Rare Group Research Articles

Planktonic eukaryotes in the Chesapeake Bay: contrasting responses of abundant and rare taxa to estuarine gradients.

Deep sequencing analysis of planktonic eukaryotes in the Chesapeake Bay reveals high community diversity with many newly recognized phytoplankton taxa. The Chesapeake Bay planktonic eukaryotes show distinct seasonal and spatial variability, with recurring annual patterns of total, abundant, and rare groups. Rare taxa mainly contribute to eukaryotic diversity compared to abundant groups, and they are more sensitive to spatiotemporal variations and environmental filtering. Temporal variations, nutrient availability, and spatial gradients significantly affect the distribution of eukaryotic microbial communities. Similar spatiotemporal patterns in prokaryotes and eukaryotes suggest common mechanisms of adjustment, substitution, and species interactions in planktonic microbiomes under strong estuarine gradients. Interannually recurring patterns demonstrate that diverse eukaryotic taxa have well adapted to the estuarine environment with a long residence time. Further investigations of how human activities impact estuarine planktonic eukaryotes are critical in understanding their essential ecosystem roles and in maintaining environmental safety and public health.

A Retrospective Review and Comprehensive Tumour Profiling of Advanced Non-Melanomatous Cutaneous Spindle Cell Neoplasms Treated with Immune-Checkpoint Inhibitors.

Non-melanomatous cutaneous spindle cell neoplasms are a rare group of malignancies that present a diagnostic challenge, and for which there is a lack of consensus on how to best manage patients with advanced disease and only limited reports of immune-checkpoint inhibitor (ICI) responses. In this study, we performed a single-center retrospective review of treatment outcomes for all advanced non-melanomatous cutaneous spindle cell neoplasms treated with ICIs. Blinded histopathology reviews occurred to confirm each diagnosis. Comprehensive tumour profiling included whole exome sequencing for tumour mutational burden (TMB) and ultraviolet(UV) signatures, and immunohistochemistry for immune-cell infiltration (CD4/CD3/CD8/CD103/CD20) and immune-checkpoint expression (PD-L1/LAG3/TIGIT). Seven patients were identified. The objective response rate was 86% (6/7) with five complete responses (CR). Responses were durable with two patients in CR > 30 months after ICI commencement. All patients had high TMB and UV signatures. One patient had PD-L1 100% (combined positive score) with abundant immune-cell infiltration and LAG3 expression. In advanced non-melanomatous cutaneous spindle cell neoplasms, excellent responses to ICIs with durable disease control were observed. ICIs are worthy of further exploration in these patients. UV signatures and high TMB could be used to help select patients for treatment.

Components of the microenvironment of soft tissue sarcomas. Part I

Soft tissue sarcomas (STS) are a rare heterogeneous group of malignant neoplasms characterized by aggressive course and poor response to treatment. This determines the relevance of research aimed at studying the pathogenesis of STS. The tumor microenvironment consists of stromal, immune cells, blood, lymphatic vessels, and extracellular matrix. By now, it is known that STS is characterized by complex relationships between tumor cells and components of the microenvironment. Dynamic interactions between tumor cells and components of the microenvironment enhance adaptation to changing environmental conditions, which provides high aggressive potential of STS and resistance to antitumor therapy. Basic research aimed at investigating the role of microenvironmental components in STS carcinogenesis may serve as a key to the discovery of both new prognostic predictor biomarkers and targets for new antitumor drugs. This review article is devoted to the role and interaction of STS cells with components of the microenvironment.

Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

PurposeLeukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients.MethodsDetails of 34 patients’ personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing.ResultsOmphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture’s results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life.ConclusionThis study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region.

Two patients with Knobloch syndrome due to mutation in COL8A1 gene: case report and review of the literature

BackgroundKnobloch syndrome (KNO, OMIM # 267,750) is a rare ciliopathy group sydrome characterized by a collagen synthesis disorder. It represents an uncommon cause of pediatric retinal detachment. This report presents two cases with different COL18A1 gene mutations, complicated by retinal detachment.Case presentationBoth cases exhibited high myopia and various degrees of occipital skull defect. The first case, a female, had bilateral congenital retinal detachment, posterior embryotoxon, and strabismus. The second case, a male, had unilateral congenital retinal detachment and neuromotor developmental delay. The first case, diagnosed in the early months of life, underwent successful retinal reattachment surgery. However, surgery was not performed on the second case, who presented with late-stage unilateral retinal detachment and pre-phthisis.ConclusionsThe report describes two patients with Knobloch syndrome, one of whom responded favorably to surgery for retinal detachment in both eyes. Successful anatomical results were achieved with early surgical interventions. It is essential to recognize the phenotypic and genetic heterogeneity within KNO.

