Hybrid cooperative complexes to decrease VAS score and enhance sexual function in women with vulvar lichen sclerosus.

OBJECTIVE: Lichen sclerosus is a chronic, inflammatory, progressive skin disease predominantly affecting anogenital areas. Vulvar lichen sclerosus (VLS) is one of the most common conditions treated in vulvar clinics; most patients report distressing symptoms of itching, burning, stinging, and pain (particularly during or after sexual intercourse). A preliminary, prospective, single-center study was performed to investigate the efficacy of hyaluronan hybrid cooperative complex (HCC) comprising high and low molecular weight hyaluronic acid to treat menopausal women with VLS. PATIENTS AND METHODS: Patients (N = 30) received two HCC injections at 32 mg/ml (one month apart). At baseline and one and six months after treatment, patients completed validated psychometric questionnaires to assess their self-reported pain, itching, and dryness using the Visual Analogue Scale (VAS) and sexual function by the Female Sexual Function Index (FSFI). RESULTS: After treatment with HCC, no side effects or complications were reported. VAS scores showed a trend towards reduced pain and itching intensity, and there was a statistically significant reduction in median VAS score for dryness at follow-up vs. baseline (p=0.038). For sexual function, there was a statistically significant improvement in lubrication (p=0.001) and orgasm (p=0.001) FSFI domains. CONCLUSIONS: Overall, this preliminary study demonstrated the promising efficacy of HCC in menopausal women with VLS without side effects.

Author Correction: Features of fragile people with SARS-CoV-2 infection in isolation in a COVID-19 hotel in Rome, Italy.

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (7): 2631-2638-DOI: 10.26355/eurrev_202204_28501-PMID: 35442479, published online on 15 April 2022. After publication, at the request of the Italian Ministry of Health, the authors asked to insert the following statement in the Acknowledgments section: "This research was funded by the Italian Ministry of Health (RC 2022)". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/28501.

Features of fragile people with SARS-CoV-2 infection in isolation in a COVID-19 hotel in Rome, Italy.

OBJECTIVE: Temporary COVID-19 hotels have been established in Italy to assist the homeless people that test positive for SARS-CoV-2 and require isolation. This observational study aimed to investigate the characteristics of the subjects who were isolated at the Casa tra Noi COVID-19 hotel in Rome between October 2020 and May 2021 and to estimate the duration of SARS-CoV-2 positivity according to their main socio-demographic, behavioural and clinical features. SUBJECTS AND METHODS: Socio-demographic data, clinical history, and anamnestic data of guests were collected by the clinicians reviewing the medical documentation and face-to-face interviewing. Nasopharyngeal swabs were performed every 7 days and the presence of SARS-CoV-2 was assessed by RT-PCR. Median duration of SARS-CoV-2 positivity according to socio-demographic, behavioral factors and clinical condition was calculated. RESULTS: The 196 guests (161 males, 82.1%) had a median age of 41 years (IQR: 30-53), and were mostly African (87, 44.4%). Only asymptomatic/paucisymptomatic infections were observed. Almost half of the individuals (84, 42.9%) were affected by at least one co-morbidity, the frequency of which was higher among women (57.1% vs. 39.8%, p=0.06). The date of the negative SARS-CoV-2 molecular test was known for 144 guests (73.5%). Among these, the median duration of positivity was 21 days (IQR: 14-26) and did not significantly vary with age, country of origin, smoking status, alcohol or drug abuse. Among the co-morbidities, only infectious diseases significantly modified the duration of positivity, which increased from 21 to 34 days (p=0.013). CONCLUSIONS: Hotel guests were frequently affected by physical/mental co-morbidities. Duration of SARS-CoV-2 positivity was significantly prolonged only in individuals affected by an infectious disease.

Platelet-rich plasma for genital lichen sclerosus: analysis and results of 94 patients. Are there gender-related differences in symptoms and therapeutic response to PRP?

BACKGROUND: Lichen sclerosus is a chronic relapsing inflammatory dermatosis with a predilection for anogenital skin in 85%-98% of cases and is more prevalent in women (3%) than in men (> 0.07%). OBJECTIVES: The purpose of this study was to investigate gender differences in clinical presentation and therapeutic response to treatment with platelet-rich plasma (PRP), an emerging innovative strategy for LS. METHODS: Forty-three male and 51 female patients affected by LS were evaluated. Each patient was subjected to PRP treatment (1 infiltration every 15 days, for 3 times). RESULTS: The PRP procedure was well tolerated by all patients and an overall significant decrease in symptoms was reported 6 months after PRP infiltration. Reduction in pain and burning sensation was significant in both gender but more accentuated in women than in men, whereas reduction of itching was similar. On the contrary, dyspareunia evidenced sex-related difference since a significant diminution was observed only in male. CONCLUSIONS: This study demonstrates that PRP based therapy may exert a relevant role in LS patient management due to its effect on Quality of Life (QoL) and sexual function in both gender. In addition, the study underlined gender-related differences in severity of symptoms and disease age onset.

