Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10−6) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10−8, explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10−4) and adult height (N = 127 513; P = 1.45 × 10−5). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Most of the observed heterogeneity in glucosamine trials is explained by brand. Trials using the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine. Large inconsistency was found, however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a small effect size.

AimsTo (1) reclassify ocular adnexal large B-cell lymphomas (OA-LBCLs) per 2016 WHO lymphoma classification and (2) determine the prevalence of MYD88 and CD79B mutations and their association with clinical parameters among OA-LBCLs.MethodsThis study is a retrospective analysis of all OA-LBCLs diagnosed in Denmark between 1980 and 2018. Medical records and tissue samples were retrieved. Thirty-four OA-LBCLs were included. Fluorescence in situ hybridisation and Epstein-Barr-encoded RNA in situ hybridisation were used for the reclassification. Mutational status was established by allele-specific PCR and confirmed by Sanger sequencing. Primary endpoints were overall survival, disease-specific survival (DSS) and progression-free survival (PFS).ResultsTwo LBCL subtypes were identified: diffuse large B-cell lymphoma (DLBCL) (27 of 32; 84%) and high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (5 of 32; 16%). cMYC/BCL2 double-expressor DLBCLs had a poorer DSS than non-double-expressor DLBCLs (5-year DSS, 25% vs 78%) (HR 0.23; 95% CI 0.06 to 0.85; p=0.014). MYD88 mutations were present in 10 (29%) of 34 lymphomas and carried a poorer PFS than wild-type cases (5-year PFS, 0% vs 43%) (HR 0.78; 95% CI 0.61 to 0.98; p=0.039). CD79B mutations were present in 3 (9%) of 34 cases.ConclusionOA-LBCL consists mainly of two subtypes: DLBCL and HGBL with MYC and BCL2 and/or BCL6 rearrangements. MYD88 mutations are important drivers of OA-LBCL. MYD88 mutations, as well as cMYC/BCL2 double-expressor DLBCL, appear to be associated with a poor prognosis. Implementing MYD88 mutational analysis in routine diagnostics may improve OA-LBCL prognostication.

Lymphomas of the nasal cavity and paranasal sinuses (NPS) are rare. Knowledge on sinonasal B-cell lymphoma (SNBCL) primarily comes from case series or singlecenter studies on small cohorts. We sought to determine the subtype distribution, clinical characteristics, disease behavior, and prognosis on a nationwide scale, with an emphasis on prognostic factors for the most common sinonasal lymphoma, primary sinonasal diffuse large B-cell lymphoma (PSDLBCL). We collated all data from medical records and national databases on patients registered with SNBCL from 1980 through 2018 in the national pathology registry and collected all tissue samples for validation of diagnosis. We included 205 patients and found 10 different subtypes of lymphoma. Diffuse large B-cell lymphoma (DLBCL) was the predominant subtype (80%). The incidence of SNBCL was 0.14/100,000 personyears. The five-year progression-free survival (PFS) and overall survival rates for PSDLBCL were 50% and 56%, respectively. For PSDLBCL, Rituximab showed a statistically significant effect (Hazard Ratio 0.22, p < 0.001), whereas consolidative radiotherapy combined with immunochemotherapy was of limited value (PFS, p = 0.93). When treatment failure occurred, DLBCL showed a distinct pattern of recurrence/dissemination to the NPS, skin, breast, central nervous system (CNS), and/or testis. Collectively, DLBCL comprised a clear majority of SNBCLs, although nine other subtypes were represented. Data showed that immunochemotherapy increased survival for PSDLBCL and that the addition of radiotherapy did not benefit patients. Furthermore, treatment failure for sinonasal DLBCL showed a possible common pathogenesis with primary extranodal lymphomas of specific locations (e.g., CNS, skin, breast, and testis).This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) can be a challenge to treat despite appropriate pharmacological therapy and endoscopic sinus surgery. With the introduction of biological treatment, costs will increase. In this study, we determine the number of patients with CRSwNP treated with endoscopic sinus surgery and revision surgery and thereby fulfil the main criterion for treatment with biologics in the newest European guidelines. Furthermore, we estimate a potential number of recipients of biologics nationwide. Methods: All adult patients registered in the Danish National Patient Registry as having undergone first endoscopic sinus surgery for CRSwNP from 2012–2018 were included. The number of operations, surgery dates, and comorbidities were extracted. The Kaplan-Meier method was used to calculate the revision rate over time. Revision surgery was used as a surrogate to determine the pool of potential recipients of biologics, as these would fulfil the eligibility criteria and ensure the necessary cost-effectiveness. Results: A total of 4667 operated patients with CRSwNP were included out of a population of 4.7 million adults (incidence 14/100,000 person-years). Approximately 18% (120 per year) was estimated to have revision surgery within seven years. The median time to revision surgery was 22 months. Of all analysed patients, 21% had registered asthma and/or allergic rhinitis, while these diseases were registered in 34% of patients treated with revision surgery. Conclusion: In Denmark, an average of 120 operated patients annually will have revision surgery within seven years and may benefit from treatment with biologics as an alternative option to revision surgery.

