Humoral and T-Cell Immune Response After 3 Doses of Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Fragile Patients: The Italian VAX4FRAIL Study.

BACKGROUND: Patients with solid or hematological tumors or neurological and immune-inflammatory disorders are potentially fragile subjects at increased risk of experiencing severe coronavirus disease 2019 and an inadequate response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: We designed a prospective Italian multicenter study to assess humoral and T-cell responses to SARS-CoV-2 vaccination in patients (n = 378) with solid tumors (ST), hematological malignancies (HM), neurological disorders (ND), and immunorheumatological diseases (ID). A group of healthy controls was also included. We analyzed the immunogenicity of the primary vaccination schedule and booster dose. RESULTS: The overall seroconversion rate in patients after 2 doses was 62.1%. Significantly lower rates were observed in HM (52.4%) and ID (51.9%) than in ST (95.6%) and ND (70.7%); a lower median antibody level was detected in HM and ID versus ST and ND (P < .0001). Similar rates of patients with a positive SARS-CoV-2 T-cell response were found in all disease groups, with a higher level observed in ND. The booster dose improved the humoral response in all disease groups, although to a lesser extent in HM patients, whereas the T-cell response increased similarly in all groups. In the multivariable logistic model, independent predictors of seroconversion were disease subgroup, treatment type, and age. Ongoing treatment known to affect the immune system was associated with the worst humoral response to vaccination (P < .0001) but had no effect on T-cell responses. CONCLUSIONS: Immunosuppressive treatment more than disease type per se is a risk factor for a low humoral response after vaccination. The booster dose can improve both humoral and T-cell responses.

Alpha, Beta, and Gamma Human Papillomaviruses in Genital Lichen Sclerosus: A Retrospective Cross-Sectional Study.

BACKGROUND: Lichen sclerosus (LS) is an inflammatory disease mostly arising at the genital level. It is unclear whether human papillomaviruses (HPVs) have an etiological significance in LS, and data on their prevalence in patients with LS are controversial. OBJECTIVES: The authors assessed alpha, beta, and gamma HPV prevalence in patients with genital LS. The association of HPV positivity with demographic and clinical factors was also investigated. METHODS: One hundred thirty-two formalin-fixed, paraffin-embedded LS samples (2016-2020) were retrieved from the archives of a pathology department. Alpha HPVs were genotyped with the INNO-LiPA HPV Genotyping Extra II kit. Beta and gamma HPVs were searched by multiplex Polymerase Chain Reaction. Immunostaining for p16 INK4a was performed on high-risk HPV-positive samples. RESULTS: Patients had a median age of 61 years, were mostly women ( n = 73, 55.3%), and with an early disease stage ( n = 79, 59.8%). Alpha HPVs were detected in 12/132 cases (9.1%). Among the 5 high-risk HPV-positive cases, only 2 displayed a strong and diffuse p16 INK4a staining. Beta genus was the most prevalent (35/132, 26.5%) and HPV5 was the most frequent beta genotype (25/132, 18.9%). There were 3 gamma HPV-positive cases among those with a valid result (3/131, 2.3%). Multiple infections with genotypes belonging to different genera were infrequent (3/131, 2.3%). No significant differences in the prevalence of the individual genera were observed according to sex and disease stage. CONCLUSIONS: Of the 3 HPV genera, beta genus showed the highest prevalence. Further research is needed to clarify whether the presence of beta HPVs in genital LS has a clinical significance.

Metastatic Melanoma: Liquid Biopsy as a New Precision Medicine Approach.

Precision medicine has driven a major change in the treatment of many forms of cancer. The discovery that each patient is different and each tumor mass has its own characteristics has shifted the focus of basic and clinical research to the singular individual. Liquid biopsy (LB), in this sense, presents new scenarios in personalized medicine through the study of molecules, factors, and tumor biomarkers in blood such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes and circulating tumor microRNAs (ct-miRNAs). Moreover, its easy application and complete absence of contraindications for the patient make this method applicable in a great many fields. Melanoma, given its highly heterogeneous characteristics, is a cancer form that could significantly benefit from the information linked to liquid biopsy, especially in the treatment management. In this review, we will focus our attention on the latest applications of liquid biopsy in metastatic melanoma and possible developments in the clinical setting.

The efficacy of injecting hybrid cooperative complexes of hyaluronic acid for the treatment of vulvar lichen sclerosus: A preliminary study.

