Dysregulation of miR-146a is associated with exacerbated inflammation, oxidative and endoplasmic reticulum stress in the progression of diabetic foot ulcer.

Recent evidence has implicated the role of microRNA-146a (miR-146a) in regulating inflammatory responses. In the present study, we investigated the role of miRNA-146a in the progression of diabetic foot ulcer (DFU) in type 2 diabetes mellitus patients (T2DM) and studied its correlation with stress mediators such as Endoplasmic Reticulum (ER) and oxidative stress. Ninety subjects were enrolled and evenly distributed among three groups: Controls (n = 30), T2DM without complications (n = 30) and T2DM with foot ulcers (n = 30). Subsequently, each group was further subdivided based on the University of Texas classification. Peripheral blood was collected from all the study subjects, while tissue biopsies were taken only from DFU patients. Total RNA from both PBMCs and wound tissues were isolated using miRNA isolation kit and qPCR was performed to check the expression of miR-146a, ER stress and oxidative stress markers. Our findings revealed a significant decrease in miR-146a expression among T2DM patients with Grade 2 and Grade 3 DFUs compared with those with Grade 0 and Grade 1 DFUs. Notably, inflammatory genes regulated by miR-146a, including TRAF6, IRAK-1 and ADAM, were all upregulated in T2DM patients with Grade 2 and Grade 3 DFUs. Moreover, reduced miR-146a levels were correlated with increased markers of ER stress and oxidative stress in Grade 2 and Grade 3 DFU patients. Furthermore, our in vitro experiment using mouse 3T3 fibroblasts demonstrated a downregulation of miR-146a following induction of hyperglycaemia, ER stress and oxidative stress in these cells. These findings suggest a potential link between diminished miR-146a expression and heightened oxidative and ER stress in T2DM patients with more severe grades of DFUs. Our results imply that targeting miR-146a may hold therapeutic promise for managing disease progression in DFU patients, as it could help alleviate oxidative and ER stress associated with diabetic complications.

Multimodal imaging device to comprehensively assess infection, oxygenation, and wound analytics-A pilot study.

Wound analytics, infection detection, and oxygenation measurement are the three critical prerequisites for appropriate wound care. Although devices that rapidly detect the above-mentioned parameters independently exist, there is no single point-of-care device that is enabled with all the three functionalities. Through this study, we are introducing and evaluating the performance of Illuminate Pro Max-a novel, rapid, hand-held non-contact, point-of-care multimodal imaging device that is equipped to measure the three wound assessment parameters. Here, a total of 60 diabetic foot ulcer patients were imaged using Illuminate Pro Max to detect bioburden and measure StO2 levels and wound dimensions (size and depth). The results were further evaluated against the current gold standard technique for each parameter, that is, culture test to detect bioburden, a transcutaneous oxygen pressure (TcPO2) measuring device-Perimed Periflux 5000 to measure oxygenation, and paper ruler to measure wound size. Culture tests reported 42 samples as infection-positive and 18 samples as infection-negative. On comparing with the culture report, the device showed 88% sensitivity and 86% PPV in detecting the bioburden. Wound dimensions (length and width) were comparable with the paper scale measurements. Wound depth was also reported by the device. The StO2 map generated by the device depicted the tissue oxygenation levels in various regions of the wound. In conclusion, this novel, comprehensive point-of-care multispectral imaging device can be an effective tool for rapid wound assessment which can help in prompt treatment.

Topical Esmolol Hydrochloride as a Novel Treatment Modality for Diabetic Foot Ulcers: A Phase 3 Randomized Clinical Trial.

