Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin.

Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of neurexins and neuroligins across the synapse. However, whether extracellular linker proteins can expand such a code is unknown. Using a combination of in vitro and in vivo approaches, we found that hevin, an astrocyte-secreted synaptogenic protein, assembles glutamatergic synapses by bridging neurexin-1alpha and neuroligin-1B, two isoforms that do not interact with each other. Bridging of neurexin-1alpha and neuroligin-1B via hevin is critical for the formation and plasticity of thalamocortical connections in the developing visual cortex. These results show that astrocytes promote the formation of synapses by modulating neurexin/neuroligin adhesions through hevin secretion. Our findings also provide an important mechanistic insight into how mutations in these genes may lead to circuit dysfunction in diseases such as autism.

Global consensus process to establish a core dataset for hidradenitis suppurativa registries.

BACKGROUND: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate. OBJECTIVES: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments. METHODS: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus. RESULTS: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally. CONCLUSIONS: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants.

The Global Hidradenitis Suppurativa Atlas Methodology: Combining Global Proportions in a Pooled Analysis.

INTRODUCTION: Data concerning the global burden of hidradenitis suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalences have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. METHODS: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital or a private/family medicine clinic. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Approximately ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). CONCLUSION: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation and synthesized using a random-effects model. The novel standardization of the Global Prevalence Studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies.

Evaluation of Postoperative Complications Following Modified Coronally Advanced Flap as Root Coverage Procedure - A Prospective Clinical Study.

BACKGROUND: Root coverage procedures are very technique sensitive and require patients' compliance for successful treatment outcomes. Post operative complications can influence patients' acceptance of treatment and compromise further periodontal maintenance. AIM: The aim of this study was to evaluate the frequency and severity of complications after a modified coronally advanced flap procedure. METHODS AND MATERIALS: A total of 78 modified coronally advanced flap procedures were performed in 42 patients for root coverage. Duration of surgical procedure, history of smoking, gender, and age were recorded for each patient. A questionnaire was given to every patient to fill in at first post operative week regarding their experience of postoperative pain, swelling, and bleeding. RESULTS: Pain and duration of surgery had a correlation (OR: 1.05, P < 0.05). Post operative bleeding was significantly correlated with duration of surgery (OR: 1.03, P < 0.05). Current smokers experienced post operative swelling (P < 0.05). However, post operative pain in current smokers was not significantly different (P > 0.05) as compared to nonsmokers. Descriptive statistics were expressed as mean and standard deviations. Odd's ratio was obtained to evaluate risk indicators for moderate to severe types of complications. P < 0.05 was considered as significant. CONCLUSIONS: The duration of the surgery, long duration, and the presence of smoking can increase the frequency and severity of post operative complications.

FGF1 supports glycolytic metabolism through the estrogen receptor in endocrine-resistant and obesity-associated breast cancer.

BACKGROUND: Obesity increases breast cancer risk and breast cancer-specific mortality, particularly for people with estrogen receptor (ER)-positive tumors. Body mass index (BMI) is used to define obesity, but it may not be the best predictor of breast cancer risk or prognosis on an individual level. Adult weight gain is an independent indicator of breast cancer risk. Our previous work described a murine model of obesity, ER-positive breast cancer, and weight gain and identified fibroblast growth factor receptor (FGFR) as a potential driver of tumor progression. During adipose tissue expansion, the FGF1 ligand is produced by hypertrophic adipocytes as a stimulus to stromal preadipocytes that proliferate and differentiate to provide additional lipid storage capacity. In breast adipose tissue, FGF1 production may stimulate cancer cell proliferation and tumor progression. METHODS: We explored the effects of FGF1 on ER-positive endocrine-sensitive and resistant breast cancer and compared that to the effects of the canonical ER ligand, estradiol. We used untargeted proteomics, specific immunoblot assays, gene expression profiling, and functional metabolic assessments of breast cancer cells. The results were validated in tumors from obese mice and breast cancer datasets from women with obesity. RESULTS: FGF1 stimulated ER phosphorylation independently of estradiol in cells that grow in obese female mice after estrogen deprivation treatment. Phospho- and total proteomic, genomic, and functional analyses of endocrine-sensitive and resistant breast cancer cells show that FGF1 promoted a cellular phenotype characterized by glycolytic metabolism. In endocrine-sensitive but not endocrine-resistant breast cancer cells, mitochondrial metabolism was also regulated by FGF1. Comparison of gene expression profiles indicated that tumors from women with obesity shared hallmarks with endocrine-resistant breast cancer cells. CONCLUSIONS: Collectively, our data suggest that one mechanism by which obesity and weight gain promote breast cancer progression is through estrogen-independent ER activation and cancer cell metabolic reprogramming, partly driven by FGF/FGFR. The first-line treatment for many patients with ER-positive breast cancer is inhibition of estrogen synthesis using aromatase inhibitors. In women with obesity who are experiencing weight gain, locally produced FGF1 may activate ER to promote cancer cell metabolic reprogramming and tumor progression independently of estrogen.

