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Background: L-glutamine (Endari ®) was approved by the US Food and Drug Administration (FDA) in July 2017 to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients, aged 5 years and older. Data collected during the phase 2 and phase 3 trials demonstrated a rather mild adverse event profile at the approved doses (approximately 0.3 g/kg administered twice daily). The combined data from the clinical trials encompassed 187 patients assigned to the L-glutamine arm and 111 patients assigned to the placebo arm. The most common side effects observed were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain. Since 2017, safety data for L-glutamine has been collected through several sources. Aim: To determine whether new safety concern signals for L-glutamine in the treatment of SCD have emerged over the post-marketing period since July of 2017. Methods: Individual case safety reports (ICSR) received from consumers, physicians, pharmacies, and other healthcare professionals that were processed in the global safety database in real time were reviewed. Continuous safety evaluations that were performed when evaluating ICSRs were collected. Additionally, signal management activities performed quarterly since July 2017, which included screening of literature and regulatory websites for the identification of potential safety information, were evaluated. Results: Overall, 1791 case reports were received with 2954 adverse events between July 07, 2017 (the date of approval) and July 06, 2021. A summary of frequently reported adverse events during the post-marketing phase is presented in Figure 1. No new safety concerns have been identified upon evaluation of these events, which has been performed on a quarterly basis from the approval date. Conclusion: Post-marketing surveillance data indicates that L-glutamine administered at approximately 0.3 g/kg twice daily is safe and well-tolerated. The most common side effects observed during clinical trials were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (Table 1). These same side effects have been observed in the post-marketing phase with the exception of "cough." Side effects reported during the post-marketing phase that were not reported in the clinical trials were abdominal discomfort, diarrhea, malaise, and pain. The majority of these reports were categorized as non-serious (Figure 1). Information pertaining to these events was limited or the event could be explained by the underlying condition or concomitant medication; therefore, these events were not considered to be new safety concerns. In summary, there were no new safety concerns identified with L-glutamine for the treatment of SCD in the post-marketing period. Figure 1 Figure 1. Disclosures Mayuzumi: Emmaus Medical, Inc: Current Employment. Razon: Emmaus Medical, Inc: Current Employment. Singh: Emmaus Medical, Inc: Current Employment. Goodrow: Emmaus Medical, Inc: Current Employment. Becerra: Emmaus Medical, Inc: Current Employment. Stark: Emmaus Medical, Inc: Current Employment. Niihara: Emmaus Lifesciences, Inc.: Current Employment.

Histone deacetylases (HDACs) are a family of deacetylase enzymes that regulate the acetylation state of histones and a variety of other non-histone proteins including key oncogenic and tumor suppressor proteins, which modulates chromatin conformation, leading to regulation of gene expression. HDACs has been grouped into classes I-IV and histone deacetylase 9 (HDAC9) belongs to class IIa which exhibits tissue-specific expression. Recent reports have demonstrated both pro-oncogenic and tumor suppressive role for HDAC9 in different cancers; however, its role in OSCC remains elusive. Here, we investigated the role of HDAC9 in pathogenesis of oral squamous cell carcinoma (OSCC). Our data showed significantly increased mRNA and protein expression of HDAC9 in clinical OSCC samples and UPCI-SCC-116 cells as compared to normal counterpart. Kaplan-Meier analysis showed that the patients with high-level of HDAC9 expression had significantly reduced overall survival than those with low-level of HDAC9 expression (p = 0.034). Knockdown of HDAC9 using siRNA interference suppressed cell proliferation, increased apoptosis, and induced G0/G1 cell cycle arrest in UPCI-SCC-116 cells. Immunofluorescence analysis showed increased nuclear localization of HDAC9 in frozen OSCC sections, and indicative of active HDAC9 that may transcriptionally repress its downstream target genes. Subsequent investigation revealed that overexpression of HDAC9 contributes to OSCC carcinogenesis via targeting a transcription factor, MEF2D, and NR4A1/Nur77, a pro-apoptotic MEF2 target.

microRNAs are the post-transcriptional regulators implicated in the initiation and progression of various cancer types, including oral squamous cell carcinoma (OSCC). Here, we investigated the role of miR-377 in OSCC tumorigenesis. miR-377 expression was reduced in OSCC samples and cell line (UPCI-SCC-116), and was associated with patient survival. In vitro restoration of miR-377 repressed cell growth, induced apoptosis, and reduced cell migration. We identified HDAC9 as a target of miR-377 and found miR-377 to regulate HDAC9 and its pro-apoptotic target, NR4A1/Nur77. Our findings show that miR-377 targets HDAC9 pathway in OSCC, suggesting that miR-377–HDAC9 axis may provide a novel therapeutic target for OSCC therapy.

