Relationship between functional status and fatigue after COVID-19 infection: a multicenter study from Türkiye.

Background/aim: Symptoms of COVID-19 may persist for months. One of the persistent symptoms of COVID-19 is fatigue, which reduces functional status. The relationship between fatigue, functional status, and various other factors has received little attention, which this study aims to address.. Materials and methods: Patients with COVID-19 infection were included in this multicenter cross-sectional study. Age, sex, body mass index (BMI), marital status, smoking status, presence and duration of chronic disease, comorbidity index, regular exercise habits, time since COVID-19 diagnosis, hospitalization status, length of hospital stay, intubation status, home oxygen therapy after discharge, participation in a pulmonary rehabilitation program, presence of dyspnea, presence of cough, presence of sputum, and modified Medical Research Council, Post-COVID Functional Status (PCFS), Fatigue Severity Scale (FSS), and EQ-5D-5L Questionnaire scores were recorded. Results: We enrolled 1095 patients, including 603 (55%) men and 492 (45%) women with a mean age of 50 ± 14 years. The most common chronic lung disease was COPD (11%) and 266 (29%) patients had nonpulmonary disease. The median time elapsed since COVID-19 diagnosis was 5 months; the hospitalization rate was 47%. The median PCFS grade was 1 (0-4) and the median FSS score was 4.4 (1-7). The PCFS and FSS were positively correlated (r = 0.49, p < 0.01; OR: 1.88, 95% CI: 1.68-2.10). Both functional status and fatigue were associated with quality of life, which was lower in older patients, those with higher BMI, those with systemic disease, those not exercising regularly, and those with more severe COVID-19 infection (defined by dyspnea, pneumonia as indicated by computed tomography, hospitalization, length of stay, ICU admission, intubation, and the need for home oxygen after discharge). Conclusion: Fatigue may cause poorer functional status regardless of the time since COVID-19 diagnosis. In this study, patients with FSS scores of >4.78 showed moderate to severe functional limitations. It is important to address modifiable patient risk factors and reduce the severity of COVID-19 infection.

Incidental parathyroidectomy after thyroid surgery and relationship with postoperative hypocalcemia: a single tertiary center analysis.

Incidental parathyroidectomy (IP) is a complication seen at varying rates after thyroid surgery, and its relationship with postoperative hypocalcemia has not been clarified. In this study, our goal was to identify the frequency and risk factors for IP in a large patient cohort and assess its correlation with postoperative hypocalcemia. A total of 4052 patients who underwent thyroid surgery between 2008 and 2020 were reviewed retrospectively. The patients were divided into two groups, the IP and non-IP groups, and compared in terms of demographics, surgical procedures, pathological diagnosis, and specimen weight. The relationships between IP and hypocalcemia were also evaluated. There were 587 (14.5%) IPs out of 4052 cases. In these patients, mostly one gland was removed (84.6%), and 23.2% of these glands were intrathyroidal. The rate of transient hypocalcemia was 39.9%, and that of permanent hypocalcemia was 1.7%. Female gender, malignancy, lower preoperative thyroid volume, presence of central lymph node dissection, lower specimen weight, presence of autotransplantation and capsule invasion in malignant cases were determined to be risk factors for IP. After excluding hemithyroidectomy and autotransplantation, transient and permanent hypocalcemia were found to be significantly higher in cases with IP (p < 0.001). Multivariate analysis showed that female sex, no multinodular goiter, central dissection, and low thyroid volume were risk-adjusted independent variables. Our findings highlight the significant role of IP in postoperative hypocalcemia. Given that most IPs are located in the perithyroidal region, precise surgical dissection is vital to preserve parathyroid gland function and prevent IP and subsequent hypocalcemia.

Sensitivity of frozen section analysis in patients with ovarian adult granulosa cell tumor, a multi-center study.

