Antiretroviral therapy as a factor protective against anal dysplasia in HIV-infected males who have sex with males.

OBJECTIVES Chronic infection with oncogenic HPV genotype is associated with the development of anal dysplasia. Antiretroviral therapy (ART) has been shown to decrease the incidence of cervical carcinoma in women with HIV. We sought to: 1) describe the prevalence and grade of anal dysplasia and HPV infection in our study subjects; 2) analyze the grade of correlation between anal cytology, PCR of high-risk HPV, and histology; 3) identify the factors associated with the appearance of ≥ AIN2 lesions. DESIGN Cross-sectional, prospective study. METHODS A cohort of HIV-positive males (n = 140, mean age  = 37 years) who have sex with males (MSM) had epidemiological, clinical and analytical data collected. Anal mucosa samples were taken for cytology, HPV PCR genotyping, and anoscopy for histological analysis. RESULTS Within the cohort, 77.1% were being treated with ART, 8.5% anoscopy findings were AIN2, and 11.4% carcinoma in situ; 74.2% had high-risk (HR), 59.7% low-risk (LR) HPV genotypes and 46.8% had both. The combination of cytology with PCR identifying HR-HPV better predicts the histology findings than either of these factors alone. Logistic regression highlighted ART as a protective factor against ≥ AIN2 lesions (OR: 0.214; 95%CI: 0.054-0.84). Anal/genital condylomas (OR: 4.26; 95%CI: 1.27-14.3), and HPV68 genotype (OR: 10.6; 95%CI: 1.23-91.47) were identified as risk factors. CONCLUSIONS In our cohort, ART has a protective effect against dysplastic anal lesions. Anal/genital warts and HPV68 genotype are predictors of ≥ AIN2 lesions. Introducing PCR HPV genotype evaluation improves screening success over that of cytology alone.

Puesta en marcha del cribado de cáncer de Colon en Andalucía

Boletín semanal para profesionales sanitarios de la Secretaría General de Calidad, Innovación y Salud Pública de la Consejería de Igualdad, Salud y Políticas Sociales

New clinical practice guideline on enteral feeding in very low birth wieght infants; second part

INTRODUCTION: The nutrition of very low birth weight (VLBW) infants is aimed at promoting a similar growth to that occurring in the uterus. However, in practice this is difficult to achieve and extrauterine growth restriction is frequent. The current tendency is to avoid this restriction by means of early parenteral and enteral nutrition. Nonetheless, uncertainty about many of the practices related with nutrition has resulted in a great variation in the way it is undertaken. In 2009 and 2011 in our hospital there was an unexpected increase in necrotizing enterocolitis. To check to see wether our nutrition policy was involved, we underlook a systematic review and drewup clinical practice guidelines (CPG) about enteral feeding in VLBW infants. New considerations about the duration of the fortification and the use of probiotics have led to an update of these CPG. METHODS: A total of 21 clinical questions were designed dealing with the type of milk, starting age, mode of administration, rate and volume of the increments, fortification, use of probiotics and protocol. Afete conducting a systematic search of the available evidence, the information was contrasted and summarized in order to draw up the recommendations. The quality of the evidence and the strength of the recommendations were determined from the SIGN scale. COMMENT: These CPG aim to help physicians in their decision making. The protocolized application of wellproven measurements reduces the variation in clinical practice and improves results.

Acute abdomen secondary to complete tubular colonic duplication.

We report the case of a 6-month-old infant who presented with a complete duplication of the large intestine, debuting clinically with acute abdomen and severe metabolic disorders. We discuss the pathogenesis and morphology of the lesions, diagnostic difficulties and peculiarities of surgical treatment.

Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-men who have sex with men be recommended?

INTRODUCTION Sexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition (1). It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) (2). The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV-MSM and the related factors. MATERIALS AND METHODS Prospective study of a cohort of asymptomatic HIV-MSM with follow-up in Malaga (southern Spain) during October 2012-May 2014. Patients with an opportunistic event or who received active antibiotic therapy for CT and/or NG in the previous month were excluded. All of them completed a questionnaire about sexual behaviour, barrier methods and recreational drugs use. Demographical, epidemiological, clinical, analytical and therapeutic data were also collected. Pharyngeal and rectal swabs, and urine samples were collected to be tested for CT and NG by nucleic acid amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) (3). STATISTICS ANALYSIS SPSS 17.0. RESULTS 255 patients were asked to participate and 248 of them accepted. Median age was 37.7 (30.6-46.3) years, median time since HIV diagnosis was 47.7 (10.5-104.1) months, and median CD4 cells count was 607 (440-824) cell/µL. There were 195 (78.6%) patients on antiretroviral therapy; 81.5% of them had undetectable viral load. 80.5% of the patients had a past history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients. Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients were co-infected by CT and NG: one with CT in urine and both in rectum, another with CT in urine and rectum and NG in pharynx. One patient presented CT in pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2-7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or recreational drugs use. CONCLUSIONS STI screening had a great acceptance in this population. There was a high prevalence of asymptomatic CT and/or NG infections. Rectum sample was the most effective one. Viral suppression could protect from these STI. Screening should be recommended in HIV-MSM.

