[Lateral osteotomy of the calcaneus in the treatment of Müller-Weiss disease]. / Osteotomía lateral de calcáneo en el tratamiento de la enfermedad de Müller-Weiss.

INTRODUCTION: The deforming condition of the navicular bone known as Müller-Weiss disease (MWD) is a rare disease. Patients present with chronic pain in the talonavicular joint and a paradoxical flat foot with a varo hindfoot. OBJECTIVE: To analyze the clinical results of a lateral osteotomy of calcaneus applied to patients with MWD. MATERIAL AND METHODS: Retrospective observational study carried out in two hospitals. The series consists of nine cases in eight patients, all of them with symptomatic Müller-Weiss disease, treated by lateral osteotomy of the calcaneus between 2012 and 2017, obtaining an average follow-up of 4 years (2-6). The mean age was 62 years (50-75). In all patients, Costa-Bartani angles (CB), Kite angle and Calcaneal Inclination (CI) were measured. In addition, the Manchester Oxford Scale (MO) to measure the post-surgical satisfaction of patients. RESULTS: All patients report having improved their pain by obtaining a postoperative score on the mean Manchester Oxford scale of 32.54 points (15.62-53.75). In 66% of patients the CB angle improves, the Kite angle in 89% and the CI in 33%. CONCLUSION: The improvement in the pain of the patients in our series is not accompanied by radiological changes in the same proportion, it is a simple and uncomplicated technique in our follow-up.

INTRODUCCIÓN: La afección deformante del hueso navicular conocida como enfermedad de Müller-Weiss (EMW) es una enfermedad rara. Los pacientes presentan dolor crónico en la articulación talonavicular y un pie plano paradójico con retropié varo. OBJETIVO: Analizar los resultados clínicos de la osteotomía valguizante de calcáneo aplicada a pacientes con EMW. MATERIAL Y MÉTODOS: Estudio observacional, retrospectivo, realizado en dos centros hospitalarios. La serie consta de nueve casos en ocho pacientes, todos ellos con enfermedad de Müller-Weiss sintomática, fueron tratados mediante osteotomía valguizante de calcáneo entre 2012 y 2017, con un seguimiento medio de cuatro años (dos a seis). La edad media fue de 62 años (50-75). En todos los pacientes se midieron los ángulos de Costa-Bartani (CB), el ángulo de Kite y la inclinación calcánea (IC). Además, se utilizó la escala Manchester Oxford (MO) para medir la satisfacción postquirúrgica de los pacientes. RESULTADOS: Todos los pacientes refieren haber mejorado en su dolor, obteniendo una puntuación postoperatoria media de 32.54 puntos (15.62-53.75) en la escala Manchester Oxford. En 66% de los pacientes el ángulo CB mejoró, al igual que en el ángulo de Kite en 89% y la IC en 33%. CONCLUSIÓN: La mejoría en el dolor de los pacientes de nuestra serie no está acompañada por cambios radiológicos en la misma proporción, es una técnica sencilla y sin complicaciones en nuestro seguimiento.

Synergism between the Black Queen effect and the proteomic constraint on genome size reduction in the photosynthetic picoeukaryotes.

The photosynthetic picoeukaryotes (PPEs) comprise a rare example of free-living eukaryotes that have undergone genome reduction. Here, we examine a duality in the process; the proposed driver of genome reduction (the Black Queen hypothesis, BQH), and the resultant impact of genome information loss (the Proteomic Constraint hypothesis, PCH). The BQH predicts that some metabolites may be shared in the open ocean, thus driving loss of redundant metabolic pathways in individual genomes. In contrast, the PCH predicts that as the information content of a genome is reduced, the total mutation load is also reduced, leading to loss of DNA repair genes due to the resulting reduction in selective constraint. Consistent with the BQH, we observe that biosynthetic pathways involved with soluble metabolites such as amino acids and carotenoids are preferentially lost from the PPEs, in contrast to biosynthetic pathways involved with insoluble metabolites, such as lipids, which are retained. Consistent with the PCH, a correlation between proteome size and the number of DNA repair genes, and numerous other informational categories, is observed. While elevated mutation rates resulting from the loss of DNA repair genes have been linked to reduced effective population sizes in intracellular bacteria, this remains to be established. This study shows that in microbial species with large population sizes, an underlying factor in modulating their DNA repair capacity appears to be information content.

