Long-term effect of tocilizumab on mortality, readmissions, persistent symptoms and lung function in SARS-CoV-2 patients 1 year after hospital discharge: A matched cohort study.

BACKGROUND: Tocilizumab is presumed to be an effective and safe treatment for severe SARS-Cov-2, but its usefulness has not been investigated yet for long-term outcomes. This study aimed to evaluate the influence of tocilizumab on mortality in patients with SARS-CoV-2 throughout the year following discharge. METHODS: A retrospective observational analysis was performed on electronic medical records of patients with SARS-CoV2 who were discharged from our hospital after surviving the first wave in March-April 2020. Logistic regression was used to analyse the effect of tocilizumab on mortality, as the main outcome, and propensity-score analysis to further validate their effect. Secondary outcomes were readmissions, persistent symptoms and lung function evolution. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables. RESULTS: A total of 405 patients were included in the mortality study (33.6 % were treated with tocilizumab) and 390 were included in the assessment of persistent symptoms. After propensity-score analysis, no association between tocilizumab use and 1-year overall mortality was found (HR= 2.05, 95 % CI: 0.21-19.98). No differences regarding persistent symptoms (OR= 1.01 95 %CI 0.57-1.79), nor lung function parameters (forced vital capacity: coefficient -0.16 95 %CI -0.45 to 0.14) were found throughout the year follow-up between control and tocilizumab group. CONCLUSIONS: The administration of tocilizumab in patients with SARS-CoV-2 did not show any effect on long-term mortality. Identically, no association were found regarding readmissions, persistent symptoms or lung function evolution and tocilizumab administration in our cohort of patients after 1 year follow-up.

Data Augmentation Techniques for Machine Learning Applied to Optical Spectroscopy Datasets in Agrifood Applications: A Comprehensive Review.

Machine learning (ML) and deep learning (DL) have achieved great success in different tasks. These include computer vision, image segmentation, natural language processing, predicting classification, evaluating time series, and predicting values based on a series of variables. As artificial intelligence progresses, new techniques are being applied to areas like optical spectroscopy and its uses in specific fields, such as the agrifood industry. The performance of ML and DL techniques generally improves with the amount of data available. However, it is not always possible to obtain all the necessary data for creating a robust dataset. In the particular case of agrifood applications, dataset collection is generally constrained to specific periods. Weather conditions can also reduce the possibility to cover the entire range of classifications with the consequent generation of imbalanced datasets. To address this issue, data augmentation (DA) techniques are employed to expand the dataset by adding slightly modified copies of existing data. This leads to a dataset that includes values from laboratory tests, as well as a collection of synthetic data based on the real data. This review work will present the application of DA techniques to optical spectroscopy datasets obtained from real agrifood industry applications. The reviewed methods will describe the use of simple DA techniques, such as duplicating samples with slight changes, as well as the utilization of more complex algorithms based on deep learning generative adversarial networks (GANs), and semi-supervised generative adversarial networks (SGANs).

Effect of tocilizumab versus standard of care in adults hospitalized with moderate-severe COVID-19 pneumonia.

Introduction and objectives: Tocilizumab is an interleukin-6 receptor-blocking agent proposed for the treatment of severe COVID-19; however, limited data are available on their efficacy. The aim of this study was to assess the effect of tocilizumab on the outcomes of patients with COVID-19 pneumonia by using propensity-score-matching (PSM) analysis. Methods: A retrospective observational analysis of hospitalized COVID-19 adult patients admitted to the Vall d'Hebron Hospital was performed between March and April 2020. We used the logistic regression to analyze the effect of tocilizumab on mortality, as main outcome, and PSM analysis to further validate their effect. Secondary outcomes were length-of-stay (LOS) and intensive-care-unit (ICU) stay. Same outcomes were also assessed for early tocilizumab administration, within 72 h after admission. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables. Results: A total of 544 COVID-19 patients were included, 197 (36.2%) were treated with tocilizumab of whom 147 were treated within the first 72 h after admission; and 347 were included in the control group. After PSM analyses, the results showed no association between tocilizumab use and overall mortality (OR = 1.03, 95%CI: 0.63-1.68). However, shorter ICU-stay in the tocilizumab group was found compared to the control group (Coefficient -4.27 95%CI: -6.63 to -1.92). Similar results were found in the early tocilizumab cohort. Conclusions: The administration of tocilizumab in patients with moderate to severe COVID-19 did not reduce the risk of mortality in our cohort of patients, regardless of the time of administration.

