Efficacy of Ceragenins in Controlling the Growth of Oral Microorganisms: Implications for Oral Hygiene Management.

Ensuring proper dental hygiene is of paramount importance for individuals' general well-being, particularly for patients receiving medical care. There is a prevailing utilization of conventional oral hygiene items, including toothbrushes and mouthwashes, which have gained widespread acceptance; nevertheless, their limitations encourage investigating novel options in this domain. Our study indicates that ceragenins (CSAs) being lipid analogs of host defense peptides, well-recognized for their wide-ranging antimicrobial properties, may be a potentially efficacious means to augment oral hygiene in hospitalized individuals. We demonstrate that ceragenins CSA-13, CSA-44, and CSA-131 as well as undescribed to date CSA-255 display potent antimicrobial activities against isolates of fungi, aerobic, and anaerobic bacteria from Candida, Streptococcus, Enterococcus, and Bacteroides species, which are well-recognized representatives of microbes found in the oral cavity. These effects were further confirmed against mono- and dual-species fungal and bacterial biofilms. While the ceragenins showed similar or slightly diminished efficacy compared to commercially available mouthwashes, they demonstrated a highly favorable toxicity profile toward host cells, that may translate into better maintenance of host mucosal membrane stability. This suggests that incorporating ceragenins into oral hygiene products could be a valuable strategy for reducing the risk of both oral cavity-localized and secondary systemic infections and for improving the overall health outcomes of individuals receiving medical treatment.

Spitz nevus and melanoma: evaluation with dermoscopy and reflectance confocal microscopy.

Introduction: Spitz nevi (SN) include a wide range of benign melanocytic nevi, which are controversial due to their morphologic resemblance to melanoma (MM). Aim: To describe dermoscopic and reflectance confocal microscopic (RCM) features of SN compared to MM and assess the RCM utility in the differential diagnosis. Material and methods: We performed a multicentre retrospective analysis of MM and SN evaluated with dermoscopy and reflectance confocal microscopy. Three RCM mosaics were obtained for each lesion. Nine dermoscopic and twenty-one microscopic features were assessed for each lesion. Results: A total of 26 lesions (15 SN and 11 MM) were included. Dermoscopically, most SN showed a "starburst" pattern. Asymmetry was marked in 8 MM. There were 6 dermoscopic features significantly more prevalent in MM than in SN. RCM showed that an atypical honeycomb pattern, atypical infiltration, and disarray of the epidermis were significant for MM. SN mostly revealed a typical honeycomb pattern. At the DEJ, most of SN had a meshwork pattern; MM revealed an atypical meshwork pattern. Atypical cells and sheet-like structures were observed in most MM. Conclusions: A combined approach using dermoscopy and RCM supports the differential diagnosis of SN and MM. Although our study showed some significant differences between SN and MM in RCM, further research on a larger group should be considered.

Clinical, Dermoscopic, and Histological Characteristics of Melanoma Patients According to the Age Groups: A Retrospective Observational Study.

BACKGROUND: Although the role of melanoma risk factors is well documented, their correlation with patients' age is less frequently analyzed. METHOD: The analysis was performed among 189 melanoma patients in different age groups, including <30 years, 31-60 years, and >60 years, to investigate the risk factors, topography, and coexistence of morphological features of 209 melanomas (dermoscopic and histopathological). RESULTS: Among the youngest age group, no correlation with the presence of estimated risk factors was found. The most common dermoscopic pattern was spitzoid and multicomponent asymmetric. The group of middle-aged patients was the most diverse in terms of the occurrence of risk factors, solar lentiginosis, dermoscopic patterns, topography, histological subtypes, and invasiveness of melanomas. The oldest group characterized a strong correlation between solar lentiginosis, NMSC comorbidity, the prevalence of facial melanomas, the dermoscopic pattern of melanoma arising on chronic sun-damaged skin, and regression. CONCLUSION: The findings regarding the presence of age-specific features in melanoma patients, especially in the youngest and middle-aged groups, might be helpful for clinicians and to target secondary prevention efforts.

Initial study on quantitative electroencephalographic analysis of bioelectrical activity of the brain of children with fetal alcohol spectrum disorders (FASD) without epilepsy.

