72.5% v 82.5%, respectively). NLP and manual coding had similar positive predictive values (88.4% v 88.9%), and NLP had a higher negative predictive value than manual coding (54% v 38.5%). When NLP and manual coding were combined, sensitivity increased to 92.3%, with a decrease in specificity to 62.85%. Combined NLP and manual coding had a positive predictive value of 87.0% and a negative predictive value of 75.2%. CONCLUSION: Our NLP algorithm was more sensitive than manual coding of CT chest reports for the identification of patients who required follow-up for suspicion of lung cancer. The combination of NLP and manual coding is a sensitive way to identify patients who need further workup for lung cancer.

A Clinical Decision Support System for Monitoring Post-Colonoscopy Patient Follow-Up and Scheduling.

This paper describes a natural language processing (NLP)-based clinical decision support (CDS) system that is geared towards colon cancer care coordinators as the end users. The system is implemented using a metadata- driven Structured Query Language (SQL) function (discriminant function). For our pilot study, we have developed a training corpus consisting of 2,085 pathology reports from the VA Connecticut Health Care System (VACHS). We categorized reports as "actionable"- requiring close follow up, or "non-actionable"- requiring standard or no follow up. We then used 600 distinct pathology reports from 6 different VA sites as our test corpus. Analysis of our test corpus shows that our NLP approach yields 98.5% accuracy in identifying cases that required close clinical follow up. By integrating this into our cancer care tracking system, our goal is to ensure that patients with worrisome pathology receive appropriate and timely follow-up and care.

The effect of pre-existing mental health comorbidities on the stage at diagnosis and timeliness of care of solid tumor malignances in a Veterans Affairs (VA) medical center.

There are limited data on the impact of mental health comorbidities (MHC) on stage at diagnosis and timeliness of cancer care. Axis I MHC affect approximately 30% of Veterans receiving care within the Veterans Affairs (VA) system. The purpose of this study was to compare stage at diagnosis and timeliness of care of solid tumor malignancies among Veterans with and without MHC. We performed a retrospective analysis of 408 charts of Veterans with colorectal, urothelial, and head/neck cancer diagnosed and treated at VA Connecticut Health Care System (VACHS) between 2008 and 2011. We collected demographic data, stage at diagnosis, medical and mental health co-morbidities, treatments received, key time intervals, and number of appointments missed. The study was powered to assess for stage migration of 15-20% from Stage I/II to Stage III/IV. There was no significant change in stage distribution for patients with and without MHC in the entire study group (p = 0.9442) and in each individual tumor type. There were no significant differences in the time intervals from onset of symptoms to initiation of treatment between patients with and without MHC (p = 0.1135, 0.2042 and 0.2352, respectively). We conclude that at VACHS, stage at diagnosis for patients with colorectal, urothelial and head and neck cancers did not differ significantly between patients with and without MHC. Patients with MHC did not experience significant delays in care. Our study indicates that in a medical system in which mental health is integrated into routine care, patients with Axis I MHC do not experience delays in cancer care.

New developments in the treatment of castration resistant prostate cancer.

In the past 5 years, the treatment and understanding of metastatic castrate resistant prostate cancer (CRPC) have improved dramatically. Our understanding of the mechanisms of castration resistance has allowed for the development of new drugs to target prostate cancer, and our understanding of genetic mutations may give us new tools with which to more accurately diagnose and be able to predict the course of this heterogeneous disease. This article summarizes the recent advances in the understanding of the development of CRPC, as well as the new drugs and targets, which have evolved from this basic research.