Rare Group Research Articles

Enhanced Disease-Specific Survival Among Individuals With Malignant Adnexal Tumors of the Skin Treated With Mohs Surgery: A National Database Study.

Malignant adnexal tumors of the skin are a rare group of tumors that can be locally aggressive and require surgical excision with strict margin control to achieve clearance. Given the rarity of these tumors, there is a limited understanding within the medical community regarding optimal treatment approaches. To examine surgical management trends and outcomes for patients diagnosed with cutaneous adnexal tumors from 2000 to 2020. The Surveillance, Epidemiology, and End Results database was queried to identify biopsy-proven cases of cutaneous adnexal tumors between 2000 and 2020. Clinical and disease characteristics were examined, and disease-specific survivals were compared between surgical approaches using Kaplan-Meier curves and Cox proportional hazards models. Mohs surgery demonstrated a significant increase in utilization from 2000 to 2020 (+447.1%) and improvements in disease-specific survival (mean 231.7 months; p < .001) compared with no surgery; wide local excision exhibited no improved disease-specific survival (227.7 months; p = .070). Multivariable Cox regression further highlighted that only Mohs surgery exhibited a reduced disease-specific mortality risk compared with no surgery (adjusted HR 0.49; p = .011). Given the enhanced disease-specific survival coupled with tissue preservation strategies, Mohs surgery emerges as a promising surgical approach for the treatment of malignant adnexal tumors of the skin.

Third ventricle teratoma with malignant transformation

Intracranial germ cell tumors(GCTs) are rare and heterogeneous group of primary brain tumors, mainly affecting pediatric population and young adults. The current understanding of the etiology of intracranial GCTs and their optimal management strategies remain controversial. Treatment plans differ depending on the subtype GCT and may vary among physicians and institutions. Central nervous system non-germinomatous germ cell tumor (NGGCT) usually requires surgical resection with histological verification, chemotherapy, and radiation. The extent of surgical resection is an important prognostic factor alongside the etiology and genetics of NGGCT. This article presents a rare clinical case of a rapidly growing teratoma located in the posterior part of third ventricle of a 17-year-old male presenting with symptoms of intracranial hypertension. Surgical total resection was preceded by endoscopic third ventriculostomy. Immunohistochemistry revealed the presence of embryonal carcinoma and immature teratoma cells turning the tumor into mixed type NGGCT with unfavorable prognosis. Despite the complete resection of the tumor and the timely initiation of adjuvant therapy, a rapid progression of the disease with subsequent unfavorable outcome was observed 3.6 months after the surgical treatment.

Livestock grazing modes induced the rapid differentiation of community recruitment in alpine meadow

Herbivores moderate grazing is a fundamental driver of plant diversity maintenance in grassland ecosystems. However, the effects of grazing with different herbivores on plant community composition and recruitment are still little known. Here, we conducted a field moderate grazing experiment to examine the effects of different grazing modes under moderate intensity in the cold season, including sheep grazing (SG), yak grazing (YG), and mixed grazing by sheep and yak (MG), on plant community composition and recruitment. Results showed that all grazing modes significantly decreased plant cover and average height of standing plant litter. Additionally, herbivores grazing significantly increased species richness but decreased community evenness (P < 0.05), with highest richness and evenness found in YG and SG plots, respectively. The trends of increasing aboveground biomass of common and rare species groups were most pronounced in the SG plots relative to the YG and MG plots. MG promoted the increasing of the common species group. From community recruitment, moderate grazing increased the sexual recruitment and decreased the asexual recruitment, and MG significantly inhibited the recruitment of asexual seedlings. Meanwhile, all grazing modes increased the species of poor palatability. These findings imply that the cold-season grazing with moderate intensity facilitated a rapid divergence succession of alpine meadow community by regulating the relative abundance of common and rare species, as well as the asexual seedlings recruitment induced by the removal of standing plant litter. Consequently, the cold-season grazing with different herbivores under moderate intensity can be used as a management tool to modulate grassland community structure and maintain species diversity in alpine grassland ecosystem.

Clinical and Morphological Aspects of Aggressive Salivary Gland Mixed Tumors: A Narrative Review.

