Comparative evaluation of analgesic sparing efficacy between dexmedetomidine and clonidine used as adjuvant to ropivacaine in thoracic paravertebral block for patients undergoing breast cancer surgery: A prospective, randomized, double-blind study.

INTRODUCTION: Thoracic paravertebral block (TPVB) is an effective method for intra- and post-operative pain management in thoracic surgeries. For a long time, various adjuvants have been tried for prolonging the duration of TPVB. OBJECTIVE: In this prospective study, we have compared the analgesic sparing efficacy of dexmedetomidine and clonidine, two α2 adrenergic agonists, administered along with ropivacaine for TPVB for breast cancer surgery patients. MATERIALS AND METHODS: Forty-four breast cancer surgery patients undergoing general anesthesia (GA) were randomly divided into Group C and Group D (n = 44 each) receiving preoperative TPVB at T3-5 level with 0.5% ropivacaine solution admixture with clonidine and dexmedetomidine, respectively. Cancer surgery was performed under GA. Intraoperative fentanyl and propofol requirement was compared. Visual analogue scale was used for pain assessment. Total dose and mean time to administration of first rescue analgesic diclofenac sodium was noted. Side effects and hemodynamic parameters were also noted. RESULTS: Intraoperative fentanyl and propofol requirement was significantly less in dexmedetomidine group than clonidine. The requirement of diclofenac sodium was also significantly less and later in Group D than Group C. Hemodynamics, and side effects were comparable among two groups. CONCLUSION: Dexmedetomidine provided better intraoperative as well as postoperative analgesia than clonidine when administered with ropivacaine in TPVB before breast cancer surgery patients without producing remarkable side effects.

Effect of Clonidine as Adjuvant in Thoracic Paravertebral Block for Patients Undergoing Breast Cancer Surgery: A Prospective, Randomized, Placebo-controlled, Double-blind Study.

BACKGROUND AND AIMS: Postoperative pain after breast cancer surgery is unavoidable. Thoracic paravertebral block (TPVB), a locoregional anesthetic technique, has been proven successful for postoperative pain management in different thoracic surgical procedures, such as thoracotomy, breast cancer surgeries. Clonidine, an adjuvant, in TPVB may enhance the quality and prolong the duration of analgesia. This prospective study was to evaluate the effectiveness of clonidine; administered with TPVB; in addition to conventional local anesthetic solution. MATERIALS AND METHODS: Fifty-two patients (25-55 years) scheduled for breast cancer surgery under general anesthesia were randomly divided into Group A (n = 26) receiving preoperative TPVB at T3 with clonidine added to local anesthesia solution and Group B (n = 26) receiving identical TPVB with local anesthesia but without any adjuvant. This was followed by balanced general anesthesia. A visual analog scale was used to assess pain postoperatively up to 48 h. Meantime to administration of the first dose of rescue analgesic was noted. Total dose of fentanyl consumption, hemodynamic parameters, and side effects were all recorded for each patient. RESULTS: The dosage of fentanyl required in the intraoperative period was significantly lower in Group A. Mean time to administration of rescue analgesic was found to be significantly longer in clonidine group. Hemodynamics and side effects were quite comparable among two groups. CONCLUSION: Clonidine as adjuvant in TPVB provided profound analgesia for up to 48 h postoperatively for patients undergoing breast cancer surgery without any appreciable side effects.

Evaluation of Preoperative Flupirtine in Ambulatory Functional Endoscopic Sinus Surgery: A Prospective, Double-Blind, Randomized Controlled Trial.

BACKGROUND: Functional endoscopic sinus surgery (FESS) is the mainstay therapeutic management for nasal pathologies. We evaluated flupirtine, a centrally acting analgesic, for producing perfect perioperative conditions in FESS for adults in a day-care setting. MATERIALS AND METHODS: Sixty-two patients (25-40 years) scheduled for FESS under general anesthesia were randomly divided into Group F (n = 31) receiving preoperative flupirtine (100 mg) and Group C (n = 31) receiving identical-looking placebo capsule per oral 60 min before induction of anesthesia. Perioperative Nasal bleeding and surgeon's satisfaction score during operation; amount and number of patients receiving fentanyl, propofol, and esmolol infusion for analgesia; maintenance of desired bispectral index (BIS) and deliberate hypotension, respectively. Postanesthesia Care Unit (PACU) and hospital stay, hemodynamic parameters, and side effects were all recorded for each patient. RESULTS: Significantly, less number of patients and less dosage of esmolol were required (P = 0.0040 and 0.0001, respectively) in Group F as compared to that in Group C. Again, number of patients requiring fentanyl and dosage of the same drug was significantly lower in Group F. Dose of propofol for the maintenance of BIS was significantly lower in Group F. However, the duration of controlled hypotension was almost similar in both groups. Group F patients suffered significantly less nasal bleeding and surgeon's satisfaction score was also high in this group. Discharge time from PACU and hospital was similar between two groups without any appreciable side effects. CONCLUSION: Flupirtine as a premedication found to be providing more favorable perioperative hemodynamic conditions, analgesia and thus allowing less nasal bleeding as well as more surgeons' satisfaction score.