Fetal alcohol spectrum disorders (FASD) are spectrum of neurodevelopmental conditions associated with prenatal alcohol exposure. The FASD manifests mostly with facial dysmorphism, prenatal and postnatal growth retardation, and selected birth defects (including central nervous system defects). Unrecognized and untreated FASD leads to severe disability in adulthood. The diagnosis of FASD is based on clinical criteria and neither biomarkers nor imaging tests can be used in order to confirm the diagnosis. The quantitative electroencephalography (QEEG) is a type of EEG analysis, which involves the use of mathematical algorithms, and which has brought new possibilities of EEG signal evaluation, among the other things-the analysis of a specific frequency band. The main objective of this study was to identify characteristic patterns in QEEG among individuals affected with FASD. This study was of a pilot prospective study character with experimental group consisting of patients with newly diagnosed FASD and of the control group consisting of children with gastroenterological issues. The EEG recordings of both groups were obtained, than analyzed using a commercial QEEG module. As a results we were able to establish the dominance of the alpha rhythm over the beta rhythm in FASD-participants compared to those from the control group, mostly in frontal and temporal regions. Second important finding is an increased theta/beta ratio among patients with FASD. These findings are consistent with the current knowledge on the pathological processes resulting from the prenatal alcohol exposure. The obtained results and conclusions were promising, however, further research is necessary (and planned) in order to validate the use of QEEG tools in FASD diagnostics.

Risk Factors and Clinicopathological Features for Developing a Subsequent Primary Cutaneous Squamous and Basal Cell Carcinomas.

BACKGROUND: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. METHODS: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. RESULTS: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. CONCLUSIONS: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs.

Dermoscopy of Small Diameter Melanomas with the Diagnostic Feasibility of Selected Algorithms-A Clinical Retrospective Multicenter Study.

OBJECTIVE: The aim of the study was to verify two hypotheses. The first concerned the possibility of diagnostic dermoscopic differentiation between cutaneous melanomas of the histopathological category in situ (pTis) and thin melanomas (pT1a) in terms of their diameter. The second assessed the diagnostic feasibility of two dermoscopic algorithms aiming to detect ≤ 5.0 mm-sized melanomas histopathologically confirmed as pTis and pT1a. METHODS: Dermoscopic images of consecutive cases of histopathologically confirmed melanomas were evaluated by three independent investigators for the presence of the predefined criteria. The melanomas were subdivided according to their diameter into small melanomas, so-called micromelanomas (microM)-sized ≤ 5.0 mm and >5.0 mm, according to published definitions of small melanocytic lesions. The Triage Amalgamated Dermoscopic Algorithm (TADA) and the revisited 7-point checklist of dermoscopy (7-point) algorithm were chosen for the diagnostic feasibility. Odds ratios and corresponding 95% confidence limits (CL) were calculated using the logistic regression adjusted for age for the melanoma-specific dermoscopic structures, the dermoscopic patterns and the diagnostic feasibility of the 7-point checklist and TADA algorithms. The p-values of the results were corrected using the Bonferroni method. RESULTS: In total, 106 patients with 109 melanomas, 50 sized ≤ 5.0 mm and 59 exceeding the diameter of 5.0 mm, were retrospectively analyzed. The prevalent general pattern of microM was the spitzoid one (48% vs. 11.86%, p = 0.0013). Furthermore, 40% of microM vs. 6.78% melanomas sized > 5.0 mm (p = 0.0023) did not present melanoma-specific patterns. The asymmetric multicomponent pattern was present in 64.41% melanomas sized > 5.0 mm and in 26.00% microM (p = 0.0034). The asymmetry of structures or colors was detected in 56% microM vs. 89.83% (p = 0.0020) and 56% microM and 94.92% (p = 0.000034) melanoma sized > 5.0 mm, respectively. The differences in frequency of the detected dermoscopic structures specific to melanomas revealed that microM are almost deprived of negative networks (p = 0.04), shiny white structures (p = 0.0027) and regression features (p = 0.00003). Neither prominent skin markings nor angulated lines were found in the entire study group. Out of the vascular structures, microM presented only dotted (32%) or polymorphous (28%) vessels, although more rarely than melanomas sized > 5.0 mm (66.1% p = 0.017 and 49% p > 0.05, respectively). The diagnostic feasibility revealed a score ≥ 3 of the 7-point algorithm (indicative for malignancy) in 60% microM and 98.31% melanomas sized > 5.0 mm (p = 0.000006). The TADA algorithm revealed melanoma-specific patterns in 64% microM and 96.61% > 5.0 mm-sized melanomas (p = 0.00006) and melanoma-specific structures in 72% and 91.53% (p > 0.05), respectively. CONCLUSION: In the dermoscopy, 40% of micromelanomas histopathologically staged as pTis and pT1a did not reveal melanoma-specific patterns. Among the general melanocytic patterns, the spitzoid one was the most frequently found in melanomas sized ≤ 5.0 mm. The 7-point checklist and TADA dermoscopic algorithms were helpful in the identification of the majority of melanomas sized ≤ 5.0 mm.