Salivary gland tumors are a rare and heterogeneous group of neoplasms of the head and neck region. The mixed category of these tumors include the following entities: pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), salivary carcinosarcoma (CS), and metastasizing PA (MPA). The most common benign tumor of the salivary glands is PA. Metastasis and malignant degeneration have been reported in cases of PA of a salivary gland origin. Judging by their behavior, MPA, CEPA, and CS can be considered aggressive tumors. Invasive CEPA has been identified in the parotid gland more frequently. MPA and CS cases reported in the current literature are rare. In this paper, we present, narratively, the clinico-morphological features of this group of mixed tumors.

Re-evaluation and operative indications after induction therapy for thymic epithelial tumors.

Thymic epithelial tumors (TETs), encompassing thymoma and thymic carcinoma, represent a rare and heterogeneous group of thoracic malignancies with varying prognoses and treatment strategies. Surgical resection is the cornerstone of therapy for localized stages, but the management of locally advanced or unresectable TETs often involves induction therapy, including chemotherapy and/or radiation therapy, as a neoadjuvant approach aimed at downstaging the tumor to facilitate subsequent resection. This review synthesizes current knowledge on the re-evaluation process and operative indications following induction therapy for TETs, highlighting the pivotal role of accurate assessment in guiding surgical decisions and optimizing patient outcomes. Induction therapy's efficacy is contingent upon precise re-evaluation methods to accurately gauge treatment response and assess resectability post-therapy. This review discusses the various modalities employed in re-evaluation, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), and the significance of tumor markers, underlining their strengths and limitations. The adoption of modified RECIST criteria for TETs by the International Thymic Malignancy Interest Group (ITMIG) underscores the necessity for standardized assessment guidelines to ensure consistency and reliability across studies and clinical practices. Furthermore, we explore the implications of induction therapy on surgical decision-making, emphasizing the criteria for determining the suitability of patients for surgical intervention post-therapy. The review addresses the challenges and future perspectives associated with the re-evaluation process, including the potential for advanced imaging techniques and the integration of molecular and genetic markers to enhance the precision of treatment response assessment. In conclusion, the re-evaluation of TETs post-induction therapy is a complex but critical component of the multidisciplinary management approach for these patients. Standardizing re-evaluation methodologies and incorporating novel diagnostic tools could significantly improve the prognostication and treatment stratification, ultimately enhancing the therapeutic outcomes for patients with advanced TETs.

Low to intermediate grade lung neuroendocrine tumours. A single centre real world experience

IntroductionLung neuroendocrine tumours (LNETs) are a rare heterogenous group of tumours whose incidence has been increasing. We investigated the diagnosis, treatment, and survival patterns of patients with low to intermediate grade LNETs. MethodsA retrospective chart review of patients with low to intermediate grade LNETs, treated at a Canadian tertiary-level cancer centre was performed. ResultsWe identified 59 patients. Most were G1or G2 and well or moderately differentiated. Forty-seven patients presented with local or locally advanced disease, of which 57.4 % received curative intent surgery. The rest were treated with definitive radiation, radical chemoradiation with platinum and etoposide, palliative chemotherapy with doxorubicin, or supportive care. The five-year overall survival (OS) for those treated surgically was 83 % versus 44 % in the non-surgical group. Metastatic disease was seen in 24/59 patients, with a five-year OS in patients with stage IV disease of 39 %. Of those with advanced or unresectable disease (n = 32), 21 received palliative systemic treatment with up to three lines of therapy. First-line treatment was most commonly chemotherapy with platinum/etoposide combination or somatostatin analogue therapy. Second-line treatment involved chemotherapy or targeted everolimus. PRRT was used once as a first-line and once as second-line therapy. Third-line included lanreotide or chemotherapy with capecitabine/temozolomide combination. ConclusionOverall, patients with surgically resectable disease had a good five-year OS. However, inoperable or more advanced disease was associated with a poorer OS. Despite many treatment options, the sequence of treatments is poorly established. This highlights the need for further development and dissemination of evidence-based guidelines for LNET patients.

Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial.

Advanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors. We therefore aimed to design a study to evaluate the safety and activity of a novel combination of decitabine, venetoclax, and the third-generation BCR::ABL1 tyrosine kinase inhibitor ponatinib in advanced phase Philadelphia chromosome-positive myeloid diseases. For this phase 2 study, patients aged 18 years or older with previously untreated or relapsed or refractory myeloid chronic myeloid leukaemia-blast phase, chronic myeloid leukaemia-accelerated phase, or advanced phase Philadelphia chromosome-positive acute myeloid leukaemia, and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients were eligible regardless of the number of previous lines of therapy received or previous receipt of ponatinib. Cycle 1 (induction) consisted of a 7-day lead-in of ponatinib 45 mg orally daily (days 1-7), followed by combination therapy with decitabine 20 mg/m2 intravenously on days 8-12, venetoclax orally daily with ramp-up to a maximum dose of 400 mg on days 8-28, and ponatinib 45 mg orally daily on days 8-28. Cycles 2-24 consisted of decitabine 20 mg/m2 intravenously on days 1-5, venetoclax orally 400 mg on days 1-21, and ponatinib orally daily on days 1-28. Response-based dosing of ponatinib was implemented in consolidation cycles, with reduction to 30 mg daily in patients who reached complete remission or complete remission with an incomplete haematological recovery and a reduction to 15 mg daily in patients with undetectable BCR::ABL1 transcripts. The primary endpoint was the composite rate of complete remission or complete remission with incomplete haematological recovery in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT04188405) and is still ongoing. Between July 12, 2020, and July 8, 2023, 20 patients were treated (14 with chronic myeloid leukaemia-blast phase, four with chronic myeloid leukaemia-accelerated phase, and two with advanced phase Philadelphia chromosome-positive acute myeloid leukaemia). The median age was 43 years (IQR 32-58); 13 (65%) patients were male and seven (35%) were female; and 12 (60%) were White, three (15%) were Hispanic, four (20%) were Black, and one (5%) was Asian. 12 (60%) patients had received 2 or more previous BCR::ABL1 tyrosine kinase inhibitors, and 14 (70%) patients had at least one high-risk additional chromosomal abnormality or complex karyotype. The median duration of follow-up was 21·2 months (IQR 14·1-24·2). The complete remission or complete remission with an incomplete haematological recovery rate was 50% (10 of 20 patients); complete remission in one [5%] patient and complete remission with incomplete haematological recovery in nine [45%]). An additional six (30%) patients had a morphologic leukaemia-free state. The most common grade 3-4 non-haematological adverse events were febrile neutropenia in eight (40%) patients, infection in six (30%), and alanine or aspartate transaminase elevation in five (25%). Eight (40%) patients had at least one cardiovascular event of any grade. There were three on-study deaths, none of which was considered related to the study treatment and all from infections in the setting of refractory leukaemia. The combination of decitabine, venetoclax, and ponatinib is safe and shows promising activity in patients with advanced phase chronic myeloid leukaemia, including those with multiple previous therapies or high-risk disease features. Further studies evaluating chemotherapy and venetoclax-based combination strategies using newer-generation BCR::ABL1 tyrosine kinase inhibitors are warranted. Takeda Oncology, the National Institutes of Health, and the National Cancer Institute Cancer Center.

Development and validation of a nomogram to predict overall survival of gastroenteropancreatic neuroendocrine carcinoma: a SEER database analysis.

Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a rare group of diseases with poor prognosis and the assessment of its prognosis is a significant challenge. This study aimed to develop and validate a prognostic nomogram to assess overall survival (OS) in patients with GEP-NEC. Patients diagnosed with poorly differentiated GEP-NEC were collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2015 and were randomly assigned to the training or validation cohort in a 7:3 ratio. The data included details of clinicopathological characteristics, therapeutic interventions and survival outcomes. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Nomogram was used to predict OS at 1 and 2 years. The nomogram was internally validated with validation cohort, and its predictive ability was evaluated using concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and integrated discrimination improvement (IDI) index. A total of 887 patients were divided into the training group (n=623) and the validation group (n=264). A total of 476 patients (53.66%) were in stage IV. Based on multivariate analysis, a nomogram was constructed with age, gender, N stage, tumor size, primary tumor resection, radiotherapy and chemotherapy (P<0.05). The C-index was 0.701 [95% confidential interval (CI): 0.677-0.725] and 0.731 (95% CI: 0.698-0.764) for the training and validation groups, respectively. The C-index, ROC, IDI and DCA results indicated that this nomogram model has a good predictive value. In this study, a nomogram model based on seven independent prognostic factors provided visualization of the risk and could help clinicians predict the 1-year and 2-year OS for GEP-NEC. This tool can provide personalized survival predictions and improve clinical decision making for the management of GEP-NEC.