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study.

INTRODUCTION Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients' well-being, assessed by several validated measures. METHODS Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. RESULTS Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001. CONCLUSIONS Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.

The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism.

Oleoylethanolamide (OEA) is an agonist of the peroxisome proliferator-activated receptor α (PPARα) and has been described to exhibit neuroprotective properties when administered locally in animal models of several neurological disorder models, including stroke and Parkinson's disease. However, there is little information regarding the effectiveness of systemic administration of OEA on Parkinson's disease. In the present study, OEA-mediated neuroprotection has been tested on in vivo and in vitro models of 6-hydroxydopamine (6-OH-DA)-induced degeneration. The in vivo model was based on the intrastriatal infusion of the neurotoxin 6-OH-DA, which generates Parkinsonian symptoms. Rats were treated 2 h before and after the 6-OH-DA treatment with systemic OEA (0.5, 1, and 5 mg/kg). The Parkinsonian symptoms were evaluated at 1 and 4 wk after the development of lesions. The functional status of the nigrostriatal system was studied through tyrosine-hydroxylase (TH) and hemeoxygenase-1 (HO-1, oxidation marker) immunostaining as well as by monitoring the synaptophysin content. In vitro cell cultures were also treated with OEA and 6-OH-DA. As expected, our results revealed 6-OH-DA induced neurotoxicity and behavioural deficits; however, these alterations were less severe in the animals treated with the highest dose of OEA (5 mg/kg). 6-OH-DA administration significantly reduced the striatal TH-immunoreactivity (ir) density, synaptophysin expression, and the number of nigral TH-ir neurons. Moreover, 6-OH-DA enhanced striatal HO-1 content, which was blocked by OEA (5 mg/kg). In vitro, 0.5 and 1 μM of OEA exerted significant neuroprotection on cultured nigral neurons. These effects were abolished after blocking PPARα with the selective antagonist GW6471. In conclusion, systemic OEA protects the nigrostriatal circuit from 6-OH-DA-induced neurotoxicity through a PPARα-dependent mechanism.

New clinical practice guideline on enteral feeding in very low birth weight infants; first part.

The nutrition of very low birth weight (VLBW) infants is aimed at promoting a similar growth to that occurring in the uterus. However, in practice this is difficult to achieve and extrauterine growth restriction is frequent. The current tendency is to avoid this restriction by means of early parenteral and enteral nutrition. Nonetheless, uncertainty about many of the practices related with nutrition has resulted in a great variation in the way it is undertaken. In 2009 and 2011 in our hospital there was an unexpected increase in necrotizing enterocolitis. To check to see whether our nutrition policy was involved, we undertook a systematic review and drew up clinical practice guidelines (CPG) about enteral feeding in VLBW infants. New considerations about the duration of the fortification and the use of probiotics have led to an update of these CPG. METHODS: A total of 21 clinical questions were designed dealing with the type of milk, starting age, mode of administration, rate and volume of the increments, fortification, use of probiotics and protocol. After conducting a systematic search of the available evidence, the information was contrasted and summarized in order to draw up the recommendations. The quality of the evidence and the strength of the recommendations were determined from the SIGN scale. COMMENT: These CPG aim to help physicians in their decision making. The protocolized application of well-proven measurements reduces the variation in clinical practice and improves results.

The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males.

OBJECTIVES To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). METHODS This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. RESULTS Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). CONCLUSIONS When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV-positive patients. HPV suppression with treatment protects against the appearance of HSIL.

Capsule endoscopy in the small bowel Crohn's disease.

