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Skin aging is influenced by intrinsic and extrinsic factors that progressively impair skin functionality over time. Investigating the skin aging process requires thorough research using innovative technologies. This review explores the use of in vitro human 3D culture models, serving as valuable alternatives to animal ones, in skin aging research. The aim is to highlight the benefits and necessity of improving the methodology in analyzing the molecular mechanisms underlying human skin aging. Traditional 2D models, including monolayers of keratinocytes, fibroblasts, or melanocytes, even if providing cost-effective and straightforward methods to study critical processes such as extracellular matrix degradation, pigmentation, and the effects of secretome on skin cells, fail to replicate the complex tissue architecture with its intricated interactions. Advanced 3D models (organoid cultures, "skin-on-chip" technologies, reconstructed human skin, and 3D bioprinting) considerably enhance the physiological relevance, enabling a more accurate representation of skin aging and its peculiar features. By reporting the advantages and limitations of 3D models, this review highlights the importance of using advanced in vitro systems to develop practical anti-aging preventive and reparative approaches and improve human translational research in this field. Further exploration of these technologies will provide new opportunities for previously unexplored knowledge on skin aging. [ABSTRACT FROM AUTHOR]

Skin aging is characterized by reactive oxygen species (ROS) accumulation, principal players in triggering events associated with aging. Our recent data on the ability of an innovative poly-component formulation (KARISMA Rh Collagen® FACE: K formulation) to suppress the biomolecular events associated with oxidative stress-induced aging prompted us to deepen the mechanisms underlying the observed effects on aged human dermal fibroblasts (HDFs). Here, we evaluated K's ability to perform a direct free radical-scavenging action and modulate anti-oxidant systems by counteracting the inflammatory process in an H2O2-induced cellular senescence model. Standard methods were used to measure scavenging capacity and enzymatic anti-oxidant system activities. Nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) levels were analyzed by Western blot. We assessed pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and advanced glycation end-products (AGEs). Our results show that K counteracted stress-induced aging in a dose-dependent manner by exerting a direct scavenging action and increasing anti-oxidant systems, such as superoxide dismutase (SOD) and catalase (CAT) up to control values. These findings could be associated with increased phospho-Nrf2 (p-Nrf2) expression, generally reduced in aged HDFs following exposure to different concentrations of K formulation. Moreover, K formulation caused a reduction of pro-inflammatory cytokines, interleukin-1β and -6, MMP-1 and -9, and AGE levels, events related to a downregulation of p-NF-κB level. The results indicate that K formulation re-established the normal physiology of HDFs by reducing p-NF-κB expression and restoring Nrf2 activation, thus supporting its efficacious reparative and regenerative action in treating skin aging. [ABSTRACT FROM AUTHOR]

The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-β1 (TGF-β1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-β1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-β1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects. [ABSTRACT FROM AUTHOR]

Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or LV impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of "arrhythmic mitral valve prolapse" as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine magnetic resonance sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy. [ABSTRACT FROM AUTHOR]

Background Lamivudine + dolutegravir maintenance dual therapy (DT) could be less effective than 3-drug therapy (TT) in the context of resistance-associated mutations to nucleoside reverse transcriptase inhibitors (NRTIs). The ARCA database was queried to test this hypothesis with a trial emulation strategy. Methods People with HIV taking 2 NRTIs plus a protease inhibitor or a non-NRTI who switched to DT or dolutegravir-based TT were followed up from the first HIV RNA <50 copies/mL (baseline) to virologic failure (VF; ie, 2 consecutive HIV RNA ≥50 copies/mL or 1 HIV RNA ≥200 copies/mL). Those switching to DT within 6 months were assigned to the treatment arm and all other patients to the control arm. Each participant was also cloned, assigned to the opposite strategy, and censored at the time of deviation from that strategy. Using inverse probability of censoring weight Cox regression models, we calculated hazard ratios of VF for DT vs TT stratified for the presence of resistance-associated mutations. Results Overall 626 people were analyzed: 204 with DT and 422 with TT (73% men; mean age, 44 years). Ten and 31 VFs occurred with DT and TT, respectively, over a median 5.8 years. When compared with a fully active TT, the DT had similar efficacy (adjusted hazard ratio, 0.88; 95% CI,.29–2.61; P =.812) when full susceptibility was confirmed at historical genotype. When previous M184V/I was present in both groups, the risk of VF was higher for DT vs TT but was not statistically significant (adjusted hazard ratio, 3.06; 95% CI,.45–20.84; P =.252). Conclusions DT was not associated with a significantly higher risk of VF than dolutegravir-based TT. [ABSTRACT FROM AUTHOR]

