Ascorbic acid reduces Ropivacaine-induced myotoxicity in cultured human osteoporotic skeletal muscle cells.

BACKGROUND: Osteoporosis is a worldwide health issue. Loss of bone mass is a potential risk factor for fragility fractures, and osteoporotic fractures place a considerable burden on society. Bone and muscle represent a functional unit in which the two tissues are intimately interconnected. Ropivacaine is a potent local anesthetic used in clinical practice for intraoperative anesthesia and postoperative pain management, in particular for hip surgery. When injected, Ropivacaine can diffuse locally through, in particular in surrounding skeletal muscle tissue, causing dose-dependent cytotoxicity, oxidative stress and myogenesis impairment. Based on those evidences, we focused our attention on Ropivacaine-induced cytotoxicity on cultured human myoblasts. METHODS: Primary human myoblasts and myotubes from healthy subjects, osteoarthritic and osteoporotic patients (OP) were cultured in the presence of Ropivacaine. In some experiments, ascorbic acid (AsA) was added as a potent antioxidant agent. Cell viability and ROS levels were evaluated to investigate the myotoxic activity and Real-Time PCR and Western blot analysis carried out to investigate the expression of proliferation and myogenic markers. RESULTS: A dose-dependent decrease of cell viability was observed after Ropivacaine exposure in both OP myoblasts and myotubes cultures, whereas those effects were not observed in the presence of Propofol, a general anesthetic. The adding of AsA reduced Ropivacaine negative effects in OP myoblast cultures. In addition, Ropivacaine exposure also increased ROS levels and upregulated Nox4 expression, an enzyme primarily implicated in skeletal muscle ROS generation. AsA treatment counteracted the oxidant activity of Ropivacaine and partially restored the basal condition in cultures. Positive myogenic markers, such as MyoD and Myf5, were downregulated by Ropivacaine exposure, whereas myostatin, a negative regulator of muscle growth and differentiation, was upregulated. The phenotypic deregulation of myogenic controllers in the presence of Ropivacaine was counteracted by AsA treatment. CONCLUSIONS: Our findings highlight the oxidative stress-mediated myotoxic effect of Ropivacaine on human skeletal muscle tissue cell cultures, and suggest treatment with AsA as valid strategy to mitigate its negative effects and allowing an ameliorated functional skeletal muscle recovery in patients undergoing hip replacement surgery for osteoporotic bone fracture.

Pyodermitis during Nivolumab Treatment for Non-Small Cell Lung Cancer: A Case Report and Review of the Literature.

Immunotherapy in oncology is replacing traditional therapies due to it specific action and limited side effects. Despite the high efficacy of immunotherapy, side effects such as bacterial infection have been reported. Bacterial skin and soft tissue infections represent one of the most important differential diagnoses in patients presenting with reddened and swollen skin and soft tissue. Among these infections, cellulitis (phlegmon) and abscesses are the most frequent. In most cases, these infections occur locally with possible contiguous spread, or as a multifocal manifestation, especially in immunocompromised patients. Herein, we report a case of pyodermitis in an immunocompromised district in a patient treated with nivolumab for non-small cell lung cancer. A 64-year-old, smoker male patient showed cutaneous lesions at a different evolution level in the left arm, all in a tattooed area, with one phlegmon and two ulcerated lesions. Microbiological cultures and gram staining revealed an infection caused by a methicillin-susceptible but erythromycin-resistant (ER-R), clindamycin-resistant (CL-R), and gentamicin-resistant (GE-R) Staphylococcus aureus strain. Despite immunotherapy becoming a milestone in oncologic treatment, more than the spectrum of immune-mediated toxicities of these agents needs to be investigated. This report highlights the importance of considering lifestyle and cutaneous background before starting immunotherapy for cancer treatment, with an emphasis on pharmacogenomics and the possibility of modified skin microbiota predisposing to cutaneous infections in patients treated with PD-1 inhibitors.

Biological acellular pericardial mesh regulated tissue integration and remodeling in a rat model of breast prosthetic implantation.

