PurposeTo investigate the ability of leucovorin (LV) to abrogate dose-limiting toxicities of pralatrexate (PDX) while maintaining efficacy, in vivo.MethodsH2052 mesothelioma cells were treated with the antifolates methotrexate (MTX), PDX and pemetrexed, with and without LV rescue 24 h later. Cell killing was evaluated 48 h later. Female nude mice bearing H2052 xenografts were treated with varying doses and schedules of the antifolate PDX and LV.ResultsIn vitro, H2052 cells were more sensitive to PDX as compared to MTX and pemetrexed. Administration of LV 24 h after antifolate treatment reduced efficacy of antifolates MTX and pemetrexed, but not PDX. In vivo, LV was found to reduce toxicity of PDX at the maximum tolerated dose without sacrificing efficacy. Lethal doses of PDX were rescued by LV, and mice bearing the H2052 tumor demonstrated prolonged and enhanced tumor regression.ConclusionsHigh-dose PDX with subsequent LV rescue may be a viable treatment strategy in mesothelioma and other cancers. The inclusion of LV rescue into new and existing PDX treatment protocols should be explored as a way to expand the tolerability and effectiveness of PDX in the clinic.
Objective: The main objective was to describe and review a unique case that presented with diabetic ketoacidosis, positive insulin autoantibodies (IAAbs, which are found in Hirata disease and are usually present with hypoglycemia), and laboratory findings characteristic of type B insulin resistance syndrome (TBIRS) and systemic lupus erythematosus. Confirmation of TBIRS was obtained in Germany as immunoassay for insulin receptor antibodies (IRAbs) is not available in the United States. Methods: A literature review on TBIRS and cases that present with IAAbs and IRAbs simultaneously was conducted.Results: We found 6 cases presenting with hypoglycemia, both antibodies, and treatment attempts with various management approaches that were different from the proposed National Institutes of Health (NIH) protocol for TBIRS. Our case is distinct because of the demographic background, presentation with diabetic ketoacidosis, comparatively lower insulin requirement, and no significant hypoglycemic episodes in the third phase. Conclusion:We propose that access to IRAb immunoassays may be important for diagnosing milder cases of TBIRS, while IAAbs may provide prognostic and therapeutic insights. Despite completely different presentation from other TBIRS patients reviewed, we observed that the proposed NIH protocol consisting of dexamethasone, rituximab, and cyclophosphamide was successfully employed in our patient. Thus, we propose that our case and the findings regarding antibody testing and the NIH treatment regimen may assist clinicians with earlier recognition and effective management of milder cases of TBIRS.
Pelvic osteomyelitis is an uncommon and challenging condition to treat. Pressure ulcers, spinal injuries, contiguous sources of tracking infections, pelvic surgical procedures, traumatic injuries and open fractures all serve as nidi for developing pelvic osteomyelitis. We present a case of pelvic osteomyelitis suspected to be caused by insufficiency fractures due to osteoporosis in an anorexic adult.51 year old postmenopausal Caucasian female with undiagnosed anorexia presented to the hospital for severe right-sided pelvic pain and nausea. She denied fevers, vomiting, trauma, surgical procedures, history of pelvic infections, abnormal vaginal discharge, travel, prolonged steroid therapy. She disclosed a strict vegetarian diet, excessive daily exercise, low dairy intake and over 100lb intentional weight loss over the past 30 years. She reported normal menses, used oral contraceptives between ages of 25 to 30, and reached menopause at 49 years. For many years, she denied medical care including age-appropriate cancer screenings. She is employed in academia and denies tobacco, alcohol or drug use. On admission, height 153cm and weight 43kg, BMI 16.7kg/m2. Examination was notable for frail body habitus, moderate RLQ and pelvic tenderness, prominent PSIS and SI joints with decreased RLE range of motion. Laboratory results showed calcium 9.5mg/dL (n 8.6–10.4), phosphorus 4.1mg/dL (2.5–4.5), ALP 181IU/L (45–115), PTH 23pg/dL (n 9–76), Vitamin D 35ng/dL (n 25–80), 24-hour urinary calcium 285mg/24h (n 50–400). Abdominopelvic CT scan showed chronic right pubic ramus and bilateral sacral insufficiency fractures confirmed on MRI with septic arthritis of the pubic symphysis, osteomyelitis of pubic bodies and intramuscular abscess extending to the right adductor muscle. Wound culture was positive for Streptococcus viridans and pelvic bone biopsy showed degenerative changes. The patient completed IV Ceftriaxone therapy and underwent DXA scan confirming osteoporosis (T-scores:-3.8 lumbar spine L1-L4, -3.6 left femoral neck, -3.3 right femoral neck). Alendronate 10mg daily and calcium citrate-vitamin D 1000mg-800IU twice daily was prescribed. Diagnostic workup for secondary causes of severe osteoporosis was unremarkable except for hypercalciuria, for which calcium supplement was held with a plan to repeat in the future. Concern for her cachectic appearance and severity of her illness also elicited a dietician referral. Pelvic osteomyelitis and septic arthritis are seldom found without inciting insults. We report an atypical cause of presumed anorexia induced osteoporosis resulting in pelvic osteomyelitis. Untreated osteoporosis may lead to fracture, resulting in inflammation and predisposing patients to infections. Thus, early recognition and evaluation of osteoporosis in patients at high risk for fracture, such as patients with anorexia, is critical for prevention.
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