Predictive and Prognostic Biomarkers in Patients With Mycosis Fungoides and Sézary Syndrome (BIO-MUSE): Protocol for a Translational Study.

Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of the disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of nonmalignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. S. aureus has also been reported to contribute to the progression of the disease. Previous reports indicate a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers. This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS. The Predictive and Prognostic Biomarkers in Patients With MF and SS (BIO-MUSE) study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. The treatments will be given according to clinical routine. The sampling of each patient will be performed every 3 months for 3 years. The blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine, and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. The life quality parameters will be evaluated. The results will be evaluated by the stage of the disease. Patient inclusion started in 2021 and is still ongoing in 2023, with 18 patients and 20 healthy controls enrolled. The publication of selected translational findings before the publication of the main results of the trial is accepted. This study aims to investigate blood and skin with a focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS. ClinicalTrials.gov NCT04904146; https://www.clinicaltrials.gov/study/NCT04904146. DERR1-10.2196/55723.

Chaetoxylariones A–G: undescribed chromone-derived polyketides from co-culture of Chaetomium virescens and Xylaria grammica enabled via the molecular networking strategy

By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A–G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8–12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7′ and C-10′; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 μM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.

Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies

IntroductionIdiopathic inflammatory myopathies (IIM) represent a rare and heterogenous group diseases, and their treatment is not fully defined yet. According to previous small case series, the combination of mycophenolate mofetil (MMF) and rituximab (RTX) may be effective in controlling difficult-to-treat patients. Our aim was to further explore the efficacy and safety of this combined approach in patients with IIM.MethodsPatients with IIM treated with the RTX/MMF combination in our Center were retrospectively identified. After the start of combination therapy, the efficacy was evaluated at 12 months (T12) according the 2016 ACR/EULAR response criteria for IIM. Cardiac imaging and pulmonary function tests were used to monitor disease activity in patients with myocarditis and interstitial lung disease, respectively. Adverse events were recorded over the follow-up period.ResultsAmong the 20 patients (median age 61 years; 70% female) included in the study, anti-synthetase syndrome was the most prevalent IIM subgroup (60%). At treatment start, muscle, heart, and lung were the most commonly actively affected organs. After 12 months, a moderate or major response was observed in all patients, and creatine kinase was significantly decreased (p-value = 0.012). Cardiac imaging and enzymes monitoring showed a reduction of heart inflammation, while pulmonary function tests improved in patients with lung involvement. No severe side effects were observed.ConclusionOur data show that combination of RTX and MMF is effective and safe in patients with severe and refractory IIM. Therefore, this combined treatment might represent a feasible approach for difficult-to-treat IIM cases.

Malignant Transformation in a Genitocrural Porokeratosis : A Case Report

Porokeratosis is a rare heterogenous group of keratinization disorder with an unclear pathogenesis, and has varied clinical presentations. It may present with annular papules or plaques with central atrophy and clinically and histologically distinct ridge-like border called 'cornoid lamella'. Common variants include porokeratosis of Mibelli (PM), disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, punctate porokeratosis and porokeratosis palmaris et plantaris disseminata (PPPD). Here we report the case of a 79 year old female, who developed malignancy of porokeratosis over the groin region which had been mismanaged as eczema for many months and has been eventually diagnosed as Squamous cell carcinoma.

Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis.

Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 μmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

Aggressive Angiomyxoma of the Lower Female Genital Tract: A Review of the MITO Rare Tumors Group.

