Publications by authors named "Rashmi Ramachandran"

73 Publications

Effect of positive end expiratory pressure on atelectasis in patients undergoing major upper abdominal surgery under general anaesthesia: A lung ultrasonography study.

J Perioper Pract 2022 Mar 24:17504589211045218. Epub 2022 Mar 24.

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi 110029, India.

Postoperative pulmonary complications vary in major upper abdominal surgery. The objective of this study was to assess the effect of positive end expiratory pressure on the incidence of atelectasis in patients undergoing major upper abdominal surgery under general anaesthesia using lung ultrasound. The patients were randomised into receiving either no positive end expiratory pressure (Group I) or positive end expiratory pressure of 5cm HO (Group II). Lung ultrasound was performed at various time points - baseline, 10 minutes, 2 hours after induction, during closure of skin and 30 minutes post extubation. The lung aeration as assessed by Total Modified Lung Ultrasound Score was worse in the Group I as compared to the Group II at 2 hours post induction. Driving pressure in Group II was significantly reduced compared to Group I. Application of positive end expiratory pressure, as minimal as 5cm HO, as a single intervention, helps in significantly reducing the Total Modified Lung Ultrasound Score after a duration of more than 2 hours and also attaining low driving pressures during intraoperative mechanical ventilation.
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http://dx.doi.org/10.1177/17504589211045218DOI Listing
March 2022

Comparison of extended totally extra peritoneal (eTEP) vs intra peritoneal onlay mesh (IPOM) repair for management of primary and incisional hernia in terms of early outcomes and cost effectiveness-a randomized controlled trial.

Surg Endosc 2022 Mar 11. Epub 2022 Mar 11.

Department of Surgical Disciplines, All India Institute of Medical Sciences, Room No. 5026A, 5th Floor, Teaching Block, Ansari Nagar, New Delhi, 110029, India.

Background: There are no randomized controlled trials comparing the eTEP with IPOM repair and this randomized study was designed to compare the two techniques in terms of early pain, cost effectiveness, and quality of life.

Method: This was a prospective randomized trial with intention to treat analysis. The primary outcome was immediate post-operative pain scores. Operative time, conversions, peri operative morbidity, hospital stay, return to daily activities, incremental cost effectiveness ratio and quality of life (WHO-QOL BREF) were secondary outcomes.

Results: Sixty patients were randomized equally. Early post-operative pain scores and seroma rates were significantly lower and with a significantly earlier return to activity in eTEP group (p value < 0.05). With negative costs and positive effects, eTEP group was 2.4 times more cost effective.

Conclusion: eTEP repair is better in terms of lesser early post-operative pain, earlier return to activities and cost effectiveness in small and medium size defects.
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http://dx.doi.org/10.1007/s00464-022-09180-3DOI Listing
March 2022

Timing of intraoperative crystalloid infusion may decrease total volume of infusate without affecting early graft function in live related renal transplant surgery: A randomized, surgeon-blinded clinical study.

Indian J Urol 2022 Jan-Mar;38(1):53-61. Epub 2022 Jan 1.

Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Early graft function is crucial for successful kidney transplantation. Intravascular volume maintenance is paramount in ensuring reperfusion of transplanted kidney. This study was planned to compare whether the timing of fluid infusion can help to decrease amount of fluid given without altering early graft function during renal transplantation.

Materials And Methods: The present study included forty recipients, randomized into standard (Group-S) or targeted fluid therapy (Group-T). Group S received fluid according to conventional fasting deficit while Group T received at 1 ml/kg/h from the start of surgery till start of vascular anastomosis after which fluid infusion rate in both group was increased to maintain a central venous pressure of 13-15 mm of Hg till reperfusion. Primary outcome measured was serum creatinine level on first postoperative day while secondary outcomes were IV fluid given, perioperative hemodynamics, onset of diuresis, graft turgidity, urine output, and renal function during first 6 postoperative days.

Results: The study showed Group T postoperatively had early fall in serum creatinine (day 3) than S (day 6) although this difference was not statistically significant. Group T had received significantly less fluid per kg of dry weight (T-42.7 ± 9.7 ml/kg, S-61.1 ± 11.1 ml/kg, < 0.001), had early diuresis, better graft turgidity and urine output than Group S.

Conclusion: Targeted hydration significantly decreases the total amount of fluid infused during the intraoperative period without altering early graft function. Targeted hydration during vascular anastomosis produced stable hemodynamics and early diuresis without any side-effects pertaining to hypo or hyper-volemia.Clinical trial identifier number-CTRI/2016/07/007111.
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http://dx.doi.org/10.4103/iju.iju_239_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796753PMC
January 2022

Temporal Evolution of the PcvCO-PaCO/CaO-CcvO Ratio vs Serum Lactate during Resuscitation in Septic Shock.