Venetoclax sensitivity in multiple myeloma is associated with B-cell gene expression.

Venetoclax is a highly potent, selective BCL2 inhibitor capable of inducing apoptosis in cells dependent on BCL2 for survival. Most myeloma is MCL1-dependent; however, a subset of myeloma enriched for translocation t(11;14) is codependent on BCL2 and thus sensitive to venetoclax. The biology underlying this heterogeneity remains poorly understood. We show that knockdown of cyclin D1 does not induce resistance to venetoclax, arguing against a direct role for cyclin D1 in venetoclax sensitivity. To identify other factors contributing to venetoclax response, we studied a panel of 31 myeloma cell lines and 25 patient samples tested for venetoclax sensitivity. In cell lines, we corroborated our previous observation that BIM binding to BCL2 correlates with venetoclax response and further showed that knockout of BIM results in decreased venetoclax sensitivity. RNA-sequencing analysis identified expression of B-cell genes as enriched in venetoclax-sensitive myeloma, although no single gene consistently delineated sensitive and resistant cells. However, a panel of cell surface makers correlated well with ex vivo prediction of venetoclax response in 21 patient samples and may serve as a biomarker independent of t(11;14). Assay for transposase-accessible chromatin sequencing of myeloma cell lines also identified an epigenetic program in venetoclax-sensitive cells that was more similar to B cells than that of venetoclax-resistant cells, as well as enrichment for basic leucine zipper domain-binding motifs such as BATF. Together, these data indicate that remnants of B-cell biology are associated with BCL2 dependency and point to novel biomarkers of venetoclax-sensitive myeloma independent of t(11;14).

A longitudinal analysis of the effect of anemia on executive functions in children with mild to moderate chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency. METHODS: A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1st-5th percentile) or very low (< 1st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates. RESULTS: Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (- 0.75, 95% CI - 1.36, - 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (ß = - 0.98; 95% CI - 1.78, - 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (ß = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (ß = - 1.33, 95% CI - 2.16, - 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (ß = - 1.09, 95% CI - 2.09, - 0.10, p = 0.03). CONCLUSIONS: The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF. A higher resolution version of the Graphical abstract is available as Supplementary information.

Assembly of higher-order SMN oligomers is essential for metazoan viability and requires an exposed structural motif present in the YG zipper dimer.

Protein oligomerization is one mechanism by which homogenous solutions can separate into distinct liquid phases, enabling assembly of membraneless organelles. Survival Motor Neuron (SMN) is the eponymous component of a large macromolecular complex that chaperones biogenesis of eukaryotic ribonucleoproteins and localizes to distinct membraneless organelles in both the nucleus and cytoplasm. SMN forms the oligomeric core of this complex, and missense mutations within its YG box domain are known to cause Spinal Muscular Atrophy (SMA). The SMN YG box utilizes a unique variant of the glycine zipper motif to form dimers, but the mechanism of higher-order oligomerization remains unknown. Here, we use a combination of molecular genetic, phylogenetic, biophysical, biochemical and computational approaches to show that formation of higher-order SMN oligomers depends on a set of YG box residues that are not involved in dimerization. Mutation of key residues within this new structural motif restricts assembly of SMN to dimers and causes locomotor dysfunction and viability defects in animal models.

Recurrent Neuroendocrine Primary Cutaneous Mucinous Carcinoma of the Scalp After Complete Excision.

