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Paclitaxel-induced peripheral neuropathy (PIPN) is one of the serious adverse events associated with paclitaxel-based cancer treatments. A recent case study showed that the antiplatelet agent clopidogrel inhibits paclitaxel metabolism via cytochrome P450 (CYP) 2C8, resulting in severe PIPN. The aim of this study was to determine the impact of clopidogrel as a risk factor for the development of PIPN, using a retrospective cohort study. Data from paclitaxel-treated patients with or without clopidogrel and low-dose aspirin treatment were retrieved from medical charts. A total of 161 adult patients were included in this study: 135 were controls, 9 were clopidogrel-treated and 17 were aspirin-treated. The clopidogrel group had a greater proportion of males and a higher rate of comorbidities, such as diabetes mellitus and dyslipidemia, than the control group. However, patient characteristics were similar between the clopidogrel and aspirin groups. Severe PIPN was diagnosed in 3 (2.2%) and 2 (22.2%) patients in the control and clopidogrel groups, respectively (odds ratio: 12.0; p = 0.031). No patients in the aspirin group presented with severe neuropathy. These pilot data suggest that concomitant treatment with clopidogrel leads to a greater risk of PIPN. The avoidance of concomitant clopidogrel use may be effective in reducing clopidogrel-associated PIPN., Author(s): Mitsuhiro Matsuo [sup.1] , Hisakatsu Ito [sup.1] , Yoshinori Takemura [sup.1] , Mizuki Hattori [sup.1] , Masaaki Kawakami [sup.1] , Norimasa Takahashi [sup.2] , Mitsuaki Yamazaki [sup.1] Author Affiliations: [...]

Key points: Our tibial fracture orthopaedic injury model in mice recapitulates the major manifestations of complex trauma, including nociceptive sensitization, bone fracture, muscle fibrosis and muscle fibre loss.Delayed exercise after complex orthopaedic trauma results in decreased muscle fibrosis and improved painLosartan, an angiotensin‐receptor blocker with anti‐fibrotic abilities, recapitulates the effect of exercise on post‐injury recovery and may provide an enhanced recovery option for those who are unable to exercise after injury Chronic pain and disability after limb injury are major public health problems. Early mobilization after injury improves functional outcomes for patients, although when and how to implement rehabilitation strategies remains a clinical challenge. Additionally, whether the beneficial effects of exercise can be reproduced using pharmacological tools remains unknown and may benefit patients who are unable to exercise as a result of immobilization. We developed a murine model of orthopaedic trauma combining tibia fracture and pin fixation with muscle damage. Behavioural measures included mechanical nociceptive thresholds and distances run on exercise wheels. Bone healing was quantified using microcomputed tomagraphic scanning, and muscle fibre size distribution and fibrosis were followed using immunohistochemistry. We found that the model provided robust mechanical allodynia, fibrosis and a shift to smaller average muscle fibre size lasting up to 5 weeks from injury. We also observed that allowing 'late' (weeks 1–2) rather than 'early' (weeks 0–1) exercise after injury resulted in greater overall running activity and greater reversal of allodynia. In parallel, the late running paradigm was associated with reduced muscle fibrosis, earlier increase in muscle fibre diameter and a short‐term benefit in reducing callus volume. Providing the anti‐fibrotic angiotensin receptor blocker losartan to mice in drinking water reduced both allodynia and muscle fibrosis. Combining losartan and late exercise provided no additional benefit. We conclude that early healing after orthopaedic trauma must be allowed prior to the initiation of exercise to achieve optimal pain, functional and physiological outcomes and that losartan is a viable candidate for translational studies. Key points: Our tibial fracture orthopaedic injury model in mice recapitulates the major manifestations of complex trauma, including nociceptive sensitization, bone fracture, muscle fibrosis and muscle fibre loss.Delayed exercise after complex orthopaedic trauma results in decreased muscle fibrosis and improved painLosartan, an angiotensin‐receptor blocker with anti‐fibrotic abilities, recapitulates the effect of exercise on post‐injury recovery and may provide an enhanced recovery option for those who are unable to exercise after injury [ABSTRACT FROM AUTHOR]

The article presents the conducted study to determine the role of bradykinin (BK) receptors in pain associated with acute pancreatitis. In the study, caerulein injection in rats resulted in tissue damage characterized by edema, acinar cell necrosis and interstitial hemorrhage, among others. It defines acute pancreatitis as the severe inflammation in the pancreas due to such causes as alcoholism and gallstones.

The article discusses the study conducted to investigate the impact of mild noxious heat stimuli on the neuronal activity in the cingulate cortex (CG) of rats with sciatic nerve ligation. The mild noxious heat stimuli administered to rats seven days after sciatic nerve ligation produced flinching behaviors and resulted in an increase in glutamate release in the CG, and phosphorylated-NR1-positive cells, under a neuropathic pain.

Introduction: Routine preoperative testing for low-risk surgeries without a clinical indication should be avoided; however, such tests are still frequently performed in Japan. This study was performed to assess the impact of routine preoperative tests in low-risk surgery in a Japanese medical setting., Methods: We performed a retrospective chart review to examine the utility of routine tests with respect to anesthetic management and postoperative complications in all patients aged ≥ 18 years whom ophthalmologists consulted with anesthesiologists before ophthalmologic surgery under general anesthesia., Results: During the 10-year study period, 1,234 anesthetic consultations and 1,211 routine preoperative tests (laboratory tests, chest X-rays, and electrocardiograms) were performed in Toyama University Hospital. In total, 59 patients (4.8% of the study population) canceled surgery after a battery of preoperative evaluation. Among them, 10 patients had incidental abnormalities that necessitated additional tests, and only three patients (0.2%) canceled surgery. In-hospital postoperative complications developed in nine patients (0.7%) whose routine test results made it difficult to predict development of these adverse events. No severe life-threatening events were noted in this survey., Conclusions: Routine tests prior to eye surgery for adults were of low value for perioperative management and prediction of development of in-hospital complications in this Japanese medical setting. Anesthesiologists and ophthalmologists should selectively order preoperative tests based on the medical interview and physical examination., Competing Interests: None, (Copyright © Japan Medical Association.)

Carcinosarcoma is defined as a malignant neoplasm that is composed of both carcinomatous and sarcomatous components. The occurrence of carcinosarcoma in the bone is extremely rare. In this report, we describe the third documented de novo case of carcinosarcoma of the bone. A 59-year-old Japanese female presented with a painful tumor in her right lower leg. Plane radiography revealed an osteolytic destructive lesion with periosteal reaction and mineralization in the right fibula. Resection of the fibula tumor was performed under a clinical diagnosis of chondrosarcoma. Histopathological study revealed that the tumor was comprised of three components. The main component was proliferation of small round to short spindle cells (approximately 50%), and the remaining components were chondrosarcoma (30%) and squamous cell carcinoma (20%). Immunohistochemically, SOX9 was expressed in the small round to spindle cells and chondrosarcoma component, and p63 and p40 were expressed in all three components. Accordingly, an ultimate diagnosis of carcinosarcoma of the bone was made. The clinicopathological analysis of carcinosarcoma of the bone revealed that this type of tumor affects the middle-aged to elderly persons and occurs in the long bone. All three de novo cases had chondrosarcoma and squamous cell carcinoma components. One of the 3 patients died of the disease. The histogenesis of carcinosarcoma of the bone remains a matter of controversy, although a multpotential stem cell theory has been proposed. Additional studies are required to clarify the clinical behavior and histogenesis of carcinosarcoma of the bone.