A gene therapy targeting medium-chain acyl-CoA dehydrogenase (MCAD) did not protect against diabetes-induced cardiac pathology.

Diabetic cardiomyopathy describes heart disease in patients with diabetes who have no other cardiac conditions but have a higher risk of developing heart failure. Specific therapies to treat the diabetic heart are limited. A key mechanism involved in the progression of diabetic cardiomyopathy is dysregulation of cardiac energy metabolism. The aim of this study was to determine if increasing the expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD; encoded by Acadm), a key regulator of fatty acid oxidation, could improve the function of the diabetic heart. Male mice were administered streptozotocin to induce diabetes, which led to diastolic dysfunction 8 weeks post-injection. Mice then received cardiac-selective adeno-associated viral vectors encoding MCAD (rAAV6:MCAD) or control AAV and were followed for 8 weeks. In the non-diabetic heart, rAAV6:MCAD increased MCAD expression (mRNA and protein) and increased Acadl and Acadvl, but an increase in MCAD enzyme activity was not detectable. rAAV6:MCAD delivery in the diabetic heart increased MCAD mRNA expression but did not significantly increase protein, activity, or improve diabetes-induced cardiac pathology or molecular metabolic and lipid markers. The uptake of AAV viral vectors was reduced in the diabetic versus non-diabetic heart, which may have implications for the translation of AAV therapies into the clinic. KEY MESSAGES: The effects of increasing MCAD in the diabetic heart are unknown. Delivery of rAAV6:MCAD increased MCAD mRNA and protein, but not enzyme activity, in the non-diabetic heart. Independent of MCAD enzyme activity, rAAV6:MCAD increased Acadl and Acadvl in the non-diabetic heart. Increasing MCAD cardiac gene expression alone was not sufficient to protect against diabetes-induced cardiac pathology. AAV transduction efficiency was reduced in the diabetic heart, which has clinical implications.

In Vivo Inhibition of miR-34a Modestly Limits Cardiac Enlargement and Fibrosis in a Mouse Model with Established Type 1 Diabetes-Induced Cardiomyopathy, but Does Not Improve Diastolic Function.

MicroRNA 34a (miR-34a) is elevated in the heart in a setting of cardiac stress or pathology, and we previously reported that inhibition of miR-34a in vivo provided protection in a setting of pressure overload-induced pathological cardiac hypertrophy and dilated cardiomyopathy. Prior work had also shown that circulating or cardiac miR-34a was elevated in a setting of diabetes. However, the therapeutic potential of inhibiting miR-34a in vivo in the diabetic heart had not been assessed. In the current study, type 1 diabetes was induced in adult male mice with 5 daily injections of streptozotocin (STZ). At 8 weeks post-STZ, when mice had established type 1 diabetes and diastolic dysfunction, mice were administered locked nucleic acid (LNA)-antimiR-34a or saline-control with an eight-week follow-up. Cardiac function, cardiac morphology, cardiac fibrosis, capillary density and gene expression were assessed. Diabetic mice presented with high blood glucose, elevated liver and kidney weights, diastolic dysfunction, mild cardiac enlargement, cardiac fibrosis and reduced myocardial capillary density. miR-34a was elevated in the heart of diabetic mice in comparison to non-diabetic mice. Inhibition of miR-34a had no significant effect on diastolic function or atrial enlargement, but had a mild effect on preventing an elevation in cardiac enlargement, fibrosis and ventricular gene expression of B-type natriuretic peptide (BNP) and the anti-angiogenic miRNA (miR-92a). A miR-34a target, vinculin, was inversely correlated with miR-34a expression, but other miR-34a targets were unchanged. In summary, inhibition of miR-34a provided limited protection in a mouse model with established type 1 diabetes-induced cardiomyopathy and failed to improve diastolic function. Given diabetes represents a systemic disorder with numerous miRNAs dysregulated in the diabetic heart, as well as other organs, strategies targeting multiple miRNAs and/or earlier intervention is likely to be required.

Comparing Preoperative Anxiety Effects of Brachial Plexus Block and General Anesthesia for Orthopedic Upper-Extremity Surgery: A Randomized, Controlled Trial.