Congenital Lung Anomalies in Adults.

Congenital lung anomaly (CLA) refers to a rare group of malformations that are typically identified prenatally or in early childhood. However, a significant proportion of cases evade detection until adulthood and either are incidentally discovered or manifest with symptoms of recurrent respiratory infection or pulmonary hemorrhage. While most CLAs have characteristic imaging findings at CT and MRI, they remain a diagnostic challenge due to the infrequency with which they are encountered in adults. Radiologists frequently play a pivotal role in suggesting the diagnosis and guiding appropriate management strategies, and recognition of characteristic imaging patterns is crucial for accurate diagnosis. The authors examine the imaging appearances and clinical manifestations in adult patients with CLA, with a focus on patients who have bronchopulmonary involvement and those with combined bronchopulmonary and vascular anomalies. Entities discussed include bronchogenic cyst, bronchial atresia, congenital lobar overinflation, congenital pulmonary airway malformation, proximal interruption of the pulmonary artery, bronchopulmonary sequestration, hypogenetic lung syndrome, placental transmogrification of the lung, and hybrid lesions. Common complications that may arise in these patients are discussed and illustrated. ©RSNA, 2024 Supplemental material is available for this article.

Network Practice of Rare Disease Bloggers and Life Narrative: Take ALS as an Example

As a healing method, narrative is widely concerned by the medical community. The characteristics of "Hyper-temporal", "sharing" and "personalized" of new media provide convenient conditions for the self-performance of rare disease groups and also encourage them to re-choose narrative content and strategies. This paper adopts in-depth interview and text analysis to analyze the network practice and narrative behavior of Amyotrophic lateral sclerosis (ALS) web celebrities. The study found that the online narrative of ALS is not only the life practice of bloggers' self-healing, self-persuasion and self-empowerment, but also their positive response to real family and social responsibilities. At the same time, the online celebrity career of rare disease bloggers reflects their life courses in a certain sense. The social media accounts of rare disease bloggers are an important carrier for them to enrich themselves and place their feelings and expectations, and the continuation of their digital life has brought new philosophical and ethical thinking.

Giant pelvic solitary fibrous tumor. Presentation of a rare case

Solitary fibrous tumors (STFs) consist a very rare and unique group of neoplasms throughout the entire human system. Basic histopathologic origin represents the mesenchymal tissue with slight exceptions. Major incidence obtains the pleura with anatomic occupations especially in the limps, necks and gastrointestinal tracts. Surgical dissection represents the gold standard of therapeutic strategy. According to recent bibliography, only a few cases have been described arising from anatomic areas from mesentery and colon. Aim of our study consists the presentation of such rare tumor group accompanied with assiduous diagnosis and therapeutic mapping.

Androgenetic/biparental mosaic/chimeric gestation: A case report

Introduction: Androgenetic/biparental mosaic/chimeric (ABMC) conceptions are a rare group of gestational trophoblastic disease (GTD) that arise as a result of mosaicism or chimerism and are characterized by hydropically enlarged and variably sized villi. Currently, there are very few reports describing ABMC conceptions; there are 13 total in the literature, and even more rare are those with a molar component. Case Report: A 27-year-old female patient at 6+4wga presented to the clinic with a complaint of new vaginal bleeding and was diagnosed with a pregnancy of unknown location. The patient re-presented to the clinic at 8+4wga by last menstrual period (LMP) for a follow-up ultrasound. A serum human chorionic gonadotropin (hCG) was ordered and returned at 424,008 mIU/mL. A transvaginal ultrasound demonstrated a heterogeneous “snowstorm” appearance throughout uterine cavity, with a concern for complete mole in the setting of a significantly elevated beta hCG. The patient underwent a suction dilation and curettage with ultrasound guidance. Pathology returned the following report: The specimen was sent to pathology and DNA ploidy returned as diploid; however, p57 demonstrated a discordant staining pattern characterized by expression in villous cytotrophoblast but the absence in villous stromal cells was characteristic of androgenetic/biparental mosaic/chimeric gestation. No fetal parts were identified in gross examination of the specimen. Conclusion: Androgenetic/biparental mosaic/chimeric (ABMC) conceptions are important to accurately diagnose because the molar form carries an increased risk for persistent gestational trophoblastic diseases. There are few case reports published regarding ABMC cases. We present this case to provide additional data to the field and emphasize the utility for p57 immunohistochemistry and genetic testing to be performed.

