Serum ferritin and risk of colonic neoplasia: Implications for the workup and treatment of iron deficiency.

Iron deficiency is the most common extraintestinal sign of colonic neoplasia, including colorectal cancer (CRC) and other lower gastrointestinal pathology. Both upper endoscopy and colonoscopy is usually recommended in the work-up of patients with unexplained iron deficiency, particularly in men and postmenopausal women. As the incidence of early-onset CRC (age <50 years) rises in the United States, there is an increasing need to identify risk predictors to aid in the early detection of CRC. It remains unknown if serum ferritin (SF), and what specific threshold, can be used as a marker to stratify those at risk for CRC and other lower gastrointestinal pathology. In this current review of the literature, we aimed to review guidelines for diagnostic workup of colonic neoplasia in the setting of iron deficiency and examine the association and specific thresholds of SF and risk of CRC by age. Some of the published findings are conflicting, and conclusions specific to younger patients are limited. Though further investigation is warranted, the cumulative findings suggest that SF, in addition to considering the clinical context and screening guidelines, may have potential utility in the assessment of colonic neoplasia.

Psychological toxicity in classical hematology.

Although considered "benign," mild blood count abnormalities, genetic factors imparting inconsequential thrombotic risk, and low-risk premalignant blood disorders can have significant psychological and financial impact on our patients. Several studies have demonstrated that patients with noncancerous conditions have increased levels of anxiety with distress similar to those with malignancy. Additionally, referral to a classical hematologist can be a daunting process for many patients due to uncertainties surrounding the reason for referral or misconstrued beliefs in a cancer diagnosis ascribed to the pairing of oncology and hematology in medical practice. If not properly triaged, incidental laboratory abnormalities can trigger extensive and costly evaluation. These challenges are compounded by a lack of consensus guidance and generalizability of modern reference ranges that do not adequately account for common influencing factors. Although often benign, incidental hematologic findings can lead to emotional suffering and careful consideration of the potential psychological and financial duress imparted to an individual must be considered. In this article, we will review the current literature describing the psychological effect of some commonly known hematologic conditions, identify benign causes for variations in hematologic laboratory values, and provide recommendations to reduce psychological toxicity as it pertains to hematologic testing.

Estrogen-based hormonal therapy and the risk of thrombosis in COVID-19 patients.

OBJECTIVE: Estrogen-containing contraceptives and hormone replacement therapy are used commonly, however, the risks of venous and arterial thrombosis imparted by such medications during COVID-19 infection or other similar viral infections remain undescribed. METHODS: To assess the risk of venous and arterial thrombosis in patients receiving oral estrogen-containing therapy (ECT) with COVID-19 as compared to those receiving non-estrogen-based hormonal therapy, we conducted a multicenter cohort study of 991 patients with confirmed COVID-19 infection, 466 receiving estrogen-containing hormonal therapy, and 525 receiving progestin-only or topical therapy. RESULTS: The use of estrogen-containing therapy was found to significantly increase the risk of venous thromboembolism (VTE) following COVID-19 diagnosis after controlling for age (HR 5.46 [95% CI 1.12-26.7, p = .036]). This risk was highest in patients over age 50, with 8.6% of patients receiving estrogen-containing therapy diagnosed with VTE compared to 0.9% of those receiving non-estrogen-based therapies (p = .026). The risk of arterial thrombosis was not significantly associated with oral estrogen use. CONCLUSIONS: These results suggest that estrogen-containing therapy is associated with a significantly increased risk of VTE in COVID-19 patients, especially in older individuals. These findings may guide provider counseling and management of patients with COVID-19 on estrogen-containing therapy.

The diagnosis and management of suspected lymphoma in general practice.

With rapid advancements in diagnosis and treatment of malignancies, the gap between generalists and subspecialists continues to widen, particularly in cancers like lymphoma where the spectrum of disease varies from indolent to rapidly progressive. Prior to establishing with a hematologist/oncologist, patients must be accurately and comprehensively diagnosed and managed for lymphoma in the generalist setting. In the following manuscript, we review the common clinical presentations in which should raise concern for lymphoma. We summarize the literature regarding the role of laboratory studies including complete blood count and peripheral blood flow cytometry, the recommendations for lymph node sampling, the role and selection of imaging modalities, and ideal patient monitoring for high-risk clinical syndromes that may be encountered in lymphoma.

The role of oral iron in the treatment of adults with iron deficiency.

