Disparities in Outcomes of Hospitalizations Due to Multiple Myeloma: A Nationwide Comparison.

Background With the advent of novel treatments, there is a declining trend in the multiple myeloma (MM) mortality rate with an increasing hospitalization rate. However, there is limited population-based data on trends and outcomes of hospitalizations due to MM in the United States (US). Methods We analyzed the publicly available Nationwide Inpatient Sample (NIS) from 2007 to 2017 to identify MM hospitalizations. Results Hospitalizations for MM increased from 17,100 (8.71%) in 2007 to 19,490 (9.92%) in 2017. The in-hospital mortality rate declined from 8.4% in 2007 to 4.9% in 2017 (P <0.001) and discharge to facilities decreased from 20.4% in 2007 to 17.4% in 2017 (P <0.001). The odds of in-hospital mortality were higher with increasing age (odds ratio (OR): 1.46; 95% confidence interval (CI): 1.38 -1.54; P <0.0001), pneumonia (OR: 4.18; 95% CI: 3.63 - 4.81, P <0.0001), septicemia (OR: 2.50; 95% CI: 2.22 - 2.82; P <0.0001), renal failure (OR: 1.48; 95% CI: 1.34 -1.64; P <0.0001), uninsured/self-pay insurance status (OR: 2.69; 95% CI: 2.18 - 3.3; P <0.0001), rural hospital (OR: 2.26; 95% CI: 1.88 -2.72; P<0.0001), and urban-non-teaching hospitals (OR: 1.38; 95% CI: 1.23 - 1.56; P <0.0001). Also, increasing age (OR: 1.14; 95% CI: 1.11-1.18, P <0.0001), Black race (OR: 1.12; 95% CI: 1.02-1.23, P <0.0001), and multiple comorbidities were associated with higher disability. Conclusion Hospitalizations for MM continued to increase, whereas in-hospital mortality continued to decrease. Advanced age, sepsis, pneumonia, and renal failure were associated with higher odds of mortality in MM patients.

A novel outpatient regimen in management of fluoropyrimidine-induced cardiotoxicity.

INTRODUCTION: Fluoropyrimidines (FP) are cornerstone drugs in the treatment of gastrointestinal (GI) malignancies. Cardiotoxicity secondary to an FP chemotherapy is a serious complication. There are no standardized guidelines on the treatment of FP induced cardiotoxicity which may result in interruption and even discontinuation of life saving treatment. We present our experience in FP rechallenge using a novel outpatient regimen based on our "up-front" triple agent antianginal protocol. METHODS: We report the retrospective study of the patients with suspected FP induced cardiotoxicity. Patients meeting the criteria were selected by C3OD (curated cancer clinical outcomes database) at Kansas University Medical Center (KUMC). We identified all patients with gastrointestinal malignancies who had suspected FP induced cardiotoxicity from January 2015 to March 2022. We then included the patients who were rechallenged with planned fluoropyrimidine regimen utilizing the three drug KU-protocol. We utilized a novel regimen by repurposing the already FDA-approved anti-anginal drugs in a manner that minimizes the risk of hypotension and bradycardia. RESULTS: In this retrospective study, 10 patients with suspected fluoropyrimidine induced cardiotoxicity were included from January-2015 to March-2022 at KUMC. Out of 10 patients who were rechallenged utilizing KU-protocol, eight patients (80%) were able to complete the previously planned fluoropyrimidine regimen. None of the patients required ER visits or hospital admission due to cardiac symptoms during the rechallenge utilizing the KU-protocol. CONCLUSIONS: Utilizing our novel outpatient regimen, we have successfully and safely allowed re-challenge of FP chemotherapy with good tolerability and completion of the intended course of chemotherapy without recurrent morbidity.

Temporal Trends, Predictors, and Outcomes of Disseminated Intravascular Coagulation in Hospitalizations With Sepsis.