Background. Enamel plays an essential role in protecting the underlying layers of the human tooth; therefore, preserving it is vital. This experimental study aimed to evaluate the potential ability of L. brevis to counteract the action of a demineralizing agent on dental enamel morphology and mineral composition in vitro. Methods. The sample consisted of 12 healthy human posterior teeth. The coronal portion of each tooth was subdivided into two equal parts longitudinally. The specimens were randomly divided into four groups: artificial saliva, L. brevis suspension, demineralizing agent (DA), and DA plus L. brevis. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were used to evaluate the surface micromorphology and the mineral content, respectively. The statistical analysis was conducted using a one-way ANOVA, followed by Tukey's post hoc test. Results. SEM analysis did not highlight significant changes in the enamel microstructure of L. brevis-treated specimens compared to the control. DA-induced damage to the enamel structure was drastically reduced when the specimens were contextually exposed to the probiotic. The treatment with DA substantially reduced the weight % of crucial enamel minerals, i.e., Ca and P. Notably, the probiotic was able to reverse the demineralization process, bringing Ca and P weight % back to basal levels, including the Ca/P ratio. Conclusions. The findings indicate that L. brevis is able to efficiently protect the dental enamel surface from the damage caused by DA and increase the enamel resistance to demineralization. Overall, L. brevis confirms its efficacy in preventing or counteracting the action of carious lesions through a novel mechanism that protects the tooth surface under a chemical challenge that mimics the caries process. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is characterized by an immunosuppressive tumor microenvironment (TME) strictly associated with therapy resistance. Cyclooxygenase-2 (COX-2) fuels GBM proliferation, stemness, and chemoresistance. We previously reported that COX-2 upregulation induced by temozolomide (TMZ) supported chemoresistance. Also, COX-2 transfer by extracellular vesicles released by T98G promoted M2 polarization in macrophages, whereas COX-2 inhibition counteracted these effects. Here, we investigated the COX-2 role in the stemness potential and modulation of the GBM immunosuppressive microenvironment. The presence of macrophages U937 within tumorspheres derived from GBM cell lines and primary cultures exposed to celecoxib (COX-2 inhibitor) with or without TMZ was studied by confocal microscopy. M2 polarization was analyzed by TGFβ-1 and CD206 levels. Osteopontin (OPN), a crucial player within the TME by driving the macrophages' infiltration, and CD44 expression was assessed by Western blot. TMZ strongly enhanced tumorsphere size and induced the M2 polarization of infiltrating macrophages. In macrophage-infiltrated tumorspheres, TMZ upregulated OPN and CD44 expression. These TMZ effects were counteracted by the concurrent addition of CXB. Remarkably, exogenous prostaglandin-E2 restored OPN and CD44, highlighting the COX-2 pivotal role in the protumor macrophages' state promotion. COX-2 inhibition interfered with TMZ's ability to induce M2-polarization and counteracted the development of an immunosuppressive TME. [ABSTRACT FROM AUTHOR]