Lichen Sclerosus is a chronic-relapsing inflammatory skin disease usually involving the anogenital region lacking a resolutive therapy. Potent to high-potent topical corticosteroids are considered to be the standard first-line treatment. The objective of this preliminary study is to evaluate the efficacy of injecting Hybrid Cooperative Complexes of Hyaluronic Acid (HCC) in the treatment of Vulvar Lichen Sclerosus (VLS). Twenty-female patients (range 21-78 years) with histopathologic diagnosis of lichen sclerosus and good general conditions were enrolled. Patients underwent HCC infiltration every month, for three times. Patients had been assessed at baseline (T0) and after 1 and 6 months from treatment (T1 and T2, respectively). Clinical evaluation was executed in every visit. Itching, burning sensation, pain and dyspareunia were reported by a patient at T0, T1, and at T2. The effectiveness of the treatment on patients' quality life and sexual life was assessed using the Dermatology Life Quality Index (DLQI) at T0 and at T2. During or after the treatment no complications or side-effects were observed. All patients had a significant reduction in most symptoms after 1 and 6 months of HCC treatment. The reduction of patients with itching (p ≤ 0.001), pain (p = 0.031), burning sensation (p = 0.004) at 6 months is significant. The analysis of DLQI scores revealed a significant improvement in patients' quality of life. The DLQI mean score (±SD) at baseline and at follow-up was 5.89 ± 3.68 and 3.42 ± 2.36 (p = 0.002), respectively. Our preliminary study has demonstrated the safety and tolerability of HCC infiltrations in patients with VLS, and the effectiveness of HCC in reducing symptoms and, thus, to improve patient Quality of Life.

Psoriasis in Tigray, Ethiopia: Focusing on available treatments.

Psoriasis has been reported to be rare in people with skin of color. However, the actual prevalence is probably underestimated by the lack of wide epidemiological studies. The aim of the study is to present our experience in Tigray, Ethiopia, focusing on the issues related to diagnosis, clinical features and therapies. A total of 1288 people affected by psoriasis were visited and 954 were included in a retrospective analysis through the review of medical records of patients attending at three Dermatologic Centers in Ethiopia from 2005 to 2016. The most common clinical form is plaque psoriasis (62.9%), followed by guttate (13.9%), pustular (9.5%), inverse (7.5%), and erythrodermic (6.1%) ones. The prevalence of psoriatic arthritis is 17%. It is often diagnosed late resulting in particularly deforming and debilitating disease. Patients with severe psoriasis often require hospitalization due to the reduced availability of effective treatments and appropriate skin care, resulting in a prolonged recurrence rate or decreased disease-free interval. In poorer rural areas, patients use some traditional African plants such as Kigelia africana which have been shown to have partial benefits in the treatment of psoriasis. Unfortunately, the only available conventional therapies are topical steroids, salicylic acid, methotrexate, and the sun. More studies concerning the appropriate management of people with psoriasis in low income countries, including standardization of indigenous therapies and a reduction of costs of conventional drugs, could help the care of people with psoriasis.

Is Melanoma Progression Affected by Thyroid Diseases?

Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic-pituitary-thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients.

Effectiveness of anti-interleukin 23 biologic drugs in psoriasis patients who failed anti-interleukin 17 regimens. A real-life experience.

Among the most recent biologic drugs available for psoriasis therapy, those targeting interleukin-17 (secukinumab and ixekizumab) or its receptor (brodalumab) have been shown to be quickly effective. However, in those patients who failed one or more of the above-cited drugs, real-life data on the effectiveness of switching to one anti-interleukin-23 biologic (guselkumab, risankizumab, or tildrakizumab) are very scarce. Here, we report our experience in treating 12 multi-failure psoriatic patients, prospectively followed-up over 6 months, who showed a significant improvement in their psoriasis after switching from an anti-interleukn-17 to an anti-interleukin-23 drug.

NB-UVB plus oral Polypodium leucotomos extract display higher efficacy than NB-UVB alone in patients with vitiligo.

