Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Cancer Antigen 125, Prostate-Specific Antigen and Other Cancer Markers: A Primer on Commonly Used Cancer Markers.

Cancer markers are molecules produced by cancer cells which may serve to identify the presence of cancer. Cancer markers can be differentiated as serum-based, radiology-based and tissue-based, and are one of the most important tools in diagnosing, staging and monitoring of treatment of many cancers. The most used cancer markers are serum cancer markers due to its relative ease and lower cost of testing. However, serum cancer markers have poor mass screening utilization due to poor positive predictive value. Several markers such as prostate-specific antigen (PSA), beta-human chorionic gonadotropin (B-hCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are used to aid in diagnosis of cancer in cases of high suspicion. Serum markers such as carcinoembryonic antigen (CEA), AFP, carbohydrate antigen 19-9 (CA 19-9), and 5-hydroxyindoleacetic acid (5-HIAA) play a significant role in assessing disease prognosis as well as response to treatment. This work reviews the role of some of the biomarkers in the diagnosis and treatment of cancer.

Bimodal Age Distribution in Cancer Incidence.

Cancer is caused by accumulation of genetic changes which include activation of protooncogenes and loss of tumor suppressor genes. The age-specific incidence of cancer in general increases with advancing age. However, some cancers exhibit a bimodal distribution. Commonly recognized cancers with bimodal age distribution include acute lymphoblastic leukemia, osteosarcoma, Hodgkin's lymphoma, germ cell tumors and breast cancer. Delayed infection hypothesis has been used to provide explanation for the early childhood peak in leukemias and lymphomas, whereas the peak at an older age is associated with accumulation of protooncogenes and weakened immune system. Further genetic analysis and histopathological variations point to distinctly different cancers, varying genetically and histologically, which are often combined under a single category of cancers. Tumor characteristics and age distribution of these cancers varies also by population groups and has further implications on cancer screening methods. Although significant advances have been made to explain the bimodal nature of such cancers, the specific genetic mechanisms for each age distribution remain to be elucidated. Further distinction among the different cancer subtypes may lead to improvements in individual risk assessments, prevention and enhancement of treatment strategies.

Analysis of Trends in Race and Gender Disparities in Incidence-Based Mortality in Patients Diagnosed with Soft Tissue Sarcomas from 2000 to 2016.

BACKGROUND: The clinical course of soft tissue sarcomas is often dependent on the grade of the tumor. The variability of incidence-based mortality in low-grade and high-grade soft tissue sarcomas (STS) with respect to gender and race over the past decade has not been well studied. This study analyzes the rates of incidence-based mortality from the years 2000 to 2016 amongst the grades, genders and racial groups of patients with STS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to conduct a nation-wide analysis for the years 2000 to 2016. Incidence-based mortality for all stages of low-grade and high-grade soft tissue sarcomas was queried and the results were grouped by race (Caucasian/White vs African American/Black) and gender. All stages and ages were included in the analysis and trend from 2000 to 2016 was analyzed. RESULTS: The incidence-based mortality rates for Caucasians are similar to African Americans in both grades and genders. Rates were not analyzed for American Indian and Asian/Pacific Islanders due to small sample size. Mortality rates of high-grade soft tissue sarcomas were significantly higher compared to low-grade tumors. A higher rate of mortality is noted in Caucasian males compared to African Americans males despite past observations of higher incidence in African Americans. There was no significant change in the rate when trended over the past decade (2007 to 2016). CONCLUSION: This study highlights the higher rate of incidence-based mortality in Caucasian males compared to African American males in the past 15 years despite a lower incidence reported in the 1995 to 2008 period. With no significant change in mortality rates/year noted during this time period, this study implies that soft tissue sarcomas in Caucasian males have worse outcomes. Further research is needed to understand the mechanism underlying this disparity.

Visibility Versus Privacy of Physicians in the Age of Social Media.