Background and objectives: Preoperative anxiety is an enormous feeling of fear that is seen in all patients undergoing surgery. The severity of anxiety may vary depending on the type of surgery and anesthesia to be performed. The aim of this study is to compare the effects of brachial plexus blocks and general anesthesia methods on preoperative anxiety levels in patients who will undergo orthopedic upper-extremity surgery and to determine the factors affecting anxiety. Materials and Methods: After randomization, the Amsterdam Preoperative Anxiety and Knowledge Scale (APAIS) questionnaire was applied to the patients to determine the preoperative anxiety level, and then anesthesia was applied according to the anesthesia type determined. Pain scores (1, 8, 16, and 24 h) and total opioid consumption of the patients were recorded postoperatively. Results: The APAIS score of the patients in the general anesthesia (GA) group was significantly higher (p = 0.021). VAS score medians at 1, 4, and 8 h postoperatively were found to be significantly higher in the GA group (p < 0.001, p < 0.001 and p = 0.044, respectively). Conclusions: USG-guided BPB may cause less anxiety than GA in patients who will undergo elective upper-extremity surgery. However, these patients have moderate anxiety, although it is more associated with advanced age, female gender, and education level.

Association between Anemia and New-Onset Atrial Fibrillation in Critically Ill Patients in the Intensive Care Unit: A Retrospective Cohort Analysis.

New-onset atrial fibrillation (NOAF) is one of the leading causes of morbidity and mortality, especially in older patients in the intensive care unit (ICU). Although many comorbidities are associated with NOAF, the effect of anemia on the onset of atrial fibrillation is still unknown. This study aimed to test the hypothesis that anemia is associated with an increased risk of developing NOAF in critically ill patients in intensive care. We performed a retrospective analysis of critically ill patients who underwent routine hemoglobin and electrocardiography monitoring in the ICU. Receiver operating characteristics analysis determined the hemoglobin (Hb) value that triggered NOAF formation. Bivariate correlation was used to determine the relationship between anemia and NOAF. The incidence of NOAF was 9.9% in the total population, and 12.8% in the patient group with anemia. Analysis of 1931 patients revealed a negative association between anemia and the development of NOAF in the ICU. The stimulatory Hb cut-off value for the formation of NOAF was determined as 9.64 g/dL. Anemia is associated with the development of NOAF in critically ill patients in intensive care.

Analgesic efficacy of ultrasound-guided transversus abdominis plane block and lateral approach quadratus lumborum block after laparoscopic appendectomy: A randomized controlled trial.

Background: Laparoscopic appendectomy is the most performed emergency surgical technique worldwide. Transversus abdominis plane (TAP) blocks, which are easier to achieve with ultrasound, are frequently used in multimodal analgesia techniques for this surgery. Quadratus lumborum (QL) block has become a standard block, first used in gynecological and other abdominal surgeries. This study was planned to compare the analgesic efficacy of ultrasound-guided QL and TAP blocks for postoperative analgesia after laparoscopic appendectomy. Materials and methods: A total of 136 patients aged 18-65 years who underwent laparoscopic appendectomy were randomized and divided into two groups. A volume of 40 ml of local anesthetic containing 0.375% bupivacaine was administered for block applications in group TAP (n = 68) and group QL (n = 68). In addition, a patient-controlled analgesia device was used to administer bolus tramadol hydrochloride at a dose of 10 mg to relieve pain in the postoperative period. Postoperative opioid consumption of patients was recorded as the primary outcome and pain scores (1, 6, 12, 18, 24 h) as the secondary outcome. Results: Both groups were statistically similar in demographic and surgical data. There were no statistically significant differences between the groups over 24 h in terms of intraoperative remifentanil consumption (p = 0.584), postoperative cumulative opioid consumption (p = 0.807), and pain scores. No complications were observed in either group related to the block. Conclusion: Ultrasound-guided lateral approach QL block may provide adequate analgesia efficacy in patients undergoing laparoscopic appendectomy, like TAP block, and may be included in multimodal analgesia in pain control.

The effect of omentectomy on the blood levels of adipokines in obese patients with endometrial cancer.

