Marijuana Use May Be Associated with Reduced Prevalence of Prostate Cancer: A National Survey on Drug Use and Health Study from United States of America.

Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use status (current, former, never), while the dependent variable was self-reported PC (yes, no). Eleven other demographic variables were assessed as covariates. PC prevalence was lower among current marijuana users (46/145, 31.7%) and former users (323/1021, 31.6%) compared to non-users (534/1337, 39.9%, p < 0.001). PC prevalence was lower among users versus non-users in the elderly (≥65) (36.4% vs. 42.4%, p = 0.016) and non-Hispanic white subgroups (28.9% vs. 38.3%, p < 0.001). There were no significant PC prevalence differences between users and non-users in the younger population (50-64) or other race/ethnicity. In the multivariable analyses, former marijuana use was associated with lower PC compared to never using (odd ratio = 0.74, 95% CI 0.62-0.90, p = 0.001). Current use was also suggestive of reduced prevalence but was not statistically significant (odd ratio = 0.77, 95% CI 0.52-1.14, p = 0.198), possibly due to low sample size. Our findings from a large national survey provide additional data to link marijuana use with lower PC prevalence.

Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel) is a type of B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell (CAR-T) approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Currently, the incidence of cardiac events associated with ide-cel remains unclear. This was a retrospective single-center observational study of patients treated with ide-cel for RRMM. We included all consecutive patients who received standard-of-care ide-cel treatment at least 1-month follow-up. Baseline clinical risk factors, safety profile, and responses were examined based on the development of a cardiac event. A total of 78 patients were treated with ide-cel, and 11 patients (14.1%) developed cardiac events: heart failure (5.1%), atrial fibrillation (10.3%), nonsustained ventricular tachycardia (3.8%), and cardiovascular death (1.3%). Only 11 of the 78 patients had repeat echocardiogram. Baseline risk factors associated with the development of cardiac events included being female sex and having poor performance status, λ light-chain disease, and advanced Revised International Staging System stage. Baseline cardiac characteristics were not associated with cardiac events. During index hospitalization after CAR-T, higher-grade (≥grade 2) cytokine release syndrome (CRS) and immune cell-associated neurologic syndrome were associated with cardiac events. In multivariable analyses, the hazard ratio for the association of the presence of cardiac events with overall survival (OS) was 2.66 and progression-free survival (PFS) was 1.98. Ide-cel CAR-T for RRMM was associated with similar cardiac events as other types of CAR-T. Worse baseline performance status and higher-grade CRS and neurotoxicity were associated with cardiac events after BCMA-directed CAR-T-cell therapy. Our results suggest that the presence of cardiac events may confer worse PFS or OS; although because of the small sample size, the power to detect an association was limited.

Geographic and Demographic Disparities in Colorectal Cancer: A National Cancer Database Analysis.

BACKGROUND AND OBJECTIVES: Area of residence may adversely affect survival and outcomes in many cancers. The objective of this study was to evaluate the impact of geographical and demographic disparities on survival of patients with colorectal cancer. MATERIALS AND METHODS: Data were obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal datasets. Patients were categorized by area of residence, namely, metropolitan (MA), urban (UA), or rural (RA). Sociodemographic and tumor-related data were collected and analyzed to evaluate variables affecting overall survival (OS). RESULTS: In total, 973,139 patients between 2004 and 2013 were included in the study, of which 83%, 15%, and 2% were MA, UA, and RA residents, respectively. RA and UA patients were mostly white male with low income and no comorbidities. In univariate analysis, OS was worse for RA (hazard ratio [HR] 1.10) and UA (HR 1.06) colorectal cancer patients than that for MA colorectal cancer patients. In multivariate analysis revealed significant association between OS and geographic residence, with worse OS for RA (HR 1.02, p = 0.04) and UA (HR 1.01, p = 0.003) patients. Black (HR 1.14) and Native American (HR 1.17) patients had worse outcomes, while Asians (HR 0.8), women (HR 0.88), and patients with higher income had improved OS (HR 0.88). CONCLUSION: The differences in the OS for RA and UA patients with colorectal cancer were significantly driven by economic disparity. Area of residence represents an important factor independently limiting access to care, particularly in geographically isolated individuals.

Metformin Use Is Associated With Lower Mortality in Veterans With Diabetes Hospitalized With Pneumonia.

