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BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been associated with detectable levels of cotinine (a nicotine metabolite) in childrens saliva. However, tobacco smoke also contains toxic and essential trace metals, including chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), nickel (Ni) and zinc (Zn). OBJECTIVE: The current study examines whether there is a relationship between ETS exposure, as gauged by salivary cotinine, and salivary levels of these metals in a subset (n = 238) of children from the Family Life Project. METHODS: Using inductively-coupled-plasma optical emission spectrophotometry, we measured levels of metals in saliva from children at ~90 months of age. Salivary cotinine was measured using a commercial immunoassay. RESULTS: We found that Cr, Cu, Mn, and Zn were detected in most samples (85-99%) with lower levels of detection for Pb and Ni (9.3% and 13.9% respectively). There were no significant differences in any of the metal concentrations between males and females, nor were levels associated with body mass index, although significant differences in salivary Cr and Mn by race, state and income-to-needs ratio were observed. Children with cotinine levels >1 ng/ml had higher levels of Zn (b = 0.401, 95% CI: 0.183 to 0.619; p = 0.0003) and Cu (b = 0.655, 95% CI: 0.206 to 1.104; p = 0.004) compared to children with levels 1 μg/L were more likely to have detectable levels of Pb in their saliva (b = 1.40, 95% CI: 0.424 to 2.459; p = 0.006) compared to children with cotinine levels

Abstract Human metabolism is complex, and is impacted by genetics, cohabitation, diet, health, and environmental inputs. As such, we applied untargeted LC-MS metabolomics to 1425 saliva samples from a diverse group of elementary school-aged children and their caregivers collected during the Family Life Project, of which 1344 were paired into caregiver/child dyads. We compared metabolomes within and between homes, performed population-wide “metabotype” analyses, and measured associations between metabolites and salivary biomeasures of inflammation, antioxidant potential, environmental tobacco smoke (ETS) exposure, metabolic regulation, and heavy metals. Children and caregivers had similar salivary metabolomes, and dyad explained most metabolomic variation. Our data clustered into two groups, indicating that “metabotypes” exist across large populations. Lastly, several metabolites—putative oxidative damage-associated or pathological markers—were correlated with the above-mentioned salivary biomeasures and heavy metals. Implications of the family environment’s effects on metabolomic variation at population, dyadic, and individual levels for human health are discussed.

Introduction: Basosquamous carcinoma is an uncommon subtype of basal cell carcinoma (BCC), characterized by aggressive local growth and metastatic potential, that mainly develops on the nose, perinasal area, and ears, representing 1.2–2.7% of all head-neck keratinocyte carcinomas. Although systemic therapy with hedgehog inhibitors (HHIs) represents the first-line medical treatment in advanced BCC, to date, no standard therapy for advanced basosquamous carcinoma has been established. Herein, we reported a case series of patients affected by locally advanced basosquamous carcinomas, who were treated with HHIs. Case Presentation: Data of 5 patients receiving HHIs for locally advanced basosquamous carcinomas were retrieved (2 women and 3 males, age range: 63–89 years, average age of 77 years). Skin lesions were located on the head-neck area; in particular, 4 tumors involved orbital and periorbital area and 1 tumor developed in the retro-auricular region. A clinical response was obtained in 3 out of 5 patients (2 partial responses and 1 complete response), while disease progression was observed in the remaining 2 patients. Hence, therapy was interrupted, switching to surgery or immunotherapy. Conclusion: Increasing evidence suggests considering HHIs for large skin tumors developing in functionally and cosmetically sensitive areas, in patients with multiple comorbidities, although their use for basosquamous carcinoma require more exploration, large cohort populations, and long follow-up assessment.

ObjectiveThe narrow therapeutic window of lithium medications necessitates frequent serum monitoring, which can be expensive and inconvenient for the patient. Compared to blood, saliva collection is easier, non-invasive, requires less processing, and can be done without the need for trained personnel. This study investigated the utility of longitudinal salivary lithium level monitoring.MethodsWe measured salivary lithium levels using ICP-OES in n = 169 passive drool samples, collected both as single observations and longitudinally for up to 18 months, from a multi-center cohort of n = 75 patients with bipolar disorder or other psychiatric conditions.ResultsSaliva and serum lithium levels were highly correlated. Adjustment for daily lithium dose, diabetes, and smoking improved this relationship (r = 0.77). Using the adjusted intersubject equation and a patient's salivary lithium value, we observed a strong correlation between the predicted vs. observed serum lithium levels (r = 0.70). Most patients had highly stable saliva/serum ratios across multiple visits, with longitudinal variability significantly greater with age. Use of the intrasubject saliva/serum ratio from a single prior observation had similar predictive power to the use of the adjusted intersubject equation. However, the use of the mean intrasubject ratio from three prior observations could robustly predict serum lithium levels (predicted vs. observed r = 0.90).ConclusionsThese findings strongly suggest that saliva could be used for lithium monitoring, and open the door for the development and implementation of a point-of-care salivary lithium device for use at home or the clinic. We propose that the use of saliva will dramatically improve treatment opportunities for patients with mood disorders.

