Superior migration ability of umbilical cord-derived mesenchymal stromal cells (MSCs) toward activated lymphocytes in comparison with those of bone marrow and adipose-derived MSCs.

Introduction: Mesenchymal stromal cells (MSCs) are activated upon inflammation and/or tissue damage and migrate to suppress inflammation and repair tissues. Migration is the first important step for MSCs to become functional; however, the migration potency of umbilical cord-derived MSCs (UC-MSCs) remains poorly understood. Thus, we aimed to assess the migration potency of UC-MSCs in comparison with those of bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AD-MSCs) and investigate the influence of chemotactic factors on the migration of these cells. Methods: We compared the migration potencies of UC-, BM-, and AD-MSCs toward allogeneic stimulated mononuclear cells (MNCs) in mixed lymphocyte reaction (MLR). The number of MSCs in the upper chamber that migrated toward the MLR in the lower chamber was counted using transwell migration assay. Results and discussion: UC-MSCs showed significantly faster and higher proliferation potencies and higher migration potency toward unstimulated MNCs and MLR than BM- and AD-MSCs, although the migration potencies of the three types of MSCs were comparable when cultured in the presence of fetal bovine serum. The amounts of CCL2, CCL7, and CXCL2 in the supernatants were significantly higher in UC-MSCs co-cultured with MLR than in MLR alone and in BM- and AD-MSCs co-cultured with MLR, although they did not induce the autologous migration of UC-MSCs. The amount of CCL8 was higher in BM- and AD-MSCs than in UC-MSCs, and the amount of IP-10 was higher in AD-MSCs co-cultured with MLR than in UC- and BM-MSCs. The migration of UC-MSCs toward the MLR was partially attenuated by platelet-derived growth factor, insulin-like growth factor 1, and matrix metalloproteinase inhibitors in a dose-dependent manner. Conclusion: UC-MSCs showed faster proliferation and higher migration potency toward activated or non-activated lymphocytes than BM- and AD-MSCs. The functional chemotactic factors may vary among MSCs derived from different tissue sources, although the roles of specific chemokines in the different sources of MSCs remain to be resolved.

Machine learning for classification of postoperative patient status using standardized medical data.

BACKGROUND AND OBJECTIVE: Real-world evidence is defined as clinical evidence regarding the use and potential benefits or risks of a medical product derived from real-world data analyses. Standardization and structuring of data are necessary to analyze medical real-world data collected from different medical institutions. An electronic message and repository have been developed to link electronic medical records in this research project, which has simplified the data integration. Therefore, this paper proposes an analysis method and learning health systems to determine the priority of clinical intervention by clustering and visualizing time-series and prioritizing patient outcomes and status during hospitalization. METHODS: Common data items for reimbursement (Diagnosis Procedure Combination [DPC]) and clinical pathway data were examined in this project at each participating institution that runs the verification test. Long-term hospitalization data were analyzed using the data stored in the cloud platform of the institutions' repositories using multiple machine learning methods for classification, visualization, and interpretation. RESULTS: The ePath platform contributed to integrate the standardized data from multiple institutions. The distribution of DPC items or variances could be confirmed by clustering, temporal tendency through the directed graph, and extracting variables that contributed to the prediction and evaluation of SHapley Additive Explanation effects. Constipation was determined to be the risk factor most strongly related to long-term hospitalization. Drainage management was identified as a factor that can improve long-term hospitalization. These analyses effectively extracted patient status to provide feedback to the learning health system. CONCLUSIONS: We successfully generated evidence of medical processes by gathering patient status, medical purposes, and patient outcomes with high data quality from multiple institutions, which were difficult with conventional electronic medical records. Regarding the significant analysis results, the learning health system will be used on this project to provide feedback to each institution, operate it for a certain period, and analyze and re-evaluate it.

Can digital health technologies exacerbate the health gap? A clustering analysis of mothers' opinions toward digitizing the maternal and child health handbook.

BACKGROUND: The use of mobile health has increased worldwide, but along with its increased utilization comes the risk of the digital divide, inequity in access to information and communications technologies, exerting greater influence on health inequity caused by socioeconomic determinants of health. There is a growing need to investigate whether the digitization of existing health interventions has a risk of worsening the health gap. METHODS: We investigated the attitudes of mothers and pregnant women toward digitization of the Maternal and Child Health Handbook (MCHH), a popular personal health record (PHR) used by almost every pregnant woman or mother in Japan, using a cross-sectional survey. We determined sociodemographic factors associated with favorable opinions toward digitization using a multivariate regression model. We then grouped the participants using partitioning around medoids clustering, a machine-learning approach, to interpret their varying attitudes toward digitization in light of their sociodemographic characteristics as well as their affinity toward the paper MCHH. FINDINGS: Higher income and educational level, older age, and less reliance on the MCHH were significantly associated with favorable opinion toward digitization. Clustering analysis identified four latent clusters. The cluster with the highest socioeconomic status (SES) was the most favorable toward digitization, while two clusters with the lowest SES, one of which relied heavily on the paper MCHH, were less favorable of digitization compared to the high SES cluster. The final cluster was comprised of mothers with the experience of raising multiple children and did not rely heavily on the MCHH. INTERPRETATION: Our study identified a socioeconomic divide in opinions toward digitization of an existing health intervention. A hasty digitization may result in an unbalanced uptake of the digitized health intervention among different social classes.