Characteristics of Liver Transplantation in Argentina: A Multicenter Study.

INTRODUCTION: There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES: This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS: We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS: A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We believe the information contained in this article might be of value for reviewing current practices and developing local policies.

Metaloproteinasa 11, potencial marcador y diana molecular en cáncer de próstata avanzado y resistente a la castración. Estudio en cultivo de fibroblastos peritumorales / Metalloproteinase 11, potential marker and molecular target in advanced and castration-resistant prostate cancer. Culture study of peritumoral fibroblasts

Objetivo: Analizar el comportamiento de la metaloprotesa 11 (MMP11) en fibroblastos cultivados procedentes de tumores prostáticos humanos con diferentes características clinicopatológicas. Material y métodos: Para este estudio se analizaron muestras de biopsias de próstata obtenidas por vía transrectal de tumores con diferentes características, tratados o no con privación androgénica (PA). Tras la optimización del método de cultivo, se aislaron y cultivaron los fibroblastos para realizar el estudio (PCR) del ARNm de MMP11. Resultados: Se estudiaron finalmente 37 casos: 5 muestras de hiperplasia benigna de próstata, 14 casos con neoplasias localizadas (7 de alto riesgo según la clasificación de D’Amico), 5 con tumores con metástasis óseas y 13 tratados con PA, de los que 6 cumplían los requisitos para ser definidos como resistentes a la castración. En los tumores sin PA, la expresión de MMP11 fue significativamente mayor (p = 0,001) en los fibroblastos de tumores de grados más altos. Se encontró una correlación significativa (p = 0,001) entre PSA y expresión de MMP11 fibroblástica y un aumento significativo de la expresión de MMP11 en los tumores metastásicos. En los tumores con PA se objetivó una expresión significativamente mayor de MMP11 en pacientes resistentes a la castración que en los sensibles a esta (p = 0,003). Conclusión: En tumores de próstata avanzados o en fases de mayor agresividad tumoral, la producción de MMP11 por los fibroblastos resulta significativamente mayor que en tumores no metastásicos o en fases de sensibilidad a la PA

Objective: To analyze the expression of metalloprotein 11 (MMP11) in cultured fibroblasts obtained from human prostate tumors with different clinical and pathological characteristics. Material and methods: For this study we analyzed samples of transrectal prostate biopsies from tumors with different characteristics, treated with or whithout androgen deprivation (AD). After optimization of the culture method, fibroblasts were isolated and cultured to perform the study (PCR) of MMP11 mRNA. Results: Finally, 37 cases were studied: 5 samples of benign prostatic hyperplasia, 14 cases with localized neoplasms (7 high-risk according to the D’Amico classification), 5 with metastasic tumors (bone metastases), and 13 treated with AD therapy, of which 6 fulfilled the requirements to be defined as resistant to castration. In tumors without AD therapy, MMP11 expression was significantly higher (P= .001) in fibroblasts of higher grade tumors. A significant (P= .001) correlation was found between PSA and expression of MMP11 in fibroblast s and a significant increase of MMP11 expression in metastatic tumors. In tumors with AD therapy, a significantly greater expression of MMP11 was observed in resistant to castration patients than in those sensitive to castration (P= .003). Conclusion: In advanced prostate tumors or in stages of increased tumor aggressiveness, the production of MMP11 by fibroblasts is significantly greater than in non-metastatic tumors or in AD sensitive tumors

Metalloproteinase 11, potential marker and molecular target in advanced and castration-resistant prostate cancer. Culture study of peritumoral fibroblasts. / Metaloproteinasa 11, potencial marcador y diana molecular en cáncer de próstata avanzado y resistente a la castración. Estudio en cultivo de fibroblastos peritumorales.

