Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature.

BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with dispiriting survival data. Immunotherapy is a promising approach to many cancer types, but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment. We describe a case of metastatic PDAC effectively treated with pembrolizumab. CASE SUMMARY: We report the case of a 67-year-old woman with unresectable locally advanced PDAC, treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine. At nine months, pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary, confirmed by left lung biopsy. Systemic immunotherapy was then initiated with pembrolizumab, an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types. The patient showed a complete metabolic response that was maintained throughout the treatment. The patient continues to be disease-free at 5.6 years since the start of immunotherapy. CONCLUSION: These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC. To our knowledge, this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery. Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.

Performance of a vaginal self-collection device versus clinician collected cervical samples for the detection of high-risk human papillomavirus.

Objective: Screening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. Methods: A cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. Results: Overall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. Conclusion: The Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

Circulating tumor cells in cancer-risk populations as a cancer interception tool.

Cancer interception (CI) is a new approach to cancer prevention and treatment in a cancer-risk population that aims to detect and treat pre-tumoral stages. It has several potential advantages over traditional cancer diagnosis and monitoring methods because it is non-invasive, making it less painful and risky than conventional biopsy procedures. The circulating tumor cells (CTCs), liquid biopsy family members, are essential for the CI approach; then, the liquid biopsy (LB) is used as a CI tool. LB can be performed frequently because of its easy sampling and early pathological stages, which allow repeated non-invasive monitoring of cancer progression and response to treatment. CTCs have been found in the bloodstream of several types of cancer patients, including in early-stage cancer and premalignant lesions, suggesting a tumor development role in cancer's early stages. This chapter will present foundational scientific studies addressing CI and the clinical impact of CTC screening in a population at risk for cancer.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study / Factores de riesgo en dispepsia funcional y enfermedad por reflujo gastroesofágico: un estudio transversal

Background: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. Methods: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. Results: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. Conclusions: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.(AU)

Antecedentes: Existen datos controvertidos sobre los factores de riesgo asociados a la enfermedad por reflujo gastroesofágico (ERGE) y la dispepsia funcional (DF). Pocos estudios han evaluado la relación entre ansiedad/depresión y los diferentes fenotipos de la DF (criterios Roma IV) y de la ERGE (erosiva [EE] y no erosiva [NERD]). Nuestro objetivo fue valorar la asociación entre diferentes factores epidemiológicos y comorbilidades y los fenotipos de la ERGE, la DF y sus síndromes, y su relación con la ansiedad/depresión. Métodos: Se seleccionaron 338 pacientes entre 357 remitidos para estudio endoscópico en 3 hospitales terciarios. Cada uno fue entrevistado individualmente y completó 3 cuestionarios validados: GERD-Q, Roma IV y HADS. Resultados: Cuarenta y cinco de los 338 pacientes fueron controles. Se clasificaron 198/58,6% como ERGE, 81/24,0% como EE (49/14,5% sintomática y 32/9,5% asintomática), 117/34,6% como NERD y 176/52,1% como DF (43/12,7% síndrome de dolor epigástrico, 36/10,7% síndrome de molestias posprandiales y 97/28,7% solapamiento epigastralgia-molestias posprandiales). Ochenta y uno solapaban ERGE-DF. El análisis multivariante encontró las siguientes asociaciones significativas: edad en NERD y DF; sexo en EE, EE asintomática y DF; IMC en NERD y DF; alcohol en EE; ansiedad/depresión en DF; toma de antagonistas del calcio en EE e inhaladores en DF. Al comparar el grupo control vs. diferentes grupos/subgrupos encontramos significativamente más ansiedad en NERD, solapamiento DF-ERGE, DF y todos sus síndromes Roma IV; más depresión en DF, solapamientos epigastralgia-molestias posprandiales y ERGE-DF; y más ansiedad+depresión en NERD, DF y solapamientos epigastralgia-molestias posprandiales y ERGE-DF. Conclusiones: La DF y la NERD comparten factores de riesgo demográficos y psicopatológicos, lo que evidencia que forman parte de un mismo espectro fisiopatológico...(AU)

Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor.

The World Health Organization's tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RT-qPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

microRNAs signature in relapse metastasis and de novo metastasis of breast cancer. A systematic review.

miRNAs have been widely identified as important players in cancer development and progression. Metastasis in breast cancer can occur as relapse of a treated primary tumour or at the time of diagnosis of the tumour. The aim of this review is to show if both metastasis are different molecular entities characterised by different miRNA signatures that could be studied as specific biomarkers for each entity. For this, we systematically searched the PubMed, Scopus and Web of Science databases. After searching and reviewing the literature, a total of 30 records were included in this review. Results showed a genetic signature including a total of 5 upregulated miRNAs in metastasis compared with early stages. Of them, miR-23b and miR-200c were exclusively present in relapse metastasis. Finally, we proposed a molecular signature for future studies that can be used as a complementary tool at clinical trials for the diagnosis and characterization of metastasis.