Importance: Preclinical and phase 1/2 studies with esmolol hydrochloride suggest its potential role in treatment of diabetic foot ulcers (DFUs). Objective: To study the efficacy of topical esmolol for healing of uninfected DFUs. Design, Setting, and Participants: A randomized, double-blind, multicenter, phase 3 clinical trial was conducted from December 26, 2018, to August 19, 2020, at 27 referral centers across India. Participants included adults with DFUs. Interventions: Participants were randomized after a run-in phase (1 week) to receive esmolol, 14%, gel with standard of care (SoC), SoC only, or vehicle with SoC (3:3:1 proportion) for 12 weeks (treatment phase) and followed up subsequently until week 24. Main Outcomes and Measures: The primary outcome was the proportion of wound closure within the 12-week treatment phase in the esmolol with SoC and SoC only groups. Analysis was conducted using an intention-to-treat safety evaluable population, full analysis set or efficacy-evaluable population, and per-protocol population comparing the esmolol plus SoC and SoC only treatment groups. Results: In the study, 176 participants (122 men [69.3%]; mean [SD] age, 56.4 [9.0] years; mean [SD] hemoglobin A1c level, 8.6% [1.6%]) with DFUs classified as University of Texas Diabetic Wound Classification system grade IA and IC (mean [SD] ulcer area, 4.7 [2.9] cm2) were randomized to the 3 groups. A total of 140 participants were analyzed for efficacy. The proportion of participants in the esmolol with SoC group who achieved target ulcer closure within 12 weeks was 41 of 68 (60.3%) compared with 30 of 72 (41.7%) participants in the SoC only group (odds ratio [OR], 2.13; 95% CI, 1.08-4.17; P = .03). A total of 120 participants completed the end of study visit which were analyzed. Target ulcer closure by the end of the study (week 24) was achieved in 44 of 57 (77.2%) participants in the esmolol with SoC group and 35 of 63 (55.6%) participants in the SoC only group (OR, 2.71; 95% CI, 1.22-5.99; P = .01). The median time for ulcer closure was 85 days for the esmolol with SoC group and was not estimable for SoC only group. Significant benefits of Esmolol with SoC were seen in patients with factors that impede the healing of DFU. Treatment-emergent adverse events were noted in 18.8% of the participants, but most (87.3%) of these events were not attributable to the study drug. Conclusions and Relevance: In this multicenter, randomized, double-blind clinical trial, the addition of esmolol to SoC was shown to significantly improve the healing of DFUs. With these results, topical esmolol may be an appropriate addition to SoC for treating DFUs. Trial Registration: ClinicalTrials.gov Identifier: NCT03998436; Clinical Trial Registry, India CRI Number: CTRI/2018/11/016295.

Evaluation of analgesic effects and hemodynamic responses of epidural ropivacaine in laparoscopic abdominal surgeries: Randomised controlled trial.

Background and Aims: The role of epidural analgesia in laparoscopic surgeries remains controversial. We evaluated intraoperative analgesic effects of epidural ropivacaine versus intravenous fentanyl in laparoscopic abdominal surgery and assessed postoperative analgesic requirements, hemodynamic changes, time to ambulation, and length of stay (LOS) in the ICU. Material and Methods: Seventy-two American Society of Anesthesiologists physical status I-III adult patients undergoing elective laparoscopic abdominal surgeries were randomized to either 0.5 mg/kg/h intravenous fentanyl (Group C) or 0.2% epidural ropivacaine at 5-8 mL/h (Group E) infusions intraoperatively and 0.25 m/kg/h fentanyl and 0.1% epidural ropivacaine infusions respectively postoperatively. Variations in mean arterial pressure (MAP) of 20% from baseline were points of intervention for propofol and analgesia with fentanyl or vasopressors. The number of interventions and total doses of fentanyl and vasopressors were noted. Postoperative analgesia was assessed at 0, 6, 12, and 24 h and when pain was reported with numerical rating scale and objective pain scores. Chi-square test and Student's t-test were used for categorical and continuous variable analysis. Results: Intraoperatively, 14 patients versus 4 needed additional fentanyl and 26 versus 14 needed additional propofol in groups C and E respectively (P = 0.007, P = 0.004). MAP at 0, 6 and 18 h was lower in Group E. Pain scores were better in Group E at 6,18, and 24 h postoperatively. Time to ambulation was comparable but LOS ICU was prolonged in Group E (P = 0.05). Conclusion: Epidural ropivacaine produces superior intraoperative analgesia and improved postoperative pain scores without affecting ambulation but increases vasopressor need and LOS ICU in comparison with intravenous fentanyl in laparoscopic abdominal surgeries.

Management of Diabetic Foot Ulcer with MA-ECM (Minimally Manipulated Autologous Extracellular Matrix) Using 3D Bioprinting Technology - An Innovative Approach.

Chronic foot ulcers are the leading cause of prolonged hospitalization and loss of social participation in people with diabetes. Conventional management of diabetic foot ulcers (DFU) is associated with slow healing, high cost, and recurrent visits to the hospital. Currently, the application of autologous lipotransfer is more popular, as the regenerative and reparative effects of fat are well established. Herein we report the efficacy of minimally manipulated extracellular matrix (MA-ECM) prepared from autologous homologous adipose tissue by using 3D bioprinting in DFU (test group) in comparison to the standard wound care (control group). A total of 40 subjects were screened and randomly divided into test and control groups. In the test group, the customized MA-ECM was printed as a scaffold from the patient autologous fat using a 3D bioprinter device and applied to the wound directly. The control group received standard wound care and weekly follow-up was done for all the patients. We evaluated the efficacy of this novel technology by assessing the reduction in wound size and attainment of epithelialization. The patients in the test group (n = 17) showed complete wound closure with re-epithelialization approximately within a period of 4 weeks. On the other hand, most of the patients in the control group (n = 16) who received standard wound dressings care showed a delay in wound healing in comparison to the test group. This technique can be employed as a personalized therapeutic method to accelerate diabetic wound healing and may provide a promising potential alternative approach to protect against lower foot amputation a most common complication in diabetes.