The use of biological meshes has proven beneficial in surgical restriction and periprosthetic capsular contracture following breast prosthetic-reconstruction. Three different types (smooth, texturized, and polyurethane) of silicone round mini prostheses were implanted under rat skin with or without two different bovine acellular pericardial biological meshes (APMs, BioRipar, and Tutomesh). One hundred eighty-six female rats were divided into 12 groups, sacrificed after 3, 6, and 24 weeks and tissue samples investigated by histology and immunohistochemistry. Implantation of both APMs, with or without prostheses, reduced capsular α-SMA expression and CD3+ inflammatory cell infiltration, increasing capillary density and cell proliferation, with some differences. In particular, Tutomesh was associated with higher peri-APM CD3+ inflammation, prosthetic capsular dermal α-SMA expression and less CD31+ vessels and cell proliferation compared with BioRipar. None differences were observed in tissue integration and remodeling following the APM + prostheses implantation; the different prostheses did not influence tissue remodeling. The aim of our study was to investigate if/how the use of different APMs, with peculiar intrinsic characteristics, may influence tissue integration. The structure of APMs critically influenced tissue remodeling after implantation. Further studies are needed to develop new APMs able to optimize tissue integration and neoangiogenesis minimizing periprosthetic inflammation and fibrosis.

In situ preservation of the partathyroid glands in total thyroidectomy: a propensity score matched analysis.

AIM: Severe hypocalcemia due to parathyroid gland damage may be a serious complication after thyroidectomy. In order to save parathyroid integrity we developed a no-touch parathyroid (NTP) thyroidectomy technique. METHODS: We performed a total extracapsular thyroidectomy with NTP technique in consecutive 50 cases of benign goiter between July 2014 and June 2015. Parathyroid glands were firstly indentified, then they were separated from the thyroid avoiding manipulation or trauma and preserving their vascularization. Traditional scissors were preferentially used for dissection around the glands. Patients operated with NTP technique were matched by a propensity score to a control group. RESULTS: NTP was feasible in all foreseen patients except one. Propensity score selected a group of 23 patients/group for matching. No mortality has been observed in either group. Operative time were comparable between groups. Blood loss were significantly less abundant in the NTP group. No laryngeal permanent paralysis was experienced. Hospital stay was shorter yet not significantly in NTP group. Neither hypocalcemic crisis nor permanent hypoparathyroidism were described in either group. Serum calcium levels (NTP Vs control) were significantly higher in NTP group at day 1 (p=0.03) and day 2 (p=0.002), respectively. Similarly, intact parathormone dosages were significantly higher at day 1 (p=0.004) and day 7 (p=0.001), respectively. CONCLUSIONS: We conclude that NTP thyroidectomy is a feasible in the majority of the patientsand, allows a significant reduction of blood loss without prolonging the operative time. After the procedureboth values of calcemia and intact parathormonewere stable and no hypocalcemic crisis was experienced. KEY WORDS: Parathyroid, Hypoparathyroidism, Hypocalcemia, Total thyroidectomy.

Intraoperative continuous intestinal loop warming technique A prospective randomised trial.

AIM: The aim of this study is to evaluate if the Intraoperative Continuous Intestinal Loop Warming (ICLW) is a valid trick to decrease the postoperative paralytic ileus. METHODS: The subjects were patients who underwent emergency open abdominal surgery for either benign or malignant diseases. Patients were divided into two groups; group A patients who was secluded for ICLW, and a control group B who was not secluded for ICLW. The primary outcomes were the time of recovery of bowel movement, 30 days postoperative mortality and morbidity, morbidity was graded by the Clavien-Dindo classification of surgical complications. Secondary outcomes were operative time, and length of hospital stay. RESULTS: A total numbers of 100 patients were randomly assigned in this prospective study. The mean time of bowel function recovery in the group A was 41.52 hours, whereas for group B was 67.20 hours, these differences were statistically significant with a P value < 0.05. In group B the bowel function recovery for 64% of the patients took between 72-96 hours furthermore, the longest time for peristaltic recovery was 96 hours which was only observed in patients of group B. There were no intra-operative complication in both groups. There is no difference in the two groups in term of 30 day postoperative morbidity. CONCLUSIONS: Intra-operative continuous intestinal loop warming technique is a simple, safe and low cost technique. It seems that intra-operative continuous intestinal loop warming technique maintain tissues hydration and conserve the body temperature limiting the stress response and help in decreasing the incidence of postoperative paralytic ileus. KEY WORDS: Paralytic Ileus, Postoperative Care, Warming.

