The Systematic Effect of Mesenchymal Stem Cell Therapy in Critical COVID-19 Patients: A Prospective Double Controlled Trial.

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-ß, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.

Mesenchymal stem cells treatment in COVID-19 patient with multi-organ involvement.

The aim of this study is to evaluate the therapeutic effect of mesenchymal stem cells (MSCs) in a severe case of brain and multiple organ involvement in a patient with COVID-19. Here, a 51-year-old male patient with multi-organ involvement due to COVID-19 infection and developing cardiac arrest is presented. MSCs were transplanted to the patient four times systematically and once intrathecally. As a result, the application of MSCs has been found to have a healing effect on organs in this patient with severe COVID-19 infection. In addition, transplantation of MSCs both systematically and intrathecally is considered to be effective in the treatment of the central nervous system (Tab. 2, Fig. 2, Ref. 24). Keywords: mesenchymal stem cell, COVID-19, organ involvement.

The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Differential Diagnosis of Simple and Hydatid Cysts of the Liver.

INTRODUCTION: The present study indicates that simple and hydatid cysts in liver are a common health problem in Turkey. The aim of the study is to differentiate different types of hydatid cysts from simple cysts by using diffusion-weighted images. MATERIALS AND METHODS: In total, 37 hydatid cysts and 36 simple cysts in the liver were diagnosed. We retrospectively reviewed the medical records of the patients who had both ultrasonography and magnetic resonance imaging. We measured apparent diffusion coefficient (ADC) values of all the cysts and then compared the findings. RESULTS: There was no statistically meaningful difference between the ADC values of simple cysts and type 1 hydatid cysts. However, for the other types of hydatid cysts, it is possible to differentiate hydatid cysts from simple cysts using the ADC values. CONCLUSION: Although in our study we cannot differentiate between type I hydatid cysts and simple cysts in the liver, diffusion-weighted images are very useful to differentiate different types of hydatid cysts from simple cysts using the ADC values.

Incidental thyroid lesions on FDG-PET/CT: a prevalence study and proposition of management.

AIM: Thyroid incidentaloma is defined as an unsuspected, asymptomatic thyroid lesion that is discovered on an imaging study. The purpose of this study is to determine incidentally identified thyroid lesions by FDG-PET/CT in cancer patients by virtue of preoperative staging and to pay attention how should be the management of these patients with thyroid lesion. METHODS: From January 2011 to January 2013, 2654 patients underwent FDG-PET/CT in our institution. Among them, 34 patients had thyroid incidentaloma. All patients underwent ultrasonographic (US) examination. If there is a nodul, fine needle aspirations (FNA) were performed to these patients. We did not perform FNA to patients who had diffuse thyroid uptake. Patients were divided into two groups; malign and non-malign patients according to FNA histo-pathologic results. Group 1 (N.=11) diagnosed malignancy in histo-pathologic evaluation, group 2 (N.=23) could not diagnosed malignancy in histo-pathologic, clinic and radiologic evaluation. These two groups were compared statistically in terms of SUV max levels that reached in PET examinations. RESULTS: Incidentally thyroid lesions were found in 34 patients in the course of FDG-PET/CT examination (25 females and 9 males), mean age 57.7 years. Nodular goitre in 12 patients, hyperthyroidism in 2 patients, sub-clinic hyperthyroidism in 3 patients and hashimoto thyroiditis in 6 patients were diagnosed in non-malignancy group (Group-2). Group 1 included 11 patients with incidentally diagnosed thyroid malignancy. 11 patients malignancy diagnoses were verified by FNA and 9 of them were operated. In PET evaluation thyroid up-take was diffuse in 9 patients, at left lob in 12 patients and at right lop in 13 patients. When we compared the groups according to SUV max levels; we found that malignant thyroid lesions had a significantly higher (P<0.001) SUVmax than benign thyroid lesions. A cut off SUVmax value (>6.2) was found in the study. CONCLUSION: The incidental finding of focal thyroid uptake on FDG-PET scanning has an elevated malignancy risk from other thyroid nodules. According to our knowledge diagnose, treatment and follow-up of these patients should be in multidiscipliner approach. Oncology, endocrinology, endocrine surgeon, interventional radiology, pathology and psychiatry should be gathered in multidiscipliner team. For these reason these patients need more careful evaluation.