Comparison of analgesic requirements in robot-assisted versus conventional laparoscopic abdominal surgeries.

BACKGROUND AND AIMS: Robot-assisted surgery is advantageous in the precision of tissue handling and shorter postoperative recovery. We compared postoperative analgesic requirements in laparoscopic versus robot-assisted surgery in the first 24 h as our primary objective. The secondary outcomes were extubation on table, time to ambulation, and length of ICU stay. MATERIAL AND METHODS: After approval from the ethics committee 48 patients undergoing either laparoscopic (group L [n = 24]) or robotic abdominal surgery (group R [n = 24]) were evaluated for analgesic requirements postoperative targeting a numerical rating scale ≤3 in a prospective comparative study. Postoperative patients were allotted to a three-tier pain management, level 1 comprising paracetamol 1 g intravenously every 8 h, level 2, 1.5 mg/kg tramadol every 8 h, and level 3 fentanyl 0.5 µg/kg. The total analgesic consumption in the first 24 h was calculated for each group. Statistical analysis was performed using the Chi-square test and Mann-Whitney U test. RESULTS: Age, weight, and types of surgery were comparable between the groups. The intraoperative opioid use was comparable between both groups but the duration of surgery was longer in group R. Postoperative analgesic requirements were significantly less in group R (P = 0.024) and the length of ICU stay was shorter (P < 0.05). The time to ambulation was significantly shorter in group R patients (P < 0.001). CONCLUSION: Analgesic requirements were significantly less in robot-assisted laparoscopic surgery in the first 24 h. The time to ambulation and length of ICU stay were shorter in the robot-assisted group in comparison to the laparoscopic group.

Prospective Randomized Study Comparing the Usefulness of Dexmedetomidine versus Esmolol in Blunting Hemodynamic Responses to Intubation in Surgical Patients.

Background: Sympathetic response due to laryngoscopy and endotracheal intubation though transient, could be life-threatening in patients with underlying cardiovascular diseases. Aim of the Study: The aim of this study is to assess the effects of dexmedetomidine and esmolol on the hemodynamic response to laryngoscopy and endotracheal intubation in patients undergoing general anesthesia for elective surgery. Settings and Design: Prospective, randomized study conducted in a tertiary care center. Materials and Methods: Sixty patients were recruited and randomly divided into two groups. Group A received 0.5 mcg.kg-1 dexmedetomidine and Group B 0.5 mg.kg-1 esmolol infusions over 10 min. All patients were induced with propofol 2 mg.kg-1 followed by succinylcholine 2 mg.kg-1 and intubated. The heart rate (HR) and mean arterial pressure (MAP) were recorded at different time points. Statistical Analysis Used: Chi-square test, independent sample t-test, and paired t-test. Results: Baseline HR was statistically different in both groups. There was significant decrease in percentage change in baseline HR in Group A compared to Group B at preinduction (20.44% ± 10.82%, 13.63% ± 11.84%), before intubation (23.49 ± 12.62, 13.95 ± 14.86), and 7 min after intubation (14.65 ± 12.62, 6.80 ± 16.11). Percentage change in HR remained comparable in all other time points. Baseline MAP was comparable between the groups. Percentage change from baseline of MAP was significantly higher in Group B before intubation. All other time points MAP were comparable. The incidence of hypotension was comparable in both groups. Conclusions: Both dexmedetomidine and esmolol suppressed the hemodynamic response to laryngoscopy and intubation, but dexmedetomidine was more effective than esmolol in maintaining hemodynamic stability.

Analysis of the Exonic Single Nucleotide Polymorphism rs182428269 of the NRF2 Gene in Patients with Diabetic Foot Ulcer.