As access to the internet has grown over the years, social media has become an important resource in the health care sector. Third-party physician-rating websites in particular have gained popularity. However, there are ethical implications of such websites. These websites provide a platform for patients to evaluate and review physicians and likewise increase visibility and advertisement of physicians, but they also violate the rights to privacy that these doctors should have. This paper aims to study and assess the ethical implications of these websites on the visibility and privacy of physicians. After presenting the ethical dilemma associated with such websites, it provides guidelines that can be incorporated by both physicians and third-party sites to help maintain physician privacy while providing public service in the form of advertisement and visibility.

Trends in the crossover of patients in phase III oncology clinical trials in the USA.

BACKGROUND: The incorporation of crossover in randomised controlled trials is accepted as an ethical obligation, especially in cancer clinical trials. The more common type of crossover is crossover allowance, which allows patients assigned to one arm to switch to another arm if there is an established benefit in the crossover arm. In contrast, crossover-designed studies involve switching patients from all arms to a different arm as part of the study design. Crossover allowance may have advantages in patient recruitment and incorporating crossover after initial positive results fulfil ethical requirements. However, crossover can also contribute to confounding major endpoints of studies, such as overall survival or the second progression-free survival interval. For this reason, it is important to investigate and identify potential trends of crossover in clinical trials testing novel therapies. METHODS: Data about cancer clinical trials were extracted from clinicaltrials.gov. The search query was limited to completed phase III studies in adult populations. Location was limited to the USA. Date range extended from 1990 to 2019. Search query included the terms: cancer; completed- recruitment status; age: 18-65+ years; sex: all; location: USA; and study phase: phase 3. Studies were then excluded if they were not randomised controlled trials (RCTs) with the primary purpose of treatment and if they did not test cancer-related interventions. RESULTS: A total of 744 clinical trials were identified. There were 459 RCTs aimed at treatment, and of those, 35 utilised crossover. The start dates of these crossover trials ranged from 1997 to 2012. Thirty studies utilised crossover allowance. Prostate, breast and gastrointestinal stromal tumour cancers were the most represented cancer types in crossover studies. Among the 30 studies, the median proportion of patients who crossed over relative to the original arm assignment ranged from 2% to 88%, with a median of 57.5%. CONCLUSIONS: The proportion of identified clinical trials with crossover compared to those without is extremely small. Crossover in clinical trials studying cancer treatment does not appear to be a widespread practice. Even though statistical approaches to mitigate confounding exist, crossover can still skew accurate reporting of the impact of experimental therapies on overall survival.

Effect of immigration on mortality trends in sickle cell patients.

BACKGROUND: Sickle cell patient population in the U.S. continues to increase due a combination of birth of sickle cell disease infants, extension of lifespan of existing patients and also possibly, a contributing immigration component. These factors and most importantly the latter, might be altering national estimates by both underestimating the number of affected individuals as well as underestimating the impact of public health strategies given the estimates for which there were conceived. METHODS: National sickle cell disease estimates as per Centers for Disease Control (CDC) and immigrant population trends obtained from the U.S. Census Bureau from years 2010-2017 were examined. Immigrant groups from geographical regions highly prevalent for sickle cell disease were evaluated throughout this period of time. RESULTS: From years 2010 to 2017 Western Africa (Nigeria, Ghana, Cape Verde, Liberia, Sierra Leona), showed a population increase of 45.2%, 44.15%, 24%, 19.0% and 16.3% respectively. Eastern Africa (Ethiopia, Kenya and Eritrea) had a population increase of 55.7%, 46.8% and 65% respectively. Caribbean island (Dominican Republic, Haiti and Jamaica) showed an increase of 31.8%, 18.6% and 46.8% respectively. Extrapolation of the prevalence in these populations shows that the sickle cell disease prevalence is likely higher than what is reported in US. CONCLUSIONS: The complexities of reaching an estimated number may be more challenging in an ever-changing and growing population. More so considering the different situations behind the immigration of each group and the migratory status which might be inducing an underestimation of the sickle cell population in the U.S. This study attempts to shed light on factors that may be skewing previous statistical estimates. Examining the migratory aspects inducing possible statistical bias may contribute to further address this disease encompassing this population's growth rate into prospective public health strategies to a more comprehensive approach to the disease.

