Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen.

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1ß, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell's median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1ß, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.

Atypical Sites of Lymphadenopathy after Anti-COVID-19 Vaccine: Ultrasound Features.

Background and Objectives: Several authors have reported cervical and axillary lymphadenopathies as known side effects following anti-COVID-19 vaccine administration. Few data are available about atypical locations of post-anti-COVID-19 vaccine lymphadenopathy. In this investigation, we evaluated the incidence and prevalence of postvaccine lymphadenopathy ultrasound (US) features in atypical sites. Materials and Methods: In this retrospective study, we retrospectively selected 64 patients on whom US was performed between January and October 2021 due to COVID-19 vaccine-related lymphadenopathy. We investigated lymph node anatomical sites, presence, number, size, shape, cortical profile, hilum outline, superb microvascular imaging (SMI), and elastosonography. Results: A total of 170 nodes were assessed. Atypical location was demonstrated in 5/64 patients (7.8%). In all these cases, atypical nodal involvement was associated with lymphadenopathy in a typical site (axillary, supraclavicular) ipsilateral to the vaccine injection site. Two patients presented lymphadenopathy in the infraclavicular station (3.1%), one in the pectoralis major muscle (1.6%), one in the left arm (1.6%), and one in the nuchal site (1.6%). All lymphadenopathies were oval-shaped, with a median size of 0.9 ± 0.2 cm. US features included a symmetric cortex with hilum evidence (4/6, 60%), vascular signal at SMI in both the hilar region and periphery of lymph node (5/6, 83.3%), and a US elastography pattern resembling that of adjacent tissues (5/6, 83.3%). The median age of patients with lymphadenopathies in an atypical location was 23 years. The main type of vaccine associated with lymph node appearance in atypical sites was Moderna's mRNA-1273 (60% of patients, 4/6 lymph nodes accounting for 66.7% among atypical locations). Conclusion: Post-COVID-19 vaccine administration lymphadenopathies in an atypical location represent an intense immune response to antigenic stimuli and they may show alarming US traits superimposed on malignant pathologies, which may complicate the patient's clinical and diagnostic pathway. Despite no distinctive US features between reactive post-COVID-19 vaccination and malignant lymph nodes being available, careful examination of atypical lymph node locations associated with accurate knowledge of patients' clinical background and delay of US exam to four to six weeks after vaccine injection should be considered.

Diaphragmatic myoclonus due to SARS-CoV-2 infection.

A wide range of neurological signs and symptoms have been associated with SARS-CoV-2 infection. In the present report, we described two Italian patients diagnosed with diaphragmatic myoclonus after COVID-19. In both cases, mild lymphocytosis at cerebrospinal fluid analysis and no structural brain changes were reported. The pathophysiological origin of the myoclonus in the two cases was different. In case 1, electroencephalogram did not reveal any cortical correlates and brain imaging of the spine was unremarkable, while in case 2, cortical origin of myoclonus was demonstrated. With the present two cases, we confirm and extend the neurological manifestations of SARS-CoV-2 infection.

The impact of homocysteine, B12, and D vitamins levels on functional neurocognitive performance in HIV-positive subjects.

BACKGROUND: The correlation among high levels of total homocysteine, low levels of B12vitamin, and neurocognitive impairment in HIV negative patients has been the main research topic in some of the latest reviews. The aim of this study was to examine if the alteration of homocysteine, B12 vitamin, and D vitamins plasma levels was present in HIV-positive, and their relationship with cognitive function. METHODS: 57 HIV infected were enrolled and underwent the serum measurement of homocysteine, B12, and D vitamins. The neurocognitive evaluation investigated 5 cognitive domains, through a neuropsychological battery test RESULTS: Homocysteine was found to be elevated in 70.2% of cases, B12 vitamin mean levels were low in 8 participants (14.0%), and 8 patients had D hypovitaminosis (14.0%). Abnormal homocysteine levels were associated with worse performance of verbal fluency (p = 0.003) and worse executive function (Stroop E test p = 0.040). The 25-OH D hypovitaminosis was associated with worse performances in executive functions in three different tests: Stroop E (p = 0.049), Trail B (p = 0.035), and Wais Digit Span (p = 0.042). Pathological levels of B12 Vitamin were also associated to worse performances in executive functions (Trail B Test and Wais Digit Span respectively p = 0.002 and 0.029) and with a lower speed in psychomotor processing (Peg Board Test on dominant hand, p = 0.014). CONCLUSIONS: In this study serum homocysteine, B12, and D vitamin levels are associated with neurocognitive performances; in fact low performance neurocognitive was correlated with hyperhomocysteine and low B12vitamin, and D vitamin levels. Evidence of the alteration of these parameters could facilitate the early identification of a neurocognitive impairment.

