An unusual case of endotipsitis: persistent infection and migration to the right atrium of a transjugular intrahepatic portosystemic shunt (TIPS).

Endotipsitis is an underdiagnosed entity mainly because it requires a high initial level of suspicion. It should be considered in the differential diagnosis of persistent bacteremia in the cirrhotic patient with TIPS. Most cases are treated conservatively with a long-term antibiotherapy, due to the impossibility of surgical removal of the TIPS, except in a liver transplant or autopsy. The patient we present had endotipsitis that manifested as persistent bacteremia with thrombosis of the TIPS. Initially, conservative management with intravenous antibiotherapy was performed; however, due to mechanical complications caused by migration of the original endoprosthesis, it was decided to perform surgery.

Microbiome-derived cobalamin and succinyl-CoA as biomarkers for improved screening of anal cancer.

Human papillomavirus can cause preinvasive, high-grade squamous intraepithelial lesions (HSILs) as precursors to cancer in the anogenital area, and the microbiome is suggested to be a contributing factor. Men who have sex with men (MSM) living with human immunodeficiency virus (HIV) have a high risk of anal cancer, but current screening strategies for HSIL detection lack specificity. Here, we investigated the anal microbiome to improve HSIL screening. We enrolled participants living with HIV, divided into a discovery (n = 167) and validation cohort (n = 46), and who were predominantly (93.9%) cisgender MSM undergoing HSIL screening with high-resolution anoscopy and anal biopsies. We identified no microbiome composition signatures associated with HSILs, but elevated levels of microbiome-encoded proteins producing succinyl coenzyme A and cobalamin were significantly associated with HSILs in both cohorts. Measurement of these candidate biomarkers alone in anal cytobrushes outperformed anal cytology as a diagnostic indicator for HSILs, increasing the sensitivity from 91.2% to 96.6%, the specificity from 34.1% to 81.8%, and reclassifying 82% of false-positive results as true negatives. We propose that these two microbiome-derived biomarkers may improve the current strategy of anal cancer screening.

Increased Prevalence of Symptomatic Human Intestinal Spirochetosis in MSM with High-Risk Sexual Behavior in a Cohort of 165 Individuals.

Human intestinal spirochetosis (HIS) can cause gastrointestinal symptoms, although asymptomatic infections have been described. Individuals from low-income countries, people living with HIV, and men who have sex with men (MSM) show increased risk. A retrospective review of all patients diagnosed with HIS (n = 165) between January 2013 and October 2020 at a tertiary hospital in Madrid, Spain, was performed to assess risk factors for symptomatic HIS, symptoms, and response to treatment. Most patients were male (n = 156; 94.5%), 86.7% were MSM, and 23.5% practiced chemsex, of whom most were symptomatic (p = 0.039). Most patients (78.4%) reported unprotected oral-anal intercourse. A total of 124 (81.1%) were symptomatic; diarrhea was the most common complaint (68.3%). Multivariable regression showed increased odds of symptoms associated with age under 41 (odds ratio 5.44, 95% CI 1.87-15.88; p = 0.002). Colonoscopy was normal in 153 (92.7%). Furthermore, 66.7% presented previous or concomitant sexually transmitted diseases (STDs). Among the patients, 102 underwent testing for other gastrointestinal pathogens, with positive results in 20 (19.6%). All symptomatic patients without concomitant gastrointestinal infection presenting improvement on follow-up (42 of 53) had received either metronidazole or doxycycline (p = 0.049). HIS should be considered as a cause of chronic diarrhea in MSM with high-risk sexual behavior after other causes have been ruled out; treatment with metronidazole is recommended. Coinfection with other STDs is common.

48-Week effectiveness and tolerability of dolutegravir (DTG) + lamivudine (3TC) in antiretroviral-naïve adults living with HIV: A multicenter real-life cohort.

BACKGROUND: The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. METHODS: A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. RESULTS: 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. CONCLUSIONS: In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

Changes in Quality of Sleep, Mood, and Other Neuropsychiatric Symptoms After Switching Dolutegravir/Lamivudine/Abacavir to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Randomized Study of People With Human Immunodeficiency Virus With Poor Sleep Quality: GESIDA 10418.

Background: Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods: This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results: We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions: In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

Initiation of antiretroviral therapy in treatment-naive adults with HIV infection at the first specialist appointment.