Introducción y objetivos: El tocilizumab es un agente bloqueador del receptor de la interleucina 6 propuesto para el tratamiento de la COVID-19 grave; sin embargo, se dispone de datos limitados sobre su eficacia. El objetivo de este estudio fue evaluar el efecto de tocilizumab en los resultados de los pacientes con neumonía por COVID-19 mediante un análisis de emparejamiento por propensity-score-matching (PSM, «puntuación de propensión¼). Métodos: Se realizó un análisis observacional retrospectivo de los pacientes adultos con COVID-19 ingresados en el Hospital Vall d'Hebron entre marzo y abril de 2020. Se utilizó la regresión logística para analizar el efecto de tocilizumab en la mortalidad, como resultado principal, y el análisis PSM para validar aún más su efecto. Los resultados secundarios fueron la duración de la estancia y la estancia en la unidad de cuidados intensivos (UCI). También se evaluaron los mismos resultados para la administración temprana de tocilizumab, dentro de las 72 h posteriores al ingreso. Los pacientes se seleccionaron mediante el emparejamiento de su propensión individual a recibir tratamiento con tocilizumab, condicionado a sus variables demográficas y clínicas. Resultados: Se incluyeron 544 pacientes de COVID-19, 197 (36,2%) fueron tratados con tocilizumab, de los cuales 147 fueron tratados dentro de las primeras 72 h tras el ingreso; y 347 fueron incluidos en el grupo control. Tras los análisis PSM, los resultados no mostraron ninguna asociación entre el uso de tocilizumab y la mortalidad global (OR = 1,03; IC del 95%: 0,63-1,68). Sin embargo, se encontró una menor estancia en la UCI en el grupo de tocilizumab en comparación con el grupo de control (coeficiente −4,27; IC del 95%: −6,63 − −1,92). Se encontraron resultados similares en la cohorte de tocilizumab temprano. Conclusiones: La administración de tocilizumab en pacientes con COVID-19 moderada a grave no redujo el riesgo de mortalidad en nuestra cohorte de pacientes, independientemente del momento de la administración.

Effect of tocilizumab versus standard of care in adults hospitalized with moderate-severe COVID-19 pneumonia.

INTRODUCTION AND OBJECTIVES: Tocilizumab is an interleukin-6 receptor-blocking agent proposed for the treatment of severe COVID-19; however, limited data are available on their efficacy. The aim of this study was to assess the effect of tocilizumab on the outcomes of patients with COVID-19 pneumonia by using propensity-score-matching (PSM) analysis. METHODS: A retrospective observational analysis of hospitalized COVID-19 adult patients admitted to the Vall d'Hebron Hospital was performed between March and April 2020. We used the logistic regression to analyze the effect of tocilizumab on mortality, as main outcome, and PSM analysis to further validate their effect. Secondary outcomes were length-of-stay (LOS) and intensive-care-unit (ICU) stay. Same outcomes were also assessed for early tocilizumab administration, within 72h after admission. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables. RESULTS: A total of 544 COVID-19 patients were included, 197 (36.2%) were treated with tocilizumab of whom 147 were treated within the first 72h after admission; and 347 were included in the control group. After PSM analyses, the results showed no association between tocilizumab use and overall mortality (OR=1.03, 95%CI: 0.63-1.68). However, shorter ICU-stay in the tocilizumab group was found compared to the control group (Coefficient -4.27 95%CI: -6.63 to -1.92). Similar results were found in the early tocilizumab cohort. CONCLUSIONS: The administration of tocilizumab in patients with moderate to severe COVID-19 did not reduce the risk of mortality in our cohort of patients, regardless of the time of administration.

Hereditary spastic paraplegia associated with a novel homozygous intronic noncanonical splice site variant in the AP4B1 gene.