p53-p21 pathway mediates cardiomyocyte hypertrophy and apoptosis and is upregulated in diabetic cardiomyopathy (DbCM). We investigated role of microRNAs in regulating p53-p21 pathway in high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis. miR-30c and miR-181a were identified to target p53. Cardiac expression of microRNAs was measured in diabetic patients, diabetic rats, and in HG-treated cardiomyocytes. Effect of microRNAs over-expression and inhibition on HG-induced cardiomyocyte hypertrophy and apoptosis was examined. Myocardial expression of p53 and p21 genes was increased and expression of miR-30c and miR-181a was significantly decreased in diabetic patients, DbCM rats, and in HG-treated cardiomyocytes. Luciferase assay confirmed p53 as target of miR-30c and miR-181a. Over-expression of miR-30c or miR-181a decreased expression of p53, p21, ANP, cardiomyocyte cell size, and apoptosis in HG-treated cardiomyocytes. Concurrent over-expression of these microRNAs resulted in greater decrease in cardiomyocyte hypertrophy and apoptosis, suggesting a synergistic effect of these microRNAs. Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53-p21 pathway in DbCM.

Background: Endotracheal intubation is important to carry out various surgical procedures. The estimation of endotracheal tube size is governed by narrowest diameter of the upper airway. The objective of the study was to assess the narrowest tracheal diameter by ultrasound for selection of the appropriate size endotracheal tube. Materials and Methods: After the approval of institution ethical committee and written informed consent, 112 patients aged 3 to 18 years of both genders with normal airways, scheduled for surgery under general anesthesia and intubation, were enrolled for this prospective clinical observational study. Preanesthetic ultrasonography of the subglottic region was performed by experienced ultrasonologist with a high-resolution linear array transducer in sniffing position for every patient and the subglottic tracheal diameter was estimated to select the appropriate-size endotracheal tube. The endotracheal tube, calculated on the basis of physical indices and by ultrasound, was statistically correlated with the appropriate size endotracheal tube used clinically for intubation. Results: The ultrasound guided selection criterion has estimated the appropriate-sized endotracheal tube better than physical indices (age or height)-based formulas. The estimated endotracheal tube size by ultrasound was significantly correlated with the clinically used endotracheal tube. Conclusion: Ultrasonography may be used for the assessment of the subglottic diameter of trachea in children to estimate the appropriate size endotracheal tube for intubation.

Background: Postoperative pain has a significant impact on patient's recovery and optimal nonopioid analgesia would reduce postoperative pain and pain-related complications. This study was aimed to evaluate the analgesic efficacy and safety of intravenous paracetamol versus parecoxib for postoperative analgesia after surgery. Materials and Methods: Sixty-eight adult consented patients belonging to ASA I and II, scheduled for surgery, were randomly allocated in two treatment groups receiving either infusion of paracetamol (1 gm) or parecoxib (40 mg). The surgical and anesthetic techniques were standardized. Postoperative pain was assessed using visual analog score (VAS) at rest, during coughing and movement. The primary variables were the differences between the mean values of postoperative pain scores, time of first dose of rescue analgesic (tramadol) required, and patient satisfaction throughout the first 12 postoperatively. Results: There was no significant difference among groups to first request for tramadol. The VAS score was significantly less in parecoxib group at rest compared to paracetamol group (P

Background: Laparoscopic cholecystectomy under general anesthesia induced intraoperative hemodynamic responses which should be attenuated by appropriate premedication. The present study was aimed to compare the clinical efficacy of clonidine and fentanyl premedication during laparoscopic cholecystectomy for attenuation of hemodynamic responses with postoperative recovery outcome. Subjects and Methods : In this prospective randomized double blind study 64 adult consented patients of either sex with ASA I and II, scheduled for elective laparoscopic cholecystectomy under general anesthesia and met the inclusion criteria, were allocated into two groups of 32 patients. Group C patients have received intravenous clonidine 1μg kg -1 and Group F patients have received intravenous fentanyl 2μg kg -1 5 min before induction. Anesthetic and surgical techniques were standardized. All patients were assessed for intraoperative hemodynamic changes at specific time and postoperative recovery outcome. Results : Premedication with clonidine or fentanyl has attenuated the hemodynamic responses of laryngoscopy and laparoscopy. Clonidine was superior to fentanyl for intraoperative hemodynamic stability. No significant differences in the postoperative recovery outcome were observed between the groups. Nausea, vomiting, shivering and respiratory depression were comparable between groups. Conclusion : Premedication with clonidine or fentanyl has effectively attenuated the intraoperative hemodynamic responses of laparoscopic cholecystectomy.

