Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Comparative analysis of the quality of life among different retinal diseases.

PURPOSE: To assess the impact on the quality of life (QoL) among different retinal diseases such as diabetic macular edema (DME), retinal vein occlusion (RVO), pathologic myopia (PM), neovascular age-related macular degeneration (nAMD) and central serous chorioretinopathy (CSC). METHODS: A cross-sectional study was carried out in 241 patients, affected by DME (n=44), RVO (n=41), PM (n=34) and nAMD (n=85) receiving intravitreal injections due to the presence of macular edema or choroidal neovascularization. The CSC patients included (n=37) were candidates for laser treatment. The patients included completed the National Eye Visual Functioning Questioning-25 (NEI VFQ-25). Best eye visual acuity (BEVA) was recorded using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. RESULTS: There were significant differences between subgroups for all the domains, except for the general vision in which all scores among diseases ranged from 40.7 to 45.2 out of 100 (P=.436), despite the difference in BEVA (CSC: 86.3±11.9; RVO: 78.5±15.5, DME: 73.3±15.2, nAMD: 72.9±12.6 and PM: 68.5±18.1 letters respectively; P<.001). The lowest VFQ-25 total score was observed in the PM patients (52.1±20.9), followed by nAMD (55.3±20.8), RVO (65.0±22.3), DME (68.6±21.0) and CSC (70.9±16.2). The DME group reported the worst score for general health (38.9±21.4). Mental health and role difficulties were lowest for PM (48.2±28.8 and 48.2±31.9, P<.007). CONCLUSIONS: This study reveals the differences in the QoL among DME, RVO, nAMD, PM and CSC, describing the different repercussions that they can suffer, observing a higher impact in PM and nAMD.

Histopathological Features of Pendred Syndrome Thyroids Align with Differences in the Expression of Thyroid-Specific Markers, Apical Iodide Transporters, and Ciliogenesis Process.

Pendred syndrome (PDS) is an autosomal recessive disorder caused by mutations in the gene that encodes pendrin. Pendred thyroid tissue is supposedly altered by the absence of functional pendrin, but it is still unknown whether other iodide exchangers could compensate for the loss of the protein. Moreover, we have recently described that primary cilium, a conserved structure present at the apical surface of normal follicular cells, suffers different alterations in functional thyroid diseases. We aimed (1) to better understand the histopathological changes experienced by PDS thyroids, (2) to analyze the expression of different thyroid-specific genes and alternative iodide transporters and, finally, (3) to determine whether those changes may alter the morphological pattern of primary cilia in follicular cells. Thyroid samples from a series of four PDS patients were analyzed by immunohistochemistry, double immunofluorescence, and morphometry to evaluate changes in primary cilia frequency and length. We found thyroid follicular nodular disease in all PDS thyroids, frequently in association with follicular adenomas. There were only slight changes in the expression of thyroid-specific markers. Although no positivity for pendrin was found, cytoplasmic immunostaining for ANO-1, CLC-5, and CFTR was stronger in diffuse hyperplastic areas when compared to areas with highly cellular follicular nodules (HCFNs). HCFNs and follicular adenomas always showed diminished ciliary frequency and length. Our results suggest a direct relationship between the absence of functional pendrin and the loss of the normal thyroid architecture in PDS patients, which was also accompanied by differences in the expression of specific immunohistochemical markers and altered ciliogenesis. The present data may help the pathologist in screening for PDS.

Usefulness of neoadjuvant chemotherapy in non-metastatic muscle-invasive bladder cancer. / Utilidad de la quimioterapia neoadyuvante en el carcinoma vesical músculo invasivo no metastásico.

