Hormone sensitive protocol for metastatic prostate cancer, an update.

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology.

Effectiveness of two probiotics in preventing necrotising enterocolitis in a cohort of very-low-birth-weight premature new-borns.

According to previous research, the incidence of necrotising enterocolitis (NEC) decreases after supplementation with probiotics. However, few studies have considered the equivalence or otherwise of different strains of probiotics in this respect. Accordingly, this prospective observational study was conducted in a cohort of 245 very-low-birth-weight (VLBW) new-borns to assess the prevalence of NEC after supplementation with the probiotic Inforan® (Berna Biotech, Madrid, Spain) 250 mg capsules containing 109 cfu of Lactobacillus acidophilus (ATCC 4356) and 109 cfu of Bifidobacterium bifidum (ATCC 15696); or with Bivos® (Ferring, Madrid, Spain) containing Lacticaseibacillus (formerly Lactobacillus) rhamnnosus (LGG) (ATCC 53103) (109 cfu); or with no probiotic supplementation. Statistical analysis was performed using multivariant regression for the duration of parenteral nutrition, length of neonatal intensive care unit stay, use of oxygen therapy and presence of chorioamnionitis. Of the VLBW new-borns in the study group, 65 received Infloran, 108 received Bivos and 72 received no probiotic. A significant association was observed between a reduced presence of NEC Stage ≥2 and probiotic supplementation. The odds risk (OR) obtained was 0.174 (95% confidence interval (CI): 0.032-0.936) for Infloran and 0.196 (95%CI: 0.053-0.732) for Bivos. Therefore, both probiotics are associated with a lower prevalence of NEC in VLBW new-borns, with no significant differences.

Caution with the use of dexamethasone in patients with COVID-19 in its initial phases.

INTRODUCTION: The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. METHOD: A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. RESULTS: All patients received a 6 mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. CONCLUSION: Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

[Caution with the use of dexamethasone in patients with COVID-19 in its initial phases]. / Precaución con el uso de dexametasona en pacientes con COVID-19 en sus fases iniciales.

INTRODUCTION: The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. METHOD: A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. RESULTS: All patients received a 6 mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. CONCLUSION: Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

Racial disparities in pre-operative pain, function and disease activity for patients with rheumatoid arthritis undergoing Total knee or Total hip Arthroplasty: a New York based study.

BACKGROUND: Black and Hispanic patients with osteoarthritis have more pain and worse function than Whites at the time of arthroplasty. Whether this is true for patients with rheumatoid arthritis (RA) is unknown. METHODS: This cross-sectional study used data on RA patients acquired between October 2013 and November 2018 prior to elective total knee (TKA) or hip arthroplasty (THA). Pain, function, and disease activity were assessed using the visual analogue scale (VAS), the Multidimensional Health Assessment Questionnaire (MDHAQ), and the Disease Activity Score (DAS28-ESR). We linked the cases to census tracts using geocoding to determine the community poverty level. Race, education, income, insurance and medications were collected via self-report. Using multivariable linear and logistic models we examined whether minority status predicted pain, function and RA disease activity at the time of arthroplasty. RESULTS: Thirty seven (23%) of the 164 patients were Black or Hispanic (minorities). The MDHAQ and DAS28-ESR were not significantly worse while VAS pain score was significantly worse in minority patients (p = 0.03). There was no significant difference in education between the groups. Insurance varied significantly; 29% of minority patients had Medicaid vs. 0% of Whites (p < 0.0001). In the multivariable analyses minority status was not significantly associated with DAS28-ESR [p = 0.66], MDHAQ [p = 0.26], or VAS pain [p = 0.18]. CONCLUSIONS: For Black and/or Hispanic patients with RA undergoing THA or TKA at a high-volume specialty hospital, unlike Black or Hispanic patients with osteoarthritis (OA), there was no association with worse pain, function, or RA disease activity at the time of elective arthroplasty.

Detection of specific immune response in sole (Solea senegalensis) against Photobacterium damselae subsp. piscicida antigens.

The pathogenic bacteria Photobacterium damselae subsp. piscicida affects the development of Solea senegalensis culture. Vaccines made with inactivated cells have produced a relative protection against the sickness, however the administration of subcellular and purified antigens as vaccine could increase the effectiveness of the immune response. Thus, the aim of this work was the determination of antigens of P. damselae subsp. piscicida involved in the specific immune response of S. senegalensis. Fish were immunized by intraperitoneal injection (i.p.) with inactivated extracellular polymeric substances (ECP) and whole cells of P. damselae subsp. piscicida, and Freund's incomplete adjuvant. Two months later fish were boosted with the same antigens. Serum from fish was collected to determine by ELISA the title of antibodies against subcellular fractions of bacteria (ECP, capsule, outer membrane proteins, O antigen and formalized whole cells). Significant differences were found between control and immunized fish, but differences between first immunization and booster were only found for O antigen and capsule. Western blots derived from 2D-PAGE of ECP and Outer Membrane Proteins (OMP), using sole immunized serum, detected two high reactive antigens from ECP. Proteins were identified, by mass spectrometry, as ATP-dependent metalloprotease and Telurite resistance proteins. In the case of OMP, three antigenic proteins were detected and identified as Nrfa Y218f, Anti-oxidant AhpC/TSA, and a protein domain DNA binding heat shock related.