Iron deficiency is the most common nutrient deficiency in the world, affecting over 20% of premenopausal women worldwide. Oral iron supplementation is often the first-line treatment for the acute and chronic management of iron deficiency due to its ease and accessibility. However, there is no consensus on the optimal formulation or dosing strategy, or which patients should be preferentially treated with intravenous iron. Management of iron deficiency is complicated by the hepcidin-ferroportin iron regulatory pathway, which has evolved to prevent iron overload and thereby creates an inherent limit on gastrointestinal iron uptake and efficacy of oral iron. Unabsorbed iron propagates many of the side effects that complicate oral iron use including dyspepsia and constipation, all of which can thus be exacerbated by excessive oral iron doses. Daily low dose and every other day dosing protocols have attempted to bypass this physiologic bottleneck to allow for effective absorption and limit side effects; however, this approach has still resulted in low fractional iron absorption. In the following manuscript, we review the pathophysiology of iron absorption and current evidence for various preparations of oral iron. Lastly, we highlight opportunities for further study to advance the care of individuals affected by iron deficiency.

Screening for occult cancer after unprovoked venous thromboembolism: Assessing the current literature and future directions.

While significant evidence has established an increased rate of thrombosis in patients with cancer, the risk of occult malignancy in the setting of an unprovoked thrombosis is less clear. Despite continued interest in developing an effective screening system for occult malignancy following unprovoked venous thromboembolism (VTE), discrepancies in the literature and guideline recommendations leave providers uncertain whether to screen or perform further diagnostics for this patient population. Evidence suggests that screening for malignancy can detect cancer sooner in patients with unprovoked VTE, but there is a lack of high-quality evidence demonstrating improvements in survival who receive early detection. In the following manuscript, we summarize VTE in relation to cancer epidemiology and pathophysiology. Our literature review summarizes the spectrum of testing strategies for occult malignancy following unprovoked VTE, including biomarker detection methods and various imaging approaches. We evaluate the benefit of additional diagnostic strategies, review current guidelines on the issue, and provide guidance to the reader on the best practice for investigating undiagnosed malignancy in patients with unprovoked VTE.

Clinical predictors for thrombus progression in cirrhotic patients with untreated splanchnic vein thrombosis.

INTRODUCTION: Splanchnic vein thrombosis (SVT) occurs in a heterogenous group of patients secondary to a variety of risk factors including liver disease. Minimal data regarding natural history and outcomes of SVT exists to inform management decisions. As such, there is equipoise regarding the utility of anticoagulation in cirrhotic patients with SVT. We sought to identify clinical factors predictive of new or progressive thrombosis in a cohort of patients with untreated SVT. METHODS: We conducted a retrospective cohort study of cirrhotic patients over 18 years of age diagnosed with SVT at the Oregon Health & Science University from 2015 to 2020, excluding those initially treated with anticoagulation. The primary study endpoint was a composite of the following: imaging-confirmed progression of SVT, development of cavernous transformation, intestinal ischemia, portal cholangiopathy or new venous or arterial thrombosis. RESULTS: 261 patients were included in the analysis (median age 61 years, 68% male, 32% female). Forty percent of all patients experienced the primary composite endpoint. Multivariable logistic regression found that only the presence of pancreatitis or abdominal infection at diagnosis was associated with an increased likelihood of experiencing thrombus progression in patients with untreated SVT (OR 3.61, P = 0.02). There was a statistically significant overall survival difference between patients that did and did not experience the primary composite endpoint after controlling for confounding variables. (p = 0.0068). CONCLUSIONS: Overall, only the presence of pancreatitis or intrabdominal infection were found to be significantly associated with thrombotic progression, with varices identified as marginally non-significant risk factor. Notably, thrombotic progression was associated with a significant reduction in overall survival.

Anticoagulation in Cirrhosis: Evidence for the Treatment of Portal Vein Thrombosis and Applications for Prophylactic Therapy.

The clinical utility of anticoagulation for patients with cirrhosis and asymptomatic portal vein thrombosis (PVT) is widely debated. Complex hemostatic derangements in cirrhosis that increase risk of both bleeding and thrombosis, as well as a lack of randomized controlled data, limit conclusive assessments regarding optimal management of anticoagulation in this setting. In this review, we summarize the relevant literature pertaining to PVT in cirrhosis, including the effect of untreated PVT on the natural progression of liver disease and the overall impact of anticoagulation on clot burden and other relevant clinical outcomes. Apart from patients who are symptomatic or listed for liver transplantation, data supporting anticoagulation for the treatment of PVT is limited and without clear consensus guidelines. In patients with cirrhosis without PVT, emerging evidence for the role of prophylactic anticoagulation to mitigate the progression of fibrosis suggests an optimal risk-benefit tradeoff with decreased rates of liver decompensation and mortality, without a heightened risk of bleeding. In summation, as our understanding of the role of both prophylactic and therapeutic anticoagulation in cirrhosis continues to evolve, ongoing risk stratification of patients with asymptomatic PVT demands further attention.

Platelet reactivity and platelet count in women with iron deficiency treated with intravenous iron.

