The effect of COVID-19 disease on patients diagnosed with skin cancer in the dermatology clinic (preprint)

Objective: We aimed to define the impact of the pandemic on patients presenting to dermatology clinic with skin cancer. Methods: In our study, the characteristics of patients who attended our dermatology clinic before six months and after six months of March 11, 2020, and whose biopsies diagnosed as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM) were evaluated and compared regarding before and after COVID-19 pandemic Results: Patients with BCC attending to the dermatology clinic were found to be younger in the pandemic period (p<0.05). Gender, duration of skin tumors, primary lesions, and their locations were found to be not statistically significant (p>0.05). Conclusion:Patients with suspicious skin lesions could be encouraged to visit a hospital with appropriate COVID-19 protection. Alternatively, teledermatology could be used to evaluate whether the lesions should be excised or biopsied.

Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by PBR28 PET correlates with vascular disease measures (preprint)

The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.

The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.

BACKGROUND: Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of £265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited. OBJECTIVES: To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care. METHODS: The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation. RESULTS: A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to £119.2-164.4 million. CONCLUSIONS: Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.

Malignant Melanoma Arising in a Prolific Nevus Sebaceus With Colonization of Trichoblastoma.

ABSTRACT: Nevus sebaceus (NS) is a cutaneous hamartoma typically found on the head and neck, with a prevalence of 0.3% in newborns. Most NS are quiescent; however, benign and malignant lesions have been reported to arise within these nevi. Malignant transformation is not common but mainly includes basal cell carcinoma and squamous cell carcinoma. Malignant melanoma arising in NS is exceedingly rare, with only 2 previously documented cases. In this article, we report the first case of malignant melanoma arising in a NS in a 68-year-old man in the United States.

Basosquamous Cell Carcinoma of the Nipple-Areola Complex-Report of a Case.

Basosquamous cell carcinoma (BSCC) is a rare malignancy usually arising on sun-exposed areas of the skin. BSCC is described as a rare variant of Basal cell carcinoma (BCC) which shows clinical and microscopic features of both BCC and of Squamous cell carcinoma (SCC). We report the case of a 70-year-old male with a cutaneous lesion of the nipple-areola complex (NAC); to the best of our knowledge, this is the first ever reported patient with BSCC in this area. The lesion had a fast growth, but, due to the COVID19 crisis, the patient only came to our observation one year after onset of this condition. Physical examination showed a bleeding red ulcerated lesion that involved the NAC, measuring 27 mm × 20 mm. Biopsy showed a BSCC. Pre-operative breast ultrasound scan, mammogram and MRI were all performed before surgery, which consisted of simple mastectomy and sentinel lymph-node biopsy. The patient was discharged home on the 4th post-operative day, and at 18-month follow-up there are no signs or clinical evidence of local recurrence or metastases. Diagnosis of BSCC of the nipple-areola complex requires high index of suspicion and a thorough differential diagnosis, management, and suitable radical treatment due to well described high rates of recurrence and of metastases. Differential diagnosis with similar lesions (e.g., Paget's disease, Bowen's disease, BCC, and SCC) should also be taken into account.

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report.

BACKGROUND: The use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers. CASE PRESENTATION: A 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient's inadequate compliance, and within 2 years, the patient's cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient's basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection. CONCLUSIONS: Our patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

Post-COVID-19 syndrome and insulin resistance 20 months after a mild COVID-19 (preprint)

