A Review of the Literature on the Multiple Forms of Stigmatization of Caregivers of Children with Autism Among Ethnic Minority Groups.

Multiple forms of stigmatization are experienced by caregivers of children with autism among ethnic minority (EM) groups in various countries. Such forms of stigmatization can lead to delayed assessment and services for mental health among children and caregivers. This review identified the research literature on the types of stigmatization experienced by caregivers of children with autism with an EM background. A total of 19 studies published after 2010 (i.e., 12 from the USA, 2 from the UK, 1 from Canada, and 1 from New Zealand) of caregivers of 20 ethnicities were identified and reviewed, and their reporting qualities systematically also assessed. Four main themes: (1) self-stigma, (2) social stigma, (3) stigma towards EM parents of children on the autism spectrum, and (4) service utilization stigma, and nine sub-themes were identified. The discrimination experienced by caregivers were extracted, synthesized, and further discussed. While the reporting quality of the studies included is good, the depth of the understanding of this under-researched yet important phenomenon is very limited. The multiple forms of stigmatization experiences are complex, and it may be difficult to disentangle whether the causes of stigmatization were autism and/or EM related, and the types of stigmatization can vary enormously among different ethnic groups in different societies. More quantitative studies are needed to quantify the impacts of multiple forms of stigmatization on families of children with autism in EM groups so that more socially inclusive support for caregivers with an EM background in host countries can be developed.

Association of sedentary time with risk of cardiovascular diseases and cardiovascular mortality: A systematic review and meta-analysis of prospective cohort studies.

Given the high prevalence of cardiovascular disease (CVD), we meta-analysed CVD relative risk (RR) in relation to high vs. low categories of self-reported and objectively assessed sedentary behaviours from cohort studies; in a sub-sample (n = 4 studies), the theoretical substitution of one hour spent sedentary with the same amount of time spent in light-intense physical activity was evaluated. Based on 19 studies (60,526 fatal and non-fatal CVD, 1,473,354 individuals and 13,559,139 persons-year) we estimated a 30% increased CVD risk for high vs. low categories of sedentary behaviour (RR = 1.29, confidence interval (CI) = 1.22;1.37). Every hour spent sedentary corresponds to a 5% increased fatal and non-fatal CVD risk (RR = 1.05, CI = 1.02;1.07). Dose-response meta-analysis revealed that sedentary behaviour is statistically significantly associated to fatal and non-fatal CVD risk following a J-shaped relation. Substituting one hour spent sedentary with physical activity of light intensity reduced the risk of fatal and non-fatal CVD events by one-fifth (RR =0.84, CI = 0.73;0.97). In meta-regression analysis, potential influential factors such as age, sex, and medical condition did not essentially alter the results.

Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications.

PURPOSE: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." METHODS: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. RESULTS: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). CONCLUSIONS: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.

Surgery after sonidegib treatment achieves complete response in locally advanced basal cell carcinoma of the face.

Basal cell carcinoma accounts for 75% of skin cancers worldwide and is the most common malignancy in Caucasians. Since chronic ultraviolet exposure is the major risk factor for its development, sun-exposed areas such as the face are frequently affected. The gold-standard treatment is surgical excision. Radiotherapy may be considered in selected cases such as unresectable primary tumors. In some patients, when the risk of a significant functional/cosmetic deficit advises against both surgery and radiotherapy, target therapy (hedgehog pathway inhibitors) can be administered alone or in a neoadjuvant setting, to reduce the tumor size and make it eligible for surgery. Vismodegib as a neoadjuvant treatment before surgery has been investigated in a single, multicentre, open-label, phase II trial (VISMONEO); however, sonidegib has not yet been evaluated in this setting. We report the cases of two patients with locally advanced basal cell carcinoma of the face who achieved complete remission with sonidegib followed by a more limited surgical excision than would have been needed without target therapy.

Line-field confocal optical coherence tomography of cutaneous vascular lesions: Morphological assessment and histopathological correlations.