Mortality trends in sickle cell patients.

BACKGROUND: Sickle cell disease affects a significant portion of US patients with African descent. It continues to be one of the leading causes of frequent hospitalizations and high in-hospital morality risk. Until the approval of disease-modifying therapies in last two years, medical therapy has relied mostly on management of pain episodes and the use of hydroxyurea. We discuss the nationwide analysis of trends in in-hospital mortality in patients with Sickle Cell Disease from 2000 to 2014. METHODS: Trends of in-hospital mortality in sickle cell patients were analyzed from a database provided by the Agency of Healthcare Research and Quality. From the data hospitalization rates and in-hospital mortality in categories by region in the US, hospital size, health insurance status, comorbidities and gender were examined. Patterns of in-hospital mortality were analyzed by logistic regression. RESULTS: Ratio for hospitalization and mortality among the four regions described Northeast, Midwest, South, West with respective values of 0.63%, 0.65%, 0.76% and 0.89% with P = 0.008 and OR = 1.07. Odds ratio for sickle cell patients that died during hospitalization and health insurance status was OR = 0.08. Comorbidities considered in sickle cell patients; diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), chronic kidney disease (CKD), smoking status. The odds ratio for comorbidities show A-fib with a value of OR = 4.47, followed by hypertension OR = 1.92, diabetes mellitus OR = 1.44 and chronic kidney disease OR = 1.29, smoking status OR = 0.60. Mortality-hospitalization ratio by gender was: males 0.77% and females 0.69% with OR = 0.87. CONCLUSIONS: In-hospital mortality by US regions, as well as health insurance status are important measurable elements that show the impact of the disease from a public health perspective. Further and more specific data of regions by states, comorbidities by states and sex, as well as health insurance status by states will provide further insight in local mortality trends.

Outcomes of hospitalized patients with myocardial infarction and immune thrombocytopenic purpura: a cross sectional study over 15 years.

BACKGROUND: Immune Thrombocytopenic Purpura (ITP) is an autoimmune disorder characterized by low platelet counts and mucocutaneous bleeding. The outcomes of hospitalized patients with ITP and myocardial infarction (MI) have not been extensively studied and may help identify risk factors associated with adverse outcomes in this unique patient population. METHODS: Patients with ITP who were admitted with MI using the National Inpatient Database for the years 2000 to 2014. Patient demographics, hospital characteristics and medical comorbidities were studied. Chi square test was used to determine associations with statistical significance and logistic regression was used to determine independent predictors of mortality. RESULTS: A total of 753732 hospitalized patients with ITP were identified over the time period of 2000 to 2014, of which 37695 patients had both ITP and acute MI. There were more females with ITP in general (60% females vs. 40 males), but more males with ITP and acute MI (55.8% males vs. 44.2% females; P=0.0000). Caucasians were affected the most (5.5%) amongst all races and the age group of 65-79 years had the highest percentage of patients with ITP and MI (7.3%). The classical risk factors of hypertension, hyperlipidemia, and diabetes were also noted to be highly prevalent in patients with ITP and MI. 10.05% of patients with ITP and acute MI died during hospitalization, while 4% of all patients with ITP died during hospitalization (P<0.05). Multiple regression showed that stent placement, female gender, blood transfusions, platelet transfusion, 80+ age group and higher Charlson's score were independent predictors of mortality in patients with ITP which have MI. CONCLUSIONS: MI is associated with an increased rate of in-hospital death in patients with ITP. Both blood transfusions and platelet transfusions adversely affect outcomes in the management of AMI in ITP patients.

Age and race distribution in patients in phase III oncology clinical trials.