Indian J Crit Care Med 2021 Dec;25(12):1370-1376

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

Background: Lactate as a target for resuscitation in patients with septic shock has important limitations. The PcvCO-PaCO/CaO-CcvO ratio may be used as an alternative for the same. The primary outcome of the study is to evaluate the correlation between serum lactate and PcvCO-PaCO/CaO-CcvO ratio measured at various time points to a maximum of 24 hours in patients with septic shock [mean arterial pressure (MAP) <65 mm Hg]. The secondary outcomes were to study the (1) relationship between the PcvCO-PaCO/CaO-CcvO ratio and lactate clearance at 6, 12, and 24 hours as compared to the initial serum lactate, (2) to ascertain whether the PcvCO-PaCO/CaO-CcvO ratio and the arterial lactate levels in the first 24 hours are able to predict mortality at day 28 of enrollment, and (3) to determine whether the PcvCO-PaCO/ CaO-CcvO ratio and arterial lactate are useful in discriminating survivors from nonsurvivors.

Materials And Methods: Thirty patients with sepsis-induced hypotension who were being actively resuscitated were enrolled. Paired arterial and central venous blood samples were obtained 0.5 hourly till stabilization of MAP and 6 hourly thereafter for the first 24 hours. Patients were followed up to day 28 of enrollment for mortality and organ system failure.

Results: A positive correlation was observed between arterial lactate and PcvCO-PaCO/CaO-CcvO ratio at 0, 6, 12, and 18 hours ( = 0.413, = 0.02; = 0.567, = 0.001; = 0.408, = 0.025; = 0.521, = 0.003, respectively). No correlation was seen between PcvCO-PaCO/CaO-CcvO ratio and lactate clearance. The subgroup analysis showed that PcvCO-PaCO/CaO-CcvO ratio >1.696 at 24 hours of resuscitation predicted 28-day mortality (sensitivity: 80%, specificity 69.2%, area under the receiver operating characteristic curve 0.82).

Conclusion: The PcvCO-PaCO/CaO-CcvO ratio and lactate are positively correlated during the first 24 hours of active resuscitation from sepsis-induced hypotension, and a threshold of 1.696 mm Hg/mL/dL at 24 hours significantly differentiates survivors from nonsurvivors (CTRI/2017/11/010342).

How To Cite This Article: Madabhushi S, Trikha A, Anand RK, Ramachandran R, Singh PM, Rewari V. Temporal Evolution of the PcvCO-PaCO/CaO-CcvO Ratio vs Serum Lactate during Resuscitation in Septic Shock. Indian J Crit Care Med 2021; 25(12):1370-1376.
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http://dx.doi.org/10.5005/jp-journals-10071-24044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693105PMC
December 2021

Effect of Change in Body Weight on Clinical Outcomes in Critically Ill Patients.

Indian J Crit Care Med 2021 Sep;25(9):1042-1048

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, Delhi, India.

Background: Intravenous fluid optimization is an essential component of managing patients in a critical care setting. A cumulative positive fluid balance is consistent with poor outcomes in patients admitted to the intensive care unit (ICU). The overall utility of net cumulative fluid balance as a surrogate for assessing fluid overload has been interrogated.

Materials And Methods: This study was a prospective single-center observational study, which was done to correlate body weight changes with fluid balance in ICU patients and evaluate its impact on clinical outcomes. Inclusion criteria consisted of adult patients who were admitted to the critical care unit on specialized beds with integrated weighing scales between September 2017 and December 2018. The evaluation of the effect of changes in body weight on ICU survival was the primary objective of the study.

Results: We enrolled 105 patients in this study. The ICU mortality was 23.80% with non-survivors showing more weight gain than the survivors. Statistically significant weight gain was documented in the non-survivors on days 3 and 4 (1.9 vs 1.05; = 0.0084 and 2.6 vs 1.6; = 0.0030) of ICU admission. Non-survivors had greater cumulative positive fluid balance on fourth, fifth, and sixth days post-ICU admission when compared to survivors (3586 vs 1659 mL, = 0.0322; 5418 vs 1255 mL, = 0.0017; and 5430 vs 2305 mL = 0.0264, respectively). In multivariate regression analysis, cumulative fluid balance did not correlate with days on mechanical ventilation or length of stay in ICU. Changes in body weight and cumulative fluid balance showed a good correlation.

Conclusion: In patients admitted to the ICU, weight gain on third and fourth days of admission is concordant with increased ICU mortality. Body weight changes were seen to correlate well with the cumulative fluid balance.

How To Cite This Article: Mishra RK, Pande A, Ramachandran R, Trikha A, Singh PM, Rewari V. Effect of Change in Body Weight on Clinical Outcomes in Critically Ill Patients. Indian J Crit Care Med 2021;25(9):1042-1048.
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http://dx.doi.org/10.5005/jp-journals-10071-23978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664026PMC
September 2021

Optimum time of LMA ProSeal removal in adult patients undergoing isoflurane anesthesia: A randomized controlled trial.

J Anaesthesiol Clin Pharmacol 2021 Jul-Sep;37(3):354-359. Epub 2021 Oct 12.

Consultant, Intensive Care Unit, Department of Intensive Care Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India.

Background And Aims: Optimum timing of laryngeal mask airway (LMA) removal after general anesthesia with isoflurane is debatable. The objective was to investigate the potential benefits of removing LMA ProSeal at ≤0.4 Minimum alveolar concentration (MAC) isoflurane over awake and "deep plane" extubation after short duration laparoscopic gynecological surgery.

