A positive feedback loop driven by fibronectin and IL-1ß sustains the inflammatory microenvironment in breast cancer.

Inflammatory alterations of the extracellular matrix shape the tumor microenvironment and promote all stages of carcinogenesis. This study aims to determine the impact of cellular fibronectin on inflammatory facets of tumor-associated macrophages (TAMs) in breast cancer. Cellular fibronectin (FN) harboring the alternatively spliced extra domain A (FN-EDA) was determined to be a matrix component produced by the triple-negative breast cancer (TNBC) cells. High levels of FN-EDA correlated with poor survival in breast cancer patients. The proinflammatory cytokine IL-1ß enhanced the expression of cellular fibronectin including FN-EDA. TAMs were frequently observed in the tumor areas rich in FN-EDA. Conditioned media from TNBC cells induced the differentiation of CD206+CD163+ macrophages and stimulated the STAT3 pathway, ex vivo. In the macrophages, the STAT3 pathway enhanced FN-EDA-induced IL-1ß secretion and NF-κB signaling. In conclusion, our data indicate a self-reinforcing mechanism sustained by FN-EDA and IL-1ß through NF-κB and STAT3 signaling in TAMs which fosters an inflammatory environment in TNBC.

Human splenic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are strategically located immune regulatory cells in cancer.

In contrast to the mouse, functional assets of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in the human spleen remain to be better elucidated. Here, we report that the spleen in gastric and pancreatic cancer adopts an immune regulatory character, harbors excessive amount of PMN-MDSC, and anatomically enables their interaction with T cells. Compared to the peripheral blood, the spleen from cancer patients contained significantly higher levels of low-density PMN-MDSC, but not early-stage MDSC (e-MDSC) and monocytic-MDSC (M-MDSC). Low-density fraction of polymorphonuclear (PMN) cells was enriched in immature myeloid cells and displayed higher levels of CD10, CD16, and ROS than their blood-derived counterparts. They were also positive for PD-L1, LOX-1, and pSTAT3. The white pulp and periarteriolar lymphoid sheath (PALS) were strategically surrounded by PMN cells that were in contact with T cells. Unlike those from the blood, both low-density and normal-density PMN cells from the human spleen suppressed T cell proliferation and IFN-γ production. Independent of clinical grade, high PMN-MDSC percentages were associated with decreased survival in gastric cancer. In summary, our results outline the immune regulatory role of the spleen in cancer where neutrophils acquire MDSC functions and feasibly interact with T cells.

CD66b+ monocytes represent a proinflammatory myeloid subpopulation in cancer.

Myeloid-derived suppressor cells (MDSC) populate the peripheral blood and contribute to immune regulation in cancer. However, there is limited knowledge on the myeloid cell types with proinflammatory capacities that may serve as opponents of MDSC. In the circulation of cancer patients, a monocyte subpopulation was identified with a specific immunophenotype and transcriptomic signature. They were predominantly CD14+CD33hiCD16-/+HLA-DR+/hi cells that typically expressed CD66b. In accordance with the transcriptomics data, NALP3, LOX-1 and PAI-1 levels were also significantly upregulated. The CD66b+ monocytes displayed high phagocytic activity, matrix adhesion and migration, and provided costimulation for T cell proliferation and IFN-γ secretion; thus, they did not suppress T cell responses. Irrespective of clinical stage, they were identified in various cancers. In conclusion, the CD66b+ monocytes represent a novel myeloid subpopulation which is devoid of immune regulatory influences of cancer and displays enhanced proinflammatory capacities.

The impact of TI-RADS in detecting thyroid malignancies: a prospective study.