Unpredictable behavior of breast phyllodes tumors.

OBJECTIVE: Phyllodes Tumor is a rare fibroepithelial breast tumor with variable malignant potential. These tumors that currently accepted nomenclature are benign, borderline and malignant according to the World Health Organization. It tends to behave in a benign way but it may undergo a malignant transformation. The purpose of this study was to present our Case load of phyllodes tumor, and evaluate the management and follow-up the behavior of these tumors. PATIENTS AND METHODS: 36 patients with phyllodes tumor were treated in Bezmialem Vakif University and Okmeydani Training and Research Hospitals analyzed retrospectively. Demographics, presenting symptoms, history, local examination, preoperative clinical diagnosis, treatment, postoperative histopatology, follow-up period were evaluated retrospectively and studied. RESULTS: A total of 36 patients treated for phyllodes tumor were analyzed. Mean age of the patients was 38 (14-79) and all were females. The presentation of the patients was breast lump in all cases, either as a primary or recurrent lump presentation. The right and left breast were affected 58% and 42% respectively. 34 of these 36 cases are briefly mentioned in this paper but the two cases, one with sarcomatous malignant transformation and the other with fatal metastatic phyllodes tumor in an adolescent female are discussed in detail. The mean duration of the symptomatic mass was 9.8 ± 7.3 months (range 0.5 to 24). CONCLUSIONS: Phyllodes tumor is a type of tumor that may be benign or malignant. The type with malignant features may be fatal. The tumors diagnosed as benign may transform and become malignant because of unknown reasons and may be an aggressive tumor.

Use of laparoscopic common bile duct exploration for failed endoscopic bile duct stone extractions.

AIM: Endoscopic retrograde cholangiopancreaticography is likely the most widely chosen option for common bile duct stone treatment. Previous abdominal surgery types, especially Billroth II gastrectomy, the failure of cannulation and stone removal and the morbidity associated with open surgery have paved the way for considering laparoscopic common bile duct exploration. The aim of this study was to present our early experiences with a special emphasis on the utility of laparoscopic common bile duct exploration in choledocholithiasis patients in whom endoscopic retrograde cholangiopancreaticography failed as a treatment. METHODS: The study enrolled a total of 32 patients in the Okmeydani Training and Research Hospital with common bile duct stones who were offered laparoscopic common bile duct exploration in situations where endoscopic retrograde cholangiopancreaticography failed from March 2010 to April 2012 were analyzed prospectively. RESULTS: Choledochoscopy was performed in all of the patients with the transcholedochal route, and the common bile duct stones were successfully extracted in 31 patients. There were two postoperative complications and one conversion to open surgery. The two patients with complications developed a bile leak that resolved spontaneously with observation. Due to dense adhesions and the abundance of stones in the common bile duct, only one case required open surgery, and a choledochoduodenostomy was performed. CONCLUSION: Undoubtedly, both endoscopic retrograde cholangiopancreaticography and laparoscopic common bile duct exploration must be considered for bile duct stone treatment; however, laparoscopic common bile duct exploration can be a savior for failed endoscopic bile duct stone extraction in experienced hands.

The relationship between serum tumor-associated trypsin inhibitor levels and clinicopathological parameters in patients with gastric cancer.

BACKGROUND: Tumor-associated trypsin inhibitor (TATI) is expressed with trypsinogen in tumors. We studied the clinical-pathologic association and significance of preoperative serum levels of TATI in gastric cancer patients. PATIENTS AND METHODS: Pre-treatment serum levels of TATI in patients with gastric cancer and healthy controls were analyzed by a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Statistically significant differences were found in serum TATI levels between patients with gastric cancer and healthy controls (p < 0.0001). There was a significant relationship between the serum levels of TATI and clinicopathological parameters. However, serum levels of TATI were significantly higher in patients with an advanced T stage (T3) (p < 0.001), lymph node metastasis (p < 0.001) and an advanced TNM stage (stage III or IV; p < 0.001). CONCLUSIONS: Our study suggests that TATI may be used to identify potentially high-risk groups of upper gastric carcinoma. Elevated level of TATI was associated with progressive disease or advanced stage.

Evaluation of the effects of hyperbaric oxygen treatment and enoxaparin on left colon anastomosis. An experimental study.