Aggressive angiomyxoma (AAM) is a rare, locally aggressive, myxoid mesenchymal neoplasm primarily found in the pelvic and perineal regions of young adult females. It is a slow growing and locally infiltrating tumor. Preoperative diagnosis is difficult due to the rarity of these tumors and absence of characteristic signs and symptoms. The primary management is tumor excision. Incomplete excision is common because of the infiltrating nature of the neoplasm and absence of a definite capsule. Other non- surgical modalities have been employed, such as radiotherapy, embolization, GnRH analogues or other anti-estrogenic agents. Local relapses occur in 30-40% of the cases, and often appear many years (sometimes decades) after the first excision. Occasional distant metastasis has also been reported. A limited number of cases have been reported in the literature, mostly in the form of small case series or isolated case reports. Therefore, the aim of this paper by a team of experts from the MITO rare tumors group is to review clinical findings, pathologic characteristics and outcome of patients affected by this rare condition in order to be able to offer up-to-date guidance on the management of these cases.

Unraveling the Enigma: A Five-Year Comprehensive Analysis of Hurthle Cell Tumors in South India's Tertiary Care Center.

Hurthle cell tumors of the thyroid gland constitute a rare and enigmatic group of neoplasms, characterized by the presence of Hurthle cells exhibiting abundant eosinophilic cytoplasm and numerous mitochondria. Despite their low incidence, they pose diagnostic challenges and display diverse clinical outcomes. This study aims to provide a comprehensive analysis of the clinicopathological profile of Hurthle cell tumors within a tertiary care center in South India. Through a retrospective approach, we analyzed cases of Hurthle cell tumors diagnosed and treated at a tertiary care center over a five-year period. Clinical, radiological, and histopathological data were meticulously collected and scrutinized. The study focused on examining demographic details, presenting symptoms, imaging features, cytological findings, surgical management, and postoperative outcomes of the patients. A total of 32 cases of Hurthle cell tumors were identified during the study period. The majority of patients were female (84%), with a mean age of 49.6 years for Hurthle cell carcinoma. Thyroid enlargement and neck mass were the most common presenting complaints. Fine-needle aspiration cytology showed characteristic features suggestive of Hurthle cell tumors in 33% of cases. Total thyroidectomy remains the mainstay surgical approach. Histopathological evaluation confirmed 62.5% of cases as benign adenomas and 37.5% as malignant carcinomas. Among malignant cases, 67% showed capsular invasion and 33% demonstrated vascular invasion. Of the patients,33.3% received adjuvant radiotherapy. The overall survival rate was 100%. In our study, we found that thyroid nodules larger than 3 cm demonstrated a higher propensity for Hurthle cell carcinoma. Our findings support the multidisciplinary approach in managing Hurthle cell tumors, with a focus on tailored treatment plans for each patient based on individual characteristics. By recognizing the female predominance, assessing nodule size, and employing a combination of thyroidectomy and ablative therapy, clinicians can optimize patient care and contribute to better long-term prognosis and quality of life for those affected by Hurthle cell tumors. Continued research and collaborative efforts are necessary to advance our understanding and refine treatment strategies, paving the way for improved outcomes and enhanced patient management in the future.

Abstract 5094: Immunotherapy in advanced cutaneous non-melanomatous spindle cell neoplasms