Prevalence of anal, oral, penile and urethral Human Papillomavirus in HIV infected and HIV uninfected men who have sex with men.

Aims of the study were to evaluate Human Papillomavirus (HPV) and type-specific prevalence in four anatomical sites in HIV infected men who have sex with men (MSM) compared with HIV uninfected MSM. Participants were recruited among the attendees of Infectious Diseases Clinics in Central Italy. A trained medical practitioner collected by interview sociodemographic data and information on medical history, sexual behavior, and drug use. Swabs from anal canal, oral cavity, urethral mucosa, and coronal sulcus were tested for HPV DNA and genotyping. Ninety MSM were enrolled, 45 subjects within each group. Overall, 48.9% MSM were HPV positive and prevalence was higher in HIV infected men (60.0% vs 37.8%, P = 0.035). HPV at multiple anatomic sites occurred in 59.1% MSM, with 34.1% and 22.7% at two and three sites, respectively. Prevalence of anal, coronal sulcus, oral, and urethral HPV was 96.3%, 37%, 21.6%, and 18.5% in HIV infected MSM, and 70.6%, 70.6%, 29.4%, and 23.5% among HIV uninfected. A similar proportion of HIV infected and uninfected MSM (59.2% and 58.8%) carried at least one high-risk genotype. Prevalence of types covered by nonavalent vaccine was 77.8% in HIV infected compared with 82.3% in HIV uninfected MSM. HPV 58 and 16 were mostly detected in HIV positive (43.7% and 31.2%) and negative MSM (50.0% and 40.0%). HPV detection rate underlined the high vulnerability of MSM to acquire multisite infections, characterized by various genotype combinations. Since nonavalent vaccine could have prevented 80% of HPV infections, study findings support the implementation of vaccination programs among MSM.

Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies.

BACKGROUND & AIMS: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. METHODS: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70). RESULTS: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. CONCLUSIONS: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

Predictive factors and prevalence of microalbuminuria in HIV-infected patients: a cross-sectional analysis.

BACKGROUND: Renal dysfunction is a common problem in the HIV+ population, due to the effect of both the HIV virus and the several classes of ARV drugs such as tenofovir (TDF). It is also known that the presence of renal damage correlates with cardiovascular risk and therefore with the risk of mortality of the patients accordingly. The detection of early renal damage is very important. Albuminuria and microalbuminuria are markers of early kidney disease and cardiovascular risk. The aim of the study is to evaluate the prevalence of microalbuminuria in a large polycentric sample, of unselected and consecutive HIV-patients followed as outpatients, and to assess its association with different therapeutic regimens. METHODS: We studied 326 patients with a mean age of 48.4 ± 1.6 years, treated at the Infectious Diseases Clinics of Chieti and Perugia for 48 weeks. The main metabolic parameters and the microalbuminuria levels in a single sample of urine were evaluated. RESULTS: Microalbuminuria was detected in 61.0% of patients at T0 and in 49.7% after 48 weeks of observation with a median values of 1.1 mg/L (IQR: 0-2.7) vs. 0 mg/L (IQR: 0-2.0). 70% of the enrolled population did not show changes in microalbuminuria levels over time, 19% showed improvement, and 11% of the population had a worsening of microalbuminuria levels without any alteration of creatinine, uric acid and GFR-MDRD. We also found a statistically significant association between the development of microalbuminuria and gender (p < 0.035), Arterial Hypertension (AH) (p < 0.028) and therapy with TDF (p < 0.050). CONCLUSION: We showed a very high prevalence of microalbuminuria, much higher than the literature data; the use of TDF affects the renal function in a statistically significant way and should therefore be considered a risk factor for kidney damage, which can be early assessed with the measurement of microalbuminuria.

High prevalence of human papillomavirus type 58 in HIV infected men who have sex with men: A preliminary report in Central Italy.