Tumor of the Nose - A Rare Manifestation of a Metastatic Lung Cancer.

Lung cancer most often metastasizes to the central nervous system, bone and liver. Although metastases to the skin are quite rare, it is estimated that they may be the first clinical manifestation of this disease in 0.7%-12% of cases. Metastases to the skin are caused by adenocarcinoma (about 30%), squamous cell carcinoma (30%) and undifferentiated carcinoma (40%). Nasal tip metastases are extremely rare. They can be confused with more common skin problems, including non-melanoma skin cancers, rhinophyma, inflammatory tumors or infectious diseases. We report two patients with a tumor on the nose, which proved to be the first sign of the metastatic lung cancer.

Deep Learning-Based High-Frequency Ultrasound Skin Image Classification with Multicriteria Model Evaluation.

This study presents the first application of convolutional neural networks to high-frequency ultrasound skin image classification. This type of imaging opens up new opportunities in dermatology, showing inflammatory diseases such as atopic dermatitis, psoriasis, or skin lesions. We collected a database of 631 images with healthy skin and different skin pathologies to train and assess all stages of the methodology. The proposed framework starts with the segmentation of the epidermal layer using a DeepLab v3+ model with a pre-trained Xception backbone. We employ transfer learning to train the segmentation model for two purposes: to extract the region of interest for classification and to prepare the skin layer map for classification confidence estimation. For classification, we train five models in different input data modes and data augmentation setups. We also introduce a classification confidence level to evaluate the deep model's reliability. The measure combines our skin layer map with the heatmap produced by the Grad-CAM technique designed to indicate image regions used by the deep model to make a classification decision. Moreover, we propose a multicriteria model evaluation measure to select the optimal model in terms of classification accuracy, confidence, and test dataset size. The experiments described in the paper show that the DenseNet-201 model fed with the extracted region of interest produces the most reliable and accurate results.

Correlation of the ALA-PDT Treatment Efficacy and the HPV Genotype Profile of Genital Warts after Cryotherapy Failure and Podophyllotoxin Therapy in Male Patients.

BACKGROUND: Genital warts are the manifestation of the human papillomavirus (HPV) infection, which may last for weeks or months before the clinical presentation. The primary aim of the study was the correlation of the DNA HPV genotypes eradication with the treatment response in male patients with persistent genital warts. METHODS: Twenty-one male patients (age range: 22-58) after failure of cryotherapy and podophyllotoxin treatment were enrolled in the study. Genetic tests (Real Time - PCR method) analyzed the presence of DNA-HPV before and 6 months after four sessions (4 weeks apart) of photodynamic therapy with 5-aminolaevulinic acid (ALA-PDT). The treatment efficacy was evaluated before each PDT session and at the end of the study. RESULTS: The single HPV DNA type was present in 15/21 of the patients (13/15 HPV6). The high-risk HPV types were found in 8/21 subjects, of which 6/8 had several types. Six months after four sessions of PDT, complete response was found in 16/21 (76.19%; p = 0.0007) of patients, and DNA HPV clearance was found in 66.67% (p = 0.03). The eradication rate differed among patients with primary low-risk and high-risk HPV types-76.92% (10/13; p = 0.0003) and 50% (4/8; p = 0.05) respectively. CONCLUSION: ALA-PDT is an effective treatment even after the failure of previous modalities. The persistence of clinical lesions and high oncological risk HPV types should be an indication for treatment prolongation.

