Understanding the impact of radiation-induced lymphopenia: Preclinical and clinical research perspectives.

Immunotherapy has revolutionized the field of cancer treatment, changing the standard of care to the use of immune checkpoint inhibitors. Radiotherapy can boost anti-tumour immune responses by changing the tumour microenvironment, but it also can cause radiotherapy-induced lymphopenia (RIL), a decrease in circulating lymphocyte counts. RIL has been associated with lower survival in patients undergoing radiotherapy, and new studies have suggested that it can also affect immunotherapy outcome. To study RIL's effects and to explore mitigation treatment strategies, preclinical models closely mimicking the clinical situation are needed. State-of-the-art image-guided small animal irradiators now offer the possibility to target specific organs in small animals to induce RIL, aiding research on its molecular mechanisms and prevention. This review covers the relationship between radiotherapy and RIL, its impact on patient survival, and future directions to generate models to investigate and prevent RIL.

Caffeic Acid Phenethyl Ester (CAPE), a natural polyphenol to increase the therapeutic window for lung adenocarcinomas.

BACKGROUND AND PURPOSE: Lung cancers are highly resistant to radiotherapy, necessitating the use of high doses, which leads to radiation toxicities such as radiation pneumonitis and fibrosis. Caffeic Acid Phenethyl Ester (CAPE) has been suggested to have anti-proliferative and pro-apoptotic effects in tumour cells, while radioprotective anti-inflammatory and anti-oxidant effects in the normal tissue. We investigated the radiosensitizing and radioprotective effects of CAPE in lung cancer cell lines and normal tissue in vitro and ex vivo, respectively. MATERIALS AND METHODS: The cytotoxic and radiosensitizing effects of CAPE in lung cancer were investigated using viability and clonogenic survival assays. The radioprotective effects of CAPE were assessed in vitro and ex vivo using precision cut lung slices (PCLS). Potential underlying molecular mechanisms of CAPE focusing on cell cycle, cell metabolism, mitochondrial function and pro-inflammatory markers were investigated. RESULTS: Treatment with CAPE decreased cell viability in a dose-dependent manner (IC50 57.6 ± 16.6 µM). Clonogenic survival assays showed significant radiosensitization by CAPE in lung adenocarcinoma lines (p < 0.05), while no differences were found in non-adenocarcinoma lines (p ≥ 0.13). Cell cycle analysis showed an increased S-phase (p < 0.05) after incubation with CAPE in the majority of cell lines. Metabolic profiling showed that CAPE shifted cellular respiration towards glycolysis (p < 0.01), together with mitochondrial membrane depolarization (p < 0.01). CAPE induced a decrease in NF-κB activity in adenocarcinomas and decreased pro-inflammatory gene expression in PCLS. CONCLUSION: The combination of CAPE and radiotherapy may be a potentially effective approach to increase the therapeutic window in lung cancer patients.

Role of A1c in the postpartum screening of women with gestational diabetes.

OBJECTIVE: This study aimed to determine whether A1c detects a different prediabetes prevalence in women with a history of gestational diabetes mellitus (GDM) compared to those diagnosed with oral glucose tolerance test (OGTT) and the influence of haemoglobin concentrations on A1c levels. DESIGN AND PATIENTS: We evaluated carbohydrate metabolism status by performing OGTT and A1c tests in 141 postpartum women with prior GDM in the first year post-delivery. RESULTS: The overall prevalence of prediabetes was 41.8%. Prevalence of isolated A1c 5.7-6.4%, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) was 10.6%, 7.1%, and 9.2%, respectively. Isolated A1c 5.7-6.4% was associated with Caucasian origin (66.7% versus 32.6%, p = 0.02) and with higher LDL cholesterol concentrations (123 ± 28.4 mg/dl versus 101.6 ± 19.2 mg/dl, p = 0.037) compared with patients diagnosed by OGTT (IFG or IGT). Women with postpartum anaemia had similar A1c levels to those with normal haemoglobin concentrations (5.5% ± 0.6% versus 5.4% ± 0.4%, p = 0.237). CONCLUSIONS: Use of A1c in postpartum screening of women with GDM detected an additional 10.6% of patients with prediabetes and a more adverse lipid profile. Haemoglobin concentrations did not influence A1c values.

[Chronic complications in type 1 diabetes mellitus. Analysis of a cohort of 291 patients with a mean evolution time of 15 years]. / Complicaciones crónicas en la diabetes mellitus tipo 1. Análisis de una cohorte de 291 pacientes con un tiempo medio de evolución de 15 años.

