Lymphomas of the submandibular gland: a nationwide cohort study.

OBJECTIVE: This study explores the epidemiology, incidence, and survival outcomes associated with lymphomas of the submandibular gland (SMG) and examines the influence of autoimmune diseases on these parameters. METHODS: This retrospective nationwide cohort study analysed data from patients diagnosed with SMG lymphomas in Denmark between 2000 and 2020. Information was extracted from medical records, the National Pathology Register, and the Danish Lymphoma Database. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, focusing on lymphoma subtypes and autoimmune diseases. RESULTS: The cohort consisted of 101 patients with a lymphoma diagnosis and involvement of the SMG. Large B-cell lymphoma (LBCL) was diagnosed in 33 cases (32.7%), follicular lymphoma (FL) in 29 cases (28.7%), extranodal marginal zone lymphoma (EMZL) in 27 cases (26.7%), and 12 cases (11.9%) with other subtypes. EMZL had a significantly longer overall survival (OS) compared to other subtypes, with a median OS of 12.4 years (95% CI 11.2-12.4) vs. 8.4 years (95% CI 6.0-12.2). EMZL and FL showed favourable 5-year OS rates of 95% and 89%, respectively. LBCL had a 5-year OS rate of 65%. Age over 60 significantly negatively impacted OS. Traditional poor prognostic indicators did not significantly affect OS. A notable association between EMZL and autoimmune diseases was observed, particularly with Sjögren's syndrome, indicated by an increased relative risk of 2.67 (CI 95% 0.45-16.01). CONCLUSIONS: Lymphomas of the SMG are rare and have ambiguous clinical presentations. This study provides novel epidemiological, clinical, and prognostic information.

Glycogen synthase kinase-3ß inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A.

Intraventricular hemorrhage (IVH) in preterm infants results in reduced proliferation and maturation of oligodendrocyte progenitor cells (OPCs), and survivors exhibit reduced myelination and neurological deficits. Wnt signaling regulates OPC maturation and myelination in a context dependent manner. Herein, we hypothesized that the occurrence of IVH would downregulate Wnt signaling, and that activating Wnt signaling by GSK-3ß inhibition or Wnt3A recombinant human protein (rh-Wnt3A) treatment might promote maturation of OPCs, myelination of the white matter, and neurological recovery in premature rabbits with IVH. These hypotheses were tested in autopsy samples from preterm infants and in a rabbit model of IVH. Induction of IVH reduced expressions of activated ß-catenin, TCF-4, and Axin2 transcription factors in preterm newborns. Both AR-A014418 (ARA) and Wnt-3A treatment activated Wnt signaling. GSK-3ß inhibition by intramuscular ARA treatment accelerated maturation of OPCs, myelination, and neurological recovery in preterm rabbits with IVH compared to vehicle controls. In contrast, intracerebroventricular rh-Wnt3A treatment failed to enhance myelination and neurological function in rabbits with IVH. ARA treatment reduced microglia infiltration and IL1ß expression in rabbits with IVH relative to controls, whereas Wnt3A treatment elevated TNFα, IL1ß, and IL6 expression without affecting microglia density. GSK-3ß inhibition downregulated, while rh-Wnt3A treatment upregulated Notch signaling; and none of the two treatments affected the Sonic-Hedgehog pathway. The administration of ARA or rh-Wnt3A did not affect gliosis. The data suggest that GSK-3ß inhibition promoted myelination by suppressing inflammation and Notch signaling; and Wnt3A treatment failed to enhance myelination because of its pro-inflammatory activity and synergy with Notch signaling. GSK-3ß inhibitors might improve the neurological outcome of preterm infants with IVH.