Material And Methods: In this prospective randomized trial 90 adult female patients undergoing elective laparoscopic surgery under general anesthesia using LMA ProSeal™ as airway device were included. At the end of surgery, LMA ProSeal™ was removed when the patient was awake, could open mouth following verbal command (Group A); at MAC ≤0.4 (Group B); or at MAC of 0.6 (Group C). Adverse airway events like nausea, vomiting, airway obstruction, coughing, bucking, laryngospasm were noted. Statistical analyses were done by SPSS statistical software (IBM SPSS Statistics for Mac OS X, Version 21.0. IBM Corp, Armonk, NY).

Results: Baseline demographic characteristics were comparable in all three groups. Coughing or bucking at the time of LMA removal was higher in group A ( = 0.004). Snoring and airway obstruction after LMA removal was significantly higher in group C compared to group A and group B ( = 0.002 and = 0.011, respectively). There was significant change in mean arterial pressure and heart rate between before and after LMA removal on group A ( = 0.008 and < 0.001, respectively) but not in other groups.

Conclusion: MAC ≤0.4 can be considered optimum depth of anesthesia for removal of LMA Proseal in adult patients undergoing isoflurane anesthesia.
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http://dx.doi.org/10.4103/joacp.JOACP_238_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562430PMC
October 2021

Colonic interposition for oesophageal replacement surgery in a patient with left broncho-oesophageal fistula: anaesthetic management.

BMJ Case Rep 2021 Aug 19;14(8). Epub 2021 Aug 19.

Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, Delhi, India

Management of an uncorrected broncho-oesophageal fistula in the perioperative period is a challenge for the anaesthesiologist. Positive pressure ventilation which is inevitable during surgery will lead to gastric insufflation and there is a high risk of aspiration of gastric contents. In this case report, we discuss how we used a double lumen tube to occlude a pericarinal broncho-oesophageal fistula. This method was quite effective as it obviated the need for isolating the lung as well as ensured smooth delivery of positive pressure ventilation during the surgery.
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http://dx.doi.org/10.1136/bcr-2021-243738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378378PMC
August 2021

Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial.

Anaesth Intensive Care 2021 Sep 18;49(5):366-378. Epub 2021 Aug 18.

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

Persistent tachycardia in patients with septic shock predicts poor outcome. This study sought to investigate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and cardio-circulatory function in patients with septic shock. After informed consent, 60 patients with septic shock and persistent tachycardia (heart rate >95 /minute) were prospectively randomly assigned to receive either standard therapy for septic shock (group S) or standard therapy along with enteral ivabradine (group I) for the initial 96 hours after enrolment. Primary outcome was the difference in heart rate between the two groups during the first 96 hours. Secondary outcomes included the effect of ivabradine on haemodynamic, oxygenation, myocardial function and organ function parameters, incidence of adverse events and 30-day overall survival. Heart rate was lower in group I compared to group S (median difference in area under the curve -25.6 (95% confidence intervals -31.4 to -15.9) /minute; <0.001). Vasopressor requirements, blood lactate levels, Sequential Organ Failure Assessment scores and E/e' ratio were lower in group I compared to group S. Stroke volume index and ejection fraction were higher in group I while cardiac index and oxygen delivery parameters were maintained similar to group S. There was no difference in 30-day mortality or in the incidence of serious adverse events. Enteral ivabradine is effective in reducing heart rate, and improving haemodynamic parameters and cardiac function in patients with septic shock and persistent tachycardia, without increasing the incidence of adverse events.
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http://dx.doi.org/10.1177/0310057X211009913DOI Listing
September 2021

HPV transcript expression affects cervical cancer response to chemoradiation.

JCI Insight 2021 08 23;6(16). Epub 2021 Aug 23.

Department of Radiation Oncology.

Persistent HPV infection is causative for the majority of cervical cancer cases; however, current guidelines do not require HPV testing for newly diagnosed cervical cancer. Using an institutional cohort of 88 patients with cervical cancer treated uniformly with standard-of-care chemoradiation treatment (CRT) with prospectively collected clinical outcome data, we observed that patients with cervical tumors containing HPV genotypes other than HPV 16 have worse survival outcomes after CRT compared with patients with HPV 16+ tumors, consistent with previously published studies. Using RNA sequencing analysis, we quantified viral transcription efficiency and found higher levels of E6 and the alternative transcript E6*I in cervical tumors with HPV genotypes other than HPV 16. These findings were validated using whole transcriptome data from The Cancer Genome Atlas (n = 304). For the first time to our knowledge, transcript expression level of HPV E6*I was identified as a predictive biomarker of CRT outcome in our complete institutional data set (n = 88) and within the HPV 16+ subset (n = 36). In vitro characterization of HPV E6*I and E6 overexpression revealed that both induce CRT resistance through distinct mechanisms dependent upon p53-p21. Our findings suggest that high expression of E6*I and E6 may represent novel biomarkers of CRT efficacy, and these patients may benefit from alternative treatment strategies.
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http://dx.doi.org/10.1172/jci.insight.138734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409981PMC
August 2021

Haemodynamic responses following orotracheal intubation in patients with hypertension---Macintosh direct laryngoscope versus Glidescope®videolaryngoscope.

Indian J Anaesth 2021 Apr 15;65(4):321-327. Epub 2021 Apr 15.