Background: Geriatric patients and minority patients are often under-represented in cancer clinical trials. The presence of multiple comorbidities makes geriatric patients ineligible for most clinical trials. Racial diversity may vary by geographical location and socio-economically backward areas may have a very different racial mix. The increase in cancer incidence in geriatric patients' raises the question of applicability of the results is such clinical trials. This study also explores the representation of different races in phase 3 clinical trials conducted in the past 10 years. Methods: Data about Phase III trials was extracted from the clinical trials.gov for 3 common solid organs and 3 hematological malignancies [breast, colon, lung, diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)]. The time period studied was for the past 10 years and included only adult patients (≥18 years). The age and race distribution of the patient population in these trials were extracted and analyzed. Results: Geriatric patients and minorities are under-represented in all phase III cancer clinical trials. The range of the proportion of geriatric patients varied from 10% to 40%. African American and Asian patients are under-represented in all phase III cancer clinical trials. Conclusions: The results of phase III clinical trials that are currently conducted on non-geriatric and Caucasian patient population may not meaningfully be applicable to geriatric patients and minorities. This study highlights the disparity of age and race for patients enrolled in clinical trials as against the patients seen in the real world.

Role of indoleamine 2,3-dioxygenase in acute myeloid leukemia.

Indoleamine 2,3 dioxygenase (IDO), first discovered in the 1960s, is an enzyme that has become a highly investigated metabolic target in cancer research. IDO is the rate-limiting step in tryptophan metabolism catabolism into its byproducts - kynurenines. Both IDO and kynurenines have been implicated in altering the tumor microenvironment, allowing for a tolerogenesis by affecting T-cell maturation and proliferation, and more specifically by inducing differentiation into T regulatory cells. Two mechanisms have been suspected in creating this environment: tryptophan starvation and metabolite toxicity. IDO has been shown to be expressed not only in cancer cells but also in antigen-presenting cells. The exact mechanisms underlying the two different sites of expression have not been fully elucidated. To date, most literature has focused on the role of IDO in solid tumors; we provide a review of IDO and its impact on hematological malignancies - more specifically, acute myeloid leukemia. The pathophysiology of IDO will be discussed, including a summarization of the literature to date on how IDO expression effects prognosis and disease progression in acute myeloid leukemia, along with current IDO-specific therapeutics with future considerations.

Analysis of outcomes in hospitalized pregnant patients with acute myeloid leukemia.

BACKGROUND: There have been significant advances in the management of acute myeloid leukemia (AML) in the past decade. However, management of AML in the pregnant patient has been challenging as most interventions are contraindicated in pregnancy. Medical termination of pregnancy is advocated over chemotherapy in the first trimester as delaying chemotherapy could often be fatal. Chemotherapy during second and third trimesters may be provided with close surveillance of fetal abnormalities. The outcomes in these patients have not been systematically studied and have been limited to case reports and case series in medical literature. METHODS: Patients hospitalized with a diagnosis of AML were identified using the International Classification of Disease (ICD-9) codes in the National Inpatient Sample database. This database is maintained by the Agency of Healthcare Research Quality under the United States Department of Health and Human Services. It represents 20% of all hospitalizations occurring in the United States every year. Amongst these AML patients, all patients who were pregnant were identified and their demographic information was extracted. Other details related to their hospitalization, hospital size, location, region and teaching status were also determined. The association of outcomes with common medical comorbidities was studied. Pregnancy related outcomes, mode of delivery and mortality rates were calculated for the 15 year time period. RESULTS: During the time period of 2000 to 2014, 678942 hospitalizations involved AML patients of which 5076 were noted to be from pregnant women. The hospitalization trend gradually increased over these years and was noted to be the highest in the age group of 18-34 years. The highest hospitalization rates were noted in African American and Native American patient populations. Hypertension, hyperlipidemia, chronic kidney disease and smoking were noted to be more prevalent in pregnant women with AML. A majority of these patients had a Charlson's comorbidity index of 1-3. 3.5% of patients underwent medical termination of pregnancy, 16.25% suffered from pregnancy related complications, 0.6% suffered from puerperal infection, 4% of patients had normal vaginal delivery, 2.8% of patients had caesarian section and 5.7% of patient died. The rate of mortality was the highest in Native Americans followed by Caucasians. Multiple regression showed that odds of mortality have decreased from 2000 to 2015 and that a higher Charlson's comorbidity score was an independent predictor of mortality. CONCLUSIONS: This is the first nationwide study to document the outcomes of pregnancy in hospitalized AML patients. AML in pregnancy is rare and this study shows that the mortality has been improving over the past 15 years. Notably, vaginal delivery has been more common than caesarian section in pregnant AML patients. Native Americans have high prevalence and high mortality rates, a likely result of healthcare disparity. Pregnant AML patients with high Charlson's comorbidity score may benefit from aggressive management of their comorbidities. Further studies are required to better characterize outcomes in pregnant women with AML.

