Loss of Hematopoietic Cell-Derived Oncostatin M Worsens Diet-Induced Dysmetabolism in Mice.

Innate immune cells infiltrate growing adipose tissue and propagate inflammatory clues to metabolically distant tissues, thereby promoting glucose intolerance and insulin resistance. Cytokines of the IL-6 family and gp130 ligands are among such signals. The role played by oncostatin M (OSM) in the metabolic consequences of overfeeding is debated, at least in part, because prior studies did not distinguish OSM sources and dynamics. Here, we explored the role of OSM in metabolic responses and used bone marrow transplantation to test the hypothesis that hematopoietic cells are major contributors to the metabolic effects of OSM. We show that OSM is required to adapt during the development of obesity because OSM concentrations are dynamically modulated during high-fat diet (HFD) and Osm-/- mice displayed early-onset glucose intolerance, impaired muscle glucose uptake, and worsened liver inflammation and damage. We found that OSM is mostly produced by blood cells and deletion of OSM in hematopoietic cells phenocopied glucose intolerance of whole-body Osm-/- mice fed a HFD and recapitulated liver damage with increased aminotransferase levels. We thus uncovered that modulation of OSM is involved in the metabolic response to overfeeding and that hematopoietic cell-derived OSM can regulate metabolism, likely via multiple effects in different tissues.

Extended Depth of Focus Versus Monofocal IOLs in Patients With High Myopia: Objective and Subjective Visual Outcomes.

PURPOSE: To compare the objective and subjective outcomes between the extended depth of focus (EDOF) Mini Well intraocular lens (IOL) and the aspheric monofocal Mini-4-Ready IOL (both SIFI S.p.A.) in patients with high myopia. METHODS: In this prospective comparative study, 40 patients with high myopia (axial length ≥ 26 mm) were enrolled: 20 patients were bilaterally implanted with the EDOF Mini Well IOL (EDOF group) and 20 patients were bilaterally implanted with the Mini-4-Ready IOL (monofocal group). Three-month follow-up data included corrected and uncorrected distance visual acuity at 4 m and 80, 67, and 40 cm, defocus curves, subjective and objective contrast sensitivity, objective optical quality (calculated with Optical Quality Analysis System; Visiometrics SL), halometry, and reading performance. Subjective visual quality was evaluated with National Eye Institute Refractive Error Quality of Life Instrument 42 scores. RESULTS: All visual acuities were significantly better in the EDOF group (P ⩽ .04) except monocular and binocular uncorrected and corrected distance visual acuities for distance (P ≥ .50). Defocus curves for myopic and hyperopic values were better in the EDOF group (P ⩽ .05), apart from +0.50 to -0.50 D (P ≥ .16). Contrast sensitivity curves was worse in the EDOF group in the mesopic-with-glare condition (P ⩽ .04). No differences were found in halometric values (P ≥ .15) and OQAS outcomes (P ≥ .47). National Eye Institute Refractive Error Quality of Life Instrument 42 subscale scores were better for expectation, near vision, activity limitations, and dependence on correction in the EDOF group (P ⩽ .04). CONCLUSIONS: Intermediate and near visual acuities were better in the EDOF group than in the monofocal group, with a comparable visual quality index between groups. [J Refract Surg. 2022;38(3):158-166.].

Double versus single suture stenting to manage hypertensive spikes after glaucoma drainage device implantation.

PURPOSE: To evaluate the safety and efficacy of double compared to single intraluminal suture stenting in reducing early postoperative hypertensive spikes (HS) and hypotony after Baerveldt glaucoma implant surgery. METHODS: For this retrospective study, we reviewed the medical charts of 60 patients (60 eyes) who underwent Baerveldt drainage device surgery between 2017 and 2019. Two groups were formed according to whether a single suture stent was placed within the tube (5-0 polypropylene, 30 eyes, group 1) or a double suture (5-0 and 6-0 polypropylene, 30 eyes, group 2). Intraocular pressure (IOP) was measured at baseline, at 6 h, and on postoperative days 1, 2, 5, 7, 14, 21, 30, 60, 90, 180. The occurrence of HS (IOP ⩾ 30 mmHg), anterior chamber reformation, decompressive paracentesis, anti-glaucoma medication, and adverse events were recorded. RESULTS: There was a greater decrease in IOP from baseline at days 1, 2, and 21 (p < 0.05) and number of HS at 6 h (p = 0.006) and postoperative day 1 (p < 0.001) in group 2. The mean number of decompressive paracentesis, anterior chamber reformation procedures, and topical anti-glaucoma medications was the same in both groups; the need for oral acetazolamide was significantly lower in group 2 at days 1, 21, and 30 (p < 0.05). CONCLUSIONS: While both stenting methods provide a gradual, controlled decrease in IOP, the double stenting technique was associated with a sooner and greater postoperative reduction in IOP and a good safety profile thanks to fewer HS in the early postoperative period and less need for oral acetazolamide.