Human papillomavirus (HPV) infection and type-specific prevalence at anal, oral, coronal sulcus, and urethral mucosa in fifty HIV positive men having sex with men (MSM) were evaluated; patients were enrolled in a non-metropolitan area of Central Italy. Clinical and socio-demographic information, drug, and sexual behaviors were obtained for each participant. HPV was detected by PCR from an overall of 200 specimens, and genotyping was performed by both Restriction Fragment Length Polymorphism analysis and sequencing. HPV DNA was found in 60.0% (n = 30) of HIV positive MSM, and prevalence was higher at anal canal (n = 28, 56.0%) compared to all the other anatomical sites (χ(2) test P < 0.01) of coronal sulcus (n = 11, 22.0%), oral (n = 8, 16.0%), and urethral mucosa (n = 5, 10.0%). We found 63.3% (n = 19) of MSM with at least one high-risk genotype, and HPV-58 was more frequently detected (n = 9, 47.4%) respect to HPV-16 (n = 6, 31.6%). This is the first report on HPV detected at four anatomical sites involved in sexual practices in HIV positive MSM. We found an unusual distribution of oncogenic genotypes with an exceeding prevalence of HPV-58 respect to HPV-16. Hence, the recently licensed nonavalent vaccine should be suitable to prevent a larger number of infections caused by potentially emerging high-risk genotypes.

May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics.

When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

Liver enzyme elevation during darunavir-based antiretroviral treatment in HIV-1-infected patients with or without hepatitis C coinfection: data from the ICONA foundation cohort.

OBJECTIVES: To investigate differences in liver enzyme elevation (LEE) between HIV-infected patients with and without HCV coinfection who start a darunavir/ritonavir-containing regimen. METHODS: HIV-infected patients enrolled in the Italian Cohort of Naïve to Antiretrovirals (ICONA) Foundation Study were included if they started darunavir/ritonavir for the first time. Patients were classified as not HCV coinfected, HCV active coinfected (HCV RNA positive), and HCV nonactive coinfected (HCV-Ab positive/HCV RNA negative). Time to LEE endpoint was defined using the ACTG toxicity scale, based on changes relative to baseline. Kaplan-Meier was used to estimate 1-year and 2-year probability of LEE. The incidence rate ratios (IRRs) of LEEs were estimated until the last follow-up (intention-to-treat analysis [ITT]) and up to darunavir/ritonavir discontinuation (on-treatment analysis [OT]). RESULTS: Overall, 703 patients were included. Ninety-one were HCV-Ab positive; of those, 68 (9.7%) had active HCV coinfection. In 879 person-years of follow-up, 101 LEEs occurred (ITT). No severe hepatotoxicity event was registered in active HCV coinfected patients. HCV active coinfection was predictive of LEE in the overall population (OT: adjusted incidence rate ratio (IRR), 2.25; 95% CI, 0.70-7.24; P = .17; ITT: adjusted IRR, 3.62; 95% CI, 1.67-7.83; P < .001) and in naïve patients (OT: adjusted IRR, 6.29; 95% CI, 2.54-15.55; P = .00; ITT: adjusted IRR, 3.87; 95% CI, 0.99-15.16; P = .05). CONCLUSIONS: No grade 3-4 LEEs occurred in HCV active coinfected patients. HCV active coinfected patients experienced low grade LEEs more frequently than HCV-Ab negative patients. Darunavir/ritonavir seems to be safe whatever the HCV status, when liver enzymes are carefully monitored.

Antimicrobial resistance in intensive care patients hospitalized with SEPSIS: a comparison between the COVID-19 pandemic and pre-pandemic era.