INTRODUCTION: We aimed to demonstrate the sensitivity of frozen section for patients with adult granulosa cell tumor (AGCT) and analyze the clinico-pathological factors that may be associated with sensitivity. MATERIAL METHODS: This is a multicenter study including data of 10 Gynecological Oncology Departments. Frozen-section results of patients who had ovarian AGCT at the final pathology report were retrospectively analyzed. The relation between clinico-pathological characteristics such as age, tumor size, Ca-125 level, presence of ascites, omental metastasis, menopausal status and peritoneal cytology, and the sensitivity of frozen section in patients with AGCT were evaluated. The sensitivity of frozen section diagnosis was determined by comparing the frozen section result with the final pathological diagnosis. RESULTS: Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52 years (range, 17-82 years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90 mm (range, 9-700 mm). The median preoperative Ca-125 level was 23 IU/mL (range, 2-995 IU/mL). The sensitivity of frozen section for detecting AGCT was 76.3%. Any association between the sensitivity of frozen section and menopausal status, presence of ascites, positive cytology, omental metastasis, tumor size, Ca-125 level, age could not be shown. CONCLUSION: It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%.

Drug-Resistant Epilepsy in Tuberous Sclerosis Complex Is Associated With TSC2 Genotype: More Findings From the Preventing Epilepsy Using Vigatrin (PREVeNT) Trial.

BACKGROUND: Children with tuberous sclerosis complex (TSC) are at high risk for drug-resistant epilepsy (DRE). The ability to stratify those at highest risk for DRE is important for counseling and prompt, aggressive management, necessary to optimize neurocognitive outcomes. Using the extensively phenotyped PREVeNT cohort, we aimed to characterize whether the TSC genotype was associated with DRE. METHODS: The study group (N = 70) comprised participants with TSC enrolled at age less than or equal to six months with detailed epilepsy and other phenotypic and genotypic data, prospectively collected as part of the PREVeNT trial. Genotype-phenotype correlations of DRE, time to first abnormal electroencephalography, and time to epilepsy onset were compared using Fisher exact test and regression models. RESULTS: Presence of a TSC2 pathogenic variant was significantly associated with DRE, compared with TSC1 and participants with no pathogenic mutation identified. In fact, all participants with DRE had a TSC2 pathogenic variant. Furthermore, TSC2 variants expected to result in no protein product were associated with higher risk for DRE. Finally, TSC1 pathogenic variants were associated with later-onset epilepsy, on average 21.2 months later than those with other genotypes. CONCLUSIONS: Using a comprehensively phenotyped cohort followed from infancy, this study is the first to delineate genotype-phenotype correlations for epilepsy severity and onset in children with TSC. Patients with TSC2 pathogenic variants, especially TSC2 pathogenic variants predicted to result in lack of TSC2 protein, are at highest risk for DRE, and are likely to have earlier epilepsy onset than those with TSC1. Clinically, these insights can inform counseling, surveillance, and management.

Evaluation and follow-up of patients diagnosed with hypophysitis: a cohort study.

OBJECTIVE: Primary hypophysitis might be challenging to diagnose, and there is a lack of evidence regarding optimal treatment strategies due to rarity of the disease. We aim to investigate the clinical features and compare the outcomes of different management strategies of primary hypophysitis in a large group of patients recruited on a nationwide basis. DESIGN: A retrospective observational study. METHODS: The demographic, clinical, and radiologic features and follow-up data were collected in study protocol templates and analyzed. RESULTS: One hundred and thirteen patients (78.8% female, median age: 36 years) were included. Lymphocytic (46.7%) and granulomatous hypophysitis (35.6%) were the prevailing subtypes out of 45 patients diagnosed after pathologic investigations. Headache (75.8%) was the most common symptom, and central hypogonadism (49.5%) was the most common hormone insufficiency. Of the patients, 52.2% were clinically observed without interventions, 18.6% were started on glucocorticoid therapy, and 29.2% underwent surgery at presentation. Headache, suprasellar extension, and chiasmal compression were more common among glucocorticoid-treated patients than who were observed. Cox regression analysis revealed higher hormonal and radiologic improvement rates in the glucocorticoid-treated group than observation group (hazard ratio, 4.60; 95% CI, 1.62-12.84 and HR, 3.1; 95% CI, 1.40-6.68, respectively). The main indication for surgery was the inability to exclude a pituitary adenoma in the presence of compression symptoms, with a recurrence rate of 9%. CONCLUSION: The rate of spontaneous improvement might justify observation in mild cases. Glucocorticoids proved superior to observation in terms of hormonal and radiologic improvements. Surgery may not be curative and might be considered in indeterminate, treatment-resistant, or severe cases.