What Is in the Field for Genetics and Epigenetics of Diabetic Neuropathy: The Role of MicroRNAs.

Despite the high prevalence of diabetic neuropathy, its early start, and its impact on quality of life and mortality, unresolved clinical issues persist in the field regarding its screening implementation, the understanding of its mechanisms, and the search for valid biomarkers, as well as disease-modifying treatment. Genetics may address these needs by providing genetic biomarkers of susceptibility, giving insights into pathogenesis, and shedding light on how to select possible responders to treatment. After a brief summary of recent studies on the genetics of diabetic neuropathy, the current review focused mainly on microRNAs (miRNAs), including the authors' results in this field. It summarized the findings of animal and human studies that associate miRNAs with diabetic neuropathy and explored the possible pathogenetic meanings of these associations, in particular regarding miR-128a, miR-155a, and miR-499a, as well as their application for diabetic neuropathy screening. Moreover, from a genetic perspective, it examined new findings of polymorphisms of miRNA genes in diabetic neuropathy. It considered in more depth the pathogenetic implications for diabetic neuropathy of the polymorphism of MIR499A and the related changes in the downstream action of miR-499a, showing how epigenetic and genetic studies may provide insight into pathogenetic mechanisms like mitochondrial dysfunction. Finally, the concept and the data of genotype-phenotype association for polymorphism of miRNA genes were described. In conclusion, although at a very preliminary stage, the findings linking the genetics and epigenetics of miRNAs might contribute to the identification of exploratory risk biomarkers, a comprehensive definition of susceptibility to specific pathogenetic mechanisms, and the development of mechanism-based treatment of diabetic neuropathy, thus addressing the goals of genetic studies.

Unusual clinical manifestation and challenging serological interpretation of syphilis: insights from a case report.

BACKGROUND: The clinical manifestations of recent syphilis can be variable, with typical and atypical patterns. Several conditions may cause atypical clinical aspects, including human immunodeficiency virus (HIV) co-infection. Besides the clinical features, co-infections may completely alter syphilis serological tests, causing interpretative difficulties and diagnostic delays. Aim of the work is to describe the difficulties encountered during the diagnostic evaluation of atypical skin manifestations and of the serology for syphilis of an HIV-infected patient who had contracted it several times. CASE PRESENTATION: In 2020, a 52-year old HIV-positive bisexual male patient was admitted to our department with a 4-month history of moderately itchy cutaneous lesions localized at his neck, trunk and arms. In 2013, the patient presented with a classic syphilitic roseola of the trunk and a secondary syphilis was diagnosed, with increased levels of rapid plasma reagin (RPR), Treponema pallidum hemagglutination assay (TPHA), anti-Treponema pallidum IgM and IgG Index. A second episode occurred in 2018, as a primary syphilis with multiple ulcerative lesions of the penis, and increased levels of RPR, IgG and IgM. In 2019, a further episode of secondary syphilis was treated with Doxycycline. In 2020, erythematous and papular lesions with vesicular components and urticarial erythema multiforme (EM)-like lesions were present at the neck, trunk and arms. Serological tests and Nucleic Acid Amplification Test (NAAT) for Treponema Pallidum were performed, as well as a cutaneous biopsy with histological and immunohistochemical evaluation of one lesion. NAAT was negative for T. pallidum. Serological test results were discordant with a new syphilis infection, showing only increased levels of RPR and anti-Treponema IgG. The cutaneous biopsy revealed a non specific histological pattern, while the immunohistochemical evaluation with anti-spirochetal antibodies was mandatory for the diagnosis of recent syphilis, showing clusters of rod-shaped elements, some of which with spiral form, focally present at the epidermis and adnexal structures. CONCLUSIONS: Nowadays, syphilis may present with atypical clinical and serological features. Physicians should be aware of these possible alterations and consider syphilis even in case of uncommon clinical aspect and unclear serological tests. Cutaneous biopsy and immunohistochemical exam may be mandatory for the diagnosis.

Usefulness of video thermography in the evaluation of platelet-rich plasma effectiveness in vulvar lichen sclerosus: preliminary study.