Introduction: Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has had a dramatic effect on the world, resulting in millions of deaths worldwide and causing drastic changes in daily life. A study reported that septic complications were associated with high mortality in COVID-19 patients. This study aimed to evaluate how the COVID-19 pandemic changed the pre-pandemic and post-pandemic prevalence of sepsis in ICUs and to evaluate the different risk factors associated with mortality and the different diffusion of microorganisms and their resistance. Materials and methods: We conducted a single-center retrospective observational clinical study, observing all patients in the ICU of the SS Annunziata Hospital in Chieti (Italy) who were diagnosed with sepsis and had a bacterial isolate from their blood culture. Sepsis was diagnosed by SEPSIIS III criteria. We enrolled all in-patients in the ICU from January 2018 to December 2021. We divided the patients into three groups: (1) non-pandemic period (Np) hospitalized in 2018-2019, (2) pandemic period (Pp)-COVID hospitalized in 2020-2021 with a diagnosis of COVID-19, and (3) Pp-non-COVID patients hospitalized in 2020-2021 without a diagnosis of COVID-19. Results: From January 2018 to December 2021, 1,559 patients were admitted to the ICU, of which 211 patients [36 (17.1%) in 2018, 52 (24.6%) in 2019, 73 (34.6%) in 2020, and 50 (23.7%) in 2021, respectively] met the selection criteria: 88 patients in period Np, 67 patients in Pp without COVID-19, and 56 patients Pp with COVID-19. The overall mortality of these patients was high (65.9% at 30 days in Np), but decreased during the Pp (60.9%): Pp-non-COVID was 56.7% vs. Pp-COVID 66.1%, with a statistically significant association with APACHE III score (OR 1.08, 95%CI 1.04-1.12, p < 0.001), SOFA score (OR 1.12, 95%CI 1.03-1.22, p = 0.004), and age (OR 1.04, 95%CI 1.02-1.07, p < 0.0001). Between the Np vs. Pp periods, we observed an increase in a few Gram-positive bacteria such as S. capitis (1 pt. -0.9% vs. 14 pt. -7.65%- p = 0.008), S. epidermidis, Streptococcus spp., and E. faecalis, as well as a decrease in a case of blood culture positive for S. aureus, S. hominis, and E. faecium. In Gram-negative bacteria, we observed an increase in cases of Acinetobacter spp. (Np 6 pt. -5.1%- vs. Pp 20 pt. -10.9%, p = 0.082), and Serratia spp., while cases of sepsis decreased from E. faecium (Np 11 pt. -9.4%- vs. Pp 7 pt. -3.8%, p = 0.047), and Enterobacter spp., S. haemolyticus, S. maltophilia, Proteus spp., and P. aeruginosa have not changed. Finally, we found that resistance to OXA-48 (p = 0.040), ESBL (p = 0.002), carbapenems (p = 0.050), and colistin (p = 0.003) decreased with time from Np to Pp, particularly in Pp-COVID. Conclusion: This study demonstrated how the COVID-19 pandemic changed the prevalence of sepsis in the ICU. It emerged that the risk factors associated with mortality were APACHE and SOFA scores, age, and, above all, the presence of ESBL-producing bacteria. Despite this, during the pandemic phase, we have observed a significant reduction in the emergence of resistant germs compared to the pre-pandemic phase.

Improved metabolic profile after switch to darunavir/ritonavir in HIV positive patients previously on protease inhibitor therapy.

Metabolic abnormalities associated with cumulative exposure to antiretroviral therapy have been linked to an increased risk of myocardial infarction in HIV positive individuals. The aim of this study was to evaluate whether the switch from lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) to darunavir/ritonavir (DRV/r) is able to improve the lipid profile. A total of 13 Caucasian subjects (7 from LPV/r and 6 from FPV/r) were enrolled in the study and received DRV/r at the dose of 800/100 mg, without change in their NRTI backbone. Viro-immunological parameters, triglycerides (TGs), total cholesterol (TCh), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting glucose, HOMA-IR, indexes of hepatic and renal functionality, microalbuminuria and cystatin C were measured at baseline (T0), 3 months (T3), 6 months (T6), and 12 months (T12). The switch to DRV/r reduced levels of TCh, LDL, and TGs at T3. Similar improvements were confirmed further at T6 and at T12. A 14% increase in CD4+ count cells (P < 0.05) was observed. Serum cystatin C values showed a statistically significant decrease. After 12 months of switching to DRV/r from LPV/r or FPV/r, patients infected with HIV with TGs above 200 mg/dl, showed a 49% decrease in TGs, along with a 16% reduction of LDL and 19% reduction of TCh. Switching to DRV/r also improved immunological parameters, such as CD4+ cells count and cystatin C plasmatic levels, which may translate into a reduction of the cardiovascular risk. In conclusion, a switch to DRV/r should be considered in those HIV positive patients undergoing antiretroviral therapy, who also present abnormal lipid profiles.

Are monoclonal antibodies effective in patients with severe obesity in SARS-CoV-2 infected?