OBJECTIVE: We analyzed the profile of patients who were candidates for neoadjuvant chemotherapy (NACT) in stage pT2-4aN0M0, the tolerability and adherence of our cisplatin-based protocol and oncological outcomes. MATERIAL AND METHODS: Retrospective observational cohort study including patients diagnosed with muscle-invasive bladder carcinoma treated with NACT. Clinical, histopathological, therapeutic and evolutionary characteristics of the patients were analyzed. The use of NACT was evaluated by the complete response in the surgical specimen (pT0). This and other pathological factors were related to overall survival and progression-free survival. RESULTS: We included 90 patients with muscle-invasive bladder carcinoma (clinical stage T2a-T4aN0M0) who received a cisplatin-based NACT regimen between January 2011 and December 2018, prior to radical surgery. Forty percent of patients presented an adverse reaction, with a compliance with the NACT regimen of 92.2%. There were no deaths related to systemic treatment and no adverse reaction to treatment made radical cystectomy impracticable. After performing radical cystectomy, the presence of complete response (pT0) was observed in 20 patients (21%), lower stage in the surgical specimen (

Chronic obstructive pulmonary disease in severe mental illness: A timely diagnosis to advance the process of quitting smoking.

BACKGROUND: This study has two main objectives: to describe the prevalence of undetected chronic obstructive pulmonary disease (COPD) in a clinical sample of smokers with severe mental illness (SMI), and to assess the value of the Tobacco Intensive Motivational Estimated Risk tool, which informs smokers of their respiratory risk and uses brief text messages to reinforce intervention. METHOD: A multicenter, randomized, open-label, and active-controlled clinical trial, with a 12-month follow-up. Outpatients with schizophrenia (SZ) and bipolar disorder were randomized either to the experimental group-studied by spirometry and informed of their calculated lung age and degree of obstruction (if any)-or to the active control group, who followed the 5 A's intervention. RESULTS: The study sample consisted of 160 patients (71.9% SZ), 78.1% of whom completed the 12-month follow-up. Of the patients who completed the spirometry test, 23.9% showed evidence of COPD (77.8% in moderate or severe stages). TIMER was associated with a significant reduction in tobacco use at week 12 and in the long term, 21.9% of patients reduced consumption and 14.6% at least halved it. At week 48, six patients (7.3%) allocated to the experimental group achieved the seven-day smoking abstinence confirmed by CO (primary outcome in terms of efficacy), compared to three (3.8%) in the control group. CONCLUSION: In this clinical pilot trial, one in four outpatients with an SMI who smoked had undiagnosed COPD. An intensive intervention tool favors the early detection of COPD and maintains its efficacy to quit smoking, compared with the standard 5 A's intervention.

Inflammatory markers as prognostic factors in metastatic castration-resistant prostate cancer. / Marcadores inflamatorios como factor pronóstico en el cáncer de próstata resistente a la castración metastásico.

INTRODUCTION: Inflammatory markers have prognostic value in various tumors due to the role of inflammatory phenomena at different stages of tumor development. The aim of this study is to demonstrate the prognostic value of these markers, as well as other clinical and analytical variables in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIAL AND METHODS: Prospective cohort study carried out on 80 patients diagnosed with mCRPC. Clinical and analytical data were collected, and the following inflammatory markers were estimated: Absolute Neutrophil Count (ANC), Neutrophil-Lymphocyte Ratio (NLR), Total Platelet Count (TPC), Platelet-Lymphocyte Ratio (PLR), Lymphocyte-Monocyte Ratio (LMR) and Systemic Inflammation Index (SII). The values of albumin, hemoglobin (Hb), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were also determined. RESULTS: Patients with ANC>7500, NLR>3, PLR>150, LMR>3 and/or SII>535,000, presented significantly lower median survival time than the remaining patients, and TPC was the only marker which did not show a significant association. Moreover, NLR, PLR and SII were inversely correlated with survival time. Patients with hypoalbuminemia, anemia, and elevated LDH values had significantly lower median survival time. Albumin and hemoglobin were directly correlated to overall survival time. The need for analgesia was also associated with shorter survival. CONCLUSION: The values of certain inflammatory markers are associated with shorter survival time in patients with mCRPC, and their use in clinical practice can be considered to evaluate the prognosis and estimate survival.