ABSTRACT: Primary cutaneous mucinous carcinoma is a rare, indolent malignancy with a debated history regarding cell of origin. Recurrence is rare but has been documented in up to a third of cases. Recent literature reviews have recognized 2 possible subtypes-neuroendocrine and nonneuroendocrine- with different possible prognostic implications for patients. We describe a case of recurrent primary cutaneous mucinous carcinoma in a 50-year-old man with subtle neuroendocrine features not initially recognized on routine H&E staining but highlighted by immunohistochemical studies. We underscore the importance of immunohistochemical use in these rare cases and emphasize that awareness of these neuroendocrine and nonneuroendocrine subtypes is essential for a complete diagnosis.

Mesenchymal Neoplasms of the Prostate and Seminal Vesicles: Spectrum of Disease with Radiologic-Pathologic Correlation.

There is a wide spectrum of benign and malignant mesenchymal neoplasms of the prostate, which account for less than 1% of all prostatic tumors. These include distinctive tumors that arise from the specialized prostatic stroma and site-agnostic neoplasms such as smooth muscle tumors, fibrous or myofibroblastic neoplasms, neurogenic tumors, vascular tumors, and a plethora of sarcomas. Select tumors show classic sites of origin within the prostate. While stromal tumors of uncertain malignant potential (STUMPs) commonly involve the peripheral zone at the prostate base, leiomyomas typically originate from the central prostate toward the apex. Some "prostatic" neoplasms such as gastrointestinal stromal tumors, solitary fibrous tumor (SFT), paragangliomas, and neurogenic tumors arise primarily from periprostatic soft tissues. Most mesenchymal tumors of the prostate and seminal vesicles manifest as large tumors that cause nonspecific symptoms; prostate-specific antigen level is not typically elevated. Diverse mesenchymal neoplasms demonstrate characteristic histopathologic and immunocytochemical features and variable cross-sectional imaging findings. While leiomyoma and SFT typically display low signal intensity on T2-weighted images, synovial sarcomas commonly show hemorrhage. Diagnosis is difficult because of the rarity and lack of awareness of the tumors and the significant overlap in histopathologic features. Select tumors show characteristic genetic abnormalities that allow the diagnosis to be established. For example, more than 90% of SFTs are characterized by a unique NAB2-STAT6 gene fusion, and more than 95% of synovial sarcomas are associated with a distinctive SYT-SSX chimeric transcript. Accurate diagnosis is imperative for optimal management owing to markedly different tumor biology as well as attendant therapeutic and prognostic implications. While STUMPs commonly recur, sarcomas typically charter an aggressive course with poor prognosis. Online supplemental material is available for this article. ©RSNA, 2022.

Ehrlichia-induced hemophagocytic lymphohistiocytosis in a pediatric kidney transplant recipient.

BACKGROUND: Kidney transplant patients are susceptible to a variety of infections in the post-transplant period due to the use of immunosuppressant medications. Ehrlichiosis is a rare infection in solid organ transplant recipients with signs and symptoms that mimic rejection and other viral infections. Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory syndrome that can be triggered by infections. METHODS: We describe a pediatric kidney transplant recipient who experienced secondary HLH due to ehrlichiosis within the initial post-transplant month. RESULT: Our patient improved after treatment with doxycycline, corticosteroids, and intravenous immunoglobulin (IVIG). CONCLUSION: Clinicians should consider infections such as ehrlichiosis as a potential cause of illness in febrile solid organ transplant recipients in immediate post-transplant period, especially when accompanied by a compatible exposure history.

Malignant Gastrointestinal Neuroectodermal Tumor: A New Kid on the Block?

ABSTRACT: Also referred to as "osteoclast-rich, clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT)," malignant gastrointestinal neuroectodermal tumor is a newly described, rare, aggressive sarcoma that commonly arises in the small bowel, stomach, and colon. Histogenesis is likely from an autonomous nervous system-related primitive cell of neural crest origin. The hallmark genetic finding of EWS-CREB1 or EWS-ATF1 fusion transcripts clinches the diagnosis. Annular constrictive lesions tend to be smaller, show homogenous contrast enhancement on computed tomography, and may present with bowel obstruction. Larger, expansile masses tend to be exophytic and show heterogeneous contrast enhancement. Surgical resection is the mainstay of treatment. Frequent recurrences, metastases, and death from disease in 75% of patients portend a poor prognosis. Targeted chemotherapy based on specific tumor pathways is being developed.