Introduction: Infected “mycotic” Aneurysm (IA) of the extracranial carotid artery is a rare condition that can be fatal if mistaken for other pathology. An 83-year-old man presented with a mass on the neck initially suspected malignant. Weeks later it grew rapidly and was found to be an IA, thus requiring acute surgery. Via this case report, we discuss diagnostics and approach when diagnosing masses in relation to vessels of the neck not readily explained.Case Report: After diagnostic imaging and clinical assessment an unknown primary tumor of the neck was suspected. Fine needle aspiration was inconclusive. The patient did not present with any signs of infection or neurological symptoms—only discomfort and pain. Approximately two weeks later, the mass grew and the patient became dysphagic, febrile, and confused. Computed tomography angiography revealed an IA of the right common carotid artery. The patient underwent acute surgery consisting of ligation of the internal and external carotid arteries and resection of the internal jugular vein. The pathogen found was E. coli, supposedly from the bladder after surgical intervention due to polyposis.Conclusion: IA is a very rare entity and can have many etiologies. Since it can be fatal, it is necessary to keep IA in mind when diagnosing masses in relation to vessels of the neck. As shown in this case of a E. coli-induced IA, patients can present with atypical symptoms, on diagnostic imaging it can be mistaken for other pathology, and pathogenesis can be unclear.

Background: Lymphoma of the sublingual gland is rare, representing 1% of all salivary gland lymphomas. In this case report, we present three new cases and compare them to previously published cases, with the aim of characterizing the clinical, morphological, histopathological, and genetic features of this type of malignancy. Materials and Methods: We provide a clinical description of three cases along with a characterization of the microscopic features, including morphology, and immunohistochemistry. In addition, we analysed possible cytogenetic rearrangements with the use of fluorescence in situ hybridization (FISH). Results: Case 1: A 61-year-old male presenting with a painless swelling of the floor of the mouth diagnosed as extranodal marginal zone lymphoma (EMZL) of the left sublingual gland. The patient is alive with no evidence of disease after his fourth treatment regimen following several relapses. Case 2: A 68-year-old female with a prior history of mantle cell lymphoma (MCL) presenting with a tender swelling of the left sublingual gland as well as the right submandibular gland. The lesions were diagnosed as relapsing MCL. The patient died of unrelated causes after 18 months of treatment. Case 3: A 75-year-old female presenting with a swelling of the floor of the mouth diagnosed as follicular lymphoma (FL) of the left sublingual gland. The patient received chemotherapy along with radiotherapy and was still alive 10 years after the diagnosis. Conclusion: The three cases of sublingual gland lymphomas presented in this case report resemble lymphomas of other major salivary glands. The clinician should be aware of this type of malignancy and that the clinical presentation may not differ from benign lesions or other more common malignancies in this location.