BACKGROUND: The pivotal role of Nuclear factor erythroid-2-related factor 2 (NRF2) in redox homeostasis and wound healing has been well documented. However, the genetic mechanisms that regulate NRF2 in type 2 diabetes and diabetic foot ulcers remain unexplored. The present study investigated the association of single nucleotide polymorphism rs182428269 (-127 C/T) in subjects with type 2 diabetes and diabetic foot ulcers. METHODS: This cross-sectional study comprised 400 participants that included group I: normal glucose tolerant subjects (NGT, n = 150), group II: type 2 diabetes mellitus subjects (T2DM, n = 150) and group III: infected diabetic foot ulcer subjects (DFU, n = 100). The non-synonymous SNP rs182428269 was selected based on in silico analysis and genotyped by PCR-restriction fragment length polymorphism (RFLP) followed by bidirectional Sanger sequencing. In addition, the gene expression of NRF2 in patients with polymorphism was analyzed by qPCR to evaluate the functional impact of the SNP. RESULTS: NRF2 expression was significantly decreased among the T2DM and DFU subjects when compared to the NGT subjects. Of particular interest, the homozygous mutant (TT) genotype of rs182428269 polymorphism was significantly associated with an increased risk for the development of T2DM (OR = 1.95 (1.02-3.72), p = 0.04) and DFU (OR = 5.66 (2.98-10.76), p = 0.0001). Furthermore, a progressive decline in NRF2 expression was observed among the T2DM and DFU subjects with "TT" genotype compared to the "CC" and "CT" genotypes. CONCLUSION: NRF2 polymorphism rs182428269 is associated with the pathogenesis of T2DM and DFU.

Evaluation of segmental epidural blockade following standard test dose versus test dose with addition of saline in abdominal surgeries.

BACKGROUND AND AIMS: Epidural analgesia is widely used for pain relief but confirmation of accurate epidural placement is poorly understood. We proposed that sensory blockade to cold sensation would predict the accurate placement of epidural. The primary outcome was the assessment of sensory blockade at 5 and 10 min with a standard epidural test dose versus test dose with additional saline. We looked at haemodynamic changes following administration as secondary outcomes. METHODS: Following Ethics Committee approval, 161 patients presenting for elective abdominal surgery needing epidural analgesia with general anaesthesia were randomly allocated into Group 1 receiving standard test dose (3 ml of 2% lignocaine with 1:2,00,000 adrenaline) or Group 2 (standard test dose with 6 ml of saline) epidurally. The blockade to cold sensation was assessed at 5 and 10 min. The heart rate (HR), systolic blood pressure (SBP), and mean arterial pressure (MAP) were recorded at baseline, 1, 5, and 10 min following epidural dosing. Statistical analysis was performed with Chi-square test for categorical and Student's t-test for continuous variables. RESULTS: The sensory blockade at 5 min was 69.5% versus 82.3% (P = 0.059), and at 10 min 85.4% versus 97.5% (P = 0.01) in Groups 1 and 2, respectively. The MAP at 5 min (P = 0.032) and the HR and MAP at 10 min (P = 0.015, 0.04) were significantly lower in Group 2. CONCLUSION: An epidural test dose of 3 ml followed by additional 6 ml saline accurately predicted sensory blockade to cold at 10 min in comparison to the standard dose of 3 ml but was associated with a decrease in the HR and MAP.

Long term outcomes after incident diabetic foot ulcer: Multicenter large cohort prospective study (EDI-FOCUS investigators) epidemiology of diabetic foot complications study: Epidemiology of diabetic foot complications study.

AIMS: This long-term prospective study evaluated limb amputation and mortality after the first neuropathic diabetic foot ulcer (DFU). METHODS: A total of 2880 patients with neuropathic DFU (DFU group) and a similar number of patients of diabetes without DFU (nDFU) matched for age and diabetes duration were prospectively assessed at five referral-centers over 14 years. Pre-defined outcome was death during follow-up. Various diabetic co-morbidities and amputation were assessed as mortality predictors. RESULTS: Overall, 501 (17.4%) patients in DFU group died compared to 89 (3.1%) (p < 0.01) in nDFU group during a median follow-up of 7(1-14) years. The 5- and 10-year mortality was 22% and 71% in the DFU group with a median survival of 7.72 (7.37-8.08) years compared to 3% (p < 0.01) and 5% (p < 0.01) and survival of 12.6 (10.5-12.7) years (p < 0.001) in nDFU group. 29.3% patients had limb amputations. The mortality risk was independent of glycemic control [OR 1.03 (0.80-1.32; p = 0.83)]. However, diabetes duration > 10 years [OR 1.31(1.02-1.70, p = 0.035)], nephropathy [OR 1.47 (1.04-2.09, p < 0.030)], minor 1.85 (1.40-2.44; p < 0.001) or major amputation 2.96 (2.01-4.34, p < 0.001)] predicted mortality. CONCLUSIONS: Every one-in-three individual with neuropathic DFU has amputation and every sixth individual has an early demise. Prevalent nephropathy and incident amputation following DFU predicts mortality.

Ultrasound Measurement of Inferior Vena Cava Collapsibility as a Tool to Predict Propofol-Induced Hypotension.