Leukocyte and platelet counts as prognostic values of testicular germ cell tumours. / Valor pronóstico del recuento de leucocitos y plaquetas, en tumores testiculares de células germinales.

INTRODUCTION: The immune system plays an essential role in the organism's response to cancer. Several haematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumours. MATERIAL AND METHODS: Retrospective cohort study on 164 patients with germ cell tumours. Clinical, analytical, histological and evolutionary data were collected. The absolute neutrophil and absolute platelet counts, neutrophil-lymphocyte (NLR), platelet-lymphocyte and lymphocyte-monocyte ratios were estimated at diagnosis. The association that these markers can have with the classic prognostic factors, as well as their effect on prognosis and survival, have been analysed. RESULTS: 17.7% had NLR>4 and 14.6% ANC>8000/µL. These patients presented higher percentages of residual disease and stage II-III tumours. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus. 7.3% presented absolute platelet >400000/µL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumours. 28.4% showed platelet-lymphocyte values>150. This data was associated to higher percentages of residual disease, progression, stage II and III tumours and seminomatous tumours. 83.3% had an lymphocyte-monocyte >3. These patients presented: higher tumour markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumours. The mean survival time was shorter in patients with NLR>4 and absolute neutrophil >8,000/µL. The ROC curves showed significance in the prediction of progression and values of lymphocyte-monocyte >3, and prediction of survival and values NLR>4. CONCLUSION: Our results indicate that the analysed haematological markers are associated with poor prognoses at diagnosis. Therefore, their use in daily clinical practice can be a valuable tool in the diagnosis and prognosis of patients with testicular germ cell tumours.

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.

Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

A finite element-based machine learning approach for modeling the mechanical behavior of the breast tissues under compression in real-time.

This work presents a data-driven method to simulate, in real-time, the biomechanical behavior of the breast tissues in some image-guided interventions such as biopsies or radiotherapy dose delivery as well as to speed up multimodal registration algorithms. Ten real breasts were used for this work. Their deformation due to the displacement of two compression plates was simulated off-line using the finite element (FE) method. Three machine learning models were trained with the data from those simulations. Then, they were used to predict in real-time the deformation of the breast tissues during the compression. The models were a decision tree and two tree-based ensemble methods (extremely randomized trees and random forest). Two different experimental setups were designed to validate and study the performance of these models under different conditions. The mean 3D Euclidean distance between nodes predicted by the models and those extracted from the FE simulations was calculated to assess the performance of the models in the validation set. The experiments proved that extremely randomized trees performed better than the other two models. The mean error committed by the three models in the prediction of the nodal displacements was under 2 mm, a threshold usually set for clinical applications. The time needed for breast compression prediction is sufficiently short to allow its use in real-time (<0.2 s).

[Polymyositis secondary to a non-Hodgkin's lymphoma]. / Polimiositis secundaria a un linfoma no Hodgkin.

TITLE: Polimiositis secundaria a un linfoma no Hodgkin.

The influence of perceived family support on post surgery recovery.

The objective of this work was to investigate the possible relationship between perceived family support, levels of cortisol and post surgery recovery. The study sample comprised 42 patients that were due to undergo open cholecystectomy surgery in a Regional Health Authority Reference Centre of the Autonomous Community of Extremadura in Spain. The FACES-II questionnaire was used for the evaluation of perceived family support and to measure the three fundamental dimensions of perceived family behaviour: cohesion, adaptability and family type. The day before surgery, a sample of saliva was taken from each subject in order to determine the level of cortisol. Results showed a clear relationship between family support and recovery. Patients with higher scores on the Cohesion Scale demonstrated better post surgery recovery (F = 8.8; gl = 40; p = .005). A relationship between levels of cortisol, perceived family support and recovery was also revealed. Patients with lower scores on the Cohesion scale and higher cortisol levels demonstrated poorer post surgery recovery (F = 10.96; gl = 40; p = .006). These results are coherent with other studies that have highlighted the beneficial effects of perceived family support on mental and physical health.