Despite effective antiretroviral therapies (ARTs), a subset of people living with HIV (PLWH) still experience low-level viremia (LLV, i.e., 50–1,000 copies/mL). The present study compared PLWH experiencing LLV with those maintaining virological suppression (VS) and explored the potential impact of preexisting drug resistance and other factors on LLV. We conducted a retrospective, 1:1 matched case–control study within a cohort of drug-experienced VS subjects from the Italian Antiviral Response Cohort Analysis database, followed in the period 2009–2019. Cases were individuals experiencing LLV, while controls were those who maintained VS. Matching was for calendar year of first ART regimen. Preexisting drug resistance was calculated as cumulative genotypic susceptibility score (GSS) according to regimen administered at the observational period start. To explore the effect of cumulative GSS, treated as a binary variable (≥2 and <2) and other factors on LLV, we performed a logistic regression analysis. Within a main population of 3,455 PLWH, 337 cases were selected. Cases were comparable to the controls for both gender and age. However, cases showed that they had experienced a longer time since HIV diagnosis, a higher number of drugs previously administered, lower baseline CD4+ T cell count and a higher zenith viral load (VL). By multivariate analysis, we found that higher zenith VL [adjusted odds ratio (aOR) (95% confidence interval [CI]) 1.30 (1.14–1.48)], a cumulative usage of both PI [aOR (95% CI): 2.03 (1.19–3.48)] and InSTI [aOR (95% CI): 2.23 (1.47–3.38)] and a cumulative GSS <2 [aOR (95% CI) 0.67 (0.46–0.98)], were associated with a higher risk in developing LLV. In current high-efficacy ART era, in drug-experienced PLWH, the predictors of increased risk of LLV were the presence of preexisting drug resistance, higher zenith VL, and previous PI, and InSTI exposure. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a severe condition and a significant public health issue worldwide, carrying the burden of an increased risk of cardiovascular events and mortality. The traditional factors that promote the onset and progression of CKD are cardiometabolic risk factors like hypertension and diabetes, but non-traditional contributors are escalating. Moreover, gut dysbiosis, inflammation, and an impaired immune response are emerging as crucial mechanisms in the disease pathology. The gut microbiome and kidney disease exert a reciprocal influence commonly referred to as "the gut-kidney axis" through the induction of metabolic, immunological, and endocrine alterations. Periodontal diseases are strictly involved in the gut-kidney axis for their impact on the gut microbiota composition and for the metabolic and immunological alterations occurring in and reciprocally affecting both conditions. This review aims to provide an overview of the dynamic biological interconnections between oral health status, gut, and renal pathophysiology, spotlighting the dynamic oral-gut-kidney axis and raising whether periodontal diseases and gut microbiota can be disease modifiers in CKD. By doing so, we try to offer new insights into therapeutic strategies that may enhance the clinical trajectory of CKD patients, ultimately advancing our quest for improved patient outcomes and well-being. [ABSTRACT FROM AUTHOR]

Evidence accumulated during past years confirm that people living with HIV (PLWH) still have to deal with comorbidities and chronic complications that can increase physical and psychological issues and can affect daily functioning, quality of life and mental health. Moreover, during the COVID-19 pandemic PLWH proved to be a population at increased risk of psychological distress. We explored the ongoing issues and the characteristics of the mental health interventions for which a cohort of Italian PLWH interacted with a psychologist over the past five years. We analysed a dataset that included 61 PLWH who underwent a psychological intervention between 2018 and 2022. We compared different frequencies in characteristics of mental health interventions according to different demographic and clinical variables, psychopathological symptoms and time of the request for intervention. We showed that psychopathological symptoms most frequently reported by patients were anxiety (55.7%), and depression (49.2%). Furthermore, we reported that most our patients undertook occasional psychological support meetings (31%), sought an intervention after the outbreak of the COVID-19 pandemic (62.3%) and complained about disclosure issues (48.5%). Disclosure issues were mainly reported by younger PLWH (p = 0.002) with a shorter disease (p = 0.031) and treatment history (p = 0.032), and higher interpersonal sensitivity (p = 0.042). It seems fundamental to integrate psychological interventions into the care of PLWH, to give particular attention to PLWH with risky demographic, clinical and mental health factors and to pay special attention to emergency conditions (such as the COVID-19 pandemic) and the most widespread issues to create ad hoc interventions. [ABSTRACT FROM AUTHOR]