Intraoperative hemodynamics predict postoperative mortality in orthotopic liver transplantation.

Liver transplantation remains the only curative treatment option for a variety of end-stage liver diseases. Prediction of major adverse events following surgery has traditionally focused on static predictors that are known prior to surgery. The effects of intraoperative management can now be explored due to the archiving of high-resolution monitoring data. We extracted intraoperative hemodynamic trend data of 55 patients undergoing orthotopic liver transplantation (OLT) and computed 12 features from the systolic arterial blood pressure (ABP), cardiac index, central venous pressure (CVP), and stroke volume variation (SVV) signals. Using a logistic regression classifier with a leave-one-out cross-validation procedure, we selected subsets of these features to predict mortality up to 180 days after surgery. Best performance was achieved with a combination of 3 features - median absolute deviation (MAD) of ABP, median CVP, and time spent with SVV <; 10% - reaching an area under the receiver-operating characteristic (or c-statistic) of 0.808. Odds ratios (OR) computed from the coefficients of the multivariate logistic regression model constructed from these features showed that greater time spent with SVV <; 10% (OR = 0.981 min(-1), p = 0.001) and greater MAD of systolic ABP (OR = 0.696 mmHg(-1), p = 0.026) were significantly associated with survival. Adding preoperative measures such as age and serum concentrations of albumin, bilirubin, and creatinine failed to improve performance of the prediction model. These results show that the course of intraoperative hemodynamics can predict 180-day mortality after OLT.

Baroreflex sensitivity variations in response to propofol anesthesia: comparison between normotensive and hypertensive patients.

The aim of this paper is to compare baroreflex sensitivity (BRS) following anesthesia induction via propofol to pre-induction baseline values through a systematic and mathematically robust analysis. Several mathematical methods for BRS quantification were applied to pre-operative and intra-operative data collected from patients undergoing major surgery, in order to track the trend in BRS variations following anesthesia induction, as well as following the onset of mechanical ventilation. Finally, a comparison of BRS trends in chronic hypertensive patients (CH) with respect to non hypertensive (NH) patients was performed. 10 NH and 7 CH patients undergoing major surgery with American Society of Anesthesiologists classification score 2.5 ± 0.5 and 2.6 ± 0.5 respectively, were enrolled in the study. A Granger causality test was carried out to verify the causal relationship between RR interval duration and systolic blood pressure (SBP), and four different mathematical methods were used to estimate the BRS: (1) ratio between autospectra of RR and SBP, (2) transfer function, (3) sequence method and (4) bivariate closed loop model. Three different surgical epochs were considered: baseline, anesthetic procedure and post-intubation. In NH patients, propofol administration caused a decrease in arterial blood pressure (ABP), due to its vasodilatory effects, and a reduction of BRS, while heart rate (HR) remained unaltered with respect to baseline values before induction. A larger decrease in ABP was observed in CH patients when compared to NH patients, whereas HR remained unaltered and BRS was found to be lower than in the NH group at baseline, with no significant changes in the following epochs when compared to baseline. To our knowledge, this is the first study in which the autonomic response to propofol induction in CH and NH patients was compared. The analysis of BRS through a mathematically rigorous procedure in the perioperative period could result in the availability of additional information to guide therapy and anesthesia in uncontrolled hypertensive patients, which are prone to a higher rate of hypotension events occurring during general anesthesia induction.

Effects of propofol anesthesia induction on the relationship between arterial blood pressure and heart rate.

This paper presents the analysis of autonomic nervous system (ANS) control of heart rate (HR) and of cardiac baroreflex sensitivity (BRS) in patients undergoing general anesthesia for major surgery through spectral analysis techniques and with the Granger causality approach that take into account the causal relationships between HR and arterial blood pressure (ABP) variability. Propofol produced a general decrease in ABP due to its vasodilatory effects, a reduction in BRS, while HR remained unaltered with respect to baseline values before induction of anesthesia. The bivariate model suggests that the feedback pathway of cardiac baroreflex could be blunted by propofol induced anesthesia and that the feedforward pathway could be unaffected by anesthesia.

Comparisons of predictors of fluid responsiveness in major surgery.

