Background: Atopic dermatitis (AD) is a chronic, pruritic and relapsing inflammatory skin disorder affecting children’s quality of life (QoL). Despite rising global prevalence, data on its impact on QoL in low-resource settings remain limited. This study aimed to assess the impact of AD and associated factors on the QoL of children and assesses the effect of educational intervention in Ethiopia. Methods: A prospective cohort study was conducted among 461 AD children and their caregivers across four randomly selected hospitals dermatology clinics in Ethiopia from October 2022 to March 2024. Assessments included AD Severity using Scoring Atopic Dermatitis (SCORAD), Infants’ Dermatitis Quality of Life Index (IDLQI) for children aged 0–4, and Children’s Dermatology Life Quality Index (CDLQI) for children aged 5 to 16. Participants received educational guidance from trained nurses during follow-up beyond routine AD treatment. Trained personnel collected clinical and sociodemographic data. AD severity and QoL were reassessed after 6 months. Descriptive, univariate, and linear regression analyses identified factors influencing QoL, with associations reported as odds ratios (95% CI) and significance set at p < 0.05. Results: Of 461 children, 424 (92%) completed follow-up. Most were under five (67%) with a median age of 3 years; 72.2% had AD onset before age two. Most caregivers were female (68.9%). After six months, clinical signs of AD, including dryness, erythema, excoriation, and lichenification, improved notably. Mild AD increased by 33.5%, while moderate and severe cases decreased by 17.5% and 16%, respectively. QoL significantly improved across all domains (p = 0.001). Baseline disease severity (β = 0.11), change in severity (ΔSCORAD) (β = 0.043), number of dependents (β = −0.71), and age at disease onset (β = 0.005) as significant predictors of QoL. Conclusions: AD significantly impairs QoL in Ethiopian children, with greater severity causing more disruption. Routine treatments with educational interventions significantly improve disease severity and QoL. Integrated clinical and psychosocial care approaches for pediatric AD are crucial in resource-limited settings.

Background: Vaccination against human papillomaviruses (HPVs) and cervical cancer screening represent effective tools for preventing this neoplasia, but access to health services is limited for vulnerable women. We investigated prevalence of high-risk HPV and abnormal cervical cytology, as well as knowledge about HPV and the HPV vaccine, among homeless and migrant women in Rome, Italy. Methods: Cytologic samples in PreservCyt (Hologic) were employed for liquid-based cytology (ThinPrep Processor 5000, Hologic) and high-risk HPV DNA testing (Xpert HPV assay, Cepheid). Socio-demographic data, anamnestic, and behavioral data were retrieved from electronic archives. A questionnaire was employed to assess knowledge about HPV and HPV vaccination. Results: A total of 134 women were included (median age: 43 years; interquartile range, IQR: 34-50), mostly coming from Central-South America (69, 51.5%). Of the 127 cytologic specimens collected, one (0.8%) was invalid for the HPV test and five (3.9%) were unsatisfactory for the morphological evaluation. High-risk HPV positivity was found in 18 women of the 126 women with a valid HPV test (14.3%). A total of 10 women of the 122 women with an adequate cytology (8.2%) had abnormal cytology. Overall, 57/134 women (42.6%) had never heard of HPV or were unsure about it. Only 29 of the 77 women who had heard of HPV (37.7%) knew of the HPV vaccine, and only 2 had been vaccinated in the entire study group (1.5%). Conclusions: Tailored preventive strategies and comprehensive information campaigns should be developed and implemented to enhance awareness of HPV infection and actively promote vaccination among women in vulnerable groups.