INTRODUCTION: Thyroid ultrasonography (US) is the first-step noninvasive and easily accessible diagnostic method widely used in the detection and characterization of nodular thyroid disease. We aimed to develop a TI-RADS, which is easy to apply and only relies on the counting of suspicious criteria. In order to measure the reliability of the system, we investigated its correlation with fine needle aspiration biopsy (FNAB) and post-surgery histological results. MATERIALS AND METHODS: In this prospective study, 242 patients who had undergone FNAB with simultaneous cytopathologist in the radiology department between April and August 2016 were analyzed. Before FNAB, the thyroid gland was re-evaluated with US, and TI-RADS classification was made. Demographic characteristics, family thyroid cancer history and radiotherapy history to the neck region were noted. RESULTS: Of the 242 patients, 17.3% were male (42 males/200 females). US-guided FNAB was applied to all patients. Mean age was 50 ± 13 years (min: 19, max: 82). Both FNAB and final post-surgery histology results showed that sex and age were not statistically significantly associated with malignancy (p = 0.193) TI-RADS criteria and FNAB results revealed a statistically significant association between irregular contours, the state of anteroposterior diameter being longer than transverse diameter, microcalcifications, marked hypoechogenicity, and malignancy (p < 0,05). Thirty patients were TI-RADS ≥ 4, 206 patients were TI-RADS ≤ 3 and there was a significant correlation between TI-RADS and Bethesda classification (p = 0.001). In addition, statistically significant associations were found between malignancy and family history of thyroid cancer (p = 0.035) and radiotherapy history to the neck region (p = 0.01). CONCLUSION: TI-RADS system after nodule identification is based only on the counting of suspicious criteria. It will be safe and effective to recommend follow-up with low score TI-RADS, benign characters and insufficient FNAB results, and thus, unnecessary thyroidectomy operations will be prevented. It will be easier for surgeons to recommend surgery and persuade the patients for it when patients have high TI-RADS scores. TI-RADS has high power in detecting malignancy by recommending biopsy of suspicious nodules.

The Correlation of Intraabdominal Pressure With Renal Resistive Index.

BACKGROUND: To evaluate the correlation between intraabdominal pressure (IAP) measured via the bladder and renal resistive index (RRI) measured by Doppler ultrasonography (USG). METHODS: Eighty consecutive surgical patients were included into this study. Before Doppler USG evaluation, IAP was measured by a Foley catheter via the bladder. The left and right RRI, the diameters of the inferior vena cava and portal vein were measured by colored Doppler USG. Spearman correlation analysis was used to evaluate the correlation between different measurements. Intraabdominal hypertension (IAH) was defined as of IAP ≥ 12 mmHg. Significantly different variables from the univariate analysis between patients with and without IAH were entered into backward stepwise binary logistic regression analysis of IAH as the dependent variable. P values < 0.05 were accepted as statistically significant. RESULTS: In total, 80 patients were included into study. In 27 patients (34%) IAP was normal and in 53 patients (66%) IAH was diagnosed. The Spearman correlation analysis of IAP and the ultrasonographic measurements revealed a strong correlation between RRI and IAP (P < 0.001). Patients with IAH were more likely to be diabetic and had abdominal incisional hernia compared with patients with normal IAP (P < 0.05). The results of the multivariate logistic regression analysis revealed right RRI as the only independent predictor of IAH (B: 57.04, S. E.: 13.7, P < 0.001). CONCLUSIONS: There is a strong correlation between IAP and RRI. RRI can be an alternative, noninvasive technique for the diagnosis and follow-up of IAH after further evaluations in different patient groups.

An evaluation of treatment results of emergency versus elective surgery in colorectal cancer patients.