Background Blood telomere length (BTL) is a validated biomarker of aging. ART reduces immunosenescence and has benefits in terms of BTL in people living with HIV (PLWH). However, it has also been observed that ART containing NRTIs, such as tenofovir or abacavir, which are potent inhibitors of human telomerase activity in vitro , might negatively affect BTL. Here we investigated the effects on BTL 1 year after switching to a dual therapy (DT) with dolutegravir + lamivudine versus maintaining a standard triple therapy (TT) with a two-NRTI backbone and an anchor drug. Methods This was a longitudinal, prospective, matched, controlled study that included virologically suppressed adults on stable three-drug ART who either switched at baseline (BL) to DT or maintained TT. The DT and TT groups were 1:1 matched for age, sex, years since HIV diagnosis, years on ART and anchor drug. BTL was assessed by a monochrome multiplex qPCR at BL and after 48 weeks (W48). Results We enrolled 120 PLWH, i.e. 60 participants in each group. At BL, the BTL means were comparable between the two groups (P  = 0.973). At W48, viro-immunological status was stable and an overall increase in the mean BTL was observed, i.e. +0.161 (95%CI, 0.054–0.268) (P  = 0.004). However, the within-group analysis showed a significant mean BTL gain in the DT group (P  = 0.003) but not in the TT group (P  = 0.656). Conclusions In this setting of virologically suppressed PLWH, simplifying to dolutegravir + lamivudine was associated with a higher gain in BTL than maintaining triple therapy after the 1 year follow-up. These findings suggest that as a simplification strategy dolutegravir + lamivudine might have a positive effect on BTL. [ABSTRACT FROM AUTHOR]

Asthma is the most frequent chronic disease of childhood, affecting up to 20% of children worldwide. The main guidelines on asthma maintenance therapy in pediatrics suggest different approaches and describe different stages of asthma to determine the most appropriate treatment. This project aims to summarize the most recent evidence regarding maintenance therapy for asthma in children and adolescents. A multidisciplinary panel of experts was asked clinical questions regarding the treatment of children and adolescents with asthma. Overall, 10 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results showed that the choice of medication depends on the severity of the child's asthma, phenotype, age, preference, and individual factors. In addition to medications, the identification of comorbidities and modifiable factors is crucial to obtaining good control. Asthma in children is heterogeneous, and its evolution varies over time. Since most recommendations for asthma management in childhood are extrapolated from clinical studies performed in adults, more clinical trials specifically designed for young children should be conducted. [ABSTRACT FROM AUTHOR]

Preterm infants are at risk of hypoxia and hyperoxia because of the immaturity of their respiratory and antioxidant systems, linked to increased morbidity and mortality. This study aimed to evaluate the efficacy of a single administration of the SLAB51 probiotic formula in improving oxygenation in respiratory distress syndrome (RDS)-affected premature babies, thus reducing their need for oxygen administration. Additionally, the capability of SLAB51 in activating the factor-erythroid 2-related factor (Nrf2) responsible for antioxidant responses was evaluated in vitro. In two groups of oxygen-treated preterm infants with similar SaO2 values, SLAB51 or a placebo was given. After two hours, the SLAB51-treated group showed a significant increase in SaO2 levels and the SaO2/FiO2 ratio, while the control group showed no changes. Significantly increased Nrf2 activation was observed in intestinal epithelial cells (IECs) exposed to SLAB51 lysates. In preterm infants, we confirmed the previously observed SLAB51's "oxygen-sparing effect", permitting an improvement in SaO2 levels. We also provided evidence of SLAB51's potential to enhance antioxidant responses, thus counteracting the detrimental effects of hyperoxia. Although further studies are needed to support our data, SLAB51 represents a promising approach to managing preterm infants requiring oxygen supplementation. [ABSTRACT FROM AUTHOR]