BackgroundSkin diseases are not uncommon among prisoners, primarily due to confined living conditions, limited access to proper hygiene facilities, and higher rates of skin-to-skin contact. The study aims to describe the skin disease spectrum among prison inmates Wolaita zone, southern Ethiopia.MethodsA cross-sectional study was conducted at the Wolaita zone prison to determine the spectrum of skin diseases among the prison inmates from January 1 to February 30, 2020. Every inmate with skin complaints underwent a comprehensive skin examination, and a detailed history of their skin-compliant was documented. The diagnosis primarily relied on clinical assessment by dermatologists. The data collected from paper-based abstraction sheets was entered into EpiData entry forms twice to ensure accuracy. A descriptive analysis was performed such as frequencies, mean, standard deviation and median. The statistical significance was set at 0.05.ResultOut of the 418 prison inmates who took part in the study, 223 (53.3%) were found to have skin disorders. The vast majority of the participants, specifically 381 (91.1%), were male. The age range of the participants varied from 17 to 60 years old, with an average age of 29.29 years ± 9.08 years. Skin infections were identified as the most prevalent type of skin disease, with 113 patients (50.67%) affected. Among the skin infections, fungal infections and scabies infestations were the most common, accounting for 41 cases (18.4%) and 37 cases (8.85%) respectively. In terms of inflammatory skin problems, 50 cases (11.9%) of Eczematous skin diseases were diagnosed. Within this category, Atopic Eczema and Nummular eczema accounted for 19 (4.5%) and 8 (1.9%) cases, respectively. Notably, a case of Leprosy was also diagnosed and linked to treatment within this prison.ConclusionIn this study, infectious skin diseases and manageable inflammatory skin diseases are commonly diagnosed as dermatoses among prison inmates at Wolaita zone Prison. The inmates have the right to the best of health, including skin health, so health professionals posted to prison services must be trained to diagnose and manage skin disorders in prisons.

Background/Objective: This retrospective observational study describes the social, health, and psychological conditions of children living in a disadvantaged and degraded suburb of Rome Metropolitan City during the COVID-19 pandemic as registered by the primary healthcare service of the Solidarity Medicine Institute, with the aim of fighting social exclusion and health disparities during lockdown and offering free health care to vulnerable families. Methods: The access to pediatric interventions was assessed from April 2020 to December 2022. For each child, biometric parameters were recorded, and the physical and psychological states of health were assessed. Furthermore, data regarding family socio-economic variables were collected. Results: From April 2020 to December 2022, 638 children, aged 0 to 18 years, had access to the healthcare system, which was provided by the Solidarity Medicine Institute, with a total of 2300 pediatric visits. Moreover, food supplements, drugs, and hygiene kits that were necessary for the containment of the COVID-19 infection were freely distributed at the center. The highest proportion of children included in this study were from African and Eastern European families (46% and 35.8%, respectively), and 41% of these children did not have a pediatrician from the public health service. Children aged 0 to 5 years comprised 50.81% of the entire population of this study. Nutritional status assessment indicated that among the 117 infants aged 0-12 months, 5.7% were below the 3rd weight percentile, while 28.9% exceeded the 85th weight percentile. BMI assessment for children aged 2 years and older (i.e., 521 children) indicated that 21.7% of these children were overweight, and 9.5% were obese. Sixty-nine cases of psychiatric disorders were also detected among these children, with a high frequency of cases of Specific Language Disorder (31.8%), Attention Deficit Hyperactivity Disorder (21.7%), and Specific Learning Disorder (14.5%). Psychiatric and rehabilitative interventions were also offered. Conclusions: The Solidarity Medicine Institute responded to the request of the municipality of Rome to remain open and offer social and health assistance to the most vulnerable people during the pandemic. The Solidarity Medicine Institute has efficaciously served a fragile pediatric population, intercepting social, health, and psychological needs and overcoming social exclusion, health disparity, and the fragmentation of welfare services exacerbated by the COVID-19 pandemic.