BACKGROUND: Fast initiation of ART has been associated with higher rates of retention in HIV care and viral suppression at 48 weeks and with lower mortality rates. However, scarce evidence exists in our setting, where diagnosis and treatment are carried out in different contexts. METHODS: An observational retrospective study evaluating efficacy and safety of ART prescribed at the first specialist appointment, without baseline laboratory data, in a tertiary hospital in downtown Madrid. Individuals with a new diagnosis of HIV infection who initiated treatment at their first appointment with an infectious diseases specialist before receiving baseline laboratory results were included, irrespective of the ART regimen chosen. RESULTS: One hundred and eight participants were included. The majority (99.1%) were MSM who had acquired infection during sexual intercourse. The efficacy of ART, without baseline laboratory results at the time of initiation, was 85.2% (92/108) in the ITT analysis and 91.7% (99/108) in the treatment-related discontinuation equals failure analysis. All but nine patients presented an undetectable viral load (<50 copies/mL) at 48 weeks from starting ART. No serious adverse effects associated with the strategy were observed. In total, 101 participants continued care at 48 weeks with retention in HIV care rate of 93.5% (101/108). CONCLUSIONS: Initiating ART at the first available opportunity without baseline laboratory data does not reduce efficacy or safety of ART and achieves rapid virological control with high rates of retention in HIV care.

Spectrum of Syphilitic Chorioretinitis and Its Evolution Based on Multimodal Imaging.

PURPOSE: To describe the different phenotypes of syphilitic chorioretinitis (SCR) and its clinical features in multimodal imaging (MI). METHODS: Complete ophthalmological examination and MI including spectral domain optic coherence tomography (SD-OCT), fundus autofluorescence (FAF) and fluorescein angiography (FA) were performed at diagnosis and during follow-up in patients diagnosed with SCR. RESULTS: 17 eyes of 10 patients were included. Clinical phenotypes included acute syphilitic posterior placoid chorioretinopathy (ASPPC), syphilitic outer retinitis (SOR) and punctate inner retinitis (PIR). Disruption of outer retinal layers were visible in all patients in SD-OCT. Inner retinal layers were only affected in PIR. FAF revealed macular hyperautofluorescence in all patients. FA showed maintained hyperfluorescence in ASPPC and SOR. CONCLUSIONS: ASPPC, SOR and PIR are different phenotypes of syphilitic chorioretinitis and present common features in SD-OCT and FAF. MI provides useful information to help the clinician during diagnosis and follow-up of these entities.

Bone Deleterious Effects of Different NRTIs in Treatment-naïve HIV Patients After 12 and 48 Weeks of Treatment.

BACKGROUND: Bone alterations have been observed in the course of HIV infection, characterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-naïve HIV patients. METHODS: We conducted a prospective study in naïve HIV-infected adults (under 50 years), separated into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment. RESULTS: Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/µL. At week 12 after starting treatment, both TDF [increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003)] and TAF [increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049)] presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences. CONCLUSION: Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks.

HIV Treatment with the Two-Drug Regimen Dolutegravir Plus Lamivudine in Real-world Clinical Practice: A Systematic Literature Review.

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE®, Embase®, PubMed, Cochrane library, and relevant international conference proceedings from 2013 to 2020. Qualitative synthesis of virologic suppression at Week 48, treatment-emergent resistance, discontinuation rates, and comorbidities was undertaken, with no statistical analyses conducted. Linked publications and potential for duplication in reporting of outcomes for cohorts and populations were identified, and the publication reporting the highest number of PWH receiving dolutegravir plus lamivudine was included in the analysis. Thirty-four studies reporting on cohorts of PWH not suspected to be linked or to include duplicate data receiving dolutegravir plus lamivudine were identified (N = 5017). Of 3744 virologically suppressed PWH who switched to dolutegravir plus lamivudine, 603 (16%) reported history of virologic failure. Nineteen studies included effectiveness data (n = 3558), four of which included data from treatment-naive PWH (n = 69). In studies with > 100 PWH, high rates of virologic suppression (Week 48, 97-100%) were maintained with dolutegravir plus lamivudine, with low rates of virologic failure (0-3.3 per 100 person-years of follow-up); one instance of emergent integrase strand transfer inhibitor resistance was reported in a complex treatment-experienced individual. Rates of discontinuation due to adverse events were low and consistent with previously observed trial data. Dolutegravir plus lamivudine minimally impacted renal function and had minimal impact on or improved lipid profiles and bone mineral density. This systematic review demonstrates that effectiveness and safety of dolutegravir plus lamivudine in clinical practice support data from randomized controlled trials with regard to high rates of virologic response, low rates of discontinuation, and a high barrier to resistance.

Compassionate use of tocilizumab in severe SARS-CoV2 pneumonia.