Background This retrospective study was conducted to analyze the temporal trends, predictors, and impact of disseminated intravascular coagulation (DIC) on outcomes among septicemic patients using a nationally representative database. Methods We derived data from the National Inpatient Sample (NIS) for the years 2008-2017 for adult hospitalizations due to sepsis. The primary outcomes were in-hospital mortality and discharge to facility. The Cochran-Armitage test and multivariable survey logistic regression models were used to analyze the data. Results Out of 12,820,000 hospitalizations due to sepsis, 153,181 (1.18%) were complicated by DIC. The incidence of DIC decreased from 2008 to 2017. In multivariable regression analysis, demographics and comorbidities were associated with higher odds of DIC. During the study period, in-hospital mortality among patients with sepsis decreased, but the attributable risk percent of in-hospital mortality due to DIC increased. We observed similar trends for discharge to facility; however, the adjusted odds of discharge to facility due to DIC remained stable over the study period. Conclusion Although the incidence of sepsis complicated by DIC decreased, the attributable in-hospital mortality rate due to DIC increased during the study period. We identified several predictors associated with the development of DIC in sepsis, some of which are potentially modifiable.

New-Onset Autoimmune Diabetes Mellitus Presenting As Diabetic Ketoacidosis in Association With Pembrolizumab Therapy and Long Term Follow-Up: Case Report.

Pembrolizumab, an immune checkpoint inhibitor (ICI) that acts against receptor programmed cell death-1 (PD-1), is currently being used in the treatment of a variety of cancers. As PD-1 is also present on other non-malignant tissues, this results in side effects involving a multitude of organ systems termed immune-related adverse effects (irAEs). Programmed cell death-1 is expressed on the beta cells of islets of the pancreas, and their destruction can result in hyperglycemia and the onset of new diabetes mellitus (DM). Thus, the anti-PD1 action of pembrolizumab can lead to autoimmune-related DM. We present a case of a 62-year-old male who developed new-onset DM after 12 cycles of pembrolizumab with a severe presentation in the form of diabetic ketoacidosis (DKA) and ICU stay. Our case underscores the importance of physician awareness, frequent lab monitoring and patient education about this rare but potentially fatal irAE of ICI. It also strengthens existing data in literature suggesting the association of irAEs with improved efficacy of ICI therapy.

Protecting High-Risk Oncology Patients During the COVID-19 Pandemic by Creating an Isolated Outpatient Clinic.

PURPOSE: Delivering care for immunocompromised, high-risk patients with cancer during a pandemic has proven challenging. Patients with cancer on chemotherapy have a high risk of mortality if contracted COVID-19. If a patient goes directly to the emergency room, multiple contact points with other individuals can lead to unnecessary exposures from any airborne virus, such as COVID-19. Our cancer center has implemented an isolated clinic with personal protective equipment and direct access to a COVID-19 rule-out floor to manage those with febrile neutropenia (FN). METHODS: We implemented an outpatient, isolated, extended-hour clinic with access to personal protective equipment, laboratories, and antibiotics for patients with FN as a pilot project from April 1 to December 31, 2020, with the aim to decrease emergency department (ED) visits for FN by 50%. RESULTS: Since the implementation of our clinic, we have screened 74 unique patients during 102 visits, of which 76 led to a discharge and 26 led to a direct admit, thus avoiding the ED. Thirty-nine of these visits were for patients with recent travel or a known COVID-19 exposure. Bringing these patients to our isolated clinic ensured safety of the approximately 200 patients undergoing active treatment in our infusion center daily. CONCLUSION: Implementing this clinic has thus far successfully decreased the social footprint of our highest-risk patients with cancer in the ED considerably. Our efforts and hopes of decreasing the possible exposure of our immunocompromised patients to COVID-19 as well as the unnecessary exposure of the infusion center patients and personnel have thus far been effective.

A Case of De Novo Psoriasis Secondary to Nivolumab in a Patient With Metastatic Renal Cell Carcinoma.