Background: Iron deficiency anemia (IDA) and heavy menstrual bleeding are prevalent, interrelated issues impacting over 300 million premenopausal women worldwide. IDA is generally associated with increased platelet counts; however, the effects of IDA and its correction on platelet function in premenopausal women remain unknown. Objectives: We sought to determine how IDA and intravenous iron affect platelet count and platelet function in premenopausal women. Methods: Hematologic indices were assessed in a multicenter, retrospective cohort of 231 women repleted with intravenous iron. Pre- and postinfusion blood samples were then obtained from a prospective cohort of 13 women to analyze the effect of intravenous iron on hematologic parameters as well as platelet function with flow cytometry and platelet aggregation assays under physiologic shear. Results: Following iron replacement, anemia improved, and mean platelet counts decreased by 26.5 and 16.0 K/mm3 in the retrospective and prospective cohorts, respectively. Replacement reduced baseline platelet surface P-selectin levels while enhancing platelet secretory responses to agonists, including collagen-related peptide and ADP. Platelet adhesion and aggregation on collagen under physiologic shear also significantly increased following repletion. Conclusion: We find that intravenous iron improves anemia while restoring platelet counts and platelet secretory responses in premenopausal women with iron deficiency. Our results suggest that iron deficiency as well as iron replacement can have a range of effects on platelet production and function. Consequently, platelet reactivity profiles should be further examined in women and other groups with IDA where replacement offers a promising means to improve anemia as well as quality of life.

The hemostatic and thrombotic complications of liver disease.

Hepatic cirrhosis leads to numerous hematologic derangements resulting in a complex and tenuously rebalanced hemostatic milieu. The utility of common hematologic tests including the INR and aPTT in assessing hemostatic and thrombotic risk in patients with cirrhosis is limited, and consensus on transfusion thresholds and proper management of thrombotic complications continues to evolve. This review summarizes the pathophysiology of key derangements of hemostasis including those of platelets, von Willebrand factor, pro- and anticoagulation factors, and fibrin. Additionally, the pathogenesis, consequences, optimal management, and prevention of major thrombotic and bleeding complications in cirrhosis arte discussed.

IDH Inhibitors in AML-Promise and Pitfalls.

PURPOSE OF REVIEW: Mutations in isocitrate dehydrogenase genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML), occurring in up to 30% of AML cases. Mutations in IDH leads to abnormal epigenetic regulation in AML cells and blocks differentiation. Inhibitors of mutated IDH1 and IDH2, ivosidenib and enasidenib, respectively, were recently approved by the FDA for relapsed/refractory AML; ivosidenib is also approved for newly diagnosed AML patients not fit for standard chemotherapy. Here, we discuss the clinical development of IDH inhibitors, their unique side effects, and outline future combination approaches in AML. RECENT FINDINGS: IDH inhibitors are well-tolerated but can induce differentiation of AML cells, which leads to the on-target side effect of differentiation syndrome in up to 20% of patients. Although IDH inhibitors demonstrate efficacy as monotherapy, recent trials have shown that they have higher response rates in combination with hypomethylating agents (HMAs). Current trials of IDH inhibitors include combination with standard induction chemotherapy, as maintenance therapy, and in combination with venetoclax-based regimens. IDH inhibitors are active and have a favorable toxicity profile in AML therapy. Current clinical trials are evaluating how to best incorporate IDH inhibitors into combination therapy to optimize outcomes and duration of response for AML patients with IDH mutations.

Head injury and neuropsychiatric sequelae in asylum seekers.

OBJECTIVE: Asylum seekers experience a high burden of physical and psychological trauma, yet there is a scarcity of literature regarding the epidemiology and sequelae of head injury (HI) in asylum seekers. We examined HI prevalence and association with neuropsychiatric comorbidities in asylum seekers. METHODS: A retrospective cross-sectional study was performed through review of 139 medical affidavits from an affidavit database. Affidavits written from 2010 to 2018 were included. Demographic and case-related data were collected and classified based on the presence of HI. For neuropsychiatric sequelae, the primary study outcome was headache and the secondary outcomes were depression, posttraumatic stress disorder, and anxiety. Multivariable logistic regression was performed to examine the association between HI and neuropsychiatric sequelae, adjusted for demographic and clinical characteristics. RESULTS: A total of 139 medical affidavits of asylum seekers were included. The mean age was 27.4 ± 12.1 years, 56.8% were female, and 38.8% were <19 years. Almost half (42.5%) explicitly self-reported history of HI. Compared to clients who did not report HI, clients with HI were older and more likely to report a history of headache, physical abuse, physical trauma, concussion, and loss of consciousness. After adjustment for demographic and clinical characteristics, clients with HI had greater odds for neuropsychological sequelae such as headache (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.0-8.7) and depression (OR 2.5, 95% CI 1.1-5.7). CONCLUSIONS: We observed a high prevalence of HI in asylum seekers. Comprehensive screening for HI and neuropsychiatric comorbidities is encouraged when evaluating asylum seekers.