BACKGROUND: Surgical interventions on left colon lead to high morbidity. The problems in wound healing are the main cause of this morbidity. Hypoxia retards wound healing and hyperbaric oxygen treatment (HBOT) has an anti-hypoxic effect. MATERIALS AND METHODS: In this experimental study we divided eighty Wistar albino rats into eight groups and numbered between 1 and 8. Normal (non-ischemic) and ischemic left colon anastomosis were performed in the first and second four groups respectively. HBOT and subcutaneous enoxaparin were applied to the groups separately and in combination for four days, except the control groups. (Group-1 and Group-5). We measured anastomotic bursting pressures and performed pathological examinations besides electron microscopic study in one sample from each group after sacrificing the rats on the fourth day. RESULTS: There were no statistically significant differences in bursting pressures when we compared Group-1 with other non-ischemic groups, and Group-5 with Group-6, but there were statistically significant differences when we compared Group-5 with Group-7 and 8. In pathological examination, there were no statistically significant differences between the groups concerning necrosis, epithelization, granulation tissue formation and collagen deposition. Statistically significant differences were found in the scores of neovascularization when we compared Group-1 with Group-3 and 4, and Group-5 with Group-8. Electron microscopic evaluation revealed a prominent increase both in neovascularization and collagen fibers in the samples taken from the groups received enoxaparine and hyperbaric oxygen treatment in combination. CONCLUSIONS: These findings suggest that HBOT increases neovascularization and bursting pressures in ischemic colon anastomosis in contrast with enoxaparin.

Treatment of ischemic colonic anastomoses with systemic transplanted bone marrow derived mesenchymal stem cells.

BACKGROUND: The aim of the study is to investigate the healing effect of the bone-marrow derived mesenchymal stem cells (BM-MSCs) on ischemic colon anastomosis in systemic application and to recovery the adverse effect of ischemia. MATERIALS AND METHODS: Fourty male Wistar Albino rats weigthing 250-300 g were divided into four equal groups (n=10 Group 1: control; ischemic left colonic anastomoses (4th day); Group 2: control; ischemic left colonic anastomoses (7th day); Group 3: ischemic left colonic anastomoses + systemic transplanted BM-MSCs (4th day); Group 4: ischemic left colonic anastomoses + systemic transplanted BM-MSCs (7th day). BMSCs labelled with bromodeoxyuridine (BrdU) were transplanted into the vena cava. Group 1 and group 3 were killed four days after surgery. In group 2 and group 4 were sacrificed seven days after the surgical procedure. Histopathological features, hydroxyproline levels in the tissue, and anastomotic strength were investigated. RESULTS: There was no mortality all of the groups.The mean bursting pressures of ischemic colonic anastomoses in group 3 were higher than in control group 1 (4th day). We found significantly higher hydroxyproline values in group 3 and were significantly higher in group 4 than in control groups. We investigated the early period of wound healing (4th day and 7th day). When comparing between group 1 and group 3, we found higher levels for all of the histological parameters except inflammation in group 3. On day 7, when comparing between group 2 and group 4, we found higher levels for parameters of necrosis, collagen deposition. CONCLUSIONS: BM-MSCs therapy significantly accelerated all of the healing parameters for ischemic colonic anastomosis except for inflammation on fourth day. On the seventh day, BM-MSCs augmented the levels of the hydroxyproline. Histological parameters, necrosis and collagen deposition were also found to be important for healing of ischemic colonic anastomoses. However, they did not accelerate the others histological parameters especially angiogenesis.

Preperitoneal repair (open posterior approach) for recurrent inguinal hernias previously treated with Lichtenstein tension-free hernioplasty.

BACKGROUND: The repair of recurrent inguinal hernias after prosthetic mesh repair is usually diffucult due to considerable technical challenge and complications. There is also a greater risk of developing further recurrence. The aim of this study was to investigate the outcome of preperitoneal repair (open posterior approach) for recurrent inguinal hernias after Lichtenstein tension-free hernioplasty. METHODS: We performed a prospective clinical study in 44 patients having recurrent inguinal hernias the period 2002- 2008. Preperitoneal repair was performed on all patients who have had Lichtenstein tension-free hernioplasty previously. The age, gender, operating time, hospital stay, postoperative complication rates and recurrence rates of patients were evaluated. RESULTS: There were no serious intraoperative complications. There were 36 men and 9 women in the study, whose average age was 38.45 (25-68) years. The average operative time and hospital stay were 44.56 (30-120) min and 1.6 (1-3) days, respectively. Complications included 4.5 % seromas, 4.5 % hematomas and urinary retention in 9.09 % patients. Follow-up to date is 1-90 months (range, median 40 months). CONCLUSIONS: We concluded that the preperitoneal repair (open posterior approach) in recurrent inguinal hernias after Lichtenstein tension-free hernioplasty is a safe and efficient method with low complication and rerecurrence rates.

