Screening for pancreatic cancer has the potential to save lives, but is it practical?

INTRODUCTION: Most patients with pancreatic cancer present with advanced stage, incurable disease. However, patients with high-grade precancerous lesions and many patients with low-stage disease can be cured with surgery, suggesting that early detection has the potential to improve survival. While serum CA19.9 has been a long-standing biomarker used for pancreatic cancer disease monitoring, its low sensitivity and poor specificity have driven investigators to hunt for better diagnostic markers. AREAS COVERED: This review will cover recent advances in genetics, proteomics, imaging, and artificial intelligence, which offer opportunities for the early detection of curable pancreatic neoplasms. EXPERT OPINION: From exosomes, to circulating tumor DNA, to subtle changes on imaging, we know much more now about the biology and clinical manifestations of early pancreatic neoplasia than we did just five years ago. The overriding challenge, however, remains the development of a practical approach to screen for a relatively rare, but deadly, disease that is often treated with complex surgery. It is our hope that future advances will bring us closer to an effective and financially sound approach for the early detection of pancreatic cancer and its precursors.

Hepatocellular Carcinoma: Does the Background Liver With or Without Cirrhosis Matter?

OBJECTIVES: The pathologic differences between hepatocellular carcinoma (HCC) arising in noncirrhotic and cirrhotic livers have not been well studied. METHODS: We performed a retrospective analysis of 378 HCC cases (95 in noncirrhotic, 283 in cirrhotic livers) from pathology archives (2010-2017). RESULTS: Patients without cirrhosis were more likely to have hepatitis B (13.68% vs 2.83%, P < .001) or no known liver disease (30.53% vs 4.24%, P < .001), while hepatitis C was more common in patients with cirrhosis (65.72% vs 30.53%, P < .001). HCCs in noncirrhotic livers were larger in size (P < .001); were more likely to have a macrotrabecular histologic pattern (13.68% vs 4.95%, P < .01); were more likely to have fibrolamellar (3.16% vs 0%, P = .02), macrotrabecular-massive (13.68% vs 6.01%, P = .03), and clear cell (16.84% vs 6.71%, P < .01) subtypes; have a higher histologic grade (P < .01); be anaplastic tumor cells (P < .001); have a higher rate of vascular invasion (P < .01); and have a higher tumor stage (P = .04). CONCLUSIONS: The findings indicate that HCCs in noncirrhotic livers demonstrate a larger tumor size; have a more macrotrabecular histologic pattern; have fibrolamellar, macrotrabecular-massive, and clear cell subtypes; have a higher tumor grade and stage; have a higher rate of vascular invasion; and have more anaplastic tumor cells compared with cirrhotic livers. Further studies to explore different pathways that promote oncogenesis in noncirrhotic livers are needed to better understand the pathogenesis of HCC.

Acute and Delayed Intracranial Hemorrhage in Head-Injured Patients on Warfarin versus Direct Oral Anticoagulant Therapy.

INTRODUCTION: Direct oral anticoagulant (DOAC) use for thrombosis treatment and prophylaxis is a popular alternative to warfarin. This study compares rates of traumatic intracranial hemorrhage (ICH) for patients on anticoagulant therapies and the effect of combined anticoagulant and antiplatelet therapies. METHODS: A retrospective observational study of trauma patients was conducted at two level I trauma centers. Patients aged ≥18 years with preinjury use of an anticoagulant (warfarin, rivaroxaban, apixaban, or dabigatran) who sustained a blunt head injury within the past day were included. Patients were evaluated by head CT to evaluate for ICH. RESULTS: Three hundred and eighty-eight patients were included (140 on warfarin, 149 on a DOAC, and 99 on combined anticoagulant and antiplatelet therapies). Seventy-nine patients (20.4%) had an acute ICH, while 16 patients (4.1%) had a delayed ICH found on routine repeat CT. Those on combination therapy were not at increased risk of acute ICH (relative risk [RR] 0.90, confidence interval [CI]: 0.56-1.44; P > 0.5) or delayed ICH (RR 2.19, CI: 0.84-5.69; P = 0.10) compared to anticoagulant use only. Those on warfarin were at increased risk of acute ICH (RR 1.75, CI: 1.10-2.78, P = 0.015), but not delayed ICH (RR 0.99, CI 0.27-3.59, P > 0.5), compared to those on DOACs. No delayed ICH patients died or required neurosurgical intervention. CONCLUSION: Patients on warfarin had a higher rate of acute ICH, but not delayed ICH, compared to those on DOACs. Given the low rate of delayed ICH with no resultant morbidity or mortality, routine observation and repeat head CT on patients with no acute ICH may not be necessary.

Lessons in Public (Mis)communication about the Laboratory from the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has put the clinical laboratory in the spotlight. The news media is regularly seeking out interviews with microbiologists, infectious disease specialists, and pathologists. Increased public exposure offers opportunities to improve how laboratory professionals communicate our insights. We can emphasize what is new, unusual, or controversial about our knowledge; utilize social media effectively; and improve relationships with journalists by understanding their workflow and traditions. While public engagement has risks and must be considerate of institutional policies, it also validates our value to patients, policy makers, and employers.

Accepting randomness in medical school admissions: The case for a lottery.

