Targeting the PANoptosome with 3,4-Methylenedioxy-ß-Nitrostyrene, Reduces PANoptosis and Protects the Kidney against Renal Ischemia-Reperfusion Injury.

OBJECTIVES: The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-ß-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury. METHODS: Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2'-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues. RESULTS: Total tubular injury score was lower in the MNS group (p < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (p < 0.001). Apoptotic index (AI) was found to be low in the MNS group (p < 0.001). CAT and SOD levels were higher in the MNS Group (p = 0.006, p = 0.0004, respectively). GPx, MDA, and 8-OH-dG levels were similar (p > 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis. CONCLUSIONS: Our results suggested that MNS administrated before the reperfusion reduces pyroptosis, apoptosis and necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of Nod-like receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.

The role of bioimpedance spectroscopy method in severity and stages of breast cancer-related lymphedema.

Objectives: The correlation between lymphedema severity and stages determined by standard diagnostic methods and Bioimpedance Spectroscopy (BIS) technique was examined in breast cancer-related lymphedema (BCRL) patients. Material and Methods: The bioimpedance analyzer device was connected to the 1.0 cm disc electrodes which were connected to the affected and unaffected (healthy) arm of the patients. We evaluated the performance of the impedance (Z) at multiple frequencies (5-50-100-200 kHz) and phase angle (PA), resistance (R), and reactance (XC) at 50 kHz on the lymphedema severity and stages. Bioimpedance measurements were applied to all volunteers in cooperation with the Physical Therapy and Rehabilitation Department. In this study, the correlation between BCRL severity and stages and bioimpedance values was examined. Results: A total of 31 female patients were recruited to compare the BIS technique with standard diagnostic techniques. The severity of lymphedema was found among the patients as follows; mild 14 (45.2%), moderate 10 (32.3%), and severe 7 (22.6%). The stage distribution of volunteers was; 15 (48.4%) patients in Stage 0, 10 (32.3%) patients in Stage 1, 5 (16.1%) patients in Stage 2, and 1 (3.2%) patient in Stage 3. The ratio of affected and unaffected arm bioimpedance mean values were calculated. Although, this ratio at 50-100-200 kHz Z and 50kHz R were significantly correlated with the lymphedema stages (p <0.05), there was no correlation and significant difference between the ratio of the bioimpedance values and lymphedema severity (p> 0.05). Conclusion: The BIS technique is timesaving and can determine lymphedema stages. We found a significant correlation between BCRL stages and BIS, and it appears that BIS is an appropriate, inexpensive, simple, and noninvasive technique for detecting the stages of BCRL.

The Effect of Primary Surgery in Patients with De Novo Stage IV Breast Cancer with Bone Metastasis Only (Protocol BOMET MF 14-01): A Multi-Center, Prospective Registry Study.

BACKGROUND: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). METHODS: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). RESULTS: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). CONCLUSION: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.

Surgical Trends in Breast Cancer in Turkey: An Increase in Breast-Conserving Surgery.

PURPOSE: Breast cancer is the most frequent cancer in women, and there is a great variability in surgical practice for treating that cancer in different countries. The aims of this study were to analyze the effect of guidelines from the Turkish Federation of Breast Diseases Societies on academic institutions that have breast centers and to evaluate surgical practice in Turkey in 2018. PATIENTS AND METHODS: Between January and March 2019, a survey was sent to breast surgeons who were working in breast centers in academic institutions. The sampling frame included 24 academic institutions with breast centers in 18 cities in Turkey to evaluate interdisciplinary differences among breast centers and seven regions in Turkey regarding patients' choices, surgical approaches, and academic institutions. RESULTS: All surgeons responded to the survey, and all 4,381 patients were included. Most of the surgeons (73.9%) were working in a breast center. Multidisciplinary tumor boards were performed in 87% of the breast centers. The average time between clinical evaluation and initiation of treatment was 29 days; the longest time was in Southeast Anatolia (66 days). Only 6% of patients had ductal carcinoma in situ. Sentinel lymph node biopsy was available in every region across the country and was performed in 64.5% of the patients. In 2018, the overall breast-conserving surgery rate was 57.3% in Turkey, and it varied from 72.2% in the Black Sea region to 33.5% in Central Anatolia (P < .001). Oncoplastic breast surgery options were available at all breast centers. However, 25% of the breast centers from the Black Sea region and half the breast centers from Eastern Anatolia and the Mediterranean region did not perform this type of surgery. CONCLUSION: Increasing rates of nonpalpable breast cancer and decreasing rates of locoregional recurrences favored breast-conserving surgery, especially in developed countries. Guidelines from the Turkish Federation of Breast Diseases Societies resulted in more comprehensive breast centers and improved breast health in Turkey.