BACKGROUND: Lichen sclerosus (LS) is a chronic-relapsing and potentially serious skin disease that has a preference for genital skin. Currently, there is no standardized method for assessing the effects of therapies. OBJECTIVE: The objective of this preliminary study is to use video thermography (VTG) in the evaluation of vulvar lichen sclerosus (VLS) before and after platelet-rich plasma (PRP) therapy. METHODS: A sample of six female patients was enrolled. Patients were subjected to PRP treatment. Patients selected for the study had been assessed at baseline (T0) and after 7 and 30 d from PRP treatment (T1 and T2, respectively). Clinical and VTG evaluation was executed in every visit. RESULTS: The VTG examination showed at least one hypothermic area (HA) in all our patients. The average temperature measured in the vulvar and perineal region taken as a reference for each patient was found to be between 33.7 °C and 36.3 °C, with a fair difference between the patients. HAs showed thermal differences which varied between 2.2 °C and 1.2 °C. CONCLUSIONS: It is demonstrated here that PRP offers satisfactory effectiveness in treating VLS and that video thermograpy could represent a useful paraclinic method in the identification and follow-up of LS.

HIV MDR is still a relevant issue despite its dramatic drop over the years.

OBJECTIVES: To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. METHODS: Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999-2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). RESULTS: Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010-18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. CONCLUSIONS: A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome-Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients.

Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren's syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P = 0.02, OR = 1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P = 0.03, OR = 1.53), pSS (P = 0.016, OR = 1.69), and RA (P = 0.0001, OR = 2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.

Profiling of how nociceptor neurons detect danger - new and old foes.

The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro-immune interplay is still ill-defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH 1-mediated immunity but also as drivers of TH 2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide-ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

Efficacy and safety of switching to dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (TDF) or elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed HIV-infected patients in clinical practice: results from a multicentre, observational study.

OBJECTIVES: The aim of the study was to compare the efficacy and tolerability of switching antiretroviral therapy to dolutegravir + emtricitabine/tenofovir disoproxil fumarate (TDF) with those of switching to elvitegravir/cobicistat/emtricitabine/TDF in clinical practice. METHODS: In a multicentre real-life observational study, we analysed data for HIV-infected patients on antiretroviral treatment with viral load < 50 HIV-1 RNA copies/mL switching to dolutegravir + emtricitabine/TDF (dolutegravir group) or elvitegravir/cobicistat/emtricitabine/TDF (elvitegravir group). Follow-up was censored at 48 weeks. RESULTS: The 48-week estimated proportion maintaining virological efficacy was 96.1% with dolutegravir (n = 123) and 95.4% with elvitegravir (n = 186; P = 0.941). Patients in the dolutegravir group showed more treatment discontinuations, but these were mainly as a result of simplification. The elvitegravir group showed more discontinuations because of renal adverse events (2.7% versus 0% with dolutegravir). Interestingly, no difference was observed between the two regimens in central nervous system toxicity-related discontinuations. Switching to dolutegravir was associated with a better blood lipid profile. CONCLUSIONS: Switching to dolutegravir + emtricitabine/TDF was associated with similar efficacy and tolerability to switching to elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed patients in clinical practice, although reasons for discontinuation showed differences between regimens. These results should be interpreted with caution, as this is a nonrandomized comparison.

Evaluation of ATG5 polymorphisms in Italian patients with systemic lupus erythematosus: contribution to disease susceptibility and clinical phenotypes.

Systemic lupus erythematosus (SLE) is a common heterogeneous autoimmune disease that is caused by the involvement both of genetic and environmental factors. There is evidence that autophagy is involved in several aspects of SLE pathogenesis. In particular, polymorphisms in the ATG5 gene have been observed to be associated with disease susceptibility. Our aim was to verify if ATG5 polymorphisms are involved in the susceptibility to disease and its clinical phenotypes in an Italian cohort of SLE patients. This study involved 315 SLE patients and 265 healthy controls. Three polymorphisms in the ATG5 gene (rs573775, rs6568431 and rs2245214) were investigated by allelic discrimination assay. A case-control association study, a genotype/phenotype correlation analysis and a haplotype study were performed. Moreover, an expression study was conducted in peripheral blood mononuclear cells from 15 SLE patients to verify a possible effect of the three SNPs on the expression of ATG5. Among the three investigated SNPs, only the rs573775 SNP was significantly associated with disease susceptibility with the variant allele conferring a higher risk of developing SLE (OR = 1.50, p = 0.018 and OR = 1.48, p = 0.007 at the genotypic and allelic level, respectively). The variant allele of rs6568431 SNP was more present in patients with anemia (OR = 1.86, p = 0.009) and renal involvement (OR = 1.63, p = 0.06), while the variant allele of rs2245214 SNP was significantly associated with a higher risk of producing anti-DNA autoantibodies (OR = 1.66, p = 0.04). Carriers of the rs6568431 variant allele showed higher messenger RNA levels compared to the carriers of the wild-type allele, suggesting also a potential variant allele dose-dependent effect on gene expression. In conclusion, our study confirms a role for ATG5 polymorphisms both in disease susceptibility and in the modulation of clinical phenotypes in an Italian SLE cohort. These results further suggest that genetic variations in autophagy genes could play a role in autoimmune diseases susceptibility and are worth further investigation.