Effect of intratympanic dimethyl sulphoxide (DMSO) in an in vivo model of cisplatin-related ototoxicity.

Although dimethyl sulfoxide (DMSO) is one of the most common solvents employed in otoprotection studies, its effect on the inner ear remains unknown. Only a few in vitro studies have addressed the effect of DMSO in cochlear cells. Up to the date, no in vivo functional studies have been reported. To determine the effect of intratympanic DMSO application in the inner ear, and to evaluate its effect in combination with cisplatin in Wistar rats, twelve Wistar rats were randomly assigned into two groups. Group A received intratympanic 1 % DMSO in both ears. Group B received intraperitoneal cisplatin (10 mg/kg) and intratympanic 0.5 % DMSO in the right ear and saline solution in the left ear. Functional changes were evaluated with Auditory Steady-State Responses before and 5 days after the procedure. Morphological changes were studied by means of confocal laser scanning microscopy following the removal of the temporal bones and cochlear dissection. Hearing threshold levels in group A did not show any statistically significant changes after the treatment. In group B, significant differences between pre- and post-treatment were found, with no statistically significant variations between right (DMSO) and left ear (saline solution). We suggest that DMSO could be safely used to dissolve hydrophobic compounds in otoprotection studies without interfering with the cochlear damage produced by cisplatin.

Determinants of fat-soluble vitamin status in patients aged 65 years and over.

In the elderly, malnutrition is highly prevalent and a major contributor to increased morbidity and mortality. We aimed to evaluate the fat-soluble vitamin status and potential determinants in patients >65 years of age. Serum vitamins A, D and E were determined by liquid chromatography in 166 patients. Gender, age, season, hospitalization, nutritional markers (albumin and cholesterol), acute-phase reactants (ferritin and C-reactive protein) and renal function (creatinine and glomerular filtrate) were assessed as potential determinants. Prevalence of vitamin deficiency was highly variable, ranging from 0 (vitamin E/cholesterol ratio) to 94% (for vitamin D in hospitalized patients). Vitamin status did not differ according to gender, but age, season, hospitalization, a poor nutritional status and impaired renal function, and the presence of acute-phase response significantly affected serum levels of vitamin A, E and D. In conclusion, in subjects >65 years both demographic and clinical factors determined the fat-soluble vitamin status.

Nephrotic syndrome and AA amyloidosis revealing adult-onset cryopyrin-associated periodic syndrome.

Cryopyrin-associated periodic syndrome (CAPS) is due to gain-of-function mutations in the cryopyrin gene, which determines an overactive inflammatory response. AA amyloidosis is a complication of this syndrome. A 53-year-old man was referred to us because of lower limb edema. Past history: at the age of 20, he complained of arthralgia/arthritis and bilateral hypoacusis. At the age of 35, he presented posterior uveitis, several episodes of conjunctivitis, and progressive loss of visual acuity. Laboratory tests disclosed nephrotic syndrome, and renal biopsy showed AA amyloidosis. He was given anakinra with improvement of arthritis. A genetic study revealed the p.D303N mutation in the cryopyrin gene, and he was diagnosed as having AA amyloidosis due to CAPS. Twenty-one months after starting anakinra, the arthritis has disappeared, although nephrotic-range proteinuria persisted. It is important to be aware of cryopyrin-associated periodic syndrome because it can cause irreversible complications, and there is effective therapy.

Tocilizumab treatment for nephrotic syndrome due to amyloidosis in Behcet's disease.

Renal involvement is an unusual but significant Behcet´s disease (BD) complication and AA amyloidosis appears to be the most common etiology. IL-6 is a pro-inflammatory cytokine with an important role in AA amyloidosis development. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that has emerged as an effective and specific treatment in AA amyloidosis secondary to chronic inflammatory disorders. We report on a patient diagnosed with BD who developed nephrotic syndrome caused by renal AA amyloidosis with an excellent response to TCZ therapy.

Young systemic lupus erythematosus patients with no hearing involvement: 10-year follow up.