Skin aging is a dynamic process that determines structural alterations in ECM and reduction in dermal fibroblasts. The recent availability on the market of an innovative polycomponent formulation (KARISMA Rh Collagen® FACE, K) containing noncrosslinked high-molecular-weight hyaluronic acid (HMW-HA), a human recombinant polypeptide of collagen-1 alpha chain, and carboxymethyl cellulose (CMC), attracted our scientific interest in evaluating its biomolecular effects on human dermal adult and aged fibroblasts. After treatment with increasing K concentrations, cell proliferation, collagen I, prolyl 4-hydroxylase (P4HA1), an essential protein in collagen biosynthesis, and α-SMA levels were assessed. The fibroblast contractility, TGF-β1 levels, and oxidative stress markers were also evaluated. K formulation exposure led to a significant and dose-dependent increase in the proliferation and migration of adult fibroblasts. Of note, the K exposure counteracted the H2O2-induced aging by promoting cell proliferation, reducing β-galactosidase activity, and neutralizing the aging-associated oxidative damage. Moreover, an increase in collagen I, P4HA1, α-SMA, TGF-β1 levels, and improved contractility of adult and aged fibroblasts were observed after treatment. Overall, our results show evidence that the K treatment is efficacious in improving biological functions in adult fibroblasts and suppressing the biomolecular events associated with H2O2-induced cellular aging, thus supporting the regenerative and bio-revitalizing action of the K formulation helpful in preventing or treating skin aging. [ABSTRACT FROM AUTHOR]

The care engagement of people living with HIV (PLWH) measured with the patient health engagement (PHE) model and its association with HIV-related internalized stigma are not well established. Indeed, currently there are no data yet about the engagement of PLWH measured with the PHE model. This study aimed to evaluate the effects of HIV-related internalized stigma on care engagement and mental health and to fill the lack of data on PHE model applied to PLWH. We found that the internalized stigma score was significantly higher for PLWH (n =82) in worse care engagement phase and both higher internalized stigma scores and worse engagement were associated to major depression symptoms. In conclusion, our findings describe for the first time the engagement in care of PLWH measured with PHE and highlight the importance of PLWH support to find strategies to cope stigma-related stress and optimize their care engagement. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor-1α (HIF-1α), a central player in maintaining gut-microbiota homeostasis, plays a pivotal role in inducing adaptive mechanisms to hypoxia and is negatively regulated by prolyl hydroxylase 2 (PHD2). HIF-1α is stabilized through PI3K/AKT signaling regardless of oxygen levels. Considering the crucial role of the HIF pathway in intestinal mucosal physiology and its relationships with gut microbiota, this study aimed to evaluate the ability of the lysate from the multi-strain probiotic formulation SLAB51 to affect the HIF pathway in a model of in vitro human intestinal epithelium (intestinal epithelial cells, IECs) and to protect from lipopolysaccharide (LPS) challenge. The exposure of IECs to SLAB51 lysate under normoxic conditions led to a dose-dependent increase in HIF-1α protein levels, which was associated with higher glycolytic metabolism and L-lactate production. Probiotic lysate significantly reduced PHD2 levels and HIF-1α hydroxylation, thus leading to HIF-1α stabilization. The ability of SLAB51 lysate to increase HIF-1α levels was also associated with the activation of the PI3K/AKT pathway and with the inhibition of NF-κB, nitric oxide synthase 2 (NOS2), and IL-1β increase elicited by LPS treatment. Our results suggest that the probiotic treatment, by stabilizing HIF-1α, can protect from an LPS-induced inflammatory response through a mechanism involving PI3K/AKT signaling. [ABSTRACT FROM AUTHOR]

Thanks to the modern ARV regimens and the fact that the morbidity and mortality of metabolic syndrome increases with age, clinicians are continuously researching effective and safe antiretroviral regimens with low impact on the lipid profile. Doravirine (DOR) is the latest non-nucleoside reverse-transcriptase inhibitor (NNRTI) that shows long-term safety and tolerability and a favorable lipid profile. The aim of this study is to assess the impact of DOR-based three-drug regimens on the lipid profile in clinical practice. We retrospectively analyzed a cohort of 38 treatment-experienced, virologically suppressed people living with HIV (PLWH) switching to this regimen, following the eligibility criteria. We carried out comparison analysis of immunological and metabolic parameters between baseline and 48 weeks of follow up. In our cohort of treatment-experienced, virologically suppressed PLWH, three-drug regimens with DOR showed good efficacy and a positive profile on lipid metabolism at 48 weeks of follow up. [ABSTRACT FROM AUTHOR]