Responses of coastal phytoplankton communities to seasonal herbicide inputs: Tolerance or degeneration?

Herbicide-induced phytoplankton inhibition threatens coastal biodiversity and ecosystem function. Although studies employing single-frequence exposure aid in understanding the phytoplankton community's responses to herbicides, it’s difficult to objectively assess their response to cyclic herbicide inputs (long-term low-dose and short-term high-dose) in marine ecosystems. Here, we analyzed the concentration and distribution of herbicides in global coastal waters and simulated this cyclic process through a two-phase atrazine exposure mesocosm experiment and laboratory tests. The results indicated that, the herbicide concentrations (0.82 nmol L−1, 95 % CI 0.55, 1.74) from May to August were significantly higher than that (0.14 nmol L−1, 95 % CI 0.02, 0.38) in the remainder months, and highest concentrations typically emerged in summer; the changes in phytoplankton community composition under environmental concentrations of triazine herbicides could recover in the short term, but sustained inhibition of biomass was produced; the dominant populations were more likely to develop tolerance through preexposure and recover from subsequent impulse of atrazine, but this process was accompanied by the loss of rare groups and a decrease in biodiversity, meanwhile, affected the bacterial community in phycosphere. Consequently, we considered that the cyclic herbicide inputs may cause more detrimental effects than single-frequence exposure, potentially leading to a large-scale decline in coastal primary productivity.

Comparative analysis of optimization algorithm-based training algorithms for a few shot continual learning

Incremental learning relies on the availability of ample training data for novel classes, a requirement that is often unfeasible in various application scenarios, particularly when new classes are rare groups that are pricey or challenging to attain. The main focus of incremental learning is on the tricky task of continuously learning to classify new classes in incoming data with no erasing knowledge of old classes. The research intends to develop a comparative analysis of optimization algorithms in training few-shot continual learning models to conquer catastrophic forgetting. The presented mechanism integrates various steps: pre-processing and classification. Images are initially pre-processed through contrast enhancement to elevate their quality. Pre-processed outputs are then classified by employing Continually Evolved Classifiers, generated to address a matter of catastrophic forgetting. Furthermore, to further enhance performance, Serial Exponential Sand Cat Swarm optimization algorithm (SE-SCSO) is employed and compared against ten other algorithms, containing Grey Wolf Optimization (GWO) algorithm, Moth flame optimization (MFO), cuckoo Search Optimization Algorithm (CSOA), Elephant Search Algorithm (ESA), Whale Optimization Algorithm (WOA), Artificial Algae Algorithm (AAA), Cat Swarm Optimization (CSO), Fish Swarm Algorithm (FSA), Genetic Bee Colony (GBC) Algorithm, and Particle swarm optimization (PSO). From the experiment results, SE-SCSO had attained the maximum performance with an accuracy of 89.6%, specificity of 86%, precision of 83%, recall of 92.3% and f-measure of 87.4%.

A multiplexed targeted method for profiling of serum gangliosides and glycosphingolipids: application to GM2-gangliosidosis