DNA damage repair deficiency as a predictive biomarker for FOLFIRINOX efficacy in metastatic pancreatic cancer.

Patients with pathogenic germline and somatic variants in DNA damage repair (DDR) genes may derive greater benefit with platinum-based chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC). This study investigates the role of DDR genes as a predictive biomarker for response to first-line platinum chemotherapy with FOLFIRINOX in metastatic PDAC patients. Demographic, clinical, and pathologic variables were collected for patients with metastatic PDAC who received FOLFIRINOX as frontline treatment and who had germline and somatic genetic testing. Kaplan-Meier analysis of overall survival (OS) and progression free survival (PFS) were correlated to the presence of DDR pathogenic variants. Forty patients with metastatic PDAC met inclusion criteria. Germline genetic testing revealed germline pathogenic variants in DDR genes in 5 patients (12%), and somatic pathogenic variants in DDR genes in 4 patients (10%). Median PFS was significantly longer in patients with any (germline or somatic) pathogenic variant in DDR genes than in those without alterations 18.5 vs. 6.9 months (log-rank P=0.003). When restricted to the presence or absence of germline pathogenic variants in DDR genes, the median PFS was 18.5 vs. 7.4 months (log-rank P=0.005). The median OS for the entire cohort was 11.5 months was not statistically different between the two groups, however there were no deaths in the subgroup with germline pathogenic variants in DDR genes treated with frontline FOLFIRINOX. A subset of patients with metastatic PDAC and germline or somatic pathogenic variants in DDR genes have a statistically superior PFS when treated with the platinum containing regimen FOLFIRINOX. The role of DDR gene alterations as a predictive biomarker for FOLFIRINOX benefit should be further evaluated in prospective trials.

Recent Advances in Understanding the Pathogenesis of Cardiovascular Diseases and Development of Treatment Modalities.

Cardiovascular Diseases (CVDs) are a leading cause of morbidity and mortality worldwide. The underlying pathology for cardiovascular disease is largely atherosclerotic in nature and the steps include fatty streak formation, plaque progression and plaque rupture. While there is optimal drug therapy available for patients with CVD, there are also underlying drug delivery obstacles that must be addressed. Challenges in drug delivery warrant further studies for the development of novel and more efficacious medical therapies. An extensive understanding of the molecular mechanisms of disease in combination with current challenges in drug delivery serves as a platform for the development of novel drug therapeutic targets for CVD. The objective of this article is to review the pathogenesis of atherosclerosis, first-line medical treatment for CVD, and key obstacles in an efficient drug delivery.

Coprevalence of type 2 diabetes mellitus and tuberculosis in low-income and middle-income countries: A systematic review.

Increasing coprevalence of diabetes mellitus (DM) and tuberculosis (TB) in low-income and middle-income countries (LMICs) indicates a rising threat to the decades of progress made against TB and requires global attention. This systematic review provides a summary of type 2 diabetes and tuberculosis coprevalence in various LMICs. We searched PubMed, Ovid Medline, Embase, and PsychINFO databases for studies that provided estimates of TB-DM coprevalence in LMICs published between 1990 and 2016. Studies that were non-English and exclusively conducted in multidrug resistant-tuberculosis or type 1 diabetes and inpatient settings were excluded. We reviewed 84 studies from 31 countries. There were huge diversity of study designs and diagnostic methods used to estimate coprevalence, and this precluded pooling of the results. Most studies (n = 78) were from small, localized settings. The DM prevalence among TB patients in various LMICs varied from 1.8% to 45%, with the majority (n = 44) between 10% and 30%. The TB prevalence among people with DM ranged from 0.1% to 6.0% with most studies (n = 9) reporting prevalences less than 2%. Coprevalence of TB-DM was higher than general population prevalence of either diseases in these countries. This study underscores the need for intervention and more focused research on TB DM bidirectional screening programs in low-income and middle-income countries as well as integrated chronic disease management.

Recent treatment modalities for cardiovascular diseases with a focus on stem cells, aptamers, exosomes and nanomedicine.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Due to the significant impact of CVD on humans, there is a need to develop novel treatment modalities tailored to major classes of cardiac diseases including hypertension, coronary artery disease, cardiomyopathies, arrhythmias, valvular disease and inflammatory diseases. In this article, we discuss recent advancements regarding development of therapeutic strategies based on stem cells, aptamers, exosomes, drug-eluting and dissolvable stents, immunotherapy and nanomedicine for the treatment of CVD. We summarize current research and clinical advances in cardiovascular therapeutics, with a focus on therapies that move beyond current oral- or sublingual-based regimens. This review article provides insight into current research and future treatment strategies that hold a great relevance for future clinical practice in pursuit of improving quality of life of patients suffering from CVD.