Pathogenic variants in the AP4B1 gene lead to a rare form of hereditary spastic paraplegia (HSP) known as SPG47. We report on a patient with a clinical suspicion of complicated HSP of the lower limbs with intellectual disability, as well as a novel homozygous noncanonical splice site variant in the AP4B1 gene, in which the effect on splicing was validated by RNA analysis. We sequenced 152 genes associated with HSP using Next-Generation Sequencing (NGS). We isolated total RNA from peripheral blood and generated cDNA using reverse transcription-polymerase chain reaction (RT-PCR). A region of AP4B1 mRNA was amplified by PCR and the fragments obtained were purified from the agarose gel and sequenced. We found a homozygous variant of uncertain significance in the AP4B1 gene NM_006594.4: c.1511-6C>G in the proband. Two different AP4B1 mRNA fragments were obtained in the patient and his carrier parents. The shorter fragment was the predominant fragment in the patient and revealed a deletion with skipping of the AP4B1 exon 10. The patient's longer fragment corresponded to an insertion of the last five nucleotides of AP4B1 intron 9. We confirmed that this variant affects the normal splicing of RNA, sustaining the molecular diagnosis of SPG47 in the patient.

Epistasis between cultural traits causes paradigm shifts in cultural evolution.

Every now and then the cultural paradigm of a society changes. While current models of cultural shifts usually require a major exogenous or endogenous change, we propose that the mechanism underlying many paradigm shifts may just be an emergent feature of the inherent congruence among different cultural traits. We implement this idea through a population dynamics model in which individuals are defined by a vector of cultural traits that changes mainly through cultural contagion, biased by a 'cultural fitness' landscape, between contemporary individuals. Cultural traits reinforce or hinder each other (through a form of cultural epistasis) to prevent cognitive dissonance. Our main result is that abrupt paradigm shifts occur, in response to weak changes in the landscape, only in the presence of epistasis between cultural traits, and regardless of whether horizontal transmission is biased by homophily. A relevant consequence of this dynamics is the irreversible nature of paradigm shifts: the old paradigm cannot be restored even if the external changes are undone. Our model puts the phenomenon of paradigm shifts in cultural evolution in the same category as catastrophic shifts in ecology or phase transitions in physics, where minute causes lead to major collective changes.

Autosomal dominant distal myopathy with nemaline rods due to p.Glu197Asp mutation in ACTA1.

In a previous report of a new phenotype with predominant scapulo-humeral-peroneal-distal myopathy associated with the Glu197Asp mutation in ACTA1, muscle biopsies did not show nemaline rods, nor could nemaline rods formation be demonstrated in an exhaustive functional in vivo or in vitro study. However, muscle biopsy in members of our family, carrying a similar clinical phenotype of some members of the original family and the same ACTA1 mutation, revealed the presence of numerous nemaline rods, suggesting that there must be other factors that explain the absence of nemaline rods.

Dose escalation with external beam radiation therapy and high-dose-rate brachytherapy combined with long-term androgen deprivation therapy in high and very high risk prostate cancer: Comparison of two consecutive high-dose-rate schemes.

PURPOSE: To compare rectal toxicity, urinary toxicity, and nadir+2 PSA relapse-free survival (bRFS) in two consecutive Phase II protocols of high-dose-rate (HDR) brachytherapy used at the authors institution from 2001 to 2012. METHODS AND MATERIALS: Patients with National Comprehensive Cancer Network high risk and very high risk prostate cancer enrolled in studies HDR4 (2001-2007, n = 183) and HDR2 (2007-2012, n = 56) were analyzed. Patients received minipelvis external beam radiation therapy/intensity-modulated external radiotherapy to 54 Gy and 2 years of androgen blockade along with HDR brachytherapy. HDR4 protocol consisted of four 4.75 Gy fractions delivered in 48 hours; the HDR2 protocol delivered two 9.5 Gy fractions in 24 hours. Average 2-Gy equivalent dose (α/ß = 1.2) prostate D90 doses for the HDR4 and HDR2 groups were 89.8 Gy and 110.5 Gy, respectively (p = 0.0001). Both groups were well balanced regarding risk factors. Prior transurethral resection of the prostate was more frequent in the HDR2 group (p = 0.001). RESULTS: After a median followup of 7.4 years (range, 2-11.2), there was no difference in adverse grade ≥ 2 rectal events (HDR4 = 10.4% vs. HDR2 = 12.5%; p = ns) or grade ≥3 (HDR4 = 2.2% vs. HDR2 = 3.6%; p = ns). No differences in urinary grade ≥2 adverse events (HDR4 = 23% vs. HDR2 = 26.8%; p = ns) or grade ≥3 (HDR4 = 7.7% vs. HDR2 = 8.9%; p = ns) were detected. The 7-year bRFS for HDR4 and HDR2 protocols was 88.7% and 87.8%, respectively (p = ns). CONCLUSIONS: HDR4 and HDR2 protocols produce similar results in terms of toxicity and bRFS at the intermediate time point of 7 years.

Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis.

Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) show numerous alterations including inflammation, apoptosis, and necrosis of myofibers. However, the molecular mechanism that explains these changes remains largely unknown. Here, the involvement of hemichannels formed by connexins (Cx HCs) was evaluated in skeletal muscle of mdx mouse model of DMD. Fast myofibers of mdx mice were found to express three connexins (39, 43 and 45) and high sarcolemma permeability, which was absent in myofibers of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice (deficient in skeletal muscle Cx43/Cx45 expression). These myofibers did not show elevated basal intracellular free Ca(2+) levels, immunoreactivity to phosphorylated p65 (active NF-κB), eNOS and annexin V/active Caspase 3 (marker of apoptosis) but presented dystrophin immunoreactivity. Moreover, muscles of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice exhibited partial decrease of necrotic features (big cells and high creatine kinase levels). Accordingly, these muscles showed similar macrophage infiltration as control mdx muscles. Nonetheless, the hanging test performance of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice was significantly better than that of control mdx Cx43(fl/fl)Cx45(fl/fl) mice. All three Cxs found in skeletal muscles of mdx mice were also detected in fast myofibers of biopsy specimens from patients with muscular dystrophy. Thus, reduction of Cx expression and/or function of Cx HCs may be potential therapeutic approaches to abrogate myofiber apoptosis in DMD.

Index lesion characterization by (11)C-Choline PET/CT and Apparent Diffusion Coefficient parameters at 3 Tesla MRI in primary prostate carcinoma.

BACKGROUND: Index lesion characterization is important in the evaluation of primary prostate carcinoma (PPC). The aim of this study was to analyze the contribution of (11) C-Choline PET/CT and the Apparent Diffusion Coefficient maps (ADC) in detecting the Index Lesion and clinically significant tumors in PPC. METHODS: Twenty-one untreated patients with biopsy-proven PPC and candidates for radical prostatectomy (RP) were prospectively evaluated by means of Ultra-High Definition PET/CT and 3T MRI, which included T2-weighted imaging (T2WI) and ADC maps obtained from diffusion weighted imaging (DWI). Independent experts analyzed all the images separately and were unaware of the pathological data. In each case, the Index lesion was defined as the largest tumor measured on histopathology (Index H). In addition, the largest lesion observed on MRI (Index MRI) and the highest avid (11) C-Choline uptake lesion (Index PET) were obtained. The Gleason scores (GS) of the tumors were determined. PET/CT and ADC map quantitative parameters were also calculated. Measures of correlation among imaging parameters as well as the sensitivity (S), specificity (Sp), negative and positive predictive values (NPV and PPV) for tumor detection were analyzed. All data was validated with the pathological study. RESULTS: In the morphological study, 139 foci of carcinoma were identified, 47 of which corresponded to clinically significant tumors (>0.5 cm(3)). The remaining foci presented a maximum diameter (dmax ) of 0.1 cm ± SD 0.75 and were not classified as clinically significant. Thirty-two tumors presented a GS (3 + 3), nine GS (3 + 4), and six GS (4 + 3). A total of 21 Index H (dmax = 1.37 cm SD ± 0.61) were identified. The S, Sp, NPV, and PPV for tumor detection with PET were 100%, 70%, 83%, 100%, and for MRI were 46%, 100%, 100%, 54%, respectively. Both Index PET and Index MRI were complementary and identified 95% of the Index H when quantitative criteria were used. CONCLUSION: In spite of the fact that PET imaging has higher tumor sensitivity than MRI, (11) C-Choline PET and ADC maps have complementary roles in the evaluation of Index Lesion in PPC. Index PET and Index MRI could be complementary targets in the therapeutic planning of PPC.