A nationwide analysis of outcomes of stroke in hospitalized patients with essential thrombocythemia: 2006 to 2014.

BACKGROUND: Essential thrombocythemia (ET) is a subtype of myeloproliferative neoplasm associated with an increased risk of thrombohemorrhagic complications such as stroke. However, studies of prevalence and outcomes of stroke in hospitalized patients with ET have been limited to case series. METHODS: Data from the National Inpatient Sample was utilized to identify outcomes in hospitalized patient with ET who were admitted for stroke. Utilizing the current procedural terminology code (CPT) for ET, outcomes of patients with ET who were hospitalized with stroke were studied for the years 2006 to 2014. Patient demographics of age, gender and race were collected and hospital characteristics of location and size were correlated to outcomes. Chi square test was used to determine odds ratios and multiple logistic regression was used to determine independent predictors of mortality. RESULTS: Between the years of 2006 to 2014, a total of 552422 hospitalizations involved patients with a diagnosis of ET, 20650 of which were due to stroke. The percentage of stroke in these hospitalizations varied between 3.64 to 4.29 over 9 years and mortality in these patients did not significantly change during this time period. The prevalence of stroke was highest amongst Asians and Caucasians (4.7% and 3.86%) with a statistically significant difference (P=0.0000). A majority of ET patients with stroke were discharged to skilled nursing facilities. Multiple regression showed that female gender, atrial fibrillation, stroke, higher Charlson's comorbidity score and 80+ age were independent predictors of mortality (OR: 0.75, 1.35, 1.8, 2 to 5.7, 13.9 respectively). CONCLUSIONS: This study demonstrated that Female gender, atrial fibrillation, stroke, higher Charlson's comorbidity score and 80+ age group were found to be statistically significant independent predictors of mortality (OR: 0.75, 1.35, 1.8, 2 to 5.7, 13.9 respectively) in patients with ET and stroke. Inclusion of these factors in the risk stratification of patients with ET may decrease the morbidity and mortality associated with the disease.

Impact of immunotherapy use in patients with stage IV pancreatic carcinoma.

BACKGROUND: Most patients with pancreatic cancer have non-resectable disease at the time of diagnosis and usually die within 6-12 months. Despite indications in other solid tumors, the role of immunotherapy (IO) is unknown for late stage, advanced pancreatic cancer. METHODS: Using the National Cancer Database (NCDB), cases of Stage IV pancreatic cancers diagnosed in the period of 2014-2016 with at least 30-day follow up were retrospectively analyzed. The following clinical demographics were included: age (younger than 70 vs. older than 70), sex (male vs. female), race (whites vs. others), insurance (uninsured vs. insured), type of institution (academic vs. nonacademic), liver metastasis (yes vs. no), lung metastasis (yes vs. no), external beam radiation (yes vs. no), systemic chemotherapy (yes vs. no) and IO (yes vs. no). survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Multivariable Cox proportional hazard models and propensity score matching analysis were also utilized. A P value <0.05 was considered significant. RESULTS: Among 25,596 eligible cases, 163 patients were treated with IO. A significant association between the use of IO and several clinical demographics (age <70, academic institution, adenocarcinoma, lung metastasis, radiation, chemotherapy) was noted. Chemotherapy was administered in 133 (82%) and 16,342 (64%) of cases in the IO and non-IO groups, respectively. Use of IO was associated with improved overall survival (OS) in both univariate and multivariate analyses (P<0.0001 for each). Median OS (in months) was 12.2 in the IO group vs. 5.8 in the non-IO group. Landmark analysis in the IO group showed 12 and 24-month survival of 51.0% and 20.0% respectively, as compared with 28.2% and 11.9% in the non-IO group. Propensity score matching analysis also demonstrated a trend toward improved OS in IO group (P=0.0753). Median survival was 12.2 and 8.9 months, respectively. CONCLUSIONS: This retrospective data analysis using a large cancer database suggests that use of IO could improve survival in patients with advanced pancreatic cancer. More studies will be needed in the future to validate these results.