Background: Patient's awareness can be reduced during ultrasound guided nerve block for inguinal herniorraphy with propofol sedation. The study was aimed to evaluate the clinical efficacy of direct visualization of anatomy of inguinal region by ultrasound and benefits of bispectral index (BIS) monitoring. Materials and Methods: After approval, 40 adult male consented patients of ASA grade I-III of 18-58 years with body mass index

Background: Anesthetic management of elderly patients is a challenge as aging makes them more susceptible to hemodynamic fluctuations during regional anesthesia. This study was aimed to compare the clinical efficacy of epidural 0.75% ropivacaine fentanyl (RF)- with 0.5% bupivacaine-fentanyl (BF) for hemiarthroplasty in high-risk elderly patients. Methods: Sixty elderly consented patients of either sex with American Society of Anesthesiologist ASA II and III, scheduled for elective hemiarthroplasty were randomized into two Groups of 30 patients to receive epidural study solution of 15 mL of 0.75% Ropivacaine or 0.5% Bupivacaine with 1 mL fentanyl (50 μg). The hemodynamic variability with onset and duration of sensory and motor blocks were recorded. The adequacy and quality of surgical anesthesia were assessed. The post-epidural nausea and vomiting, shivering, respiratory parameters, or any other side effects were also recorded. Results: There was no difference in the demographic profile between groups. The mean onset time to achieve sensory block to the T 10 dermatome was rapid in the Group BF (12.4±6.9 vs. 17.5±3.7 min in Group RF). The mean time to achieve motor block was 17.5±3.4 min in Group BF versus 21.7±7.8 min in Group RF. The intraoperative hemodynamic fluctuations showed statistically significant differences between groups. The pruritis was observed in five patients but post-epidural shivering, nausea, vomiting, respiratory depression, or urinary retention were not observed in any patient. Conclusion: Epidural 0.75% Ropivacaine with fentanyl showed better clinical profile as compared to 0.5% Bupivacaine with fentanyl for hemiarthroplasty in elderly patients.

A young epileptic woman with twin pregnancy (IUD) was posted for orthopaedic correction under general anaesthesia on assisted ventilation with laryngeal mask airway (LMA). The present article focuses on anaesthetic concerns in pre-operative preparation and management of such patients.

– Panfacial fractures present a unique set of problems to the anaesthesiologist and surgeon. Airway management in panfacial fractures is still a challenge to the anaesthesiologist as all modalities available such as orotracheal intubation, nasotracheal intubation, tracheostomy, etc., have their own advantages and disadvantages. When all the conventional modalities to secure airway seem unsuitable then submental route offers an excellent alternative to manage airway in such patients. Here we describe our experience with submental intubation technique in 10 patients with panfacial injuries over a period of two years.

The immunomodulatory properties of ethanol insoluble fraction of aqueous extract of Tridax procumbens Linn. (TPEIF) have been investigated. After intraperitoneal administration of TPEIF in doses of 0.25 and 0.5 g/kg body weight (BW) a significant increase in phagocytic index, leukocyte count and spleenic antibody secreting cells was noticed. Stimulation of humoral immune response was further observed with elevation in heamagglutination antibody titer. Heightened delayed type hypersensitivity reaction suggested convincing evidence for activation of cellular immune system. Protective action of herbal medicine in case of anaphylactic shock was also studied. In addition, elicitation of specific antibody titer against tetanus toxoid (TT) challenge was measured in order to explore the possible use as adjuvant along with clinical vaccination program to reduce number of non-responders. The results suggest that TPEIF influences both humoral as well as cell mediated immune system vis-a-vis assists in genesis of improved antibody response against specific clinical antigen.

Background: Epidural adjuvants enhance the quality and duration of surgical anesthesia. The present study was aimed to compare the hemodynamic, sedative, and analgesia potentiating effects of dexmedetomidine versus fentanyl with epidural 0.5% levobupivacaine for vaginal hysterectomy. Patients and Methods: Sixty consented females of ASA physical status I and II aged 35-65 years weighing 55-75 kg, were double blindly randomized into two treatment groups. Patients received epidural 0.5% levobupivacaine 15 ml either with of 25 μg dexmedetomidine (Group LD) or 50 μg fentanyl (Group LF) and the total volume of study solution was kept 16 ml. Onset of analgesia at T10, sensory and motor block levels and duration of analgesia were observed. Intra-operatively, they were assessed for sedation, hemodynamic changes, respiratory efficiency, and side effects. The data obtained, was compiled systematically and analyzed statistically using Chi-square test and ANOVA. Value of P < 0.05 is considered significant. Result: The demographic profile was comparable between groups. The onset of sensory analgesia at T10 (7.25 ± 2.3 versus 9.27 ± 2.79 min) and time to achieve complete motor blockade (19.27 ± 4.7 versus 22.78 ± 5.57 min) was significantly earlier in patients of LD Group. The intraoperative hemodynamic changes were comparable between groups. Ramsey Sedation score was better in LD group with statistically significance. Postoperative analgesia was significantly prolonged in LD Group. Incidence of nausea, vomiting, and pruritus was high in LF group. Conclusion: Dexmedetomidine was better than fentanyl as an epidural adjuvant for providing early onset of sensory analgesia, adequate sedation with no respiratory depression and prolonged postoperative analgesia.