BACKGROUND: Cutaneous vascular lesions (VLs) are benign or malignant processes involving blood and/or lymphatic vessels, usually readily diagnosed with dermoscopy. However, cases showing unclear clinical/dermoscopic findings may require further investigations. Line-field confocal optical coherence tomography (LC-OCT) is a new, non-invasive imaging technique displaying high resolution and deep penetration. The aim of this study was to describe the LC-OCT features of the most common benign and malignant VLs and to correlate them with histopathological substrates. METHODS: Clinical, dermoscopic, LC-OCT and histopathological images of VLs were retrospectively collected. Detailed LC-OCT description and histopathological correlations were produced for different types of VLs. RESULTS: The study included 71 VLs belonging to 50 caucasian patients [31 (62%) females; median age 56.8 (30-83) years] study lesions included 25 cherry haemangiomas, 15 angiokeratomas, 10 thrombosed haemangiomas, six pyogenic granulomas, five venous lakes, four targetoid haemosiderotic haemangiomas, four Kaposi's sarcomas and two extraungual glomus tumours. LC-OCT detected increased dermal vascularity, assuming different size and shape according to the particular type of VLs. LC-OCT criteria correlated well to established histopathologic findings. CONCLUSION: The results of our preliminary observations indicate that in vivo evaluation with LC-OCT may provide practical clues for the identification of the vascular nature of a lesion and its differential diagnosis.

Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?

Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date.

Computerized tomography texture analysis of pheochromocytoma: relationship with hormonal and histopathological data.

OBJECTIVES: Pheochromocytomas are rare tumors which can present with heterogeneous secretion profiles, clinical manifestations, and radiologic appearance. Under a histopathological point of view, they can be characterized as more or less aggressive with the Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score. The aim of this study is to analyze the texture analysis characteristics of pheochromocytoma and identify whether the texture analysis can yield information aiding in the diagnosis and the characterization of those tumors. METHODS: Radiological, biochemical, and histopathological data regarding 30 consecutive patients with histologically confirmed pheochromocytoma were analyzed. Images obtained in the unenhanced, late arterial, venous, and delayed phases were used for the texture analysis. RESULTS: Urinary epinephrine and metanephrine levels showed a significant correlation (R2 = 0.946; R2 = 699) in the multivariate linear model with texture features, as well as Ki-67 (R2 = 0.397), PASS score (R2 = 0.182), GAPP score (R2 = 0.705), and cellularity showed a significant correlation (R2 = 0.389). The cluster analysis based on radiomic features resulted in 2 clusters, with significative differences in terms of systolic and diastolic blood pressure values at the time of diagnosis (p = 0.025), GAPP score (4 vs 6, p = 0.05), histological pattern (1-2, p = 0.039), and comedonecrosis (0% vs 50%, p = 0.013). CONCLUSION: In conclusion, our study provides the proof of concept for the use of texture analysis on contrast-enhanced CT images as a noninvasive, quantitative tool for helping in the characterization of the clinical, biochemical, and histopathological features of pheochromocytoma.

Predictors of disease recurrence after curative surgery for nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNENs): a systematic review and meta-analysis.

PURPOSE: Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs. METHODS: Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival. RESULTS: Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15-26%). Study quality (Odds ratio, OR 0.94, P = 0.016) and G3-PanNENs rate (OR 2.18, P = 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P < 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P < 0.001, G1 versus G3 HR 2.57, P < 0.001), microvascular (HR 1.25, P = 0.046) and perineural (HR 1.29, P = 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P = 0.253) and status of resection margins (R0 versus R1, P = 0.173) did not show any significant relationship with NF-PanNENs recurrence. CONCLUSION: Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.

Association of sleep quality, media use and book reading with behavioral problems in early childhood. The Ulm SPATZ Health Study.

Study Objectives: The objective of the study was to investigate the association of sleep quality, media use and book reading on internalizing, externalizing and prosocial behavior in early childhood. Methods: In this cross-sectional study, we investigated a data set consisting of three consecutive yearly waves of the prospective Ulm SPATZ Health Study, conducted in southern Germany with 565, 496, and 421 children of 4-6 years of age, respectively.Standardized effects of the overall score and subscales of the Children's Sleep Habits Questionnaire, parent-reported child media use and book reading as well as their interaction term on the total score of the Strengths and Difficulties Questionnaire along with its externalizing, internalizing and prosocial subscales were estimated by multivariate adjusted random intercept mixed models. Results: Overall sleep quality was associated more with internalizing than externalizing behavior; parasomnias associated with both behaviors. Night waking and sleep anxiety associated only with internalizing behavior. High levels of media use were associated with less internalizing behavior. More book reading resulted in less externalizing and internalizing behavior but more prosocial behavior. Finally, book reading and media use do not interact to determine child's behavior. Conclusions: The current work supports a strategy of monitoring sleep quality, reducing media use and promoting book reading in order to avoid behavioral problems in early childhood.