HPV Infection of the Oropharyngeal, Genital and Anal Mucosa and Associated Dysplasia in People Living with HIV.

BACKGROUND: The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors. MATERIAL AND METHODS: This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study. RESULTS: The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with Treponema pallidum (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)). CONCLUSIONS: The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.

Role of Low-Risk HPV PCR Monoinfection in Screening for HSIL and Anal Cancer in Men Who Have Sex with Men Living with HIV.

To determine the value of low-risk human papillomavirus (HPV) PCR to screen for "high-grade anal squamous intraepithelial lesion and anal cancer" (HSIL-plus), rate of patients with low-grade anal squamous intraepithelial lesion (LSIL) progressing to HSIL-plus, and progression-related factors. Prospective, longitudinal study of consecutive MSM-LHIV attended between May 2010 and December 2021 and followed for 43 months (IQR: 12-76). HIV-related variables were gathered at baseline, performing anal cytology for HPV detection/genotyping, thin-layer cytological study, and high-resolution anoscopy (HRA). Follow-up was annual when HRA was normal or LSIL, and post-treatment in cases of HSIL-plus, re-evaluating sexual behavior, viral-immunological status, and HPV infection of anal mucosa. The 493 participants had mean age of 36 years: CD4 nadir < 200 cells/uL in 23.1%, virological failure in 4.1%, and tetravalent HPV vaccine > 5 years earlier in 15%. HSIL-plus was ruled out in patients with monoinfection by low-risk HPV genotype and normal cytology (100% sensitivity, 91.9% specificity, PPV 2.9%, and NPV 100%). Progression from LISL to HSIL-plus occurred in 4.27% of patients within 12 months (IQR: 12-12): risk factors were acquisition of high-risk (HR: 4.15; 95% CI: 1.14-15.03) and low-risk (HR: 3.68 95% CI: 1.04-12.94) HPV genotypes, specifically genotype 6 (HR: 4.47, 95% CI: 1.34-14.91), and history of AIDS (HR: 5.81 95% CI: 1.78-18.92). Monoinfection by LR-HPV genotypes in patients with normal cytology is not associated with anal cancer or precursor lesions. Progression from LSIL to HSIL-plus, observed in <5% of patients, was related to acquisition of HR and LR HPV genotypes, especially 6, and a history of AIDS.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study.

BACKGROUND: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. METHODS: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. RESULTS: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. CONCLUSIONS: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.

Anorectal malignant melanoma, a diagnostic challenge.

Malignant anorectal melanoma is an extremely rare cause of rectal neoplasia, accounting for less than 1% of all melanomas and about 4% of all malignant colorectal neoplasms. We present the endoscopic and pathological images of a case in our clinical practice.

Generation of a H9 Clonal Cell Line With Inducible Expression of NUP98-KDM5A Fusion Gene in the AAVS1 Safe Harbor Locus.

Pediatric acute myeloid leukemia (AML) is a rare and heterogeneous disease that remains the major cause of mortality in children with leukemia. To improve the outcome of pediatric AML we need to gain knowledge on the biological bases of this disease. NUP98-KDM5A (NK5A) fusion protein is present in a particular subgroup of young pediatric patients with poor outcome. We report the generation and characterization of human Embryonic Stem Cell (hESC) clonal lines with inducible expression of NK5A. Temporal control of NK5A expression during hematopoietic differentiation from hESC will be critical for elucidating its participation during the leukemogenic process.

Accuracy in optical diagnosis for polyps between 5 and 15 mm and its implications on surveillance. A prospective, multicenter study. (POPS study).

