From bimodal to unimodal: The transformed incidence of osteosarcoma in the United States.

Background: Osteosarcoma is the most common primary bone malignancy. It has classically been described as having a bimodal incidence by age. We sought to identify whether the bimodal incidence distribution still exists for osteosarcoma using the SEER and NIS databases. Methods: Incidence rates of primary osteosarcoma between 2000-2021 were analyzed by age at diagnosis, year of occurrence, sex, and tumor site from the SEER Research Data, 17 Registries, Nov 2023 Sub (2000-2021). The incidence of cases in 35-64 year-olds and 65 and above was compared statistically to determine if there is an increased incidence in the later ages. Incidence of tumors of the long bones of the lower limbs from the NIS discharge database 2012-2019 was also analyzed for comparison. Results: Overall, 5,129 cases of osteosarcoma were reported in the SEER database. Across the 22 calendar year span, a consistent first peak appeared in the second decade of life. There was no consistent second peak in the 35+ age group. There were 86,100 discharges with long bone tumors analyzed in the NIS data which exhibited nearly identical patterns. Conclusions: Our analysis shows that the incidence of osteosarcoma is no longer bimodally distributed but rather unimodally distributed.

Topical Ruxolitinib in the Treatment of Necrobiosis Lipoidica: A Prospective, Open-Label Study.

Necrobiosis lipoidica (NL) is a rare granulomatous disease. There are few effective treatments for NL. We sought to investigate the efficacy and safety of the Jak1/2 inhibitor, ruxolitnib, in the treatment of NL and identify the biomarkers associated with the disease and treatment response. We conducted an open-label, phase 2 study of ruxolitinib in 12 patients with NL. We performed transcriptomic analysis of tissue samples before and after treatment. At week 12, the mean NL lesion score decreased by 58.2% (SD = 28.7%, P = .003). Transcriptomic analysis demonstrated enrichment of type I and type II IFN pathways in baseline disease. Weighted gene coexpression network analysis demonstrated post-treatment changes in IFN pathways with key hub genes IFNG and signal transducer and activator of transcription 1 gene STAT1. Limitations include small sample size and a study group limited to patients with <10% body surface area. In conclusion, ruxolitinib is an effective treatment for NL and targets the key pathogenic mediators of the disease.

Oral Baricitinib in the Treatment of Cutaneous Lichen Planus.

Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon (IFN)-γ, a cytokine implicated in the pathogenesis of LP. Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre-and post-treatment samples. Results: An early and sustained clinical response was seen with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8+, CXCL13+ cytotoxic T-cell population in LP skin and demonstrate a rapid decrease in interferon signature within 2 weeks of treatment, most prominent in the basal layer of the epidermis. Conclusion: This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. Trial Registration Number : NCT05188521.

Reactive Granulomatous Dermatitis in a Child with Acute Lymphoblastic Leukemia.

Reactive granulomatous dermatitis (RGD) is an umbrella term to describe a reaction pattern characterized by skin-colored to erythematous papules, plaques, and nodules although other morphologies have been described. RGD has rarely been reported in children, and in this report, we present the case of a 3-year-old girl with acute lymphoblastic leukemia (ALL) who presented with firm, tender nodules, and ulcerated plaques on her extremities. Histopathologic examination showed foci of dense granulomatous inflammatory infiltrates composed of histiocytes, neutrophils, and multinucleate giant cells. The constellation of clinical symptoms, negative infectious workup, and histopathology support the diagnosis of RGD.

Langerhans Cell Histiocytosis Presenting With Clinical Features of Hidradenitis Suppurativa.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disease of myeloid dendritic cells with a widely variable presentation of organ system involvement and severity. In this case report, we share the details of a rare case of cutaneous LCH resembling hidradenitis suppurativa (HS).

Drug-Induced IgA Vasculitis in an Adult.

A 65-year-old man developed palpable purpuric papules and plaques on his lower extremities, which quickly spread to his trunk and upper extremity after being prescribed cephalexin and doxycycline in the emergency room. Here, we define the details of a textbook-like presentation of IgA vasculitis, formerly referred to as Henoch-Schönlein purpura, in an adult.

No Longer Cutaneous T-cell Lymphoma Dermal Nodule.

Primary cutaneous CD4+ small and medium pleomorphic T-cell lymphoproliferative disorder (PCSM-LPD) is a rare and typically asymptomatic proliferation of CD3+/CD4+ small and medium pleomorphic T-cells. In this case report, we share the details of a 41-year-old male presenting with a two-centimeter soft, mobile forehead nodule that was determined by clinical symptoms, histology, and immunostaining to be PCSM-LPD. We would like to emphasize the clinical resolution that was seen with minimal treatment.

Evaluation of a toxoid fusion protein vaccine produced in plants to protect poultry against necrotic enteritis.

BACKGROUND: Necrotic enteritis (NE) is caused by type A strains of the bacterium Clostridium perfringens. Total global economic losses to the poultry industry due to NE is estimated to be over two billion dollars annually. Traditionally, NE has been effectively controlled by inclusion of antibiotics in the diet of poultry. However, recent concerns regarding the impact of this practice on increasing antibiotic resistance in human pathogens have led us to consider alternative approaches, such as vaccination, for controlling this disease. NE strains of C. perfringens produce two major toxins, a-toxin and NetB. Immune responses against either toxin can provide partial protection against NE. METHODS: We have developed a fusion protein combining a non-toxic carboxyl-terminal domain of a-toxin (PlcC) and an attenuated, mutant form of NetB (NetB-W262A) for use as a vaccine antigen to immunize poultry against NE. We utilized a DNA sequence that was codon-optimized for Nicotiana benthamiana to enable high levels of expression. The 6-His tagged PlcC-NetB fusion protein was synthesized in N. benthamiana using a geminiviral replicon transient expression system, purified by metal affinity chromatography, and used to immunize broiler birds. RESULTS: Immunized birds produced a strong serum IgY response against both the plant produced PlcC-NetB protein and against bacterially produced His-PlcC and His-NetB. Immunized birds were significantly protected against a subsequent in-feed challenge with virulent C. perfringens when treated with the fusion protein. These results indicate that a plant-produced PlcC-NetB toxoid is a promising vaccine candidate for controlling NE in poultry.

Salmonella-vectored vaccine delivering three Clostridium perfringens antigens protects poultry against necrotic enteritis.

Necrotic enteritis is an economically important poultry disease caused by the bacterium Clostridium perfringens. There are currently no necrotic enteritis vaccines commercially available for use in broiler birds, the most important target population. Salmonella-vectored vaccines represent a convenient and effective option for controlling this disease. We used a single attenuated Salmonella vaccine strain, engineered to lyse within the host, to deliver up to three C. perfringens antigens. Two of the antigens were toxoids, based on C. perfringens α-toxin and NetB toxin. The third antigen was fructose-1,6-bisphosphate aldolase (Fba), a metabolic enzyme with an unknown role in virulence. Oral immunization with a single Salmonella vaccine strain producing either Fba, α-toxoid and NetB toxoid, or all three antigens, was immunogenic, inducing serum, cellular and mucosal responses against Salmonella and the vectored C. perfringens antigens. All three vaccine strains were partially protective against virulent C. perfringens challenge. The strains delivering Fba only or all three antigens provided the best protection. We also demonstrate that both toxins and Fba are present on the C. perfringens cell surface. The presence of Fba on the cell surface suggests that Fba may function as an adhesin.