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Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson's Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates. [ABSTRACT FROM AUTHOR]

Summary: Abnormalities of platelet function were reported in patients with severe COVID‐19 (severe‐C), but few data are available in patients with mild COVID‐19 (mild‐C) and after COVID‐19 recovery. The aim of this study was to investigate platelet parameters in mild‐C patients (n = 51), with no evidence of pneumonia, and severe‐C patients (n = 49), during the acute phase and after recovery, compared to 43 healthy controls. Both mild‐C and severe‐C patients displayed increased circulating activated platelets, low δ‐granule content (ADP, serotonin), impaired platelet activation by collagen (light transmission aggregometry) and impaired platelet thrombus formation on collagen‐coated surfaces under controlled flow conditions (300/s shear rate). The observed abnormalities were more marked in severe‐C patients than in mild‐C patients. Overall, 61% (30/49) of mild‐C and 73% (33/45) of severe‐C patients displayed at least one abnormal platelet parameter. In a subgroup of just 13 patients who showed no persisting signs/symptoms of COVID‐19 and were re‐evaluated at least 1 month after recovery, 11 of the 13 subjects exhibited normalization of platelet parameters. In conclusion, mild abnormalities of platelet parameters were present not only in severe‐C but also, albeit to a lesser extent, in mild‐C patients during the acute phase of COVID‐19 and normalized in most tested patients after clinical recovery. [ABSTRACT FROM AUTHOR]

Purpose of Review: HIV/AIDS and COVID-19 have been the major pandemics overwhelming our times. Given the enduring immune disfunction featuring people living with HIV (PLWH) despite combination antiretroviral therapy (cART), concerns for higher incidence and severity of SARS-CoV-2 infection as well as for suboptimal responses to the newly developed vaccines in this population arose early during the pandemics. Herein, we discuss the complex interplay between HIV and SARS-CoV-2, with a special focus on the immune responses to SARS-CoV-2 natural infection and vaccination in PLWH. Recent Findings: Overall, current literature shows that COVID-19 severity and outcomes may be worse and immune responses to infection or vaccination lower in PLWH with poor CD4 + T-cell counts and/or uncontrolled HIV viremia. Data regarding the risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among PLWH are extremely scarce, yet they seem to suggest a higher incidence of such condition. Summary: Scarce immunovirological control appears to be the major driver of weak immune responses to SARS-CoV-2 infection/vaccination and worse COVID-19 outcomes in PLWH. Therefore, such individuals should be prioritized for vaccination and should receive additional vaccine doses. Furthermore, given the potentially higher risk of developing long-term sequelae, PLWH who experienced COVID-19 should be ensured a more careful and prolonged follow-up. [ABSTRACT FROM AUTHOR]

Aims: Antiretroviral (ARV) therapy reduces inflammation and immune activation in people with HIV, but not down to the levels observed in people without HIV. Limited drug penetration within tissues has been argued as a potential mechanism of persistent inflammation. Data on the inflammation role on ARV plasma/intracellular (IC) pharmacokinetics (PK) through to expression of cytochrome P450 3A/membrane transporters are limited. The aim of this study was to investigate the correlation between inflammation markers (IM) and plasma/IC PK of ARV regimen in HIV‐positive patients. Methods: We included ART‐experienced patients switching to three different ARV regimens. Plasma and IC ARV drug concentration means at the end of dosing interval (T0), IM on samples concomitantly with ARV PK determination: sCD14, CRP, IL‐6 and LPS were analysed. Results: Plasma and IC drug concentrations were measured in 60 samples. No significative differences between CRP, sCD14, IL‐6 and LPS values in the three arms were observed. A significant inverse correlation between tenofovir plasma concentration and sCD14 (rho = −0.79, P <.001), and between DRV IC/plasma ratio and Log10 IL‐6 concentrations (rho = −0.36, P =.040), and a borderline statistically significant positive trend between DRV plasma concentration and sCD14 (rho = 0.31, P =.070) were suggested. Furthermore, a borderline statistically significant inverse trend between DTG IC concentrations and sCD14 (rho = −0.34, P =.090) was observed in 24 patients on DTG‐based triple therapy. Conclusions: Our preliminary data support the hypothesis of lower DRV and DTG IC concentrations and lower TFV plasma exposure in patients with higher plasma IM suggesting an interplay between HIV drug penetration and persistent inflammation in cART‐treated HIV‐positive patients. [ABSTRACT FROM AUTHOR]

