Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes.

INTRODUCTION: Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aß) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented. METHODS: Sixty-five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 µg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up Aß positron emission tomography (PET) scans at 18 to 24 months. RESULTS: CAD106 induced measurable serum Aß immunoglobulin G titers in 41/42 participants, slower rates of Aß plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic). DISCUSSION: Despite early termination, these findings support the potential value of conducting larger prevention trials of Aß active immunotherapies in individuals at risk for AD. HIGHLIGHTS: This was the first amyloid-lowering prevention trial in persons at genetic risk of late-onset Alzheimer's disease (AD). Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial. CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes. CAD106 was generally safe and well tolerated, with only three amyloid-related imaging abnormality cases (one symptomatic). Such an approach deserves further evaluation in larger AD prevention trials.

Angiomatosis bacilar y sarcoma de Kaposi en lesión cutánea de paciente VIH positivo / Bacillary angiomatosis and Kaposi's sarcoma in skin lesion of HIV positive patient

La angiomatosis bacilar (AB) es una enfermedad infec-ciosa poco frecuente, causada por bacterias del género Bartonella spp. transmitidas por vectores como pulgas, piojos y mosquitos. En el ser humano provoca diferentes síndromes clínicos. En pacientes con infección por el virus de inmunodeficiencia humana (VIH) con recuento de LT CD4 + <100 cél/µL se asocia a lesiones angiomatosas con neovascularización que comprometen la piel y, en menor medida, mucosas, hígado, bazo y huesos.El sarcoma de Kaposi (SK) es una neoplasia caracteriza-da por hiperplasia vascular multifocal de origen endotelial relacionada con el herpes virus humano 8. También puede afectar piel, mucosas y vísceras, siendo la variante epidé-mica una enfermedad marcadora de la infección avanzada por VIH. El principal diagnóstico diferencial clínico para las lesiones cutáneas y mucosas del SK es la AB.Presentamos un paciente con enfermedad VIH/sida que desarrolló AB y SK en forma concomitante en la misma lesión cutánea

Bacillary angiomatosis (BA) is a rare infectious disease, caused by bacteria of the genus Bartonella spp, transmitted by vectors such as fleas, lice and mosquitoes. It causes different clinical syndromes in humans. In patients with human immunodeficiency virus (HIV) infection with an LT CD4 + <100 cell/µL count, it is associated with the development of angiomatous lesions with neovascularization involving the skin and, with less frequency, mucous membranes, liver, spleen and bones. Kaposi's sarcoma (KS) is a neoplasm characterized by multifocal vascular hyperplasia of endothelial origin related to human herpes virus 8. It can also compromiso the skin, mucous membranes and viscera, with the epidemic variant being a marker disease of advanced HIV infection. The main clinical differential diagnosis for KS skin and mucosal lesions is the BA.Herein we present a patient with HIV/AIDS disease that developed BA and KS concomitantly in the same skin lesion

Effectiveness of Fingolimod versus Natalizumab as Second-Line Therapy for Relapsing-Remitting Multiple Sclerosis in Spain: Second-Line GATE Study.

BACKGROUND: There is a lack of head-to-head studies comparing the efficacy of fingolimod (FIN) and natalizumab (NTZ) as second-line therapy for relapsing-remitting multiple sclerosis (RRMS). METHODS: Multicenter, observational study, in which, information of 388 patients randomly selected and treated with FIN or NTZ in routine clinical practice was retrospectively collected with the main objective of comparing the annualized relapse rate (ARR) over the first year, after FIN or NTZ treatment initiation. RESULTS: Mean ARR during the first year of treatment was 0.28 in FIN group and 0.12 in NTZ group (p = 0.0064); nevertheless, the difference between groups lost statistical significance when the propensity score analysis was performed. Time to disability -progression was similar in both treatment groups (12.3 ± 6.7 months in FIN, and 12.8 ± 0.1 months in NTZ; p = 0.4654). Treatment persistence after the first year of treatment was higher in patients treated with FIN (95%) than in those treated with NTZ (84%; p = 0.0014). CONCLUSIONS: After 12 months of treatment, both FIN and NTZ reduced the ARR, but ARR percent reduction was significantly higher with NTZ. Treatment persistence was higher in patients receiving FIN.

First detection of Cryptosporidium DNA in blood and cerebrospinal fluid of HIV-infected patients.

Human cryptosporidiosis is an intestinal infection caused by different species belonging to the genus Cryptosporidium in both immunocompetent and immunocompromised individuals. The life cycle of Cryptosporidium sp. when affecting the digestive system is well known but the infection of other organs is less studied. Molecular methods are necessary for species and subtypes identification. The goal of this work is to propose a new approach that contributes to the diagnosis of the extra-intestinal dissemination process of Cryptosporidium infection. Cryptosporidium sp. was detected in stool and biopsy samples of two HIV-infected patients. DNA was extracted from feces, biopsy specimens, blood, and cerebrospinal fluid (CSF). All samples were analyzed by nested PCR-RFLP of the 18S rDNA, real-time PCR, and gp60 subtyping. Cryptosporidium DNA was detected in stool and tissue samples and it was also present in blood and CSF samples. Both cases were characterized as Cryptosporidium hominis subtype IeA11G3T3. This is the first report that demonstrates the presence of Cryptosporidium DNA in blood and CSF of HIV-infected patients.

Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study.

BACKGROUND: A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale. METHODS: In the core study, patients were randomized to receive mavoglurant (25, 50, or 100 mg BID) or placebo over 12 weeks. In the extension, patients received 100 mg BID mavoglurant (or the highest tolerated dose) for up to 32 months. Global improvement, as a measure of treatment response, was assessed using the CGI-I scale. Investigators assigning CGI-I scores of 1 (very much improved), 2 (much improved), 6 (much worse), or 7 (very much worse) were provided a standard narrative template to collect further information about the changes observed in patients. Investigator feedback was coded and clustered into categories of improvement or worsening to identify potential areas of improvement with mavoglurant. Treatment effect in each category was characterized using the Cochran-Mantel-Haenszel test. RESULTS: A total of 134 and 103 patients had reached 2 weeks or more of core and extension study treatment, respectively, by the pre-assigned cutoff date for investigator feedback. In the core study, 34 CGI-I scores of 1 or 2 were reported in 28 patients; one patient scored 6. Analysis of the CGI-I narratives did not indicate greater treatment response in patients receiving mavoglurant compared with placebo in any specific improvement domain. There were 54 CGI-I scores of 1 or 2 in 47 patients in the extension study. The most frequently reported categories of improvement were behavior and mood (79.3 and 76.6 % in core and extension studies, respectively), engagement (75.9 and 78.7 %), and communication (69.0 and 61.7 %). CONCLUSIONS: A method was established to capture and categorize FXS symptoms using CGI-I narratives. Although this method did not show benefit of drug over placebo, narratives from investigators were mostly based on parental report and thus do not represent a completely objective alternative assessment. TRIAL REGISTRATION: The studies described are registered at ClinicalTrials.gov with clinical trial identifier numbers NCT01357239 and NCT01433354.

Diagnóstico, seguimiento y tratamiento de las infecciones por hepatitis B y C en personas privadas de su libertad en Argentina / Diagnosis, monitoring and treatment of hepatitis B and C in Argentinian prisoners

Hasta un tercio de las personas privadas de su libertad presentan serología positiva para virus de la hepatitis C y hasta un 5% refiere ser HIV positivo. No hay a la fecha estudios específicos de esta población en nuestro país. Objetivo: implementar en el Servicio Penitenciario un protocolo de diagnóstico, seguimiento y tratamiento de internos infectados con virus de hepatitis B y C. Material y métodos: Estudio prospectivo de diagnóstico, seguimiento y tratamiento realizado entre marzo 2010 y noviembre 2012 en una prisión federal de máxima seguridad. Se ofreció realizar biopsia hepática previo al tratamiento de hepatitis C. Resultados: Fueron evaluados en total de 55 internos con serologías positivas, para Anti HBc (n=15) o Elisa HCV (n=51). El 62% de los mismos (n=34) se encontraban co-infectados con HIV. El genotipo HCV más frecuente fue el número 1. La biopsia hepática se realizó en 16 pacientes. El 44% de ellos (n=7) fueron informados como METAVIR FO-F1. El tratamiento con interferón pegilado-ribavirina fue indicado a 10 internos. Conclusiones: En un lapso de 2 años se implementó con éxito un servicio de atención médica para el diagnóstico, seguimiento y tratamiento de las hepatitis crónicas por HBV-HCV en personas privadas de libertad. Se trata de un modelo único en Latinoamérica. Una correcta selección inicial de los pacientes permitió en el corto plazo tener una respuesta al tratamiento en HCV similar a reportes internacionales...

Up to one third of prisoners have tested positive for hepatitis C and up to 5% report being HIV positive. Until now, there are no reports of treatment in this population in our country. Objective: to implement in federal prisons a protocol for diagnosis, monitoring and treatment of inmates infected with hepatitis B and C. Methods: prospective study of monitoring and treatment between March 2010 and November 2012 in a maximum security federal prison. Liver biopsy was offered prior to treatmente of hepatitis C. Results: We evaluated a total of 55 inmates, with Anti HBc positive serology (n=15) or HCV positive (n=51). 62% of them (n=34) were co-infected with HIV. The most frequent hepatitis C genotype was number 1. Liver biopsy was performed in 16 patients. 44% of them (n=7) were informed as METAVIR FO-F1. Treatmente with pegylated interferon-ribavirin was given to 10 inmates. Conclusions: with in a 2 year period we successfully implemented a health care service for the monitoring and treatment of chronic hepatitis B and C. This is a unique model in Latin America. Proper initial selection of patients allowed us in the short term to have treatment responses in hepatitis C similar to international reports...