BACKGROUND AND OBJECTIVE: Micro- and macrovascular complications are the main cause of morbidity and mortality in type 1 diabetes mellitus (T1D). Given the scarcity of data on the subject in our population, we have analyzed the prevalence of vascular complications and possible risk factors in a cohort of T1D patients. PATIENTS AND METHODS: A cross-sectional study including patients aged 18 and over diagnosed of T1D with at least 6 months' evolution, seen in the Hospital del Mar, Barcelona and Hospital de Granollers during 2008 was carried out. RESULTS: We recruited 291 patients (166 men) with a mean age of 38 years and a T1D duration of 15.3 years. There was one or more diabetes-related vascular complications in 110 (37.8%) patients. Of these, 104 (35.7%) had microvascular complications, 22 (7.6%) macrovascular, and 16 (5.5%) both. Patients with microvascular complications had a higher prevalence of tobacco use (57% smokers Vs. 47.5%, P<.05), dyslipidemia (65.4% Vs. 28.3%, P <.05), hypertension (43.3% Vs. 23.5%, P <.05) and metabolic syndrome (41.3% Vs. 18.7%, P<.001). Moreover, they were older, had a longer duration of diabetes and higher values of glycosylated hemoglobin, triglycerides and systolic blood pressure. In the logistic regression analysis, diabetes duration (OR: 1.19 [95%CI: 1.07-1.32], P=.002), glycosylated hemoglobin levels (OR: 3.33 [95%CI: 1.58-7.03], P=.002) and the absence of metabolic syndrome (OR: 0.04 [95% CI:0.002-0.72], P=.03) showed an independent association with microangiopathy. Patients with T1D and macroangiopathy had longer diabetes duration (23.3±12.6 years Vs. 14.7±10.9 years, in patients without complications, P <.001), higher prevalence of metabolic syndrome (50% Vs. 24.9%, in patients without complications, P=.011) and were more frequently receiving lipid lowering treatment (59.1% Vs. 27.1%, in patients without complications, P=.002). In the multiple regression model, only diabetes duration (OR: 1.047 [95% CI: 1.01-1.09], P=.019) remained independently associated with macroangiopathy. CONCLUSIONS: More than 1/3 of the T1D patients suffered a diabetes-related complication, mainly microvascular, at the time of the study. Diabetes duration and metabolic syndrome are the two mostly strongly related factors to chronic complications of DM1.

Clinical Value of Thyrotropin Receptor Antibodies for the Differential Diagnosis of Interferon Induced Thyroiditis.

OBJECTIVE: The clinical value of thyrotropin receptor antibodies for the differential diagnosis of thyrotoxicosis induced by pegylated interferon-alpha remains unknown. We analyzed the diagnostic accuracy of thyrotropin receptor antibodies in the differential diagnosis of thyrotoxicosis in patients with chronic hepatitis C (CHC) receiving pegylated interferon-alpha plus ribavirin. METHODS: Retrospective analysis of 274 patients with CHC receiving pegylated interferon-alpha plus ribavirin. Interferon-induced thyrotoxicosis was classified according to clinical guidelines as Graves disease, autoimmune and non- autoimmune destructive thyroiditis. RESULTS: 48 (17.5%) patients developed hypothyroidism, 17 (6.2%) thyrotoxicosis (6 non- autoimmune destructive thyroiditis, 8 autoimmune destructive thyroiditis and 3 Graves disease) and 22 "de novo" thyrotropin receptor antibodies (all Graves disease, 2 of the 8 autoimmune destructive thyroiditis and 17 with normal thyroid function). The sensitivity and specificity of thyrotropin receptor antibodies for Graves disease diagnosis in patients with thyrotoxicosis were 100 and 85%, respectively. Patients with destructive thyroiditis developed hypothyroidism in 87.5% of autoimmune cases and in none of those with a non- autoimmune etiology (p<0.001). CONCLUSION: Thyrotropin receptor antibodies determination cannot replace thyroid scintigraphy for the differential diagnosis of thyrotoxicosis in CHC patients treated with pegylated interferon.

[The value of the parathyrin-related protein (PTH-RP) in the diagnosis of cancer-associated hypercalcemia]. / Valor de la proteína relacionada con la paratirina (PTH-RP) en el diagnóstico de la hipercalcemia asociada al cáncer.