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Background And Aims: Glidescope®videolaryngoscope (GVL) is a video intubation system with 60° angle blade that provides excellent laryngeal view, does not require alignment of oral, pharyngeal, and laryngeal axes for visualisation of glottis, thus causing less stimulation of orolaryngopharynx. The aim of this study was to compare haemodynamic responses (blood pressure and heart rate) and airway morbidity using the Macintosh direct laryngoscope (MDL) and the Glidescope®videolaryngoscope (GVL) in hypertensive patients.

Methods: Fifty patients with hypertension controlled on antihypertensive medications scheduled for elective surgery under general anaesthesia were randomly assigned to group GVL ( = 25) or group MDL ( = 25). Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) were recorded at baseline, after induction, pre-intubation, at intubation, 1, 2, 3, 4, and 5 min after intubation. Time to intubation, number of attempts, complications during intubation, and postoperative airway complications (sore throat, hoarseness, dysphagia, and cough) were also recorded.

Results: There was a statistically significant increase in SBP, DBP, and MBP at intubation [( = 0.003, 0.013, 0.03), 1 min ( = 0.001, 0.012, 0.02), 2 min ( = 0.04, 0.02, 0.04), and 3 min ( = 0.02, 0.01)] in the MDL group as compared to GVL group. The time to intubate was significantly greater in the GVL group as compared to MDL group ( = 0.0006). There was no significant difference in the incidence of intraoperative and postoperative airway complications.

Conclusion: In the hands of an experienced anaesthesiologist, the use of GVL in controlled hypertensive patients is associated with less haemodynamic response as compared to Macintosh Laryngoscope without any increase in airway complications.
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http://dx.doi.org/10.4103/ija.IJA_417_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174590PMC
April 2021

Standardized Uptake Value for F-Fluorodeoxyglucose Is a Marker of Inflammatory State and Immune Infiltrate in Cervical Cancer.

Clin Cancer Res 2021 08 5;27(15):4245-4255. Epub 2021 Apr 5.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

Purpose: Chemoradiotherapy for locally advanced cervical cancer fails in over a third of patients. Biomarkers with therapeutic implications are therefore needed. We investigated the relationship between an established prognostic marker, maximum standardized uptake value (SUV) on F-fluorodeoxyglucose positron emission tomography, and the inflammatory and immune state of cervical cancers.

Experimental Design: An SUV most prognostic for freedom from progression (FFP) was identified and compared with known prognostic clinical variables in a cohort of 318 patients treated with definitive radiation with prospectively collected clinical data. Gene set enrichment analysis (GSEA) and CIBERSORT of whole-transcriptome data from 68 patients were used to identify biological pathways and immune cell subpopulations associated with high SUV. IHC using a tissue microarray (TMA, = 82) was used to validate the CIBERSORT findings. The impact of macrophages on cervical cancer glucose metabolism was investigated in coculture experiments.

Results: SUV <11.4 was most prognostic for FFP ( = 0.001). The GSEA showed that high SUV is associated with increased gene expression of inflammatory pathways, including JAK/STAT3 signaling. CIBERSORT and CD68 staining of the TMA showed high SUV tumors are characterized by a monocyte-predominant immune infiltrate. Coculture of cervical cancer cells with macrophages or macrophage-conditioned media altered glucose uptake, and IL6 and JAK/STAT3 signaling contribute to this effect.

Conclusions: SUV is a prognostic marker in cervical cancer that is associated with activation of inflammatory pathways and tumor infiltration of myeloid-derived immune cells, particularly macrophages. Macrophages contribute to changes in cervical cancer glucose metabolism..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338789PMC
August 2021

Integrating imaging and RNA-seq improves outcome prediction in cervical cancer.

J Clin Invest 2021 03;131(5)

Department of Radiation Oncology.

Approaches using a single type of data have been applied to classify human tumors. Here we integrate imaging features and transcriptomic data using a prospectively collected tumor bank. We demonstrate that increased maximum standardized uptake value on pretreatment 18F-fluorodeoxyglucose-positron emission tomography correlates with epithelial-to-mesenchymal transition (EMT) gene expression. We derived and validated 3 major molecular groups, namely squamous epithelial, squamous mesenchymal, and adenocarcinoma, using prospectively collected institutional (n = 67) and publicly available (n = 304) data sets. Patients with tumors of the squamous mesenchymal subtype showed inferior survival outcomes compared with the other 2 molecular groups. High mesenchymal gene expression in cervical cancer cells positively correlated with the capacity to form spheroids and with resistance to radiation. CaSki organoids were radiation-resistant but sensitive to the glycolysis inhibitor, 2-DG. These experiments provide a strategy for response prediction by integrating large data sets, and highlight the potential for metabolic therapy to influence EMT phenotypes in cervical cancer.
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http://dx.doi.org/10.1172/JCI139232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919714PMC
March 2021

Anaesthetic considerations in a child with methylmalonic acidemia and its literature review.

BMJ Case Rep 2020 Dec 9;13(12). Epub 2020 Dec 9.

Anaesthesiology, Pain Medicine and Critical care, All India Institute of Medical Sciences, New Delhi, India.

