Diabetes compromises bone cell metabolism and function, resulting in increased risk of fragility fracture. Advanced glycation end products (AGEs) interact with the receptor for AGEs (RAGE) and can make a meaningful contribution to bone cell metabolism and/or alter function. Searches in PubMed using the key words “advanced glycation end-product,” “RAGE,” “sRAGE,” “bone,” and “diabetes” were made to explain some of the clinical outcomes of diabetes in bone metabolism through the AGE–RAGE signaling pathway. All published clinical studies were included in tables. The AGE–RAGE signaling pathway participates in diabetic complications, including diabetic osteopathy. Some clinical results in diabetic patients, such as reduced bone density, suppressed bone turnover markers, and bone quality impairment, could be potentially due to AGE–RAGE signaling consequences. However, the AGE–RAGE signaling pathway has some helpful roles in the bone, including an increase in osteogenic function. Soluble RAGE (sRAGE), as a ligand decoy, may increase in either conditions of RAGE production or destruction, and then it cannot always reflect the AGE–RAGE signaling. Recombinant sRAGE can block the AGE–RAGE signaling pathway but is associated with some limitations, such as accessibility to AGEs, an increase in other RAGE ligands, and a long half-life (24 hours), which is associated with losing the beneficial effect of AGE/RAGE. As a result, sRAGE is not a helpful marker to assess activity of the RAGE signaling pathway. The recombinant sRAGE cannot be translated into clinical practice due to its limitations.

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Setting Drug resistance threatens tuberculosis (TB) control, particularly among HIV-infected persons. Objective We surveyed antiretroviral therapy (ART) programs from lower-income countries on prevention and management of drug-resistant TB. Design We used online questionnaires to collect program-level data in 47 ART programs in Southern Africa (14), East Africa (8), West Africa (7), Central Africa (5), Latin America (7) and Asia-Pacific (6 programs) in 2012. Patient-level data were collected on 1,002 adult TB patients seen at 40 of the participating ART programs. Results Phenotypic drug susceptibility testing was available at 36 (77%) ART programs, but only used for 22% of all TB patients. Molecular drug resistance testing was available at 33 (70%) programs and used for 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the whole treatment, 16 (34%) during intensive phase only and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line TB regimens; 18 (38%) reported TB drug shortages. Conclusions Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower income countries. DOT was not always implemented and drug supply was regularly interrupted, which may contribute to the global emergence of drug resistance.

Context. Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Twin pregnancies with GTD and coexisting normal fetus are extremely rare with an estimated incidence of 1 case per 22,000–100,000 pregnancies. Molecular mimicry between human chorionic gonadotrophin (hCG) and thyroid-stimulating hormone (TSH) leads to gestational trophoblastic hyperthyroidism (GTH) which is further associated with increased maternal and fetal complications. This is the first reported case in literature describing the delivery of a baby with biochemical euthyroid status following a twin pregnancy with hydatidiform mole (HM) associated with gestational trophoblastic hyperthyroidism (GTH). Case Description. A 24-year-old G4 P3 Caucasian female with twin gestation was admitted to hospital for gestation trophoblastic hyperthyroidism. She was later diagnosed to have twin pregnancy with complete mole and coexisting normal fetus complicated by gestational trophoblastic hyperthyroidism (GTH). Despite the risk associated with the continuation of molar pregnancy, per patient request, pregnancy was continued till viability of the fetus. The patient underwent cesarean section due to worsening preeclampsia and delivered a euthyroid baby at the 24th week of gestation. Conclusions. Twin pregnancy with gestational trophoblastic disease and coexisting normal fetus is associated with high risk of hyperthyroidism, and careful monitoring of the thyroid function test along with dose titration of thionamides is of utmost importance throughout the gestation. If normal thyroid hormone levels are maintained during the pregnancy, euthyroidism could be successfully achieved in the baby.

Background: Hypercalcemia is uncommon in HIV infection but can occur in the setting of lymphoma. We describe a patient with HIV with hypercalcemia and hypoglycemia due to an initially undetected EBV-associated lymphoma. Clinical Case: A 32-year old Caucasian male with recent diagnosis of HIV was admitted for HIV arthropathy and sepsis, and found to have hypercalcemia (Ca 10.7mg/dL, n 8.9-10.2mg/dL; ionized Ca 6.1mg/dL, n 4.6-5.7mg/dL). PTH was suppressed (<10pg/mL, n 12-72pg/mL). PTH-independent causes of hypercalcemia were unremarkable for humoral hypercalcemia of malignancy (PTHrP 0.2pmol/L, n <2.0pmol/L), vitamin D toxicity (24-hydroxyvitamin D 41ng/mL, n 30-80ng/mL), granulomatous disorders (1,25-dihydroxyvitamin D 24.8pg/mL, n 19.9-79.3pg/mL; quantiferon negative), hyperthyroidism, and adrenal insufficiency. Renal function was normal and there was no thiazide, lithium, calcium, or vitamin A use. Serum protein electrophoresis (PEP) showed hypogammaglobinemia consistent with immunodeficiency. Urine PEP was negative for immunoglobulin light chains. Hypercalcemia was initially attributed to HIV with immobilization and calcium level was expected to normalize with antiretroviral therapy. Workup for infectious etiology was negative, his arthralgia and overall clinical status improved, and he was discharged. Three days later, he was readmitted for altered mental status and anemia. He was hypoglycemic, which was new on readmission, and required dextrose-containing IV fluids in addition to tube feeds to keep his serum glucose within normal range. Work up was negative for insulinoma (C peptide 0.48ng/mL, n 0.81-5.3ng/mL; glucose 31mg/dL) but IGF-2 to IGF-1 ratio was elevated at 4.57 which was suggestive of IGF-2-mediated tumor-associated hypoglycemia. Persistent leukocytosis and type B lactic acidosis also suggested an underlying malignancy. Bronchoscopy, bone marrow biopsy, and CSF cytology were negative for malignancy. CSF was positive for EBV (77,100 copies/mL). CT imaging showed liver lesions and biopsy led to the diagnosis of high-grade B-cell lymphoma. He was started on chemotherapy. Hypoglycemia resolved 10 days later, as did the lactic acidosis. Hypercalcemia was treated with pamidronate with return to normal levels. Conclusion: Hypercalcemia in an HIV patient warrants diligent workup. Hypercalcemia in lymphomas are often attributed to elevated 1,25-dihydroxyvitamin D. A possible explanation for normal 1,25-dihydroxyvitamin D observed in our patient is the effect of antiretroviral therapy on accelerated catabolism of vitamin D. Hypoglycemia may be due to IGF-2 production by tumor and malignancy-related glucose consumption via glycolytic pathway with lactic acid production. Literature on concurrent hypercalcemia and hypoglycemia with B-cell lymphoma is sparse and, to our knowledge, occurrence in the setting of HIV has not been reported.