Search

PURPOSE: Inflammation and dysplasia may affect the ileal pouch after restorative proctocolectomy and ileal pouchanal anastomosis. The aim of this prospective study was to evaluate the morphologic changes and the risk of dysplasia within the pouch after ileal pouch-anal anastomosis. METHODS: Thirty-seven patients with ileal pouch-anal anastomosis underwent endoscopies and biopsies of the pouch: 21 patients were affected by ulcerative colitis and 16 by Crohn's colitis. The mucosal biopsy specimens were studied to investigate the degree of acute and chronic inflammation and the occurrence of dysplasia. A score system was calculated for each patient and correlated with the histologic diagnosis of ulcerative colitis or Crohn's colitis. RESULTS: After a median follow-up of 85 (range, 7-198) months, the inflammation histologic score evaluated was 3.8 (95 percent confidence interval, 2.4-5.1) and 3.5 (95 percent confidence interval, 2.6-4.3), respectively, in patients with Crohn's colitis and ulcerative colitis (mean and 95 percent confidence interval; P = 0.74, not significant), and no patient developed mucosal dysplasia. Fifteen patients (40.5 percent) developed clinical pouchitis that occurred in Crohn's colitis (9/16 patients or 56 percent) and in ulcerative colitis (6/21 patients or 28 percent; P not significant). The score was 4.1 (95 percent confidence interval, 3.2-5) in patients with pouchitis and 3.2 (95 percent confidence interval, 2.1-4.3) in patients without clinical pouchitis (P = 0.012) and was 4.1 (95 percent confidence interval, 2.6-5.5) and 4 (95 percent confidence interval, 2.9-5.3), respectively, in pouchitis patients with Crohn's colitis and ulcerative colitis. CONCLUSION: No difference in the inflammation histologic score was observed in ileal pouches after restorative proctocolectomy for ulcerative and Crohn's colitis. In our series, which includes those patients with longer follow-up (>5 years) or with chronic unremitting pouchitis, no case of dysplasia was found. The occurrence of pouchitis was higher in the case of ileal pouch-anal anastomosis for Crohn's disease than for ulcerative colitis, but no difference in the severity of the histologic score was noted. [ABSTRACT FROM AUTHOR]

Objective: Given the aging of people living with HIV (PLWH) and the high prevalence of HIV-associated neurocognitive disorders, we aimed at describing the clinical, instrumental, and CSF features of PLWH diagnosed with Alzheimer dementia (AD)., Methods: The databases of 3 large Italian outpatient clinics taking care of more than 9,000 PLWH were searched for the diagnosis of AD. After obtaining patients' or their next of kin's consent for publication, anonymous data were collected in an excel spreadsheet and described. Routinely collected CSF biomarkers and radiologic imaging results were recorded whether available., Results: Four patients were included in this case series who were diagnosed with AD aged between 60 and 74 years. All participants were on highly active antiretroviral therapy and showed nondetectable serum HIV RNA. Memory impairment was the most prominent cognitive feature. The diagnosis was obtained considering the exclusion of other potential causes, MRI and fluorodeoxyglucose-PET features, and, in (in 2/4), CSF AD biomarkers levels. In 1 patient, longitudinal CSF tau/p-tau increased, and beta-amyloid 1-42 decreased over time despite antiretroviral therapy containing nucleotide reverse transcriptase inhibitors., Conclusions: In older PLWH cognitive symptoms may represent the onset of AD: a multidisciplinary team may be needed for reaching a likely in vivo diagnosis., (© 2021 American Academy of Neurology.)

