Efficacy for Lidocaine and Articaine in Inferior Alveolar Nerve Block - A Comparative Study.

AIMS: Compare the efficacy of 2% lidocaine with adrenaline (1:200,000) and 4% articaine with adrenaline (1:100,000) in inferior alveolar nerve block prior to extraction of bilateral teeth posterior to canine in interval of one week. METHODS AND MATERIAL: Thirty-five patients were selected for the study. Patients were divided into two different groups: Group 1 - (2% lignocaine with adrenaline (1:200,000)) and Group 2 - (4% articaine with adrenaline (1:100,000)) solution. The study variables for each anaesthetic agent were: onset of action and depth of anaesthesia. A pulp tester was used to demonstrate quantitative values and a visual analogue scale (VAS) was used for qualitative evaluation of the two anaesthetic drugs in 2 min cycle for 10 min with respect to test canine. Anaesthesia was considered successful when pulp tester value 64 was achieved in 10 min for both the anaesthetic agent. STATISTICAL ANALYSIS USED: The difference in the efficacy of lignocaine and articaine was analysed using Student's t test. Within group comparison of the response to the pulp vitality test and VAS over various time periods was analysed using repeated measures Analysis of Variance (ANOVA) with post-hoc Bonferroni test. RESULTS: Data analysis showed statistical differences in onset and depth of anaesthesia between the two groups (P < 0.05). CONCLUSIONS: 4% Articaine with adrenaline (1:100,000) onset of action is faster and depth of anaesthesia is better compared to 2% lignocaine with adrenaline (1:200,000). Many previous studies reported onset of anaesthesia, but this study evaluates onset and depth of both the anaesthetic agent quantitatively and qualitatively.

Microbiota and Gut-Liver Axis: An Unbreakable Bond?

The gut microbiota, amounting to approximately 100 trillion (1014) microbes represents a genetic repertoire that is bigger than the human genome itself. Evidence on bidirectional interplay between human and microbial genes is mounting. Microbiota probably play vital roles in diverse aspects of normal human metabolism, such as digestion, immune modulation, and gut endocrine function, as well as in the genesis and progression of many human diseases. Indeed, the gut microbiota has been most closely linked to various chronic ailments affecting the liver, although concrete scientific data are sparse. In this narrative review, we initially discuss the basic epidemiology of gut microbiota and the factors influencing their initial formation in the gut. Subsequently, we delve into the gut-liver axis and the evidence regarding the link between gut microbiota and the genesis or progression of various liver diseases. Finally, we summarise the recent research on plausible ways to modulate the gut microbiota to alter the natural history of liver disease.

Randomized controlled trial of sustained release tacrolimus vs twice daily tacrolimus in adult living donor liver transplantation.

BACKGROUND: To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). METHODS: In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3-7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. RESULTS: There was no statistically significant difference in eGFR between the two groups at 6 months (ODT -96 ± 19, BDT -91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. CONCLUSION: Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT.

Open to robotic right donor hepatectomy: A tectonic shift in surgical technique.

Robotic right live donor hepatectomy (r-LDRH) has been reported with reduced morbidity compared to open donor right hepatectomy (o-LDRH) in few recent series. Nevertheless, its routine use is debated. We present a large series comparing pure r-LDRH with o-LDRH. Consecutive r-LDRH performed from June 2018 to June 2020 (n = 102) were compared with consecutive donors undergoing o-LDRH (n = 152) from February 2016 to February 2018, a period when r-LDRH was not available at this center. Propensity score matched (PSM) analysis of 89 case-control pairs was additionally performed. Primary endpoints were length of high dependency unit (HDU) and hospital stay and Clavien-Dindo graded complications among donors. Although r-LDRH took longer to perform (540 vs. 462 min, P < .001), the postoperative peak transaminases levels (P < .001), the length of HDU (3 vs. 4 days, P < .001), and hospital stay (8 vs. 9 days, P < .001) were lower in in donors undergoing r-LDRH. Clavien-Dindo graded complications were similar (16.67% in r-LDRH and 13.16% in o-LDRH). The rates of early allograft dysfunction (1.6% vs. 3.3%), bile leak (14.7% vs. 10.7%), and 1-year mortality (13.7% vs. 11.8%) were comparable between r-LDRH and o-LDRH recipients. PSM analysis yielded similar results between the groups. These data support the safety and feasibility of r-LDRH in select donors.

A randomized, double-blinded, placebo-controlled trial analyzing the effect of synbiotics on infectious complications following living donor liver transplant-PREPRO trial.