Abstract Background: Non-melanomatous cutaneous spindle cell neoplasms (NMCSpC) are a rare group of malignancies including pleomorphic dermal sarcoma (PDS) and spindle-cell cutaneous squamous cell carcinoma (SpSCC). They present a diagnostic challenge with overlapping morphological features and variable patterns of immunohistochemical (IHC) staining. There is a lack of consensus on how to best manage advanced NMCSpC and limited reports of immunotherapy (IO) responses. This study reviews the efficacy of IO in NMCSpC and performs comprehensive tumor profiling to identify biological rationale for IO use in this rare group of tumors. Methods: We performed a single-center retrospective review of all locally-advanced or metastatic NMCSpCs treated with IO. Blinded histopathology reviews occurred to confirm each diagnosis. Overall response rates (ORR) were collected as per Response Evaluation Criteria in Solid Tumors 1.1 or Positron Emission Tomography Response Criteria 1.0. Comprehensive tumor profiling included whole exome sequencing for tumor mutational burden (TMB) and ultraviolet(UV)-signatures, and IHC for immune-cell infiltration (CD103/CD4/CD3/CD8/CD20) and immune-checkpoint expression (PD-L1/TIGIT/LAG3). Results: 7 patients were identified. Median follow up was 18.1 months (range: 5.3-34.7). ORR 86% (6/7) with five complete responses (CR). One patient who achieved stable disease progressed. Responses were durable with two patients in CR &amp;gt;30 months after IO commencement. Blinded pathological review identified 3 SpSCC, 2 PDS and 2 spindle cell tumors of unclear sub-classification. All patients had high TMB and UV-signatures. One patient had PD-L1 100% (combined positive score) with abundant immune-cell infiltration and LAG3 expression (Table 1). Conclusion: In advanced NMCSpC, excellent responses to IO with durable disease control was observed. IO is worthy of further exploration in these patients. UV-signatures and high TMB could be used to help select patients for treatment. Immunohistochemistry (IHC)^, tumor mutational burden and ultraviolet signatures Patient T-cell markers B-cell marker Immune-checkpoints Tumor mutational burden (mutations/megabase) Ultraviolet-mutational signature Best response assessment# CD103 CD4 CD3 CD8 CD20 PD-L1 TIGIT LAG3 1 1 20 1 1 0 7 0 0 17.94 Yes Stable metabolic response 2 1 20 30 10 0 100 0 10 35.34 Yes Complete metabolic response 3 1 10 10 5 0 5 0 0 104.87 Yes Complete metabolic response 4 1 0 1 0 0 0 0 0 74.04 Yes Partial metabolic response 5* NA NA NA NA NA NA NA NA 29 Yes Complete metabolic response 6 1 0 0 5 0 0 0 4 12.02 Yes Complete metabolic response 7 1 0 5 1 0 0 0 0 41.17 Yes Complete response ^IHC scores are % of positively stained cells, except for PD-L1 which is combined positive score (CPS). *Insufficient tissue for IHC on Patient 5. #As per PERCIST 1.0 on FDG-PET/CT or RECIST1.1 on CT. Citation Format: Luke S. McLean, Annette M. Lim, Christopher Angel, Richard J. Young, Angela Pizzolla, Stuart Archer, Alesha A. Thai, Benjamin Solomon, Jeremy Lewin, Danny Rischin. Immunotherapy in advanced cutaneous non-melanomatous spindle cell neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5094.

Soil microbial responses to multipollutant exposures in megacity's parks of Beijing

Soil life revolves around microorganisms that are crucial for soil ecosystems and health. In megacities, the combined exposure of multiple pollutants exerts a significant impact on the structures and functions of soil microorganisms; however, there is a lack of empirical studies on this topic. Hence, we conducted a study including urban parks in Beijing, China. The results indicate that bacteria were abundant in the soils of Beijing parks, showing the same dominant groups but different rare groups. The dominant groups included Actinobacteria and Proteobacteria. Candidate phyla radiation bacteria, a large evolutionary radiation of bacterial lineages whose members remain mostly uncultivated, were the main specialists. Under the combined exposure of multiple pollutants, the structures of soil microbial communities in different parks were similar. Community change due to pollutants (31%) was greater than that due to natural factors (2.4%). Among multipollutants, organophosphate esters, led by dibutyl phosphate, had the highest influence on microbial abundance and distribution. An increase in dibutyl phosphate concentration decreased the abundance of Firmicutes, while the abundance of Synergistota was increased. The interactions among pollutants affecting the bacteria were different. Bis(2-chloroethyl) phosphate, nickel and benzo[g,h,i]perylene influenced microorganisms by working with organophosphate esters. High-molecular-weight polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and benzo[g,h,i]perylene, mainly acted on the functional genes and thus affected multiple biogeochemical cycles. Benzo[a]anthracene, bis(2-chloroethyl) phosphate, and arsenic were the primary pollutants affecting metabolic pathways. Our research helps to better understand the impacts of urban environmental pollution on soil microorganisms.

Genetic causes of infection induced encephalitis

IntroductionPatients with encephalitis following a viral infection are often thought to have a para infectious, inflammatory, or autoimmune cause for their presentation. These diagnoses usually result in treatments with immunosuppressant therapies which can have side effects. However, there is an increasing body of evidence demonstrating that patients can have a direct genetic cause mediating viral infection triggered encephalitis, where inflammation is a secondary response. These patients may benefit not from immunosuppressive therapies, but from protection from infection through dedicated immunisation programs and early antiviral therapies at times of infection. MethodsA small case series of paediatric neurology patients (n = 2) from a single institution with infection induced encephalitis and an underlying genetic cause, is presented. Patients with a confirmed genetic cause of infection induced encephalitis were identified and consented by their treating neurologist for inclusion in this case series. Ethics approval was gained for this case series and review of the surrounding literature. ConclusionA case of both DBR1 and NUP214 genetic changes resulting in infection induced encephalitis is presented. This case series raises awareness of this rare group of disorders and provides clues to their identification. Features to prompt clinician consideration of such genetic conditions are also highlighted. Although rare, identification of these patients is important due to implications on treatment, prognosis, and family planning.