A cytokine storm drives the pathogenesis of severe COVID-19 infection and several biomarkers have been linked to mortality. Chronic kidney disease (CKD) emerged as a risk factor for severe COVID-19. We investigated the association between selected biomarkers and mortality in 77 patients hospitalized for COVID-19, and whether they differ in patients with eGFR higher and lower than 45 mL/min. The association between patients' characteristics, plasma biomarkers and mortality was conducted by univariate logistic regression models and independent predictors of mortality were then used to create a multivariate prediction model through Cox regression. Patients with lower eGFR had a significant increase of GDF-15, CD-25 and RAGE, with higher plasma levels in non-survivors and in patients who needed ventilation. At univariate analysis, low and mid-low GDF-15 quartiles (<4.45 ng/mL) were associated with lower mortality risk, while mid-high and high quartiles (>4.45 ng/mL) were associated with higher mortality risk. Independent association between GDF-15 quartiles and mortality risk was confirmed in the Cox model and adjusted for eGFR, age, fever and dyspnea (HR 2.28, CI 1.53–3.39, p < 0.0001). The strength of the association between GDF-15 quartiles and mortality risk increased in patients with lower compared to higher eGFR (HR 2.53, CI 1.34–4.79 versus HR 1.99, CI 1.17–3.39). Our findings may suggest a further investigation of the effect of GDF-15 signaling pathway inhibition in CKD. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR < 30 (n = 23), 30 < eGFR < 60 (n = 33), eGFR > 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases. [ABSTRACT FROM AUTHOR]

HIV-HCV co-infected subjects are at risk of liver fibrosis which may be linked to immune imbalances. Direct-acting antivirals (DAAs) represent the mainstay of HCV treatment in co-infected individuals, yet their effects on immune cell populations playing a role in fibrogenesis is unknown. We assessed γδ T-cell phenotype and function, Treg and Th17 frequencies, as well as γ-globulins and B-cell activation in 47 HIV-HCV co-infected and 35 HCV mono-infected individuals prior to and following DAA treatment (SVR12). Γδ T-cell activation decreased in both groups yet persisted at higher levels in the HIV-HCV co-infected subjects. No differences were registered in terms of γδT-cell function. Of note, the Vδ2/Th17 ratio, inversely linked to liver damage, increased significantly in the two groups upon treatment, yet a negative correlation between the Vδ2/Th17 ratio and liver function enzymes was found in the co-infected subjects alone. B-cell activation and γ-globulin levels decreased in both settings, yet B-cell activation remained higher in the HIV-HCV co-infected individuals. In HIV-HCV co-infected and HCV mono-infected participants, the effect of DAA was limited to γδ T- and B-cell activation as well as γ-globulin concentrations and the Vδ2/Th17 ratio, with no changes in γδ T-cell function and Treg frequencies. Importantly, γδ T- and B-cell activation remained at higher levels in the co-infected individuals than in those with HCV mono-infection alone. The persistence of such alterations within these cell subsets may be associated with the risk of hepatic and extrahepatic complications. [ABSTRACT FROM AUTHOR]