The analysis of gangliosides and glycosphingolipids is crucial for understanding cellular membrane structure and function as well as to accurately diagnose certain inborn errors of metabolism. GM2-gangliosidosis represents a rare and fatal group of lysosomal storage disorders characterized by accumulation of GM2 gangliosides in various tissues and organs. These disorders arise due to deficiency or functional impairment of the β-hexosaminidase A or B enzymes, which are responsible for degradation of GM2 ganglioside. Deficient enzyme activity primarily leads to the accumulation of GM2 gangliosides within the lysosomes of cells. Accurate and rapid diagnostic methods that detect increased levels of GM2 gangliosides in patients with GM2-gangliosidosis can play a significant role in early diagnosis and appropriate treatment of this condition. To address this need, we developed a multiplexed liquid chromatography-tandem mass spectrometry method targeting 84 species of gangliosides and other glycosphingolipids involved in ganglioside metabolism. Reproducibility, linearity, extraction efficiency, and sample stability were evaluated and proof-of-concept data obtained from analysis of serum samples from confirmed cases of GM2-gangliosidosis. This method has the potential to simultaneously monitor the biosynthesis of gangliosides and the lysosomal catabolic pathway serving as a valuable tool for screening and diagnosing an important group of lysosomal storage disorders.

Incidence of Primary Progressive Apraxia of Speech and Primary Progressive Aphasia in Olmsted County, MN, 2011-2022.

No epidemiologic studies have formally assessed the incidence of primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS). Thus, we decided to assess the incidence of these disorders in Olmsted County, MN, between 2011 and 2022, and to characterize clinical, radiographic, and pathologic characteristics of these patients. This was a retrospective examination of data from a population-based cohort of patients with PPA and PPAOS prospectively identified in Olmsted County, MN, from 2011 to 2022. The incidence of PPA among adults (older than 18 years) was calculated for Olmsted County as the number of patients per 100,000 person-years during the study period. The adult population of Olmsted County was determined by the annual catchment population reported by the Rochester Epidemiological Project for each year 2011-2022. A behavioral neurologist verified the clinical diagnoses and determined subtypes. We identified 10 patients (60% female) within the study period (median age of symptoms onset: 70 years; range: 66-73), 8 with PPA and 2 with PPAOS. Of the 8 patients with PPA (6 female patients, 2 male patients), 2 met criteria for non-fluent variant PPA (nfvPPA), 3 for logopenic variant PPA (lvPPA), and 3 for semantic variant (svPPA). Speech evaluation confirmed the clinical diagnoses in all patients and all showed typical imaging findings consistent with their respective subtype. Six patients (2 PPAOS, 2 nfvPPA, 2 lvPPA) died and 3 underwent autopsy (2 PPAOS, 1 nfvPPA), confirming the pathologic diagnosis of progressive supranuclear palsy. The incidence of PPA + PPAOS was 0.70 persons per 100,000 person-years (95% CI 0.34-1.29 persons per 100,000) during the study period. The incidence of PPAOS was 0.14 persons per 100,000 person-years (95% CI 0.02-0.55 persons per 100,000), whereas for the 8 patients with PPA, the incidence was 0.56 persons per 100,000 person-years (95% CI 0.24-1.10 cases per 100,000). The incidence of nfvPPA was 0.14 persons per 100,000 person-years (95% CI 0.02-0.55), 0.21 persons per 100,000 person-years (95% CI 0.04-0.61) for lvPPA, and 0.21 persons per 100,000 person-years (95% CI 0.04-0.61) for svPPA. As a group, PPA and PPAOS are a relatively rare group of diseases. PPAOS has a slightly lower incidence than PPA as a group but similar incidence to the individual PPA variants.

CureSCi Metadata Catalog-finding and harmonizing studies for secondary analysis of hydroxyurea use for sickle cell disease.

Sickle cell disease (SCD) is a rare group of inherited red blood cell disorders that affect hemoglobin, resulting in serious multi-system complications. The limited number of patients available to participate in research studies can inhibit investigating sophisticated relationships. Secondary analysis is a research method that involves using existing data to answer new research questions. Data harmonization enables secondary analysis by combining data across studies, especially helpful for rare disease research where individual studies may be small. The National Heart, Lung, and Blood Institute Cure Sickle Cell Initiative (CureSCi) Metadata Catalog is a web-based tool to identify SCD study datasets for conducting data harmonization and secondary analysis. We present a proof-of-concept secondary analysis to explore factors associated with discontinuation of hydroxyurea, a safe and effective first line SCD therapy, to illustrate the utility of the CureSCi Metadata Catalog to expedite and enable more robust SCD research. We performed secondary analysis of SCD studies using a multi-step workflow: develop research questions, identify study datasets, identify variables of interest, harmonize variables, and establish an analysis method. A harmonized dataset consisting of eight predictor variables across five studies was created. Secondary analysis involved a generalized linear model was employed to identify factors that significantly impact hydroxyurea discontinuation. The CureSCi Metadata Catalog provided a platform to efficiently find relevant studies and design a harmonization strategy to prepare data for secondary analysis. Multivariate analysis of the harmonized identified that patients who are older, are female, had a history of blood transfusion therapy, had episodes of acute chest syndrome, and had the SC sickle cell genotype are more likely to stop hydroxyurea treatment. This secondary analysis provides a template for how the CureSCi Metadata Catalog expedites dataset discovery of sickle cell studies for identifying relationships between variables or validating existing findings.