Extended Depth of Focus Versus Monofocal IOLs: Objective and Subjective Visual Outcomes.

PURPOSE: To evaluate and compare the objective and subjective outcomes between bilateral implantation of the extended depth of focus (EDOF) Mini Well intraocular lens (IOL) and the aspheric monofocal Mini-4-Ready IOL (both SIFI S.p.A., Catania, Italy). METHODS: This prospective comparative study included 25 patients (50 eyes) bilaterally implanted with an EDOF Mini Well IOL (EDOF group) and 25 patients (50 eyes) bilaterally implanted with a Mini-4-Ready IOL (monofocal group). Three-month follow-up data included corrected and uncorrected distance visual acuity at 4 m and 80, 67, and 40 cm. Defocus curves, subjective and objective contrast sensitivity, and objective optical quality (modulation transfer function cutoff and Strehl ratio calculated with Optical Quality Analysis System [OQAS]; Visiometrics SL, Terrassa, Spain), halometry, and reading performance were measured. Subjective visual quality was evaluated based on National Eye Institute Refractive Error Quality of Life Instrument 42 (NEI RQL-42) scores. RESULTS: Postoperative uncorrected and corrected monocular and binocular intermediate and near visual acuity was significantly better in the EDOF group (P < .001). No differences were observed for distance visual acuity (P ⩾ .312). Defocus curve outcomes for myopic values were better in the EDOF group (P < .001). No significant differences were found in hyperopic (obtained in steps of +0.50 diopters [D] from emmetropia to 1.50 D) values (P ⩾ .095), contrast sensitivity curves (P ⩾ .087), or OQAS outcomes (P ⩾ .138). Halometric values were significantly better in the monofocal group (P < .05). There was a correlation between mean keratometry values and intermediate/near visual acuity. Significantly better NEI RQL-42 subscale scores for near vision, far vision, activity limitations, glare, dependence on correction, and suboptimal correction were noted in the EDOF group (P < .05). CONCLUSIONS: Intermediate and near visual acuity was better after EDOF IOL than after aspheric monofocal IOL implantation while maintaining similar levels of visual quality, except for halo perception. [J Refract Surg. 2020;36(4):214-222.].

HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections.

BACKGROUND: Detecting recent HIV infections is important to evaluate incidence and monitor epidemic trends. We aimed to evaluate the diagnostic performance and accuracy of the avidity index (AI) for discriminating for recent HIV infections. METHODS: We collected serum samples from HIV-1 positive individuals: A) with known date of infection (midpoint in time between last HIV-negative and first HIV-positive test); B) infected for >1 year. Samples were divided into two aliquots: one diluted with phosphate buffered saline (PBS) and the other with 1 M guanidine. Both aliquots were assayed by the Architect HIV Ag/Ab Combo 4th generation assay (Abbott). We compared AI found in recent (RI=<6 months from seroconversion) and established (EI) infections. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. The proportion of samples misclassified as recent (FRR) was calculated. RESULTS: In total, 647 samples were collected: 455 in group A (51.6% RI and 48.4% EI) and 192 in group B. Among these, sixteen samples were from elite controllers, 294 from treated patients, 328 from patients infected with non-B subtypes. Samples before antiretroviral initiation showed a mean AI significantly lower among RI compared to EI (0.66+0.28 vs. 1.00±0.12; p<0.000). The FRR was 0% using a cut-off of ≤0.70. An extremely low FRR was observed among elite controllers, samples with low VL or CD4. HIV subtype had no impact on AI misclassifications. All individuals in group A reached the AI threshold of 0.80 within 24 months after seroconversion. CONCLUSIONS: The AI is an accurate serological marker for discriminating recent from established HIV infections and meets WHO requirements for HIV incidence assays.

Hepatitis B virus reactivation after effective sofosbuvir and ribavirin treatment in a patient with occult hepatitis B virus infection.

Reactivation of the hepatitis B virus (HBV) has been reported in patients with occult infection (OBI), i.e. HBV surface antigen (HBsAg) negative, HBV core antibody (anti-HBc) positive ± antibodies against HBsAg (anti-HBs) and detectable HBV DNA in serum or liver, receiving immunosuppressive or cytotoxic therapies. Recently, concerns have been raised regarding the risk of HBV reactivation in OBI patients treated with direct acting antiviral agents (DAAs) for chronic hepatitis C (CHC). Here we describe a case of HBV reactivation in a 72-year-old woman with OBI as a possible consequence of effective treatment with sofosbuvir (SOF) and ribavirin (Rbv) for genotype 2a/2c CHC.