OBJECTIVE: Colorectal cancer is still one of the most common causes of cancer related deaths in the world despite improvements in diagnosis and treatment modalities, and application of community-based screening methods. Symptoms of colorectal cancer are non-specific and usually manifest following local progression. A number of patients with advanced stage colorectal cancer present to emergency departments with obstruction as the first sign of disease without any previous symptoms. This presentation is an indication for emergency surgery that has a high rate of morbidity and mortality. In this study, we aimed to determine the factors associated with early diagnosis and survival by comparing postoperative results of colorectal cancer patients who underwent surgery under emergency or elective situation. MATERIAL AND METHODS: Files of colorectal patients treated between 2009-2013 were retrospectively analyzed. Data on patient age, gender, operation type, intraoperative results, length of hospital stay, co-morbidities, postoperative complications and pathological results were evaluated and compared. RESULTS: There was no statistical difference between groups in terms of age, gender, and pathology results (p>0.05). The difference between groups in terms of postoperative length of hospital stay, presence of co-morbid diseases, pathological stage, and postoperative complications was statistically significant (p<0.05). Length of hospital stay, advanced stage on admission, complications such as surgical site infection, evisceration, and anastomosis leakage rates were higher in patients in the emergency surgery group. CONCLUSION: Risk groups should be determined in order to diagnose colorectal cancer patients at an early stage while they are still asymptomatic, and this information should be incorporated into effective screening programs. This approach will be beneficial to treatment outcomes, complication rates, length of hospital stay, and survival and treatment results.

Diagnosis of acute pancreatitis by diffusion-weighted magnetic resonance imaging.

Diffusion-weighted magnetic resonance imaging has emerged as a successful technique in the early diagnosis of acute pancreatitis. An 82-year-old male patient suspected of acute pancreatitis refused to undergo intravenous contrast-enhanced abdominal computed tomography due to a history of previous allergic reactions to contrast medium. He was imaged with diffusion-weighted magnetic resonance imaging without the use of oral or intravenous contrast material. Diffuse hyperintensity in the pancreas with a relevant apparent diffusion coefficient map showing diffuse hypointensity was demonstrated. The findings were interpreted as restricted diffusion and were diagnostic for acute pancreatitis. Diffusion-weighted magnetic resonance imaging, an imaging modality that does not involve ionizing radiation and does not require the use of contrast material, can successfully demonstrate the manifestations of acute pancreatitis.

Appropriateness of selection criteria for CT examinations performed at an emergency department.

In the diagnosis of traumatic and nontraumatic emergencies, computed tomography (CT) is the most frequently performed procedure. The aims of this study were to find out whether CT report results can be used as a reliable tool for the diagnosis and management of patients at an emergency department and to evaluate the appropriateness of the selection criteria for CT examinations. For this reason, we analysed the emergency CT procedures according to the diagnostic hypothesis written on CT request forms, the results of the CT reports and the final diagnosis of the patients. One thousand consecutive CT procedures in the emergency department of a research hospital were retrospectively analysed. When the CT reports and the final diagnosis were evaluated, the sensitivity and specifity of the CT were found to be 0.81 and 0.85. According to the analysis of the CT reports, 55.8 % of all the patients were reported to be normal. When the patient files were examined for the final diagnosis of the patients, 55.7 % of the patients did not receive a final diagnosis related to the diagnostic hypothesis. The lowest correlation was found between the diagnostic hypothesis, the CT reports and the final diagnosis of the patients who underwent cranial CT procedure for trauma. The results of the CT reports can be used as a reliable parameter for the diagnosis and management of the patients at emergency departments. On the other hand, a high negative rate of CT reports was noted especially for the cranial CT examinations. CT selection criteria for the head trauma patients should be reconsidered. Since CT is a procedure involving ionising radiation, it is important that it is performed with the correct indications and the relevant clinical information is specified on the CT request forms.

The role of elastosonography, gray-scale and colour flow Doppler sonography in prediction of malignancy in thyroid nodules.