Sporadic non-functioning pancreatic neuroendocrine tumours: multicentre analysis.

BACKGROUND: Outcomes after surgery for sporadic pancreatic neuroendocrine neoplasms (Pan-NENs) were evaluated. METHODS: This multicentre study included patients who underwent radical pancreatic resection for sporadic non-functioning Pan-NENs. In survival analysis, the risk of mortality in this cohort was analysed in relation to that of the matched healthy Italian population. Relative survival (RS) was calculated as the rate between observed and expected survival. Factors related to RS were investigated using multivariable modelling. RESULTS: Among 964 patients who had pancreatic resection for sporadic non-functioning Pan-NENs, the overall RS rate was 91.8 (95 per cent c.i. 81.5 to 96.5) per cent. 2019 WHO grade (hazard ratio (HR) 5.75 (s.e. 4.63); P = 0.030) and European Neuroendocrine Tumour Society (ENETS) TNM stage (6.73 (3.61); P < 0.001) were independent predictors of RS. The probability of a normal lifespan for patients with G1, G2, G3 Pan-NENS, and pancreatic neuroendocrine carcinomas (Pan-NECs) was 96.7, 54.8, 0, and 0 per cent respectively. The probability of a normal lifespan was 99.8, 99.3, 79.8, and 46.8 per cent for those with stage I, II, III, and IV disease respectively. The overall disease-free RS rate was 73.6 (65.2 to 79.5) per cent. 2019 WHO grade (HR 2.10 (0.19); P < 0.001) and ENETS TNM stage (HR 2.50 (0.24); P < 0.001) significantly influenced disease-free RS. The probability of disease-free survival was 93.2, 84.9, 45.2, and 6.8 per cent for patients with stage I, II, III, and IV disease, and 91.9, 45.2, 9.4, and 0.7 per cent for those with G1, G2, G3 Pan-NENS, and Pan-NECs, respectively. CONCLUSION: A surgical approach seems without benefit for Pan-NECs, and unnecessary for small G1 sporadic Pan-NENs. Surgery alone may be insufficient for stage III-IV and G3 Pan-NENs.

Diabetes mellitus induced by immune checkpoint inhibitors: type 1 diabetes variant or new clinical entity? Review of the literature.

Immune Check-Point Inhibitors (CPIs) have improved long-term patients' outcomes in several advanced cancers. Diabetes mellitus induced by CPIs (CPI-DM) is considered the second most frequent endocrine CPIs' side effects with a variable prevalence up to 2%. The aim of our study was to identify CPI-DM characteristics and differences from the classical form of diabetes. Therefore, we conducted a structured Pubmed® search collecting publications dated from January 2015 to December 2019. A total of 642 citations were identified and 121 publications met our study criteria. We analyzed 200 case reports, including our 3 cases under publication. The majority of CPI-DM occurred with anti-Programmed cell Death-1 in monotherapy or in combination, although few cases with Programmed cell Death Ligand-1 and Cytotoxic T Lymphocyte Antigen 4 were reported. Generally, CPI-DM arose early (an average of 9 weeks after CPIs starting), but also after the end of CPIs treatment. In all patients, CPI-DM has an acute onset and in 67.5% of cases diabetic ketoacidosis occurs. C-peptide levels were usually and permanently compromised, requiring lifelong insulin therapy. Moreover, autoimmunity and genetic profile was not always helpful. In particular, anti-glutamic acid decarboxylase (anti-GAD) antibodies and Human Leukocyte Antigen (HLA) DR4 were present in only 43.0% and 51.3% of cases respectively. In 51.0% of subjects a mild exocrine impairment coexisted. In short, though CPI-DM has similarities to type 1 diabetes mellitus, it represents a new, largely unknown, clinical entity. In addition, as CPI-DM is a relative frequent side-effect under CPI, a close monitoring of the glucose levels and early signs and symptoms of diabetes in patients affected by neoplasm is recommended.

Mortality in relation to profiles of clinical features in Ghanaian severely undernourished children aged 0-59 months: an observational study.