Objective SARS-CoV-2 infection is associated with impaired glucose metabolism. Although the mechanisms are not fully understood, insulin resistance (IR) appears to be a central factor. Patients who had a severe acute phase, but even asymptomatic or with mild COVID-19, have an increased risk of T2DM. After the acute phase, post-COVID-19 syndrome (PCS) also seems to be related to this metabolic disturbance, but there is a paucity of studies. This study aims to evaluate a possible relationship between PCS and IR after mild COVID-19 and, if confirmed, whether there are differences by sex. Subjects and methods Retrospective observational cohort study including subjects who had mild COVID-19 between April and September 2020 in a community setting. None had been vaccinated against SARS-CoV-2 at inclusion, and previous T2DM and liver disease were exclusion criteria. Patients who met NICE criteria were classified as PCS+. Epidemiological and laboratory data were analysed. Three assessments were performed: 1E (pre-COVID-19, considered baseline and reference for comparisons), 2E (approximately 3 months after the acute phase), and 3E (approximately 20 months after the acute phase). A triglyceride-to-glucose (TyG) index [≥]8.74 was considered IR. Albumin-to-globulin ratio (AGR) and lactate dehydrogenase (LDH) were assessed as inflammatory markers. Bivariate analyses were performed, using nonparametric and repeated measures tests. A subsample without metabolic disorder or CVD (age< median, BMI<25 kg/m^2, elevated AGR, TyG index=7.80 [0.5]) was generated to reasonably rule out prior baseline IR that could bias the results. The relationships between PCS and TyG in 3E (TyG3) were modeled in 8 multiple regressions, stratifying by sex and BMI combinations. Results A total of 112 subjects (median [IQR] of age= 44 [20] years; 65 women) were analysed. Up to 14.3% was obese and 17% was hypertensive. Significant increases between 1E and 3E were registered regarding (i) basal glycemia (BG), 87 [14] mg/dL vs. 89 [14]; p=0.014, (ii) TyG index (8.25 [0.8] vs. 8.32 [0.7]; p=0.002), and (iii) LDH in 3rd tertile (16.1% vs 32.1%; p=0.007). A total of 8 previously normoglycemic subjects, showed BG2 or BG3 >126 mg/dL. The subgroups with IR highest prevalence at 3E were those of BMI [≥]25 kg/m^2 and PCS+. The subgroup without CVD presented a significant increase in the TyG index (TyG1=7.80 [0.1] vs. TyG3= 8.28 [0.1]; p=0.017). LDH1 was significantly correlated with TyG3 in both sexes (rho=0.214 in women, rho=0.298 in men); in contrast, LDH2 and LDH3 did not present such an association. In multivariable analysis, PCS has shown to be an independent and predictive variable of TyG index in women with BMI<25 kg/m^2, after adjustment for age, hypertension, BMI, Charlson comorbidity index, AGR1, AGR2, LDH1, number of symptoms of acute COVID-19, and number of days of the acute episode (beta coefficient=0.350; p=0.039). Conclusions PCS has played a secondary role in predicting IR, showing a modest effect compared to BMI or prior hypertension. A significant increase in IR has been noted 20 months after mild COVID-19, both in cases of previous baseline IR and in those without previous IR. Basal serum LDH has shown to be predictive of current TyG, regardless of elevated LDH after SARS-CoV-2 infection. There were profound differences between women and men, confirming the need for a sex-stratified analysis when addressing the relation between PCS and glycemic alterations.

Cutaneous Basal Cell Carcinoma: Does Noninvasive Ventilation Accelerate Tumor Progression?

A 56-year-old woman presented to the emergency to be department with diarrhea, asthenia, cough, and dysgeusia. The patient had chronic obstructive pulmonary disease (COPD) and was found infected with coronavirus disease 2019 (COVID-19). On physical examination, a small basal cell carcinoma (BCC) lesion was identified on her scalp; however, following the administration of noninvasive ventilation, the appearance of both macroscopic and microscopic BCC worsened dramatically. Our findings point to positive pressure noninvasive ventilation used to treat COVID-19 associated with COPD as a possible causative agent for the progression of cutaneous BCC. (SKINmed. 2022;20:463-465).

Study protocol of the BASINEL Study: a pragmatic randomised controlled trial investigating treatment versus no treatment of low-risk basal cell carcinomas in older persons.

INTRODUCTION: Basal cell carcinomas (BCCs) represent 70% of all skin cancers. These tumours do not metastasise but are locally invasive if left untreated. There is a high incidence of BCC in the elderly, and clinicians frequently face important treatment dilemmas. The approach to BCC in the elderly should be investigated thoroughly. METHODS AND ANALYSIS: Data on health-related quality of life (HrQoL), survival and complication rate will be examined in a treatment and a non-treatment arm (1:1 allocation). In the non-treatment arm, in vivo biological behaviour of low-risk BCCs in elderly patients will be examined. The main objective is to combine tumour characteristics with demographic data, in order to determine whether treatment will positively affect the patients' HrQoL within a predetermined time frame. A monocentric randomised controlled trial (RCT) was designed at the Ghent University Hospital. The study population consists of patients with the minimum age of 75 years and a new diagnosis of (a) low-risk BCC(s). Patients in the treatment arm will receive standard care. Patients in the non-treatment arm will be closely monitored: the tumour will be intensively evaluated using multispectral dermoscopy, reflectance confocal microscopy and high-definition optical coherence tomography. All patients will be asked to fill in a questionnaire concerning their HrQoL at consecutive time points. Patient-reported side effects will be evaluated via an additional questionnaire.Primary outcomes will include the difference in HrQoL and the difference in complication risks (treatment vs non-treatment) at different time points of the study. Secondary endpoints are the evolution of the BCCs in the non-treatment arm and the long-term survival in both study arms. Tertiary endpoint is the treatment effectiveness in the treatment arm. The sample size calculation was performed and resulted in a target sample size of 272 patients in this study with a 1:1 allocation. ETHICS AND DISSEMINATION: Subjects can withdraw from participating in this study at any time for any reason without any consequences. Approval for this study was received from the Ethics Committee of the Ghent University Hospital on 26 August 2021.The results of this RCT will be submitted for publication in one or more international, peer-reviewed medical journals, regardless of the nature of the study results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05110924).