Fluorimetric methods for determination of aluminum in water resources utilizing newly synthesized N,N'-bis(2,5-dihydroxybenzylidene)-4,4'-diamino diphenyl ether.

Industrial waste contaimnation of water sources is a serious environmental problem. As a result, it's critical to identify metallic contamination in water with precision, sensitivity, and accuracy. In acetonitrile, the fluorimetric parameters of N,N-'bis(2,5-dihydroxybenzylidene)-4,4'-diamino diphenyl ether (DHDPE) and aluminum complex were determined. In the acetonitrile medium, the best fluorescence intensity of the DHDPE-Al complex was observed at λex = 280 nm, λem = 391 nm (excitation and emission wavelengths). For optimum complex formation, the ideal pH, duration, and temperature were 4.5, 20 min, and 25 °C, respectively. Within the ranges of 0.027-0.27 and 0.27-2.70 ppm aluminum concentrations, [Al3+]-F.I. Calibration graphs were linear. The fluorimetric aluminum measurement method was applied to diverse water sources using the newly synthesized macro molecular Schiff base DHDPE as the ligand. The aluminum concentration in water inflow to KOSKI (Konya Water and Sewerage Administration) was doubled as a result of the examination when compared to other samples of water.

The experiance of tertiary center for adult granulosa cell tumor: which factors predict survival?

BACKGROUND: This retrospective study aims to evaluate the clinical course and long-term outcomes of patients diagnosed with adult granulosa cell tumors (AGCT). METHODS: The study analyzed a cohort of 112 AGCT patients with a median follow-up of 87 months. Data regarding disease-free survival (DFS), overall survival (OS), recurrence rates, and prognostic factors were collected and analyzed. Surgical interventions, including lymphadenectomy and cytoreductive surgery, were assessed for their impact on outcomes. RESULTS: The study revealed favorable long-term outcomes, with a 5-year DFS of 85% and a 10-year DFS of 83%. Additionally, a 5-year OS of 100% and a 10-year OS of 96% were observed. Recurrence occurred in 13.4% of cases, with advanced stage and positive peritoneal cytology identified as independent poor prognostic factors for DFS. Lymph node involvement was rare, and routine lymphadenectomy did not improve outcomes. Conservative surgery showed comparable DFS rates to definitive surgery in early-stage disease. However, cytoreductive surgery was crucial for advanced and recurrent tumors, with complete tumor resection enhancing survival outcomes. CONCLUSION: The study underscores the importance of vigilant follow-up and individualized treatment strategies for AGCT patients. Despite the retrospective nature of the analysis, the substantial patient cohort and meticulous surgical interventions contribute valuable insights into AGCT management. Prospective multicenter studies are warranted to further elucidate prognostic factors and optimize treatment approaches for this rare malignancy.

Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome.

Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, the most severe symptoms of TSC are often neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities. TSC is caused by loss of function mutations in the TSC1 or TSC2 genes and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1). While TSC neurological phenotypes are well-documented, it is not yet known how early in neural development TSC1/2-mutant cells diverge from the typical developmental trajectory. Another outstanding question is the contribution of homozygous-mutant cells to disease phenotypes and whether such phenotypes are also seen in the heterozygous-mutant populations that comprise the vast majority of cells in patients. Using TSC patient-derived isogenic induced pluripotent stem cells (iPSCs) with defined genetic changes, we observed aberrant early neurodevelopment in vitro, including misexpression of key proteins associated with lineage commitment and premature electrical activity. These alterations in differentiation were coincident with hundreds of differentially methylated DNA regions, including loci associated with key genes in neurodevelopment. Collectively, these data suggest that mutation or loss of TSC2 affects gene regulation and expression at earlier timepoints than previously appreciated, with implications for whether and how prenatal treatment should be pursued.

AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient.

There are more than 10,000 individual rare diseases and most are without therapy. Personalized genetic therapy represents one promising approach for their treatment. We present a road map for individualized treatment of an ultra-rare disease by establishing a gene replacement therapy developed for a single patient with hereditary spastic paraplegia type 50 (SPG50). Through a multicenter collaboration, an adeno-associated virus-based gene therapy product carrying the AP4M1 gene was created and successfully administered intrathecally to a 4-year-old patient within 3 years of diagnosis as part of a single-patient phase 1 trial. Primary endpoints were safety and tolerability, and secondary endpoints evaluated efficacy. At 12 months after dosing, the therapy was well tolerated. No serious adverse events were observed, with minor events, including transient neutropenia and Clostridioides difficile gastroenteritis, experienced but resolved. Preliminary efficacy measures suggest a stabilization of the disease course. Longer follow-up is needed to confirm the safety and provide additional insights on the efficacy of the therapy. Overall, this report supports the safety of gene therapy for SPG50 and provides insights into precision therapy development for rare diseases. Clinical trial registration: NCT06069687 .

Common human leucocyte antigensassociated with the development of subacute thyroiditis and COVID-19.

PURPOSE: Case reports of subacute thyroiditis (SAT) following coronavirus disease-19 (COVID-19) have been reported. Because the relationship between SAT and human leucocyte antigen (HLA) alleles is known, we aimed to determine HLA alleles that may predispose a patient to coronavirus infection and/or post-COVID-19 SAT. METHOD: This retrospective study was conducted in 51 patients with SAT and 190 healthy bone marrow donor volunteers. HLA-A, -B, -C, -DRB1, and -DQB1 were genotyped using next-generation sequencing. The study population was grouped into four groups according to SAT and COVID-19 history. RESULTS: The frequency of HLA-DQB1*04:02 was higher in the COVID-19(-) participants than in the COVID-19(+) participants (=0.045). The presence of HLA-DQB1*04:02 was associated with a lower risk of developing COVID-19 in all groups. The frequencies of HLA-B*35:01, HLA-B*35:03, HLA-DRB1*12:01, and HLA-DRB1*14:01 were different in the SAT(+) group than in the SAT(-) group in COVID-19(-) group. The frequencies of HLA-C*12:03, HLA-DQB1*06:04, HLA-DRB1*13:02, and HLA-DRB1*13:03 were different in the SAT(+) group than in the SAT(-) group in the COVID-19 (+) group. The difference in the frequency of these HLA types remains significant when the four groups are included together as follows: In the COVID-19(+) group, the frequencies of HLA-DRB1*13:02, and HLA-DRB1*13:03 were higher in the SAT(+) group than in the SAT(-) group. In the COVID-19(-) group, the frequencies of HLA-B*35:03, HLA-DRB1*12:01, and HLA-DRB1*14:01 were higher in the SAT (+) group than in the SAT(-) group. CONCLUSION: HLA alleles associated with SAT susceptibility may vary with COVID-19 history.

Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multi-system genetic disease that causes benign tumors in the brain and other vital organs. The most debilitating symptoms result from involvement of the central nervous system and lead to a multitude of severe symptoms including seizures, intellectual disability, autism, and behavioral problems. TSC is caused by heterozygous mutations of either the TSC1 or TSC2 gene and dysregulation of mTOR kinase with its multifaceted downstream signaling alterations is central to disease pathogenesis. Although the neurological sequelae of the disease are well established, little is known about how these mutations might affect cellular components and the function of the blood-brain barrier (BBB). METHODS: We generated TSC disease-specific cell models of the BBB by leveraging human induced pluripotent stem cell and microfluidic cell culture technologies. RESULTS: Using microphysiological systems, we demonstrate that a BBB generated from TSC2 heterozygous mutant cells shows increased permeability. This can be rescued by wild type astrocytes or by treatment with rapamycin, an mTOR kinase inhibitor. CONCLUSION: Our results demonstrate the utility of microphysiological systems to study human neurological disorders and advance our knowledge of cell lineages contributing to TSC pathogenesis and informs future therapeutics.

