We conducted a retrospective review of medical charts of patients, aged 18 to 59 years old, who underwent either a total knee replacement (TKR) or total hip replacement (THR) from January 2002 to December 2004. Of the 204 study subjects, 52% had a TKR while 48% had a THR. Obesity was significantly associated with the need for a TKR or THR when comparing the study group to adults of similar age in the general population (P< 0.0001). Seventy-two percent (146) of the study group was obese and 21% (42) overweight (BMI 25.0 to 29.9 kg/m 2 ) compared to only 26% (596) obese and 34% (732) overweight in the general population. Patients undergoing a TKR were significantly more likely to be obese (BMI>30 kg/m 2 ) than those having a THR, 83% (89) compared to 59% (57) (P< .0006). Our findings support those previously observed in the elderly population. Primary and secondary prevention programs aimed at reducing obesity are strongly recommended.Résumé Nous avons réalise une étude rétrospective chez les patients âgés de 18 à 59 ans et ayant nécessité la mise en place d'une prothèse totale de hanche ou du genou de janvier 2002 à décembre 2004. 204 patients ont été étudiés : 52% pour une prothèse du genou, 48% pour une prothèse de hanche. L'obésité est un facteur significativement associé à la nécessité de la mise en place d'une prothèse totale du genou ou d'une prothèse de hanche. Si l'on compare ce groupe, à un groupe similaire de personnes du même âge dans la population générale (p<0.001). 70% soit 146 patients du groupe étudié étaient obèses et 21%, soit 42 patients, en surpoids Kg/m 2 ) comparé à 26%, soit 596 patients obèses et 34% soit 732 patients en surpoids de la population générale. Les patients nécessitant un remplacement du genou étaient en surcharge pondérale plus importante que les patients nécessitant une prothèse de hanche (BMI> 30 kg/m 2 ) 83% soit 89 patients contre 59% soit 57 patients. Il nous apparaît donc important à la lumière de ces constatations de préconiser une prévention de réduction de l'obésité dans la population.
Calcific myonecrosis is a rare and latent condition characterized by a dystrophic calcified lesion that can present 10-64 years following initial trauma. Of the 25 cases documented in English world literature, all have occurred in the lower extremity exclusively. We report a case of a 60-year-old man with a painless enlarging left forearm mass that was subsequently diagnosed as calcific myonecrosis. Awareness of this lesion arising outside of the lower extremity is important to avoid unnecessary surgical intervention and patient reassurance.
BackgroundAs the most powerful T cell agonists known, superantigens (SAgs) have enormous potential for cancer immunotherapy. Their development has languished due to high incidence (60%–80%) of seroreactive neutralizing antibodies in humans and tumor necrosis factor-α (TNFα)-mediated cardiopulmonary toxicity. Such toxicity has narrowed their therapeutic index while neutralizing antibodies have nullified their therapeutic effects.MethodsFemale HLA-DQ8 (DQA*0301/DQB*0302) tg mice expressing the human major histocompatibility complex II (MHCII) HLA-DQ8 allele on a high proportion of PBL, spleen and lymph node cells were used. In the established tumor model, staphylococcal enterotoxin G and staphylococcal enterotoxin I (SEG/ SEI) (50 µg each) were injected on days 6 and 9 following tumor inoculation. Lymphoid, myeloid cells and tumor cell digests from tumor tissue were assayed using flow cytometry or quantitated using a cytometric bead array. Tumor density, necrotic and viable areas were quantitated using the ImageJ software.ResultsIn a discovery-driven effort to address these problems we introduce a heretofore unrecognized binary complex comprizing SEG/SEI SAgs linked to the endogenous human MHCII HLA-DQ8 allele in humanized mice. By contrast to staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) deployed previously in clinical trials, SEG and SEI does not exhibit neutralizing antibodies in humans or TNFα-mediated toxicity in humanized HLA-DQ8 mice. In the latter model wherein SAg behavior is known to be ‘human-like’, SEG/SEI induced a powerful tumoricidal response and long-term survival against established melanoma in 82% of mice. Other SAgs deployed in the same model displayed toxic shock. Initially, HLA-DQ8 mediated melanoma antigen priming, after which SEG/SEI unleashed a broad CD4+ and CD8+ antitumor network marked by expansion of melanoma reactive T cells and interferon-γ (IFNy) in the tumor microenvironment (TME). SEG/SEI further initiated chemotactic recruitment of tumor reactive T cells to the TME converting the tumor from ‘cold’ to a ‘hot’. Long-term survivors displayed remarkable resistance to parental tumor rechallenge along with the appearance of tumor specific memory and tumor reactive T memory cells.ConclusionsCollectively, these findings show for the first time that the SEG/SEI-(HLA-DQ8) empowers priming, expansion and recruitment of a population of tumor reactive T cells culminating in tumor specific memory and long-term survival devoid of toxicity. These properties distinguish SEG/SEI from other SAgs used previously in human tumor immunotherapy. Consolidation of these principles within the SEG/SEI-(HLA-DQ8) complex constitutes a conceptually new therapeutic weapon with compelling translational potential.