Abstract Background Currently, European and especially Italian healthcare systems are being challenged with providing medical care to an increasing number of refugees but also to the homeless living on the streets, in reception facilities or cohabitation. In 2022, over 200,000 irregular arrivals of migrants to Europe were recorded, coming from mainly African and also Asian countries and frequently via Mediterranean migration routes. Objectives This study aims to report the results of a social support programme to provide treatment and improve health‐related quality of life (HrQoL) in refugees and homeless people. Methods Observational study during the year 2022, including patients with an immigration background visiting the Clinica dell'Istituto di S. Maria e S. Gallicano di Roma, Italy (IRCCS), or being homeless during this observational study. Results We have seen 210 patients. In 177 cases (84.3%), a definitive diagnosis is known. Most frequent skin conditions were infectious, allergic or due to secondary inflammation. We also saw rare cutaneous conditions like Madelung disease or Darier disease. Conclusions We provided dermatological consultation and treatment to this very vulnerable population, and our experience shows that this social support programme to enable access to dermatological consultation for the poor was able to improve not only the clinical condition but also the HrQoL 4 weeks after consultation and beginning of treatment.

BackgroundFew data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients.ObjectiveTo investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy.MethodsWe measured SARS-CoV-2 anti-spike antibodies, anti-Omicron neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80–92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti-Omicron). T cell response was assessed at T post-3D.ResultsAn increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the Omicron variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti-Omicron neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the Omicron variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts.ConclusionFHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response.

Abstract Background Patients with human immunodeficiency virus (HIV) infection may present a large variety of skin manifestations, often associated with significant morbidity. In turn, dermatological diseases may represent an early sign of HIV infection, particularly in resource‐limited settings. Objectives This study aimed to assess the spectrum of dermatological diseases and their potential value as clinical proxies for the early detection and management of HIV in a rural region of Ethiopia. Methods The study was performed on a population of 67,161 patients with skin diseases attending the Italian Dermatological Center in Mekele, Tigray region, Ethiopia. HIV infection was diagnosed in 1892 individuals (1065 female), all naïve to antiretroviral therapy. Results Infectious skin diseases were present in 57.2% of the total HIV population. Among the infectious skin manifestations, dermatophytosis (20.5%), impetigo (5.9%), candidiasis (4.7%) and molluscum contagiosum (4.7%) were significantly more represented in patients with HIV infection (p < 0.001). Regarding the noninfectious manifestations, pruritus and atrophy of the papillae on the tongue were significantly associated with HIV (p < 0.001). Notably, females had a significantly higher incidence of dermatophytosis and seborrheic dermatitis as compared to their male counterparts (p < 0.001), whereas scabies, psoriasis and leishmaniasis were significantly more frequent in males (p < 0.001). Conclusions Skin manifestations are common in HIV patients, often reflecting compromised immune status. In addition, Dermatophytosis and pruritus were the most frequently reported manifestations of HIV, thus representing useful clinical proxies to raise the suspicion of an underlying HIV infection. Besides, gender differences in skin manifestations should also be considered in the clinical evaluation.

Background: Hashimoto’s thyroiditis (HT) is an autoimmune disease that progressively leads to thyroid gland destruction and hypothyroidism. Patients produce antibodies against two thyroid-specific antigens: thyroglobulin and thyroid peroxidase. As a result of the abnormal amount of thyroid hormone produced and its autoimmune etiology, patients with HT display a higher frequency of either autoimmune or non-autoimmune dermatological disorders. On ultrasound examination, HT can be detected by observing an enlarged thyroid gland with hypoechoic parenchymal regions or by observing a small gland indicating atrophy and diffusely heterogeneous parenchyma. Changes in the parenchymal vascularity can be observed as decreased or increased levels of vascularization. Objective: This study aimed to analyze the role of clinical data and ultrasound evaluation of patients with HT in suggesting an association with dermatological disorders. Patients and methods: Complete dermatological and endocrinological assessments as well as ultrasonography of the thyroid and lymphnodes were performed in HT patients. Results: The data obtained showed that a family history of thyroid disease, increased diameter of the inferior thyroid artery, and the presence of cervical lymphadenopathy were more frequent in the group of patients with dermatological diseases. Taken together, our results suggest the usefulness of ultrasound in determining a possible association between HT and dermatological disorders.