[PERSIRIS study: observational study, postmarketing, prospective, to evaluate the persistence to treatment with monthly risedronate in women with osteoporosis]. / Estudio PERSIRIS: estudio observacional, postautorización, prospectivo, para evaluar la persistencia al tratamiento con risedronato mensual en mujeres con osteoporosis.

OBJECTIVE: To assess the persistence of treatment with monthly risedronate and know the reasons of persistence and nontherapeutic persistence and the profile of the non-persistent patients. DESING: Observational, postmarketin and prospective study. LOCATION: Primary care, traumatology, rheumatology, gynecology and geriatrics of Catalonia. PARTICIPANTS: Women with osteoporosis treated with monthly risedronate that previously had abandoned weekly bisphosphonate therapy. MAIN MEASUREMENTS: Percentage of patients on persistent monthly risedronate year of their prescription, reasons for persistent and non persistent and profile of non persistent patients in relation to biodemographic data, clinical data and risk factors for fracture. RESULTS: 289 evaluable patients with a mean age of 68.3. At 12 months of initiation with monthly risedronate, 58.1% of patients remained on treatment. Most frequent reasons for leaving: fear of having side effects and belief that the disease is typical of the age. Reasons remarkable persistence: comfort/ease and dosage. Significant differences were observed between persistent and non-persistent patients relative to: employment status, number of concomitant therapy and height; however the results of possible associated factors must be contextualized within the study characteristics and the difference in size does not seem clinically relevant. CONCLUSIONS: The administration of therapeutic patterns more comfortable as monthly risedronate in osteoporosis, could facilitate persistence in patients improving the effectiveness of the drug. However in that persistence can also influence biodemographic and clinical variables and diverse of various kinds.

Best clinical practice in botulinum toxin treatment for children with cerebral palsy.

Botulinum toxin A (BoNT-A) is considered a safe and effective therapy for children with cerebral palsy (CP), especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS) of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age.

[Indicator condition guided human immunodeficiency virus requesting in primary health care: results of a collaboration]. / Solicitud de VIH en condiciones indicadoras en atención primaria: resultados de una colaboración.

INTRODUCTION: The search of HIV infected patients guided by indicator conditions (IC) is a strategy used to increase the early detection of HIV. The objective is to analyze whether a collaboration to raise awareness of the importance of early detection of HIV in 3 primary care centers influenced the proportion of HIV serology requested. METHODS: Multicenter retrospective study was conducted comparing the baseline and a post-collaboration period. The collaboration consisted of training sessions and participation in the HIDES study (years 2009-2010). Patients between 18 and 64 years old with newly diagnosed herpes zoster, seborrheic eczema, mononucleosis syndrome, and leucopenia/thrombocytopenia in 3 primary care centers in 2008 (baseline period) and 2012 (post-collaboration period). The sociodemographic variables, HIV risk conditions, requests for HIV serology, and outcomes were evaluated. RESULTS: A total of 1,219 ICs were included (558 in 2008 and 661 in 2012). In 2008 the number of HIV tests in patients with an IC was 3.9%, and rose to 11.8% in 2012 (P<.0001). The HIV infection rate was 2.2% (95% CI: 0.4-7.3) (n=2). It was estimated that 25 new cases (12 in 2008 and 13 in 2012) would have been diagnosed if they had performed the test on all patients with IC. Predictors of HIV request were, having an IC in 2012, a younger age, having an mononucleosis syndrome, and not being Spanish. CONCLUSIONS: The HIV request demand tripled, after the collaboration with primary care centers, however in 88% the test was not requested, resulting in diagnostic losses. New strategies are needed to raise awareness of the importance of early detection of HIV.

Validity and applicability of a new recording method for hypertension.