Methyl malonyl coenzyme A mutase deficiency is a rare autosomal inherited inborn error in branched-chain amino acid metabolism characterised by the accumulation of methylmalonic acids. There is relative paucity of literature regarding anaesthetic management of these children presenting for incidental major abdominal surgery. Preoperative management includes goal-directed correction of dehydration, metabolic acidosis and hyperammonemia. Anaesthetic goals include avoidance of factors that can trigger metabolic crisis like hypercapnia, hypothermia, hypoxia, surgical stress, hypovolaemia, hypotension and so on. Herein, we are reporting the anaesthetic management of a 17-month-old child with methylmalonic acidemia (MMA) posted for a major upper abdominal surgery for excision of an adrenal mass, which was incidentally diagnosed during admission for an episode of metabolic crisis. We aim to highlight the specific nuances of pathophysiology of the disease, preoperative optimisation, anaesthetic considerations, role of advanced monitoring and regional anaesthesia and current literature on the management of patients with MMA.
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http://dx.doi.org/10.1136/bcr-2020-237270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733119PMC
December 2020

Successful Pregnancy Outcomes After Laparoscopic Management of Pheochromocytoma.

J Endourol Case Rep 2020 17;6(3):170-173. Epub 2020 Sep 17.

Department of Urology, All India Institute of Medical Sciences, New Delhi, India.

Pheochromocytoma is a rare cause of hypertension in pregnancy, which is often overlooked; especially in late pregnancy because of more prevalent pre-eclampsia. It has been associated with significant morbidity and mortality rates in both mother and fetus, if not diagnosed and treated in time. Minimally invasive surgery has been infrequently used for surgical management of pheochromocytoma in pregnancy, with <20 reported cases in English literature. A 26-year-old pregnant woman presented at 9 weeks of gestation with complaints of palpitations, sweating, and headache; with past history of first trimester spontaneous abortion caused by accelerated hypertension. She was found to have hypertension and diabetes, but no pedal edema, weight gain, or proteinuria. Ultrasonogram and MRI of abdomen revealed a left adrenal mass and 24 hours urinary catecholamines levels were increased, suggesting a pheochromocytoma. After preoperative optimization in consultations with obstetricians, endocrinologists, and anesthetists, she underwent laparoscopic left adrenalectomy during 15th week of gestation. Perioperative hospital course was uneventful for both mother and the fetus. After adrenalectomy, her diabetes was cured and hypertension was controlled with single antihypertensive. She was readmitted at 31 weeks of gestation with accelerated hypertension and underwent emergency caesarean for impending eclampsia at 32 weeks, and delivered a healthy female baby. 131I-meta-iodobenzylguanidine (MIBG) scan and 68Ga-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-octreotide positron emission tomography-CT (68Ga-DOTANOC PET-CT) scan was obtained in postpartum period to rule out any extra-adrenal pheochromocytoma, both of which did not reveal any abnormality. At 1 year follow-up, she is normoglycemic and hypertension controlled on single antihypertensive. Pheochromocytoma in pregnancy is a rare but potentially lethal condition, and high index of suspicion is required for early diagnosis. Multidisciplinary coordination is required for effective management of this rare condition. Laparoscopic adrenalectomy is safe in second trimester of pregnancy for both mother and fetus.
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http://dx.doi.org/10.1089/cren.2019.0139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580628PMC
September 2020

Glutaminase Inhibitors Induce Thiol-Mediated Oxidative Stress and Radiosensitization in Treatment-Resistant Cervical Cancers.

Mol Cancer Ther 2020 12 21;19(12):2465-2475. Epub 2020 Oct 21.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

The purpose of this study was to determine if radiation (RT)-resistant cervical cancers are dependent upon glutamine metabolism driven by activation of the PI3K pathway and test whether PI3K pathway mutation predicts radiosensitization by inhibition of glutamine metabolism. Cervical cancer cell lines with and without PI3K pathway mutations, including SiHa and SiHa PTEN cells engineered by CRISPR/Cas9, were used for mechanistic studies performed in the presence and absence of glutamine starvation and the glutaminase inhibitor, telaglenastat (CB-839). These studies included cell survival, proliferation, quantification of oxidative stress parameters, metabolic tracing with stable isotope-labeled substrates, metabolic rescue, and combination studies with L-buthionine sulfoximine (BSO), auranofin (AUR), and RT. studies of telaglenastat ± RT were performed using CaSki and SiHa xenografts grown in immune-compromised mice. PI3K-activated cervical cancer cells were selectively sensitive to glutamine deprivation through a mechanism that included thiol-mediated oxidative stress. Telaglenastat treatment decreased total glutathione pools, increased the percent glutathione disulfide, and caused clonogenic cell killing that was reversed by treatment with the thiol antioxidant, N-acetylcysteine. Telaglenastat also sensitized cells to killing by glutathione depletion with BSO, thioredoxin reductase inhibition with AUR, and RT. Glutamine-dependent PI3K-activated cervical cancer xenografts were sensitive to telaglenastat monotherapy, and telaglenastat selectively radiosensitized cervical cancer cells and These novel preclinical data support the utility of telaglenastat for glutamine-dependent radioresistant cervical cancers and demonstrate that PI3K pathway mutations may be used as a predictive biomarker for telaglenastat sensitivity.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208465PMC
December 2020

Coronavirus disease 2019 and laparoscopic surgery in resource-limited settings.