The incidence and clinical analysis of non-melanoma skin cancer.

Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.

Approach to Preventive Epilepsy Treatment in Tuberous Sclerosis Complex and Current Clinical Practice in 23 Countries.

Tuberous sclerosis complex (TSC) is associated with a high risk of early-onset epilepsy and developmental delay. Recently, EEG monitoring in infants with TSC and preventive antiepileptogenic treatment have been proposed to improve epilepsy and neurodevelopmental outcome. We explored how recent studies and recommendations regarding EEG monitoring and preventive epilepsy treatment have influenced the clinical practice of epilepsy management among children with TSC. METHODS: A survey on the epilepsy management approach in infants with TSC was sent by e-mail to 165 clinicians who actively participated in TSC international research conferences in years 2016 - 2019. Additionally, the e-mail addresses of TSC referral centers were collected from national TSC organizations. The survey was also distributed in the American Epilepsy Society newsletter. Only responses from centers providing neurological care for children with TSC were included in the study. RESULTS: Sixty-one responses from 23 countries were analyzed. Sixty respondents answered questions concerning infants, and 57 of 60 respondents (95%) perform at least one EEG study before epilepsy onset and 42 (70.0%) conduct regular EEG monitoring. Most of the clinicians perform video EEG (42/61, 68.8%). Overall, 51.7% of respondents, mostly from Europe, Australia, and South America, endorse preventive antiepileptic treatment in infants with TSC. Vigabatrin is a preferred drug in patients younger than two years old for both focal (61.7%) and generalized (56.7%) seizures. CONCLUSIONS: Despite the lack of published results of randomized trials, the concepts of preseizure EEG monitoring and epilepsy prevention are already being implemented in the majority of surveyed centers.

Clinical and epidemiological analysis of basosquamous carcinoma: results of the multicenter study.

Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer that shares the characteristic features of both basal and squamous cell carcinomas (BCC, SCC). Our research enables better characterization of BSC in comparison to high-risk subtypes of BCC and SCC. Paper includes a retrospective analysis of BSC cases regarding sex, age, number of tumors and anatomical distribution in comparison to BCC and SCC evaluating the differences and defining the implications. Histologically confirmed carcinomas recorded between 1999 and 2019 were studied. 181 diagnosed BSC cases were identified, making this study the largest cohorts of BSC patients reported worldwide. Most cases were reported on head and neck. Analysis of facial anatomic distribution shows that most commonly affected sites were the nose (43%) and the cheek (25%). The age at excision of metatypical BCC was higher than those of low-risk BCC (P < 0.05), however similar to high-risk BCC (P = 0.20). We revisited that the concept of BSC is the most similar to high-risk subtypes of BCC. Patients with diagnosed BSC have higher risk of second nonmelanoma skin cancer. Therefore, the frequency of follow-up examination should be adjusted to the individual risk of another skin cancer.

Oral Findings in Children, Adolescents and Adults with Tuberous Sclerosis Complex.

Objectives: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder characterized by the development of benign tumors. The aim of the study was to assess the prevalence of oral lesions in patients with TSC and healthy individuals. Study design: The study included 120 patients aged 1.1 to 42.7 years: 60 patients with TSC and 60 controls. Clinical assessment of oral hygiene (Plaque Index-PLI), gingiva (Gingival Index-GI, Gingival Overgrowth Index-GOI), oral mucosa and dentition (caries, tooth wear, enamel defects) was performed. Statistical analysis was performed. Results: 40 patients with TSC received anticonvulsants. Neglected hygiene (PLI: 1.50±0.96 vs 0.92±0.72), gingival hyperplasia (50.0% vs.1.7%), gingivitis (80.7% vs. 53.4%), oral mucosal fibromas (10.0% vs. 0.0%), mucous membrane traumatic lesions (11.7% vs. 1.7%), enamel pits and hypoplasia of incisal borders (41.7% vs. 6.7%), tooth wear (35.0% vs. 11.7%) were more common in patients with TSC compared to controls; increased gingival hyperplasia was correlated with vigabatrin and levetiracetam treatment (r = 0.266 and 0.279, respectively), gingivitis was correlated with PLI (r= 0.635). Conclusions: Although gingival fibromas in TSC are independent of patient's age, young age, anticonvulsant therapy and local factors increase their severity. Enamel defects in TSC include pits, but also enamel loss on the incisal edges and tooth wear.