The Knowledge, Attitudes, and Practices of Parents Regarding Sun Protection for Their Children.

OBJECTIVE: To evaluate the knowledge, attitudes, and practices of parents toward protecting their children against skin cancer and the sun. METHODS: This cross-sectional study was performed in Turkey from March through October 2022. The authors used a questionnaire investigating the parents' and children's characteristics, attitudes, and practices toward sun protection and the Skin Cancer and Sun Knowledge (SCSK) scale to collect data. RESULTS: Of 465 parents, 60.2% were women, 83.2% were light-skinned, 20.2% perceived their children as risk-free, 43.8% perceived their children as low risk in terms of skin cancer, 14.6% examined their children from head to foot, 62.3% applied sunscreen to their children, 9.7% made them wear long-sleeved clothing, 60.0% made them wear headgear, 61.1% made them remain in the shade or under a sunshade, and 32.3% made them wear sunglasses. The mean parental SCSK scale score was 14.3 ± 4.1. Scale scores were higher among those who perceived their children as being at high risk for skin cancer (P = .000), whose children had not experienced red or painful sunburn in the previous year (P = .000), and who informed their children about sun protection (P = .000). CONCLUSIONS: Although knowledge of skin cancer and solar protection was high, parental perception of the risk of skin cancer was very low, and attitudes toward skin examination were also very relaxed.

Variation in neuroimaging and outcomes in patients with Sturge Weber syndrome Type III.

OBJECTIVES: Sturge Weber syndrome (SWS) is a neurovascular condition with an estimated incidence of 1 in 20,000 to 50,000 live births. SWS Types I and II involve cutaneous and ophthalmological findings, with neurological involvement in Type I. SWS Type III is exclusive to brain stigmata. Our study aims to describe the characteristics of brain MRI findings and report neuroradiological features with seizure and cognitive outcomes in patients with SWS Type III. METHODS: This is a retrospective case series examining the clinical, radiological, and cognitive characteristics of patients with SWS Type III referred to the SWS Clinic at Boston Children's Hospital. We analyzed brain MRI findings based on vascular and parenchymal features. Clinical and cognitive outcomes were based on a validated assessment tool in this population (Neuroscore). RESULTS: This dedicated case series of patients with Type III SWS from a single center identified ten patients. All patients had classic stigmata indicative of SWS. Two distinct radiological phenotypes were found, one characterized by more pronounced deep venous enlargement, and the other, with more pronounced parenchymal abnormalities. There was heterogeneity in seizure presentation and outcome. Earlier age of onset and seizures predict more severe outcomes, as seen in classic SWS. CONCLUSION: We could not find significant divergence in outcomes between patients with differing neuroimaging phenotypes. These results raise the question of whether the two distinct radiological phenotypes found in SWS Type III are reflective of different disease entities, with underlying genetic heterogeneity. These results suggest the need for larger, multi-center natural history studies.

Abnormality of Early White Matter Development in Tuberous Sclerosis Complex and Autism Spectrum Disorder: Longitudinal Analysis of Diffusion Tensor Imaging Measures.

Background: Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data. Methods: Eligible participants (3-12 months) underwent brain magnetic resonance imaging (MRI) at repeated time points from ages 3 to 36 months. Positive Autism Diagnostic Observation Schedule-Second Edition classification at 36 months was used. Linear mixed effects models were fine-tuned separately for fractional anisotropy values (using fractional anisotropy corpus callosum as test outcome) and mean diffusivity values (using mean diffusivity right posterior limb internal capsule as test outcome). Fixed effects included participant age, within-participant longitudinal age, and autism spectrum disorder diagnosis. Results: Analysis included data from n = 78. After selecting separate optimal models for fractional anisotropy and mean diffusivity values, we applied these models to fractional anisotropy and mean diffusivity of all 27 white matter tracts. Fractional anisotropy corpus callosum was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = 0.0093, P = .0612), and mean diffusivity right inferior cerebellar peduncle was related to positive Autism Diagnostic Observation Schedule-Second Edition classification (coefficient = -0.00002071, P = .0445), though these findings were not statistically significant after multiple comparisons correction. Conclusion: These optimized linear mixed effects models possibly implicate corpus callosum and cerebellar pathology in development of autism spectrum disorder in tuberous sclerosis complex, but future studies are needed to replicate these findings and explore contributors of heterogeneity in these models.

