Hypoxemia and stroke in a patient with a pacemaker

We report a woman with a VVI pacemaker and a history of stroke and severe hypoxemia due to a right-to-left shunt. Anomalous blood flow was through a patent foramen oval, and was related directly with severe tricuspid regurgitation because the ventricular pacemaker electro de was adhered to the tricuspid valve. She was treated successfully with surgery. We review the role of patent foramen ovale from a clinical point of view, and current therapeutic options.     

Uptake and use of a diabetes management program with a mobile glucometer

ObjectiveInnovative mobile health technologies (mHealth) may facilitate self-management of blood glucose. This study evaluates uptake, use, and predictors of uptake and long-term use of a diabetes mHealth intervention, which comprises an FDA-approved mobile glucometer and nurse coaching, in a real-world setting.Methodsn = 4438 commercially-insured adults with diabetes were recruited from 2014 to 2015 via an opt-in, phone-based process. In this post-only study, we obtained data on recruitment, glucometer use, demographics, and insurance and employer characteristics. We calculated percent uptake and reasons for unsuccessful recruitment. We used logistic regression to model predictors of uptake and survival analysis to examine duration of testing and predictors of discontinuation.ResultsOf the recruited members, 556 (12.5%) signed up for the mHealth program and 324 (7.3%) began testing. Of those who did not sign up, the majority (70.6%) were unable to be reached by phone. Male (OR = 1.60, 95% CI: 1.25, 2.03) and Spanish-speaking (OR = 8.34, 95% CI: 5.40, 12.88) members were more likely to start testing. Two-thirds (66.2%) of those who started testing had a first test value that indicated hyperglycemia; 97% tested more than once and the median time between first and last test was 407 days. Older age was the only significant predictor of long-term use.ConclusionsAlthough uptake of the mHealth program was low, most members who started testing had initial glucose values that indicated a need for better glucose management and the majority of patients engaged with the program for over a year. Male and Spanish-speaking members were more likely to initiate the program.     

Progressive and Fatal Course of a Patient with a Multifocal Leiomyomatous Tumor

The case history of a 53-yr-old woman exhibiting the progressive appearance of several hundreds of subcutaneous leiomyomatous tumors in a 15-yr period is presented. The occurrence of multiple tumors in the gastrointestinal tract, mesentery, and retroperitoneum, necessitated several laparotomies because of pain and chronic blood loss. On light microscopy high mitotic activity, which is generally a characteristic of sarcoma, was only encountered in lesions, surgically removed a few months before death. It is argued that our patient suffered from multiple leiomyomatous tumors with progressive growth capacity, which may represent a multifocal origin rather than a metastasized sarcoma.     

Evaluation and outcomes of women with a breast lump and a normal mammogram result

BACKGROUND: Many women experience a breast lump. Clinical guidelines suggest that a normal mammogram result alone is not adequate to exclude a diagnosis of cancer. OBJECTIVE: To examine the characteristics of women with a breast lump and a normal mammogram that were associated with receiving further evaluation, and to examine cancer outcomes. DESIGN: Observational cohort. PARTICIPANTS: Women aged 35 to 70 years who participated in a population-based mammography registry and who did not have a history of breast cancer noted at the time of their mammogram that they had a breast lump, and had a "normal" (Breast Imaging Reporting and Data System 1 or 2) mammogram result (n=771). MEASUREMENTS: Telephone survey performed 6 months after the mammogram to ascertain information about evaluation. Cancer outcomes within 12 months of the index mammogram were confirmed through linkage with a cancer registry. RESULTS: Only 56.9% of women reported receiving an adequate evaluation for their breast lump, including a subsequent clinical breast exam, a visit to a breast specialist, an ultrasound, a biopsy, or aspiration. Latinas were less likely than white women to have received adequate evaluation, as were obese women compared with normal-weight women, and uninsured women compared with women with insurance. Among women with at least 12 months of follow-up, 1.4% were diagnosed with cancer. CONCLUSIONS: Many women do not receive adequate evaluation for a recent breast lump. Interventions should be designed to improve the follow-up of women with this common clinical problem.     

Successful Management of a Pregnant Woman with a TSH Secreting Pituitary Adenoma with Surgical and Medical Therapy

We described a 39-yr-old asian female who was initially diagnosed with prolactinoma and presented with increase nervousness and weight loss. Laboratory evaluation revealed an inappropriately normal TSH level with elevated free T4, total T3, alpha-subunit and prolactin level. The alpha-subunit/TSH molar ratio was 4. MRI showed a macroadenoma extending to the suprasellar cistern. Treatment was begun with propylthiouracil and bromocriptine. After 5 months of therapy, she became pregnant. At 27 weeks of gestation, she developed headache and decreased visual acuity in her left eye. MRI showed a slightly increase in tumor size compressing the optic chaiasm. Transphenoid macroadenectomy was performed with immediate relief of the visual field abnormality. At 39 weeks gestation a baby with no malformations was delivered. This is the second case report of TSH secreting pituitary adenoma which was exarcerbated during pregnancy. In contrast to the first case, our case was managed with both surgical and medical approach. The judicious use of both medical and surgical therapy can result in a successful outcome to mother and fetus in a patient with TSH secreting pituitary adenoma.     

Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.Proteasomes are multisubunit complexes that degrade intracellular proteins through the ubiquitin–proteasome pathway (1). The three catalytic β subunits β1, β2, and β5 in the proteasome complex are replaced by proteasome (prosome, macropain) subunit B9 (PSMB9)/β1i, PSMB10/β2i, and PSMB8/β5i, respectively, to form the immunoproteasome (2). The immunoproteasome generates peptides suitable for binding onto HLA I molecules, facilitating antigen presentation for CD8⁺ T-cell responses. Lack of expression or down-regulation of the immunoproteasome may contribute to immune evasion through antigen loss (3).The impact of immunoproteasome expression on antigen presentation in tumors of epithelial origin is not well established. We have investigated the constitutive and induced expression patterns of immunoproteasome subunits in non-small cell lung carcinoma (NSCLC) and their impact on antigen presentation. We provide evidence for dysregulated expression of immunoproteasome subunits in NSCLC cells with a mesenchymal phenotype, associated with a markedly reduced repertoire of HLA-bound peptides. Reduced expression of immunoproteasome subunits in NSCLC was also associated with reduced disease free survival.