BACKGROUND: Hypotension is common under anesthesia and can cause organ underperfusion and ischemia, especially during induction. This could be because of the cardiovascular depressant and vasodilatory effects of anesthetic agents, as well as lack of surgical stimulation. AIM OF STUDY: The aim was to evaluate the utility of preinduction inferior vena cava (IVC) measurement to predict significant hypotension after induction of anesthesia with propofol. SETTINGS AND DESIGN: This was a prospective, open-label study conducted in a tertiary care institute. SUBJECTS AND METHODS: This study was conducted on 50 patients undergoing general anesthesia. Ultrasound machine (Mindray® M7) was used to visualize IVC. The measurements taken were maximum diameter of IVC (IVCmax) and minimum diameter of IVC (IVCmin). IVC collapsibility index (IVC-CI) was calculated as (IVCmax - IVCmin)/IVCmax and was expressed as a ratio. STATISTICAL TESTS USED: Receiver operating characteristic (ROC) curve analysis and Chi-square test were used for statistical tests. RESULTS: The relation between significant hypotension and IVC-CI was evaluated using ROC curve analysis. We found the area under curve to be 0.959 and a cutoff of 0.43 (43% collapsibility). The association of significant hypotension with IVC-CI of >43% was calculated and found to be statistically significant (P < 0.001). The sensitivity of IVC CI of >43% in predicting development of significant hypotension was 86.67% and the specificity was 94.29%. It had very high negative and positive predictive values (94.29% and 86.67%, respectively) with an accuracy of 92%. CONCLUSION: Patients with an IVC collapsibility of more than 43%, as assessed by ultrasonography, are more likely to develop significant hypotension after induction with propofol.

Comparison of Hemodynamic Changes to Nasal Application of Lignocaine Jelly versus Lubricant Gel and Responses to Ryle's Tube Insertion Following Their Use in Patients Under General Anesthesia.

BACKGROUND: Awake patients complain of burning sensation following nasal application of lignocaine jelly. AIM OF THE STUDY: The aim of the study was to assess hemodynamic changes, ease of insertion, number of attempts taken, and time required for insertion of Ryle's tube following nasal application of 2% lignocaine jelly versus lubricant gel in patients undergoing surgeries under general anesthesia. SETTINGS AND DESIGN: This was a prospective, randomized, open-label study conducted in a tertiary care institute. SUBJECTS AND METHODS: Eighty patients undergoing surgeries under general anesthesia who required insertion of a Ryle's tube were included. In Group A, 2% lignocaine jelly was used, whereas in Group B, lubricant gel was used prior to Ryle's tube insertion, after induction of anesthesia. Hypertension and/or tachycardia were managed by increasing sevoflurane by 0.5%-1%, followed by propofol bolus of 0.5 mg.kg-1. STATISTICAL TESTS USED: Chi-square test and Independent samples t test. RESULTS: Both heart rate and mean arterial pressure were significantly higher at 1 min after nasal application of lignocaine jelly and 1 and 5 min after Ryle's tube insertion in Group A compared to Group B. Ease of insertion of Ryle's tube, number of attempts, and time taken for insertion were comparable in both groups. Significantly higher number of patients in Group A required sevoflurane to be increased and needed propofol boluses. CONCLUSION: Use of lubricant gel for aiding insertion of Ryle's tube in patients under general anesthesia was associated with attenuated heart rate and blood pressure responses without affecting the ease, number of attempts, or time taken for successful insertion of the Ryle's tube.

miR-23c regulates wound healing by targeting stromal cell-derived factor-1α (SDF-1α/CXCL12) among patients with diabetic foot ulcer.

Diabetic Foot Ulcer (DFU) is the most common in patients who have diabetic peripheral neuropathy and angiopathy as well as a foot deformity. The delayed process of wound healing in diabetic condition is mainly due to reduced expression of the growth factors, persistent inflammatory response and endothelial dysfunction. Emerging evidence indicate that miRNAs play a crucial role in regulating angiogenesis, collectively called as "angiomiRs". The present study aimed to screen the expressions of angiomiRs particularly miR23 family and its association with the various angiogenic factors including SDF-1α in the tissue biopsies isolated from DFU patients. Among the 40 enrolled subjects for this study, 10 were subjected in each group as healthy controls, type 2 diabetic subjects (T2DM), T2DM subjects with uninfected DFU, and T2DM subjects with infected DFU. The expression of both the miR23 family such as hsa-miR-23a, hsa-miR-23b, hsa-miR-23c and angiogenic factors such as SDF-1α, HIF-1α, VEGF, eNOS were investigated in peripheral blood mononuclear cells and tissue biopsy samples using qPCR. We found that the angiogenic factor SDF-1α was significantly decreased in both the circulation and tissue biopsies of patients with T2DM and infected DFU. The SDF-1α at the 3'-untranslated region pairs with target miRNAs namely hsa-miR-23a-3p, hsa-miR-23b-3p and hsa-miR-23c as established using miRNA target prediction algorithm. Further, the tissue-specific expressions of miR-23a and miR-23b were found to be low whereas miR-23c was increased in patients with infected DFU. Moreover, correlation analysis showed that SDF-1α was found to have a significant inverse association with miR-23c. In conclusion, miR-23c may function as a new regulator to inhibit angiogenesis by targeting SDF-1α.