Cutaneous findings in patients with acromegaly and its relationship with concomitant endocrinopathies.

OBJECTIVES: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies. DESIGN, PATIENTS, AND MEASUREMENTS: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated. RESULTS: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035). CONCLUSIONS: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier.

Can we manage the melanocytic lesions with peripheral globules according to the grade of dysplasia?

BACKGROUND/OBJECTIVES: Although excision of melanocytic nevi with high-grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based on the grading dysplasia of melanocytic lesions with peripheral globules (PGs) are lacking. We investigated the grades of dysplasia and their distinguishable dermoscopic and clinical features to provide accurate data for managing these lesions. METHODS: We retrospectively classified histologically confirmed melanocytic lesions with PGs according to the 2018 WHO Classification of Skin Tumours criteria in a university hospital in Turkey. Dermoscopic features, lesions, and patient characteristics were recorded. RESULTS: Sixty-six lesions of 56 patients were included. After classification, 9.1% (n: 6) of lesions were melanomas, 39.4% (n: 26) were high-grade dysplastic nevi, and 50% (n: 33) were low-grade dysplastic nevi (n: 33, 50%). There was one nevus with no dysplasia (n: 1, 1.5%). Univariate analysis revealed that ≥31 years of age, irregular shape of peripheral globules, black colour, total colour count, and maximum diameter of the lesion were associated with high-grade dysplasia and melanoma. In the multivariate analyses, ≥31 years of age (OR = 3.80, 95% CI, 1.17-12.37), irregular shape of peripheral globules (OR = 3.90, 95% CI, 1.15-13.2), and total colour count (OR = 3.21, 95% CI, 1.2-8.5) were significant predictive factors for the lesions with high-grade dysplasia and melanomas. CONCLUSIONS: To avoid the underdiagnosis of both melanomas and high-grade dysplastic nevi with PGs, the irregular shape of peripheral globules and multiple colours after the third decade may be useful in making an excision decision. The risk increases every 1-year increase in age. Excision is suggested for all melanocytic lesions with PGs for patients 60 years or older because of the high risk of melanoma and melanocytic nevus with high-grade dysplasia.

Automatic Segmentation of Vestibular Schwannomas: A Systematic Review.

BACKGROUND: Vestibular schwannomas (VSs) are benign tumors often monitored over time, with measurement techniques for assessing growth rates subject to significant interobserver variability. Automatic segmentation of these tumors could provide a more reliable and efficient for tracking their progression, especially given the irregular shape and growth patterns of VS. METHODS: Various studies and segmentation techniques employing different Convolutional Neural Network architectures and models, such as U-Net and convolutional-attention transformer segmentation, were analyzed. Models were evaluated based on their performance across diverse datasets, and challenges, including domain shift and data sharing, were scrutinized. RESULTS: Automatic segmentation methods offer a promising alternative to conventional measurement techniques, offering potential benefits in precision and efficiency. However, these methods are not without challenges, notably the "domain shift" that occurs when models trained on specific datasets underperform when applied to different datasets. Techniques such as domain adaptation, domain generalization, and data diversity were discussed as potential solutions. CONCLUSIONS: Accurate measurement of VS growth is a complex process, with volumetric analysis currently appearing more reliable than linear measurements. Automatic segmentation, despite its challenges, offers a promising avenue for future investigation. Robust well-generalized models could potentially improve the efficiency of tracking tumor growth, thereby augmenting clinical decision-making. Further work needs to be done to develop more robust models, address the domain shift, and enable secure data sharing for wider applicability.

Exploring the neurological features of individuals with germline PTEN variants: A multicenter study.