CD is a chronic inflammatory disorder associated to mucosal and transmural inflammation of the bowel wall. It is well known that CD can affect the entire gastrointestinal. Therefore, ileocolonoscopy and biopsies of the terminal ileum as well as of each colonic segment to look for microscopic evidence of CD are the first-line procedures to establish the diagnosis. However, it has been observed that up to 30% of the patients have only small bowel involvement. Evaluation of the small bowel has been made with radiological procedures, barium radiography, and abdominal computed tomography or by ileocolonoscopy or enteroscopy, but they have many recognized limitations. CE is undoubtedly a very useful diagnostic tool proposed to observe small-bowel lesions undetectable by conventional endoscopy or radiologic studies. We review different studies that have been published reporting the use of CE in suspected and evaluation of the extension or the recurrence in CD and also its use in pediatric population and its complications.

Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile.

Substantial proportion of Crohn's disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276* G/rs3014866* C/rs724781* C/rs3006488* A; P = 0.05); G0S2 (rs4844486* A/rs1473683* T; P = 0.15); TNFAIP6 (rs11677200* C/rs2342910* A/rs3755480* G/rs10432475* A; P = 0.10); and IL11 (rs1126760* C/rs1042506* G; P = 0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway.

Metastatic Crohn’s disease.

A 51 year old man presented to the department of Dermatology, Regional University Hospital of Málaga, Málaga, Spain, in May 2013, with remarkable lesions on the perineal, perianal and gluteal regions reaching the top of the lower limbs, which he had first noted two years earlier. The physical examination revealed large erythematous-brownish plaques with a granulomatous appearance, polypoid lesions and areas of ulceration. In addition, Mycobacterium tuberculosis culture and serum QuantiFERON® TB Gold were negative. The patient was diagnosed to have metastatic Crohn’s disease which is an uncommon complication of Crohn’s disease.

Role of double-balloon enteroscopy in malignant small bowel tumors.

AIMTo assess the double-balloon enteroscopy (DBE) role in malignant small bowel tumors (MSBT). METHODS This is a retrospective descriptive study performed in a single center. All consecutive patients who underwent a DBE with final diagnosis of a malignant neoplasm from 2004 to 2014 in our referral center were included. Patient demographic and clinical pathological characteristics were recorded and reviewed. MSBT diagnosis was achieved either by DBE directed biopsy with multiple tissue sampling, endoscopic findings or histological analysis of surgical specimen. We have analyzed double-balloon enteroscopy impact in outcome and clinical course of these patients. RESULTS Of 627 patients, 28 (4.5%) (mean age = 60 ± 17.3 years) underwent 30 procedures (25 anterograde, 5 retrograde) and were diagnosed of a malignant tumor. Patients presented with obscure gastrointestinal bleeding (n = 19, 67.9%), occlusion syndrome (n = 7, 25%) and diarrhea (n = 1, 3.6%). They were diagnosed by DBE biopsy (n = 18, 64.3%), histological analysis of surgical specimen (n = 7, 25%) and unequivocal endoscopic findings (n = 2, 7.1%). Gastrointestinal stromal tumor (n = 8, 28.6%), adenocarcinoma (n = 7, 25%), lymphoma (n = 4, 14.3%), neuroendocrine tumor (n = 4, 14.3%), metastatic (n = 3, 10.7%) and Kaposi sarcoma (n = 1, 3.6%) were identified. DBE modified outcome in 7 cases (25%), delaying or avoiding emergency surgery (n = 3), modifying surgery approach (n = 2) and indicating emergency SB partial resection instead of elective approach (n = 2). CONCLUSION DBE may be critical in the management of MSBT providing additional information that may be decisive in the clinical course of these patients.

Phytobezoar by aloe vera as long term complication after oesophagectomy resolved using cellulase.

Bezoars are uncommon diseases caused by the presence of indigestible mass of strange material in the gastrointestinal tract. Gold-standard treatment remains unclear and there are not clinical guidelines to follow. We present a very rare case of 53-year-old man suffering phytobezoar in a gastroplasty after oesophagectomy due to aloe vera ingestion as natural medicine. Finally it was solved with cellulase. Therefore, this is a scarcely complication after esophagectomy. Cellulase is a very good option to treat phytobezoar avoiding reintervention in this kind of patient.

Phytobezoar by aloe vera as long term complication after oesophagectomy resolved using cellulase.

Bezoars are uncommon diseases caused by the presence of indigestible mass of strange material in the gastrointestinal tract. Gold-standard treatment remains unclear and there are not clinical guidelines to follow. We present a very rare case of 53-year-old man suffering phytobezoar in a gastroplasty after oesophagectomy due to aloe vera ingestion as natural medicine. Finally it was solved with cellulase. Therefore, this is a scarcely complication after esophagectomy. Cellulase is a very good option to treat phytobezoar avoiding reintervention in this kind of patient.