Trigger-oriented HIV testing at Internal Medicine hospital Departments in Northern Italy: an observational study (Fo.C.S. Study).

BACKGROUND: Early detection of undiagnosed HIV infected patients is of paramount importance. The attitude of Italian hospital-based Internal Medicine physicians to prescribe HIV testing following the detection of HIV-associated signs, symptoms and behaviours (triggers) has been reported to be poor. The aim of the study is to quantify the extent of the missed opportunities for early HIV diagnosis in Internal Medicine Departments (IMD). METHODS: Patients admitted to IMD of a General University Hospital in Italy in March-June 2013 were interviewed using a structured questionnaire investigating the presence of triggers for HIV testing, including patient's characteristics, symptoms and conditions associated with HIV infection. HIV tests performed during hospitalisation were recorded. RESULTS: HIV testing was performed in 73 (6.6%) out of 1113 hospitalisations (1072 patients), providing positive results in three cases (4.1%). All of them presented ≥1 triggers. Conversely, 853 triggers were identified in 528 hospitalisations with at least one trigger (47.4%). The proportion of hospitalisations where an HIV testing was prescribed was 3.1%, 9.5% and 16.0% in the presence of zero, one-to-two or more triggers, respectively. Age <70 years, female gender, length of hospital stay, haematological disease, HBV infection, multiple sexual partners and lymphadenopathy were predictors of HIV testing by logistic regression analysis. CONCLUSIONS: Although chances of an HIV test being performed in patients hospitalised in IMD increases along with the number of triggers, the number of tests being performed in people presenting with triggers is unacceptably low and requires educational interventions in order to obtain individual and public health advantages.

Hepatitis C virus core antigen: analytical performances, correlation with viremia and potential applications of a quantitative, automated immunoassay.

BACKGROUND: Testing for hepatitis C virus core antigen (HCV Ag) may represent a complementary tool to anti-HCV and HCV-RNA in the diagnosis and monitoring of HCV infection. OBJECTIVE: To evaluate the performance characteristics of the automated Abbott ARCHITECT HCV Ag assay. STUDY DESIGN: Five sites analyzed over 3000 routine serum samples from populations at different risk, comparing HCV Ag results with anti-HCV screening and supplemental assay results and with HCV-RNA. RESULTS: The HCV Ag assay showed a specificity of 100%, a good precision (CV<10%) and excellent dilution linearity (r>0.999). The sensitivity (3 fmol/L) corresponds to 700-1100 IU/mL of HCV-RNA. A non-linear correlation with HCV-RNA was found: r=0.713 vs. Siemens bDNA (523 specimens), r=0.736 vs. Roche Cobas TaqMan (356 specimens) and r=0.870 vs. Abbott Real-Time PCR (273 specimens). HCV Ag quantitation was equally effective on different HCV genoypes (239 for genotype 1/1a/1b/1c, 108 for genotype 2/2a/2c, 86 for genotype 3/3a, 50 for genotype 4/4a/4c/4d). Testing of subjects at high risk for HCV and with potential or actual impairment of the immune system identified 2 cases negative for anti-HCV and positive for HCV Ag on 361 hemodialyzed (0.6%) and 7 cases on 97 (7.2%) among transplant recipients. HCV Ag positivity anticipated anti-HCV seroconversion in all three cases of acute hepatitis C. CONCLUSIONS: HCV Ag may be used as reflex testing on anti-HCV positive individuals to confirm or exclude an active infection, and on subjects with acute hepatitis or belonging to high risk groups.

Avidity Index for anti-HIV antibodies: comparison between third- and fourth-generation automated immunoassays.

The development of assays for detecting recent HIV infections has become crucial for analyzing trends in infection in different populations, both for surveillance and prevention activities. The anti-HIV avidity index (AI), measured with third-generation immunoassays (which detect anti-HIV antibody), has been shown to be an accurate tool for discriminating recent HIV infections (<6 months) from established infections (≥ 6 months). We compared a third-generation immunoassay (AxSYM HIV 1/2 gO; Abbott Diagnostics) to a fourth-generation immunoassay (Architect HIV Ag/Ab Combo; Abbott Diagnostics; which detects anti-HIV antibody and p24 antigen) in terms of AI performance in distinguishing between recent and established HIV infections. A total of 142 samples from 75 HIV-infected individuals with an estimated date of seroconversion were assayed. The two assays showed the same accuracy in identifying a recent infection (91.5%), using an AI cutoff of 0.80, although Architect HIV Ag/Ab Combo was slightly more sensitive (89.4% versus 84.8%; P > 0.05) and yet less specific (93.4% versus 97.4%; P > 0.05). The correlation between assays was high (r = 0.87). When 20 specimens falling in the gray zone around the cutoff point (0.75 ≤ AI ≤ 0.84) were excluded, the accuracy of AI with Architect HIV Ag/Ab Combo was 94.7%, and the concordance between the two assays was 99.2%. The anti-HIV AI is a serological marker that accurately discriminates recent from established HIV infections. It can be successfully applied on fully automated fourth-generation HIV Ab/Ag immunoassays, which have several advantages, including increased throughput, high reproducibility, no need for specific technical skills, and easy comparability of results obtained in different settings.