Introduction Immunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines. Methods Here we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation. Results We show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus. Discussion These data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.

Skin pigmentation is the most variable human characteristic that can be observed and has been used throughout history to classify humans into distinct groups. Many factors influence skin colour, but the melanin pigment is considered the most important because its type and quantity can determine variations in pigmentation shades. The evolution of skin pigmentation started around 1.6-2 million years ago. As a result of migratory phenomena to places with less ultraviolet radiation (UVR) and other seasonal regimes, the selection of depigmented skin and different tanning capabilities occurred over time. Thus, genetic adaptation to new environmental conditions gradually led to changes in skin pigmentation. Despite the biological importance of pigmentation, variation in skin colour has led to social and health inequalities. Since Linnaeus, skin colour classifications have been used to describe different human groups, encouraging the misuse of a biological characteristic. This review examines the characterisation of pigmentation and its evolution through history and society. The unequal perception of pigmentation diversity has led to an incomplete state of dermatological training and issues in medical approach in dermatology. The consciousness of all these aspects increases the need to address and overcome dermatologic and social health disparities related to skin pigmentation.

Stimulation of melanocytes and murine melanoma cells with αMSH plus the PI3K inhibitor LY294002 resulted in ROS increase, oxidative DNA damage, and pigment retention. We performed cellular and molecular biology assays (Western blot, FACS, immunofluorescence analysis, scratch assay) on murine and human melanoma cells. Treatment with αMSH plus LY294002 altered cortical actin architecture. Given that cytoskeleton integrity requires energy, we next evaluated ATP levels and we observed a drop in ATP after exposure to αMSH plus LY294002. To evaluate if the αMSH-activated PI3K pathway could modulate energy metabolism, we focused on glucose uptake by analyzing the expression of the Glut-1 glucose translocator. Compared with cells treated with αMSH alone, those exposed to combined treatment showed a reduction of Glut-1 on the plasma membrane. This metabolic alteration was associated with changes in mitochondrial mass. A significant decrease of the cell migratory potential was also observed. We demonstrated that the αMSH-dependent PI3K pathway acts as a regulator of energy metabolism via glucose uptake, influencing the actin cytoskeleton, which is involved in melanosome release and cell motility. Hence, these results could constitute the basis for innovative therapeutical strategies.

OBJECTIVE:This study aimed to investigate COVID-19 spread among people experiencing homelessness (PEH), undocumented migrants (UMs), and shelter staff of homeless service sites. Another aim has been to prevent an outbreak among these populations. A San Gallicano Institute's initiative to sustain the health system in helping hard-to-reach populations, very often with no community medical care coverage.SUBJECTS AND METHODS:The San Gallicano Dermatological Institute performed active surveillance for COVID-19 on PEH and UMs living in Rome and Latina, Italy. The screening was performed with two swabs: real-time polymerase chain reaction (RT-PCR) and antigen rapid tests.RESULTS:From June 2020 to January 2022, we performed 10,651 tests: 5,442 molecular swabs and 5,209 antigen rapid tests. A total of 3,503 individuals were screened. The prevalence of SARS-CoV-2 infection was 2.9% among the health and social workers and 5.7% among PEH and UMs. None of the people positive for COVID-19 had symptoms or signs of several illnesses. PEH and UMs who tested positive for COVID-19, asymptomatic or pauci-symptomatic, were transferred to a COVID Hotel or dedicated apartment for further clinical monitoring.CONCLUSIONS:People experiencing homelessness and undocumented migrants are often not registered in the National Health Service and, therefore, difficult to trace. These data could aid in estimating the spread of SARS-CoV-2 among people experiencing homelessness, undocumented migrants, and shelter staff in two Italian cities.