BACKGROUND: Recent studies suggest that metformin use may be associated with improved infectious disease-related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia. METHODS: We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002-2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1. RESULTS: We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P < .003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P < .0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]: .86; 95% confidence interval [CI]: .78-.95) and 90-day (RR: .85; 95% CI: .79-.92) mortality was significantly lower for metformin users. CONCLUSIONS: Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections.

Etiology and Management of Dyslipidemia in Patients With Cancer.

Patients with cancer are now living longer than ever before due to the growth and expansion of highly effective antineoplastic therapies. Many of these patients face additional health challenges, of which cardiovascular disease (CVD) is the leading contributor to morbidity and mortality. CVD and cancer share common biological mechanisms and risk factors, including lipid abnormalities. A better understanding of the relationship between lipid metabolism and cancer can reveal strategies for cancer prevention and CVD risk reduction. Several anticancer treatments adversely affect lipid levels, increasing triglycerides and/or LDL-cholesterol. The traditional CVD risk assessment tools do not include cancer-specific parameters and may underestimate the true long-term CVD risk in this patient population. Statins are the mainstay of therapy in both primary and secondary CVD prevention. The role of non-statin therapies, including ezetimibe, PCSK9 inhibitors, bempedoic acid and icosapent ethyl in the management of lipid disorders in patients with cancer remains largely unknown. A contemporary cancer patient needs a personalized comprehensive cardiovascular assessment, management of lipid abnormalities, and prevention of late CVD to achieve optimal overall outcomes.

"Off-the-shelf" immunotherapies for multiple myeloma.

Over the past couple of decades, the life expectancy of patients with multiple myeloma (MM) has progressively increased, however, the disease per se remains incurable. This has resulted in a subset of the patient population who have progressed despite multiple standard treatment options but remain amenable for novel therapies to achieve durable remission. With the discovery of the role of B-Cell Maturation Antigen (BCMA) in the pathogenesis of MM, strategies targeting the BCMA have been the focus of many treatment modalities in development. Although autologous CAR-T cell therapy has shown an overall efficacy of >80% across various phases of studies, it has its own set of limitations and challenges. There is now an increasing focus on identifying novel therapeutic targets for multiple myeloma and developing "off-the-shelf" immunotherapeutic approaches for treatment of MM. This review discusses and highlights the emerging data from various ongoing trials on "off-the-shelf" approaches like antibody-drug conjugates, bispecific antibodies, and allogeneic cellular therapies demonstrating feasibility, acceptable safety, and promising preliminary efficacy. Ongoing and future efforts will need to focus on comparative effectiveness of these different approaches, possible combination strategies, and ensuring equitable and affordable access to these therapies globally.

Effectiveness of Beta-Lactam plus Doxycycline for Patients Hospitalized with Community-Acquired Pneumonia.

BACKGROUND: Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal evidence supporting this recommendation. Our aim was to examine the association between beta-lactam plus doxycycline and mortality for patients hospitalized with community-acquired pneumonia. METHODS: We identified patients >65 years of age admitted to any US Department of Veterans Affairs hospital in fiscal years 2002-2012 with a discharge diagnosis of pneumonia. We excluded those patients who did not receive antibiotic therapy concordant with the 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical practice guidelines. Using propensity score matching, we examined the association of doxycycline with 30- and 90-day mortality. RESULTS: Our overall cohort was comprised of 70533 patients and 5282 (7.49%) received doxycycline. Unadjusted 30-day mortality was 6.4% for those who received a beta-lactam plus doxycycline versus 9.1% in those who did not (P < .0001), and 90-day mortality was 13.8% for those who received a beta-lactam + doxycycline versus 16.8% for those who did not (P < .0001). In the propensity score matched models, both 30- (odds ratio 0.72, 95% confidence interval [CI], .63-.84) and 90-day (0.83, 95% CI, .74-.92) mortality were significantly lower for those who received doxycycline. CONCLUSIONS: In this retrospective observational cohort study, we found that doxycycline use, as part of guideline-concordant antibiotic therapy, was associated with lower 30- and 90-day mortality than regimens without doxycycline. While this supports the safety and effectiveness of antibiotic regimes that include doxycycline, additional studies, especially randomized clinical trials, are needed to confirm this.

Often Overlooked Diagnosis: Median Arcuate Ligament Syndrome as a Mimicker of Crohn's Disease.