Locally Advanced Osteosarcoma of the Ethmoid Sinus: A Report of Successful Management.

Osteosarcoma of the skull has poor outcomes. This case report describes the presentation and clinical course of a patient who was diagnosed with osteosarcoma of the skull involving the cribriform plate. After her initial diagnosis, she developed esotropia with severe unremitting headaches. She received palliative radiation, followed by chemotherapy, and responded well. Her initial symptoms involving the cranial nerves subsided, and her response was sustained. This report illustrates the need to effectively treat osteosarcoma of the skull despite its reported poor outcomes.

Weather the Cytokine Storm: A Report of Successful Management of a Colon Cancer Survivor and a Critically Ill Patient with COVID-19.

Patients with novel corona virus infection (COVID-19) can develop acute respiratory failure secondary to acute respiratory distress syndrome. Cytokine storm is suggested as one of underlying mechanisms for the rapid clinical decline. Immunocompromised patients and cancer patients are at particular risk for poor outcomes due to COVID-19 infection. This case report describes the presentation and clinical course of a cancer survivor who became critically ill and required mechanical ventilation. The patient was treated with hydroxychloroquine, azithromycin, and ceftriaxone; however, he remained febrile, hypoxemic, continued to require full mechanical ventilator support and his chest X-ray showed increased bilateral infiltrates. The patient was treated with tocilizumab, after which he improved and was successfully extubated. This report illustrates a possible role of tocilizumab in management of cytokine storm in critically ill patients with COVID-19 infection.

Thyroiditis: A Rare Manifestation of Enasidenib-Induced Differentiation Syndrome.

Enasidenib is an FDA-approved isocitrate dehydrogenase 2 (IDH2) inhibitor, which is used in the treatment of acute myeloid leukemia (AML). We present a case of AML with an IDH2 mutation treated with a regimen of enasidenib and 5-azacitidine, where thyroiditis was noted to be a part of differentiation syndrome. The patient is a 77-year-old woman with IDH2-mutated AML who had initially been started on 100 mg of enasidenib and then presented with dyspnea and was diagnosed with pleural effusion - a common presentation with enasidenib - but was also noted to have thyroiditis. She was started on steroids, but due to continued hyperbilirubinemia and thyroiditis, her dose of enasidenib was reduced to half, which resulted in clinical improvement. This case demonstrates thyroiditis as one of the rare manifestations in the treatment of AML with enasidenib-induced differentiation syndrome.

Management of a 75-Year-Old Lady with Refractory Chronic Myelogenous Leukemia.

Chronic myelogenous leukemia (CML) is a hematopoietic disorder caused by the BCR/ABL gene or Philadelphia chromosome. The first Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treatment of CML was imatinib in 2001. Since then, multiple therapies, such as nilotinib, dasatinib, bosutinib, and, more recently, ponatinib, have made their way as viable treatment options for first-line and secondary therapies. Most patients tend to respond to first-line treatment. Although there is a subset of patients who do not achieve complete molecular response with first line, newer options have proven beneficial. As we progress through therapies, there still remain some patients who do not adequately respond to current available therapies. The treatment options and guidelines become more difficult in such situations, not only with respect to cost but also patient quality of life and satisfaction. We discuss a 75-year-old white female with CML, who has had multiple therapies with hematological remission but has never achieved complete molecular remission, currently on bosutinib and tolerating it well.