BACKGROUND AND AIMS: Polyps histology and diameter up to 1 cm determine whether a patient needs a colonoscopy after 3 years or less, or far ahead. Endoscopists' and pathologists' size estimations can be imprecise. Our aim was to assess endoscopist ability to correctly recommend surveillance colonoscopies for patients with polyps around the 10 mm threshold, based on its endoscopic sizing and optical diagnosis by NBI. METHODS: NBI-assisted diagnosis and endoscopist estimation of polyp size were compared with reference standard, considering this as the post resection polyp measurements by the nurse assistant and the pathologic results, in a prospective, multicenter, real life study, that recruited adults undergoing colonoscopy in five hospitals. By comparing the endoscopic and pathologist size estimation, with polyps' measurement after resection, and optical and histological diagnoses in patients with polyps between 5 and 15 mm, sensitivity was assessed at the patient level by means of two characteristics: the presence of adenoma, and the surveillance interval. Surveillance intervals were established by the endoscopist, based on optical diagnosis, and by another gastroenterologist, grounded on the pathologic report. Determinants of accuracy were explored at the polyp level. RESULTS: 532 polyps were resected in 451 patients. Size estimation was more precise for the endoscopist. Endoscopist sensitivity for the presence of adenoma or carcinoma was 98.7%. Considering the presence of high-grade dysplasia or cancer, sensitivity was 82.6% for the endoscopic optical diagnosis. Sensitivity for a correct 3-year surveillance interval was 91.5%, specificity 82.3%, with a PPV of 93.2% and NPV of 78.5% for the endoscopist. 6.51% of patients would have had their follow-up colonoscopy delayed, whereas 22 (4.8%) would have it been performed earlier, had endoscopist recommendations been followed. CONCLUSION: Our study observes that NBI optical diagnosis can be recommended in routine practice to establish surveillance intervals for polyps between 5 and 15 mm. CLINICAL TRIALS REGISTRATION NUMBER: NCT04232176.

Proctitis in men having sex with men: anything else you can think of?

We report two cases of proctitis in men having sex with men.

Strongyloides stercoralis with Gastroduodenal Involvement and Complicated with SIADH: An Unusual Diagnosis to Consider in Immunosuppressed Patients with Hyperemesis and Eosinophilia.

Strongyloides stercoralis is an intestinal nematode that colonizes and reproduces in the upper small intestinal mucosa. Infection in immunocompetent hosts is self-limited but in immunocompromised patients it can be complicated and cause hyperinfection. We present a 60-year-old female who was admitted due to an exacerbation of acquired thrombotic thrombocytopenic purpura requiring high doses of corticosteroids. The patient began to experience persistent pyrosis, nausea, vomiting, and oral intolerance. She was di-agnosed with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Upper endoscopy was performed and showed esophageal, gastric, and duodenal mucosa with edema and erythema. Moreover, there were superficial erosions and thickened folds in duodenum. Gastric and duodenal biopsies were taken. Abdominal computed tomography and magnetic enteroresonance displayed duodenal dilation and inflammatory changes. The histological study of biopsies showed colonization by S. stercolaris in the antrum and duodenum. S. stercolaris is a human parasite that is endemic in tropical, subtropical, and temperate regions. Its lifecycle is complex because it completes its entire cycle within the human host; it penetrates the skin, migrates to the lungs, and reach the gastrointestinal tract. The most affected site is the duodenum and upper jejunum. The lifecycle includes autoinfection through the intestinal mucosa or perianal skin, especially in immunocompromised hosts. Immunossuppression can lead to hyperinfection syndrome and disseminated disease. However, involvement of the stomach has relatively rarely been reported. SIADH has been related to systemic hyperinfection, although the mechanism is not clear. The relatively nonspecific clinical and imaging features and the low sensitivity of routine parasite tests make the diagnosis challenging and delayed.

Strongyloides stercoralis é um nematódo intestinal que coloniza e se reproduz na mucosa do intestino delgado proximal. A infeção em hospedeiros imunocompetentes é auto-limitada mas em doentes imunocomprometidos pode ter um curso complicado e causar hiperinfeção. Apresentamos um caso de uma mulher de 60 anos que é admitida devido a uma exacerbação de uma púrpura trombocitopénica trombótica adquirida com necessidade de altas doses de corticoides. A doente inicia quadro de pirose persistente, náuseas, vómitos e intolerância alimentar. Faz-se o diagnóstico de síndrome de secreção inapropriada de hormona antidiurética (SIADH). A endoscopia digestiva alta evidencia mucosa gástrica e duodenal com edema e eritema, para além de erosões e pregas espessadas duodenais. O TC e a enteroRMN mostram dilatação duodenal e alterações inflamatórias. A histologia mostra S. stercoralis a colonizar a mucosa do antro e duodeno. O S. stercolaris é um parasita humano, endémico em regiões tropicais e subtropicais. Tem um ciclo de vida complexo já que completa o seu ciclo todo dentro do organismo humano: penetra pela pele, migra para os pulmões e atinge o trato gastrointestinal. Os sítios mais afetados são o duodeno e o jejuno proximal. O ciclo de vida envolve autoinfeção na mucosa intestinal ou pele perianal, especialmente em doentes imunocomprometidos, com a imunodepressão podendo levar a síndrome de hiperinfeção e doença disseminada. Contudo, o envolvimento gástrico é raramente descrito. O SIADH tem sido relacionado com o síndrome de hiperinfeção, contudo, o seu mecanismo não é claro. O relativo inespecífico quadro clínico e alterações imagiológicas, assim como a baixa sensibilidade dos testes de parasitas de rotina atrasam e fazem o diagnóstico desafiante.

Risk factors for ≥high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments.