B7-H4 (VTCN1, B7x, B7S1) is a transmembrane protein belonging to the B7 family of costimulatory proteins and has been shown to inhibit T cell proliferation, cytokine secretion, and cytotoxic lymphocyte (CTL) induction. B7-H4 expressed on tumor cells or macrophages has been associated with poor prognosis and impaired T cell function in renal cell and ovarian cancers. Here we show B7-H4 is abundantly expressed in human breast cancer with triple negative breast cancer (TNBC) having the highest overall B7-H4 mRNA expression. We developed a specific and sensitive immunohistochemistry (IHC) assay for evaluation of B7-H4 protein and quantified B7-H4 expression in 156 breast tumor samples. Approximately 70% of the breast tumor samples had detectable B7-H4 expression whereas none of the normal or benign breast tissues stained positive for B7-H4. Multiplex IHC and flow cytometry studies showed that the majority of B7-H4 expression was restricted to the tumor epithelial cells, the CD45+ immune cells were negative for B7-H4 expression. Interestingly none of the TNBC samples that were positive for B7-H4 showed detectable expression of PD-L1 suggesting that B7-H4 and PD-L1 checkpoint proteins may act in a mutually exclusive manner. To evaluate the role of B7-H4 on tumor immune evasion, we overexpressed murine or human B7-H4 on the mouse colon-26 (CT26) tumor cell line and injected these cells intravenously into Balb/c mice. By day 14 we observed significantly more tumors as well as larger percent tumor area in the lungs of mice given CT26 cells transduced with human or mouse B7-H4 as compared to vector control transduced cells. These data suggest B7-H4 expression in tumors can accelerate tumor growth in immune competent mice and that targeting B7-H4 may provide therapeutic benefit. Given the mutually exclusive expression patterns of B7-H4 and PD-L1 a B7-H4 targeting agent may provide particular benefit in those patients where current anti-PD-1/PD-L1 therapies are not effective. Citation Format: Shaffer DR, Nagashima K, Cortez-Retamozo V, Feldman I, Smith J, Zafari M, Larson R, Mabry R, Novorantseva T, Briskin M, Sathyanaryananan S. Mutually exclusive expression pattern of the immune co-inhibitory molecules B7-H4 and PD-L1 in triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-11-07.
Ethiopians depend on sunlight for vitamin D synthesis due to limited dietary sources. This qualitative study investigated sociocultural factors affecting sun exposure for infants of women from three categories: initial pregnancies, mothers of infants <1 y, and grandmothers. Eighteen focus groups with ≅10 participants each were held in three urban and three rural communities. In‐depth interviews were conducted with local health extension workers (HEWs). Reports from grandmothers indicated that awareness of benefits of sun exposure for infants has increased in the last generation. Mothers currently stay indoors after delivery for ≅45 days in rural and ≅15 days in urban areas. Women stated that 15‐30 minutes of morning sunlight, never afternoon sun, was best for infant health. Most reported rubbing their infants with oil or butter before sunlight exposure. Barriers mentioned were skin irritation, eye problems, catching cold from drafts, and fear of the evil eye. Only 2 of 82 rural and 26 of 88 urban women freely associated sunlight with vitamin D. HEWs provided health information for 96% of rural and 88% of urban women. Variable understanding of the importance of sun exposure and of sources of vitamin D indicated disparities in knowledge transfer. Our data support additional training of both rural and urban HEWs and mothers regarding benefits of sun exposure for infants and children. (Supported by Don & Kathy Humphreys, Wentz and Miller Grants)
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