Rationale: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected women., Patient Concerns: A 52-year-old woman diagnosed with SARS-CoV-2/HIV-1 coinfection, ten HIV-1-positive women and five age-matched-healthy individuals were enrolled in this study., Diagnoses: SARS-CoV-2 infection caused severe pneumonia in the second week of illness in HIV-1-positive patient under protease inhibitors. Chest high-resolution computed tomography images of the SARS-CoV-2/HIV-1-coinfected patient showed bilateral ground-glass opacities., Interventions: SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFNα/β mRNA levels and CD4 and CD8 T cell (CD38, human leukocyte antigen-DR [HLA-DR], CD38 HLA-DR) frequencies were performed by RT/real-time PCR assays and flow cytometry, respectively. Median relative difference (MRD) was calculated for each immunological variable. For values greater than reference, MRD should be a positive number and for values that are smaller, MRD should be negative., Outcomes: The severe pneumonia observed in SARS-CoV-2/HIV-1-positive patient under protease inhibitors was reversed by a 7-days hydroxychloroquine therapy. At the end of treatment, on day 7, patient reported resolution of fever, normalization of respiratory rate (14 breaths/min), and improved oxygen arterial pressure with a FiO2 of 30%. MRD values for IFNα/β and CD4 and CD8 T cells expressing CD38 and/or HLA-DR found in SARS-CoV-2-/HIV-1-coinfected woman were approximatively equal to 0 when refereed respectively to HIV-1-positive female patients [MRDs IFNα/β: median -0.2545 (range: -0.5/0.1); T cells: median -0.11 (range: -0.8/1.3)] and ≥ 6 when referred to healthy individuals [MRDs IFNα/β: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)]., Lessons: These results indicate that SARS-CoV-2 infection in HIV-1-positive female patient was associated with increased levels of IFNα/β-mRNAs and T cell activation compared to healthy individuals.

Objective: HIV-1-associated dysbiosis is most commonly characterized by overall decreased diversity, with abundance of the genus Prevotella, recently related to inflammatory responses., Design: A pilot study including 10 antiretroviral therapy-treated HIV-1-infected men and 50 uninfected controls was performed to identify the main gut dysbiosis determinants (e.g. Prevotella enrichment), that may affect mucosal antiviral defenses and T cell immunity in HIV-1-infected individuals., Methods: 16rRNA gene sequencing was applied to the HIV-1-infected individuals' fecal microbiota and compared with controls. Measurements of CD4 and CD8 T cell activation [CD38, human leukocyte antigen (HLA)-DR, CD38 HLA-DR] and frequencies of Th17, obtained from lamina propria lymphocytes isolated from five different intestinal sites, were performed by flow cytometry. IFNβ, IFNAR1 and MxA gene expression level was evaluated by real-time PCR in lamina propria lymphocytes. Nonparametric t tests were used for statistical analysis., Results: HIV-1-infected men had a significant fecal microbial communities' imbalance, including different levels of genera Faecalibacterium, Prevotella, Alistipes and Bacteroides, compared with controls. Notably, Prevotella abundance positively correlated with frequencies of CD4 T cells expressing CD38 or HLA-DR and coexpressing CD38 and HLA-DR (P < 0.05 for all these measures). The same trend was observed for the activated CD8 T cells. Moreover, Prevotella levels were inversely correlated with IFN-I genes (P < 0.05 for IFNβ, IFNAR1 and MxA genes) and the frequencies of Th17 cells (P < 0.05). By contrast, no statistically significant correlations were observed for the remaining bacterial genera., Conclusion: Our findings suggest that Prevotella enrichment might affect gut mucosal IFN-I pathways and T cell response in HIV-1-infected patients, thus contributing to immune dysfunction.