BACKGROUND: The objective of this study in MSM living with HIV was to determine the incidence of HSIL and ASCC, related factors, and the response to treatment. PATIENTS AND METHODS: Data were gathered in 405 consecutive HIV-infected MSM (May 2010-December 2018) at baseline and annually on: sexual behavior, anal cytology, and HPV PCR and/or high-resolution anoscopy results. They could choose mucosectomy with electric scalpel (from May 2010) or self-administration of 5% imiquimod 3 times weekly for 16 weeks (from November 2013). A multivariate logistic regression model was developed for ≥HSIL-related factors using a step-wise approach to select variables, with a significance level of 0.05 for entry and 0.10 for exit, applying the Hosmer-Lemeshow test to assess the goodness of fit. RESULTS: The study included 405 patients with a mean age of 36.2 years; 56.7% had bachelor´s degree, and 52.8% were smokers. They had a mean of 1 (IQR 1-7) sexual partner in the previous 12 months, median time since HIV diagnosis of 2 years, and mean CD4 nadir of 367.9 cells/uL; 86.7% were receiving ART, the mean CD4 level was 689.6 cells/uL, mean CD4/CD8 ratio was 0.77, and 85.9% of patients were undetectable. Incidence rates were 30.86/1,000 patient-years for ≥high squamous intraepithelial lesion (HSIL) and 81.22/100,000 for anal squamous cell carcinoma (ASCC). The ≥HSIL incidence significantly decreased from 42.9% (9/21) in 2010 to 4.1% (10/254) in 2018 (p = 0.034). ≥HSIL risk factors were infection with HPV 11 (OR 3.81; 95%CI 1.76-8.24), HPV 16 (OR 2.69, 95%CI 1.22-5.99), HPV 18 (OR 2.73, 95%CI 1.01-7.36), HPV 53 (OR 2.97, 95%CI 1.002-8.79); HPV 61 (OR 11.88, 95%CI 3.67-38.53); HPV 68 (OR 2.44, CI 95% 1.03-5.8); low CD4 nadir (OR1.002; 95%CI 1-1.004) and history of AIDS (OR 2.373, CI 95% 1.009-5.577). Among HSIL-positive patients, the response rate was higher after imiquimod than after surgical excision (96.7% vs 73.3%, p = 0.009) and there were fewer re-treatments (2.7% vs 23.4%, p = 0.02) and adverse events (2.7% vs 100%, p = 0.046); none developed ASCC. CONCLUSIONS: HSIL screening and treatment programs reduce the incidence of HSIL, which is related to chronic HPV infection and poor immunological status. Self-administration of 5% imiquimod as first-line treatment of HSIL is more effective than surgery in HIV+ MSM.

Effectiveness of the Quadrivalent HPV Vaccine in Preventing Anal ≥ HSILs in a Spanish Population of HIV+ MSM Aged > 26 Years.

Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM, and to study the immunogenicity of the vaccine and risk factors for ≥ HSILs. This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. A vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope). The study included 129 patients (mean age of 38.8 years, 40 [31%] with a history of AIDS, 119 [92.2%] receiving ART, and 4 [3.3%] with virological failure), 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p = 0.98) or EAGL (11.1 vs. 6.8%, p = 0.4) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p = 0.047). A between-arm difference (p = 0.0001) in antibodies against qHPV vaccine genotypes was observed at 7 months (76.9% in vaccine arm vs. 30.2% in placebo arm), 12 months (68.1% vs. 26.5%), 24 months (75% vs. 32.5%), 36 months (90% vs. 24.4%), and 48 months (87.2% vs. 30%). Finally, the factor associated with the risk of anal ≥ HSIL onset during the four-year follow-up was the receipt of the last dose of the vaccine less than 6 months earlier in comparison to those vaccinated for a longer period (82.4% vs. 17.6% (OR 0.869 [95% CI, 0.825-0.917]). Vaccine and placebo arms did not significantly differ in ≥ HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier.

Intestinal spirochetosis: normal intestinal flora or etiology of diarrhea?

A 22-year-old male began with up to 12 loose stools per day, with mucus and no blood. They were present for two months, even during the night. Moreover, he complained of abdominal pain and weight loss. There were no findings on the blood tests. Fecal calprotectin was 225 µg/g. Stool microbiology tests were negative. Ileocolonoscopy displayed normal mucosa but the histological study of the biopsies showed Treponemas genus Brachispira. The patient had a sexual risk behavior. Treatment with metronidazole was initiated with clinical improvement.

Diagnóstico mediante EBUS-TBNA de reacción granulomatosa secundaria a Surgicel en adenopatía mediastínica / EBUS-TBNA diagnosis of a granulomatous reaction to Surgicel in mediastinal adenopathy

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