Background: Postoperative nausea and vomiting is commonly associated with adverse consequences and hamper the postoperative recovery in spite of the availability of many antiemetic drugs and regimens for its prevention. The study was aimed to compare the prophylactic effects of intravenously administered palonosetron, ondansetron, and granisetron on prevention of postoperative nausea and vomiting after general anesthesia. Materials and Methods: This prospective, double-blind study, comprised 120 adult consented patients of ASA grade I and II of either gender, was carried out after approval of Institutional Ethical Committee. Patients were randomized into three equal groups of 40 patients each in double-blind manner. Group P received inj. palonosetron (0.075 mg), group O received inj. ondansetron (4 mg), and group G received inj. granisetron (2 mg) intravenously five minutes before induction of anesthesia. The need for rescue antiemetic, episode of postoperative nausea and vomiting, and side effects were observed for 12 hours in the post-anesthesia care unit. At the end of study, results were compiled and statistical analysis was done by using ANOVA, Chi-square test, and Kruskal Wallis Test. Value of P < 0.05 was considered significant. Results: The incidence of nausea and vomiting was maximal during the first four hours postoperatively. The complete control of postoperative nausea and vomiting for first 12 hours was achieved in 30% patients of ondansetron group, 55% patients of granisetron group, and 90% patients of palonosetron group. Safety profile was more with palonosetron. Conclusion: Palonosetron was comparatively highly effective to prevent the PONV after anesthesia due to its prolonged duration of action than ondansetron and granisetron.

Background: Anesthesia and surgery-induced neuroendocrine stress response can be modulated by appropriate premedication. The present study was designed to assess the clinical efficacy of dexmedetomidine versus fentanyl premedication for modulation of neuroendocrine stress response by analyzing the perioperative variation of blood glucose level during laparoscopic cholecystectomy under general anesthesia. Subjects and Methods: In a prospective randomized double-blind study, 60 adult consented patients of either sex with ASA I and II, scheduled for elective laparoscopic cholecystectomy under general anesthesia and meeting the inclusion criteria, were allocated into two groups. Group D patients ( n = 30) were given intravenous dexmedetomidine 1μg/kg and Group F patients ( n = 30) received fentanyl 2 μg/kg, given over a 10-min period, before induction of anesthesia. Perioperative blood glucose levels were analyzed preoperatively, at 30 min after beginning of surgery, and 2.5 h after surgery. Anesthetic and surgical techniques were standardized. All patients were also assessed for intraoperative hemodynamic changes of heart rate and mean arterial pressure at specific timings. Results: Blood glucose concentration has shown 20% increase after surgery. The differences between groups were not statistically significant as observed by analyzing the variation of serial perioperative blood glucose estimation. Both premedicants had attenuated the hemodynamic and neuroendocrine stress response of pneumoperitoneum and general anesthesia. The dexmedetomidine group showed more stabilization of intraoperative hemodynamics of mean arterial blood pressure and heart rate when compared to fentanyl group. Conclusion: During the laparoscopic cholecystectomy, dexmedetomidine and fentanyl, both premedicants have effectively modulated the neuroendocrine stress response of general anesthesia as assessed by analysis of perioperative blood glucose variation, but dexmedetomidine was better.

Background: Subarachnoid anesthesia is used as the sole anesthetic technique for below umbilical surgeries, but patients with deformed spine represent technical difficulty for its establishment. This study was aimed to find out whether training of Taylor's approach to residents on normal spine is beneficial for establishing subarachnoid block in patients with deformed spine. Materials and Methods: The total of 174 patients of ASA I-III with normal and deformed spine of both genders scheduled for below umbilical surgeries under the subarachnoid block and met the inclusion criteria, were enrolled for this two-phased clinical teaching study. All participating residents have performed more than 100 subarachnoid block with the median and paramedian approach. Residents were randomized into two equal groups. During the first phase program, Group I was taught Taylor's approach by hands on method for the subarachnoid block while Group II kept on observation for the technique. During the second phase of program, Group II was also taught Taylor's approach for establishing the subarachnoid block. Block success was defined according to clinical efficacy. Results: The results of teaching of Taylor's approach were encouraging. Initially, the residents faced difficulty for establishing the subarachnoid block in deformed spine but after learning by observation and practical hands on, both groups had successfully performed the subarachnoid block by Taylor's approach in one or more attempts in patient with deformed spine with the acceptable failure rate of 15%. Conclusion: Taylor's approach for establishing subarachnoid block in deformed spine should be taught to residents on normal spine.

