Reduction of Postoperative Pain by Addition of Intravenous Acetaminophen after Total Hip Arthroplasty: A Retrospective Cohort Study

We evaluated the analgesic effects of multimodal pain control in which intravenous acetaminophen (IV APAP) was added to the standard protocol for Japanese patients who had undergone a total hip arthroplasty (THA). We performed a retrospective cohort study of 180 patients aged 66.4±10.5 years (30% male) who had undergone a THA (Oct. 2014 to Feb. 2015) at our hospital. The control patients were administered the standard analgesic protocol: flurbiprofen axetil as a continuous intravenous infusion and oral celecoxib (NAPAP; n=109). The patients in the new analgesic protocol group received IV APAP in addition to the standard analgesic protocol (APAP; n=71). The primary outcome was the maximum value of postoperative pain the patients reported on a numerical rating scale (NRS) during the first 24 h post-surgery. A univariate analysis and multivariate analyses adjusted for age, sex, the stage of hip osteoarthritis, preoperative pain, and surgical time showed that the maximum postoperative pain NRS scores during the first 24 h after surgery was significantly lower when the APAP protocol was used. The addition of IV APAP to the current standard multimodal analgesia protocol for Japanese patients who have undergone a THA may decrease the patients’ postoperative pain

A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations

The Ras/RAF/MEK/ERK pathway is an essential signaling cascade for various refractory cancers, such as those with mutant KRAS (mKRAS) and BRAF (mBRAF). However, there are unsolved ambiguities underlying mechanisms for this growth signaling thereby creating therapeutic complications. This study shows that a vital component of the pathway CRAF is directly impacted by an end product of the cascade, glutathione transferases (GST) P1 (GSTP1), driving a previously unrecognized autocrine cycle that sustains proliferation of mKRAS and mBRAF cancer cells, independent of oncogenic stimuli. The CRAF interaction with GSTP1 occurs at its N-terminal regulatory domain, CR1 motif, resulting in its stabilization, enhanced dimerization, and augmented catalytic activity. Consistent with the autocrine cycle scheme, silencing GSTP1 brought about significant suppression of proliferation of mKRAS and mBRAF cells in vitro and suppressed tumorigenesis of the xenografted mKRAS tumor in vivo. GSTP1 knockout mice showed significantly impaired carcinogenesis of mKRAS colon cancer. Consequently, hindering the autocrine loop by targeting CRAF/GSTP1 interactions should provide innovative therapeutic modalities for these cancers

Capsaicin inhibits the production of tumor necrosis factor α by LPS-stimulated murine macrophages, RAW 264.7: a PPARγ ligand-like action as a novel mechanism

AbstractCapsaicin, a major ingredient of hot pepper, is considered to exhibit anti-inflammatory properties. Our previous study demonstrated that capsaicin inhibited the production of pro-inflammatory mediators through NF-κB inactivation in LPS-stimulated macrophages. In order to further clarify the mechanism underlying the anti-inflammatory action of capsaicin, we investigated whether capsaicin alters PPARγ activity, which regulates the production of the pro-inflammatory cytokine TNFα. Capsaicin significantly inhibited the production of TNFα by macrophages in a dose-dependent manner. Simultaneous exposure of the cells to capsaicin and PPARγ agonist troglitazone or RXR agonist LG100268 resulted in stronger inhibition of TNFα production compared to the cells treated with either capsaicin, troglitazone, or LG100268 alone. Luciferase reporter assay revealed that capsaicin induced GAL4/PPARγ chimera and full length PPARγ (PPRE) transactivations in a dose-dependent manner. Furthermore, a specific PPARγ antagonist T0070907 abrogated the inhibitory action of capsaicin on LPS-induced TNFα production by RAW 264.7 cells, indicating that capsaicin acts like a ligand for PPARγ. Our data demonstrate for the first time that the anti-inflammatory action of capsaicin may be mediated by PPARγ activation in LPS-stimulated RAW 264.7 cells

Surgical resection of hepatic and rectal metastases of pancreatic acinar cell carcinoma (PACC): a case report

BackgroundPancreatic acinar cell carcinoma (PACC), a rare variant of pancreatic malignancy, is generally managed the same way as pancreatic ductal adenocarcinoma (PDAC). Surgical resection is the gateway to curing it; however, once it metastasizes (usually to the liver, lungs, lymph nodes, or peritoneal cavity), systemic chemotherapy has been the only option, but with unfavorable results.Case presentationA 67-year-old man with symptoms of loss of appetite and weight underwent surgery for malignancy of the pancreatic tail extending into the entire pancreas. The pathological diagnosis was PACC following total pancreatectomy. Twenty-four months after the pancreatectomy, a solitary liver metastasis was treated by partial hepatectomy, and, subsequently, 4 months later, he presented with melena. Further examination revealed a type-2 rectal tumor. Histological examination following biopsy revealed it to be rectal metastasis of PACC, and it was treated by abdominoperineal resection. Subsequently, the patient did not have tumor recurrence as of 40 months after pancreatectomy.ConclusionsThis is a rare case of PACC presenting with metachronal metastases in the liver and rectum, and we successfully treated them by surgical resections. Since the malignant behavior of PACC is usually less than that of PDAC, surgical resection could be an option even for metastatic lesions when the number and extent of metastases are limited