BACKGROUND: The parathyrine related protein (PTH-RP) is very similar, both in structure and in function, to the PTH and is considered as a mediator in humoral hypercalcemia in cancer. The aim of this study was to know the clinical value of PTH-RP measurement. METHODS: Serum PTH-RP concentrations were studied in 22 healthy subjects, 13 patients with primary hyperparathyroidism, 9 patients with solid neoplasms and normocalcemia, 26 patients with solid neoplasms and hypercalcemia and 4 patients with hematologic neoplasms and hypercalcemia. The PTH-RP was quantified by a competitive radioimmunoassay technique using a specific antibody of the PTH-RP 1-40 fragment. Intact parathyrine (i-PTH) was quantified by an IRMA method using 2 polyclonal antibodies (INCSTAR). RESULTS: Fifteen (68%) of the healthy controls presented undetectable serum PTH-RP concentrations. The serum PTH-RP concentration was normal in all those patients with hyperparathyroidism. Elevated serum PTH-RP values were not found in patients with solid neoplasms and normocalcemia or in those with hematologic neoplasms and hypercalcemia. High values of PTH-RP were observed in 8 out of 9 (88%) of the patients with solid neoplasms and hypercalcemia with bone metastasis and in 7 out of 11 (63%) of the patients with bone involvement. CONCLUSIONS: Serum parathyrine-related protein was found to be high in a large proportion of patients with solid neoplasms and hypercalcemia. Serum PTH-RP determination is useful in the clinical investigation of patients with hypercalcemia. Even in patients with bone metastasis, hypercalcemia may have a humoral background.

Impact of restrictive (sleeve gastrectomy) vs hybrid bariatric surgery (Roux-en-Y gastric bypass) on lipid profile.

BACKGROUND: Few studies have evaluated the impact of hybrid versus purely restrictive bariatric surgery on lipid profile, with the results being contradictory. The effect of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) on lipid profile was compared. METHODS: A nonrandomized prospective cohort study was conducted on severely obese patients undergoing bariatric surgery. Indication for the type of surgical procedure was based on clinical criteria. Patients on lipid-lowering drugs and those that could not be matched for age, sex, and body mass index were excluded. Finally, 51 patients who underwent LSG and 51 undergoing LRYGB completed this study. RESULTS: During the first year post-surgery, no differences in percentage of excess weight loss and triglyceride reduction were found between groups. After LRYGR, low-density lipoprotein (LDL) cholesterol concentrations fell significantly (125.9 ± 29.3 to 100.3 ± 26.4 mg/dl, p < 0.001), whereas no significant changes were observed in the LSG group (118.6 ± 30.7 to 114.6 ± 33.5 mg/dl, p = 0.220). High-density lipoprotein (HDL) cholesterol increase was significantly greater after LSG (15.4 ± 13.1 mg/dl) compared with LRYGB (9.4 ± 14.0 mg/dl, p = 0.032). Factors independently associated with LDL cholesterol reduction were higher baseline total cholesterol and undergoing LRYGB. A greater increase in HDL cholesterol was associated with LSG, older age, and baseline HDL cholesterol. CONCLUSIONS: LRYGB produces an overall improvement in lipid profile, with a clear benefit in all lipid fractions. Although LSG does not alter LDL cholesterol levels, its effect on HDL cholesterol is comparable to or greater than that obtained with malabsorptive techniques.

Giant intrasellar aneurysm presenting with panhypopituitarism and subarachnoid hemorrhage: case report and literature review.

A 52-year-old woman was admitted to our hospital presenting with subarachnoid hemorrhage, left ophthalmoplegia, and right hemiparesis. Previous symptoms and signs suggested the presence of panhypopituitarism. A giant intracranial aneurysm of the internal carotid artery, diagnosed by magnetic resonance imaging, showed the characteristic flow void phenomenon with black appearance. Analysis of endocrine function disclosed panhypopituitarism and hyperprolactinemia. After proximal balloon occlusion of the aneurysm, diabetes insipidus developed. Pituitary function reassessed 6 months after initial admission confirmed anterior and posterior hypopituitarism and hyperprolactinemia. Possible mechanisms are discussed. A review of the literature on pituitary dysfunction caused by carotid artery aneurysms discloses that the pituitary-gonadal axis is the most frequently involved (67.5% of cases), followed by the pituitary-adrenal axis (48.6%) and the pituitary-thyroid axis (40.5%). These frequencies are very similar to those described in other types of hypopituitarism.

Expression of ICAM-1 in distant metastatic thyroid carcinoma.

Distant metastasis from follicular thyroid carcinoma developed in a 48-year-old woman 11 yr after the resection of the primary tumor. Distant metastasis consisted in invasion of the left infraspinatus muscle by malignant thyroid cells. After its surgical removal, in the following 6-8 months multiple metastasis to distant skeletal muscle and brain appeared, and despite chemotherapy and local radiotherapy, the patient finally died. Intercellular adhesion molecule-1 (ICAM-1), a single chain transmembrane glycoprotein, was detected on the surface of cells of the metastatic tissue. Although ICAM-1-positive staining has been recently described in primary tumors such as papillary adenocarcinoma, and metastatic tumors from skin, brain, thymus, liver, adrenal gland and prostate, to our knowledge its expression on distant metastasis from thyroid carcinoma has not been previously reported.