AMPA-Kainate Receptor Inhibition Promotes Neurologic Recovery in Premature Rabbits with Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) in preterm infants leads to cerebral inflammation, reduced myelination of the white matter, and neurological deficits. No therapeutic strategy exists against the IVH-induced white matter injury. AMPA-kainate receptor induced excitotoxicity contributes to oligodendrocyte precursor cell (OPC) damage and hypomyelination in both neonatal and adult models of brain injury. Here, we hypothesized that IVH damages white matter via AMPA receptor activation, and that AMPA-kainate receptor inhibition suppresses inflammation and restores OPC maturation, myelination, and neurologic recovery in preterm newborns with IVH. We tested these hypotheses in a rabbit model of glycerol-induced IVH and evaluated the expression of AMPA receptors in autopsy samples from human preterm infants. GluR1-GluR4 expressions were comparable between preterm humans and rabbits with and without IVH. However, GluR1 and GluR2 levels were significantly lower in the embryonic white matter and germinal matrix relative to the neocortex in both infants with and without IVH. Pharmacological blockade of AMPA-kainate receptors with systemic NBQX, or selective AMPA receptor inhibition by intramuscular perampanel restored myelination and neurologic recovery in rabbits with IVH. NBQX administration also reduced the population of apoptotic OPCs, levels of several cytokines (TNFα, IL-ß, IL-6, LIF), and the density of Iba1(+) microglia in pups with IVH. Additionally, NBQX treatment inhibited STAT-3 phosphorylation, but not astrogliosis or transcription factors regulating gliosis. Our data suggest that AMPA-kainate receptor inhibition alleviates OPC loss and IVH-induced inflammation and restores myelination and neurologic recovery in preterm rabbits with IVH. Therapeutic use of FDA-approved perampanel treatment might enhance neurologic outcome in premature infants with IVH. SIGNIFICANCE STATEMENT: Intraventricular hemorrhage (IVH) is a major complication of prematurity and a large number of survivors with IVH develop cerebral palsy and cognitive deficits. The development of IVH leads to inflammation of the periventricular white matter, apoptosis and arrested maturation of oligodendrocyte precursor cells, and hypomyelination. Here, we show that AMPA-kainate receptor inhibition by NBQX suppresses inflammation, attenuates apoptosis of oligodendrocyte precursor cells, and promotes myelination as well as clinical recovery in preterm rabbits with IVH. Importantly, AMPA-specific inhibition by the FDA-approved perampanel, which unlike NBQX has a low side-effect profile, also enhances myelination and neurological recovery in rabbits with IVH. Hence, the present study highlights the role of AMPA-kainate receptor in IVH-induced white matter injury and identifies a novel strategy of neuroprotection, which might improve the neurological outcome for premature infants with IVH.

A diagnostic dilemma-to operate or not to operate-a rare case report.

A 41-year-old male presented with a swelling in the right flank present since 2 years. Initially, it was small in size but increased in size for the past 6 months. Examination revealed a large swelling in the right flank that was soft in consistency and attached to the deeper muscle. CT scan revealed a heterogenous complex swelling with attachment to the underlying muscle. Core biopsy of the lesion was reported as undifferentiated sarcoma. After immunohistochemistry markers, the diagnosis was revised to a malignancy of a lymphomatous origin. Gene sequencing studies and extensive higher marker studies were done and a final diagnosis of plasmacytic infiltrate of uncertain clinical significance was reported. With no further diagnostic options available, the case still remains to be a diagnostic challenge as the choice of treatment between surgical resection and nonsurgical treatment with chemotherapy and/or radiation cannot be decided upon.

Multi-recurrent Asynchronous Bilateral Malignant Phyllodes.

In this comprehensive study, we present an exceptionally rare case characterized by the occurrence of multi-recurrent asynchronous bilateral malignant phyllodes tumors. Phyllodes tumors, known for their rapid growth, originate within the stromal tissue of the breast and predominantly manifest as benign entities. Our case stands out as an extraordinary anomaly, not only due to its bilateral malignant nature but also owing to the manifestation of a multi-recurrent pattern on both sides. This unprecedented presentation underscores the complexity and heterogeneity of malignant phyllodes tumors, necessitating further in-depth investigation to unravel the underlying mechanisms driving their aggressive behavior and to explore innovative therapeutic strategies aimed at optimizing patient outcomes and prognosis.

Lymphomas of the salivary glands: a systematic review.