McMaster University's medical school, faced with the need to socially distance during the COVID-19 pandemic, recently replaced their structured admission interview process with a partial lottery. At first, it may seem that leaving medical school admissions partly to chance could erode autonomy and meritocracy. Yet our current system for selecting medical students is strained by a limited predictive ability. In the search for good doctors, we lack meaningful, quantifiable, and comparable criteria. Partial or weighted admissions lotteries can offer us an escape. They have the potential to reduce mental and financial burdens on both applicants and medical schools, avoiding an overemphasis on marginal differences between applicants. Lotteries are also a simple way to address persistent admissions disparities by being truly non-discriminatory. At the very least, lotteries represent a useful benchmark against which we can rigorously compare current and future selection methods.

Antiplatelet therapy is associated with a high rate of intracranial hemorrhage in patients with head injuries.

BACKGROUND: Antiplatelet agents are increasingly used in cardiovascular treatment. Limited research has been performed into risks of acute and delayed traumatic intracranial hemorrhage (ICH) in these patients who sustain head injuries. Our goal was to assess the overall odds and identify factors associated with ICH in patients on antiplatelet therapy. METHODS: A retrospective observational study was conducted at two level I trauma centers. Adult patients with head injuries on antiplatelet agents were enrolled from the hospitals' trauma registries. Acute ICH was diagnosed by head CT. Observation and repeat CT to evaluate for delayed ICH was performed at clinicians' discretion. Patients were stratified by antiplatelet type and analyzed by ICH outcome. RESULTS: Of 327 patients on antiplatelets who presented with blunt head trauma, 133 (40.7%) had acute ICH. Three (0.9%) had delayed ICH on repeat CT, were asymptomatic and did not require neurosurgical intervention. One with delayed ICH was on clopidogrel and two were on both clopidogrel and aspirin. Patients with delayed ICH compared with no ICH were older (94 vs 74 years) with higher injury severity scores (15.7 vs 4.4) and trended towards lower platelet counts (141 vs 216). Patients on aspirin had a higher acute ICH rate compared with patients on P2Y12 inhibitors (48% vs 30%, 18% difference, 95% CI 4 to 33; OR 2.18, 95% CI 1.15 to 4.13). No other group comparison had significant differences in ICH rate. CONCLUSIONS: Patients on antiplatelet agents with head trauma have a high rate of ICH. Routine head CT is recommended. Patients infrequently developed delayed ICH. Routine repeat CT imaging does not appear to be necessary for all patients. LEVEL OF EVIDENCE: Level III, prognostic.

Euglycemic Diabetic Ketoacidosis Precipitated by SGLT-2 Inhibitor Use, Pericarditis, and Fasting: A Case Report.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Less prevalent is euglycemic DKA (eDKA)-DKA with serum glucose less than 200 mg/dL; however, it is increasing in frequency with the introduction of sodium glucose cotransporter 2 (SGLT-2) inhibitors for treatment of type 2 diabetes. CASE REPORT: We report a case of SGLT-2 inhibitor-associated eDKA presenting with concurrent acute pericarditis. DISCUSSION: Our case suggests that the cause of eDKA can be multifactorial when decreased oral intake occurs in the setting of an acute cause of physiologic stress. CONCLUSION: Prompt recognition of eDKA in the emergency department may allow earlier diagnosis and treatment directed at one or more of its underlying causes.

Strengthening the Medical Error "Meme Pool".

The exact number of patients in the USA who die from preventable medical errors each year is highly debated. Despite uncertainty in the underlying science, two very large estimates have spread rapidly through both the academic and popular media. We utilize Richard Dawkins' concept of the "meme" to explore why these imprecise estimates remain so compelling, and examine what potential harms can occur from their dissemination. We conclude by suggesting that instead of simply providing more precise estimates, physicians should encourage nuance in public medical error discussions, and strive to provide narrative context about the reality of the complex biological and social systems in which we practice medicine.

False-positive pathology: improving reproducibility with the next generation of pathologists.

The external validity of the scientific literature has recently come into question, popularly referred to as the "reproducibility crisis." It is now generally acknowledged that too many false positive or non-reproducible results are being published throughout the biomedical and social science literature due to misaligned incentives and poor methodology. Pathology is likely no exception to this problem, and may be especially prone to false positives due to common observational methodologies used in our research. Spurious findings in pathology contribute inefficiency to the scientific literature and detrimentally influence patient care. In particular, false positives in pathology affect patients through biomarker development, prognostic classification, and cancer overdiagnosis. We discuss possible sources of non-reproducible pathology studies and describe practical ways our field can improve research habits, especially among trainees.

Comparative Genomic Screen in Two Yeasts Reveals Conserved Pathways in the Response Network to Phenol Stress.

Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.

Pacemaker-associated Phlegmasia Cerulea Dolens Treated with Catheter-directed Thrombolysis.

Phlegmasia cerulea dolens (PCD) is a rare and severe form of deep venous thrombosis that is classically associated with the lower extremities. We report a case of upper extremity PCD developing abruptly in a 37-year-old female with an indwelling cardiac pacemaker who presented to the emergency department complaining of pain and paresthesias in her left arm, adjoining left chest wall, and inferior neck. Her condition was promptly diagnosed and successfully treated with intravenous unfractionated heparin and balloon venoplasty with catheter-directed thrombolysis without any known residual signs or symptoms at hospital discharge.