OBJECTIVE: To analyze the expression of metalloprotein 11 (MMP11) in cultured fibroblasts obtained from human prostate tumors with different clinical and pathological characteristics. MATERIAL AND METHODS: For this study we analyzed samples of transrectal prostate biopsies from tumors with different characteristics, treated with or whithout androgen deprivation (AD). After optimization of the culture method, fibroblasts were isolated and cultured to perform the study (PCR) of MMP11 mRNA. RESULTS: Finally, 37 cases were studied: 5 samples of benign prostatic hyperplasia, 14 cases with localized neoplasms (7 high-risk according to the D'Amico classification), 5 with metastasic tumors (bone metastases), and 13 treated with AD therapy, of which 6 fulfilled the requirements to be defined as resistant to castration. In tumors without AD therapy, MMP11 expression was significantly higher (P=.001) in fibroblasts of higher grade tumors. A significant (P=.001) correlation was found between PSA and expression of MMP11 in fibroblast s and a significant increase of MMP11 expression in metastatic tumors. In tumors with AD therapy, a significantly greater expression of MMP11 was observed in resistant to castration patients than in those sensitive to castration (P=.003). CONCLUSION: In advanced prostate tumors or in stages of increased tumor aggressiveness, the production of MMP11 by fibroblasts is significantly greater than in non-metastatic tumors or in AD sensitive tumors.

Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer.

Patients with metastatic breast cancer in complete remission are the ones most likely to have an improved outcome with subsequent high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC-PBSCT). Peripheral blood stem cells are usually procured following mobilization with single agent chemotherapy and colony-stimulating factor support. We utilized a dose-intense regimen of paclitaxel 200 mg/m2 i.v., etoposide 60 mg/kg i.v., and cyclophosphamide 3 g/m2 i.v. (TEC) followed by daily administration of granulocyte colony-stimulating factor. The aim was not only to mobilize stem cells but also to achieve optimal tumor cytoreduction prior to HDC/PBSCT. One hundred consecutive patients with metastatic breast cancer received 257 cycles of TEC between March 1994 and June 1997, with the aim of collecting 5 x 106 CD34-positive cells/kg usually following the second cycle of chemotherapy. Patient characteristics included a median age of 45 years, a median of two organ systems involved by disease, a median of two prior chemotherapy regimens and eight prior chemotherapy cycles, and a median interval of 8 months from diagnosis of metastases to first cycle of TEC. There were 61 febrile episodes during neutropenia and 13 of these were associated with bacteremia or fungemia. Mortality rate was 1%. An adequate number of stem cells was collected in 90% of patients. The overall response rate of the tumor was 58.8% with 23.7% complete responders among 97 evaluable patients. Multivariate analysis demonstrated chemosensitivity to the most recent standard chemotherapy regimen administered for metastatic disease, an ECOG performance score of 0 as opposed to 1, 2 or 3, and involvement by disease of only one organ system as significant variables for achieving a complete remission with TEC. This novel dose-intense regimen was safe and well tolerated, highly active against metastatic breast cancer, and capable of excellent stem cell mobilization. Bone Marrow Transplantation (2000) 25, 123-130.

Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diagnosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myeloablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal distention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vancomycin or metronidazole was prompt despite the presence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infection in such a setting. Finally, C. difficile is not uncommon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea.

Varicella zoster virus infection associated with high-dose chemotherapy and autologous stem-cell rescue.

A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the incidence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five percent of patients demonstrated cutaneous or systemic dissemination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors disclosed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reducing the risk of VZV infection. Moreover, the use of busulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobilization chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mononuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplantation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting.

Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group.

