TGF-β signaling regulates several different biological processes involving cell-growth, differentiation, apoptosis, motility, angiogenesis, epithelial mesenchymal transition and extracellular matrix production that affects embryonic development and pathogenesis of various diseases, including cancer, its effects depending on the cellular context and physiological environment. Growth suppression mediated by TGF-β signaling often associated with inhibition of c-myc, cdks and induction of p15, p27, Bax and p21. Despite its growth inhibitory effect, in certain conditions TGF-β may act as a promoter of cell proliferation and invasion. Loss of responsiveness to growth suppression by TGF-β due to mutation or loss of TGF-beta type II receptor (TβRII) and Smad4 in several different cancer cells are reported. In addition, TGF-β binding to its receptor activates many non-canonical signaling pathways. Radiation induced TGF-β is primarily involved in normal tissue injury and fibrosis. Seminal studies from our group have used radio-adjuvant therapies, involving classical components of the pathway such as TβRII and SMAD4 to overcome the growth promoting effects of TGF-β. The main impediment in the radiation-induced TGF-β signaling is the induction of SMAD7 that blocks TGF-β signaling in a negative feedback manner. It is well demonstrated from our studies that the use of neutralizing antibodies against TGF- β can render a robust radio-resistant effect. Thus, understanding the functional interactions of TGF-β signaling components of the pathway with other molecules may help tailor appropriate adjuvant radio-therapeutic strategies for treatment of solid tumors.
The results of this study suggest that there is a significant increase in intraoperative and postoperative complications for obese patients undergoing laparoscopic adrenalectomy compared with healthy weight individuals.
Objective: To determine the influence of initial prescription size on opioid consumption after minor hand surgeries. Secondary outcomes include efficacy of pain control, patient satisfaction, and refill requests. Background: Retrospective studies have shown that opioid prescriptions for acute pain after surgical procedures are often excessive in size, which encourages misuse. This is the first prospective randomized trial on the influence of initial prescription size on opioid consumption in the setting of acute postsurgical pain. Methods: In a prospective randomized trial at a single-academic institution, patients were provided an initial prescription of either 10 or 30 hydrocodone/acetaminophen (5/325 mg) pills after surgery. Two hundred opioid-naive patients, aged 19 to 69, undergoing elective outpatient minor hand surgeries were enrolled over 9 months, with a follow-up period of 10 to 14 days. Results: One hundred seventy-four patients were included in this analysis. Patients initially prescribed 30 pills (n = 79), when compared with patients initially prescribed 10 pills (n = 95), used significantly more opioid (P = <0.001, mean 11.9 vs 6.4 pills), had significantly more leftover medication (P = <0.001, mean 20.0 vs 5.2 pills), and were over 3 times more likely to still be taking opioid at follow-up (15% vs 4%). There was no significant difference in refills requested, or in patient satisfaction with postoperative pain control. Conclusions: Providing large opioid prescriptions for the management of acute pain after minor upper extremity surgeries increases overall opioid use when compared with smaller initial prescriptions. The size of initial opioid prescription is a modifiable variable that should be considered both in patient care and research design.
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