INTRODUCTION AND OBJECTIVES: Blood pressure measurement methods and conditions are determinants of hypertension diagnosis. A recent British guideline recommends systematic 24-h ambulatory blood pressure monitoring. However, these devices are not available at all health centers and they can only be used by 1 patient per day. The aim of this study was to test a new blood pressure recording method to see if it gave the same diagnostic results as 24-h blood pressure monitoring. METHODS: One-hour blood pressure monitoring under routine clinical practice conditions was compared with standard method of day time recording by analyzing the coefficient of correlation and Bland-Altman plots. The Kappa index was used to calculate degree of agreement. Method sensitivity and specificity were also analyzed. RESULTS: Of the 102 participants, 89 (87.3%) obtained the same diagnosis regardless of method, with high between-method agreement (κ= 0.81; 95% confidence interval, 0.71-0.91). We observed robust correlations between diastolic (r=0.85) and systolic blood pressure (r=0.76) readings. Sensitivity and specificity for the new method for diagnosing white coat hypertension were 85.2% (95% confidence interval 67.5%-94.1%) and 92% (95% confidence interval, 83.6%-96.3%), respectively. CONCLUSIONS: One-hour blood pressure monitoring is a valid and reliable method for diagnosing hypertension and for classifying hypertension subpopulations, especially in white coat hypertension and refractory hypertension. This also leads to a more productive use of monitoring instruments.

Survival analysis of patients with biochemical relapse after radical prostatectomy treated with androgen deprivation: Castration-resistance influential factors.

INTRODUCTION: We evaluate the prognosis of patients with biochemical recurrence (BCR) treated with androgen deprivation therapy (ADT) and to determine the influential factors to castration resistance (CR) and death. METHODS: From a series of 1310 patients with T1-T2 prostate cancer treated with radical prostatectomy between 1989 and 2012, 371 had BCR. Patients with lymph node involvement were excluded. We analyzed only the 159 treated with salvage ADT. At the end of the study, 77 (48%) had developed CR. RESULTS: The median follow-up to CR was 9.2 years. The CR-resistant free survival (RFS) was 76 ± 3%, 62 ± 3% and 43 ± 9% in 5, 10 and 15 years, respectively. The RFS median time was 14 years. In the multivariate study, the prostate-specific antigen (PSA) doubling time (PSA-DT) was <6 months (p = 0.01) (hazard ratio [HR] 3; 95% confidence interval [CI] 1.4-6.8, p = 0.007); seminal vesicle involvement (HR 3.1; 95% CI 1.5-6.2, p = 0.01) and PSA velocity in ng/mL/year (HR 1.3; 95% CI 1.1-1.5, p = 0.002) with better cut-off points of 0.84 ng/mL/year (p = 0.04) (HR 4; 95% CI 1.7-9.4, p = 0.001) were influential variables. Specific survival (SS) at 5, 10 and 15 years since surgery was 96 ± 1, 85 ± 2 and 76 ± 4, respectively. The time of CR to death was 30 ± 6% at 5 years, with the median at 3.2 years. In the multivariate only Ki 67 (HR 1.04; 95% CI 1.005-1.08, p = 0.02) had an independent influence. CONCLUSIONS: In BCR patients treated with ADT, the median to CR was 14 years. PSA-DT <6 months, PSA velocity (ng/mL/year) and seminal vesicle involvement were influential variables. From the CR, the median time to death was 3.2 years. Ki-67 marker was an independent influence.

Radical prostatectomy. Detailed surgical margins. Prognostic value of multifocal involvement in pT2 (+).