Lung remodeling regions in long-term Covid-19 feature basal epithelial cell reprogramming (preprint)

Respiratory viruses, including SARS-CoV-2, can trigger chronic lung disease that persists and even progresses after expected clearance of infectious virus. To gain an understanding of this process, we examined a series of consecutive fatal cases of Covid-19 that came to autopsy at 27-51 d after hospital admission. In each patient, we identify a stereotyped bronchiolar-alveolar pattern of lung remodeling with basal epithelial cell hyperplasia and mucinous differentiation. Remodeling regions also feature macrophage infiltration and apoptosis and a marked depletion of alveolar type 1 and 2 epithelial cells. This entire pattern closely resembles findings from an experimental model of post-viral lung disease that requires basal-epithelial stem cell growth, immune activation, and differentiation. The present results thereby provide evidence of possible basal epithelial cell reprogramming in long-term Covid-19 as well and thereby a pathway for explaining and correcting lung dysfunction in this type of disease.

Sonic hedgehog pathway for the treatment of inflammatory diseases: implications and opportunities for future research.

The Sonic hedgehog (Shh) signaling pathway is an essential pathway in the human body that plays an important role in embryogenesis and tissue homeostasis. Aberrant activation of this pathway has been linked to the development of different diseases, ranging from cancer to immune dysregulation and infections.Uncontrolled activation of the pathway through sporadic mutations or other mechanisms is associated with cancer development and progression in various malignancies, such as basal cell carcinoma, medulloblastoma, pancreatic cancer, breast cancer and small-cell lung carcinoma. Targeted inhibition of the pathway components has therefore emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Currently, two main components of the pathway, the smoothened receptor and the glioma-associated oncogene homolog transcriptional factors, have been investigated for the development of targeted drugs, leading to the marketing authorization of three smoothened receptor inhibitors for the treatment of basal cell carcinoma and acute myeloid leukemia.The Shh pathway also seems to be involved in regulating the immune response, possibly playing a role in immune system evasions by tumors, development of autoimmune diseases, such as rheumatoid arthritis and Crohn's disease, airway inflammation, and diseases related to aberrant activation of T-helper 2 cellular response, such as allergy, atopic dermatitis, and asthma.Finally, the Shh pathway is involved in pathogen-mediated infection, including influenza-A and, more recently, SARS-CoV-2 viruses. Therefore, agents that inhibit the Shh signaling pathway might be used to treat pathogenic infections, shifting the therapeutic approach from strain-specific treatments to host-based strategies that target highly conserved host targets.

[Impact of the COVID-19 pandemic on skin cancer screening : Results of a large dermatology practice in Bavaria's largest county by area]. / Der Einfluss der COVID-19-Pandemie auf das Hautkrebsscreening : Ergebnisse einer großen Hautarztpraxis im flächengrößten Landkreis Bayerns.

BACKGROUND: The advantages and disadvantages of the nationwide skin cancer screening which was introduced in 2008 are regularly discussed. OBJECTIVES: Do missed skin cancer screenings change the tumor depths? METHODS: Evaluation and analysis of office data from the second quarters of 2019, 2020 and 2021 were compared using the one-way analysis of variance (ANOVA) with Welch's F test. RESULTS: There was a significant increase in the tumor thickness in squamous cell carcinoma and basal cell carcinoma, while there was only a tendency due to the small amount of data available for malignant melanoma. CONCLUSIONS: The results of the analysis emphasize the importance of the skin cancer screening as a method of early detection and reduction of mutilating operations and expensive immunotherapies by the prompt detection of malignant tumors.

The impact of treatment delay on skin cancer in COVID-19 era: a case-control study.

BACKGROUND: The outbreak of COVID-19 pandemic led to a 2-month lockdown in Europe. Elective surgeries, including skin cancer excisions, were postponed. The purpose of this prospective case-control study was to assess the impact of the treatment delay on patients with non-melanoma skin cancer (NMSC) or melanoma operated in the first post-lockdown period. METHODS: A comparative study of skin cancer operations performed in a 4-month period either in 2020 or in 2019 was conducted. All data were collected from a prospectively maintained clinic database and the pathological reports. Continuous variables were compared with t test or Mann-Whitney U test according to their distribution. Categorical variables were compared with Fisher exact test. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the risk of excising high-risk NMSC in 2020 compared with 2019. RESULTS: Skin cancer excision was performed in 158 cases in 2020 compared to 125 cases in 2019 (26.4% increase). Significantly, more SCC were excised in 2020 (p = 0.024). No significant difference for several clinical parameters regarding BCC, SCC, and melanoma was identified. However, the reconstructive method applied, following NMSC excision, was significantly different, requiring frequently either skin grafting or a flap. CONCLUSION: These results indicate that skin cancer treatment delay, due to COVID-19 pandemic, is related to an increased incidence of SCC and more complicated methods of reconstruction. Considering the relapsing COVID-19 waves, significant skin cancer treatment delays should be avoided. TRIAL REGISTRATION: The study adhered to the STROBE statement for case-control studies.