BACKGROUND: Following liver transplantation (LT), bacterial infections occur in over 70% of recipients leading to significant morbidity and mortality. While synbiotics have been reported to decrease infectious complications in various surgical procedures, the evidence of their benefits following LT remains limited. METHODS: In this 18-month double-blinded, investigator-initiated, placebo-controlled trial, 100 recipients of live donor liver transplant (LDLT) were randomized to receive either the synbiotic drug Prowel® (Prepro arm) or a placebo, starting 2 days pretransplant and continued for 2 weeks. The primary endpoint was culture-proven bacterial infection in blood, urine or drain fluid within 30 days. Secondary endpoints were hospital stay, noninfectious complications, antibiotic usage and 30-day mortality. RESULTS: Overall infectious complications were significantly lower in the Prepro arm in comparison to the Placebo arm (44% vs 22%, P = .019, OR 0.359; CI: 0.150-0.858). Blood stream infections were significantly less in the study arm (21.7% vs 53.3%, P = .020, OR 0.243; CI: 0.072-0.826), whereas urinary tract and intra-abdominal infections were similar. Length of hospital stay, noninfectious complications, deviation from protocol antibiotics and 30-day mortality were comparable. CONCLUSION: Synbiotics administered for 2 weeks following LDLT significantly reduced overall and blood stream infectious complications in the early postoperative period. However, there was no difference in hospital stay, noninfectious complications, antibiotic usage and mortality. Clinical Trial Registry of India registration number - CTRI/2017/09/009869.

Extended criteria donors for robotic right hepatectomy: A propensity score matched analysis.

BACKGROUND: Robotic right donor hepatectomy (RDH) has been reported from experienced centers with reduced morbidity when compared to open RDH. However, outcomes in donors with large grafts/complex biliovascular anatomy are unknown. METHODS: Out of 170 robotic RDH, 100 had one or more of the following: graft weight ≥800 g, type 2/3 portal vein, >1 bile duct or hepatic artery and inferior hepatic veins >5 mm requiring reconstruction (extended criteria donors [ExRDH]), while the remaining 70 had standard anatomy (SRDH). After propensity score matching, 66 ExRDH were compared with 66 SRDH. Additionally, all robotic RDH performed were analyzed in three temporal phases (60, 60, and 50). RESULTS: Peak AST and ALT were higher amongst donors and recipients in the ExRDH arm compared to SRDH. Other intraoperative parameters and postoperative complications were similar between the two groups. During the last phase, donors demonstrated reduction in duration of surgery, postoperative complications, and hospital stay while recipients showed decreased blood loss and hospital stay. CONCLUSION: Robotic right hepatectomy performed in donors with extended criteria have similar perioperative outcomes as standard donors. However, a significant learning curve needs to be traversed. Further studies are required before safely recommending robotic RDH for all donors.

Technique of robotic right donor hepatectomy.

BACKGROUND: Although minimally invasive right donor hepatectomy (RDH) has been reported, this innovation is yet to be widely accepted by transplant community. Bleeding during transection, division of right hepatic duct (RHD), suturing of donor duct as well as retrieval with minimal warm ischemia are the primary concerns of most donor surgeons. We describe our simplified technique of robotic RDH evolved over 144 cases. PATIENTS AND METHODS: Right lobe mobilization is performed in a clockwise manner from right triangular ligament over inferior vena cavae up to hepatocaval ligament. Transection is initiated using a combination of bipolar diathermy and monopolar shears controlled by console surgeon working in tandem with lap CUSA operated by assistant surgeon. With the guidance of indocyanine green cholangiography, RHD is divided with robotic endowrist scissors (Potts), and remnant duct is sutured with 6-0 PDS. Final posterior liver transection is completed caudocranial without hanging manoeuvre. Right lobe with intact vascular pedicle is placed in a bag, vascular structures then divided, and retrieved through Pfannenstiel incision. CONCLUSION: Our technique may be easy to adapt with the available robotic instruments. Further innovation of robotic platform with liver friendly devices could make robotic RDH the standard of care in future.

Middle hepatic vein reconstruction in adult living donor liver transplantation: a randomized clinical trial.

BACKGROUND: In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV. METHODS: Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems. RESULTS: There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group. CONCLUSION: In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality. REGISTRATION NUMBER: CTRI/2018/11/016315 (www.ctri.nic.in).

Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT).

BACKGROUND: Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). METHODS: We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. RESULTS: The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). CONCLUSION: Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.

Double-blind placebo-controlled randomized trial of N-acetylcysteine infusion following live donor liver transplantation.

BACKGROUND: The role of N-acetylcysteine (NAC) in improving outcomes following live donor liver transplantation (LDLT) is not well established. We designed a randomized double-blind placebo-controlled trial to study the role of NAC infusion in recipients undergoing LDLT. METHODS: We assigned 150 patients who underwent LDLT by computer-generated random sequence on 1:1 ratio to either NAC group or placebo group. Patients in the NAC group received NAC infusion which was started at beginning of graft implantation at an initial loading dose of 150 mg/kg/h over 1 h, followed by 12.5 mg/kg/h for 4 h and then at 6.25 mg/kg/h continued for 91 h. Placebo group received normal saline. The primary endpoint was composite occurrence of acute kidney injury (AKI) and early allograft dysfunction (EAD) in the recipient. Secondary endpoints included levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, INR, primary graft non-function, intraoperative bleeding, post-transplant hospital stay and in-hospital mortality. RESULTS: The composite endpoint did not show any significant difference between the NAC and placebo group (21.3% vs 29.3%, p = 0.35). Peak AST (425.65 IU/L vs 702.24 IU/L, p = 0.02) and peak ALT (406.65 IU/L vs 677.99 IU/L, p = 0.01) levels were significantly lower in the study group. Time to normalization of transaminases was also significantly low in the study group. CONCLUSIONS: Perioperative NAC infusion following LDLT resulted in significantly lower postoperative AST and ALT levels. Rapid normalization of transaminases was also observed. This, however, did not translate to improvement in AKI or EAD.