Median arcuate ligament syndrome occurs when the celiac artery and/or the celiac plexus nerves is compressed by the median arcuate ligament during expiration causing a variety of gastrointestinal symptoms. Here, we present a case of median arcuate ligament syndrome in a persistently symptomatic 35-year-old man that presented as a mimicker of Crohn's disease. Symptomatology, computed tomography angiography, and abdominal ultrasound Doppler were consistent with celiac artery compression syndrome. After surgical decompression of the ligament and removal of the celiac ganglion, he reported a definitive relief of abdominal pain and resolution of symptoms.

COVID-19 and Cancer: A Review of the Registry-Based Pandemic Response.

Importance: The COVID-19 pandemic has had consequences for patients with cancer worldwide and has been associated with delays in diagnosis, interruption of treatment and follow-up care, and increases in overall infection rates and premature mortality. Observations: Despite the challenges experienced during the pandemic, the global oncology community has responded with an unprecedented level of investigation, collaboration, and technological innovation through the rapid development of COVID-19 registries that have allowed an increased understanding of the natural history, risk factors, and outcomes of patients with cancer who are diagnosed with COVID-19. This review describes 14 major registries comprising more than 28 500 patients with cancer and COVID-19; these ongoing registry efforts have provided an improved understanding of the impact and outcomes of COVID-19 among patients with cancer. Conclusions and Relevance: An initiative is needed to promote active collaboration between different registries to improve the quality and consistency of information. Well-designed prospective and randomized clinical trials are needed to collect high-level evidence to guide long-term epidemiologic, behavioral, and clinical decision-making for this and future pandemics.

HER-2 Neu gene: A valuable therapeutic target in metastatic mucoepidermoid carcinoma.

INTRODUCTION: Salivary gland neoplasms (SGNs) respond poorly to the traditional chemotherapy agents limiting the availability of systemic treatment options in the metastatic setting. The recent identification of actionable molecular targets in SGNs has led to the evaluation of targeted therapies in non-approved advanced SGNs. CASE REPORT: We present the case of an elderly male with HER-2 Neu overexpressing metastatic mucoepidermoid carcinoma (MEC) who demonstrated a prompt and sustained disease response to targeted therapies directed against HER-2 Neu with long survival interrupted by hepatoxicity to Trastuzumab emtansine (TDM-1) treatment.Management and Outcome: The patient was started on Trastuzumab and Pertuzumab on a clinical trial and resulted in an objective improvement sustained over 3 years. Following the disease progression, TDM-1 was started with a response until the patient developed severe hepatotoxicity as an adverse effect of TDM-1 therapy resulting in its discontinuation. Close follow-up post-treatment-discontinuation demonstrated continued clinical improvement until 6 months, when the patient developed brain metastasis. He passed away a few months later in hospice care. DISCUSSION: The metastatic MEC in our patient overexpressed HER-2 Neu. Owing to Trastuzumab and Pertuzumab response, Trastuzumab emtansine (TDM-1) was initiated on a compassionate basis which further extended the survival but had to be terminated owing to adverse effects. Given the paucity of data on targeted therapies in the treatment of metastatic SGNs and the safety, tolerability, and efficacy of TDM-1 therapy among the elderly, further studies are warranted to answer these important questions and to identify eligible patients for this novel treatment option.

Successful Rechallenge with Osimertinib after Very Acute Onset of Drug-Induced Pneumonitis.

Drug-induced interstitial lung disease (DI-ILD) is a rare, yet life-threatening complication associated with tyrosine-kinase inhibitor (TKI) therapy. Third-generation epidermal growth factor receptor-TKI, osimertinib use can be associated with a benign radiological finding called transient asymptomatic pulmonary opacities that can be confused with an infectious pulmonary process resulting in overtreatment with antibiotics or premature treatment withdrawal or severe DI-ILD. In this case, our patient with newly diagnosed metastatic non-small cell lung cancer on treatment with osimertinib developed very early onset severe DI-ILD (grade-IV) with a unique pattern of pulmonary involvement and was treated with high-dose corticosteroids with a response. She was later successfully rechallenged with osimertinib and responded well to the treatment. Our case highlights the importance of being cognizant of the possibility that DI-ILD can rarely occur within a week of treatment initiation with osimertinib and safe reintroduction of the drug is possible in select patients following complete resolution of pulmonary radiographic findings and clinical symptoms even with high-grade adverse events.