Otomastoiditis por Tsukamurella tyrosinosolvens, en un paciente HIV positivo / Tsukamurella tyrosinosolvens, otomastoiditis in an HIV positive patient

Tsukamurella spp. es un bacilo gram positivo, aeróbico, catalasa positivo, no móvil, no esporulado, que pertenece al orden de los actinomicetales. Los géneros incluidos en este orden son Nocardia, Gordonia, dietza, Skermania, Williamsia, Turicella, Streptomyces y Rhodococcus. Otros géneros relacionados son Corynebacterium y Mycobacterium. Las infecciones por esos microorganismos se han asociado con neumopatías crónicas, inmunodepresión (leucemia, tumores, infección por el HIV) e infecciones postoperatorias de heridas. Se notificó la presencia de tsukamurella en hemocultivos asociada al uso de sondas o catéteres, otros dispositivos médicos y en casos individuales de tenosinovitis necrosante con abscesos subcutáneos, infecciones óseas y cutáneas, meningitis, peritonitis y conjuntivitis y también como germen colonizante. Se presenta un caso de otomastoiditis en un paciente HIV positivo causado por este germen.

Enfermedad de whipple en paciente HIV positivo / Whipple disease in an HIV patient

La enfermedad de Whipple es una enfermedad crónica sistématica de infrecuente presentación, causada por una bacteria, Tropheryma Whipplei, del orden Actinomycetales. Existen cerca de 1.000 casos reportados en la actualidad. Presentamos un caso de enfermedad de Whipple en un paciente HIV (+).

Diagnóstico de HIV en contexto de cinco enfermedades oportunistas simultáneas / HIV diagnosis in context of 5 simultaneous opportunistic diseases

Cada día más de 6.800 personas adquieren HIV y más de 5.700 fallecen diariamente a causa de sida, en su mayoría por acceso inadecuado a los servicios de prevención y tratamiento...

Everyday more than 6.800 people get infected by HIV and more than 5.700 died because of AIDS, mainly related to inadequate access to prevention and treatment facilities...

[Phlebectomies or foam sclerosis for treatment of the distal venous segment in the 3-S saphenectomy technique]. / Flebectomías o esclerosis con espuma para el tratamiento del segmento venoso distal en la técnica 3-S safenectomía.

INTRODUCTION: The aim of this study was to compare the recurrent rates of varicose veins after treatment with two surgical techniques: 3-S saphenectomy and 3-S saphenectomy with distal sclerosis. PATIENTS AND METHOD: 105 patients with trunk varicose veins were randomly assigned. The control group consisted of 51 patients who underwent the 3-S saphenectomy technique (the sapheno-femoral junction sclerosis with foam, saphenectomy and distal phlebectomies); test group: 3-S saphenectomy with distal sclerosis technique (the sapheno-femoral junction sclerosis with foam, saphenectomy and distal segment sclerosis). RESULTS: Overall recurrence: group I 35.3%, group II 57.4% (p < 0.001). Trunk recurrence: group I 17.7%, group II 38.9% (p = 0.028). Collateral recurrence: group I 9.8%, group II 11.1% (p = 1). Perforator vein recurrence: group I 5.9%, group II 5.6% (p = 1). Reticulated recurrence: group I 2%, group II 1.9% (p = 1). CONCLUSIONS: The substitution of Müller phlebectomy instead of foam sclerosis, is not a better treatment of the distal venous segment, and has a greater recurrence rate. The 3-S saphenectomy technique is the most suitable for the treatment for trunk varicose veins.

[Classical surgery versus 3-S saphenectomy in the treatment of lower extremity varices]. / Cirugía clásica frente a 3-S safenectomía para el tratamiento de las varices del miembro inferior.

INTRODUCTION: The rate of recurrence requiring redo surgery after primary surgical treatment of varicose veins is between 20 and 30%. Several techniques to reduce the high rate of recurrence after stripping have been designed over the years, especially reticulated recurrences at the sapheno-femoral junction. The aim of this study was to compare the recurrence rates of varices after treatment with two surgical techniques: stripping and 3-S saphenectomy. PATIENTS AND METHOD: One hundred patients with leg varicose veins were randomly assigned to two groups. Group I consisted of 50 patients who underwent classical surgery (ligature and section at the sapheno-femoral junction and collateral veins, with saphenectomy). Group II consisted of 50 patients who underwent the 3-S saphenectomy technique (sclerosis injection at the sapheno-femoral junction with microfoam through a catheter, with saphenectomy and distal phlebectomies). The rate and type of recurrences were evaluated through echo-Doppler 12 months after the procedure. RESULTS: Overall recurrence: group I: 78%, group II: 44% (P< .05). Trunk recurrence: group I 12%, group II 16% (P=NS). Collateral recurrence: group I 16%, group II 6% (P=NS). Perforator vein recurrence: group I 18%, group II 18% (P=NS). Reticulated recurrence: group I 32%, group II 4% (P=.002). CONCLUSIONS: The 3-S saphenectomy technique decreases the overall rate of recurrence, particularly reticulated type recurrences. We recommend avoidance of surgery of the branches at the sapheno-femoral junction.