Functional and structural damage of the intestinal mucosal barrier significantly contribute to translocation of gut microbial products into the bloodstream and are largely involved in HIV‐1 associated chronic immune activation. This microbial translocation is largely due to a progressive exhaustion of intestinal macrophage phagocytic function, which leads to extracellular accumulation of microbial derived components and results in HIV‐1 disease progression. This study aims to better understand whether the modulation of gut microbiota promotes an intestinal immune restoration in people living with HIV (PLWH). Long‐term virologically suppressed PLWH underwent blood, colonic, and fecal sampling before (T0) and after 6 months (T6) of oral bacteriotherapy. Age‐ and gender‐matched uninfected controls (UC) were also included. 16S rRNA gene sequencing was applied to all participants' fecal microbiota. Apoptosis machinery, mitochondria, and apical junctional complex (AJC) morphology and physiological functions were analyzed in gut biopsies. At T0, PLWH showed a different pattern of gut microbial flora composition, lower levels of occludin (p = 0.002) and zonulin (p = 0.01), higher claudin‐2 levels (p = 0.002), a reduction of mitochondria number (p = 0.002), and diameter (p = 0.002), as well as increased levels of lipopolysaccharide (LPS) (p = 0.018) and cCK18 (p = 0.011), compared to UC. At T6, an increase in size (p = 0.005) and number (p = 0.008) of mitochondria, as well as amelioration in AJC structures (p < 0.0001) were observed. Restoration of bacterial richness (Simpson index) and biodiversity (Shannon index) was observed in all PLWH receiving oral bacteriotherapy (p < 0.05). Increased mitochondria size (p = 0.005) and number (p = 0.008) and amelioration of AJC structure (p < 0.0001) were found at T6 compared to T0. Moreover, increased occludin and zonulin concentration were observed in PLWH intestinal tracts and decreased levels of claudin‐2, LPS, and cCK18 were found after oral bacteriotherapy (T0 vs. T6, p < 0.05 for all these measures). Oral bacteriotherapy supplementation might restore the balance of intestinal flora and support the structural and functional recovery of the gut mucosa in antiretroviral therapy treated PLWH. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of a treatment switch to dolutegravir plus lamivudine on the soluble inflammatory biomarkers of HIV-infected patients treated in a real-life setting. Materials and methods: This was a longitudinal study that enrolled virologically-suppressed patients on stable 3-drug ART who switched at baseline to dolutegravir + lamivudine (2DR-group), based on the clinician's decision, or maintained triple therapy (3DR-group). Subjects in the 3DR-group were matched with those in the 2DR-group for age, gender and type of anchor drug. Plasma levels of interleukin-6 (IL-6), I-FABP, D-dimer and C-reactive protein (CRP) were quantified by a microfluidic ultrasensitive ELISA assay at baseline and at 48 weeks. Results: Overall 208 subjects were enrolled: 101 in the 2DR-group and 107 in the 3DR-group. At baseline, biomarker levels were comparable between groups. The differences in mean log10 change from baseline to 48 weeks between groups (2DR versus 3DR) were: IL-6 (pg/L) −0.051(95% CI −0.115/0.009) versus 0.004 (95% CI −0.046/0.054) (p = 0.159); I-FABP (pg/mL), −0.088 (95% CI −0.14/-0.041) versus 0.033 (95%CI −0.007/0.072) (p < 0.001); D-dimer (pg/mL), −0.011(95% CI-0.055/0.033) versus −0.021 (95% CI −0.071/0.030) (p = 0.780) and CRP (pg/mL), −0.028 (95%CI −0.118/0.063) versus 0.118 (95% CI 0.024/0.211) (p = 0.028). Conclusions: At 1 year, switching to a dolutegravir plus lamivudine dual regimen in this setting showed a favorable trend for two biomarkers analyzed, i.e., I-FABP and CRP, as compared to continuing a triple therapy. These results add important new data in support of the safety of this approach in terms of its effect on the inflammatory milieu. [ABSTRACT FROM AUTHOR]