OBJECTIVE: PTEN, a known tumor suppressor gene, is a mediator of neurodevelopment. Individuals with germline pathogenic variants in the PTEN gene, molecularly defined as PTEN hamartoma tumor syndrome (PHTS), experience a variety of neurological and neuropsychiatric challenges during childhood, including autism spectrum disorder (ASD). However, the frequency and nature of seizures and the utilization of allied health services have not been described. METHODS: Young patients with PHTS and sibling controls were recruited across five centers in the United States and followed every 6-12 months for a mean of 2.1 years. In addition to the history obtained from caregivers, neurodevelopmental evaluations and structured dysmorphology examinations were conducted, and brain MRI findings, received therapies, and epilepsy characteristics were reported. RESULTS: One hundred and seven patients with PHTS (median age 8.7 years; range 3-21 years) and 38 controls were enrolled. ASD and epilepsy were frequent among patients with PHTS (51% and 15%, respectively), with generalized epilepsy strongly associated with ASD. Patients with epilepsy often required two antiseizure medications. Neuroimaging revealed prominent perivascular spaces and decreased peritrigonal myelination in individuals with PHTS-ASD. Allied therapy use was frequent and involved physical, occupational, speech, and social skills therapies, with 89% of all patients with PHTS, regardless of ASD diagnosis, utilizing at least one service. INTERPRETATION: This prospective, longitudinal study highlights the wide neurological spectrum seen in young individuals with PHTS. ASD is common in PHTS, comorbid with epilepsy, and allied health services are used universally. Our findings inform care discussions with families about neurological outcomes in PHTS.

Emergent approach to small bowel tumors: diagnosis and treatment.

BACKGROUND: This study presents the diagnosis and treatment of rare small bowel tumors through clinical cases. METHODS: Patients treated between 2000 and 2023 were included in the study. The clinical records of the patients were analyzed retrospectively. RESULTS: A total of 34 patients were included in the study. Of these patients, 26 (75.5%) were male and eight (23.5%) were female. The mean age of the patients was 62.1 years. The most common symptoms and signs were abdominal pain (76.4%), bloating (38.2%), and nausea and vomiting (17.6%). Diagnostic methods included computed tomography (CT) (82.3%), upper gastrointestinal double balloon enteroscopy (35.2%), and capsule endoscopy (5.8%). Diagnoses included adenocarcinoma in 13 cases, gastrointestinal stromal tumors (GISTs) in 12 cases, and neuroendocrine tumors (NETs) in two cases. CONCLUSION: Small bowel tumors frequently present with abdominal pain, bloating, and nausea and vomiting. CT and endoscopic procedures are the primary diagnostic tools. Small bowel cancers are often diagnosed late due to subtle clinical findings and the limitations of endoscopic imaging. Targeted screening strategies may be beneficial for certain at-risk and symptomatic patient groups. Early surgical intervention offers significant advantages for diagnosed patients.

Common epilepsy variants from the general population are not associated with epilepsy among individuals with tuberous sclerosis complex.

Common genetic variants identified in the general population have been found to increase phenotypic risks among individuals with certain genetic conditions. Up to 90% of individuals with tuberous sclerosis complex (TSC) are affected by some type of epilepsy, yet the common variants contributing to epilepsy risk in the general population have not been evaluated in the context of TSC-associated epilepsy. Such knowledge is important to help uncover the underlying pathogenesis of epilepsy in TSC which is not fully understood, and critical as uncontrolled epilepsy is a major problem in this population. To evaluate common genetic modifiers of epilepsy, our study pooled phenotypic and genotypic data from 369 individuals with TSC to evaluate known and novel epilepsy common variants. We did not find evidence of enhanced genetic penetrance for known epilepsy variants identified across the largest genome-wide association studies of epilepsy in the general population, but identified support for novel common epilepsy variants in the context of TSC. Specifically, we have identified a novel signal in SLC7A1 that may be functionally involved in pathways relevant to TSC and epilepsy. Our study highlights the need for further evaluation of genetic modifiers in TSC to aid in further understanding of epilepsy in TSC and improve outcomes.