Severe acute malnutrition (SAM) is associated with a complex pattern of various clinical conditions. We investigated how risk factors cluster in children with SAM, the relationship between clusters of risk factors and mortality as well as length of stay in children with SAM. A prospective observational study design was used. Data were extracted from medical records of 601 infants and children aged 0-59 months admitted and treated for SAM in three Ghanaian referral hospital between June 2013 and June 2018. Among the 601 medical records extracted, ninety-nine died. Three clusters of medical features clearly emerged from data analyses. Firstly, an association was defined by eye signs, pallor, diarrhoea and vomiting with gastrointestinal infections and malaria. In this cluster, pallor and eye signs were related to 2- to 5-fold increased mortality risk. Secondly, HIV, oedema, fast pulse, respiratory infections and tuberculosis; among those features, HIV increased child mortality risk by 2-fold. Thirdly, shock, convulsions, dermatitis, cold hands and feet, weak pulse, urinary tract infections and irritability were clustered. Among those features, cold hands and feet, dermatitis, convulsions and shock increased child mortality risk in a range of 2- to 9-fold. Medical conditions and clinical signs in children diagnosed with SAM associate in patterns and are related to clinical outcomes.

Thr92Ala polymorphism in the type 2 deiodinase gene: an evolutionary perspective.

PURPOSE: In the past, a role of thyroid hormones in human evolution has been hypothesized. T3, the metabolically active form, derives from extrathyroidal conversion of T4 by deionidase 2 (D2) enzyme encoded by DIO2 gene. In thyroid-deficient patients, decreased levels of free T3 have been associated with the polymorphism rs225014 A/G in DIO2, which causes the substitution of Threonine with Alanine (p.Thr92Ala) at protein level. METHODS: We compared DNA and protein sequences of D2 from archaic human subspecies with those of contemporary humans. RESULTS: Neanderthals and Denisovans displayed only the G allele at the rs225014 polymorphism, which encodes for an Alanine on the amino acid level. These data suggest that these hominines were homozygous for the Ala amino acid. These arcaic humans often lived in condition of iodine deficiency and thus, defective mechanisms of T3 biosynthesis could be life threatining. A reduced D2 activity is likely to cause decreased T3 levels, which could be critical for those individuals. Neanderthals and Denisovans were hunters/gatherers, and their diet was mainly based on the consumption of meat, with a low intake of carbohydrates. The need for circulating T3 is reduced at such alimentary conditions. On the basis of our genome comparisons the A allele, corresponding to Threonine and associated with higher levels of circulating T3 in thyroid-deficient patients, appeared for the first time during evolution in Anatomically Modern Humans during the Upper Pleistocene and has been conserved during the Neolithic age. With the advent of agriculture and herding, individuals carrying A allele might have a higher probability for surviving and reproducing. Thus, the variant was positively selected during the evolution. CONCLUSION: Here we present an evolutionary perspective for p.Thr92Ala variant of D2 from Neanderthals to Anatomically Modern Humans.

Searching for novel multimodal treatments in oligometastatic pancreatic cancer.

BACKGROUND: Metastatic pancreatic cancer has a median overall survival of less than 12 months, even if treated with chemotherapy. Selected patients with oligometastatic disease could benefit from multimodal treatments connecting chemotherapy and surgical treatment or radiofrequency ablation (RFA) of metastases. CASE PRESENTATION: We present a patient with oligometastatic pancreatic cancer recurrence who was successfully treated with a multimodal therapeutic approach. A 57-year-old male initially presenting with resectable pancreatic cancer underwent pancreatoduodenectomy. The histopathological diagnosis revealed ductal pancreatic adenocarcinoma with positive surgical resection margins and negative lymph nodes. He completed six cycles of adjuvant therapy with gemcitabine (1000 mg/mq 1,8,15q 28), followed by external radiotherapy (54 Gy in 25 fractions) associated with gemcitabine 50 mg/mq twice weekly. Three years later, the patient developed multiple liver metastases, and he started FOLFIRINOX (oxaliplatin 85 mg/mq, irinotecan 180 mg/mq, leucovorin 400 mg/mq and fluorouracil 400 mg/mq given as a bolus followed by 2400 mg/mq as a 46 h continuous infusion,1q 14) as a first-line treatment. The CT scan showed a partial response after 6 cycles. After multidisciplinary discussion, the patient underwent a laparotomic metastasectomy of the three hepatic lesions. After additional postsurgical chemotherapy with 4 cycles of the FOLFIRINOX schedule, the patient remained free of recurrence for 12 months. A CT scan showed a new single liver metastasis, which was treated with radiofrequency ablation (RFA). A second radiofrequency ablation was performed when the patient developed another single liver lesion 12 months after the first RFA; currently, the patient is free from recurrence with an overall survival of 6 years from the diagnosis. CONCLUSIONS: Our case has benefited from successful multimodal treatment, including surgical and local ablative techniques and systemic chemotherapy. A multimodal approach may be warranted in selected patients with oligometastatic pancreatic cancer and could improve overall survival. Further research is needed to investigate this approach.