Uterine cervical squamous cell carcinoma with reactive multinucleated giant cells expressing cluster of differentiation 204: A case report and literature review.

Uterine cervical squamous cell carcinoma (SCC) with reactive multinucleated giant cells (MGC) is extremely rare. Here we present the case of a 49-year-old woman treated with radical hysterectomy, bilateral adnexectomy and lymph node dissection. Histologically, the cervical tumor was diagnosed as nonkeratinizing SCC of pT1b1N0M0, with negative surgical margin. Many MGC including osteoclast-like giant cells with immunohistochemical expression of cluster of differentiation 204, a marker for the M2 macrophage, were present around the tumor nests. The patient received postoperative radiation therapy and achieved 22 months of disease-free survival after the surgery. M2 macrophages promote aggressiveness of the carcinoma and it is suggested that SCC of the cervix with reactive MGC might have poor prognosis; however, our case paradoxically showed a favorable course. From literature review of six cases, including our case, the effect of MGC-reaction may vary with respect to other factors, such as age, cancer stage or histological type.

Two cases of adenocarcinoma in situ arising in lobular endocervical glandular hyperplasia indicating localization of mucin on the cluster surface as an early cytological finding of malignant transformation.

Lobular endocervical glandular hyperplasia (LEGH) is an endocervical glandular hyperplastic lesion containing pyloric gland-like mucin, and has recently been recognized as a precursor lesion of malignant glandular lesions of the endocervix. The pyloric gland-like mucin contained in LEGH and gastric-type adenocarcinoma is observed as golden-yellowish by Papanicolaou staining. However, to our knowledge, the chronological course of the endocervical cytology of LEGH, eventually resulting in malignancy, has never been demonstrated to date. Here, we report two cases of gastric-type adenocarcinoma in situ (AIS) arising in LEGH, together with an analysis of their cytological course. In both cases, localization of mucin on the surface of glandular cell clusters was observed prior to nuclear atypia in endocervical cytology. In addition, the diagnosis of gastric-type AIS arising in LEGH was confirmed by pathological diagnosis of hysterectomy specimens in both cases. Histologically, all glandular cells of the LEGH without nuclear atypia contained a large amount of PAS-positive mucin. On the other hand, in atypical glandular cells, localization of the mucin on the luminal surface was observed, although mucin was abundant throughout the cytoplasm in some areas. Our cases show the course of acquirement of cytological atypia of LEGH, and indicate the significance of localization of mucin on the surface of glandular cell clusters as an early finding of the malignant transformation of LEGH in endocervical cytology. Our results indicate that the distribution of mucin in glandular cells should be analyzed together with nuclear atypia in the endocervical cytology of suspected cases of LEGH.

[A Patient with Recurrent Ovarian Cancer Who Was Hypersensitive to Carboplatin Exhibited Complete Response to Gemcitabine and Nedaplatin].

A 57-year-old multiparous woman with FIGO stage IV ovarian cancer underwent primary surgery and was administered postoperative chemotherapy consisting of paclitaxel and carboplatin (TC). Complete response was confirmed on computed tomography. After a 20-month platinum free interval (PFI), an elevated serum CA125 level and recurrence in the peritoneum were confirmed, and she was retreated with TC as second-line chemotherapy. A hypersensitivity reaction occurred after administering the second dose of carboplatin; therefore, carboplatin was changed to nedaplatin. Complete response was confirmed on computed tomography, and the serum CA125 level returned to normal. After an 8-month PFI, an elevated serum CA125 level and recurrence in the peritoneum and liver were confirmed, and she was treated with 6 cycles of combination chemotherapy consisting of gemcitabine (1,000 mg/m2: day 1 and 8 q3 weeks)and nedaplatin (80 mg/m2: day 1 q3 weeks). Only cytopenia (grade 2: CTCAE v4.0) was noted as a complication during chemotherapy. Complete response was confirmed on computed tomography. This report presents the case of a patient with recurrent ovarian cancer who was platinum sensitive and successfully treated with gemcitabine and nedaplatin after showing a hypersensitivity reaction to carboplatin.

[A case of stage IVb vulvar cancer effectively treated by concurrent chemoradiotherapy with cisplatin].

A 72-year-old woman was hospitalized because of a 10 cm tumor in her right inguinal area. Furthermore, a 6 cm tumor mass was observed in her right vulva. Computed tomography revealed multiple swollen lymph nodes in the para-aortic and pelvic areas. On the basis of these findings, the patient was diagnosed with stage IVb squamous cell carcinoma of the vulva. Radiation therapy of 67.4 Gy/33 Fr was administered to the pelvis, inguinal area and vulva. Four courses of chemotherapy with cisplatin (40 mg/m(2)) were concurrently administered every week during radiation therapy. The response to chemoradiotherapy was assessed to be complete. The patient has been doing well without any recurrence for 24 months.