INTRODUCTION: Tocilizumab (TCZ) is an interleukin-6 receptor antagonist, which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), which aims to ameliorate the cytokine release syndrome (CRS) induced acute respiratory distress syndrome (ARDS). However, there are no consistent data about who might benefit most from it. METHODS: We administered TCZ on a compassionate-use basis to patients with SSP who were hospitalized (excluding intensive care and intubated cases) and who required oxygen support to have a saturation >93%. The primary endpoint was intubation or death after 24 h of its administration. Patients received at least one dose of 400 mg intravenous TCZ from March 8, 2020 to April 20, 2020. RESULTS: A total of 207 patients were studied and 186 analyzed. The mean age was 65 years and 68% were male patients. A coexisting condition was present in 68% of cases. Prognostic factors of death were older age, higher IL-6, d-dimer and high-sensitivity C-reactive protein (HSCRP), lower total lymphocytes, and severe disease that requires additional oxygen support. The primary endpoint (intubation or death) was significantly worst (37% vs 13%, p < 0·001) in those receiving the drug when the oxygen support was high (FiO2 >0.5%). CONCLUSIONS: TCZ is well tolerated in patients with SSP, but it has a limited effect on the evolution of cases with high oxygen support needs.

Poblaciones diana para el cribado del virus del papiloma humano (VPH) y lesiones precursoras de carcinoma anal; resultados de un estudio piloto en varones VIH con factores sexuales de riesgo / Target population for the screening of human papillomavirus (HPV) and anal carcinoma precursor lesions - Results from a pilot study in HIV-infected males with sexual risk factors

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Target population for the screening of human papillomavirus (HPV) and anal carcinoma precursor lesions - Results from a pilot study in HIV-infected males with sexual risk factors.

Ninety-five percent of precursor lesions -high-grade squamous intraepithelial lesions (HSIL) and anal intraepithelial neoplasms (AIN)- and their progression to squamous anal cancer (AC) are induced by high-risk HPV (HR-HPV) serotypes 16 and 18. Their incidence is higher particularly in HIV-infected male patients who have sex with other males (HIV-MSM) (144/100,000/patients/year).

Primary effusion lymphoma involving cerebrospinal fluid, deep cervical lymph nodes and adenoids. Report of a case supporting the lymphatic connection between brain and lymph nodes.

We describe an unusual presentation of primary effusion lymphoma in CSF of a 45-year-old HIV-positive man, with no evidence of involvement of pleural, peritoneal or pericardial cavities. Cytologic examination and flow cytometric analysis suggested the diagnosis, eventually made in an excised deep cervical lymph node, in which the neoplastic cells involved selectively the sinuses. This case represents the fifth reported example of CSF involvement by this type of lymphoma, and supports the alleged connection between CSF and cervical lymph nodes via lymphatic vessels. Interestingly, review of an adenoidectomy specimen obtained 9 months before presentation for nonspecific complaints showed rare clusters of neoplastic cells involving surface epithelium and chorium, a finding that might represent a homing mechanism and implies an asymptomatic, occult phase of lymphoma development.

Geohelmintos / Geohelminths

Los helmintos presentes en el suelo, Ascaris lumbricoides, Trichuris trichiura, uncinarias (Ancylostoma duodenale y Necator americanus) y Strongyloides stercoralis, infestan a millones de personas que habitan sobre todo en áreas rurales y deprimidas de regiones tropicales y subtropicales. Los grandes flujos migratorios han facilitado su extensión a todo el mundo. Además de ser debilitantes y causar una mortalidad significativa, conllevan una alta morbilidad y afectan al desarrollo físico e intelectual de millones de niños que viven en áreas deprimidas. Junto con los benzimidazoles albendazol y mebendazol, las campañas internacionales de prevención y tratamiento a gran escala, han conseguido disminuir el número de afectados, pero la reinfestación y la resistencia a los benzimidazoles son frecuentes, por lo que es muy aconsejable mantener la atención sobre estos parásitos olvidados

Millions of people in in rural areas and deprived tropical and subtropical regions are infected by soil-transmitted helminths: Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenaleand Necator americanus), and Strongyloides stercoralis. Large migratory flows have made their worldwide distribution easier. Besides being debilitating and producing a significant mortality, they cause high morbidity, leading to physical and intellectual impairment in millions of children who live in poverty. Along with the use of benzimidazoles (albendazole and mebendazole), large-scale international campaigns for treatment and prevention have decreased the number of affected individuals. However, re-infestations and benzimidazole-resistance are frequent, so there needs to be awareness about the importance and consequences of these neglected parasites

Anorectal Lymphogranuloma Venereum in Madrid: A Persistent Emerging Problem in Men Who Have Sex With Men.