Doege-Potter Syndrome with a Benign Solitary Fibrous Tumor: A Case Report and Literature Review.

Doege-Potter syndrome is a rare paraneoplastic syndrome that is often diagnosed incidentally during the workup of hypoglycemia of unclear etiology. It is characterized by a non-islet cell tumor hypoglycemia secondary to excessive production of partially processed IGF-II hormone from a solitary fibrous tumor (SFT). Often these tumors are intrathoracic, benign, and asymptomatic. Occasionally they present as a paraneoplastic event; hypertrophic osteoarthropathy in Pierre-Marie-Bamberger syndrome and hypoglycemia in Doege-Potter syndrome. The NAB2-STAT6 gene fusion is the hallmark of the SFT. Complete surgical resection of the tumor often results in resolution of symptoms and cure in most cases. Here we present the case of an 83-year-old non-diabetic female with recurrent syncopal events who was diagnosed with the Doege-Potter syndrome secondary to a SFT of pleura. Her tumor was positive for NAB2-STAT6 gene fusion on RT-PCR. Following the resection of the giant tumor mass, she became symptom-free within 24 h, and has remained asymptomatic at 4 months follow-up.

Etiology and management of hypertension in patients with cancer.

The pathophysiology of hypertension and cancer are intertwined. Hypertension has been associated with an increased likelihood of developing certain cancers and with higher cancer-related mortality. Moreover, various anticancer therapies have been reported to cause new elevated blood pressure or worsening of previously well-controlled hypertension. Hypertension is a well-established risk factor for the development of cardiovascular disease, which is rapidly emerging as one of the leading causes of death and disability in patients with cancer. In this review, we discuss the relationship between hypertension and cancer and the role that hypertension plays in exacerbating the risk for anthracycline- and trastuzumab-induced cardiomyopathy. We then review the common cancer therapies that have been associated with the development of hypertension, including VEGF inhibitors, small molecule tyrosine kinase inhibitors, proteasome inhibitors, alkylating agents, glucocorticoids, and immunosuppressive agents. When available, we present strategies for blood pressure management for each drug class. Finally, we discuss blood pressure goals for patients with cancer and strategies for assessment and management. It is of utmost importance to maintain optimal blood pressure control in the oncologic patient to reduce the risk of chemotherapy-induced cardiotoxicity and to decrease the risk of long-term cardiovascular disease.

Cardiovascular risk management in cancer survivors: Are we doing it right?

Although under-recognized, cancer survivors continue to be at an increased risk of death from cardiovascular complications post-remission or cure. This increased burden of cardiovascular disease results from the interplay of various factors. Adequate cardiovascular risk assessment and timely intervention through a multi-disciplinary approach in these patients plays a pivotal role in the prevention of cardiovascular morbidity and mortality. We discuss the shortcomings of using current risk prediction scores in cancer survivors and provide some insights into cardiovascular risk management relevant for primary care physicians, oncologists, and cardiologists alike.

Pneumothorax in Mechanically Ventilated Patients with COVID-19 Infection.

Data on patient-related factors associated with pneumothorax among critically ill patients with COVID-19 pneumonia is limited. Reports of spontaneous pneumothorax in patients with coronavirus disease 2019 (COVID-19) suggest that the COVID-19 infection could itself cause pneumothorax in addition to the ventilator-induced trauma among mechanically ventilated patients. Here, we report a case series of five mechanically ventilated patients with COVID-19 infection who developed pneumothorax. Consecutive cases of intubated patients in the intensive care unit with the diagnosis of COVID-19 pneumonia and pneumothorax were included. Data on their demographics, preexisting risk factors, laboratory workup, imaging findings, treatment, and survival were collected retrospectively between March and July 2020. Four out of five patients (4/5; 80%) had a bilateral pneumothorax, while one had a unilateral pneumothorax. Of the four patients with bilateral pneumothorax, three (3/4; 75%) had secondary bacterial pneumonia, two had pneumomediastinum and massive subcutaneous emphysema, and one of these two had an additional pneumoperitoneum. A surgical chest tube or pigtail catheter was placed for the management of pneumothorax. Three out of five patients with pneumothorax died (3/5; 60%), and all of them had bilateral involvement. The data from these cases suggest that pneumothorax is a potentially fatal complication of COVID-19 infection. Large prospective studies are needed to study the incidence of pneumothorax and its sequelae in patients with COVID-19 infection.