Objective: The influence of sex on gut mucosal T-cell response in HIV-1 infection remains largely unknown. We explored whether the frequencies of interferon-γ and/or IL-17 producing naive, T central memory and T effector memory (TEM) CD4+ (Th1, Th17) and CD8+ T (Tc1, Tc17) cells measured in gut and peripheral districts differed between female and male HIV-1-infected patients., Methods: Thirty long-term-treated HIV-1-infected individuals were enrolled. The frequencies of Th1, Th17, Tc1, Tc17-cell subsets (single and double) were evaluated by multiparametric flow cytometry in lamina propria lymphocytes and peripheral blood mononuclear cells (PBMC)., Results: A sex-based pattern was recorded in the differences of Th1, Th17, Tc1, Tc17-cell subset (single and double) frequencies between gut and peripheral blood. Female patients had stronger alterations in the gut mucosal T-cell repertoire, especially increased Th1, Th17, and Th1/Th17-cell subset frequencies, compared with the blood district than their male counterparts. Higher naive Tc1, Tc17, Tc1/Tc17, TEM Tc17, and TEM Tc1/Tc17 levels were also recorded in the gut mucosa than in the PBMC of HIV-1-infected women. Males and females also differed in their gut T-cell response, with women being characterized by higher Th1, Th17, Tc1, Tc17, and Th1/Th17 cells subset levels than men. By contrast, only TEM Th1/Th17 and TEM Tc17 in PBMC differed between males and females., Conclusion: Sex-based differences observed in the gut T-cell response of HIV-1-infected patients might contribute to the disease dimorphism.

: No consensus has been reached on how to define cerebrospinal fluid HIV-1 escape (CSF-E). We describe its prevalence in 1095 paired CSF-plasma HIV-RNA measurements from antiretroviral-treated patients according to several definitions and neurological affections. CSF-E prevalence varied substantially (9.0-38.9%) and was higher in patients with cerebrovascular disorders, HIV-associated dementia and white matter abnormalities. Considering the variability in HIV-RNA quantification assays, the biological relevance of viral escape at different thresholds needs to be accurately assessed.

Introduction: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity., Conclusion: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route.

Aims: HIV and highly active antiretroviral therapy (HAART) may affect cardiac conduction, and a higher incidence of sudden death has been recognized in HIV-positive patients. Nevertheless, predictors of prolonged corrected QT interval (cQT) have been poorly described. The aim of the study was to investigate the prevalence and predictors of long cQT in a cohort of HIV-positive patients., Methods: Consecutive HIV-positive patients followed in a primary prevention clinic at two Italian institutions were retrospectively enrolled. A 12-lead ECG was recorded in all patients; main clinical features were collected. Prevalence of long cQT (defined as cQT >470 ms in women and >450 ms in men) was the primary end-point. Secondary end-points were the identification of predictors of cQT prolongation, and the association between HAART and HIV-related features with long cQT., Results: Three hundred and fifty-one HIV-positive patients were included, 26 (7.4%) with long cQT. Mean age was higher among those with long cQT (51.6 vs. 57.6 years; P = 0.007). A higher prevalence of long cQT was reported for patients with a CD4+ cell count below 200 cells/μl at the moment of ECG (60 vs. 24.2%; P = 0.002) and with a nadir of CD4+ cell count below 200 cells/μl (91.3 vs. 58.6%; P = 0.001). At multivariate analysis, only the nadir of CD4+ cell count below 200 cells/μl consistently related to the presence of long cQT (odds ratio 5.8, 95% confidence interval 1.3-26.4)., Conclusion: A low CD4+ cell count is associated with long cQT independently from HAART in HIV-positive patients and may be useful to correctly stratify arrhythmic risk in these patients.

Objective: To characterize anal human papillomavirus (HPV) infections in terms of genotype prevalence and type-specific DNA load in HIV-positive men., Design: HIV-positive men attending the colo-proctological clinic of a University Hospital in Rome were recruited prospectively from November 2004 to July 2007. HIV-negative outpatients attending the same clinic over the same period were used as a control group., Methods: Anal brushings were tested for HPV-DNA using polymerase chain reactions and direct sequencing; type-specific HPV-DNA copies were measured in most positive samples. HPV data were correlated with patient HIV status and risk factors., Results: HPV-DNA infection was detected in 81% of HIV-positive men. Almost all homosexual men were HPV-infected. The infection rate in low-risk HPV types was higher than in high-risk types. The spectrum of HPV genotypes was comparable between HIV-positive and HIV-negative men. Numbers of HPV-DNA copies varied greatly between samples but did not differ significantly between HIV-positive and HIV-negative men. In many samples, low-risk (HPV 6, 61, 70, and 74) viral loads were comparable with those of high-risk HPVs., Conclusion: Type-specific HPV-DNA copies at baseline appear to be independent of patient immune status and of HPV genotype. HPV genotype risk and viral load should be further evaluated for their potential predictive role in persistence and progression.