Two years into Coronavirus Disease 2019 (COVID-19) pandemic, a comprehensive characterization of the pathogenesis of severe and critical forms of COVID-19 is still missing. While a deep dysregulation of both the magnitude and functionality of innate and adaptive immune responses have been described in severe COVID-19, the mechanisms underlying such dysregulations are still a matter of scientific debate, in turn hampering the identification of new therapies and of subgroups of patients that would most benefit from individual clinical interventions. Here we review the current understanding of viral and host factors that contribute to immune dysregulation associated with COVID-19 severity in the attempt to unfold and broaden the comprehension of COVID-19 pathogenesis and to define correlates of protection to further inform strategies of targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background People with HIV are at increased risk of human papillomavirus (HPV) disease progression, given the persistence of immune activation and residual inflammation despite effective combination antiretroviral therapy (cART). Whether a low CD4:CD8 T-cell ratio, known to mirror peripheral immune dysfunction, is associated with squamous intraepithelial lesions (SILs) is unknown. Methods This was a retrospective cohort study on cART-treated HIV-positive subjects undergoing screening for HPV-related dysplasia (anal/cervical cytology and HPV genotyping). SIL was defined as the presence of either atypical squamous cells of undetermined significance (ASCUS), low-grade SILs, or high-grade SILs. Demographic and viro-immunological parameters (T-cell count, CD4:CD8 T-cell ratio, CD8+ CD38+ T-cell percentage) at the time of screening were analyzed by the chi-square test, Mann-Whitney test, and multivariate logistic regression analysis. Results A total of 419 cART-treated subjects were included. Half of the patients had cervical/anal SIL. Individuals with SIL were more commonly males, were men who have sex with men, were coinfected with Treponema pallidum , had been treated with integrase inhibitor (INSTI)–based cART regimens, and had a shorter time since HIV diagnosis and cART initiation than subjects with normal cytology. CD38+ CD8+ T-cell percentage, but not the CD4:CD8 T-cell ratio, correlated with SILs. HPV infection, especially with multiple and high-risk genotypes, was confirmed to be associated with SIL. In multivariate analysis, the only factors independently associated with cervical/anal dysplasia were HPV infection and harboring higher percentages of peripheral activated CD38+ CD8+ T cells. Conclusions HPV infection is the major driver of dysplasia in the setting of HIV infection. In this study, CD8+ CD38+ T cells were an independent predictor of dysplasia in cART-treated subjects, while CD4:CD8 T-cell ratio was not. In the setting of HIV–HPV coinfection, CD4:CD8 T-cell ratio may not fully capture the alterations of HPV-specific immunity. [ABSTRACT FROM AUTHOR]

Background: We explored the long-term effects of cART on markers of gut damage, microbial translocation, and paired gut/blood microbiota composition, with a focus on the role exerted by different drug classes. Methods: We enrolled 41 cART naïve HIV-infected subjects, undergoing blood and fecal sampling prior to cART (T0) and after 12 (T12) and 24 (T24) months of therapy. Fifteen HIV-uninfected individuals were enrolled as controls. We analyzed: (i) T-cell homeostasis (flow cytometry); (ii) microbial translocation (sCD14, EndoCab, 16S rDNA); (iii) intestinal permeability and damage markers (LAC/MAN, I-FABP, fecal calprotectin); (iv) plasma and fecal microbiota composition (alpha- and beta-diversity, relative abundance); (v) functional metagenome predictions (PICRUSt). Results: Twelve and twenty four-month successful cART resulted in a rise in EndoCAb (p = 0.0001) and I-FABP (p = 0.039) vis-à-vis stable 16S rDNA, sCD14, calprotectin and LAC/MAN, along with reduced immune activation in the periphery. Furthermore, cART did not lead to substantial modifications of microbial composition in both plasma and feces and metabolic metagenome predictions. The stratification according to cART regimens revealed a feeble effect on microbiota composition in patients on NNRTI-based or INSTI-based regimens, but not PI-based regimens. Conclusions: We hereby show that 24 months of viro-immunological effective cART, while containing peripheral hyperactivation, exerts only minor effects on the gastrointestinal tract. Persistent alteration of plasma markers indicative of gut structural and functional impairment seemingly parallels enduring fecal dysbiosis, irrespective of drug classes, with no effect on metabolic metagenome predictions. [ABSTRACT FROM AUTHOR]