Introduction In advanced basal cell carcinoma (BCC), the issue of whether Hedgehog inhibitors (HHIs) should be stopped or not after clinical complete response (cCR) achievement remains an unmet clinical need. Materials and Methods We conducted a retrospective, multicenter study across 7 Italian dermato-oncology units including patients with BCC who continued vismodegib after cCR between 2012 and 2019. We assessed the relationship between the duration of vismodegib intake (days to cCR [DTCR], days to stop after cCR [DTS], total treatment days [TTD]), and disease-free survival (DFS). Reasons to stop vismodegib were (R1) toxicity and (R2) disease recurrence. The relationship between DTCR, DTS, TTD, and DFS in the whole population and in R1 subgroup was assessed by Pearson's correlation coefficient (P  < .05) and Bayesian statistics (BF10). Results Sixty-eight BCC patients with a median (m) age of 75.5 years (39-100) were included. Most patients were male (N  = 43, 63%), without Gorlin syndrome (N  = 56, 82%) and with head and neck area as primary site (N  = 51, 75%). After cCR, out of 68 patients, 90% (N = 61/68) discontinued vismodegib: 82% (N  = 50/61) due to toxicity (R1), and 18% (N  = 11/61) due to recurrence (R2). Conversely, 10% (N  = 7/68) continued vismodegib until last follow-up. In the whole population (N  = 68), cCR was achieved with a mDTCR of 180.50 days. DFS showed a significant correlation with DTS (P  < .01, BF10 = 39.2) and TTD (P  < .01, BF10 = 35566), while it was not correlated to DTCR (BF10 < 0.1). The analysis of R1 subgroup (N  = 50) confirmed these results. DFS correlated with DTS in all recurrent patients (N  = 38, r  = 0.44, P  < .01) and in the recurrent patients who stopped vismodegib for toxicity (N  = 26, r  = 0.665, P  < .01). DFS was longer when vismodegib was maintained for >2 months after cCR (mDFS > 2 months, N  = 54 vs. ≤ 2 months, N  = 14: 470 vs. 175 d, P  < .01). Conclusions Our retrospective results suggest that HHIs should be continued after cCR to improve DFS in BCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHIs) changed the treatment landscape for this complex patient population. Objectives: The aims of the present study are to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC and to investigate effectiveness and safety of HHI. Methods: A multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 – October 15, 2022. Patients aged ≥18 years and diagnosed with aBCC (locally advanced [laBCC] and metastatic BCC [mBCC]) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: We enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome were available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of laBCC (n = 84, sonidegib; n = 45, vismodegib) and 3 patients of mBCC (n = 2, vismodegib; n = 1, sonidegib, off-label). Objective response rate was 76.7% (95% confidence interval [CI]: 82.3–68.7) and 33.3% (95% CI: 88.2–1.7) for laBCC (complete response [CR]: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with nonresponse to HHI therapy ([OR: 2.61; 95% CI: 1.09–6.05; p: 0.03] and [OR: 2.74; 95% CI: 1.03–7.9; p: 0.04]), respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity. Conclusions: Our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting. [ABSTRACT FROM AUTHOR]

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The continuous improvement of life expectancy of patients with chronic lymphocytic leukemia (CLL) has resulted in increased risk of second primary malignancy that potentially may affect survival and quality of life of CLL patients. We performed a systematic review to assess the risk and the clinical‐pathological features and prognosis of cutaneous squamous cell carcinoma (cSCC) in patients with CLL. We searched PubMed, Embase, and Cochrane Central Register of Control Trials databases for articles published from database inception to December 31, 2019. English‐language studies reporting original data on patients with a specific diagnosis of CLL and cSCC were included. Data were extracted using a standardized extraction form, and any discordance was resolved by consensus. Descriptive data were generated by pooling patients from eligible studies. Of the 4588 non‐duplicate records identified, 55 articles met our inclusion criteria. These studies reported that CLL patients have a 3.2% prevalence of cSCC, with an 11.5% cSCC‐related lethality and an overall risk of metastasis of 5.7% (7.3% for regional lymph node involvement and 3.8% for distant metastasis). The quality of evidence was limited by the high heterogeneity in the design, populations, and objectives of the included studies. This systematic review suggests that cSCC in CLL patients tends to behave less aggressively compared with the solid organ transplant recipients but has a higher morbidity and mortality than in the general population. Future prospective studies are needed to increase the quality of evidence and to determine the best treatment modalities and screening intervals for these patients. [ABSTRACT FROM AUTHOR]

Common primary cutaneous squamous cell carcinoma (CSCC) accounts for 20% of keratinocyte cancers that is usually successfully treated with surgery or radiotherapy. In a minority of cases, CSCC lesions may progress to locally advanced or metastatic disease that may be difficult to be treated causing significant morbidity and mortality. Chemotherapies and targeted therapy with anti‐epidermal growth factor receptor antibodies have been used off‐label in small studies and case reports of advanced CSCC, but data are scarce and response short‐lived. Recently, two PD‐1 immune checkpoint inhibitors, cemiplimab and pembrolizumab, have been approved for the treatment of advanced CSCC; specifically the former can be administered in patients with locally advanced and metastatic tumours, while the latter in case of recurrent metastatic CSCC. The introduction of immune checkpoint inhibitors represents a breakthrough in the treatment of CSCC, since numerous clinical trials showed that these agents may provide remarkable clinical benefit with an acceptable safety profile, in a high‐need population who had no standard of care. In addition, real‐world studies are needed to validate the results observed in clinical trials and numerous clinical trials in the neoadjuvant or adjuvant setting are ongoing. Finally, further studies should investigate predictive biomarkers useful to better select patients to maximize the treatment efficacy. [ABSTRACT FROM AUTHOR]