Objective: To study virologic and immunologic factors associated with discordant treatment response in HIV-infected patients receiving highly active antiretroviral therapy (HAART)., Design: Study participants included a total of 27 patients: (a) 10 discordant patients (mean CD4+ cell count, 396.1 x 10 cells/l; mean HIV-RNA, 5.4 log copies/ml); (b) seven responder patients (mean CD4+ cell count, 997.5 x 10 cells/l); and (c) 10 failing patients (mean CD4+ cell count 66.5 x 10 cells/l; mean HIV-RNA, 5.4 log copies/ml).(10) (10), Methods: The HIV-1 isolation rate and biological phenotype, drug resistance genotypic mutations of HIV-1 strains, recall and HIV-1-specific antigen lymphocyte proliferation (LP), and interleukin (IL)-15 production were studied., Results: Virus isolation was obtained in 30% of discordant patients, and in 100% of failing patients. A higher replication constant was reported in discordant patients. No difference in the number of drug resistance mutations and biological phenotypes of HIV-1 was found in discordant patients with respect to failing patients. Discordant patients developed positive LP responses to and HIV-1 p24. LP in response to, HIV-1 p24 and gp160 was positive in responder patients. No significant LP was found in failing patients. Increased levels of IL-15 after stimulation with lipopolysaccaride (LPS) and were found in both discordant patients and responder patients. Conversely, a strong reduction of IL-15 levels was observed in failing patients., Conclusion: The present results suggest that decreased virus isolation rate, restoration of both lymphocyte proliferation and IL-15 production are factors involved in the discordant antiretroviral therapy response of HIV-infected patients.

Objective: To investigate the immunological and virological interactions between interleukin (IL)-15 and HIV in antiretroviral-naive and highly active antiretroviral therapy (HAART)-treated patients., Design: Three groups of HIV-infected patients were studied: 20 untreated patients with advanced disease; eight patients with viral suppression and immunological response to HAART; and 10 patients with virological and immunological treatment failure. Eleven healthy blood donors were included as controls., Methods: The following parameters were evaluated: the production of IL-15 by peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide,Candida albicans and Mycobacterium avium complex; the ability of IL-15 to induce the secretion of IL-8 and monocyte chemotactic protein-1 (MCP-1) from HIV-positive monocytes; and the virological effect of IL-15 and IL-2 on HIV replication in mononuclear cells., Results: IL-15 production by PBMC was significantly decreased in antiretroviral-naive patients and in those with treatment failure. On the contrary, in patients with response to HAART IL-15 production was comparable to that of healthy donors. IL-15 was able to stimulate HIV-positive monocytes to produce chemokines, such as IL-8 and MCP-1, that specifically attract neutrophils and monocytes to the site of inflammation thus possibly improving immune response to pathogens during HIV infection. Finally, IL-15 had no major effect on HIV replication in vitro, while only simultaneous administration with IL-2 may induce high levels of HIV production., Conclusions: This in vitro study provides new insights in the area of IL-15-HIV interactions and suggests that IL-15 may represent a potential candidate for cytokine treatment in combination with HAART during HIV infection.

Background: Modifications of the in situ split liver technique are needed for safe transplantation in two adult recipients with a single donor., Methods: The graft from a brain-dead donor, 187 cm tall and weighing 89 kg, was split in situ with a transection performed along the main portal fissure retaining the middle hepatic vein with the left graft. The right and left grafts, which weighed 985 and 760 g, respectively, were transplanted in two adult recipients weighing 70 and 56 kg, respectively., Results: Both recipients had minor intraoperative blood loss and were discharged from intensive care on day 3. Both grafts were rapidly functional, and the two patients were in excellent condition with normal liver function tests 9 months after surgery., Conclusion: In situ split liver transplantation can be performed with the middle hepatic vein retained in the left graft to obtain a sufficient volume of the two grafts suitable for two adult recipients. This modification of the technique could expand the donor pool for adult recipients.

