Association Between Obesity and Cancer Mortality: An Internal Medicine Outpatient Clinic Perspective.

BACKGROUND: Obesity is one of the leading preventable causes of cancer that has a causal relationship with cancers of esophagus, breast and colon. Paradoxically, there are studies demonstrating that obesity is associated with improved survival in cancer patients. The aim of our study was to investigate the association of obesity and cancer mortality in adult patients. METHODS: Retrospective medical record review of 784 adult patients was performed who had a diagnosis of cancer and who were seen in our outpatient Internal Medicine Clinic between January 1, 2019 and December 31, 2019. RESULTS: Forty-three (5.2%) patients were cancer non-survivors and 741 (94.8%) were cancer survivors. The mean age of the cancer non-survivors group was significantly higher than that of the cancer survivors (78.7 vs. 68.0 years, respectively; P < 0.001). For every unit increase in age, there was 7.6% increased odds of cancer death (95% confidence interval (CI): 3-12%) (P = 0.001). Average body mass index (BMI) of the patients in the cancer non-survivors group was significantly lower than that of the cancer survivors group (25.0 vs. 28.1 kg/m2; P = 0.008). Non-obese patients had 4.9 times greater odds of cancer death (95% CI: 1.51 - 15.81) (P = 0.008). The mean glycosylated hemoglobin (HbA1c) was significantly higher in the cancer non-survivors group compared to the cancer survivors group (7.1% vs. 6.0%; P < 0.001), and for every unit increase in HbA1c there was 1.6 times greater odds of cancer death (95% CI: 1.14 - 2.23) (P = 0.006). Patients with peripheral artery disease (PAD) had 3.5 times greater odds of cancer death compared to those without PAD (95% CI: 1.18 - 10.19) (P = 0.023). CONCLUSIONS: Non-obese patients with cancer had higher odds of cancer death. Rising HbA1c, increasing age, and presence of PAD were associated with increased cancer mortality.

Impact of Correcting Nutritional Deficiency Anemias in the Elderly on Hospitalizations, Falls, and Mortalities.

BACKGROUND: The incidence and prevalence of anemia increase with age, particularly in adults older than 65 years, and it is associated with a number of adverse health outcomes (AHO), particularly hospitalizations, falls and mortalities. Given that approximately one-third of these anemias are due to reversible causes, we studied whether the treatment of nutritional deficiency anemia (NDA), namely iron deficiency anemia (IDA), cobalamin deficiency anemia (CDA), and folate deficiency anemia (FDA), improves AHO; and explored whether each NDA had different AHO. METHODS: We reviewed electronic medical records of our internal medicine office patients aged 65 years or older, who had a diagnosis of anemia in a non-acute setting. RESULTS: Total 600 patients were included. Mean age was 75.2 years. Thirty-one point three percent had NDA (CDA 15.3%, IDA 12.3%, FDA 3.7%); and 68.7% had other anemias whom we categorized as non-nutritional deficiency anemias (NNDA), which included anemia of chronic disease (11.2%), myelodysplastic syndrome (6.2%), renal insufficiency anemia (5.7%) and unexplained anemia (45.6%). Even after adequate treatment, IDA group had significantly more hospitalizations (median, 25th - 75th: 2 (0 - 4) vs. 0 (0 - 1), P < 0.001), falls (median, 25th - 75th: 1 (0 - 3) vs. 0 (0 - 1), P < 0.001) and mortalities (10.8% vs. 3.4%, P = 0.011); CDA group had significantly more hospitalizations (median, 25th - 75th: 1 (0 - 2) vs. 0 (0 - 1), P = 0.007), but no difference in falls (median, 25th - 75th: 0 (0 - 1) vs. 0 (0 - 1), P = 0.171) and mortalities (7.6% vs. 3.4%, P = 0.083); and FDA group had significantly more hospitalizations (median, 25th - 75th: 1 (0 - 2) vs. 0 (0 - 1), P = 0.001), but no difference in falls (median, 25th - 75th: 0 (0 - 1) vs. 0 (0 - 1), P = 0.615) and mortalities (4.5% vs. 3.4%, P = 0.550), compared to the NNDA group. Age, Black race, higher number of comorbidities, presence of malignancy and use of direct oral anticoagulants were associated with increased odds of AHO in patients with NDA. CONCLUSIONS: Compared to the patients with NNDA, patients with IDA had more hospitalizations, falls and mortalities even after adequate treatment; while patients with CDA and FDA had only more hospitalizations. Adequate treatment mitigated falls and mortalities in elderly patients with CDA and FDA.

Aplastic anemia in a patient with CVID due to NFKB1 haploinsufficiency.

Acquired aplastic anemia (AA) is a life-threatening bone marrow failure caused by an autoimmune cytotoxic T lymphocyte attack on hematopoietic stem and progenitor cells. Factors contributing to aberrant autoimmune activation in AA include a deficit of T regulatory cells and high levels of inflammatory cytokines. Several acquired conditions of immune dysregulation and genetic polymorphisms in inflammatory cytokines and human leukocyte antigen genes have been linked to an increased risk of AA. However, AA has not been reported in patients with Mendelian disorders of immune regulation. Here we report a patient with familial common variable immunodeficiency (CVID) caused by a pathogenic variant in NFKB1, who developed AA as an adult. The patient had a difficult clinical course and was unable to tolerate standard AA therapy with cyclosporine A and eltrombopag, with complications attributed in part to the effect of cyclosporine A on NF-κB signaling. Our case suggests a novel link between genetic disorders of immune regulation and AA and highlights the importance of recognizing inherited autoimmunity syndromes in AA patients for the selection of optimal therapy and prognostic counseling.

mTORC2 regulates multiple aspects of NKT-cell development and function.

Invariant NKT (iNKT) cells bridge innate and adaptive immunity by rapidly secreting cytokines and lysing targets following TCR recognition of lipid antigens. Based on their ability to secrete IFN-γ, IL-4 and IL-17A, iNKT-cells are classified as NKT-1, NKT-2, and NKT-17 subsets, respectively. The molecular pathways regulating iNKT-cell fate are not fully defined. Recent studies implicate Rictor, a required component of mTORC2, in the development of select iNKT-cell subsets, however these reports are conflicting. To resolve these questions, we used Rictorfl/fl CD4cre+ mice and found that Rictor is required for NKT-17 cell development and normal iNKT-cell cytolytic function. Conversely, Rictor is not absolutely required for IL-4 and IFN-γ production as peripheral iNKT-cells make copious amounts of these cytokines. Overall iNKT-cell numbers are dramatically reduced in the absence of Rictor. We provide data indicating Rictor regulates cell survival as well as proliferation of developing and mature iNKT-cells. Thus, mTORC2 regulates multiple aspects of iNKT-cell development and function.

Natural and inducible TH17 cells are regulated differently by Akt and mTOR pathways.

Natural T helper 17 (nTH17) cells are a population of interleukin 17 (IL-17)-producing cells that acquire effector function in the thymus during development. Here we demonstrate that the serine/threonine kinase Akt has a critical role in regulating nTH17 cell development. Although Akt and the downstream mTORC1-ARNT-HIFα axis were required for generation of inducible TH17 (iTH17) cells, nTH17 cells developed independently of mTORC1. In contrast, mTORC2 and inhibition of Foxo proteins were critical for development of nTH17 cells. Moreover, distinct isoforms of Akt controlled the generation of TH17 cell subsets, as deletion of Akt2, but not of Akt1, led to defective generation of iTH17 cells. These findings define mechanisms regulating nTH17 cell development and reveal previously unknown roles of Akt and mTOR in shaping subsets of T cells.