Background: The radical surgical procedures are associated with perioperative blood loss. This study was aimed to evaluate the clinical efficacy and safety of tranexamic acid in reducing perioperative blood loss in patients undergoing radical surgery. Materials and Methods: Sixty ASA class I and II adult consented female patients, scheduled for elective radical surgery and met the inclusion criterion, were blindly randomized into two groups to receive either intravenous 1 g tranexamic acid 20 min before skin incision or an equivalent volume of normal saline as placebo (P). All patient's total blood loss was measured and recorded perioperatively at the 12thh postoperatively. The preoperative and postoperative hemoglobin, hematocrit values, serum creatinine, activated thromboplastin time, prothombin time, thrombocyte count, fibrinogen, D-dimer, and symptoms of pulmonary embolism were comparatively evaluated. Results: The tranexamic acid significantly reduced the quantity of total blood loss, 576 ± 53 mL in study group as compared to 823 ± 74 mL in the control group (P

Background: Ketamine-induced hemodynamic pressor response and psychomimetic effects should be attenuated by appropriate premedication. The present study was designed to evaluate the clinical efficacy and safety of dexmedetomidine premedication for balancing the ketamine-induced hemodynamic pressor response and psychomimetic effects. Materials and Methods: A total of 80 normotensive adult consented patients of ASA grade I and II of both genders, aged 21 to 55 years, who met the inclusion criteria for elective surgery under ketamine anesthesia were randomized for this prospective blind study and divided into two treatment groups of 40 patients each. Group I patients received premedication of midazolam and Group II patients received premedication of dexmedetomidine. Anesthetic and surgical techniques were standardized. Both groups were assessed for changes in heart rate and systolic blood pressure intraoperatively and psychomimetic effects with behavioral changes postoperatively. Results: Preoperatively, all patients were awake. Intraoperatively, the heart rate was 116.6±4.2 in group I versus 76.8±5.8 in group II (P value 0.0004) and systolic blood pressure was 153.07±16.05 in group I versus 139.17±19.9 in group II (P value 0.001). Post-anesthetic psychomimetic responses were not statistically significant between groups. Conclusion: The dexmedetomidine premedication effectively attenuated the ketamine induced hemodynamic pressor response and post-anesthetic delirium effects.

Context: Fluid absorption is inevitable complication of transuretheral resection of prostate and serum electrolytes changes can indirectly assess the irrigation fluid absorption. Aims: To monitor the extent of 1.5% glycineirrigation fluid absorption during transurethral resection of prostate (TURP), by measuring the changes of serum sodium and potassium levels peri-operatively. Settings and Design: This is a randomized prospective cohort observational study. Materials and Methods: The 86 male patients of ASA grades I to III in the age group of 50 to 80 years, scheduled for elective TURP surgery under central neuraxial block, were studied. Their preoperative and post-operative serum sodium, potassium and calcium levels were measured. When duration of surgery exceeds 60 min, serum sodium and potassium levels were done intra-operatively with venous blood samples by using blood gas analyser. The height of irrigation fluid column was kept constant at 60 cm. These changes were correlated with the volume of irrigating fluid used, duration of procedure and the volume of prostate gland resected. Statistical Analysis Used: The values of pre and postoperative sodium, potassium and calcium serum levels were compared and statistical significance of the difference in values was assessed using Student′s paired t test. Results: Statistically significant reduction of serum sodium levels (hyponatremia) and elevation of serum potassium levels (hyperkalemia) were observed post-operatively, which was directly proportional to volume of irrigating fluid used, duration of procedure and volume of prostate gland resected. No significant changes in serum calcium level were observed. Conclusions: To measure serum electrolytes changes during TURP surgery, it is simple and economical method for indirect assessment of fluid absorption for early identification of TURP syndrome.

The experience in treating three patients with hemangiopericytoma is reviewed. One patient was given irradiation alone, and the others were both treated with surgery and irradiation. Our experience reinforces reports of the usefulness of irradiation in treating this neoplasm and its metastases.