Morphological and Molecular Analysis of Fungal Species Associated with Blast and Brown Spot Diseases of Oryza sativa.

Fungal diseases blast and brown spot in rice cause severe yield losses worldwide. Blast is caused by Magnaporthe oryzae, and Bipolaris oryzae is reported as the main causal organism of brown spot. Both diseases cause leaf lesions that are difficult differentiate until the later stages. Early detection and differentiation of the lesions would help the adoption of disease management strategies specific to the pathogens and prevent reductions in the quality and quantity of rice yields. This study was conducted in the Northern Province of Sri Lanka over five consecutive rice cultivating seasons to characterize the causal fungi of rice blast and brown spot diseases by morphological and molecular means and to develop a visual guide to differentiate the two diseases. Disease incidence was recorded in 114 fields from 2017 to 2019, and fungal isolates associated with the lesions of both diseases were cultured and subjected to morphological and molecular characterization. Competitive growth interactions between M. oryzae and the more common individual fungal isolates of the brown spot lesions were evaluated. Fungal metagenomic analysis was conducted for the fungal species isolated from brown spot lesions. A suppression of blast accompanied by an increased incidence of brown spot disease was observed during the study period. M. oryzae was confirmed to be the causal organism of the blast, and >20 species of fungi were identified to be associated with brown spot lesions through morphological and molecular studies and metagenomic analyses. Fungal internal transcribed spacer region sequencing revealed genetic variation in the highly conserved region of DNA sequences of blast and brown spot fungal isolates. B. oryzae, Curvularia, and Microdochium species were commonly isolated from brown spot lesions. In vitro competitive growth interactions between the fungal isolates revealed growth suppression of M. oryzae by the fungal isolates associated with brown spot lesions. Similarly, it can be speculated that the abundance and severity of blast in the field may have an influence on brown spot-associated fungi. A simple visual guide was developed to differentiate blast and brown spot lesions. The findings would be highly useful in the timely management of these major fungal diseases affecting rice.

"I took the road less traveled, and that has made all the difference": Making a case for high-dose therapy and autologous stem cell transplantation in elderly patients with newly diagnosed multiple myeloma.

LAY SUMMARY: Elderly patients with myeloma derive benefits from transplantation similar to those for younger patients. Age should not be the sole criterion for determining transplant eligibility. Performance status assessment and other tools for assessing comorbidities such as the Charlson comorbidity score may potentially help in determining transplant eligibility and will allow us to move away from our heavy reliance on numerical age.

"Save the Vein" Initiative in Children With CKD: A Quality Improvement Study.

RATIONALE & OBJECTIVE: The preferred vascular access for hemodialysis recipients is an arteriovenous fistula in the nondominant arm. Prior placement of a peripheral intravenous (PIV) catheter can lead to vascular injury and limit options for arteriovenous fistula creation, a particular problem for children, who may need hemodialysis for their entire lifetime. We instituted an initiative to increase the frequency of PIV catheter placement in the dominant arm for hospitalized pediatric patients with advanced chronic kidney disease (CKD). STUDY DESIGN: Quality improvement initiative. SETTING & PARTICIPANTS: Children with CKD stage 3-5, receiving dialysis, and/or following kidney transplantation who were hospitalized at one children's hospital between September 2018 and August 2020. QUALITY IMPROVEMENT ACTIVITIES: Retrospective data on PIV catheter location for patients from January 1 to June 30, 2017, served as baseline data. Quality improvement activities consisted of: 1) education of the multidisciplinary treatment team, patients, and parents regarding importance of vein preservation; 2) placement of individualized notes in the electronic medical record identifying the preferred arm for PIV catheter placement; 3) use of "restricted extremity" arm bands; and 4) vascular access team participation to minimize attempts for PIV catheter placement. OUTCOME: Monthly compliance with placement of PIV catheters in dominant arms. ANALYTICAL APPROACH: Location of PIV catheter placements were determined monthly and used to create run charts describing compliance. RESULTS: At baseline and before institution of this initiative, 34 of 72 (47%) PIV catheters were placed in patients' dominant arms, with only 2 of 8 (25%) PIV catheters placed in the dominant arm for children aged<5 years. After instituting the initiative, 345 of 371 (93%) PIV catheters were placed in the dominant arm of 93 children; in children aged<5 years, 58 of 62 (94%) PIV catheters were placed in the dominant arm. Only 38 of 371 (10%) PIV catheters were placed in the antecubital vein. LIMITATIONS: Single-center study. CONCLUSIONS: Education regarding the importance of vein preservation, along with implementation of a standardized process for identifying children for whom vein preservation is important, can help direct PIV catheter placement and potentially preserve vasculature in pediatric patients with CKD.

