Elite controllers long-term non progressors present improved survival and slower disease progression.

Different phenotypes exhibiting no evidences of disease progression have been described in ART-naïve HIV-1 positive individuals. Long-term non progressors (LTNP) and elite controllers (EC) are low frequent examples of immunological and virological control in HIV-1 positive subjects, respectively. The combination of both phenotypes is even less frequent and studied despite being considered as models of HIV-1 functional cure. A multicenter, prospective study in retrospect including clinical and epidemiological data collected from 313 LTNP of 21 Spanish hospitals was carried out. LTNPs maintaining CD4+ T cell counts over 500 cells/µl and viral loads (VL) under 10,000 copies/mL for at least 10 years in the absence of antiretroviral therapy were followed for a median of 20.8 years (IQR = 15.6-25.5). A 52.1% were considered EC (undetectable VL) and LTNP (EC-LTNP) and a total of 171 (54.8%) and 42 (13.5%) out of the 313 participants maintained LTNP status for at least 20 and 30 years, respectively. EC-LTNP showed lower CD4+ T cell count loss (9.9 vs 24.2 cells/µl/year), higher CD4/CD8 ratio (0.01 vs - 0.09 in ratio), and lesser VL increase (no increase vs 197.2 copies/mL/year) compared with LTNPs with detectable VL (vLTNP). Survival probabilities for all-cause mortality at 30 years from HIV + diagnosis were 0.90 for EC-LTNP and 0.70 for vLTNP (p = 2.0 × 10-3), and EC-LTNP phenotype was the only factor associated with better survival in multivariate analyses (HR = 0.28; 95% CI 0.10-0.79). The probability to preserve LTNP status at 30 years was 0.51 for EC-LTNP and 0.18 for vLTNP (p < 2.2 × 10-16). Risk factors associated to the loss of LTNP status was: higher age at diagnosis and the increase of VL, whereas the increase of CD4+ T cell counts and CD4/CD8 ratio, the initial EC-LTNP phenotype and HCV coinfection were protective factors. EC-LTNP phenotype was associated with improved survival and slower disease progression compared with other phenotypes of LTNP. EC-LTNP individuals represent one of the most favorable phenotypes of immune activation against HIV-1 found in nature and, therefore, are strong candidates to be considered a model of functional cure of HIV-1 infection.

Omic Technologies in HIV: Searching Transcriptional Signatures Involved in Long-Term Non-Progressor and HIV Controller Phenotypes.

This article reviews the main discoveries achieved by transcriptomic approaches on HIV controller (HIC) and long-term non-progressor (LTNP) individuals, who are able to suppress HIV replication and maintain high CD4+ T cell levels, respectively, in the absence of antiretroviral therapy. Different studies using high throughput techniques have elucidated multifactorial causes implied in natural control of HIV infection. Genes related to IFN response, calcium metabolism, ribosome biogenesis, among others, are commonly differentially expressed in LTNP/HIC individuals. Additionally, pathways related with activation, survival, proliferation, apoptosis and inflammation, can be deregulated in these individuals. Likewise, recent transcriptomic studies include high-throughput sequencing in specific immune cell subpopulations, finding additional gene expression patterns associated to viral control and/or non-progression in immune cell subsets. Herein, we provide an overview of the main differentially expressed genes and biological routes commonly observed on immune cells involved in HIV infection from HIC and LTNP individuals, analyzing also different technical aspects that could affect the data analysis and the future perspectives and gaps to be addressed in this field.

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection.

Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them. The administration of treatment produces 18 DE miRNAs in typical progressors. LTNP condition shows 14 DE miRNA when compared to typical progressors, allowing LTNP phenotype differentiation. A set of four miRNAs: miR-144-3p, miR-18a-5p, miR-451a, and miR-324 is strongly downregulated in LTNP and related to protein regulation as AKT, mTOR, ERK or IKK, involved in immune response pathways. Deregulation of 28 miRNA is observed between EC-LTNP and viremic-LTNP, including previously described anti-HIV miRNAs: miR-29a, associated with LTNP phenotype, and miR-155, targeting different pre-integration complexes such as ADAM10 and TNPO3. A holistic perspective of the changes observed in the miRNome of patients with different phenotypes of HIV-control and non-progression is provided.

Molecular performance of Prl and Gh/Igf1 axis in the Mediterranean meager, Argyrosomus regius, acclimated to different rearing salinities.