Polypodium leucotomos displayed a synergic effect with NB-UVB in psoriasis, but its application on vitiligo remains understudied. The aim of this study was to investigate whether oral supplementation with leaves extract of Polypodium leucotomos (PL) improves narrow band (NB) UVB phototherapy-induced repigmentation. Forty-four patients with generalized vitiligo were enrolled in this randomized, prospective, placebo controlled study. Twenty-three patients were randomly selected to receive combined treatment with NB-UVB phototherapy and 480 mg oral PL twice daily while 21 patients received NB-UVB phototherapy combined with placebo. All subjects were treated with NB-UVB twice weekly for 6 months. Our results demonstrated that oral PL combined with NB-UVB improved repigmentation as well as increased the response rate compared with patients treated with NB-UVB alone (47.8% vs 22%). Our study suggests that oral supplementation of PL and NB-UVB phototherapy enhance the extent of repigmentation.

Instrumental evaluation of skin barrier function and clinical outcomes during dupilumab treatment for atopic dermatitis: An observational study.

BACKGROUND: Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by pruritus, xerosis, and skin barrier dysfunction. Skin barrier alteration is associated with an increase in trans-epidermal water loss (TEWL) and reduction in skin hydration. Dupilumab is a monoclonal antibody targeting interleukin-13 modulating pro-inflammatory signal transduction, which has been approved for moderate to severe AD. The aim of this study is to evaluate the effects of Dupilumab on skin barrier functions, using non-invasive instruments and clinical evaluation. MATERIALS AND METHODS: Thirty patients affected by moderate-severe AD, who had been administered dupilumab, were evaluated by clinical examination and through the instrumental measurements of TEWL and corneometry at the baseline (T0) and 8 weeks (T1) on lesional skin. The clinical evaluation was performed using the Eczema Area and Severity Index (EASI) score. Moreover, a Dermatology Life Quality Index (DLQI) and 7-day numeric rating scale (NRS) questionnaires were administered to each patient. RESULTS: The instrumental parameters of skin barrier recovery confirmed the clinical improvement outcomes with a statistically significant reduction of TEWL at T1. CONCLUSION: Our data confirm the clinical outcomes already reported in the literature and show that there was an inverse proportional correlation between TEWL levels and clinical severity after 8 weeks of treatment with dupilumab.

Precision Medicine and Melanoma: Multi-Omics Approaches to Monitoring the Immunotherapy Response.

The treatment and management of patients with metastatic melanoma have evolved considerably in the "era" of personalized medicine. Melanoma was one of the first solid tumors to benefit from immunotherapy; life expectancy for patients in advanced stage of disease has improved. However, many progresses have yet to be made considering the (still) high number of patients who do not respond to therapies or who suffer adverse events. In this scenario, precision medicine appears fundamental to direct the most appropriate treatment to the single patient and to guide towards treatment decisions. The recent multi-omics analyses (genomics, transcriptomics, proteomics, metabolomics, radiomics, etc.) and the technological evolution of data interpretation have allowed to identify and understand several processes underlying the biology of cancer; therefore, improving the tumor clinical management. Specifically, these approaches have identified new pharmacological targets and potential biomarkers used to predict the response or adverse events to treatments. In this review, we will analyze and describe the most important omics approaches, by evaluating the methodological aspects and progress in melanoma precision medicine.

Adipose tissue stromal vascular fraction and adipose tissue stromal vascular fraction plus platelet-rich plasma grafting: New regenerative perspectives in genital lichen sclerosus.

Lichen sclerosus (LS) is a chronic relapsing, inflammatory skin disorder usually involving the anogenital region of both sexes lacking a resolutive therapy. This study compared adipose tissue derived-stromal vascular fraction (AD-SVF) and AD-SVF-enriched platelet-rich plasma (PRP) therapy in the management of genital LS patients. Additionally, in vitro evaluation of cells and growth factors contained in the injected SVF has been evaluated as possible predictive factors for treatment outcome. The study population was 40 patients diagnosed with LS who were symptomatic despite medical treatment. Patients (age 43-78 years) randomized into two groups using a 1:1 allocation ratio, were evaluated clinically and assessing dermatology life quality index (DLQI) before and 6 months after treatment. Both procedures demonstrated a strong safety profile with no complications linked to the therapy. After 6 months, both treatments allowed for a significant improvement respect to baseline. Combinatory therapy demonstrated decreased efficacy in late stage patients. No correlations have been found between clinical and biological findings. AD-SVF and AD-SVF plus PRP are safe and effective regenerative approaches for genital LS patients. Clinical results support the preferential use of combinatory therapy for early stage patients confirming a synergic effect of AD-SVF and PRP. In contrast, AD-SVF plus PRP is discouraged for late stage patients.

