Design optimization of functionally graded lattice infill total hip arthroplasty stem for stress shielding reduction.

Reducing stress shielding of stem-inserted femurs in total hip arthroplasty caused by the high stiffness of the stem is an emerging medical engineering issue. In this study, a numerical design optimization methodology lattice infill stem was developed to realize a stem, balancing the low stiffness and strength requirements. Two pairs of models and loading conditions were introduced for the stress shielding and strength criteria. The objective function was set as the weighted sum of the criteria. Its effective density distribution was optimized by handling the representative size of the lattice as a design variable, assuming that the so-called body-centered cubic lattice was the base shape of the lattice. In the optimization, the approximated model of the lattice was handled as a solid material with the effective physical properties of the lattice derived by the homogenization method. After optimization, the detailed lattice stem geometry was modeled based on the obtained optimal lattice distribution, and the actual performance was numerically evaluated. The developed stem increased the stress applied to the remaining femur by 32.4% compared with the conventional stem.

[Nivolumab and Gamma Knife Radiosurgery for a Gastric Cancer Patient with Brain Metastasis-A Case Report].

The prognosis of patients with brain metastasis is very poor. Very few cases of combined treatment with nivolumab(240 mg/body, day 1, q2w, a programmed cell death-1[PD-1]inhibitor)and gamma knife radiosurgery(GKR)(27 Gy/3 Fr) for gastric cancer patients with brain metastasis have been reported. Here, we discuss the case of a 55-year-old man with HER2-positive poorly differentiated gastric adenocarcinoma with multiple bone and intra-abdominal lymph node metastases. After 25 courses of SOX(oxaliplatin 100 mg/m2, day 1, q3w plus S-1 120 mg/day, day 1-14, po, q3w)plus trastuzumab( 6 mg/kg, q3w)treatment, brain metastasis was detected. Subsequently, combined treatment with GKR and nivolumab(8 courses, anti-PD-1 monotherapy)was initiated. Both intra-abdominal and brain lesions decreased in response to this treatment, showing that combined therapy with nivolumab and GKR could be effective for treating gastric cancer patients with brain metastasis.

Successful resection of asymptomatic paraganglioma mimicking lymph node metastasis from gastric cancer 5 years after distal gastrectomy:a case report.

A 61-year-old man visited our hospital for treatment of a retroperitoneal tumor. The patient had undergone distal gastrectomy for gastric cancer in the past. At 5 years after distal gastrectomy, a retroperitoneal tumor with a large diameter of 30mm was detected by computed tomography and the patient underwent chemotherapy for suspected lymph node metastasis from gastric cancer at a local hospital. However, the retroperitoneal tumor gradually increased, and it was diagnosed finally as asymptomatic paraganglioma. The patient underwent tumor resection and made a satisfactory recovery. He was discharged 11 days after the surgery in a good general condition. Here, we report a case of successful resection of asymptomatic paraganglioma in a patient 5 years after distal gastrectomy for gastric cancer.

Enantioselective, biocatalytic reduction of 3-substituted cyclopentenones: application to the asymmetric synthesis of an hNK-1 receptor antagonist.

A convergent and enantioselective route to the hNK-1 receptor antagonist (1) is described, which sets all six stereogenic centers with high diastereoselectivity and delivers 1 in only 11 steps and 23% overall yield. The process was enabled by the development of the enantioselective enzymatic reduction of 3-functionalized cyclopentenones and stereospecific Pd-catalyzed etherification coupling of fragments 6 and 7.

Discovery of novel diarylketoxime derivatives as selective and orally active melanin-concentrating hormone 1 receptor antagonists.

Optimization of the lead 2a led to the identification of a novel diarylketoxime class of melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. Our focus was directed toward improvement of hERG activity and metabolic stability. The representative derivative 4b showed potent and dose-dependent body weight reduction in diet-induced obese (DIO) C57BL/6J mice after oral administration. The synthesis and structure-activity relationships of the novel diarylketoxime MCH-1R antagonists are described.