Long-Term Use of Ruxolitinib in an AML Patient with Posttransplant Steroid Refractory GVHD.

Ruxolitinib has become a new therapeutic option for steroid refractory graft-versus-host disease (srGVHD), with a substantial remission rate. Its anti-inflammatory properties by blocking interleukin pathways have made it a novel therapeutic approach to inflammatory disease processes, such as GVHD. The long-term use of ruxolitinib has not been explicitly studied outside the context in the treatment of multiple myeloma. With current clinical trials underway for the use of ruxolitinib in srGVHD, there are still no current guidelines or protocols for long-term clinical use. Of the available literature showing ruxolitinib utilization for srGVHD, most cases lead to resolution and eventual discontinuation. We present a case of a 32-year-old male on ruxolitinib with GVHD status postmatched unrelated donor stem cell transplant (MUD SCT) for acute myeloid leukemia (AML) with FLT3 mutation currently on ruxolitinib for 5 years who is not able to tolerate reduction in dosage due to flare-ups. We discuss the clinical implications and nuance of therapy with ruxolitinib with unknown long-term effects and weigh the risks and benefits.

Outcomes of adult critically ill patients with hemophagocytic lymphohistiocytosis in united states-analysis from an administrative database from 2007 to 2015.

BACKGROUND: Severe infections caused by the novel coronavirus 2 display similarities to secondary hemophagocytic lymphohistiocytosis (HLH). However, HLH is a rare disease and has not been well described in critically ill patients. METHODS: We used the Nationwide Inpatient Sample (NIS), the largest all-payer inpatient care database publicly available in the United States to identify all adult discharges with Hemophagocytic syndrome (ICD-9 CM code 288.4) between 2007 and 2015. Critical illness was considered present if patient had either ICD-9 CM code indicating the requirement of invasive mechanical ventilation or the presence of shock. We used ICD-9-CM codes to identify various infections (inf-HLH), malignancies (mal-HLH) and autoimmune diseases associated with HLH (MAS-HLH) and classified them in their respective groups. Primary outcome was in-hospital mortality in critically ill patients. We developed multivariable regression model to examine variables associated with mortality in critically ill HLH patients. P value was kept at < 0.05. RESULTS: Of the 7420 (95% CI 6959-7881) estimated discharges with HLH, 2313 (31%) were critically ill. Of the critically ill patients, 442 (34%) were mal-HLH, 422 (43.3%) were inf-HLH, 403 (30.7%) were MAS-HLH and 1046 (27.3%) were unable to be classified. In hospital mortality rates were 6.4% in non-critically ill and 48.4% in critically ill patients. Among the subtypes of HLH, in-hospital mortality was 53% in mal-HLH, 49.4% in inf-HLH, 26% in MAS-HLH and 54.6% in unclassified group. On multivariable regression analysis, development of acute renal failure requiring hemodialysis (OR 2.06, 95% CI 1.29-3.3, P=0.002) and acute hepatic failure (OR 2.21, 95% CI 1.38-3.52, P=0.001) were significantly associated with higher mortality. CONCLUSION: Inpatient mortality of critically ill patients is remarkably high. Patients with MAS-HLH had better outcomes when compared to other groups of HLH.

Management of nephrotoxicity of chemotherapy and targeted agents: 2020.

Nephrotoxic effects of certain chemotherapeutic agents such as cisplatin and ifosfamide has been well documented and these effects are carefully managed by oncologists during their usage. The introduction of targeted agents has added a new challenge to cancer management as their nephrotoxic effects and associated management is in the process of being adopted by oncologists. This work is a compilation of side effects on the renal system due to various chemotherapeutic, immunotherapeutic and targeted agents followed by their recommended management.