BACKGROUND: Ultrasound is as a noninvasive method commonly used in the work-up of thyroid nodules. This study aimed to evaluate the usefulness of sonographic and elastosonographic parameters in the discrimination of malignancy. PATIENTS AND METHODS: 150 thyroid nodules were evaluated by gray-scale, Doppler and elastosonography. The cytological analysis revealed that 141 nodules were benign and 9 were malignant. RESULTS: Orientation of the nodule was the only sonographic parameter associated with malignancy (p = 0.003). In the strain ratio analysis the best cut-off point was 1.935 to discriminate malignancy (p = 0.000), with 100% sensitivity, 76% specificity, 100% negative predictive value, 78.5% positive predictive value and 78% accuracy rate. There was a statistically significant correlation between the elasticity score and malignancy (p = 0.001). Most of the benign nodules had score 2 and 3, none of them displayed score 5. On the other hand, none of the malignant nodules had score 1 and 2, most of them displaying score 5. CONCLUSIONS: A change in the diagnostic algorithm of the thyroid nodules should be considered integrating the elastosonographic analysis.

Factors affecting the safety of drains and catheters in surgical patients.

OBJECTIVE: Drains and catheters are used for both prophylactic and therapeutic reasons in clinical practice. This study aimed to investigate the factors that affect safety of drains, catheters, nasogastric tube and central venous line in patients who underwent surgery. MATERIAL AND METHODS: Two hundred and four consecutive patients who were operated at the general surgery clinics under general anesthesia were included in the study. Factors that affect the safety of drains and catheter were followed and recorded prospectively. RESULTS: During follow-up period, 12 (5.8%) patients have experienced problems regarding safety of drains/catheters. The mean age of patients who were followed-up in terms of security problems was 63.1 (39-86) years. Eight (66.7%) patients had been operated emergently, and four (33.3%) patients electively. Three (25%) patients had psychiatric/neurological co-morbidities and 3 (25%) patients were confused due to anesthesia/intensive care unit treatment when the drain safety was broken. Eight (66.7%) patients withdrew the drains or catheters by themselves, in 2 (16.7%) patients the drains spontaneously came out and in 2 (16.7%) patients the wrong drain was withdrawn. One patient had dementia, one patient had Alzheimer's disease and one patient was being followed-up with a diagnosis of schizophrenia. In three (25%) patients the abdominal drain, in four (33.3%) patients nasogastric tube, in one (8.3%) patient intubation tube, in one (8.3%) patient central venous catheter, and in three (25%) patients multiple drains were removed. CONCLUSION: The inaccurate use of drains or re-intervention for an unintentionally removed drain causes problems regarding patient safety. Close monitoring of surgical patients in terms of security, and submission of additional measures for patients with confusion and neurological/psychiatric disorders are of great importance.

Would hyperbaric oxygen therapy be a supportive treatment method for refractory idiopathic granulomatous mastitis?

BACKGROUND: Refractory IGM causes patients to use antibiotics, steroid therapy, immunosuppressive agents for a very long time and even leads to surgical procedures resulting in the loss of breast tissue. Hyperbaric Oxygen Therapy (HBOT) is a frequently used method in the treatment of wounds that are difficult to heal. We thought that HBOT would be an alternative treatment method for refractory IGM patients. METHODS: It is a retrospective cohort study on refractory IGM patients conducted at three tertiary care treatment centers between January 2021 and July 2023. The patients were evaluated in two groups: those who only took steroid treatment and those who received HBOT and steroid treatment. The demographic and clinical characteristics of the patients, the types of treatment applied and their responses to treatment were evaluated. RESULTS: There were no significant differences generally in the demographic and clinical features in both groups. The incidence of multicentric GM was found to be higher in the HBOT group (66.67 %; p = 0.044). Although the recovery results were similar in both groups, the average daily steroid dose and duration of drug use were found to be higher in the group receiving only steroid treatment (16 mg vs. 4 mg and 270 days vs. 30 days) (p < 0.001). CONCLUSION: In our study, we showed for the first time in the literature that HBOT is effective in the treatment of refractory IGM patients. Our study needs to be supported by prospective studies evaluating cost effectiveness and possible long term complications.

Differential Diagnosis of Diabetic Foot Osteomyelitis and Charcot Neuropathic Osteoarthropathy with Deep Learning Methods.