Oxygen consumption rate of Caenorhabditis elegans as a high-throughput endpoint of toxicity testing using the Seahorse XFe96 Extracellular Flux Analyzer.

Caenorhabditis elegans presents functioning, biologically relevant phenotypes and is frequently used as a bioindicator of toxicity. However, most C. elegans in vivo effect-assessment methods are laborious and time consuming. Therefore, we developed a novel method to measure the oxygen consumption rate of C. elegans as a sublethal endpoint of toxicity. This protocol was tested by exposing 50 larval stage one C. elegans individuals for 48 h (at 20 °C) to different concentrations of two toxicants i.e. benzylcetyldimethylammonium chloride (BAC-C16) and cadmium (Cd). Following exposures, the oxygen consumption rate of the C. elegans individuals were measured using the high-throughput functionality of the Seahorse XFe96 Extracellular Flux Analyzer. Dose-response curves for BAC-C16 (R2 = 0.93; P = 0.001) and Cd (R2 = 0.98; P = 0.001) were created. Furthermore, a strong, positive correlation was evidenced between C. elegans oxygen consumption rate and a commonly used, ecologically relevant endpoint of toxicity (growth inhibition) for BAC-C16 (R2 = 0.93; P = 0.0001) and Cd (R2 = 0.91; P = 0.0001). The data presented in this study show that C. elegans oxygen consumption rate can be used as a promising functional measurement of toxicity.

Prevalence of cervical HPV and attitude towards cervical screening in IBD patients under immunomodulatory treatment: a multidisciplinary management experience.

OBJECTIVE: Therapeutic strategies for Inflammatory Bowel Diseases (IBD: Crohn's disease and Ulcerative Colitis) have improved but the risk for HPV infection in patients under immunomodulatory/biologic treatment is unclear. Objective of the study is to identify the attitude of patients and caregivers to cervical screening. To determine the prevalence of HPV and cervical lesions in IBD patients receiving immunomodulatory/biological treatment. PATIENTS AND METHODS: IBD patients treated with immunomodulators were enrolled from November 2016 to September 2017, thanks to a multidisciplinary cooperation. A survey was administered to enrolled patients as well as to a selected network of IBD expert physicians. Patients who consented underwent gynecological examination, smear, HPV DNA test, colposcopy, vaginal and cervical microbiological swabs. RESULTS: 294 patients from AMICI Onlus Association, 119 patients from the hospital clinic, 30 doctors from national IBD centers participated to the survey. 19 patients from the IBD clinic underwent cervical screening. More than 90% of doctors consider their patients at risk of cervical cancer. A low prevalence of high-risk genotypes and related HPV lesions and an increased prevalence of bacterial vaginosis emerged in the studied population. CONCLUSIONS: Biological drugs could lead to a positive immunomodulation towards HPV infection. In IBD patients an alteration of the vaginal and intestinal microbiota seems to be coexisting.

Prospective observational study on the complications and tolerability of a peripherally inserted central catheter (PICC) in neuro-oncological patients.

