Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumour microenvironment. CAFs have recently attracted attention for their function as a regulator of immune cell recruitment and function in addition to their tumour-promoting roles. In this study, we aimed to determine the role of CAFs on monocyte recruitment and macrophage polarization in breast cancer. CAFs, which were α-SMA expressing fibroblasts in contrast to normal fibroblasts (NFs), effectively recruited monocytes. Recruitment of monocytes by CAFs might be mediated by monocyte chemotactic protein-1 (MCP-1) as well as stromal cell-derived factor-1 (SDF-1) cytokines. CAFs differentiated the recruited monocytes into M2-like macrophages which are capable of exerting their immunosuppressive roles via the PD-1 axis. CAF-educated monocytes exhibited strong immune suppression unlike NF-educated monocytes and enhanced the motility/invasion of breast cancer cells in addition to increasing the expressions of epithelial–mesenchymal transition (EMT)-related genes and vimentin protein in cancer cells. CAF-educated M1 macrophages displayed increased expression of M2 markers and production of anti-inflammatory cytokine IL-10 in contrast to decreased production of pro-inflammatory cytokine IL-12 compared with control M1 macrophages; suggesting that CAFs were also able to induce the trans-differentiation of M1 macrophages to M2 macrophages. We then investigated the relationship between the infiltration of CAFs and tumour associated macrophages (TAMs) using tissue samples obtained from breast cancer patients. High grade of CAFs significantly correlated with the number of TAMs in human breast cancer tissue samples. It was also associated with higher Ki-67 proliferation index, and higher tumour volume. This result is in line with our finding of increased breast cancer cell proliferation due to the effects of CAF-educated monocytes in vitro . Our results concluded that CAFs play pivotal roles in sculpturing the tumour microenvironment in breast cancer, and therapeutic strategies to reverse the CAF-mediated immunosuppressive microenvironment should be taken into consideration.

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The final hearing status of patients with cleft palate is a result of a combination of surgical correction, developmental factors, and treatment of middle ear disease. Early and aggressive ventilation tube placement is the standard of cleft care in many countries. Our long-term hearing outcome is relatively good in a population not treated with routine insertion of ventilation tubes. The majority of patients also have satisfactory speech. Patients with cleft palate should have close follow-up for middle ear disease, but further research is warranted to determine the aggressive usage of ventilation tubes.

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Diabetic foot is a serious complication of diabetes mellitus and the risk of lower extremity amputation is very high in this population when compared with people without diabetes. We have previously reported the lower-extremity amputation rate and significant factors in determining the risks for patients who had been admitted to Hacettepe University Hospital, a tertiary reference center for Turkey, between the years 1992 and 1996. In January 2000, a diabetic foot care team including an infectious diseases specialist, orthopaedic surgeons, endocrinologists, a plastic and reconstructive surgeon, a radiologist, and a diabetic foot nurse was assembled. To determine whether a change has occurred in the rate and the risk factors of lower extremity amputations after the establishment of this team, medical records of 66 patients (39 men, 27 women) with diabetic foot who had been admitted to Hacettepe University Hospital between 2000 and 2002 have now been retrospectively analysed. The grade distribution of diabetic foot according to Wagner classification was quite similar in the two studies (grade 1: 0 % vs. 4.5 %, grade 2: 15.6 % vs. 19.7 %, grade 3: 48 % vs. 33.3 %, grade 4: 24.4 % vs. 30.3 %, grade 5: 11.5 % vs. 12.1 % in the former and current study, respectively). The overall amputation rate in the current study was 39.4 % (36.7 % in the former study). Ray amputation (35 %) and below-knee amputations (30 %) were the two most commonly applied procedures. The rates of Syme, above knee, other amputations (i.e., Boyd, talonavicular amputations and partial calcanectomy) were 8 %, 8 % and 19 %, respectively. These data suggest that amputation is still a frequently encountered outcome for our patients with diabetic foot, but the amputation profile has changed. The implementation of a diabetic foot care team has relatively decreased the rate of major amputations in an attempt for limb salvage to improve the quality of life of the patients. Presence of osteomyelitis, peripheral vascular disease and gangrene still remain as significant predictors of amputation in our population.