Screening and Management of HIV-2-Infected Individuals in Northern Italy.

There is a lack of updated estimates of HIV-2 infection in Italy. Moreover, lack of standardized HIV-2 viral load (VL) and drug resistance tests challenges clinical practice. Among 2941 HIV-positive patients followed in our center (Brescia, Northern Italy), 220 (7.5%) were African at the beginning of the study period. We assessed a population of 151 HIV-Ab positive patients (141 of African origin), presenting for routine blood testing from January 2006 to May 2007. Those found infected with HIV-2 started an appropriate disease management with HIV-2 VL and genotypic drug resistance testing. Sixteen of 151 (10.6%) patients were positive for HIV-2. Of those 16 patients, 14 came from Africa. Among 7 experienced patients, 1 was responding to nelfinavir and 4 to lopinavir/ritonavir-containing regimens. Two patients were failing treatment: 1 patient was switched to a saquinavir/ritonavir-containing regimen and responded. The remaining patient switched to lamivudine + atazanavir + saquinavir + ritonavir did not respond, having had previous experience to multiple ineffective drugs, resulting in a very complex HIV-2 drug-resistance pattern. Accurate screening programs and integration of virological tools must be implemented urgently, given the high prevalence of HIV-2, particularly in immigrant patients.

Immune-mediated hepatitis-associated aplastic anemia caused by the emergence of a mutant hepatitis B virus undetectable by standard assays.

Hepatitis-associated aplastic anemia (HAA) is characterized by marrow failure developing after acute seronegative hepatitis. A patient with agammaglobulinemia developed HAA in association with HBsAg-negative, hepatitis B virus (HBV) DNA-positive acute hepatitis. Sequence analysis showed several substitutions in the major antigenic determinant of HBsAg, potentially affecting the detection by diagnostic immunoassays. Viral mutants may therefore be implicated as etiologic agents of HBsAg-negative HAA. HBV DNA determination may be necessary to exclude mutant HBV as a cause of HAA, particularly in categories at high risk of mutant selection such as agammaglobulinemic and transplanted patients.

Quantitative analysis of HBsAg, IgM anti-HBc and anti-HBc avidity in acute and chronic hepatitis B.

BACKGROUND AND OBJECTIVES: We evaluated hepatitis B virus (HBV) serological markers by novel, quantitative immunoassays in order to study their behaviours and possible role in the various phases of HBV infection. STUDY DESIGN: The quantitative determination of HBsAg and anti-HBc/IgM by chemiluminescent immunoassays (Abbott Architect) and the calculation of anti-HBc avidity index have been carried out on repository specimens from patients with acute or chronic hepatitis B. RESULTS: In acute hepatitis the levels of HBsAg were generally >10,000 UI/mL and decreased sharply in the recovery phase. In 35 anti-HBe-positive chronic hepatitis cases HBsAg levels were generally lower than 10,000 UI/mL (mean: 2655), whereas in five HBeAg-positive chronic hepatitis patients the mean value was 78,756 UI/mL and 90% of specimens exceeded 10,000 UI/mL. The lowest values (mean: 1029 IU/mL) were found in the seven patients with minimal hepatic damage. IgM anti-HBc antibodies were positive in all acute cases and in 68/207 samples (32.85%) from patients with chronic hepatitis, with significantly lower levels (average sample/cutoff (S/CO) ratio: 2.95 in chronic cases versus 25.96 in acute cases; p<0.005). A S/CO value of 10 for anti-HBc IgM had a 100% negative predictive value and a 99.13% positive predictive value for acute hepatitis B. The study of anti-HBc avidity by an experimental procedure showed that an avidity index (AI) threshold of 0.7 had a good efficacy to discriminate the cases of chronic hepatitis, among whom only 2 specimens out of 193 (1.04%) had an AI<0.7. CONCLUSION: The quantitative determination of HBsAg, anti-HBc/IgM and anti-HBc avidity provides additional information and may be useful in the differential diagnosis of acute and chronic HBV infections and in the follow-up of chronically infected patients.