The majority of studies on fluid responsiveness is focused on volume expansion maneuvers in intensive care unit (ICU), while fewer studies have analyzed the same problem during major surgery. Among them, the results are contrasting. The aim of this work was to compare the performance of different hemodynamic indices in the prediction of cardiac output variations following fast fluid infusion. The study was limited to a particular type of major surgery, i.e. liver transplantation and hepatectomy. Our results showed that pulse pressure variation (PPV) estimated according to the definition, i.e. within single respiratory cycles, and PPV estimated by PiCCO monitor system are coherent and very similar. Moreover, PPV and stroke volume variation (SVV) produced good values of sensitivity and specificity in separating the subjects into responsive and non responsive to maneuvers.

Arterial blood pressure regulation following aorta clamping and declamping during surgery.

In this paper, we propose the use of black box models for the system identification of the cardiopulmonary baroreflex control of arterial resistance and of ventricular contractility and of arterial baroreflex control of heart rate (HR) from invasive, continuous measurements of arterial blood pressure (ABP) and central venous pressure (CVP), and non invasive, continuous recordings of ECG and respiration. Two crucial phases of the abdominal aortic aneurism (AAA) repair were investigated: the clamping and declamping of aorta. The objective of the present work is to evaluate and to test the ability to monitor baroreflex responses to clamping and declamping maneuvers preceding and following aneurism removal.

Estimation of baroreflex sensitivity during anesthesia induction with propofol.

This paper presents the analysis of the autonomic nervous system (ANS) control and cardiac baroreflex sensitivity in patients undergoing general anesthesia for major surgery, with the goal of evaluating the effects of anesthesia bolus induction with propofol on autonomic control of heart rate (HR) and arterial blood pressure (ABP). The increase in baroreflex gain in the LF band observed through two different methods hints at the fact that the baroreflex may increase heart period (HP) following a transient ABP decrease, but its response displays a larger amplitude, to compensate for the blunting of the sympathetic action on heart rate and vascular resistance.

Continuous femoral nerve block provides superior analgesia compared with continuous intra-articular and wound infusion after anterior cruciate ligament reconstruction.

BACKGROUND AND OBJECTIVES: This prospective, randomized, clinical trial compared pain intensity and analgesic drug consumption after anterior cruciate ligament (ACL) reconstruction with patellar tendon under femoral-sciatic nerve block anesthesia in patients who received either a continuous femoral nerve block (CFNB) or continuous local anesthetic wound and intra-articular infusions. METHODS: Fifty patients were randomized to CFNB (n = 25) or an ON-Q device (I-Flow Corp, Lake Forest, Calif) (n = 25). All patients received sciatic nerve block (25 mL of ropivacaine 7.5 mg/mL and clonidine 30 microg). The first group received a CFNB (2 mg/mL of ropivacaine at 7 mL/hr), and the second group received a single-shot femoral nerve block (both using 25 mL of ropivacaine 7.5 mg/mL and clonidine 30 microg). At the end of the intervention, an ON-Q device was positioned on the ON-Q patients to continuously infuse the patellar tendon wound and intra-articular cavity with ropivacaine 2 mg/mL at 2 mL/hr for each catheter. Data regarding demographic, hemodynamic, pain scores, adverse effects, and need for supplemental analgesia were registered in a 36-hr follow-up period. RESULTS: The CFNB group reported lower visual analog scale values than the ON-Q group: at rest at 12 hrs (2.4 [SD, 2.2] vs 5.4 [SD, 3.1]; P < 0.001) and on movement at 12 (3.1 [SD, 2.5] vs 6.3 [SD, 2.9]; P < 0.001) and 24 hrs (2.7 [SD, 1.9] vs 4.6 [SD, 2.6]; P = 0.01) after surgery. The number of morphine and ketorolac boluses was lower in the CNFB group (morphine: 3.2 [SD, 2.2] vs 6.2 [SD, 2.5]; P < 0.001; ketorolac: 1.1 [SD, 1.0] vs 2.4 [SD, 0.9]; P < 0.001). CONCLUSION: Continuous femoral nerve block provides better analgesia than the continuous patellar tendon wound and intra-articular infusions after anterior cruciate ligament reconstruction with patellar tendon.