COVID-19 in Older Individuals with Cancer: Problem and Potential Solutions.

The ongoing coronavirus disease-2019 (COVID-19) pandemic has radically affected medical practice and healthcare delivery in the United States and beyond. Its impact on vulnerable populations especially older adults battling cancer is striking. Older adults with baseline immunosenescence compounded with multimorbidity and reduced physiological reserves are at even higher risk of succumbing to infection. When it comes to older adults with cancer mortality, it often multifactorial with modifiable risk factors. A specific approach with attention to advance care planning and how cancer care is delivered coupled with a comprehensive geriatric assessment may ultimately be the key to improve overall survival.

5-Fluorouracil Rechallenge After Cardiotoxicity.

BACKGROUND 5-Fluorouracil (5-FU) is a widely used intravenous chemotherapy agent that is highly effective in the treatment of a variety of solid malignancies. Cardiotoxicity related to 5-FU is a complex clinical entity associated with significant morbidity and mortality. Whether a patient who experienced a major cardiac side effect from 5-FU can be safely rechallenged with this drug is a clinical dilemma. CASE REPORT We present the case of a patient with stage III colorectal adenocarcinoma who experienced ventricular fibrillation during the first cycle of FOLFOX (5-FU, folinic acid, and oxaliplatin) regimen in the adjuvant setting. Post-resuscitation electrocardiogram revealed ST-elevation in the inferior leads with reciprocal changes. Coronary angiogram revealed no obstructive coronary artery disease. Cardiac workup led to the conclusion of probable fluorouracil-induced vasospasm as the cause of his cardiac arrest. He received implantable cardioverter defibrillator. The decision was made to hold 5-FU. At 3-month follow-up, there was evidence of progressive metastasis. After comprehensive risk-benefit discussions, the decision was made for palliative chemotherapy using 5-FU/leucovorin. A pre-treatment regimen including isosorbide dinitrate, diltiazem, and metoprolol was used. The patient tolerated 5-FU rechallenge without recurrent cardiovascular complication. CONCLUSIONS The cardiotoxicity profile of 5-FU can range from anginal chest pain to sudden cardiac death. When considering 5-FU rechallenge, clinicians should adopt a multidisciplinary approach, favor using prophylactic antianginal therapy, change to bolus dosing, and use continuous telemetry monitoring. Screening patients for dihydropyrimidine dehydrogenase deficiency prior to 5-FU administration may facilitate an individualized strategy for optimal dosing and safety.

Socio-Demographic Disparities in Gastric Adenocarcinoma: A Population-Based Study.

Background: Gastric cancer is one of the leading causes of cancer-related mortality worldwide, accounting for 8.2% of cancer-related deaths. The purpose of this study was to investigate the geographic and sociodemographic disparities in gastric adenocarcinoma patients. METHODS: We conducted a retrospective study in gastric adenocarcinoma patients between 2004 and 2013. Data were obtained from the National Cancer Data Base (NCDB). Univariate and multivariable analyses were performed to evaluate overall survival (OS). Socio-demographic factors, including the location of residence [metro area (MA) or rural area (RA)], gender, race, insurance status, and marital status, were analyzed. RESULTS: A total of 88,246 [RA, N = 12,365; MA, N = 75,881] patients were included. Univariate and multivariable analysis showed that RA had worse OS (univariate HR = 1.08, p < 0.01; multivariate HR = 1.04; p < 0.01) compared to MA. When comparing different racial backgrounds, Native American and African American populations had poorer OS when compared to the white population; however, Asian patients had a better OS (multivariable HR = 0.68, p < 0.01). From a quality of care standpoint, MA patients had fewer median days to surgery (28 vs. 33; p < 0.01) with fewer positive margins (6.3% vs. 6.9%; p < 0.01) when compared to RA patients. When comparing the extent of lymph node dissection, 19.6% of MA patients underwent an extensive dissection (more than or equal to 15 lymph nodes) in comparison to 18.7% patients in RA (p = 0.03). DISCUSSION: This study identifies socio-demographic disparities in gastric adenocarcinoma. Future health policy initiatives should focus on equitable allocation of resources to improve the outcomes.