How have US colorectal cancer mortality trends changed in the past 20 years?

In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States. However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. We analyzed the mortality trends of different subtypes of CRC based on Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research data from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Our study shows that the overall CRC rates decreased significantly from 26.42 to 15.98 per 100,000 individuals, with an AAPC of -2.41. However, the AAMR of rectosigmoid cancer increased significantly from 0.82 to 1.08 per 100,000 individuals, with the AAPC of +1.10. Men and Black individuals had the highest AAMRs respectively (23.90 vs. 26.93 per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. Rural populations had a higher AAMR than the urban populations (22.40 vs. 19.60 per 100,000 individuals). Although overall CRC mortality declined, rising trends in young-onset CRC and rectosigmoid cancer warrant attention. Disparities persist in terms of sex, race, and geographic region, and urbanization level, emphasizing the need for targeted public health measures.

Pseudo-Progression of Melanoma Treated with Nivolumab/Ipilimumab: A Case Report.

BACKGROUND Melanoma is an aggressive skin cancer that can be difficult to manage. Its treatment has been transformed by immunotherapy. Melanoma cells frequently have mutations that make them vulnerable to attack by the immune system, and this is how immunotherapy can fight this cancer. Immunotherapy with checkpoint inhibitors targets mechanisms that malignant cells use to evade immune system detection, blocking proteins produced by the tumor, and allowing the immune system to identify and attack cancerous cells. CASE REPORT A 74-year-old woman presented with a lump on the right side of her chest. Tests revealed a metastatic malignant tumor with melanocytic differentiation. Stage IV melanoma was diagnosed, and the patient started therapy with nivolumab/ipilimumab for palliative intent, which she tolerated without adverse effects. However, she was hospitalized for Clostridioides difficile colitis after 3 treatment cycles, and computed tomography (CT) scan findings suggested disease progression. Positron emission tomography (PET)-CT obtained after her discharge from the hospital showed a complete metabolic response at all disease sites, indicating the initial progression was most likely a pseudo-progression from the use of immunotherapy. The patient continued with nivolumab as a single agent and has been doing well. CONCLUSIONS This case highlights the importance of careful evaluation of immunotherapy response in patients with melanoma. The initial progression noted in this patient was most likely pseudo-progression, which resolved with further immunotherapy. Clinicians should consider PET-CT imaging in cases of suspected pseudo-progression to avoid unnecessary changes in therapy. Patient response to immunotherapy demonstrates the effectiveness of immunotherapy in treating advanced melanoma.

Association of Elevated Glycated Hemoglobin (HbA1c) in COVID-19 Patients Admitted to the Intensive Care Unit and Their Clinical Outcomes.

Aim The study aimed to collect retrospective data to investigate the association between elevated glycated hemoglobin (HbA1c) levels and clinical outcomes in COVID-19 patients admitted to the ICU, including in-hospital mortality and 90-day mortality.  Methods This is an observational retrospective study using electronic health records of patients with diabetes admitted to the ICU with COVID-19 across the University of Pittsburgh Medical Center (UPMC) in Central PA Hospitals. Our retrospective analysis was performed on patients admitted to the ICU between May 1st, 2021, to May 1st, 2022. The HbA1c level obtained within three months before their admission was evaluated and stratified to show their association with clinical outcomes, including in-hospital mortality and 90-day mortality. Additionally, the need for insulin drip and ICU and hospital length of stay were compared among these patients.  Results We analyzed 384 patients, which were distributed in three groups. The majority of the patients (183 patients or 47.66%) had an HbA1c below 7%, 113 patients (29.43%) had an HbA1c between 7-9%, and 88 patients (22.92%) had an HbA1c above 9%. The group with an HbA1c<7% had a mortality rate of 54.1% during the hospital stay, with a median stay of 13 days. The patients with an HbA1c between 7-9% had a higher mortality rate of 65.49% with a median stay of 12 days. The patients with HbA1c>9% had a mortality rate of 43.18% with a median stay of 11.5 days.  Conclusion This retrospective study found that there was no linear association between higher HbA1c levels and a higher risk of mortality during hospitalization. The 90-day mortality rate was not statistically different among the three HbA1c groups. The need for insulin drip was higher in patients with higher HbA1c levels. The majority of patients in all three groups were classified as low-risk based on their BMI, and there were no significant differences in the distribution of patients across BMI categories in the HbA1c groups.