Liver disease secondary to hepatitis C virus (HCV) infection is a rising cause of morbidity and mortality among individuals who have been infected parenterally with human immunodeficiency virus (HIV) such as injection drug users, hemophiliacs, and transfused patients. We analyzed both the efficacy of interferon (IFN) alpha therapy in these patients and the predictors of response to this agent. A total of 119 patients with chronic hepatitis C (90 of whom were infected with HIV and 29 of whom were not) were included in a multicenter, prospective, open, nonrandomized observational study. IFN-alpha was given subcutaneously in a dosage of 5 million units three times a week during a 3-month period; those patients who responded received a dose of 3 million units given subcutaneously three times a week for an additional 9 months. One hundred seven patients completed the study; the level of aminotransferases returned to normal and sera became negative (complete response) for HCV RNA in 26 (32.5%) of 80 HIV-infected patients and 10 (37.0%) of 27 non-HIV-infected patients (P = .666) after completion of the treatment. Two variables were independently associated with a response in HIV-infected patients: a CD4+ T lymphocyte count of > 500 x 10(6)/L and a baseline HCV viremia level of < 10(7) copies/mL. In the 12 months following treatment, relapses occurred in 30.8% of the HIV-infected patients and 12.5% of non-HIV-infected patients (P = .403).

[The treatment of chronic hepatitis C with interferon in patients infected with the human immunodeficiency virus. The Spanish Group for the Study of Viral Hepatitis in HIV+ Patients]. / Tratamiento de la hepatitis crónica C con interferón en pacientes infectados por el virus de la immunodeficiencia humana. Grupo Español para el Estudio de las Hepatitis Víricas en Pacientes VIH+.

BACKGROUND: Alfa-interferon (aIFN) is widely recommended for the treatment of chronic hepatitis C (CHC). Hepatitis C virus (HCV) infection is very common in injecting drug users (IDUs), which in Spain represent the large number of HIV-infected persons. Interaction between human immunodeficiency virus (HIV) and HCV in coinfected patients might accelerate the clinical course of HCV-associated liver disease. The efficacy and safety of aIFN therapy in HIV-infected patients with CHC is not well known. PATIENTS AND METHODS: In a multicenter, prospective, open, non randomized and partially controlled study, we compared the efficacy and safety of aIFN therapy in 119 patients with CHC, of whom 90 were HIV-positive and 29 HIV-negative. Interferon was started at 5 mega U tiw for 3 months, followed in responders by 3 megaU tiw for additional 9 months. RESULTS: One hundred seven patients completed the study. A normalization of the aminotransferase values at the end of treatment (complete response, CR) was observed in 26/80 (32.5%) HIV-positive and 10/27 (37.0%) HIV-negative individuals (p = 0.666). Relapses at 12 months of stopping aIFN were seen in 30.8% of HIV-positive subjects and 12.5% of HIV-negatives (p = 0.403). Side effects were uncommon and did not have severity; only one patient required to stop the medication. However, 3 HIV-positive subjects treated with aIFN (3.5% of them) showed an irreversible fall of CD4+ T-cells below half the baseline values. CONCLUSION: HIV-infected patients with CHC seems to respond to aIFN with a similar rate than HIV-negatives. Moreover, the drug is similarly well tolerated in both groups of patients, although a fall of CD4+ T-cells is an unusual side effect of particular relevance observed in HIV-infected patients.

[Soteria House. Environment or new therapy ? A personal experience.]. / Soteria House : Milieu de vie ou nouvelle thérapie? Une expérience personnelle.

Soteria House is an alternative treatment resource offering an approach very different from that of the hospital milieu. The staff is non-professional and the residents are treated without neuroleptics. They are permitted to experience their "fragmentation" and their "psychotic break" while providing them with what they say they need, and with as little as possible interference with the expression of these needs. Our personal experience, as a member of staff, and of life with the residents of Soteria House, gave us the opportunity to inspect this approach and to confront the currently espoused belief about psychotics which hold that they are irresponsible and incomprehensible, and require a closed, highly professionalized treatment milieu, and the use of neuroleptics. Soteria House challenges the traditional treatment forms, just as much as the treatment provides themselves and their tools. The Soteria approach does not represent a miracle treatment, but rather a new way of considering the occurrence of rupture, that is to say " a potential experience of positive and constructive growth which allows the person to better face the demands of life" (L. Mosher). It is therefore necessary that this experience (psychotic) not be prematurely aborted by psycho-biological or chemical intrusion which act to straitjacket this evolution.