Our study aims to evaluate the potential of a deep learning (DL) algorithm for differentiating the signal intensity of bone marrow between osteomyelitis (OM), Charcot neuropathic osteoarthropathy (CNO), and trauma (TR). The local ethics committee approved this retrospective study. From 148 patients, segmentation resulted in 679 labeled regions for T1-weighted images (comprising 151 CNO, 257 OM, and 271 TR) and 714 labeled regions for T2-weighted images (consisting of 160 CNO, 272 OM, and 282 TR). We employed both multi-class classification (MCC) and binary-class classification (BCC) approaches to compare the classification outcomes of CNO, TR, and OM. The ResNet-50 and the EfficientNet-b0 accuracy values were computed at 96.2% and 97.1%, respectively, for T1-weighted images. Additionally, accuracy values for ResNet-50 and the EfficientNet-b0 were determined at 95.6% and 96.8%, respectively, for T2-weighted images. Also, according to BCC for CNO, OM, and TR, the sensitivity of ResNet-50 is 91.1%, 92.4%, and 96.6% and the sensitivity of EfficientNet-b0 is 93.2%, 97.6%, and 98.1% for T1, respectively. For CNO, OM, and TR, the sensitivity of ResNet-50 is 94.9%, 83.6%, and 97.9% and the sensitivity of EfficientNet-b0 is 95.6%, 85.2%, and 98.6% for T2, respectively. The specificity values of ResNet-50 for CNO, OM, and TR in T1-weighted images are 98.1%, 97.9%, and 94.7% and 98.6%, 97.5%, and 96.7% in T2-weighted images respectively. Similarly, for EfficientNet-b0, the specificity values are 98.9%, 98.7%, and 98.4% and 99.1%, 98.5%, and 98.7% for T1-weighted and T2-weighted images respectively. In the diabetic foot, deep learning methods serve as a non-invasive tool to differentiate CNO, OM, and TR with high accuracy.

Effectiveness of Peripheral Nerve Block in Terms of Search for a Standardized Treatment Protocol in Diabetic Foot Patients Using Anticoagulants: A Double-Center Study.

BACKGROUND: Lower-extremity amputation for a diabetic foot is mainly performed under general or central neuraxial anesthesia. Ultrasound-guided peripheral nerve block (PNB) can be a good alternative, especially for patients who require continuous anticoagulation treatment and patients with additional comorbidities. We evaluated bleeding due to PNB application in patients with diabetic foot receiving antiplatelet or anticoagulant therapy. Perioperative morbidity and mortality and the need for intensive care hospitalization were analyzed. METHODS: This study included 105 patients with diabetic foot or debridement who underwent distal foot amputation or debridement between February and October 2020. Popliteal nerve block (17 mL of 5% bupivacaine and 3 mL of saline) and saphenous nerve block (5 mL of 2% lidocaine) were applied to the patients. Postoperative pain scores (at 4, 8, 12, and 24 hours) and complications due to PNB were evaluated. Intensive care admission and 1-month mortality were recorded. RESULTS: The most common diseases accompanying diabetes were hypertension and peripheral artery disease. No complications due to PNB were observed. Mean ± SD postoperative first analgesic need was determined to be 14.1 ± 4.1 hours. Except for one patient, this group was followed up without the need for postoperative intensive care. In 16 patients, bleeding occurred as leakage from the surgical area, and it was stopped with repeated pressure dressing. Mean ± SD patient satisfaction score was 8.36 ± 1.59. Perioperative mortality was not observed. CONCLUSIONS: Ultrasound-guided PNB can be an effective and safe anesthetic technique for diabetic patients undergoing distal foot amputation, especially those receiving antiplatelet or anticoagulant therapy and considered high risk.

A prospective evaluation of the risk factors for development of wound dehiscence and incisional hernia.