Evaluation of conventional imaging techniques on preoperative localization in primary hyperparathyroidism.

We aimed to evaluate the diagnostic and preoperative localization capacity of 99mTc methoxyisobutylnitrile (MIBI) parathyroid scintigraphy and ultrasonography (USG) in enlarged parathyroid glands in the primary hyperparathyroidism (pHPT) as well as the relationship between the success rate of these techniques and biochemical values. In this study, we retrospectively evaluated 39 patients with clinical and biological evidence of pHPT who referred to the university hospital for MIBI parathyroid scintigraphy. Patients were examined with USG and double-phase MIBI parathyroid scintigraphy for the detection of enlarged parathyroid glands. Preoperative serum intact parathyroid hormone (iPTH) levels, calcium (Ca), phosphate and alkaline phosphatase measurements were obtained. A total of 45 parathyroid lesions in 39 patients were reviewed. Thirty-four patients had a single adenoma and 5 patients with multi-gland disease had 11 abnormal parathyroid glands including three adenomas, whereas the remaining 8 glands showed hyperplasia. The overall sensitivities of MIBI parathyroid scintigraphy, USG and combined techniques were 85.3%, 72.5% and 90.4%, respectively; the positive predictive values (PPV) were 89.7%, 85.2% and 92.6%, respectively. The most successful approach for detection of enlarged parathyroid glands in hyperparathyroidism is the concurrent application of USG and MIBI parathyroid scintigraphy modalities. The concomitancy of thyroid diseases decreases the sensitivity of both MIBI parathyroid scintigraphy and USG in enlarged parathyroid glands.

A cyclin D1 (CCND1) gene polymorphism contributes to susceptibility to papillary thyroid cancer in the Turkish population.

Cyclin D1 is an important positive regulator of the G1/S phase of the cell cycle. We investigated the association between the CCND1 G870A polymorphism and susceptibility to papillary thyroid cancer in Turkish people. This study covered 102 patients with papillary thyroid cancer and 174 healthy controls. CCND1 genotyping was determined by the PCR-RFLP method. We found that the A allele frequency was higher in the cases than in the controls (p=0.042). On stratification analysis, papillary thyroid cancer risk was significantly elevated in individuals older than 45 years with the A allele (OR=1.91, 95% CI, 1.09-3.35, p=0.024) and in females with the A allele (OR=1.73, 95% CI, 1.06-2.84, p=0.029), compared to the G allele. According to the subject age, there was an increased papillary thyroid cancer risk for the individuals older than 45 years with the AA genotype (OR=2.28, 95% CI, 1.02-5.13, p=0.046) compared to the AG+GG combined genotypes. In conclusion, it is suggested that the CCND1 G870A polymorphism may contribute to the susceptibility to papillary thyroid cancer, especially in those who were older subjects (45 ≤ years old) and female, in the Turkish population.

Pain management with intrathecal clonidine in a colon cancer patient with opioid hyperalgesia: case presentation.

Hyperalgesia is normally an increase in the response to a painful stimulant. Opioid-induced hyperalgesia (OIH) is a situation frequently encountered in algology clinics. Its treatment is complicated and problematic and often requires alternative methods. A 40-year-old male patient 45 kg weighing had been diagnosed with stage IV colon cancer 2.5 years ago. He had used non-steroid antiinflammatory drugs, opioid analgesics and steroid preparations casually for his increased pain without any monitoring for one year. He was admitted five times for pain control. In the last visit, he complained of severe abdominal, pubic and rectal pain (visual analogue scale [VAS] 8), which was unresponsive to epidural analgesic, and later presented to the algology clinic; he was sleep-deprived, restless and in a panic state. Intrathecal morphine (1 mg) was applied considering his opioid tolerance. Because of increased pain (VAS 8-9) one hour after surgery for abscess in the liver and peritonea, the patient was given intravenous dexketoprofen trometamol and diazem considering his OIH. Then, bolus dexmedetomidine (1 µg/kg) followed by dexmedetomidine infusion (0.2 µg/kg/h) was started. Three days later, diagnostic intrathecal clonidine (30 µg) was applied, and the patient's complaints regressed. With the patient reporting relaxed pain (VAS 1-2) after 30 minutes, an intrathecal port was placed. Both cancer pain and OIH were controlled with clonidine 90 µg/day. He was more relaxed, and his pain was tolerable until his death. Intrathecal clonidine administration may be an effective method for the treatment of OIH.