How I treat peripheral T-cell lymphomas

Introduction. Peripheral T-cell lymphomas (PTCL) — a rare group of lymphoproliferative diseases characterized by an aggressive course and an unfavorable prognosis. The group is represented by heterogeneous nosological forms, in which standard treatment options lead to unsatisfactory results. Aim: to present the protocols for the treatment of PTCLMain findings. In total, 12 years of experience in the treatment of 724 patients with T-cell lymphomas (430 patients with primary cutaneous forms, 110 patients with leukemic variants and 184 with peripheral T-cell lymphomas) has been accumulated. The treatment results and therapeutic algorithms were analyzed. In the general group of patients, the 3-year overall survival (OS) and relapse-free survival (EFS) were 76 % and 70 %, respectively. The best treatment results were achieved in the groups of intestinal T-cell lymphoma, specifically (EATL), and angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell ALK-positive lymphoma (ALCL ALK+), and the worst — in the group of ALCL ALK- (5-year EFS 31 %). High-dose chemotherapy under the NHL BFM-90 program in the treatment of ALK+ ALCL allows achieving 10-year OS and EFS 87 % and 84 %, respectively, but the less toxic CHOEP program was not inferior in effectiveness: 5-year OS and EFS amounted to 93 % and 88 %, respectively. High survival rates of patients with EATL were achieved with the use of high-dose chemotherapy according to the LB-M-04 program followed by auto-HSCT in the first line of therapy: 5-year OS and EFS amounted to 79 % and 74 %, respectively. The positive role of AITL maintenance therapy has been shown: 5-year OS and EFS during its implementation amounted to 75 % and 49 % versus 41 % and 20 % in the absence of it. In the protocols for the treatment of extranodal NK/T cell lymphoma, radiation therapy was used in the first line of therapy, 5-year OS and EFS were 60 % and 42 %, respectively. The role of autologous hematopoietic stem cell transplantation (auto-HSCT) in all PTCL was evaluated: 5-year OS and EFS were 82 % and 58 % compared with 67 % and 49 % without auto-HSCT. The transplantation of allogeneic hematopoietic stem cells (allo-HSCT), even in the treatment of relapses of the disease, has shown its effectiveness: 9 out of 11 patients are alive and remain in remission of the disease.

Service evaluation suggests variation in clinical care provision in adults with congenital adrenal hyperplasia in the UK and Ireland.

Congenital adrenal hyperplasia (CAH) encompasses a rare group of autosomal recessive disorders, characterised by enzymatic defects in steroidogenesis. Heterogeneity in management practices has been observed internationally. The International Congenital Adrenal Hyperplasia registry (I-CAH, https://sdmregistries.org/) was established to enable insights into CAH management and outcomes, yet its global adoption by endocrine centres remains unclear. We sought (1) to assess current practices amongst clinicians managing patients with CAH in the United Kingdom and Ireland, with a focus on choice of glucocorticoid, monitoring practices and screening for associated co-morbidities, and (2) to assess use of the I-CAH registry. We designed and distributed an anonymised online survey disseminated to members of the Society for Endocrinology and Irish Endocrine Society to capture management practices in the care of patients with CAH. Marked variability was found in CAH management, with differences between general endocrinology and subspecialist settings, particularly in glucocorticoid use, biochemical monitoring and comorbidity screening, with significant disparities in reproductive health monitoring, notably in testicular adrenal rest tumours (TARTs) screening (p = .002), sperm banking (p = .0004) and partner testing for CAH (p < .0001). Adoption of the I-CAH registry was universally low. Differences in current management of CAH continue to exist. It appears crucial to objectify if different approaches result in different long-term outcomes. New studies such as CaHASE2, incorporating standardised minimum datasets including replacement therapies and monitoring strategies as well as longitudinal data collection, are now needed to define best-practice and standardise care.