OBJECTIVE: Post-laparotomy wound dehiscence, evantration and evisceration are important complications leading to an increase in both morbidity and mortality. Incisional hernias are frequently observed following abdominal surgeries and their occurrence is related to various local and systemic factors. This study aims to analyze the factors affecting wound healing by investigating the parameters that may cause wound dehiscence, incisional hernia, sinus formation and chronic incisional pain. MATERIAL AND METHODS: The records of 265 patients who underwent major abdominal surgery were analyzed. The data on patient characteristics, medication, surgical procedure type, type of suture and surgical instruments used and complications were recorded. The patients were followed up with respect to sinus formation, incisional hernia occurrence and presence of chronic incision pain. Statistical analysis was performed using SPSS 10.00 program. The groups were compared via chi-square tests. Significance was determined as p<0.05. Multi-variate analysis was done by forward logistic regression analysis. RESULTS: 115 (43.4%) patients were female and 150 (56.6%) were male. Ninety-four (35.5%) patients were under 50 years old and 171 (64.5%) were older than 50 years. The median follow-up period was 28 months (0-48). Factors affecting wound dehiscence were found to be; creation of an ostomy (p=0.002), postoperative pulmonary problems (p=0.001) and wound infection (p=0.001). Factors leading to incisional hernia were; incision type (p=0.002), formation of an ostomy (p=0.002), postoperative bowel obstruction (p=0.027), postoperative pulmonary problems (p=0.017) and wound infection (p=0.011). CONCLUSION: Awareness of the factors causing wound dehiscence and incisional hernia in abdominal surgery, means of intervention to the risk factors and taking relevant measures may prevent complications. Surgical complications that occur in the postoperative period are especially related to wound healing problems.

Determination of Diabetes Health Literacy Levels of Patients Followed Up With Diabetic Foot Diagnosis: A Cross-Sectional Descriptive Study.

The number of studies on the diabetes health literacy of patients with diabetic foot is very limited. The aim of this study was to determine the diabetes health literacy levels of patients with diabetic foot. The data in this cross-sectional, descriptive study were collected using a sociodemographic data collection form and the Health Literacy Scale (HLS). Data were analyzed using SPSS for Windows Version 25.0 software. The HLS total score was 35.96 ± 10.70, and the Functional, Interactive and Critical subscale scores were 11.90 ± 5.04, 13.10 ± 4.80, and 10.96 ± 4.19, respectively. The diabetic health literacy level of the patients was seen to be affected by general education level, the status of having received education about diabetes, and family history of diabetes (P < .05). The diabetes health literacy level of patients with diabetic foot can be said to be low. This demonstrates the necessity of determining and increasing the health literacy levels of patients diagnosed with diabetes before the development of diabetic foot.

Radiomics method in the differential diagnosis of diabetic foot osteomyelitis and charcot neuroarthropathy.

OBJECTIVES: Our study used a radiomics method to differentiate bone marrow signal abnormality (BMSA) between Charcot neuroarthropathy (CN) and osteomyelitis (OM). METHODS AND MATERIALS: The records of 166 patients with diabetic foot suspected CN or OM between January 2020 and March 2022 were retrospectively examined. A total of 41 patients with BMSA on MRI were included in this study. The diagnosis of OM was confirmed histologically in 24 of 41 patients. We clinically followed 17 patients as CN with laboratory tests. We also included 29 nondiabetic patients with traumatic (TR) BMSA on MRI as the third group. Contours of all BMSA on T 2 - and T1 -weighted images in three patient groups were segmented semi-automatically on ManSeg (v.2.7d). The T1 and T2 features of three groups in radiomics were statistically evaluated. We applied the multi-class classification (MCC) and binary-class classification (BCC) methodologies to compare results. RESULTS: For MCC, the accuracy of Multi-Layer Perceptron (MLP) was 76.92% and 84.38% for T1 and T2, respectively. According to BCC, for CN, OM, and TR BMSA, the sensitivity of MLP is 74%, 89.23%, and 76.19% for T1, and 90.57%, 85.92%, 86.81% for T2, respectively. For CN, OM, and TR BMSA, the specificity of MLP is 89.16%, 87.57%, and 90.72% for T1 and 93.55%, 89.94%, and 90.48% for T2 images, respectively. CONCLUSION: In diabetic foot, the radiomics method can differentiate the BMSA of CN and OM with high accuracy. ADVANCES IN KNOWLEDGE: The radiomics method can differentiate the BMSA of CN and OM with high accuracy.