Asian J Endosc Surg 2021 Apr 27;14(2):305-308. Epub 2020 Jul 27.

Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, the use of laparoscopy has been discouraged by the Intercollegiate General Surgery because of its potential for aerosol generation and infection. In contrast, the Society of American Gastrointestinal and Endoscopic Surgeons and the European Association of Endoscopic Surgery recommend continuing to use laparoscopy but with devices to filter released CO aerosol particles. However, commercially available systems are costly and may not be readily available. Herein, we describe a custom-made system to safely remove surgical smoke and CO , as well as a case of laparoscopic cholecystectomy in which we used it.

Materials And Surgical Technique: The patient had had multiple episodes of biliary pancreatitis and required urgent cholecystectomy during the COVID-19 pandemic. Although India was in complete lockdown, it was decided to operate with precaution. A system was designed using underwater seal chest tube drainage and an electrostatic membrane filter with a viral retention function greater than 99.99%. The system was connected to an extra port for continuous controlled egression of CO pneumoperitoneum. A regular four-port cholecystectomy was performed at an intra-abdominal pressure of 12 mm Hg. The gas flow rate was 10 L/min. CO for pneumoperitoneum, surgical aerosol, and effluents passed through the system before collecting in the suction apparatus. The exchange of operating instruments through the ports was kept to a minimum. It was done after the abdomen was temporarily desufflated using this system.

Discussion: The system we designed appears safe and is cost-effective. In resource-limited settings, it will be handy in patients requiring laparoscopic surgery both during and after the COVID-19 pandemic.
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http://dx.doi.org/10.1111/ases.12835DOI Listing
April 2021

Long-term Outcomes Following Primary Closure of Common Bile Duct Following Laparoscopic Common Bile Duct (CBD) Exploration: Experience of 355 Cases at a Tertiary Care Center.

Surg Laparosc Endosc Percutan Tech 2020 Dec;30(6):504-507

Departments of Surgical Disciplines.

Introduction: Primary closure of common bile duct (CBD) after laparoscopic common bile duct exploration (LCBDE) is now becoming the preferred technique for closure of choledochotomy. Primary CBD closure not only circumvents the disadvantages of an external biliary drainage but also adds to the advantage of LCBDE. Here, we describe our experience of primary CBD closure following 355 cases of LCBDE in a single surgical unit at a tertiary care hospital.

Materials And Methods: All patients undergoing LCBDE in a single surgical unit were included in the study. Preoperative and intraoperative parameters including the technique of CBD closure were recorded prospectively. The postoperative recovery, complications, hospital stay, antibiotic usage, and postoperative intervention, if any, were also recorded.

Results: Three hundred fifty-five LCBDEs were performed from April 2007 to December 2018, and 143 were post-endoscopic retrograde cholangiopancreatography failures. The overall success rate was 91.8%. The mean operative time was 98±26.8 minutes (range, 70 to 250 min). Transient bile leak was seen in 10% of patients and retained stones in 3 patients. Two patients required re-exploration and 2 patients died in the postoperative period. Follow-up ranged from 6 months to 10 years, with a median follow-up of 72 months. No long-term complications such as CBD stricture or recurrent stones were noted.

Conclusions: Primary closure of CBD after LCBDE is safe and associated with minimal complications and no long-term problems. The routine use of primary CBD closure after LCBDE is recommended based on our experience.
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http://dx.doi.org/10.1097/SLE.0000000000000830DOI Listing
December 2020

A three-arm randomized study to compare sexual functions and fertility indices following open mesh hernioplasty (OMH), laparoscopic totally extra peritoneal (TEP) and transabdominal preperitoneal (TAPP) repair of groin hernia.

Surg Endosc 2021 06 15;35(6):3077-3084. Epub 2020 Jun 15.

Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India.

Background: With evolving technology, the focus of groin hernia repair has shifted to sexual function and fertility outcomes.

Methods: This three-arm randomized study was conducted in tertiary care hospital from 1st July 2017 to 30th March 2019. Consecutive patients of groin hernia were randomized into 3 groups, TAPP (Group 1), TEP (Group 2), and OMH (Group 3). Demographic profile and hernia characteristics were assessed preoperatively. Sexual functions (using BMSFI) and fertility (using surrogate fertility indices, viz., semen analysis and anti-sperm antibodies (ASA)) were assessed preoperatively at 3 months after the surgery.

Results: A total of 121 patients were included in the study with 41 patients in TAPP (Group 1) and 40 each in TEP (Group 2) and OMH (Group3) group. All the 3 groups were comparable in terms of demographic profile, hernia characteristics, intra-operative and early post-operative outcomes. Significant improvement was found in most of the domains of BMSFI score in the study population (p value < 0.001) with no intergroup difference. There was significant increase of anti-sperm antibody level in OMH group as compared to TAPP and TEP (p = 0.001), however, the levels were within normal limit.