It is important to block SARS-CoV-2 infection immediately with early therapies, such as monoclonal antibodies (MonoAbs). Also, several studies show that obesity is associated with a high risk of severe COVID-19 disease. We enrolled 32 SARS-CoV-2 infected patients who received MonoAbs, all patients were not vaccinated for SARS-CoV-2, and they received therapy after 7 ± 2 days from the onset of COVID-19 symptoms. In the days following administration, patients followed home therapy with Pidotimod 800 mg bid for 10 days and cholecalciferol 2000 UI for 20 days, prescribed the same day they received MonoAbs therapy. Our study found that there are no differences in the therapeutic response between obese and nonobese patients with SARS-CoV-2 infection undergoing MonoAbs therapy, in fact, none of them underwent hospitalization. Furthermore, the effect of the immunostimulant Pidotimod and cholecalciferol may have contributed to the resolution of COVID-19 symptoms in these patients.

Approach to COVID-19 in older adults and indications for improving the outcomes.

Background: COVID-19 continues to present challenges in the care of older adults with frailty and/or comorbidities and very old patients, who can be hospitalized with severe COVID-19 despite full vaccination. Frailty is a heterogeneous syndrome characterized by an increased aging-related vulnerability due to a reduced physiological reserve and function of systemic organs, and is associated with an impairment of activities of daily living. Frail older adults remain at elevated risk of mortality from COVID-19 compared to older adults without frailty, and some pre-existing risk factors such as malnutrition, prolonged bed rest, and the association with comorbidities can aggravate the SARS-CoV-2 infection. Furthermore, the severity of COVID-19 can impact on long-term functioning of older patients surviving from the infection. Persistent symptoms are another emerging problem of the post-vaccination phase of pandemic, as most patients suffer from chronic symptoms which can become debilitating and affect the daily routine. Aim of this review: In this complex relationship, the evaluation of COVID-19 in vulnerable categories is still a matter of high interest and personalized care plans based on a comprehensive geriatric assessment, tailored interventions; specific therapeutic algorithms among older adults are thus recommended in order to improve the outcomes.

Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

Ultrasound imaging of the axilla.

Axilla is a pyramidal-in-shape "virtual cavity" housing multiple anatomical structures and connecting the upper limb with the trunk. To the best of our knowledge, in the pertinent literature, a detailed sonographic protocol to comprehensively assess the axillary region in daily practice is lacking. In this sense, the authors have briefly described the anatomical architecture of the axilla-also using cadaveric specimens-to propose a layer-by-layer sonographic approach to this challenging district. The most common sonographic pathological findings-for each and every anatomical compartment of the axilla-have been accurately reported and compared with the corresponding histopathological features. This ultrasound approach could be considered a ready-to-use educational guidance for the assessment of the axillary region. CRITICAL RELEVANCE STATEMENT: Axilla is a pyramidal-in-shape "virtual cavity" housing multiple anatomical structures and connecting the upper limb with the trunk. The aim of this review article was to describe the anatomical architecture of the axilla, also using cadaveric specimens, in order to propose a layer-by-layer sonographic approach to this challenging district.

Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies.

Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005-2009 to 3.0% in 2010-2014 and 5.1% in 2015-2019 (P = 0.007) (OR[95%CI]:11.04[1.42-85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0-2905]IU/mL for complex profiles vs 2078[115-6037]IU/ml and 1881[410-7622]IU/mL for single or no vaccine-escape mutation [P < 0.02]). Even more, the presence of complex profiles correlates with HBsAg-negativity despite HBV-DNA positivity (HBsAg-negativity in 34.8% with ≥2 vaccine-escape mutations vs 6.7% and 2.3% with a single or no vaccine-escape mutation, P < 0.007). These in-vivo findings are in keeping with our in-vitro results showing the ability of these mutations in hampering HBsAg secretion or HBsAg recognition by diagnostic antibodies. In conclusion, vaccine-escape mutations, single or in complex profiles, circulate in a not negligible fraction of HBV genotype-D infected patients with an increasing temporal trend, suggesting a progressive enrichment in the circulation of variants able to evade humoral responses. This should be considered for a proper clinical interpretation of HBsAg-results and for the development of novel vaccine formulations for prophylactic and therapeutic purposes.

Optimization of comorbidity therapy to achieve sustained viral response in HCV patients.

Several studies indicate that insulin resistance and diabetes influence sustained viral response in treatment for chronic HCV infection. We describe the case of a relapsed patient with HCV infection who achieved a sustained viral response due to an improvement in insulin resistance through modification of antihypertensive therapy. By improving insulin resistance with telmisartan, an ARB with PPAR gamma agonist propriety, sustained viral response was obtained with the same antiviral therapy. Optimization of comorbidity therapy is useful for improving the possibility of achieving a sustained viral response.