Immune-mediated adverse events are commonly seen with immune checkpoint inhibitors like nivolumab. Oncology specialists usually have to screen patients for risk factors for autoimmune diseases, since immune checkpoint inhibitors can potentially exacerbate these events. Some of the immune-mediated side effects include polyneuropathies, colitis, and cutaneous adverse effects. Non-specific maculopapular rash, pruritus, lichenoid reactions, eczema, and vitiligo are the most common dermatologic side effects. It is thought that these adverse events are due to the blocking of the programmed cell death protein-1 (PD-1) pathway and are mediated by the cytotoxic T cells. Psoriasis has been previously reported as a side effect in a few case reports and most commonly presented as an exacerbation of preexisting psoriasis. However, de novo psoriasis occurrence as a result of nivolumab is a rare entity, especially in a non-melanoma patient. Here, we present a case of renal cell carcinoma treated with immunotherapy with nivolumab, who developed de novo psoriasis with palmoplantar involvement.

Incidental Finding of Squamous Cell Carcinoma on a 68Ga-DOTATATE PET Scan.

Neuroendocrine tumors (NETs) are a relatively rare entity; however, the incidence and prevalence of these tumors are increasing, likely attributed to improved diagnostic accuracy. The diagnosis of suspected NETs is facilitated by clinical symptoms, laboratory test abnormalities such as elevated chromogranin-A, and other diagnostic modalities such as the use of computed tomography scans, magnetic resonance imaging scans, positron emission tomography (PET) scans, and biopsy. The expression of high levels of somatostatin receptors in NETs enables the use of a specialized PET scan using the radiolabeled somatostatin analogues 68Ga-DOTATATE. The sensitivity and specificity of 68Ga-DOTATATE PET is very high for the diagnosis of NETs, but the specificity decreases especially with no clear symptoms and with only borderline elevated tumor markers. We present a case of a suspected NET, which was initially diagnosed as a metastatic NET by virtue of a positive 68Ga-DOTATATE PET scan; however, on biopsy it was revealed to be a squamous cell carcinoma originating from the head and neck.

Systemic adverse effects and toxicities associated with immunotherapy: A review.

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use of immuno-therapeutic agents, it is vital for physicians to acquaint themselves with these adverse effects. The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents. We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems, as well as an extensive discussion of the current recommendations for treatment and clinical trial data. As we continue to see increasing usage of these agents in clinical practice, it is vital for physicians to familiarize themselves with these effects.

Review of Bone Modifying Agents in Metastatic Breast Cancer.

Bone is the most common site for distant metastases in breast cancer and can cause significant morbidity and mortality. Bone modifying agents (BMAs) that include bisphosphonates (BPAs) and denosumab help in decreasing and delaying skeletal-related events (SREs) associated with metastatic breast cancer. BPAs approved for use by the Food and Drug Administration (FDA) in bone metastases (BM) in the United States are pamidronate and zolendronic acid, while clodronate and ibandronate are licensed for use in other countries. Current American Society of Clinical Oncology (ASCO) guidelines recommend denosumab 120 mg subcutaneously every four weeks, or zolendronic acid 4 mg every four weeks or every 12 weeks, or intravenous pamidronate 90 mg every four weeks. Current guidelines do not recommend one BMA over another, however, zolendronic acid and denosumab were the most commonly used BMAs in population-based studies. Side effects of BMAs include acute phase reactions, hypocalcemia, nephrotoxicity, osteonecrosis of jaw, etc. While other side effects are common with both BPAs and denosumab, the latter has less nephrotoxic potential and is preferred for use in patients with renal failure. Current ASCO guidelines recommend continuing BMAs indefinitely, however, in clinical practice, this decision needs to be individualized, especially since there is no data on the impact of long-term use of BMAs. Further studies would need to be developed to develop an algorithm of SRE risk assessment and to determine which patients would benefit from BMAs.

Current immunotherapy in gastrointestinal malignancies A Review.