Conclusions: In conclusion, this study has shown that inguinal hernia repair whether open or laparoscopic (TEP or TAPP) leads on to improvement in sexual functions and fertility indices and can have a significant impact on pre-op counseling of the patient in terms of choice of repair, depending on the available expertise in a given center.
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http://dx.doi.org/10.1007/s00464-020-07697-zDOI Listing
June 2021

Randomized controlled trial to compare outcomes with and without the enhanced recovery after surgery protocol in patients undergoing radical cystectomy.

Indian J Urol 2020 Apr-Jun;36(2):95-100. Epub 2020 Apr 7.

Department of Urology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Very few randomized controlled trials are available globally to support routine use of enhanced recovery after surgery (ERAS) protocol after radical cystectomy (RC), and none so far has been conducted in the Indian subcontinent. The aim of the present study was to evaluate hospital stay and 30-day perioperative outcomes following RC with the implementation of the ERAS protocol.

Materials And Methods: Fifty-four patients undergoing open RC were randomized to ERAS versus conventional surgical care (CSC) at our center from April 2017 to May 2018. Key interventions included avoidance of mechanical bowel preparation, early nasogastric tube removal, early enteral feeding, and early obligatory ambulation. Follow-up was done till 30-day postoperatively or till discharge, whichever longer.

Results: Twenty-seven patients in each group were analyzed. The demographic profile of the groups was similar. Length of stay in each group (8 days [5-57] ERAS vs. 9 days [5-31] CSC group, = 0.390) was similar, with time to recovery of bowel function being significantly less in ERAS group (12 h [12-108] vs. 36 h [12-60] for bowel sounds [P = 0.001], 48 h [12-108] vs. 72 h [36-156] for passage of flatus [P = 0.001], and 84 h [36-180] vs. 96 [60-156] for passage of stools [P = 0.013]). Perioperative complication rate (12 patients (44.4%) vs. 14 (51.9%), = 0.786) was similar.

Conclusions: ERAS protocol leads to faster bowel recovery compared to conventional care in patients undergoing open RC but fails to demonstrate a shorter length of stay and lower complication rate.
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http://dx.doi.org/10.4103/iju.IJU_11_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279092PMC
April 2020

Open surgery for pheochromocytoma: Current indications and outcomes from a retrospective cohort.

Indian J Urol 2020 Jan-Mar;36(1):21-25

Department of Urology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Minimally invasive approaches are the current standard of care for pheochromocytoma/paraganglioma (PC/PG) surgery. However, a number of patients still undergo open surgery for these tumors. We evaluated the current indications and outcomes of open surgery for PC/PG to define the role of this approach.

Methods: Data of patients undergoing PC/PG surgery between July 2008 and July 2017 were retrieved from our prospectively maintained electronic database and hospital records. Tumor characteristics, operative and recovery parameters, and complications were evaluated for indications of open procedure and outcomes.

Results: During the study period, 106 patients underwent 124 procedures for PC/PG, including 18 simultaneous bilateral procedures. Surgeries included 102 adrenalectomies, 18 PG excisions, one partial adrenalectomy, and three partial cystectomies. Twenty-five (23.6%) patients (mean age 38.2 ± 16.1 years) underwent an open procedure, including four bilateral procedures. This included 16 adrenalectomies and 9 PG excisions. The indications for open surgery were unilateral large tumours (5; size 8-16, mean 11 cm), bilateral large tumours (2; size 6-10, mean 8.2 cm), retrocaval tumour extension (4), inter aortocaval PGs (8), Retro-mesenteric PG (1), concomitant procedures (3), and conversion from laparoscopy (2). Mean operative time was 217 ± 63.8 min, blood loss was 868 ± 734.2 ml, 11 patients required blood transfusion, and hospital stay was 6.44 ± 2.4 days. All these parameters were higher than for minimally invasive surgery (MIS) in this cohort. Three patients (12%) suffered a postoperative complication, and the rate of complications was not higher than MIS cohort (16%).

Conclusions: Open surgery was most often indicated for large tumors or those located in the inter-aortocaval region. Most such procedures require large incisions and possible hepatic mobilization on the right side. The procedures can be safely completed with few complications.
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http://dx.doi.org/10.4103/iju.IJU_186_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961438PMC
January 2020

Cerebrospinal Fluid Proteomics For Identification Of α2-Macroglobulin As A Potential Biomarker To Monitor Pharmacological Therapeutic Efficacy In Dopamine Dictated Disease States Of Parkinson's Disease And Schizophrenia.

Neuropsychiatr Dis Treat 2019 2;15:2853-2867. Epub 2019 Oct 2.

Department of Biophysics.

Aim: Parkinson's disease and schizophrenia are clinical end points of dopaminergic deficit and excess, respectively, in the mid-brain. In accordance, current pharmacological interventions aim to restore normal dopamine levels, the overshooting of which culminates in adverse effects which results in psychotic symptoms in Parkinson's disease and extra-pyramidal symptoms in schizophrenia. Currently, there are no laboratory assays to assist treatment decisions or help foresee these drug side-effect outcomes. Therefore, the aim was to discover a protein biomarker that had a varying linear expression across the clinical dopaminergic spectrum.