Aquaculture industry in the Mediterranean region exhibits a growing interest for the Mediterranean meager Argyrosomus regius. Some preliminary works showed a good growth performance of the species in nearly isosmotic salinities. However, the patterns of alteration of prolactin (Prl) as well as growth hormone (Gh)/insulin growth factor-1 (Igf1) axis at the molecular level are not yet described in this species. Therefore, we cloned and sequenced partial cDNAs for pituitary prolactin (prl) and growth hormone (gh), hepatic insulin-like growth factor (igf1), and ß-actin (actb). Expression patterns of these transcripts were tested in juveniles of A. regius acclimated to four different environmental salinities: (1) 5 ‰ (hyposmotic); (2) 12 ‰ (isosmotic); (3) 38 ‰ (hyperosmotic; seawater control); and (4) 55 ‰ (extremely hyperosmotic). All investigated transcripts shared high sequence identities with their counterparts in other perciformes. prl mRNA levels showed inverse pattern with increasing salinities. gh mRNA enhanced significantly in both 12 and 55 ‰ salinity groups in comparison with the control group, while igf1 showed its maximum expression levels under the nearly isosmotic environment. The results indicated clear sensitivity of prl, gh and igf1 to changes in environmental salinity, which can possibly control the euryhalinity capacity of this species.

Surgical site infection in surgery for benign prostatic hyperplasia: comparison of two skin antiseptics and risk factors.

BACKGROUND: Surgical site infection (SSI) is the second most common type of nosocomial infections in the United States. In Uruguay, the incidence after prostatectomies is 2.6%. The aim of our study was to compare the efficacy of two skin antiseptics and to determine possible risk factors for SSI in patients undergoing surgery for benign prostatic hyperplasia (BPH). METHODS: A randomized trial included 70 patients operated on for BPH, of whom 56 (80%) underwent open surgery. Patients were treated by the same surgical team in a tertiary general hospital that is a referral center for patients with urologic diseases. Skin antisepsis was performed randomly using either 0.5% povidone-iodine or chlorhexidine in an alcohol base (Chemisol(®)). Possible risk factors investigated were age, renal dysfunction, bladder stones, preoperative urinary catheter, positive preoperative urine culture, operative time and technique, and vesicocutaneous fistula. RESULTS: Of all patients, 41 (59%) had a urinary catheter preoperatively. Urine cultures were positive in 31 patients, of whom 29 (94%) had a urinary catheter. Surgical site infection occurred in 10 patients (18%), and 100% of the causative microorganisms were gram-negative bacteria characteristic of the urinary flora. The type of antiseptic did not affect the risk of SSI (p=1.00). The most important risk factor for infection was the presence of a urinary catheter preoperatively (p=0.003); also significant were the formation of a vesicocutaneous fistula (p=0.008), increasing age (p=0.02), and the presence of a positive preoperative urine culture (p=0.03). CONCLUSIONS: In a cohort of patients submitted to open prostatectomy, SSI was not related to the type of antiseptic. The main risk factor was the presence of a urinary catheter preoperatively. All microorganisms isolated from the SSIs were characteristic of urinary tract infections.

Community-acquired methicillin resistant Staphylococcus aureus: a new aetiological agent of prostatic abscess.

Prostatic abscess is rare. Its potentially serious course requires a high level of clinical suspicion and prompt and effective treatment. The causative germs are usually either enterobacteria or Enterococcus. The authors highlight the importance of considering epidemiological and clinical aspects in the early diagnosis and treatment. Prostatic abscess due to community-acquired methicillin resistant Staphylococcus has three typical characteristics: skin entry point, periprostatic compromise, and anaemia and low prothrombin.

Can selective retroperitoneal lymphadenectomy be better than unilateral retroperitoneal lymphadenectomy?

OBJECTIVE: To propose a new modality of retroperitoneal lymphadenectomy as a complementary treatment for patients with high risk, stage I nonseminomatous testicular tumor. MATERIALS AND METHODS: We studied 76 patients with stage I nonseminomatous testis tumor (T1-T4, NX, M0) treated by orchiectomy and retroperitoneal lymphadenectomy. Among them, 33 patients underwent unilateral retroperitoneal lymphadenectomy (URL) and 43 selective retroperitoneal lymphadenectomy (SRL). URL consisted in removing the lymph nodes located around the great vessel homolateral to the tumor (aorta or vena cava and iliac vessels), and anterior and posterior to the contralateral great vessel (aorta or vena cava). SRL was performed removing the lymph nodes located anterior and between the great vessels (aorta or vena cava) and laterally to the homolateral great vessel, extending the distal dissection until the level of inferior mesenteric artery. In these groups of patients, the incidence of disease recurrence, disease-free survival index, and frequency of post-operative aspermia were assessed. Mean post-operative follow-up time was 96 months. RESULTS: In the SRL group there was only 5 percent of aspermia versus 79 percent in the URL group (p < 0.0001). Tumor recurrence was observed in only 5 of the 76 patients and was not related to the surgical technique. The disease-free survival rate after the mean follow-up of 96 months was similar in both groups, being 94 percent in the SRL group and 93 percent in the URL group. CONCLUSION: The selective retroperitoneal lymphadenectomy constitutes an effective technique with a lower morbidity than unilateral lymphadenectomy, representing an excellent option for the management of patients with high-risk, stage I nonseminomatous testis tumor.