Biochemical and histopathological changes of intra-abdominal hypertension on the kidneys: Experimental study in rats.

OBJECTIVE: This study aimed to evaluate the effects of experimentally induced intra-abdominal hypertension on renal functions, with the combination of biochemical and histopathological properties. MATERIAL AND METHODS: Thirty male Wistar albino rats were used in this experimental study. Rats were divided into four groups. Group 1 (control group, n=6) only received anesthesia. After the induction of anesthesia, a 20 G catheter was introduced intraperitoneally to Group 2 (sham group, n=8), Group 3 (n=8) and Group 4 (n=8). The intra-abdominal pressure was not increased in Group 2. We applied 20 mmHg intra-peritoneal pressure to Group 3 and 30 mmHg to Group 4 for 3 hours. After withdrawing 3 mL intracardiac blood from all groups, the kidneys were removed for histopathological examination. Serum urea and creatinine levels were measured in all groups. RESULTS: Biochemical examination showed that blood urea and creatinine levels were statistically different among all groups (p<0.05). Serum creatinine levels in Group 3 and serum urea and creatinine levels in Group 4 were significantly increased. In the histopathological examination, the kidneys in Group 1 and Group 2 were classified as normal. In Group 3, areas with congestion were detected in the glomeruli and interstitial regions. In addition to these findings seen in Group 3, dilatation of the pelvi-caliceal structures and proximal ureters were noticed in Group 4. CONCLUSION: The levels of serum urea and creatinine are elevated when intra-abdominal pressure is increased due to kidney damage. Foci of hemorrhage in the interstitial area, dilatations in the proximal ureter, renal pelvis, and lymphatics were the pathologic findings seen in the kidneys under such circumstances.

Long-term results in the treatment of fistula-in-ano with fibrin glue: a prospective study.

PURPOSE: This prospective study was done to analyze the efficacy of commercial fibrin glue application in the healing of patients with fistulas-in-ano from a long-term (mean 4.5 years) research period. METHODS: This clinical trial of forty-six patients was performed during the period from January 2004 to February 2005. Thirty-nine men and seven women were treated for a fistula-in-ano with a commercial fibrin glue application. In the operating room, the patients underwent an anorectal examination under spinal anesthesia. The external and internal fistula tract openings were then identified. The fistula tract was curetted. Fibrin glue was injected into the external fistula opening until the fibrin glue could be seen coming from the internal opening. RESULTS: The overall initial success rate was 86.95% (40/46). Recurrence rate was 41.30% (19/46). Two patients underwent a re-application with fibrin glue and the fistulas of these patients closed. The total recurrence rate was 36.95% (17/46). The long-term overall success rate was 63.04% (29/46). CONCLUSION: Fibrin glue application was thus found to be an easy, safe, acceptable, successful alternative treatment in the management of fistulas-in-ano. Choosing the patient correctly is very important because long (more than 4 cm) and non-ramificate fistula tracts usually close with commercial fibrin glue.

The efficacy of Ankaferd Blood Stopper for the management of bleeding following total thyroidectomy.

PURPOSE: Postoperative hematoma remains an uncommon but potentially life-threaten complication of thyroid surgery. The aim of this study is to assess the efficacy of Ankaferd Blood Stopper (ABS) in comparison to hemostasis by conventional technique (HCT) for the controlling of oozing-type bleeding following total thyroidectomy. METHODS: We randomized 61 patients with benign euthyroid multinodular goiter who underwent total thyroidectomy subject to one of the two different hemostasis techniques. There were 31 patients in the HCT group and 30 patients in the ABS group. The study was designed prospectively to compare ABS and HCT groups in terms of operation time, postoperative drainage, duration of postoperative stay, and complications. RESULTS: Mean postoperative drainage from the closed suction drains at first 24 hr were 24.6 ± 8.6 ml and 12.0 ± 9.2 ml (p = .001) and mean total postoperative drainage were 38.5 ± 13.2 ml and 20.6 ± 12.2 ml (p = .001) in the HCT and ABS groups, respectively, indicating statistically significant differences. CONCLUSIONS: On the basis of the results of this trial, the use of ABS seems to be more effective than HCT to control hemorrhage following total thyroidectomy.

The effects of low thyroid hormone levels on the formation of stress gastritis: an experimental study on the rats.