Cytotoxic and antimicrobial metabolites from the marine-derived fungus Aspergillus sp. OPR23-FS01

Chemical investigation of a marine-derived fungus Aspergillus sp. OPR23-FS01 resulted in the isolation of a new unsaturated fatty acid featuring a terminal olefin, 10-methoxy-2-methylene-10-oxodecanoic acid (1), two new natural compounds, 2-carboxy-2′-methyl-azobenzene (2) and 1,3,9-trimethyluric acid (3), and 11 previously described metabolites, pantheric acid C (4), pantheric acid D (5), 2-furoic acid (6), 5-(hydroxymethyl)-2-furancarboxylic acid (7), sporogen-AO 1 (8), gliocladic acid (9), hydroheptelidic acid (10), ditryptophenaline (11), emodin (12), uridine (13), and thymidine (14). Their structures were identified by comprehensive analyses of the spectroscopic methods, including NMR and HRESI mass spectra. Compound 2 possesses a rare diazenyl group among the previously reported fungal metabolites. Compound 8 showed significant cytotoxicity against both HepG2 and MCF-7 cell lines in a dose-dependent manner, with IC50 values of 4.66 ± 0.24 and 5.54 ± 0.28 μM, respectively. Compounds 1−5 and 8−11 displayed antimicrobial effect against Enterococcus faecalis ATCC299212, with MIC values ranging from 32 to 128 μM, whereas 1, 4, 5, and 8−11 inhibited Candida albicans ATCC10231 growth, with MIC values in a range of 32–256 μM.

Social Determinants of Outcomes Disparity among Pediatric Patients with Solid Tumor.

Socioeconomic factors have a significant impact on healthcare outcomes. Metrics such as area deprivation index (ADI) are used to quantify the anticipated influence of these factors. Here, we sought to assess the impact of socioeconomic factors on clinical outcomes among pediatric patients with solid tumor in our region. We identified 3,863 pediatric patients who were diagnosed with a malignant solid tumor in the Texas Cancer Registry between 1995 and 2019. ADI was used to quantify socioeconomic determinants of health. These outcome variables were determined: stage of disease at diagnosis, time between diagnosis and treatment initiation, and overall mortality. Statistical analysis was performed using logistic regression, linear regression, Cox proportional hazards regression, and Kaplan-Meier survival curves. A total of 53.5% of patients were male and the average age at diagnosis was 4.5 years. Forty-seven percent of patients were White, 13.3% were Black, 36.2% were Hispanic, 1.7% were Asian, and other rare minority groups made up 1.8%. On multivariable analysis, increased risk of death was associated with Black race, rare minority race, residence in a border county, and increasing ADI score, with the risk of death at 5 years rising 4% with each increasing ADI point. Social determinants of health are associated with disparate outcomes among pediatric patients with solid tumor. Our results suggest that patients who are part of racial minority groups and those who reside in socioeconomically disadvantaged neighborhoods or regions near the Texas-Mexico border are at an increased risk of death. This information may be useful in strategizing outreach and expanding resources to improve outcomes in at-risk communities.

A rapid diagnostic technology for isolating rare blood group patients under medical emergency using a three-fold paper-polymer microfluidic kit

Patients under medical emergency may require urgent blood transfusion as life-saving measures, including the situations demanding for operative intervention. However, while traditional blood grouping is an established practice before such procedures are administered, possibilities of having rare blood groups (like Bombay factor/hh group) remain to be undetected. Unfortunately, such rare blood groups may trigger adverse haemolytic reactions post the intervention, disrupting the success of blood transfusion, organ transplantation, and in vitro fertilization process-flow, among others. Currently, the established option for isolating such patients is to carry out elaborate DNA sequencing, albeit only after they start presenting life-threatening symptoms that may be difficult to arrest, whereas any approach of detecting such patients a-priori remains to be introduced. Here, we report the development of an affordable three-fold test kit that integrates the isolation and purification of the DNA sample from few drops of blood (∼70 microliter), perform its isothermal amplification and arrive at a rapid readout that is agnostic to any colorimetric inference. We demonstrate the efficacy of this methodology in a portable, user-friendly and inexpensive sample-to-answer framework that is amenable for execution at the patient’s site without demanding laboratory-centric procedures, within about 30 min of sample dispensing. The favourable sensitivity and specificity of the technology presents it as a value proposition for routine screening prior to administering blood-group sensitive clinical procedures – a paradigm that has thus far not been reported.