Advancements in Systemic Therapy for Pancreatic Cancer.

Outcomes for patients with advanced pancreatic cancer have improved in the past 12 years, mainly because of progress made in systemic therapies. New treatment strategies for advanced pancreatic cancer include switch maintenance with cytotoxic therapies, induction maintenance, and the utilization of targeted agents for patients with actionable variants, as well as ongoing development of cytotoxic regimens, such as NALIRIFOX. The activity of immunotherapy has been disappointing to date, but novel combinations and identifying appropriate patient populations may further unlock its potential.

Nonsteroidal anti-inflammatory drugs as a targeted therapy for bone marrow failure in Ghosal hematodiaphyseal dysplasia.

Advances in genomic diagnostics hold promise for improved care of rare hematologic diseases. Here, we describe a novel targeted therapeutic approach for Ghosal hematodiaphyseal dysplasia, an autosomal recessive disease characterized by severe normocytic anemia and bone abnormalities due to loss-of-function mutations in thromboxane A synthase 1 (TBXAS1). TBXAS1 metabolizes prostaglandin H2 (PGH2), a cyclooxygenase (COX) product of arachidonic acid, into thromboxane A2. Loss-of-function mutations in TBXAS result in an increase in PGH2 availability for other PG synthases. The current treatment for Ghosal hematodiaphyseal dysplasia syndrome consists of corticosteroids. We hypothesize that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-1 and COX-2, could ameliorate the effects of TBXAS1 loss and improve hematologic function by reducing prostaglandin formation. We treated 2 patients with Ghosal hematodiaphyseal dysplasia syndrome, an adult and a child, with standard doses of NSAIDs (aspirin or ibuprofen). Both patients had rapid improvements concerning hematologic parameters and inflammatory markers without adverse events. Mass spectrometry analysis demonstrated that urinary PG metabolites were increased along with proinflammatory lipoxygenase (LOX) products 5-hydroxyeicosatetraenoic acid and leukotriene E4. Our data show that NSAIDs at standard doses surprisingly reduced both COX and LOX products, leading to the resolution of cytopenia, and should be considered for first-line treatment for Ghosal hematodiaphyseal dysplasia syndrome.

Association Between Depressive Symptoms and Cardiac Structure and Function in a Peruvian Population.

Depressive disorders are a leading cause of disability and are globally pervasive. It is estimated that 80% of depression occurs in low-income and middle-income countries. Depression is associated with worse outcomes in patients with cardiac disease including heart failure (HF); however, mechanistic understanding to explain heightened risk in HF remains poorly characterized. We examined the association between depressive symptoms and cardiac structure and function by transthoracic echocardiography. We selected a random sample of adult participants in Puno and Pampas de San Juan de Miraflores, Peru, from the CRONICAS cohort study. Depression symptoms were self-reported and measured with the Center for Epidemiological Studies Depression Scale in 2010. Participants underwent transthoracic echocardiography in 2014. Multivariable linear regression was used to examine the relationship between depressive symptoms and echocardiographic measures of cardiac structure and function and was adjusted for relevant covariates. Three hundred and seventy-three participants (mean age 56.7 years, 57% female) were included in this analysis of which 91 participants (24%) had clinically significant depressive symptoms. After adjustment, clinically significant depressive symptoms were associated with a reduced diastolic relaxation velocity compared to non-depressed subjects (-0.72 cm/s, 95% CI -1.21 to -0.24, p = 0.004). Other differences between depressed and non- depressed participants were less obvious. In conclusion, clinically significant depressive symptoms were associated with a lower septal e' velocity in the Peruvian population. Depressive symptoms were not obviously associated with other abnormalities in cardiac structure or function.

A Psycholgical Intervention Delivered by Automated Mobile Phone Messaging Stabilized Hip and Knee Function During the COVID-19 Pandemic: A Randomized Controlled Trial.

BACKGROUND: We conducted a randomized controlled trial to evaluate the effectiveness of acceptance and commitment therapy (ACT) delivered via a mobile phone messaging robot to patients who had their total hip arthroplasty or total knee arthroplasty procedures postponed due to the COVID-19 pandemic. METHODS: Ninety patients scheduled for total hip arthroplasty or total knee arthroplasty who experienced surgical delay due to the COVID-19 pandemic were randomized to the ACT group, receiving 14 days of twice daily automated mobile phone messages, or the control group, who received no messages. Minimal clinically important differences (MCIDs) in preintervention and postintervention patient-reported outcome measures were utilized to evaluate the intervention. RESULTS: Thirty-eight percent of ACT group participants improved and achieved MCID on the Patient-Reported Outcome Measure Information System Physical Health compared to 17.5% in the control group (P = .038; number needed to treat [NNT] 5). For the joint-specific Hip Disability and Osteoarthritis Outcome Score Joint Replacement and Knee Disability and Osteoarthritis Outcome Score Joint Replacement (KOOS JR), 24% of the ACT group achieved MCID compared to 2.5% in the control group (P = .004; NNT 5). An improvement in the KOOS JR was found in 29% of the ACT group compared to 4.2% in the control group (P = .028; NNT 5). Fourteen percent of the ACT group participants experienced a clinical important decline in the KOOS JR compared to 41.7% in the control group (P = .027; NNT 4). CONCLUSION: A psychological intervention delivered via a text messaging robot improved physical function and prevented decline in patient-reported outcome measures in patients who experienced an unexpected surgical delay during the COVID-19 pandemic. LEVEL OF EVIDENCE: 1.

PARP Inhibitors in Pancreatic Cancer.

ABSTRACT: Despite representing only 5% of all annual cancer diagnoses in the United States, pancreatic cancer is projected to become the second leading cause of cancer-related death within the next 10 years. Progress in the treatment of advanced pancreatic cancer has been slow. Systemic therapies rely on combination cytotoxic agents, with limited options at progression. Recently, poly(ADP-ribose) polymerase inhibitors have demonstrated clinical activity in patients with advanced pancreatic cancer and pathogenic variants in BRCA1, BRCA2, and PALB2. In this review, we discuss the development of poly(ADP-ribose) polymerase inhibitors in pancreatic cancer, relevant clinical trials, and future directions.

Social capital and self-rated health in Argentina.

The potential link between social capital and health suggests important pathways by which health may be improved. We examine this relationship using a unique data set from Argentina. This national survey allows us to determine whether the relationships between social capital and health that have been found in the US and Europe also apply to countries in South America (Argentina is the second-largest country in South America with a population of approximately 40 million). We estimate a causal effect of individual-level social capital on health using a measure of informal social interactions as our measure of social capital. Using information about access to public transportation as instrumental variables, we find that both men and women with higher levels of social capital report better health.