Objectives: In order to evaluate the role played by cytokine profile as a co-factor involved in the resistance to HIV infection in couples serodiscordant for HIV, we studied HIV-seronegative subjects with multiple unprotected sexual exposures., Design and Methods: Twenty-one HIV-exposed seronegative subjects (HEPS), their 21 HIV-seropositive partners and 10 HIV-seronegative unexposed individuals were studied for T helper (Th) types 1-2 cell pattern and CCR5 receptor., Results: Twelve out of 21 HIV-seropositive partners of HEPS showed a CD4 cell count below 200 lymphocytes/microl. HIV strains were isolated from peripheral blood mononuclear cells (PBMC) in 17 patients (81%): seven subjects with syncytium-inducing strains and 10 with non-syncytium-inducing isolates. Low Th1 cytokine production and high levels of IL-4 were detected in HIV-seropositive subjects. A significant reduction of IL-2 and IFN-gamma expression in the CD4 and CD8 cells of HEPS was found compared with HIV-seronegative unexposed individuals. Similar levels of low IL-4 were present in both HEPS and controls. The partial deletion of a single allele (wild type/delta32) of CCR5 was found in only one HEPS., Conclusion: The downregulated Th1 profile we observed in HEPS could be related to a cellular anergy state with a protective role in the transmission rate of HIV. Low levels of IL-2 and IFN-gamma could be involved in a low-grade activation state of CD4 lymphocytes. A decrease of IFN-gamma levels could render macrophage cells incapable of antigen presentation, thus resulting in a reduction of the cell-to-cell spread of infection.

Objective: To investigate the effect of highly active antiretroviral treatment (HAART) on neutrophil and monocyte function in patients with moderately advanced HIV-1 infection., Design: Eighteen HIV-1-infected patients with CD4 T cell counts below 350/microl, no concomitant active infection, and no previous use of protease inhibitors were treated with indinavir or ritonavir and two reverse-transcriptase inhibitors and were followed up for 9 months. Ten age- and sex-matched healthy subjects were included as controls., Methods: The functional activity of neutrophils and monocytes was measured by assessing chemotaxis towards a bacterial peptide, killing activity against Candida albicans, and oxidative burst as measured by chemiluminescence production., Results: Neutrophils and monocytes from the treatment group exhibited a significantly diminished baseline chemotactic and fungicidal activity compared with healthy controls (P < 0.001). After starting HAART, there was a significant improvement in chemotaxis and fungicidal activity of phagocytic cells (P < 0.001). Values of chemotaxis reached normal ranges in 13 out of 18 patients (72%) for neutrophils and eight out of 18 (44%) for monocytes, whereas phagocyte killing was rarely restored to normal values (3/18 cases for monocytes and 0/18 for neutrophils). The administration of HAART was also associated with significantly increased phagocyte chemiluminescence production in response to phorbol-12-myristate 13-acetate or opsonized C. albicans (P < 0.01)., Conclusion: The functional improvement of two critical components of innate antimicrobial immunity, such as neutrophils and monocytes, may contribute to the improved cell-mediated immune responses against opportunistic infections in HAART-treated patients.

The term very far-advanced otosclerosis is proposed to indicate otosclerotic patients with both bone and air conduction thresholds nonmeasurable on a standard clinical audiometer (blank audiogram). Three of these patients have undergone stapedotomy with satisfactory results. This confirms that cochlear implantation is not the best treatment for all profoundly deaf patients at least with implants available today. Some of the patients with a blank audiogram are better off with exploratory tympanotomy and stapedotomy.