Liver Transplant in Acute Liver Failure - Looking Back Over 10 Years.

BACKGROUND: Acute liver failure (ALF) is the leading cause for emergency liver transplantation (LT) all over the world. We looked at the profile of cases who required LT for ALF from a single centre to identify the possible predictors of poor outcomes. METHODOLOGY: During the 10-year period starting from 2007, 320 cases of ALF were treated at our institution, of which 70 (median age 24 years, Male:Female 1:2) underwent LT. Retrospective analyses of these 70 patients were performed. RESULTS: Etiology was identifiable in 73% (n = 51) of cases (yellow phosphorous [YP] poisoning [n = 16], Hepatitis A virus [HAV] [n = 15], Hepatitis B virus [HBV] [n = 5], Hepatitis E virus [HEV] [n = 1], anti-tubercular therapy [ATT] induced [n = 6], acute Wilson's [n = 3], and autoimmune [n = 5]]. Upon meeting King's College Hospital criteria, 69 had live donor LT (61 right lobe grafts, three left lobe grafts, five left lateral segment grafts) and one had deceased donor LT. Among these, there were five auxiliary partial orthotopic grafts and four ABO-incompatible transplants. Overall, 90-day mortality was 35.7% (n = 25), predominantly due to sepsis. Significant risk factors for mortality on multivariate analysis included indeterminate etiology, pre-op renal dysfunction, and Grade IV hepatic encephalopathy (HE). Cumulative 10-year survival of the remaining survivors was 95.6% (n = 45). CONCLUSION: LT for ALF carries high perioperative mortality (35.7%) in those presenting with indeterminate etiology, pre-op renal dysfunction, and Grade IV HE. Nevertheless, if they survive the perioperative period, long-term survival is excellent.

Antegrade Hepatic Artery and Portal Vein Perfusion Versus Portal Vein Perfusion Alone in Living Donor Liver Transplantation: A Randomized Trial.

Traditionally, deceased donor liver grafts receive dual perfusion (DP) through the portal vein and the hepatic artery (HA) either in situ or on the back table. HA perfusion is avoided in living donor liver grafts for fear of damage to the intima and consequent risk of hepatic artery thrombosis (HAT). However, biliary vasculature is predominantly derived from the HA. We hypothesized that antegrade perfusion of the HA in addition to the portal vein on the back table could reduce the incidence of postoperative biliary complications. Consecutive adult patients undergoing living donor liver transplantations were randomized after donor hepatectomy to receive graft perfusion of histidine-tryptophan-ketoglutarate solution either via both the HA and portal vein (DP group, n = 62) or only through the portal vein (standard perfusion [SP] group, n = 62). The primary endpoint was the occurrence of biliary complications (biliary leak/stricture). Secondary endpoints included HAT and patient survival. The incidence of biliary stricture was significantly lower in the DP group (6.5% versus 19.4%; odds ratio, 0.29; 95% confidence interval, 0.09-0.95; P = 0.04). There was no significant reduction in the incidence of HAT, bile leak, or hospital stay between the 2 groups. The 3-year mortality and graft survival rates were significantly higher among patients who received DP compared with SP (P = 0.004 and P = 0.003, respectively). On multivariate analysis, nonperfusion of the HA and preceding bile leak were found to be risk factors for the development of biliary stricture (P = 0.04 and P < 0.001, respectively). In conclusion, DP of living donor liver grafts through both the HA and portal vein on the back table may protect against the development of biliary stricture. This could translate to improved patient survival in the short term.

Lack of Association of B-type Raf Kinase V600E Mutation with High-risk Tumor Features and Adverse Outcome in Conventional and Follicular Variants of Papillary Thyroid Carcinoma.

INTRODUCTION: Somatic B-type Raf kinase (BRAF) V600E mutation in exon 15 was frequently found in high frequencies associated with papillary thyroid cancer (PTC). The phenotype of these cancers expressed aggressive clinical and pathological features. The present study aimed to assess the prevalence of BRAF V600E mutation among conventional and follicular variants of PTC and its association with aggressive tumor factors and outcome. STUDY DESIGN: Patients who were operated and received further treatment for PTC during 2012 were included in the study. BRAF V600E mutation analysis was done by extracting genomic DNA from tumor tissue. RESULTS: Of the 59 patients included in the study, 51% harbored BRAF V600E mutation, but the mutation status was not associated with aggressive tumor factors and adverse outcome. CONCLUSION: BRAF V600E mutation was not significant predictor of aggressive tumor behavior in conventional and follicular variants of PTC.