Background and Aims: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes. Diabetic macroangiopathies, particularly cardiovascular (CV) diseases, seem closely related to diabetes microvascular complications. Aspirin represents the most prescribed compound in CV prevention. Aspirin impact on DR is still object of debate. As it is already recommended among diabetics at high CV risk, aim of this study was to assess a potential relationship between DR and aspirin therapy, in a type 2 diabetes cohort of patients screened through telemedicine.Methods and Results: NO Blind is a cross-sectional, multicenter, observational study, which involved nine Italian outpatient clinics. Primary endpoint was the assessment of the relationship between aspirin treatment and DR. 2068 patients were enrolled in the study, subsequently split in two subpopulations according to either the presence or absence of DR. Overall, 995 subjects were under aspirin therapy. After adjusting for most common potential confounders, age and gender, aspirin reveals significantly associated with DR (OR: 1.72, 95%CI: 1.58-2.89, p = 0.002) and proliferative DR (PDR) (OR: 1.89, 95%CI: 1.24-2.84, p = 0.003). Association comes lost further adjusting for MACEs (OR: 1.28, 95%CI: 0.85-1.42, p = 0.157) (Model 4) and eGFR (OR: 0.93; 95%CI: 0.71-1.22; p = 0.591) (Model 5).Conclusion: In this multicenter cross-sectional study including a large sample of outpatients with T2DM, we showed that aspirin was not associated with DR after adjustment for several cardio-metabolic confounders. However, as partially confirmed by our findings, and related to the well-known pro-hemorrhagic effect of aspirin, its use should be individually tailored, even by telemedicine tools. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the effectiveness of toric intraocular lenses (IOLs) for treating corneal astigmatism in patients with cataract and previous deep anterior lamellar keratoplasty (DALK). Setting. San Giovanni-Addolorata Hospital, Rome, Italy. Design. Prospective interventional case series. Methods. Patients undergoing cataract surgery after DALK for keratoconus were enrolled. Total corneal astigmatism (TCA) was assessed by a rotating Scheimpflug camera combined with Placido-disk corneal topography (Sirius; CSO, Firenze, Italy). A customized toric IOL (FIL 611 T, Soleko, Rome, Italy) was implanted in all eyes. One year postoperatively, refraction was measured, the IOL position was recorded, and vectorial and nonvectorial analyses were performed to evaluate the correction of astigmatism. Results. Ten eyes of 10 patients were analyzed. The mean preoperative TCA magnitude was 4.92 ± 1.99 diopters (D), and the mean cylinder of the IOL was 6.18 ± 2.44. After surgery, the difference between the planned axis of orientation of the IOL and the observed axis was ≤10° in all eyes. The mean surgically induced corneal astigmatism was 0.35 D at 20°. The mean postoperative refractive astigmatism power was 1.13 ± 0.94 D; with respect to preoperative TCA, the reduction was statistically significant (p<0.0001). The mean change in astigmatism power was 3.80 ± 1.60 D, corresponding to a correction of 77% of preoperative TCA power. Nine eyes out of 10 had a postoperative refractive astigmatism power ≤ 2D. Conclusions. Toric IOLs can effectively correct corneal astigmatism in eyes with previous DALK. The predictability of cylinder correction is partially lowered by the variability of the surgically induced changes of TCA. This trial is registered with NCT03398109. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tracheostomy mechanical ventilation (TMV) is performed in amyotrophic lateral sclerosis (ALS) patients with a respiratory failure or when the non-invasive ventilation (NIV) is no longer effective. We evaluated the clinical characteristics and survival of a cohort of tracheostomized ALS patients, followed in a single ALS Clinical Center. Methods: Between 2001 and 2010, 87 out of 279 ALS patients were submitted to TMV. Onset was spinal in 62 and bulbar in 25. After tracheostomy, most patients were followed up through telephone interviews to caregivers. A complete survival analysis could be performed in fifty-two TMV patients. Results: 31.3% ALS patients underwent tracheostomy, with a male prevalence (M/F=1.69) and a median age of 61years (interquartile range=47–66). After tracheostomy, nearly all patients were under home care. TMV ALS patients were more likely than non-tracheostomized (NT) patients to be implanted with a PEG device, although the bulbar-/spinal-onset ratio did not differ between the two groups. Kaplan–Meyer analysis showed that tracheostomy increases median survival (TMV, 47months vs NT, 31months, p=0.008), with the greatest effect in patients younger than 60 at onset (TMV≤60years, 57.5months vs NT≤60years, 38.5months, p=0.002). Conclusions: TMV is increasingly performed in ALS patients. Nearly all TMV patients live at home and most of them are fed through a PEG device. Survival after tracheostomy is generally increased, with the stronger effect in patients younger than 60. This survival advantage is apparently lost when TMV is performed in patients older than 60. The results of this study might be useful for the decision-making process of patients and their families about this advanced palliative care. [Copyright &y& Elsevier]