Gastrointestinal stromal tumors (GISTs): CD117, DOG-1 and PKCθ expression. Is there any advantage in using several markers?

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKCθ was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to determine the sensitivity and diagnostic value of these markers. KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified by PCR and sequenced. A total of 94/99 (94%) GISTs stained positive for CD117, 81/99 (82%) for PKCθ and 90/99 (91%) for DOG-1. A significant correlation was noted between CD117 and DOG-1 expression (p=0.0001). All three markers were expressed in 74% (73/99) of GISTs. Of the five CD117-negative cases, two were PKCθ-negative/DOG1-negative and had mutations in KIT exon 11. Two were PKCθ-positive/DOG1-positive and had mutations in PDGFRA (one each in exons 12 and 18), and one was DOG1-negative/PKCθ-positive, with a PDGFRA exon 18 mutation. The most sensitive marker was CD117, followed by DOG-1 and PKCθ. Although PKCθ was less sensitive, and its staining is more challenging and difficult to interpret, the use of this marker is highly recommended, particularly in CD117-negative/DOG-1-negative GISTs.

The cadherin-catenin complex in laryngeal squamous cell carcinoma.

Abnormal Wnt signaling and impaired cell-cell adhesion due to abnormal E-cadherin and ß-catenin function have been implicated in many cancers, but have not been fully explored in laryngeal squamous cell carcinoma. In this study, ß-catenin cellular location and E-cadherin expression levels were analyzed in 16 laryngeal squamous cell carcinomas (LSCCs) (9 glottic and 7 supraglottic) and 11 samples of non-tumoral inflammatory larynx tissue, using immunohistochemical methods. All non-tumoral tissues showed equally strong membranous expression of ß-catenin, while cytoplasmic expression was found in only 3 of the 11 samples. By contrast, whereas 8/9 glottic LSCCs exhibited only membranous expression of ß-catenin, 6/7 supraglottic LSCCs displayed both membranous and cytoplasmic expression (p = 0.003). Strong E-cadherin staining was observed in 9/11 non-tumoral tissues and 7/9 glottic LSCCs, whereas 4/7 supraglottic LSCCs exhibited weak expression. Reduced membrane expression of E-cadherin and cytoplasmic retention of ß-catenin in supraglottic LSCC seems to be related with more aggressive biological behavior which has been described in clinical studies. Further research is required to clarify the involvement of ß-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

Changes of lactate levels during cardiopulmonary bypass in patients undergoing cardiac transplantation: possible early marker of morbidity and mortality.

OBJECTIVES: High levels of lactate are associated with tissue hypoperfusion during cardiac surgery resulting in postoperative morbidity and mortality among patients undergoing cardiopulmonary bypass (CBP). Our goal was to evaluate the change in lactate levels during CBP for their possible predictive value for complications after heart transplant surgery. MATERIALS AND METHODS: From January to December 2010 we studied lactate levels in 16 heart transplant patients. Arterial blood samples were collected before, during, and after cardiopulmonary bypass on admission to the intensive care unit (ICU). Lactate levels were measured using the cobas B221 (Roche Diagnostic). The neurological, lung, and kidney complications were associated with mortality within 30 days. RESULTS: One patient displayed lactate levels > 2 mmol/L before bypass while 4 (25%) showed levels > 4 mmol/L during CPB. Lactate values higher than or equal to 4 mmol/L on ICU admission occurred in nine patients (56%). Postoperative mortality was higher among the group with levels above below 4 mmol/L on ICU admission (18.7% vs 6.2%). Neurological complications were observed in 22% of patients with elevated levels as opposed to none of the patients with levels below 4 mmol/L. Pulmonary complications were noted in 22% of patients with high lactate values versus 0% among the other group. CONCLUSION: Hyperlactemia above certain levels occurring during CPB serve as a biomarker to identify early postoperative morbidity and mortality.

Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression in gastrointestinal stromal tumors.

AIM: To characterize the differentially-activated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like growth factor 1 receptor (IGF1R) expression. MATERIALS AND METHODS: Ninety-nine paraffin-embedded gastrointestinal stromal tumors (GISTs) were selected. CD117, IGF1R, phospho-ERK1/2, phospho-Akt, p70S6, eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and pS6 expression were investigated using immunohistochemical methods. KIT exons 9, 11, 13 and 17 and platelet derived growth factor receptor alpha (PDGFRA) exons 12 and 18 were amplified by PCR and sequenced. RESULTS: Significant differences were found in the expression of phospho-ERK1/2 between mGISTs and wtGISTs. Complex evaluation of all PI3K/Akt/mTOR pathway markers revealed greater activation in mGISTs, particularly in PDGFRA-mutated GISTs. No significant correlation was observed between IGF1R expression and either mutational status or pathway activation. CONCLUSION: There appears to be no MAPK pathway activation in wtGISTs. Tumors harboring PDGFRA mutations tended to use the PI3K/Akt/mTOR signaling pathway. Most adult GISTs, irrespective of mutational status, displayed no IGFR1 expression; tumors positive for IGFR1 showed no preferential activation of the MAPK or AKT pathways.

Involvement of cytosolic ascorbate peroxidase and Cu/Zn-superoxide dismutase for improved tolerance against drought stress.

In order to understand the role of cytosolic antioxidant enzymes in drought stress protection, transgenic tobacco (Nicotiana tabacum cv. Xanthi) plants overexpressing cytosolic Cu/Zn-superoxide dismutase (cytsod) (EC 1.15.1.1) or ascorbate peroxidase (cytapx) (EC 1.11.1.1) alone, or in combination, were produced and tested for tolerance against mild water stress. The results showed that the simultaneous overexpression of Cu/Znsod and apx or at least apx in the cytosol of transgenic tobacco plants alleviates, to some extent, the damage produced by water stress conditions. This was correlated with higher water use efficiency and better photosynthetic rates. In general, oxidative stress parameters, such as lipid peroxidation, electrolyte leakage, and H(2)O(2) levels, were higher in non-transformed plants than in transgenic lines, suggesting that, at the least, overexpression of cytapx protects tobacco membranes from water stress. In these conditions, the activity of other antioxidant enzymes was induced in transgenic lines at the subcellular level. Moreover, an increase in the activity of some antioxidant enzymes was also observed in the chloroplast of transgenic plants overexpressing cytsod and/or cytapx. These results suggest the positive influence of cytosolic antioxidant metabolism on the chloroplast and underline the complexity of the regulation network of plant antioxidant defences during drought stress.

[Pheochromocytoma: more than a decade of experience. Review of the literature]. / Feocromocitoma: más de una década de experiencia. Revisión de la literatura.

OBJECTIVES: We present 18 patients with pheochromocytoma in the past 12 years. MATERIAL AND METHODS: It is a retrospective observational study evaluating the clinical, biochemical and pathological most important. RESULTS: The mean age was 53.5 years with male predominance and monitoring of five years, being the most frequent incidental findings (29%). Four patients had a familial syndrome hereditary. The tumors were equally distributed with a bilateral case. For the clinical study was made and plasma catecholamines and metanephrines in urine for 24h and subjected to control blood pressure before surgery and beta blockers. Until the introduction of laparoscopic surgery in our department in 2003, the treatment of choice was open surgery. Transabdominal subcostal access was more frequent (47%) and average duration of 207 min. No patients showed metachronous tumors and two patients developed distant metastases to death in short time. CONCLUSIONS: Pheochromocytoma in a threatening disease by cardiovascular disease, which needs to perform an analytical and functional. Surgical treatment, by open or laparoscopic surgery, depending on the characteristics of the tumor and the patient, is satisfactory and comparable results.