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV-1 replication.

OBJECTIVES: We evaluated the efficacy and tolerability of lamivudine + dolutegravir in a cohort of HIV-1 infected, treatment-experienced patients with undetectable HIV-RNA. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) and their predictors were assessed in a multicenter cohort of HIV-1 infected patients, starting lamivudine + dolutegravir after reaching viral suppression. Secondary objective was the evaluation of changes in lipid profile, renal and immunological functions at week 48. RESULTS: We enrolled 206 patients (72.8% male, with 51 years median age), who mainly switched their antiretroviral therapy for simplification (32.5%) or drug toxicity (54.5%). The estimated probability of maintaining virological suppression at 48 and 96 weeks was 98.2% and 95.1%, respectively. VF was independently predicted by cumulative time on antiretroviral therapy. The estimated probability of remaining on lamivudine plus dolutegravir was 86.7% and 80.5% at week 48 and 96, respectively. A significant improvement in immunological function (CD4 count and CD4/CD8 ratio) was evidenced at week 48, as well as a decrease in total cholesterol/HDL ratio, triglycerides and estimated glomerular filtration rate. CONCLUSIONS: Lamivudine plus dolutegravir was effective in maintaining viral suppression in our cohort and led to an improvement in metabolic and immunologic functions.

Structural modification of titanium surface by octacalcium phosphate via Pulsed Laser Deposition and chemical treatment.

In the present study, the Pulsed Laser Deposition (PLD) technique was applied to coat titanium for orthopaedic and dental implant applications. Calcium carbonate (CC) was used as starting coating material. The deposited CC films were transformed into octacalcium phosphate (OCP) by chemical treatments. The results of X-ray diffraction (XRD), Raman, Fourier Transform Infrared Spectroscopy (FTIR) and scanning electron microscopy (SEM) studies revealed that the final OCP thin films are formed on the titanium surface. Human myofibroblasts from peripheral vessels and the primary bone marrow mesenchymal stromal cells (BMMSs) were cultured on the investigated materials. It was shown that all the investigated samples had no short-term toxic effects on cells. The rate of division of myofibroblast cells growing on the surface and saturated BMMSs concentration for the OCP coating were about two times faster than of cells growing on the CC films.

A polymorphism upstream MIR1279 gene is associated with pericarditis development in Systemic Lupus Erythematosus and contributes to definition of a genetic risk profile for this complication.

Recently, a study has shown that a polymorphism in the region of MIR1279 modulates the expression of the TRAF3IP2 gene. Since polymorphisms in the TRAF3IP2 gene have been described in association with systemic lupus erithematosus (SLE) susceptibility and with the development of pericarditis, our aim is to verify if the MIR1279 gene variability could also be involved. The rs1463335 SNP, located upstream MIR1279 gene, was analyzed by allelic discrimination assay in 315 Italian SLE patients and 201 healthy controls. Moreover, the MIR1279 gene was full sequenced in 50 patients. A case/control association study and a genotype/phenotype correlation analysis were performed. We also constructed a pericarditis genetic risk profile for patients with SLE. The full sequencing of the MIR1279 gene in patients with SLE did not reveal any novel or known variation. The variant allele of the rs1463335 SNP was significantly associated with susceptibility to pericarditis ( P = 0.017 and OR = 1.67). A risk profile model for pericarditis considering the risk alleles of MIR1279 and three other genes (STAT4, PTPN2 and TRAF3IP2) showed that patients with 4 or 5 risk alleles have a higher risk of developing pericarditis ( OR = 4.09 with P = 0.001 and OR = 6.04 with P = 0.04 respectively). In conclusion, we describe for the first time the contribution of a MIR1279 SNP in pericarditis development in patients with SLE and a genetic risk profile model that could be useful to identify patients more susceptible to developing pericarditis in SLE. This approach could help to improve the prediction and the management of this complication.