OBJECTIVE: To investigate the blood levels of adipokines in obese patients with endometrial cancer who have and have not undergone omentectomy. METHODS: Between September 2017 and September 2019, the study recruited 54 patients with endometrial cancer. Measurements were taken of blood levels of human leptin, perilipin-1, adiponectin, adipolin, resistin, visfatin, and estrone preoperatively and postoperatively before adjuvant therapy or at the end of one month. The serum samples were separated by centrifugation for 10 mins at 3,000 revolutions/min, then stored at -80 °C until assay. RESULTS: In this prospective study, a total of 54 endometrial cancer patients were analyzed in two separate groups according to the omentectomy status. Comprehensive staging surgery with omentectomy and without omentectomy was performed in 26 patients and 28 patients, respectively. The age, body mass index, body fat index, waist circumference, and skin thickness values of the patients with and without omentectomy were found to be similar. No statistically significant difference was determined between the patients with and without omentectomy in respect of the blood level of the adipokines measured preoperatively. A strong statistically significant correlation was determined between the pre and postoperative levels of Human Leptin (p = 0.002), perilipin-1(p = 0.001), adipolin (p < 0.001), adiponectin (p < 0.001), resistin (p = 0.001), visfatin (p < 0.001), and estrone (p = 0.004) (r = -0.43, -0.47, 0.75, 0.84, -0.47, - 0.58, -0.41, respectively) CONCLUSIONS: Omentectomy affected the postoperative blood levels of adipokines in obese patients with endometrial cancer. As omentectomy may have some positive effects on metabolism in these patients, it may be considered during endometrial cancer surgery due to the possible positive metabolic effects.

Evaluation of aerosol box use for ultrasound-guided internal jugular vein cannulation in patients with COVID-19: A short-term randomised study.

Background and Aims: During the coronavirus disease 2019 (COVID-19) pandemic, health care workers are at a high risk of infection from aerosols. In this study, we compared the ease of using the aerosol box (AB) with the traditional method during internal jugular vein cannulation attempts (IJVCA). Methods: The study included 40 patients with COVID-19 who required central venous catheterisation during treatment in the ward. The patients were randomly allocated to one of the two protective equipment (PPE) groups and then randomly assigned to one of the five anaesthesiologists with at least 5 years of experience. Group P and A had both PPE and AB used, whereas Group P included patients where PPE was used alone. The physicians completed a survey after performing the procedure to evaluate the use of the AB. Results: The preparation for the procedure and procedure durations were observed to be statistically longer in Group P and A (P = 0.002 and P = 0.001, respectively). The first attempt in Group P and A was unsuccessful in six patients, whereas the first attempt in Group P was unsuccessful in only two patients (P = 0.235). Anaesthesiologists described difficulty with manipulation during the procedure, discomfort using the box, and resulting cognitive load increase in Group P and A. Conclusion: The IJVCA procedures were faster and easier and had greater satisfaction for physicians when the AB was not used. Also, the high complication rate, including carotid artery punctures and disruption of sterility and PPE, albeit not statistically significant, has clinical implications. Therefore, we do not recommend the use of ABs for IJVCA.

Efficacy of ultrasound-guided erector spinae plane block versus paravertebral block for postoperative analgesia in single-port video-assisted thoracoscopic surgery: a retrospective study.

BACKGROUND: Thoracic paravertebral block (TPVB) is an analgesic method recommended in the enhanced recovery after surgery (ERAS) protocol and proven successful in thoracoscopic surgery. The study aimed to investigate whether the erector spinae plane block (ESPB) administered single-injection in uniportal video-assisted thoracoscopic surgery (VATS) can be an alternative to TPVB as an analgesic method. METHODS: In this study, American Society of Anesthesiologists (ASA) physical status class I-II-III patients aged between 18-70 years who underwent thoracoscopic wedge resection surgery were analyzed retrospectively; 136 patients in the ESPB group and 114 patients in the TPVB group were included in the study. Postoperative cumulative morphine consumption numerical rating scale (NRS) scores were compared at 1, 6, 12, and 24 hours after surgery at rest and during coughing between the groups. Also, rescue analgesia requirements, postoperative nausea, vomiting and other complications were evaluated. RESULTS: The mean cumulative morphine consumption in the postoperative 24 hours was 20.06 mg in the ESPB group and 11.35 mg in the TPVB group. A statistically significant difference was observed between groups in terms of total morphine consumption in the postoperative 24 hours (P<0.001). NRS score was significantly lower in the TPVB group at postoperative 6th and 24th hours during coughing (P=0.003 and P=0.034, respectively) and at 24th hour at rest (P=0.008) than ESPB group. Median NRS scores at rest were low (<4) in both groups. There was no significant difference between the groups in terms of postoperative pulmonary complications as atelectasis and length of hospital stay (LOS) (P=0.643 and P=0.867 respectively). CONCLUSIONS: Ultrasound (US)-guided single-injection TPVB provided superior analgesia in patients undergoing single-port VATS than ESPB. In addition to this, TPVB showed more opioid sparing by reducing morphine consumption.