Comparison of the Analgesic Efficacy of a Single Dose of Epidural Dexmedetomidine versus Fentanyl as an Adjuvant to Bupivacaine in Abdominal Surgery.

BACKGROUND: Fentanyl as an epidural additive act on spinal opioid receptors, while dexmedetomidine has selective alpha-2 receptor agonist action enhancing analgesic effects. AIMS: We aimed to compare the postoperative analgesic efficacy of single doses of dexmedetomidine against fentanyl as epidural adjuvant to 0.125% bupivacaine. SETTINGS AND DESIGN: A prospective, randomized, controlled, double-blind trial was conducted in a tertiary care teaching institute. PATIENTS AND METHODS: Forty-six patients undergoing abdominal surgery under general anesthesia with epidural analgesia were allocated into two groups to receive postoperative analgesia with single doses of 10 mL 0.125% bupivacaine with the addition of dexmedetomidine 0.5 µg.kg-1 (Group D) or fentanyl 0.5 µg.kg-1 (Group F). The primary outcome was the duration of postoperative analgesia between the two groups. The secondary outcomes were hemodynamic variations, vasopressor need, and motor blockade. STATISTICAL ANALYSIS: Chi-square test for static parameters and Student's t-test or Mann-Whitney test for continuous variables were used for analysis. RESULTS: The duration of analgesia was longer in Group D (5.0 ± 2.0 h) versus Group F (2.9 ± 1.4 h), Sixteen patients in Group D versus seven patients in Group F needed vasopressors after the bolus to maintain the blood pressure (BP) within 20% of prebolus value (P = 0.018). Heart rate and mean and systolic BP were lower in Group D at various time points following bolus administration. CONCLUSION: A single dose of dexmedetomidine as an additive to epidural local anesthetic postoperatively prolongs the duration of analgesia in comparison to fentanyl but is associated with changes in hemodynamics, including the need for the administration of vasoactive drugs.

Evaluation of Renal Function with Administration of 6% Hydroxyethyl Starch and 4% Gelatin in Major Abdominal Surgeries: A Pilot Study.

BACKGROUND: Synthetic colloids, both starches and gelatins, are commonly used as intravascular fluid replacements on account of increased vascular persistence. The safety on renal outcomes during perioperative use is poorly understood. AIMS: We evaluated renal outcomes of hydroxyethyl starch 6% (HES) and gelatins 4% (G) in patients undergoing elective abdominal surgery. The primary outcome was serum creatinine measurements at baseline, 12 h, 36 h, and 1 week postoperatively (T0, T12, T36, and D7). The secondary outcomes were measurements of prothrombin time (PT), international normalized ratio (INR), fibrinogen, and activated partial thromboplastin time (aPTT) at baseline, 12 h, and 36 h postoperatively. SETTING AND DESIGN: A prospective randomized study was conducted at a tertiary care institute. MATERIALS AND METHODS: Seven-five adult patients received either HES (Group H) or gelatin (Group G) at 20-ml/kg body weight or only crystalloids (Group C) during surgery. Statistical tests used were one-way ANOVA, Student's t-test, Pearson correlation method, and Chi-square test. RESULTS: Serum creatinine assessed at T0, T12, T36, and D7 was comparable between the three groups. PT/INR and aPTT showed no significant increase in values of T12 and T36 in comparison to T0. Fibrinogen level was significantly higher in Group C at T12 and T36. Intraoperative vasopressor use, need for product transfusion, length of intensive care unit stay, and return of bowel function were similar between the three groups. CONCLUSIONS: Intraoperative use of HES (130/0.4) or gelatin (4%) at 20-ml/kg body weight was not associated with renal dysfunction or altered PT and aPTT in adult patients undergoing elective abdominal major surgeries.

Robot-assisted supine extraperitoneal retroperitoneal lymph node dissection: a novel approach for template dissection in post-chemotherapy residual mass in non-seminomatous germ cell tumours.