Homologous recombination proficiency in ovarian and breast cancer patients.

Homologous recombination and DNA repair are important for genome maintenance. Genetic variations in essential homologous recombination genes, including BRCA1 and BRCA2 results in homologous recombination deficiency (HRD) and can be a target for therapeutic strategies including poly (ADP-ribose) polymerase inhibitors (PARPi). However, response is limited in patients who are not HRD, highlighting the need for reliable and robust HRD testing. This manuscript will review BRCA1/2 function and homologous recombination proficiency in respect to breast and ovarian cancer. The current standard testing methods for HRD will be discussed as well as trials leading to approval of PARPi's. Finally, standard of care treatment and synthetic lethality will be reviewed.

Improving natural product research translation: From source to clinical trial.

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

The abscopal effect of radiation therapy.

Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells. T cells then exert a targeted response throughout the body at areas not subjected to RT. These effects are further augmented through the use of immunotherapeutic drugs resulting in increased T-cell activity. Tumor-infiltrating lymphocyte presence and TREX1, KPNA2 and p53 signal expression are being explored as prognostic biomarkers.

A comprehensive review on tannase: Microbes associated production of tannase exploiting tannin rich agro-industrial wastes with special reference to its potential environmental and industrial applications.

Microorganisms have been used for the production of various enzymes, including inducible tannase for various industrial and environmental applications. Tannases have lot of potential to convert hydrolysable tannins to gallic acid, which is one of the important industrial and therapeutic significant molecules whose demand is over 10000 tons per year. Tannins invariably occur in angiosperms, gymnosperms and pteridophytes, and predominantly present in various parts of plants such as, leaves, roots, bark and fruit. Furthermore, tannery effluents are frequently loaded with significant levels of tannic acid. Tannase can be effectively used to decrease tannin load in the toxic tannery effluent thus providing the opportunity to minimize the operational cost. Over the past three decades, tannase from microbial sources has been proposed for the degradation of natural tannins. The availability of various agro-industrial residues paves a way for maximum utilization of tannase production for the degradation of tannin and eventually the production of gallic acid. In this review, an illustrative and comprehensive account on tannase from microbial source for current day applications is presented. The present review emphasises on up-to-date microbial sources of tannases, biochemical properties, optimization of tannase production in solid state and submerged fermentation and its industrial and environmental applications.

Clinical, Radiographic, Pathologic Characterization and Survival Outcomes of Nuclear Protein of the Testis Carcinoma.

INTRODUCTION: Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor with characteristic BRD4-NUTM1 translocation and a poor prognosis. The primary objective of this study was to describe the clinical and radiologic features, treatment response, and survival of NUT carcinoma (NC). MATERIALS AND METHODS: This retrospective single-center study was based on the review of medical records of NC patients with a specific genetic rearrangement or positive anti-NUT nuclear staining. Overall survival (OS) was analyzed according to primary tumor location. RESULTS: This series of 22 patients had a mean age of 36.27 ± 2.68 years with 68% women and 32% men. The median age at diagnosis was 34 years (range, 17-55 years). The primary tumor was located in the chest (n = 12/22; 55%), head and neck (n = 9/22; 40%), and 1 patient had a renal tumor. About 68% (n = 15/22) patients presented with regional lymph nodal involvement and 77% (n = 17/22) had distant metastases. All the bone metastases were lytic (100%) with mixed lytic and sclerotic metastases in 5 patients. Only 18% (n = 4/22) of the patients showed response to treatment, with progression in the remaining 18 patients. The median OS was 7 months. The OS was significantly (P = 0.024) more in patients with primary head and neck NC (n = 9; OS, 16 months) versus those with pulmonary and other locations (n = 13; OS, 6 months). CONCLUSIONS: Nuclear protein of the testis carcinoma is an aggressive disease refractory to conventional therapy. Imaging with the complementary use of computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography is important for staging, guiding management, assessing the treatment response, and surveillance.