Perioperative goal-directed fluid management using noninvasive hemodynamic monitoring in gynecologic oncology.

BACKGROUND: Intraoperative fluid management is important for the prevention of perioperative morbidity and mortality. Our study aimed to investigate the perioperative feasibility and benefits of Goal-Directed Fluid Management (GDFM) using noninvasive hemodynamic monitoring in gynecologic oncology patients with acute blood loss and severe fluid loss. We assessed the effects of GDFM on hemodynamics, organ perfusion, complications, and mortality outcomes. METHODS: This randomized prospective study included 104 patients over the age of 18 years, including 56 patients with endometrial cancer and 48 patients with ovarian cancer who had open surgery. The anesthetic approach was standardized for all patients. We compared the perioperative results of the subjects who were randomized into GDFM (n = 51) and Liberal Fluid Management (LFM) (n = 53) groups using a computer program. RESULTS: The median perioperative crystalloid replacement (2000 vs. 2700; p < 0.001) and total volume of fluid (2260 vs. 3200; p < 0.001) were lower in the GDFM group compared to the LFM group. The hemodynamic findings and the HCO3 and lactate levels of the GDFM group did not significantly change perioperatively. The heart rate, mean arterial pressure, and HCO3 levels of the LFM group decreased and serum lactate levels increased perioperatively. The hospitalization rate in ICU (7.8% vs. 28.3%; p = 0.010), rate of patients with comorbidity conditions indicated in ICU (2% vs. 17%; p = 0.024), and rate of complications (17.6% vs. 35.8%; p = 0.047) were lower in the GDFM group compared to the LFM group. CONCLUSION: The amount of intraoperatively administered crystalloid solution and complication rates were significantly lower in gynecologic oncologic surgery patients who received GDFM. Besides, hemodynamic findings, and lactate levels of the GDFM group did not change significantly during the perioperative period.

The Association between the Preoperative Prognostic Nutritional Index and the Controlling Nutritional Status Score on Tumor Stage, Chemotherapeutic Response and Overall Survival in Ovarian Cancer.

This study aimed to investigate the association between preoperative prognostic nutritional index (PNI) and controlling nutritional status (CONUT) scores on the stage of ovarian cancer (OC), chemotherapeutic response, and overall survival (OS) in patients with OC.The data of the patients who operated due to OC between January 2015 and January 2020 in a tertiary referral hospital were recorded. The patients' basic characteristics, preoperative total cholesterol, albumin, lymphocyte count, tumor markers, disease stage, grade, chemotherapeutic response, OS, and progression-free survival were recorded. The PNI and the CONUT score were calculated.The mean PNI level was considerably higher in the early-stage group than the advanced-stage group (50.02 ± 6.8 vs. 46.3 ± 7.4, p = 0.005). The AUC was 63% for the cutoff point 45.98 of PNI, whereas the AUC was 42% for the cutoff point 1.5 of CONUT score in predicting early-stage disease. The PFS and OS were significantly higher in the high PNI group than the low PNI group (p = 0.01, p = 0.002, respectively).The patients with early-stage OC had significantly higher PNI levels and lower CONUT scores in our study population.

Comparison of hysterectomy cases performed via conventional laparoscopy or vaginally assisted natural orifice transluminal endoscopic surgery: a paired sample cross-sectional study.