Introduction: Anaphylaxis is one of the most frequent and misdiagnosed emergencies in the pediatric emergency department (PED). We aimed to assess which factors play a major role for a correct diagnosis and an appropriate therapy. Methods: We reviewed the records of children discharged with a diagnosis of anaphylaxis or an allergic reaction over 11 years from 3 hospitals in the Bologna city area. Results: One hundred and sixteen cases matched the criteria (0.03% of the total admittances) and were divided according to the patients' symptoms at arrival: active acute patients [AP], n = 50, or non-acute patients ([NAP], n = 66). At the patients' discharge, anaphylaxis was diagnosed in 39 patients (33.6%). Some features seemed to favor a correct diagnosis: active symptoms at arrival (AP vs. NAP, p < 0.01), high-priority triage code (p < 0.01), and upper airway involvement (p < 0.01). Only 14 patients (12.1%), all in the AP group, received epinephrine, that was more likely administered to patients recognized to have anaphylaxis (p < 0.01) and with cardiovascular, respiratory, or persistent gastrointestinal symptoms (p < 0.02), as confirmed by logistic regression analysis. Conclusions: Anaphylaxis is still under-recognized and under-treated. Correct triage coding and a proper diagnosis seem to foster an appropriate treatment. Physicians often prefer third-line interventions. Specific training for nurses and physicians might improve the management of this disease. [ABSTRACT FROM AUTHOR]

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children's exposure to risk factors that may permanently affect respiratory health. [ABSTRACT FROM AUTHOR]

Byline: Tullio. Messana, Francesca. Lombardi, Andrea. Canini, Angelo. Russo, Chiara. Landini, Arcangela. Curatolo, Antonella. Pini, Chiara. Ghizzi Bilateral facial nerve palsy (FNP) is an extremely rare clinical condition. Different from [...]

Cabotegravir and rilpivirine are the first drugs to be approved as injectable therapy to treat individuals with HIV. Despite encouraging results, the guidelines specify strict criteria for eligibility that could limit the feasibility of this strategy. We collected the clinical data of HIV‐positive patients who were being treated at a single, third‐level center in Italy. All patients were on stable therapy and showed suppressed viral load on their most recent analyses. We performed a cross‐sectional analysis of the clinical and viro‐immunological characteristics of this population and excluded patients who had previous virological failures, resistance‐associated mutations (RAMs) to rilpivirine or integrase inhibitors in the historical genotype, hepatitis B infection, absence of previous genotypes, and the coexistence of HIV‐subtype A and obesity. Our aim was to evaluate the proportion of patients who could be eligible for switching to this strategy. one thousand seven hundred fifty‐two patients were eligible. One hundred and forty‐eight were excluded because of a detectable viral load. With regard to the exclusion criteria, 48 patients had coinfection with hepatitis B virus, and 744 had a history of previous virological failures. Of the 896 patients with at least one genotypic resistance test, 161 had one or more RAMs to rilpivirine and 3 had RAMs to cabotegravir. None of the patients presented the combination of obesity and the A viral subtype. Overall, 31.2% of the patients were ineligible for cabotegravir–rilpivirine, and the proportion increased to 47.3% when we considered only patients with all available information concerning resistance tests. Approximately half of our cohort of patients did not fulfill the criteria and even more patients were potentially ineligible for cabotegravir–rilpivirine due to the lack of genotypic resistance tests. Also, fertile women had to be excluded due to the lack of data about this combination during pregnancy and breastfeeding. [ABSTRACT FROM AUTHOR]