Background Sentinel lymph node (SLN) biopsy in cutaneous melanoma patients evaluates the regional draining basin for occult micrometastatic disease. Occasionally, nonidentification of SLN impairs the acquisition of this important prognostic factor. Objectives To investigate the outcomes of melanoma patients with negative lymphoscintigraphic findings and patients who underwent SLN biopsy from 2004 to 2015 (n = 1200) were retrospectively reviewed for tumor characteristics and clinical outcomes. Methods Patients with nonvisualized lymph nodes (NV group) who underwent only preoperative lymphoscintigraphy were separated and compared with a cohort drawn from all melanoma patients who completed the surgical procedure within the same period (V group). Results A negative lymphoscintigraphic scan was observed in 38 cases (3.2% of all patients). The NV group showed a significantly older age (median 66.0 vs. 48.3 years; P < 0.0001). Head and neck melanomas were more frequent in the NV group compared to the control group (25.1 vs. 7.8%; P = 0.009). Tumor characteristics such as ulceration and Breslow thickness do not influence the lymphoscintigraphy result. No differences were found in overall survival (OS) and disease-free survival (DFS) between the groups. Conclusions The nonvisualization of regional lymph nodes by lymphoscintigraphy is more frequent in older patients with head and neck melanomas. From the clinical point of view, no specific recommendation emerged for patients’ management because the nonvisualization of the SLN did not show a significant influence on DFS and OS rates. However, lack of knowledge of lymph node status suggests performing a tighter follow-up eventually by ultrasound evaluation of all potential lymph node drainage basins.

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. Compared with healthy individuals, fragile patients have a lower rate of humoral and cellular response after primary vaccination schedule and booster dose. The type of immunosuppressive treatment has greater impact on humoral response than disease subtype, but it has a lower influence on T-cell response.

BackgroundLichen sclerosus is a chronic relapsing inflammatory skin disease, which involves most commonly the anogenital region. The gold standard in treatment is ultra-potent topical steroids (clobetasol propionate): it aims at controlling the symptoms, stopping further scarring and distortion, and reducing the risk of cancer. ObjectivesThe aim of this preliminary study is to evaluate the efficacy of injecting Hybrid Cooperative Complexes of Hyaluronic Acid (HCC) for the treatment of vulvar lichen sclerosus (VLS). MethodsTwenty female adult patients (range: 21-78 years), aged over 18, with histopathological diagnosis of lichen sclerosus and good general conditions were enrolled. Patients underwent HCC infiltration every month, for 3 times. Patients were evaluated at baseline (T0) and after one (T1) and six months (T2) after treatment. During every visit, each patient was studied clinically and with videothermography. Itching, burning sensation, pain, and dyspareunia were reported by patients at T0, T1, and T2. The effectiveness of the treatment on patients' quality of life and sexual function was evaluated using the Dermatology Life Quality Index (DLQI) and the Female Sexual Function Index (FSFI) at T0 and at T2. ResultsThe results of this preliminary study are very promising, in fact, all patients had a significant reduction in most symptoms after 1 and 6 months of HCC treatment. The reduction of patients with itching (p value <= 0.001), pain (p value = 0.031), and burning sensation (p = 0.004) at 6 months is significant. The analysis of DLQI scores revealed a significant improvement in patients' quality of life. At baseline, the average score of DLQI (+/- SD) was 5.89 +/- 3.68 while at follow-up it was 3.42 +/- 2.36 (p = 0.002). ConclusionsOur preliminary study has demonstrated the validity and tolerability of HCC infiltrations in patients with VLS, and the effectiveness of HCC in reducing symptoms and, thus, to improve sexuality and patient quality of life.