Parasitic infestation as cause of acute appendicitis.

AIM: The role of parasitic infestation in the cause of acute appendicitis has been long time discussed. The aim of this study is to evaluate the role of parasitic infestation in the etiology of acute appendicitis. PATIENTS AND METHODS: This retrospective study includes 5.100 patients undergoing surgical therapy for acute appendicitis between 1996 and 2005. Patients were divided into two groups according to the presence of the parasites in the appendix lumen: in Group 1 (n=24) we observed parasitic infestation, whereas in patients of the Group 2 (n=5.076) no parasitic infestation was present. RESULTS: Parasitic infestation was detected in 24 (0.5%). Of 24 parasitic infestation, 12 (50%) were enterobiasis, 6 (25%) were schistosomiasis, 4 (17%) were Ascaris lumbricoides, and 2 (8%) were Taenia saginata. The ratios of the patients with suppurative, gangrenous or perforative appendicitis were similar in both groups. The ratio of the normal histological findings in the Group 1 patients (25%) was significantly higher than that in the Group 2 patients (4.8%, p=0.001). CONCLUSION: Although parasitic infestation may result in symptoms resembling acute appendicitis, parasitic infestation can't be considered in the etiology of acute appendicitis.

Curcumin nutrition for the prevention of mesenteric ischemia-reperfusion injury: an experimental rodent model.

BACKGROUND: Curcumin is an anti-oxidant molecule known to be a potent inhibitor of nuclear factor-kappaB (NF-kappaB). It has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In this study, we sought to investigate the effects of curcumin on the prevention of superior mesenteric artery I/R injury in rats. METHODS: Wistar albino rats were randomly allocated to 3 groups: group I, sham operated (n = 10); group II, I/R injury only (n = 10); group III, curcumin-treated I/R cohort (n = 10). Group I animals underwent laparotomy without I/R injury. After group II animals underwent laparotomy, 60 minutes of superior mesenteric artery ligation were followed by 3 hours of reperfusion. In the curcumin group, 15 days before I/R, curcumin (40 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion. Intestinal tissue samples were obtained to investigate intestinal mucosal injury; in addition we estimated levels of myeloperoxidase (MPO) activity, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. RESULTS: There were statistically significant decreases in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, NO, IL-6, and TNF-alpha in group I when compared with groups II and III (P = .01). Curcumin treatment in group III produced a significant increase in GSH levels, as well as a decrease in intestinal mucosal injury scores, MPO activity, MDA, and NO levels when compared with group II (P < .05). CONCLUSION: This study showed that curcumin treatment significantly attenuated reperfusion injury in a superior mesenteric artery I/R model in rats.

[Splenic trauma and treatments. Haseki Educational and Research Hospital Surgical Department survey of the feasibility of surgery for splenic trauma]. / Dalak yaralanmalari ve tedavisi haseki egitim ve arastirma hastanesi acil cerrahi servisinde dalak yaralanmalarinda uygulanan cerrahi girisimler.

184 patients were admitted with splenic injuries, between 1992 and 1998. 131 (71%) patients were male and 53 (29%) patients were female. The average age of patients were 20.4 years. There were 176 (95%) blunt and 8 (5%) penetrating injuries. The management of our cases involved splenectomy in 164 (89%), splenorraphy in 12 (7%) and partial splenectomy in 8 (4%). 172 (93%) of the operated patients had isolated splenic injuries and 12 (7%) concomitant organ injuries. The lenght of hospital stay of splenectomies; partial splenectomy and splenorraphy were 7.9, 7 and 6 days respectively. The complication rate of splenectomy, partial splenectomies; and splenorraphy after the operation were 3 (2%), 1 (0.5%) and 0. No deaths occurred as a result of splenic injury and operation.