Robot-assisted retroperitoneal lymph node dissection (RA-RPLND) in testicular cancer is conventionally performed through transperitoneal route. We report a case of robot-assisted supine extraperitoneal RPLND (RASE-RPLND), not previously described in the literature, which was performed for post-chemotherapy residual mass in a case of non-seminomatous germ cell tumour (NSGCT). RASE-RPLND apart from providing the benefits of robotic assistance has a significant advantage over transperitoneal approach, as the procedure can be performed in supine position without any bowel handling. Herein, we provide a detailed description of the novel surgical technique employed by us in this case.

Evaluation of the Metabolic Profile of Ringer Lactate versus Ringer Acetate in Nondiabetic Patients Undergoing Major Surgeries.

BACKGROUND: Stress-induced neuroendocrine and metabolic changes lead to intraoperative hyperglycemia which is related to surgery and the type of intravenous fluids used. AIMS: The primary objective was to assess the incidence of hyperglycemia with use of lactate versus acetate-based intravenous fluids in nondiabetics undergoing major surgeries. Incidence of lactatemia and metabolic acidosis were also assessed. SETTINGS AND DESIGN: Prospective parallel group observational study conducted in a tertiary care institute. SUBJECTS AND METHODS: A total of 208 nondiabetic patients undergoing major head and neck free flap or abdominal surgeries were included in the study. Group A received Ringer lactate, and Group B received Ringer acetate as intraoperative maintenance fluid. Intraoperative blood sugar, pH, and lactate levels were monitored. STATISTICAL TESTS USED: Chi-square test and independent "t" test were used for analysis. RESULTS: Intraoperative hyperglycemia was more frequent in Group A than B (17.3 vs. 18.4%). Group B patients undergoing gastrointestinal (GI) surgeries showed higher blood glucose at 2, 4, 6, and 8 h when compared to flap surgeries. In Group A, significantly higher blood sugar values were noted at 2 and 8 h in those undergoing GI surgeries. Group B patients undergoing GI surgeries had significantly higher lactate levels at 6 and 8 h. Group B patients had significant acidosis when surgeries lasted >6 h. CONCLUSION: Nondiabetic patients undergoing major abdominal surgeries who received acetate-based fluids had relatively higher intraoperative blood sugar levels as compared to those receiving lactated solutions, but the incidence of hyperglycemia was comparable. When the duration of surgery exceeded 6 h, acetate-based solutions resulted in significantly higher lactate levels with progressive metabolic acidosis.

Efficiency and Efficacy of Two Techniques of Preoxygenation during Modified Rapid Sequence Intubation.

BACKGROUND: Apneic mass movement of oxygen by applying continuous positive airway pressure (CPAP) is possible only when the airway is kept patent which helps to reduce the rate of desaturation. AIMS: The aim of this study was to check the efficiency of preoxygenation and apneic oxygenation by assessing the drop in partial pressure of arterial oxygen (PaO2) during apnea with and without keeping an oropharyngeal airway to maintain the patency of airway. SETTINGS AND DESIGN: This prospective observational study was conducted at a tertiary care center. MATERIALS AND METHODS: Sixty patients undergoing robotic and laparoscopic-assisted surgeries requiring modified rapid sequence intubation were recruited for the study. In Group A, CPAP was not applied during preoxygenation and oropharyngeal airway was not used, but oxygen was administered at 5 L/min during the apnea. In Group B, CPAP of 5 cmH2O was maintained during preoxygenation and after induction an oropharyngeal airway was inserted. Patients in both the groups were induced and paralyzed following standardized anesthesia protocol. STATISTICAL ANALYSIS USED: Chi-square test, independent t-test, and ANCOVA were used as applicable. RESULTS: Group B showed significantly higher mean PaO2 levels after preoxygenation (525.3 ± 42.5 vs. 500.8 ± 51) and at 90 s of apnea (494.8 ± 42.6 vs. 368.6 ± 98.4) as compared to Group A. The fall in PaO2 was significantly lower in Group B. The rise in partial pressure of arterial carbon dioxide was comparable in both groups. CONCLUSION: Preoxygenation with CPAP of 5 cmH2O followed by apneic oxygenation with CPAP keeping the airway patent with an oropharyngeal airway results in significantly higher PaO2 after preoxygenation and slower reduction in PaO2 during apnea.

Effect and Safety of Labor Epidural Analgesia with Intermittent Boluses of 0.1% Bupivacaine with Fentanyl on Fetal and Maternal Outcomes and Wellbeing.