BACKGROUND: The aim of this study was to investigate the effect of low circulating thyroid hormone levels on the development of acute stress gastritis in rats. METHODS: Sixty adult Sprague-Dawley rats were divided into six groups: Control group, surgically thyroidectomized group, stressed group, surgically thyroidectomized + stressed group, surgically thyroidectomized + T4 + stressed group, and surgically thyroidectomized + T3 + stressed group. Damage to the gastric mucosa was studied using millimetric acetate papers on photographs enlarged 3.5 times and the number and the size of the lesions was recorded. RESULTS: Acute stress gastritis was significantly increased in stress + surgically thyroidectomized rats as compared to rats that were only put under stress (group III) (stress gastritis scores; group IV: 44, group III: 16, p<0.001). The stress gastritis score in group VI was significantly decreased compared to rats in group IV (stress gastritis scores; group VI: 10, group IV: 44, p<0.001). CONCLUSION: Low circulating thyroid hormone levels in rats increased the development of stress gastritis. This effect could be prevented by thyroid hormone replacement therapy.

Tuberculous spondylitis: abscess drainage after failure of anti-tuberculous therapy.

Spinal tuberculous abscesses usually respond to anti-tuberculous drugs. The purpose of this study was to evaluate the results of surgical drainage after failure of first-line anti-tuberculous drugs. Patients with spinal instability or vertebral collapse were excluded from the study. The authors retrospectively reviewed 11 patients. The operation was successful in all patients. Anterior/posterior spinal fusion or curettage was not performed. Drains were removed after two to three days. None of the patients required a second operation. Complications, such as spinal instability, vertebral collapse, or death did not occur.

The use of fibrin glue in the treatment of fistula-in-ano: a prospective study.

PURPOSE: This prospective study was done to analyze the efficacy of commercial fibrin glue application in the healing of patients with fistulas-in-ano. METHODS: This clinical trial of 36 patients was performed during the period from November 2003 to May 2004. Thirty men and six women were treated for a fistula-in-ano with commercial fibrin glue application. None of the patients had undergone prior attempts to correct fistulas-in-ano surgically. All patients received preoperative mechanical bowel preparation and prophylactic intravenous antibiotics. In the operating room, the patients underwent an anorectal examination under spinal anesthesia. The external and internal fistula tract openings were then identified. The fistula tract was curetted. Fibrin glue was injected into the external fistula opening until fibrin glue could be seen coming from the internal opening. No dressing was applied over the external opening. Thereafter, the patient was discharged. A 1-week course of oral antibiotics was prescribed. The patients were followed up for 70 weeks with a mean of 54 weeks (range 40-70 weeks). RESULTS: The cause of the fistula-in-ano was cryptoglandular in all patients. The overall initial success rate was 77.8% (28/36). No complications were encountered related to the application. Two patients underwent a reapplication with fibrin glue and the fistulas of these patients were all closed. The overall success rate was 83.3% (30/36). CONCLUSION: Fibrin glue application was thus found to be an easy, safe, effective, and useful alternative treatment in the management of fistulas-in-ano. However, our findings need substantiation by increasing the number of patients and prolonging the follow-up duration, as well as carrying out comparative studies.

A prospective randomised study of local anaesthetic injection after multiple rubber band ligation of haemorrhoids.

One hundred and forty-two patients with second and third degree internal haemorrhoids were randomised to rubber band ligation only (n = 72) or rubber band ligation + local anaesthetic injection (n = 70). Pain was assessed by the patients at intervals of 6 hours and 1, 2, 3 and 4 days after banding. Other symptoms, complications, analgesic requirements and patient satisfaction were also recorded for 10 days following the treatment. There was a significant reduction in pain at 60 minutes and 6 hours after the procedure in the rubber band ligation plus local anaesthetic injection patients compared with the rubber band ligation only group (P < 0.05), but there was no reduction in pain when local anaesthetic was used compared with rubber band ligation only on days 1, 2, 3 and 4 days after ligation. On day 10 after banding, there was no difference between the two groups with respect to symptoms such as nausea, feeling of heaviness and/or tenesmus, fainting; complications, analgesic consumption or overall patient satisfaction. Bupivacaine injection after multiple rubber band ligation may be useful in reducing pain during the first 6 hours of the postbanding period.

Adrenal cyst.

Adrenal cysts are rarely seen lesions. Most are asymptomatic and less than 10 cm. Adrenal cysts, most of which are diagnosed incidentally, can be diagnosed more by wide usage of diagnostic imaging methods. Symptoms appear when they grow to a large size causing pain or gastrointestinal disturbance or become palpable. In this article, a case of a large left adrenal cyst, 12 cm diameter was causing abdominal pain in a 20-year-old female patient subsequently removed totally by surgical excision with adrenalectomy is presented and treatment modalities was discussed.