Immunotherapy is an extremely important breakthrough and an exciting new modality of treatment for a wide spectrum of cancers. It is focused around developing agents to stimulate or suppress the immune system, in a specific manner, to fight off a wide spectrum of diseases, particularly cancers. Traditional therapies available for the treatment of cancers include surgical intervention, chemotherapy, radiation therapy or a combination of these, which tend to be very non-specific. However, immunotherapy shows a stark difference from conventional therapy, in fact, that it has a high level of specificity for the tumor-specific antigens. The recent success of cancer immunotherapies in clinical trials is slowly revolutionizing the landscape for cancer therapy. The US Food and Drug Administration has approved numerous agents, after clinical trials showed promising results, for the treatment of multiple cancers. The role of immunotherapy in gastrointestinal cancers has also been very promising, particularly in patients with advanced metastatic disease or malignancies refractory to initial treatment. In this review of literature, we detail and discuss the immunotherapy agents approved for the treatment of GI cancers and glance at the future of immunotherapy for patients with these cancers.

Epidemiology and Outcomes of Hospitalizations Due to Hepatocellular Carcinoma.

Background Hepatocellular Carcinoma (HCC) is a severe complication of cirrhosis and the incidence of HCC has been increasing in the United States (US). We aim to describe the trends, characteristics, and outcomes of hospitalizations due to HCC across the last decade. Methods We derived a study cohort from the Nationwide Inpatient Sample (NIS) for the years 2008-2017. Adult hospitalizations due to HCC were identified using the International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM). Comorbidities were also identified by ICD-9/10-CM codes and Elixhauser Comorbidity Software (Agency for Healthcare Research and Quality, Rockville, Maryland, US). Our primary outcomes were in-hospital mortality and discharge to the facility. We then utilized the Cochran-Armitage trend test and multivariable survey logistic regression models to analyze the trends, outcomes, and predictors. Results A total of 155,436 adult hospitalizations occurred due to HCC from 2008-2017. The number of hospitalizations with HCC decreased from 16,754 in 2008 to 14,715 in 2017. Additionally, trends of in-hospital mortality declined over the study period but discharge to facilities remained stable. Furthermore, in multivariable regression analysis, predictors of increased mortality in HCC patients were advanced age (OR 1.1; 95%CI 1.0-1.2; p< 0.0001), African American (OR 1.3; 95%CI 1.1-1.4;p< 0.001), Rural/ non-teaching hospitals (OR 2.7; 95%CI 2.4-3.3; p< 0.001), uninsured (OR 1.9; CI 1.6-2.2; p< 0.0001) and complications like septicemia and pneumonia as well as comorbidities such as hypertension, diabetes mellitus, and renal failure. We observed similar trends in discharge to facilities. Conclusions In this nationally representative study, we observed a decrease in hospitalizations of patients with HCC along with in-hospital mortality; however, discharge to facilities remained stable over the last decade. We also identified multiple predictors significantly associated with increased mortality, some of which are potentially modifiable and can be points of interest for future studies.

Impact of early dose intensity reduction of Palbociclib on clinical outcomes in patients with hormone-receptor-positive metastatic breast cancer.