Hysterectomy is one of the most frequent gynaecological procedures performed for various uterine pathologies. There are several approaches for conducting hysterectomies, including abdominal, vaginal, laparoscopic and robotic. Recently, natural orifices transluminal endoscopic surgery (NOTES) has emerged as an alternative approach for conducting hysterectomies. In this study, we aimed to compare the results of total laparoscopic hysterectomy (TLH) and vaginally assisted-NOTES (vNOTES) hysterectomy procedures for the treatment of benign gynaecological diseases. Ninety-nine patients, who underwent conventional TLH or vNOTES hysterectomies, were included in this study. The operation time, presence of per/postoperative complications, visual analogue scale (VAS) scores at postoperative sixth and 24th hours, and the duration of hospital stays were all analysed. The duration of surgery was significantly shorter in the vNOTES hysterectomy group (79.56 ± 32.54 min) compared to the TLH group (120.67 ± 38.35 min) (p: < .001). Also, postoperative hospital stays were significantly shorter in favour of the vNOTES hysterectomy group (44 ± 16.47 h) compared to the TLH group (57.86 ± 21.31 h) (p: .002). These results indicate that vNOTES hysterectomy can be a promising approach for treating a variety of different uterine pathologies and, furthermore, that it can be an alternative to TLH.Impact statementWhat is already known on this subject? A hysterectomy can be done in a variety of different ways, such as abdominal, laparoscopic, vaginal, and robotic. Even though the standard practice guidelines recommend that a vaginal hysterectomy (VH) should be the first choice of treatment, it can be challenging in cases of non-descendent and large uteruses. In such cases, NOTES hysterectomy can be an alternative option.What do the results of this study add? The study has shown that vNOTES is associated with a shorter operation and briefer postoperative hospitalisation time, in comparison to TLH.What are the implications of these findings for clinical practice and/or further research? This study speculates that vNOTES is an approach which may offer better outcomes than a conventional laparoscopy. Further randomised controlled trials with larger sample sizes, however, should be conducted in order to establish the place of vNOTES in hysterectomy surgeries.

Chronic NaHS treatment decreases oxidative stress and improves endothelial function in diabetic mice.

Hydrogen sulphide (H2S) is endogenously produced in vascular tissue and has anti-oxidant and vasoprotective properties. This study investigates whether chronic treatment using the fast H2S donor NaHS could elicit a vasoprotective effect in diabetes. Diabetes was induced in male C57BL6/J mice with streptozotocin (60 mg/kg daily, ip for 2 weeks) and confirmed by elevated blood glucose and glycated haemoglobin levels. Diabetic mice were then treated with NaHS (100 µmol/kg/day) for 4 weeks, and aortae collected for functional and biochemical analyses. In the diabetic group, both endothelium-dependent vasorelaxation and basal nitric oxide (NO•) bioactivity were significantly reduced ( p < 0.05), and maximal vasorelaxation to the NO• donor sodium nitroprusside was impaired ( p < 0.05) in aorta compared to control mice. Vascular superoxide generation via nicotine adenine dinucleotide phosphate (NADPH) oxidase ( p < 0.05) was elevated in aorta from diabetic mice which was associated with increased expression of NOX2 ( p < 0.05). NaHS treatment of diabetic mice restored endothelial function and exogenous NO• efficacy back to control levels. NaHS treatment also reduced the diabetes-induced increase in NADPH oxidase activity, but did not affect NOX2 protein expression. These data show that chronic NaHS treatment reverses diabetes-induced vascular dysfunction by restoring NO• efficacy and reducing superoxide production in the mouse aorta.

Luteolin ameliorates colistin-induced nephrotoxicity in the rat models.

INTRODUCTION AND AIM: To study the protective, preventive effect of luteolin from colistin-induced nephrotoxicity. MATERIAL AND METHOD: Four different treatment options were tested on rats: colistin, luteolin, and a combination of colistin and luteolin, intraperitoneally as two doses a day, for seven days. Another group of rats were used as the control and treated with sterile saline. Serum creatinine levels were measured before and after treatment. Histological changes and colistin-induced apoptosis (Insitu BrdU-red DNA Fragmentation Assay Kit) of the renal tissues were examined after the scarification procedure. RESULTS: In the Colistin Group, post-treatment creatinine levels were statistically higher than the pretreatment levels (p = .001). In the remaining groups, no significant changes were observed. Cells that undergo apoptosis were counted and it was shown that all groups except the colistin-treated group had a similar number of apoptotic cells, whereas the colistin-treated group had statistically higher number of apoptotic cells compared to other groups (p = .0001). Renal histological damage was also measured and the score of the colistin treated group was higher as compared to other groups. CONCLUSION: The results obtained from this study demonstrated us that luteolin was capable of preventing colistin-induced nephrotoxicity and that this effect was significant at histopathological level.