Perineural Nalbuphine in Ambulatory Upper Limb Surgery: A Comparison of Effects of Levobupivacaine with and without Nalbuphine as Adjuvant in Supraclavicular Brachial Plexus Block - A Prospective, Double-blinded, Randomized Controlled Study.

BACKGROUND AND AIMS: Various opioid additives have been trialed to prolong brachial plexus block. We evaluated the effect of adding nalbuphine hydrochloride to levobupivacaine for supraclavicular brachial plexus blockade. The primary end-points were the onset and duration of sensory and motor blocks and duration of analgesia. MATERIALS AND METHODS: Seventy-eight patients (aged 25-45 years) posted for ambulatory forearm and hand surgery under supraclavicular brachial plexus block were divided into two equal groups (Groups LN and LC) in a randomized, double-blind fashion. In Group LN (n = 39), 30 ml 0.5% levobupivacaine + 10 mg (diluted in 2 ml 0.9% saline) nalbuphine hydrochloride, and in Group LC (n = 39), 30 ml 0.5% levobupivacaine + 2 ml normal saline (0.9%) were administered in supraclavicular block. Sensory and motor block onset times and block durations, time to first analgesic use, total analgesic need, postoperative visual analog scale (VAS), hemodynamics, and side effects were recorded for each patient. RESULTS: Although with similar demographic profile and block (sensory and motor) onset time, sensory and motor block duration and time to first analgesic use were significantly longer and the total need for rescue analgesics was lower in Group LN (P < 0.05) than Group LC. Postoperative VAS value at 24 h was significantly lower in Group LN (P < 0.05). Intraoperative hemodynamics was comparable between two groups, and no any appreciable side effect was noted throughout the study period. CONCLUSION: It can be concluded that adding nalbuphine hydrochloride to supraclavicular brachial plexus block increases the sensory and motor block duration and time to first analgesic use, and decreases total analgesic use with no side effects.

Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury.

Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the adoption of myofibroblast fate, collagen I expression and expression of fibrosis-related genes. Taken together this data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after hypoxic injury and contributes to myofibroblast phenotype and a fibrotic scar formation. Resultant collagen deposition in the scar can maintain elevated SNAIL1 expression in the myofibroblasts and help propagate fibrosis.

Mechanical signals regulate and activate SNAIL1 protein to control the fibrogenic response of cancer-associated fibroblasts.

Increased deposition of collagen in extracellular matrix (ECM) leads to increased tissue stiffness and occurs in breast tumors. When present, this increases tumor invasion and metastasis. Precisely how this deposition is regulated and maintained in tumors is unclear. Much has been learnt about mechanical signal transduction in cells, but transcriptional responses and the pathophysiological consequences are just becoming appreciated. Here, we show that the SNAIL1 (also known as SNAI1) protein level increases and accumulates in nuclei of breast tumor cells and cancer-associated fibroblasts (CAFs) following exposure to stiff ECM in culture and in vivo SNAIL1 is required for the fibrogenic response of CAFs when exposed to a stiff matrix. ECM stiffness induces ROCK activity, which stabilizes SNAIL1 protein indirectly by increasing intracellular tension, integrin clustering and integrin signaling to ERK2 (also known as MAPK1). Increased ERK2 activity leads to nuclear accumulation of SNAIL1, and, thus, avoidance of cytosolic proteasome degradation. SNAIL1 also influences the level and activity of YAP1 in CAFs exposed to a stiff matrix. This work describes a mechanism whereby increased tumor fibrosis can perpetuate activation of CAFs to sustain tumor fibrosis and promote tumor metastasis through regulation of SNAIL1 protein level and activity.

Regional anesthesia in transurethral resection of prostate (TURP) surgery: A comparative study between saddle block and subarachnoid block.