BACKGROUND: Palbociclib is commonly added to an aromatase inhibitor (AI) as first-line therapy in ER + HER2- metastatic breast cancer (MBC). There are no data on the effect of the relative dose intensity (RDI) of palbociclib in first-line setting on clinical outcomes. The objective of this study is to explore the association of RDI and dose reduction of palbociclib in the first-line setting with PFS. METHODS: This is a retrospective study of ER + HER2- MBC patients who received palbociclib plus AI in first-line setting. Subjects ≥ 18 years old with MBC, who were started on palbociclib 125 mg daily, had completed ≥ 1 cycle of palbociclib, and did not progress within the first 12 weeks were eligible. Analyses were performed at 12- and 36-week landmarks (LM). RDI was defined as the total amount of palbociclib taken per the total amount planned. RDI-high-12 and RDI-low-12 cohorts were defined as patients receiving palbociclib with RDI ≥ 80% and RDI < 80% during the first 12 weeks, respectively. Reduction-12 and No-reduction-12 cohorts were defined as patients who had any dose reduction and patients who had no reduction during the first 12 weeks, respectively. RESULTS: 56 patients were eligible. Kaplan-Meier analysis from 12-week LM showed a median PFS of 17.1 months in RDI-high-12 versus 6.8 months in RDI-low-12 cohort (p = 0.0006). There was a 7.0-month improvement in median PFS in No-reduction-12 versus Reduction-12 cohort (p = 0.0638). Median PFS at 36-week LM was not reached in RDI-high-36 versus 8.6 months in RDI-low-36 cohort (p = 0.0703). CONCLUSIONS: RDI < 80% of palbociclib during the first 12 weeks, when used in combination with an AI in first-line setting in ER + HER2- MBC, is associated with significantly shorter PFS compared to RDI ≥ 80%. There is a trend towards shorter PFS among patients with RDI < 80% versus RDI ≥ 80% at 36 weeks. A larger study is needed to validate these findings.

Isolated Left Ventricular Metastasis from Renal Cell Carcinoma: Diagnostic and Therapeutic Dilemma.

BACKGROUND: The treatment of metastatic renal cell carcinoma (RCC) has been radically changed by the advent of tyrosine kinase inhibitors (TKIs). However, few reports have described their role in cardiac metastases. We present a case of a left ventricular metastasis from RCC that was managed with pazopanib therapy. CASE REPORT: A 74-year-old male with stage I RCC underwent right nephrectomy in 2004 and right lung metastasis resection in 2009. He was well till March 2016, when he presented with chest pain. Cardiac catheterization revealed a highly vascular mass in the apex. Cardiac magnetic resonance imaging revealed a left ventricular mass with full-thickness involvement of the myocardium, and the open cardiac biopsy was consistent with metastatic RCC. The patient was initially treated with pazopanib with response but later developed therapy-related side effects, and the dose was reduced. Due to tumor progression, he is currently on nivolumab instead and is stable. CONCLUSION: RCC with cardiac metastasis poses unique challenges with regard to diagnosis as well as treatment. The use of TKI therapy is associated with cardiotoxicity and has not been adequately studied in cardiac metastasis. Choosing the right treatment for this subgroup of patients continues to pose an ongoing dilemma.

Percutaneous Coronary Intervention Versus Surgery in Left Main Stenosis-A Meta-Analysis and Systematic Review of Randomised Controlled Trials.

OBJECTIVE: To investigate the safety and efficacy of percutaneous coronary interventions (PCI) versus coronary artery bypass graft (CABG) surgery for left main coronary artery (LMCA) disease. METHODS: Six randomised controlled trials (RCTs) were reviewed by searching PubMed/Medline, Embase and the Cochrane Library. Estimates were pooled according to random effects model. Binary outcomes were reported as risk ratio (RR) and continuous outcomes were reported as mean difference (MD) with 95% confidence interval (CI). RESULTS: 3794 patients were randomised into PCI and CABG arms. Mean age of the total population was 64.7 years, 74.4% were male and mean Logistic EURO score (LES) was 2.9. When compared with CABG, patients treated with PCI had reduced risk of major adverse cardiovascular events (MACE) at 30 days: (RR: 0.55; 95% CI, 0.41-0.75; p<0.001; I2=0) but similar risk at 1year (RR: 1.15; 95% CI, 0.92-1.45; p=0.22; I2=0). Five years MACE rates favoured CABG (RR: 1.32; 95% CI, 1.13-1.53; p<0.001; I2=0) driven by a higher rate of target vessel revascularisation (TVR) (RR: 1.71; 95%CI, 1.38-2.12; p<0.001; I2=0) and myocardial infarction (MI) (RR: 1.97; 95%CI, 1.28-3.04; p<0.001; I2=22). Percutaneous coronary intervention was comparatively a safer procedure with lower rates of periprocedural adverse events including MI, stroke, bleeding events and need for blood transfusions. CONCLUSION: Percutaneous coronary intervention reduced MACE at 30days with comparable MACE at 1year. However, CABG was a more effective modality when considering mid- to long-term outcomes. PCI is a safer procedure with regards to periprocedural adverse events.