Can selective retroperitoneal lymphadenectomy be better than unilateral retroperitoneal lymphadenectomy?

OBJECTIVE: To propose a new modality of retroperitoneal lymphadenectomy as a complementary treatment for patients with high risk, stage I nonseminomatous testicular tumor. MATERIALS AND METHODS: We studied 76 patients with stage I nonseminomatous testis tumor (T1-T4, NX, M0) treated by orchiectomy and retroperitoneal lymphadenectomy. Among them, 33 patients underwent unilateral retroperitoneal lymphadenectomy (URL) and 43 selective retroperitoneal lymphadenectomy (SRL). URL consisted in removing the lymph nodes located around the great vessel homolateral to the tumor (aorta or vena cava and iliac vessels), and anterior and posterior to the contralateral great vessel (aorta or vena cava). SRL was performed removing the lymph nodes located anterior and between the great vessels (aorta or vena cava) and laterally to the homolateral great vessel, extending the distal dissection until the level of inferior mesenteric artery. In these groups of patients, the incidence of disease recurrence, disease-free survival index, and frequency of post-operative aspermia were assessed. Mean post-operative follow-up time was 96 months. RESULTS: In the SRL group there was only 5% of aspermia versus 79% in the URL group (p < 0.0001). Tumor recurrence was observed in only 5 of the 76 patients and was not related to the surgical technique. The disease-free survival rate after the mean follow-up of 96 months was similar in both groups, being 94% in the SRL group and 93% in the URL group. CONCLUSION: The selective retroperitoneal lymphadenectomy constitutes an effective technique with a lower morbidity than unilateral lymphadenectomy, representing an excellent option for the management of patients with high-risk, stage I nonseminomatous testis tumor.

Manejo intervencionista en el tratamiento del dolor por cáncer / Interventionist management in the treatment of cancer pain

Se consideran las alternativas y el papel del manejo intervencionista en dolor por cáncer. Entre las múltiples opciones de intervencionismo están las siguientes: La cirugía neuroaumentativa, neurocirugía del dolor, procedimientos mieloendoscópicos, terapia infusional (acueductal, intratecal, peridural, intrapleural y de plexos), crioanalgesia, neurólisis por radiofrecuencia y finalmente los bloqueos neurolíticos por métodos químicos. El que los profesionales no cuenten con el entrenamiento calificado en el tratamiento del dolor crónico y el que no se tenga el soporte técnico adecuado como un área física, instrumental, rayos X, etc., da como resultado un incremento en la incidencia de fallas técnicas y terapéuticas. El manejo del dolor crónico de origen oncológico requiere de una adecuada evaluación para elegir la mejor opción de tratamiento. Partiendo del uso de procedimientos sencillos como la terapia farmacológica, la cual es recomendada y validada primordialmente por la Organización Mundial de la Salud por su simplicidad, confiabilidad y alto grado de efectividad, hasta los procedimientos más complicados de tipo intervencionista. El manejo intervencionista del dolor de origen oncológico, es considerado como una importante alternativa analgésica confiable, predecible y que puede beneficiar a un importante número de pacientes que no responden satisfactoriamente al tratamiento farmacológico o que desean un control analgésico libre de fármacos, y que además es compatible con el manejo extrahospitalario del paciente

Utilidad de la clonidina en prostatectomía / Usefulnes of clinidine in prostatectomy

Se estudió a futuro 25 pacientes con hipertrofia prostática benigna que fueron sometidos a resección transuretral. Como parte del protocolo de anestesia se utilizó clonidina, 150 µg como dosis única. Se tomó en consideración la edad, presiones arteriales basal, operatoria y de recuperación, analgesia posoperatoria y volumen administrado. La clonidina contribuyó a mantener las cifras de tensión en límites normales sin que hubiera hipotensión marcada. La analgesia posoperatoria fue catalogada como buena utilizando la Escala Visual Análoga. La clonidina, en conclusión, es un fármaco útil en este tipo de operaciones