Aims: Diabetic retinopathy (DR) represents the main cause of blindness among adults in the industrialized Countries. Use of telemedicine could offer an easy, smart specialist fundus oculi examination, as well as putting in a screening programme many patients who otherwise would be excluded.Materials and Methods: The NO BLIND is a transversal, multicentre, observational study. Its pilot phase involved nine public outpatient clinics for 6 months. As endpoint of the study, we assessed the prevalence of DR by retinography in a subset of the Italian population. Patients' fundus oculi photos were performed by trained diabetologists through a digital smart ophthalmoscope.Results: According to our endpoint, in the final study population (n = 1461), obtained excluding patients for whom retinography was not able to provide any diagnosis, DR prevalence was equal to 15.5%. According to the receiver operating characteristic (ROC) curve performed, we can observe how retinography appears a highly accurate method to detect DR (AUROC 0.971, 95% confidence interval, 0.954-0.989), with a specificity of the 100% and a sensitivity of the 94.3%.Conclusions: Our findings, in an Italian setting, confirm main data in the literature about DR prevalence. Hence, telemedicine could represent an accurate, fast, and cheap method for screening of DR. [ABSTRACT FROM AUTHOR]

Abstract: Clinical evidence for parkinsonism may accompany Amyotrophic Lateral Sclerosis with a frequency ranging from 5% to 17%. The concurrence of Amyotrophic Lateral Sclerosis and Parkinson''s disease, outside the known Guam and Kii Peninsula foci, is instead rare, but this raises the possibility of a common pathogenesis. Clinically this complex presents with a levodopa-responsive parkinsonism and Amyotrophic Lateral Sclerosis and has been termed Brait–Fahn–Schwartz disease. Here we describe two patients with this uncommon neurodegenerative complex. Both presented with Parkinson disease and progressed to a full blown Amyotrophic Lateral Sclerosis. We further suggest that the association of Parkinson disease and Amyotrophic Lateral Sclerosis represents a distinct nosological entity, which should be kept separated from extrapyramidal signs and symptoms that may occur in Amyotrophic Lateral Sclerosis. [Copyright &y& Elsevier]

Purpose: To compare the visual outcomes, reading performance, and quality of life (QoL) of working-age cataractous patients bilaterally implanted with 3 different diffractive multifocal intraocular lenses (MIOLs). Design: Two-center, randomized, prospective, double-masked study. Participants: Sixty-three consecutive patients (126 eyes) seen at Ophthalmology Section, Palermo and Florence University, Italy, randomized to receive the ReSTOR SN6AD3 (Alcon Laboratories, Inc, Irvine, CA) (20 patients, group A), ReSTOR SN6AD1 (Alcon Laboratories, Inc) (21 patients, group B), or TECNIS ZMA00 (Abbott Medical Optics, Santa Ana, CA) (22 patients, group C) MIOL. Intervention: Phacoemulsification. Main Outcome Measures: One-year follow-up differences among the 3 MIOL groups in visual acuity, reading performance by MNREAD (Minnesota Laboratory for Low-Vision Research, University of Minnesota, Minneapolis, MN) reading acuity (RA), critical print size (CPS), and maximum reading speed (MRS) under mesopic and photopic conditions. Secondary Outcome Measures: Photopic and mesopic contrast sensitivity (CS) by Pelli–Robson test and patient satisfaction by National Eye Institute Refractive Error Quality of Life Instrument-42 (NEI RQL-42) questionnaire. Results: Mean photopic uncorrected near visual acuity (UNVA), distance-corrected near visual acuity (DCNVA), and corrected near visual acuity (CNVA) did not differ among groups, with a preferred reading distance greater in group B (P < 0.0005). Photopic distance-corrected intermediate visual acuity (DCIVA) was best in group B (P = 0.001) and better in group C than in group A. Mesopic UNVA and DCNVA were worse in groups A and B compared with group C (P < 0.0005 in both cases), with better DCNVA in group B than in group A (P = 0.031). Mesopic uncorrected intermediate visual acuity (UIVA) and DCIVA were worst in group A, with better results in group C (P < 0.0005 and P = 0.001, respectively). Mesopic MNREAD RA was better in group C (P = 0.02), and mesopic MRS was higher in groups B and C than in group A (P = 0.002). The QoL scores by the NEI RQL-42 test exhibited no differences among groups in 9 over 13 scales. “Near vision” (P = 0.005), “symptoms” (P = 0.001), and “satisfaction with correction” scale scores (P = 0.030) were lowest in group A, and “appearance” scale score was lowest in group B (P = 0.045). Conclusions: Newer-generation aspheric diffractive MIOLs, especially low-add hybrid apodized or full diffractive, are highly suited for working-age cataractous patients in terms of visual outcomes, reading performance, and QoL. Intrinsic optical differences, such as optimization for computer or dim-light working, or night driving, could be useful tools to customize the IOL in each single case. [Copyright &y& Elsevier]