PURPOSE: The use of central venous catheters with peripheral insertion (PICC) has increased rapidly in recent years, particularly in cancer patients. The benefits provided may occasionally be affected by relevant complications, such as infections and thrombotic events, especially in neuro-oncological patients. To date, the risk of PICC-related complications in this subset of patients is unknown, as is tolerability. As a primary objective, this study aimed to collect complications related to PICCs in primary neuro-oncological patients. As a secondary objective, the study aimed to evaluate PICC tolerability. METHODS: Neuro-oncological patients with PICCs that were placed as part of normal clinical practice at IRCCS Neurologico C. Besta were consecutively enrolled in the study. PICC-related complications were recorded immediately (during the procedure), early (within 1 week after PICC insertion), and late (1-3-5 months after PICC placement). At the same time points, all patients were also evaluated for tolerability through interviews with semi-structured, open-ended questions. RESULTS: Sixty patients were enrolled (41 males and 19 females, with a median age of 56.2 years). Excluding loss to follow-up, 33/49 patients developed at least one complication related to the PICC. Immediate complications mainly included hematoma (8), accidental arterial puncture (4), and primary malpositioning (3). Regarding early and late complications, 3 device-related infections, 8 thrombotic events, and 20 mechanical complications were registered. Semi-structured interviews revealed an overall positive experience with the device. The most negative impact was on hygiene habits, with 34 patients becoming caregiver-dependent. Over time, almost all patients became used to the device and perceived greater security during chemotherapy. A strongly negative issue was the difficulty of relying on competently trained healthcare personnel in outpatient setting. CONCLUSION: The results showed a nonnegligible increased thromboembolic risk in neuro-oncological patients with PICCs, almost double that in historical oncological populations. It is essential to extend the study to a greater number of patients to achieve reliable results and to identify patients at high risk. The device seems to be positively accepted by the majority of patients, without affecting activities of daily living.

Prognostic Impact of MCPyV and TIL Subtyping in Merkel Cell Carcinoma: Evidence from a Large European Cohort of 95 Patients.

Merkel cell carcinoma is a rare (∼ 2000 cases/year in the USA) but aggressive neuroendocrine neoplasm of the skin. In 2008, the Merkel cell polyomavirus (MCPyV) was found to be clonally integrated in approximately 80% of Merkel cell carcinomas. The remaining 20% have large numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens in virus-negative Merkel cell carcinoma and the Merkel cell polyomavirus oncogenes that are required for virus-positive tumor growth are highly immunogenic. Indeed, antigen-specific T cells detected in patients are frequently "dysfunctional/exhausted," and the inhibitory ligand PD-L1 is often expressed by Merkel cell carcinoma cells. These data led to point our attention on the quantity and the quality of the immune response in Merkel cell carcinoma. Here, we found CD8+ lymphocytes are the only singly evaluated lymphocyte subclass that strongly influenced overall survival and disease-specific survival in Merkel cell carcinoma. In addition, we highlighted as Merkel cell polyomavirus is a strong prognostic factor and as it prompts a host immune response involving various lymphocyte subclasses (CD3, CD8, FoxP3, and PD-L1 positive) in MCC. For this reason, we proposed a novel eye-based "immunoscore" model, obtained by tumor infiltrating lymphocytes subtyping (CD3, CD8, FoxP3, and PD-L1) that could provide additional prognostic information in Merkel cell carcinoma.

Variants in MCT10 protein do not affect FT3 levels in athyreotic patients.

PURPOSE: Several single-nucleotide polymorphisms in genes encoding for transporters have been associated with serum thyroid hormone concentrations with inconsistent results. The aim of this study was to assess the clinical significance of the rs17606253 in SLC16A10 gene alone and in combination with the DIO2 Thr92Ala variation in athyreotic patients. METHODS: One-hundred patients submitted to total thyroidectomy and treated with levothyroxine were included. Pre- and post surgical serum TSH levels did not differ by more than ± 0.5 mIU/l. RESULTS: Both patients carrying the wild-type allele or heterozygous for rs17606253 in SLC16A10 gene had a significant reduction in FT3 post surgical levels (p = 0.01 and p < 0.0001, respectively) while Thr92Ala in DIO2 gene was associated with reduced FT3 levels for heterozygous and rare homozygous patients (p < 0.0001 and p = 0.01, respectively). We identified two groups ("FT3 unchanged" and "FT3 reduced") using a cutoff of at least 0.5 pg/ml as a significant variation between pre- and post surgical FT3 values. In this case, the rs17606253 was not statistically associated with reduced FT3 levels at genotype and allele levels. On the contrary, the Thr92Ala in DIO2 gene was confirmed statistically associated with reduced FT3 levels after surgery with a p = 0.035 at genotype level and p = 0.014 at allele level. CONCLUSIONS: We confirmed the role of DIO2 Thr92Ala polymorphism on T3 levels. On the contrary, SLC16A1 rs17606253 polymorphism did not impair hormone levels in athyreotic patients treated with levothyroxine therapy.