OBJECTIVE: To evaluate patients with systemic lupus erythematosus and normal hearing over 10 years, compared with healthy controls. METHODS: Thirty patients diagnosed with systemic lupus erythematosus were evaluated in a prospective, descriptive study. Eight patients fulfilled the inclusion criteria, i.e. normal otoscopy, normal hearing, normal imaging and disease duration of less than one year. Eleven healthy companions of ENT patients were recruited as controls. RESULTS: At study commencement, the mean patient age was 32.75 years (range, 15-49 years) and there were no statistically significant audiometric differences between patients and controls. No statistically significant audiometric changes were found either within or between the patient and control groups at 10-year follow up. CONCLUSION: These results supply no evidence for progressive hearing loss in systemic lupus erythematosus patients with no hearing involvement at study commencement. Therefore, we recommend audiometric tests only for systemic lupus erythematosus patients complaining of hearing loss, or for other clinical purposes. It is conceivable that asymptomatic hearing loss could be observed over a more extended follow-up period (i.e. more than 10 years).

Isoflurane but not halothane minimum alveolar concentration-sparing response of dexmedetomidine is enhanced in rats chronically treated with selective α2-adrenoceptor agonist.

Halothane minimum alveolar concentration (MAC)-sparing response is preserved in rats rendered tolerant to the action of dexmedetomidine. It has been shown that halothane and isoflurane act at different sites to produce immobility. The authors studied whether there was any difference between halothane and isoflurane MAC-sparing effects of dexmedetomidine in rats after chronic administration of a low dose of this drug. Twenty-four female Wistar rats were randomly allocated into four groups of six animals: two groups received 10 µg/kg intraperitoneal dexmedetomidine for five days (treated groups) and the other two groups received intraperitoneal saline solution for five days (naive groups) prior to halothane or isoflurane MAC determination (one treated and one naive group of halothane and one treated and one naive group of isoflurane). Halothane or isoflurane MAC determination was performed before (basal) and 30 min after an intraperitoneal dose of 30 µg/kg of dexmedetomidine (post-dex) from alveolar gas samples at the time of tail clamp. Administration of an acute dose of dexmedetomidine to animals that had chronically received dexmedetomidine resulted in a MAC-sparing effect that was similar to that seen in naive animals for halothane; however, the same treatment increased the MAC-sparing response of dexmedetomidine for isoflurane. Isoflurane but not halothane MAC-sparing response of acutely administered dexmedetomidine is enhanced in rats chronically treated with this drug.

Dose escalation of certolizumab pegol from 200 mg to 400 mg every other week provides no additional efficacy in rheumatoid arthritis: an analysis of individual patient-level data.

OBJECTIVE: To determine whether certolizumab pegol (CZP) dosage escalation from 200 mg to 400 mg every other week benefits some patients with rheumatoid arthritis (RA). METHODS: In the extension of the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) study into an open-label study, all patients received CZP 400 mg every other week in combination with methotrexate (MTX). Before the open-label phase of the study, patients had received CZP 200 mg or 400 mg every other week, or placebo every other week, as add-on therapy to MTX. The open-label study included those who had completed the RAPID 1 study (to week 52) and also those who had been withdrawn from the study (at week 16, due to inadequate response). At 12 weeks and 48 weeks after enrollment in the open-label study, changes in the Disease Activity Score in 28 joints (DAS28) were compared in dose-escalation patients (200 mg increased to 400 mg every other week) versus stable-dosage patients (400 mg every other week), using cumulative probability plots of individual patient-level data. RESULTS: In the group of patients who had completed the RAPID 1 study and had moderate or severe disease activity at entry into the open-label study, and in those who had been withdrawn early from the RAPID 1 study, the median DAS28 improvements 12 weeks after enrollment into the open-label study were similar in the dose-escalation and stable-dose groups. Individual patient-level data revealed no greater likelihood of response in the group of patients who received an increased dosage of CZP versus those in whom a stable dosage was maintained, whether they had completed the RAPID 1 study or had been withdrawn early. CONCLUSION: Although patient heterogeneity in clinical settings is acknowledged, the present results indicate that increasing the dose of CZP from 200 mg to 400 mg offers little additional benefit in RA, even for selected patients.

Gitelman syndrome due to p.A204T mutation in CLCNKB gene.

A 45-year-old woman presented with phenotypical features suggestive of Gitelman syndrome (adult age at diagnosis, normal-low blood pressure, hypokalaemia, metabolic alkalosis, hypomagnesaemia, and hypocalciuria). Mutational analysis revealed no significant abnormality in SLC12A3 gene, but homozygous p.A204T mutation was found in the CLCNKB gene. This is a founder effect mutation described in Spanish patients with classic and atypical Bartter syndrome. This report confirms previous descriptions and expands the clinical spectrum of this mutation.