Preventive Antiepileptic Treatment in Tuberous Sclerosis Complex: A Long-Term, Prospective Trial.

BACKGROUD: Drug-resistant epilepsy is the main risk factor for future intellectual disability in patients with tuberous sclerosis complex. Clinical epileptic seizures are often preceded by electroencephalographic changes, which provide an opportunity for preventive treatment. We evaluated the neuropsychologic and epilepsy outcomes at school age in children with tuberous sclerosis complex who received preventive antiepileptic treatment in infancy. METHODS: We performed a prospective, nonrandomized clinical trial with 14 infants diagnosed with tuberous sclerosis complex in whom serial electroencephalographic recordings were performed and preventive treatment with vigabatrin initiated when active epileptic discharges were detected. An age-matched control group consisted of 31 infants with tuberous sclerosis complex in whom treatment with vigabatrin was given only after onset of clinical seizures. Results of clinical assessment of epilepsy and cognitive outcomes were analyzed. RESULTS: All patients in the preventive group (n = 14) and 25 of 31 patients in the standard treatment group were followed through minimum age five years, median 8.8 and 8.0 years in the preventive and standard groups, respectively. The median intelligence quotient was 94 for the preventive group when compared with 46 for the standard group (P < 0.03). Seven of 14 patients (50%) in the preventive group never had a clinical seizure when compared with one of 25 patients (5%) in the standard treatment group (P = 0.001). CONCLUSIONS: This study provides evidence that preventive antiepileptic treatment in infants with tuberous sclerosis complex improves long-term epilepsy control and cognitive outcome at school age.

Prevention of epilepsy in humans - truth or myth? The experience from Sturge-Weber syndrome and Tuberous Sclerosis Complex.

INTRODUCTION: Epilepsy is a chronic neurological disease, usually decreasing the quality of life and often resulting in other comorbidities e.g. cognitive impairment in children. Despite the recent discovery of new antiepileptic drugs, roughly one in three patients suffers from drug-resistant seizures. Therefore, the prevention of epilepsy is becoming one of the most important challenges in medicine. Is it, however, in fact possible to prevent epilepsy? CLINICAL REFLECTIONS AND IMPLICATIONS: We present the results of preventive antiepileptic treatment in children with Sturge-Weber syndrome and Tuberous Sclerosis Complex as examples of the possible prevention of epilepsy and epilepsy-associated cognitive impairment in children.

Long-term Outcome of Intravenous Lidocaine in Pediatric Cluster Seizures: A Preliminary Study.

BACKGROUND: Cluster seizures are life-threatening conditions. They may easily evolve into status epilepticus and are reported in up to 20% to 30% of patients with epilepsy. Sometimes cluster seizures become drug resistant, leading to the use of unconventional therapies. One of these unconventional approaches may be the use of lidocaine, which is a sodium-channel-blocking drug mostly known as a local anesthetic and antiarrhythmic agent. METHODS: We describe the outcome of four children who were treated with continuous intravenous infusion of 2% lidocaine due to drug-resistant focal cluster seizures. Lidocaine was administered as an initial dose of 1 mg/kg/hour and, subsequently, was increased to 2 to 4 mg/kg/hour. The therapy was continued for five to 10 days. Patients remained under careful cardiological surveillance during the treatment. RESULTS: Complete seizure remission was achieved in all four children. None of the patients experienced adverse events. Although seizures recurred in all patients within an average time of 2.4 months, they appeared with reduced frequency, and within the follow-up period (mean 7.5 months) no additional cluster seizures occurred. CONCLUSIONS: Treatment with lidocaine in pediatric cluster seizures may be useful and may be considered as a therapeutic option. Our patients encountered no side effects and experienced prolonged seizure remission, possibly resulting from the effect of lidocaine on sodium channels or from its anti-inflammatory properties. However, more studies are required to confirm the safety and long-term effectiveness of this approach. Clinicians should be aware of possible adverse effects and necessity of sustained cardiological surveillance during the treatment.