BACKGROUND: Labor analgesia has been shown to have few undesirable effects on the course and outcome of the labor as well as on the fetal well-being. AIMS: This study aims to assess neonatal outcome following lumbar epidural analgesia with intermittent boluses of 0.1% bupivacaine with fentanyl. The secondary objectives included assessment of maternal analgesia, complications, and outcome of labor. SETTING AND DESIGN: Prospective observational study conducted at a tertiary care teaching institute. SUBJECTS AND METHODS: Sixty-three patients for labor epidural analgesia were recruited. Epidural catheter was inserted in L4-L5 or L3-L4 interspace. After confirmation of the position of catheter, 3 mL of 0.5% bupivacaine with 20 µg of fentanyl made to 15 mL was administered. After 30 min, efficacy of analgesia was assessed by visual analog scale (VAS). The same bolus dose was repeated after 90 min if the patient complained of pain. A maximum of five top-up doses were allowed. STATISTICAL TEST USED: Mean and standard deviation, number and percentage. RESULTS: After 30 min of first bolus dose, 93.3% had VAS score of <4. More than 90% patients had adequate analgesia till 4th epidural bolus. During contraction stress test, only two fetuses had late deceleration. About 80% and 98.3% newborns had Apgar of >7 at 1 and 5 min, respectively. Umbilical cord blood pH was ≥7.1 in 98.3% neonates with base excess of >-12. 58.3% delivered normally, 23.3% had instrumental vaginal delivery, and 18.3% required cesarean section. CONCLUSION: Lumbar epidural analgesia with 0.1% bupivacaine with fentanyl provides optimal neonatal outcome, labor analgesia, and labor outcome.

Potential of circulatory procalcitonin as a biomarker reflecting inflammation among South Indian diabetic foot ulcers.

OBJECTIVE: Diabetic foot ulcer (DFU), the major complication associated with diabetes mellitus, has been shown to precede amputation in up to 90% of cases. Recent data reveal that procalcitonin (PCT) is a valid marker for the diagnosis of bacterial infections compared with traditional markers like white blood cell count, C-reactive protein levels, and erythrocyte sedimentation rate in DFU patients. Furthermore, cytokines are proposed to act as modulators and mediators for the expression and release of PCT into the circulation. Hence, this preliminary study was conducted to evaluate the diagnostic accuracy of PCT compared with other traditional markers and to predict the association of PCT plasma levels with inflammatory cytokines and clinical parameters of incident diabetes among South Indian DFU subjects. METHODS: There were 185 subjects with type 2 diabetes mellitus (T2DM) selected in this cross-sectional study, subdivided into three groups: group I, control/T2DM subjects free from DFU (n = 75; male, 43; female, 32); group II, T2DM subjects with noninfected DFU (n = 34; male, 19; female, 15); and group III, T2DM subjects with infected DFU (IDFU; n = 76; male, 46; female, 30). Patients with IDFU were further divided into three subgroups as per the Infectious Diseases Society of America-International Working Group on the Diabetic Foot classification criteria: grade 2 (n = 27), grade 3 (n = 38), and grade 4 (n = 11). Subjects with type 1 diabetes, gestational diabetes, pneumonia, sepsis, inflammatory bowel disease, meningitis, or hematologic diseases and those who underwent surgery in the past 2 to 3 weeks were excluded from this study. For investigation of clinical parameters, blood samples were drawn from all the study subjects; plasma samples were used for estimating PCT by the enzyme-linked immunosorbent assay method. The profiling of plasma cytokines was carried out using a multiplex bead-based assay. Data are presented as mean ± standard deviation for clinical and biochemical variables and as geometric mean with 95% confidence interval (CI) for cytokines. All analysis was done using the Statistical Package for the Social Sciences (version 20.0; IBM Corp, Armonk, NY); P < .05 was considered to be statistically significant. RESULTS: We found PCT to be a valid diagnostic marker for IDFU with higher sensitivity and specificity than other traditional markers. For PCT, the area under the receiver operating characteristic curve was found to be high (0.99; 95% CI, 0.96-1.0), followed by C-reactive protein levels (0.78; 95% CI, 0.65-0.81), white blood cell count (0.76; 95% CI, 0.67-0.86), and erythrocyte sedimentation rate (0.74; 95% CI, 0.68-0.80) in IDFU subjects. We found the cutoff value of ≥0.5 ng/mL to have 54% sensitivity and 100% specificity for PCT with a positive predictive value of 100% and a negative predictive value of 12% for IDFU diagnosis. Moreover, PCT circulatory levels showed a positive correlation with helper T-cell subtype 1 cytokines, such as interferon γ (r = 0.21; P = .03) and interleukin 28A (r = 0.31; P = .003), and subtype 17 cytokines, such as interleukin 29/interferon λ1 (r = 0.20; P = .037). CONCLUSIONS: PCT could be a valuable marker for diagnosis of T2DM patients with IDFU.