A meta-analysis of continuous positive airway pressure therapy in prevention of cardiovascular events in patients with obstructive sleep apnoea.

Aims: To assess whether continuous positive airway pressure (CPAP) therapy reduces major adverse cardiovascular events (MACE) in patients with moderate-to-severe obstructive sleep apnoea (OSA). Methods and results: A total of 235 articles were recovered using MEDLINE, EMBASE and Cochrane library (inception-December 2016) and references contained in the identified articles. Seven randomized controlled trials (RCTs) were selected for final analysis. Analysis of 4268 patients demonstrated non-significant 26% relative risk reduction in MACE with CPAP [risk ratio (RR) 0.74; 95% confidence interval (CI) 0.47-1.17; P = 0.19, I2 = 48%]. A series of sensitivity analyses suggested that increased CPAP usage time yielded significant risk reduction in MACE. and stroke. Subgroup analysis revealed that CPAP adherence time ≥4 hours (h)/night reduced the risk of MACE by 57% (RR 0.43; 95% CI 0.23-0.80; P = 0.01, I2 = 0%). CPAP therapy showed no beneficial effect on myocardial infarction (MI), all-cause mortality, atrial fibrillation/flutter (AF), or heart failure (HF) (P > 0.05). CPAP had positive effect on mood and reduced the daytime sleepiness [Epworth Sleepiness Scale (ESS): mean difference (MD) -2.50, 95% CI - 3.62, -1.39; P < 0.001, I2 = 81%]. Conclusion: CPAP therapy might reduce MACE and stroke among subjects with CPAP time exceeding 4 h/night. Additional randomized trials mandating adequate CPAP time adherence are required to confirm this impression.

Safety and efficacy of anti-thrombotic regimens in patients with percutaneous coronary intervention requiring oral anticoagulation: A traditional and network meta-analysis.

BACKGROUND: Previous reports have been inconsistent in generating a consensus for optimal treatment strategy for patients with percutaneous coronary intervention (PCI) who also require oral anticoagulation (OAC). We conducted a traditional and network meta-analysis to evaluate the safety and efficacy of anti-thrombotic regimens in this subset of patients. METHODS: 30 articles were recovered through preferred reporting items for systematic reviews and meta-analyses (PRISMA) using MEDLINE, EMBASE and Cochrane Central Register of Controlled Clinical Trials (CENTRAL) from inception to December 2016. RESULTS: Dual antiplatelet therapy (DAPT) was found to be the safest treatment modality when compared to triple therapy (TT) or combination of OAC and single antiplatelet agent (OAC+SAP) [Major bleeding: (DAPT vs OAC+SAP: odds ratio (OR), 0.53; 95% credible interval (CrI), 0.30-0.91) (DAPT vs TT: OR, 0.45; 95% CrI, 0.31-0.64)]. There were no significant differences in major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular (CV) or total survival, stent thrombosis or target vessel revascularization (TVR) amongst the three treatment arms. TT was ranked superior for stroke reduction (SUCRA, 69%) followed by OAC+SAP and DAPT. When traditional analysis was adjusted for randomized data, OAC+SAP was equivalent to TT with regards to stroke (OR, 0.74; 95% confidence interval (CI), 0.38-1.46; p=0.39) and showed significant reduction in MACE and total mortality. CONCLUSION: DAPT was found to be the safest and equally effective regimen when compared to TT and OAC+SAP. However this strategy bears considerable risk to patients with high thromboembolic risk. This issue can be encountered by using OAC+SAP as an alternative of TT in patients with intermediate to high stroke risk and intermediate to high bleeding propensity.