Anti-photoaging activity of triterpenoids isolated from Centella asiatica

Centella asiatica (L.) Urban is a medical plant rich in triterpenoids, frequently used in Asia to treat skin conditions such as acne. To search for anti-photoaging agents, 16 known triterpenoids and five undescribed triterpenoids, including three ursane, one oleanane and one nor-ursane were isolated from the whole herb of C. asiatica. The structures and relative stereochemistry of these compounds were elucidated by detailed NMR spectra and HRESIMS. Compounds 1 and 2 were isomers of ursane-type and oleane-type triterpenes with rare aldehyde groups on C-23. Compound 4 was a unique example of a nor-ursane type triterpenoid. The Ultraviolet B (UVB) induced HaCaT cell damage model was used to measure the in vitro anti-photoaging activity of all 21 compounds. Twenty compounds significantly increased HaCaT viability and inhibited lactate dehydrogenase (LDH) release after UVB exposure. These findings highlight the protective effects of C. asiatica-derived triterpenoids against UVB damage and indicate their potential as natural agents that can protect the skin against photoaging.

Endoscopic Extended Transsphenoidal Surgery for Transbasal Tuberculum Sellae Meningioma: 2-Dimensional Operative Video.

Transbasal meningiomas1 are a rare group of tumors that grow intracranially, invade the skull base, and propagate extracranially; they are usually located at the level of the olfactory cribra and sphenoid wing.1-4 Transbasal tuberculum sellae meningiomas are a subset of these tumors, which extend into the suprasellar and sphenoid regions. The traditional transcranial approach for some transbasal meningiomas has recently evolved toward the transnasal endoscopic approach, which allows the removal of both the intranasal and intracranial components, reducing the manipulation of the optic nerves and neurovascular structures. Nevertheless, specific anatomical criteria must be present; the knowledge of specific anatomy5,6 and the surgeon's experience are fundamental for reaching the most favorable outcome.7-11 In this video, we present the case of a 50-year-old woman with a history of progressive visual impairment and scotoma in the left inferotemporal quadrant. Radiological examinations suggested a transbasal tuberculum meningioma that extended into the suprasellar region, sphenoid sinus, and optic canals. An endoscopic transtuberculum approach with intraoperative visual-evoked potentials12 was performed, allowing an early devascularization with the preservation of the superior hypophyseal arteries and the removal of the component extending in the medial portion of both optic canals. The postoperative MRI documented a gross total resection without complications. The patient reported an immediate improvement of the visual symptoms. Histopathology documented a meningioma (CNS World Health Organization grade 1) with bone invasion. The patient consented to the procedure and to the publication of her image; Institutional Review Board approval was not required for this single case report.

Combination of pericardial celomic cyst and thymus cyst

The combination of the pericardial celomic cyst and the thymus cyst represent a rare group of diseases. Clinical diagnosis of the pericardial and thymus gland formations is complex, as the patient’s symptoms may be non-specific, associated with concomitant pathology. Although a diagnostic examination often begins with chest X-rays, it may not be informative and requires CT and MRI of the thorax to visualize the entire pericardium and thymus. Brief information on the etiology and pathogenesis of these diseases is given; clinical statistics on the frequency of occurrence of thymus cysts and pericardial cysts in different age groups are used as an example. The results of observation and analysis of literary sources have established that thoracoscopic removal of the thymus cyst and tumors is a priority in terms of effective diagnosis and is justified as minimally invasive and efficient surgical treatment in this combination of pathologies.