BACKGROUND: Since 2003, outbreaks of lymphogranuloma venereum (LGV) with anorectal syndrome have been increasingly recognized in many Western countries. All of them have been classified as LGV serovar L2b, mainly occurring in human immunodeficiency virus (HIV)-infected men who have had sex with men (MSM). We describe a series of 26 diagnosed cases of LGV proctitis in downtown Madrid, Spain, in 2014, after implementing routine diagnostic procedures for this disease in symptomatic MSM. METHODS: We conducted an observational study of patients with symptomatic proctitis attending an outpatient infectious diseases clinic in Madrid, Spain during calendar year 2014. Clinical, epidemiological, laboratory, and therapeutic data were gathered and analyzed. RESULTS: Twenty-six patients were included in the analysis. All were MSM, and 24 of them were HIV-positive. All patients reported having acute proctitis symptoms including tenesmus (85%), pain (88%), constipation (62%), or anal discharge (96%). Proctoscopy showed mucopurulent exudate (25 patients [96%]), and rectal bleeding, with mucosal erythema and/or oedema in all cases. Rectal swabs were obtained from all patients, and LGV serovar L2 was confirmed in all of them. The cure rate was 100% after standard treatments with doxycycline 100 mg twice per day for 3 weeks. Simultaneous rectal infections with other sexually transmitted pathogens (gonorrhoea, herpes simplex virus, Mycoplasma genitalium) and systemic sexually transmitted diseases (STDs) (syphilis, acute HIV, and hepatitis C infections) were also documented in 12 patients (46%), but these co-infections did not appear to influence the clinical manifestations of LGV. CONCLUSIONS: Anorectal LGV is a common cause of acute proctitis and proctocolitis among HIV-infected MSM who practice unprotected anal sex, and it is frequently associated with other rectal STDs. The implementation of routine screening and prompt diagnosis of these rectal infections should be mandatory in all clinical settings attended by HIV and STD patients.

Meningoencefalitis criptocócica. Epidemiología y factores de riesgo de mortalidad en la era pre- y pos-TARGA / Cryptococcal meningoencephalitis. Epidemiology and mortality risk factors in pre- and post-HAART era

Introducción y objetivo: La meningoencefalitis criptocócica (MC), aunque infrecuente, sigue siendo una importante causa de morbimortalidad en pacientes con sida. Material y métodos: Revisión de los casos de MC en un hospital universitario (1990-2014). El diagnóstico se determinó mediante el aislamiento de Cryptococcus neoformans en el LCR. Se analizó la morbimortalidad temprana (< 12 semanas) y tardía (3-18 meses). Resultados: Se analizaron 32 pacientes de los 2.269 diagnósticos de sida (1,41%): 10 entre 1990-1996 y 22 entre 1997-2014. El antígeno criptocócico en el LCR fue positivo en todos los casos, con títulos > 1.024 en 19 pacientes (63%), presentando este grupo unos recuentos de CD4+ menores (40 ± 33 frente a 139 ± 78 cél/μl) y mayor afectación diseminada que el resto. Tras el primer episodio de MC la tasa de recaídas fue del 34%. La mortalidad global fue del 28% (9/32), muy superior en el período pre-TARGA. Conclusiones: La morbimortalidad de la MC viene determinada por padecer una inmunodeficiencia grave, la presencia de enfermedad diseminada, títulos elevados de antígeno en el LCR y el retraso en el inicio del TARGA (AU)

Introduction and objective: Cryptococcal meningoencephalitis (CM) is an uncommon entity, but remains a major cause of morbidity and mortality in patients with AIDS. Material and methods: Review of CM cases in a university hospital. The diagnosis was determined by isolation of Cryptococcus neoformans in cerebrospinal fluid. Morbidity and mortality was assessed at 12 weeks (early mortality) and between 3 and 18 months after diagnosis (late mortality). Results: We analyzed 32 patients from 2,269 AIDS cases (1.41%). 10 patients between 1990-1996 and 22 between 1997-2014. Cryptococcal antigen in CSF was positive in all cases, with titers > 1,024 in 19 patients (63%); this group had lower CD4+ counts (40 ± 33 vs. 139 ± 78 cel/μL) and greater disseminated involvement. After a first CM episode the relapse rate was 34%. Global mortality rate was 28% (9/32), much higher in the pre-HAART era. Conclusions: CM morbidity and mortality is related to severe immunodeficiency, disseminated disease, high titers of antigen in CSF and delayed initiation of HAART (AU)

[Geohelminths]. / Geohelmintos.

Millions of people in in rural areas and deprived tropical and subtropical regions are infected by soil-transmitted helminths: Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus), and Strongyloides stercoralis. Large migratory flows have made their worldwide distribution easier. Besides being debilitating and producing a significant mortality, they cause high morbidity, leading to physical and intellectual impairment in millions of children who live in poverty. Along with the use of benzimidazoles (albendazole and mebendazole), large-scale international campaigns for treatment and prevention have decreased the number of affected individuals. However, re-infestations and benzimidazole-resistance are frequent, so there needs to be awareness about the importance and consequences of these neglected parasites.