BACKGROUND: Lymphomas constitute 2% of all salivary gland tumors and are the second most common group of malignancies in the head and neck region. OBJECTIVES: In this systematic review, the demographics and characteristics of salivary gland lymphomas are presented. METHODS: All types of studies that involve data of salivary gland lymphomas between 1990 and 2020 were identified and screened. RESULTS: A total of 169 articles with 1640 patients were identified. The median age of the patients was 59 years with a range between 10 and 87 years. The anatomic locations of salivary gland lymphomas were distributed with 88% in the parotid glands, 9% in the submandibular glands, 1% in the minor salivary glands, and 0.3% in the sublingual glands. The overall survival at 12 months is high and in line with the outcome of indolent lymphomas in general. The predominant indolent subtypes were extranodal marginal zone lymphomas and follicular lymphomas, whereas the more aggressive subtypes were mainly diffuse large B-cell lymphomas, mantle cell lymphomas, and T-cell lymphomas. CONCLUSION: In conclusion, lymphomas occur in all salivary glands and mainly in elderly female patients. Sjögren's syndrome is frequently associated. Depending on the anatomical location, the lymphoma subtypes vary in aggressiveness, stage, and prognosis.

The Impact of COVID-19 on Students' Marks: A Bayesian Hierarchical Modeling Approach.

Due to COVID-19, universities across Canada were forced to undergo a transition from classroom-based face-to-face learning and invigilated assessments to online-based learning and non-invigilated assessments. This study attempts to empirically measure the impact of COVID-19 on students' marks from eleven science, technology, engineering, and mathematics (STEM) courses using a Bayesian linear mixed effects model fitted to longitudinal data. The Bayesian linear mixed effects model is designed for this application which allows student-specific error variances to vary. The novel Bayesian missing value imputation method is flexible which seamlessly generates missing values given complete data. We observed an increase in overall average marks for the courses requiring lower-level cognitive skills according to Bloom's Taxonomy and a decrease in marks for the courses requiring higher-level cognitive skills, where larger changes in marks were observed for the underachieving students. About half of the disengaged students who did not participate in any course assessments after the transition to online delivery were in special support.

Comparative Study Between Topical Gatifloxacin 0.5% and Moxifloxacin 0.5% as a Prophylactic Measure Before Intraocular Surgery.

Purpose: To compare equal concentrations (0.5%) of moxifloxacin and gatifloxacin ophthalmic solutions with regard to conjunctival bacterial reduction as well as anterior chamber penetration. Methods: One hundred patients were divided into 2 groups. Group A received moxifloxacin 0.5% ophthalmic solution and group B received gatifloxacin 0.5% ophthalmic solution 4 times a day for 3 days before surgery and 5 times with 30 min intervals on the day of surgery. Two conjunctival swabs were obtained: one before instillation of antibiotic and the second 30 min after instillation of the last antibiotic drop. Specimens were sent for culture and susceptibility testing. At the time of surgery, 0.1 mL of aqueous fluid was aspired, and aqueous concentration of fluoroquinolones was identified using reverse-phase high-pressure liquid chromatography assay technique. Results: The most common flora isolated was coagulase-negative Staphylococcus (32.9%), followed by Staphylococcus aureus (24.8%) and Corynebacterium diphtheria (19.1%). Moxifloxacin aqueous concentration was higher compared with gatifloxacin [1.75 ± 0.98 standard deviation (SD) and 0.75 ± 0.22 SD, respectively]. This 2.3-fold difference in aqueous humor antibiotic concentrations was statistically significant (P ≤ 0.001). There was significant difference between the means of conjunctival colony-forming unit after antibiotic administration in both the study groups (2.17 ± 1.54 SD in group A and 1.56 ± 1.09 SD in group B). Conclusions: Moxifloxacin 0.5% was found to penetrate anterior chamber more than gatifloxacin 0.5%, enforcing its use for prophylaxis before intraocular surgeries. However, gatifloxacin 0.5% eye drops were able to reduce conjunctival bacterial load, more supporting its use before extraocular and refractive surgeries.