BACKGROUND: Spinal anesthesia is the technique of choice in transurethral resection of prostate (TURP). The major complication of spinal technique is risk of hypotension. Saddle block paralyzed pelvic muscles and sacral nerve roots and hemodynamic derangement is less. AIMS AND OBJECTIVES: To compare the hemodynamic changes and adequate surgical condition between saddle block and subarachnoid block for TURP. MATERIAL AND METHODS: Ninety patients of aged between 50 to 70 years of ASA-PS I, II scheduled for TURP were randomly allocated into 2 groups of 45 in each group. Group A patients were received spinal (2 ml of hyperbaric bupivacaine) and Group B were received saddle block (2 ml of hyperbaric bupivacaine). Baseline systolic, diastolic and mean arterial pressure, heart rate, oxygen saturation were recorded and measured subsequently. The height of block was noted in both groups. Hypotension was corrected by administration of phenylephrine 50 mcg bolus and total requirement of vasopressor was noted. Complications (volume overload, TURP syndrome etc.) were noted. RESULTS: Incidence of hypotension and vasopressor requirement was less (P < 0.01) in Gr B patients. Adequate surgical condition was achieved in both groups. There was no incidence of volume overload, TURP syndrome, and bladder perforation. CONCLUSION: TURP can be safely performed under saddle block without hypotension and less vasopressor requirement.

Comparison between propofol and dexmedetomidine on depth of anesthesia: A prospective randomized trial.

BACKGROUND AND AIMS: Intravenous agents such as propofol are commonly used to maintain adequate depth of anesthesia. Dexmedetomidine which has an anesthetic sparing effect is being considered for maintaining intraoperative depth of anesthesia. We hypothesized to compare the effect of dexmedetomidine on depth of anesthesia with propofol and evaluated whether dexmedetomidine can be used as sole anesthetic agent in maintaining depth of anesthesia. MATERIALS AND METHODS: Sixty patients of ASA PS I, 18-65 years of age, scheduled for laparotomy under general anesthesia were randomly divided into two groups of 30 each. Group A received propofol 1 mg/kg bolus followed by infusion (50 mcg/kg/min) and Group B received dexmedetomidine 1 mcg/kg bolus followed by infusion (0.5 mcg/kg/h). Both the groups were administered standard general anesthesia with routine monitoring along with Bispectral index (BIS) and values were recorded at intervals of 10 min. In all patients Ramsay sedation score was recorded after extubation and they were assessed for recall of intraoperative events using Modified Brice questionnaire. RESULTS: Heart rate and mean arterial pressure were less in Group B than Group A. Intraoperative BIS values were significantly lower in Group B (P < 0.0001). Although sedation score was more in Group B it did not prolong recovery. No recall was found in any patient. CONCLUSION: Dexmedetomidine was comparable with propofol in maintaining anesthesia and it can produce better control of hemodynamics and BIS value. Thus dexmedetomidine can be used as the sole maintenance anesthetic agent.

Temporal and spatial cooperation of Snail1 and Twist1 during epithelial-mesenchymal transition predicts for human breast cancer recurrence.

Epithelial-mesenchymal transition (EMT) is a normal developmental program that is considered to also play an important role in cancer metastasis. Ultimate inducers of EMT are transcriptional repressors that individually can induce experimental EMT, yet in many cells, particularly cancer cells, multiple inducers are expressed simultaneously. Why, and if, and how they interact to regulate EMT is unanswered. Using RNA interference technology to affect protein knockdown and avoid potential overexpression artifact coupled with transient TGFß treatment to better mimic in vivo conditions we show, in both nontumorigenic and tumorigenic epithelial cancer cells, that Snail1 is uniquely required for EMT initiation, whereas Twist1 is required to maintain late EMT. Twist1, present in resting epithelial cells, is dispensable for EMT initiation. Mechanistically, in response to transient TGFß treatment, transient Snail1 expression represses Twist1 transcription directly, which is subsequently upregulated, as Snail1 levels decrease, to sustain E-cadherin downregulation and growth arrest of EMT. Persistent Twist1 expression is associated with a p38 and extracellular signal-regulated kinase signal feedback loop that sustains growth-inhibitory signals characteristic of quiescent micrometastatic tumors. This Snail1-Twist1 temporal and spatial cooperation was also observed in vivo during human breast cancer progression to metastasis. Twist1 level, but not Snail1 level, and Twist1:Snail1 ratio in disseminated micrometastatic bone marrow tumor cells was found to correlate with survival and treatment resistance and is highly predictive of metastatic or recurrent disease.