BACKGROUND: Pesticides are widely used fin greenhouses and they may be toxic to humans and greenhouse workers are very susceptible to pesticide exposure. The aim of this study was to evaluate the clinical and instrumental features of occupational contact dermatitis in greenhouse workers and to investigate the role of the skin barrier before and after the activity in the greenhouse.METHODS: Twenty-nine greenhouse workers were enrolled. All the subjects were evaluated by an expert dermatologist, and skin prick tests and patch tests were performed. Finally, clinical evaluation has been integrated with non-invasive diagnostic techniques, such as telethermography, corneometry and trans-epidermal water loss (TEWL) measurements.RESULTS: Clinical examination revealed early cutaneous photo-aging, located in the chronically sun-exposed areas, xerosis, fissures and hyperkeratosis of the hands. The non-invasive diagnostic techniques showed alteration of skin barrier function.CONCLUSIONS: Skin barrier alteration can favor the persistence of pesticides on the skin can be responsible for chronic dermatitis of the hands.

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.

Over the last few decades, the need to reduce and optimize patient medical radiation exposure has prompted the introduction of novel reconstruction algorithms in computed tomography (CT). Against this backdrop, the present study aimed to assess whether reduced radiation dose CT images reconstructed with the new-generation adaptive statistical iterative reconstruction (ASiR-V) maintain the same image quality as that of routine image reconstruction. In addition, the optimization of image quality parameters for the ASiR-V algorithm (e.g., an optimal combination of blending percentage and noise index (NI)) was investigated. An abdominal reference phantom was imaged using the routine clinical protocol (fixed noise index of 18 and 40% ASiR reconstruction). Reduced radiation dose CT scans were performed with varying NI (22, 24, and 30) and using the ASiR-V reconstruction algorithm. Quantitative and qualitative analyses of image noise, contrast, and resolution were performed against NI and reconstruction blending percentages. Our results confirm the ability of the ASiR-V algorithm to provide images of high diagnostic quality while reducing the patient dose. All the parameters were improved in ASiR-V images as compared to ASiR. Both quantitative and qualitative analyses showed that the best agreement was obtained for the images reconstructed using ASiR-V with NI24 and a high percentage of blending (70–100%). This preliminary study results show that ASiR-V allows for a significant reduction in patient dose (about 40%) while maintaining a good overall image quality when appropriate NI (i.e., 24) is used.

BACKGROUND:Approximately 20-50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need.METHODS:RNA sequencing of primary colorectal cancer specimens vs adjacent liver tissue vs synchronous and asynchronous liver metastases. Pathways enrichment analyses. The Library of Integrated Network-based Cellular Signatures (LINCS)-based and Connectivity Map (CMAP)-mediated identification of FDA-approved compounds capable to interfere with a 22 gene signature from primary CRC and liver metastases. Testing the identified compounds on CRC-Patient Derived Organoid (PDO) cultures. Microscopy and Fluorescence Activated Cell Sorting (FACS) based analysis of the treated PDOs.RESULTS:We have found that liver metastases acquire features of the adjacent liver tissue while partially losing those of the primary tumors they derived from. We have identified a 22-gene signature differentially expressed among primary tumors and metastases and validated in public databases. A pharmacogenomic screening for FDA-approved compounds capable of interfering with this signature has been performed. We have validated some of the identified representative compounds in CRC-Patient Derived Organoid cultures (PDOs) and found that pentoxyfilline and, to a minor extent, dexketoprofen and desloratadine, can variably interfere with number, size and viability of the CRC -PDOs in a patient-specific way. We explored the pentoxifylline mechanism of action and found that pentoxifylline treatment attenuated the 5-FU elicited increase of ALDHhigh cells by attenuating the IL-6 mediated STAT3 (tyr705) phosphorylation.CONCLUSIONS:Pentoxifylline synergizes with 5-Fluorouracil (5-FU) in attenuating organoid formation. It does so by interfering with an IL-6-STAT3 axis leading to the emergence of chemoresistant ALDHhigh cell subpopulations in 5-FU treated PDOs. A larger cohort of CRC-PDOs will be required to validate and expand on the findings of this proof-of-concept study.