OBJECTIVES: We intend to analyze the prognostic value of positive surgical margins depending on their number and location in pT2 patients. METHODS: We analyze 448 (34.3%) patients with positive surgical margins from a series of 1,310 T1-T2 patients treated with radical prostatectomy between 1989-2012. Of them 164 are pT2 (+). 119 (72.6% ) have unifocal affectation (41 (34.5%) unifocal in right lobe; 35 (29.4%) unifocal in left lobe, 40 (33.6%) unifocal in apex, 3 (2.5% ) unifocal proximal) and 45 (27.4%) multifocal involvement. RESULTS: Unifocal and multifocal pT2(+)patients have not evidenced significant differences in any of the clinicopathologic variables compared. However the BPFS at 5 and 10 years is significantly worse in the multifocal group, (p<0.000) In the BPFS multivariate study of 164 pT2(+ )influential variables are: multifocal involvement (HR: 3.4; 95%IC 1.7-6.9 p<0.000) and PSA (HR: 1.03; 95%IC 1.02-1.05 p<0.000), being PSA >15 ng/ml )HR: 3.7; 95%IC 2.1-6.6 p<0.000 ( the best cut-off point. Risk groups: Using the independent influence variables, the best model (using Cox models ) includes two risk groups: Group 1 (0 variables): They are pT2(+) with unifocal affectation and PSA<15 ng/ml, (63%). Their BPFS are 81±4% and 77±4% (5 and 10 years). Grupo 2 (1-2 variables): They are pT2 (+) with multifocal involvement, PSA> 15 ng/ml or both of them, (37%). Their BPFS are 46±6% and 26±7% (5 and 10 years). The BPFS differs significantly between the two groups (p<0.000). The Group 1 BPFS is similar to the pT2 (-) patients, (p:0.242). The Group 2 BPFS is similar to the pT3(+) patients, (p:0.637). The model explained significantly better the BPFS than any of the individual variables analyzed. CONCLUSIONS: In pT2(+) patients the prognosis is significantly worse in multifocal involvement. In addition two groups of patients can be clearly distinguished from the BPFS point view according to their influential variables. The data suggest that since the prognostic point view the second group is understaged while the first is overstaged.

Radical prostatectomy. Prognostic value of positive surgical margins in pT2 patients.

OBJECTIVES: We intend to assess the prognostic influence of surgical margins on the biochemical progression free survival (BPFS) in patients classified as pT2 after radical prostatectomy. METHODS: We analyze a series of 1,132 T1-T2 patients with prostate cancer treated with radical prostatectomy between 1989-2009. PT3b, pT4 and patients with lymph node involvement were excluded from the series. The clinicopathologic variables and the BPFS of pT2(+), pT2(-) and pT3 patients are compared. The influential clinicopathologic variables in the BPFS are identified in the pT2(+) group and risk groups are designed. RESULTS: Of 1,051 patients evaluated finally: 598 (59,6) were pT2(-) 163 (15,5%) pT2(+)80 (7,6%) pT3a(-) and 210 (20%) pT3(+). Clinical characteristics of pT2(+). It is homogeneous with the pT2(-) group and significantly better than pT3(+) group in all the clinicopathologic variables evaluated. 5 and 10 year BPFS of the pT2(68 ± 3% and 57 ± 5%) is significantly worse than pT2( -)(87 ± 1% and 79 ± 2%), similar to pT3a(-) (75 ± 5% and 64 ± 7%and better than pT3(+) (44 ± 3% and (36 ± 3%) BPFS pT2(+) influential factors: Univariate study : Pathological Gleason score 7-10 (HR:2.1 95% IC: 1.1-4.1), (p=0.02)MRI that indicates T3 (HR:3.2 95%IC: 1.4-7.3), (p=0.04) PSA > 15 ng-ml (HR:4 95% IC: 2-8.2), (p < 0.0001) and high risk D'Amico group (HR:3.3 95%IC: 1.3-8.5), (p=0.01) are influential variables. A risk model with the involved variables can be designed. Each variable present is a point. Two groups are designed : Group 1 (0-1 variable) Group 2 (2-3 variables). 5 and 10 year BPFS for Group 1 are 71±5% and 69 ± 5%, and are 37 ± 12% and 22 ± 11% for Group 2. (p < 0.0001). CONCLUSIONS: Surgical margins in pT2 patients have independent influence in the BPFS. The group is heterogeneous and it can be divided into two risk groups accordingly to the BPFS influential variables: a larger group (86% pT2(+) with worse prognosis than pT2(-), and a smaller group (remaining 14%) with similar prognosis to pT3 (+).It is likely that pT2(+) patients are a mixture of understaged patients with others with iatrogenic margins or false margins due to poor assessment of the surgical specimen.