Elevated HbA1c level associated with disease severity and surgical extension in diabetic foot patients.

BACKGROUND: Diabetic foot is a complex syndrome that is associated with other diabetic complications, such as peripheral arte-rial disease and peripheral neuropathy. Optimization of plasma glucose and glycated hemoglobin (HbA1c) is one of the main principles of standard care and treatment approaches in individuals with diabetes mellitus (DM). In this study, the relationship of HbA1c level at the time of diagnosis was evaluated with diabetic foot disease severity score and surgical extension in patients with Type 2 DM. METHODS: This study included 301 consecutive patients who were diagnosed with diabetic foot in the general surgery diabetic foot clinic and were hospitalized for surgery. The relationships between the HbA1c levels of the patients with the Wagner and PEDIS (Perfusion, Extent, Dept, Infection, Sensation) classification system grades, and the surgical procedures performed were analyzed and the treatment outcomes were evaluated. RESULTS: It was determined that there was a 90% statistically significant relationship between HbA1c values of ≥10.1% and the de-velopment of Wagner Grade 4 diabetic foot ulcer (DFU) (P=0.037). A strong statistically significant relationship at the rate of 85% was determined between HbA1c values of ≥10.1% and the development of PEDIS Grade 3 ulcers. As the HbA1c values increased, so there was determined to be a statistically significant relationship with the development of PEDIS Grade 3 ulcer (P=0.003). In the comparison of the HbA1c values according to the type of surgery performed, a weak relationship was determined at the rate of 26%, and it was determined that as the HbA1c values increased, so there could be an increase in the amputation level. CONCLUSION: The results of this study showed that as HbA1c values at diagnosis increased in patients with diabetic foot; Wagner/PEDIS grades, disease severity, surgical extension, amputation level, and tissue loss increased. To reduce the severity of diabetic foot disease and prevent amputation, compliance with diabetic treatment and glycemic control should be increased.

3D printed hydrogel scaffold promotes the formation of hormone-active engineered parathyroid tissue.

The parathyroid glands are localized at the back of the thyroid glands in the cervical region and are responsible for regulation of the calcium level in the blood, through specialized cells that sense Ca2+and secrete parathyroid hormone (PTH) in response to a decline in its serum level. PTH stimulates the skeleton, kidneys and intestines and controls the level of Ca2+through specialized activities. Iatrogenic removal of the parathyroid gland, as well as damage to its vascular integrity during cauterization are some of the common complications of thyroid surgery. Therefore, regeneration and/or replacement of malfunctioning parathyroid tissue is required. Tissue engineering is an emerging and promising field for patients with organ failure with recent pioneering clinical applications. The success of tissue engineering strategy depends on the use of proper cells, bioactive factors that stimulate the activities of these cells and scaffolds that are produced to recapitulate the tissue structure and support the function of the engineered tissues. 3D printing is a developing strategy for the production of these scaffolds by providing a delicate control over their structure and properties. In this study, human primary parathyroid cells were successfully isolated and their viability and ability to secrete PTH upon stimulation with different levels of Ca2+were shownin vitro. These cells were then seeded onto 3D printed alginate scaffolds and 3D bioprinted within alginate bioink, and cell viability as well as the ability to secrete PTH upon stimulation were also demonstrated. Therefore, functional hormone-active parathyroid tissue substitute was engineeredin vitrothrough 3D printed hydrogels and autologous cells.