Insights into the tumor microenvironment of B cell lymphoma.

The standard therapies in lymphoma have predominantly focused on targeting tumor cells with less of a focus on the tumor microenvironment (TME), which plays a critical role in favoring tumor growth and survival. Such an approach may result in increasingly refractory disease with progressively reduced responses to subsequent treatments. To overcome this hurdle, targeting the TME has emerged as a new therapeutic strategy. The TME consists of T and B lymphocytes, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), and other components. Understanding the TME can lead to a comprehensive approach to managing lymphoma, resulting in therapeutic strategies that target not only cancer cells, but also the supportive environment and thereby ultimately improve survival of lymphoma patients. Here, we review the normal function of different components of the TME, the impact of their aberrant behavior in B cell lymphoma and the current TME-direct therapeutic avenues.

Treating Hypertriglyceridemia-Induced Pancreatitis With Intravenous Insulin and Plasmapheresis.

Hypertriglyceridemic pancreatitis (HTGP) is well-known but it is extremely rare, especially in younger patients. The main treatment modalities for HTGP are apheresis and intravenous insulin. However, apheresis in severe HTGP is not well established and the efficacy of the treatment is lacking. Herein, we discuss a case of a 17-year-old female patient with no significant past medical history who initially presented to the emergency department with severe diabetic ketoacidosis (DKA) and was intubated due to severe metabolic acidosis and impending respiratory failure on arrival. Further investigation showed evidence of HTGP. Initially, her condition did not improve with intravenous insulin. However, a course of apheresis along with supportive care improved her condition drastically. Hence, this is a case report which showed the efficacy of concomitant use of insulin infusion and plasmapheresis in regard to treating HTGP. Outcomes of HTGP based on different treatment modalities are discussed in this literature as well. However, to date, there are no randomized studies to draw a solid treatment algorithm, thus further research on the most efficient treatment regimes is required for the management of HTGP.

Increasing tissue requirements in lymphoma trials may exclude patients with high-risk disease or worse prognosis.

An enhanced understanding of the molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) has opened the door to clinical trials evaluating novel agents with subtype-specific activity. It is an emerging question whether core needle biopsies (CNB) can adequately meet the increasing tissue requirements of these clinical trials. This can potentially lead to selective enrollment of patients who can undergo excisional biopsy (EB). It is also important to know whether patients who can undergo extensive diagnostic work up differ in their disease characteristics and outcomes from those who cannot. In this observational study, we describe the characteristics, outcomes, and adequacy of diagnostic tissue in patients with newly diagnosed DLBCL and primary mediastinal large B-cell lymphoma who underwent EB vs CNB. Of the 1061 patients, 532 (49.8%) underwent EB and 529 (50.1%) underwent CNB. A significantly higher proportion of patients with CNB had advanced stage disease, an international prognostic index of ≥3, and inadequate tissue for molecular analyses. Patients with CNB had significantly worse 5-year event-free survival (67.6% vs 56.9%; hazard ratio [HR], 0.76; confidence interval [CI]95, 0.6-0.9, P < .001) and 5-year overall survival (76.4% vs 69.2%; HR, 0.8; CI95, 0.6-0.9, P < .001). Thus, patients who underwent CNB have poor-risk features and inferior outcomes on frontline chemoimmunotherapy, are more likely to have inadequate tissue for molecular analyses, and might not meet the tissue requirements of biomarker-driven clinical trials. Thus, the increasing tissue requirements of biomarker-driven clinical trials may result in the exclusion of patients with high-risk DLBCL who need novel agents.