Recreational drugs and STI diagnoses among patients attending an STI/HIV reference clinic in Rome, Italy.

BACKGROUND: An observational study was conducted to assess recreational drug use in association with recent STIs among clients of an STI/HIV reference centre in Rome, Italy. METHODS: Attendees self-compiled a questionnaire concerning sexual behaviours and drug use, including the nine drugs used for sex (amphetamines, poppers, cocaine, ketamine, erectile dysfunction agent (EDA), steroids and the three chemsex drugs, ie, chems: γ-hydroxybutyric acid/γ-butyrolactone, crystal and Mcat). RESULTS: Overall, 703 patients participated, with men who have sex with men (MSM) accounting for 50.4% of the total and 73.2% of HIV-positive patients. Apart from condylomatosis, whose prevalence was higher among females (38.8%) and non-MSM (45.8%) than MSM (14.4%), STIs were more frequent among MSM, particularly syphilis (14.1%), gonorrhoea (4.8%), urethritis (3.4%) and hepatitis A (6.5%). Recreational drug use was significantly more frequent among MSM (39.8% vs 17.6% in females and 22.7% in non-MSM). A total of 26.3% of MSM used at least one of the nine drugs and 5.1% at least one of the three chems. Cocaine (13.3%) and poppers (13.0%) were the most used sex drugs in MSM.The use of any of the nine drugs was associated with being MSM (adjusted OR (AOR): 1.94, 95% CI 1.05 to 3.58), sex with partner contacted online (1.99, 95% CI 1.14 to 3.45), group sex (4.08, 95% CI 2.40 to 6.93) and STI in the last year (1.65, 95% CI 1.05 to 2.61). Use of any of the nine chems among MSM was associated with condomless sex (2.24, 95% CI 1.21 to 4.14), group sex (2.08, 95% CI 1.01 to 4.31) and STI diagnosis in the last year (4.08, 95% CI 2.32 to 7.19). CONCLUSIONS: Our data suggest that recreational drug use is quite common among MSM in Italy. No evidence of association with STI was found among non-MSM and females, where only cannabis and cocaine use was reported. The use of chems is still limited, but cocaine, poppers and EDA are widely used among MSM. Recreational drug use appears associated with high-risk sexual behaviours and a higher risk of STI.

Treatment of severe psoriasis with ixekizumab in a liver transplant recipient with concomitant hepatitis B virus infection.

Treatment of severe psoriasis (PsO) in organ transplant (OT) patients is difficult. In fact, systemic drugs used for PsO therapy can be detrimental to transplanted organs and/or can increase the risk of serious infections in subjects already taking antireject medicines. Current guidelines fail to give indications on how to manage PsO OT subjects. Moreover, only a few cases of patients with the above-cited characteristics treated with systemic therapies have been published so far. Here, we report our experience concerning a liver transplant patient successfully treated with ixekizumab for his psoriasis throughout 1 year.

Recommendations for infectious disease screening in migrants to Western Europe with inflammatory arthropathies before starting biologic agents. Results from a multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI) facing the largest impact of the flow of migrants today.

OBJECTIVES: Inflammatory arthritis needs infectious disease screening before starting a biologic agent, however, few data are known about migrant patients, who represent a peculiar population which requires a multidisciplinary approach among international health specialists and should also be considered by health authorities. For this reason, the Italian and Spanish Societies of Rheumatology (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a multidisciplinary task force in order to produce specific recommendations about screening and advices to be considered in migrant patients with inflammatory arthritis candidate to receive biological therapy, according to their geographical origin. METHODS: The experts provided a prioritised list of research questions and the eligible spectrum of inflammatory arthritis, biologic drugs and infectious disease were defined in order to perform a systematic literature review. A search was made in Medline, Embase and Cochrane library, updated to March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are already considered in national and international recommendations, were not included. The strength of each recommendation was determined. RESULTS: The task force members agreed on 7 overarching principles. The risk of reactivation of selected potentially latent infectious disease was addressed in migrants with inflammatory arthritis candidates for biologics was considered and 15 potentially relevant infections were identified. CONCLUSIONS: Fifteen disease-specific recommendations were formulated on the basis of high level of agreement among the experts panel.