Materials And Methods: iTRAQ-based proteomic experiments along with mass spectrometric analysis was used for comparative proteomics using cerebrospinal fluid (CSF). CSF fluid was collected from 36 patients with Parkinson's disease, 15 patients with urological diseases that served as neurological controls, and seven schizophrenic patients with hallucinations. Validation included ELISA and pathway analysis to highlight the varying expression and provide plausible molecular pathways for differentially expressed proteins in the three clinical phenotypes.

Results: Protein profiles were delineated in CSF from Parkinson's disease patients, neurological control and schizophrenia, respectively. Ten of the proteins that were identified had a linear relationship across the dopaminergic spectrum. α-2-Macroglobulin showed to be having high statistical significance on inter-group comparison on validation studies using ELISA.

Conclusions: Non-gel-based proteomic experiments are an ideal platform to discover potential biomarkers that can be used to monitor pharmaco-therapeutic efficacy in dopamine-dictated clinical scenarios. α-2 Macroglobulin is a potential biomarker to monitor pharmacological therapy in Parkinson's disease and schizophrenia.
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http://dx.doi.org/10.2147/NDT.S214217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781638PMC
October 2019

[Awake nasal fibre optic intubation --- a simple manoeuvre for easy navigation of the fiberscope through the nasopharynx].

Braz J Anesthesiol 2019 Nov - Dec;69(6):641. Epub 2019 Oct 17.

All India Institute of Medical Sciences, Department of Otorhinolaryngology, Ansari Nagar, Índia.

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http://dx.doi.org/10.1016/j.bjan.2019.06.011DOI Listing
July 2020

Alteration of Cellular Reduction Potential Will Change Cu-ATSM Signal With or Without Hypoxia.

J Nucl Med 2020 03 4;61(3):427-432. Epub 2019 Oct 4.

Department of Radiation Oncology, Washington University, St. Louis, Missouri.

Therapies targeting reductive/oxidative (redox) metabolism hold potential in cancers resistant to chemotherapy and radiation. A redox imaging marker would help identify cancers susceptible to redox-directed therapies. Copper(II)-diacetyl-bis(4-methylthiosemicarbazonato) (Cu-ATSM) is a PET tracer developed for hypoxia imaging that could potentially be used for this purpose. We aimed to demonstrate that Cu-ATSM signal is dependent on cellular redox state, irrespective of hypoxia. We investigated the relationship between Cu-ATSM signal and redox state in human cervical and colon cancer cells. We altered redox state using drug strategies and single-gene mutations in isocitrate dehydrogenases (IDH1/2). Concentrations of reducing molecules were determined by spectrophotometry and liquid chromatography-mass spectrometry and compared with Cu-ATSM signal in vitro. Mouse models of cervical cancer were used to evaluate the relationship between Cu-ATSM signal and levels of reducing molecules in vivo, as well as to evaluate the change in Cu-ATSM signal after redox-active drug treatment. A correlation exists between baseline Cu-ATSM signal and cellular concentration of glutathione, nicotinamide adenine dinucleotide phosphate (NADPH), and nicotinamide adenine dinucleotide (NADH). Altering NADH and NADPH metabolism using drug strategies and IDH1 mutations resulted in significant changes in Cu-ATSM signal under normoxic conditions. Hypoxia likewise changed Cu-ATSM signal, but treatment of hypoxic cells with redox-active drugs resulted in a more dramatic change than hypoxia alone. A significant difference in NADPH was seen between cervical tumor orthotopic implants in vivo, without a corresponding difference in Cu-ATSM signal. After treatment with β-lapachone, there was a change in Cu-ATSM signal in xenograft tumors smaller than 50 mg but not in larger tumors. Cu-ATSM signal reflects redox state, and altering redox state impacts Cu-ATSM metabolism. Our animal data suggest there are other modulating factors in vivo. These findings have implications for the use of Cu-ATSM as a predictive marker for redox therapies, though further in vivo work is needed.
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http://dx.doi.org/10.2967/jnumed.119.230805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067520PMC
March 2020

Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson's disease and schizophrenia.

Neuropsychiatr Dis Treat 2019 19;15:2073-2085. Epub 2019 Jul 19.

Department of Biophysics.

Background And Objective: Dopamine plays an important role in the disease pathology of Parkinson's disease and schizophrenia. These two neuropsychiatric disorders represent disease end points of the dopaminergic spectrum where Parkinson's disease represents dopamine deficit and schizophrenia represents dopamine hyperactivity in the mid-brain. Therefore, current treatment strategies aim to restore normal dopamine levels. However, during treatment patients develop adverse effects due to overshooting of physiological levels of dopamine leading to psychosis in Parkinson's disease, and extrapyramidal symptoms in schizophrenia. Absence of any laboratory tests hampers modulation of pharmacotherapy. Apolipoprotein E and α-synuclein have an important role in the neuropathology of these two diseases. The objective of this study was to evaluate cerebrospinal fluid (CSF) concentrations of apolipoprotein E and α-synuclein in patients with these two diseases so that they may serve as biomarkers to monitor therapy in Parkinson's disease and schizophrenia.

Methods: Drug-naïve Parkinson's disease patients and Parkinson's disease patients treated with dopaminergic therapy, neurological controls, schizophrenic patients treated with antidopaminergic therapy, and drug-naïve schizophrenic patients were recruited for the study and CSF was collected. Enzyme-linked immunosorbent assays were carried out to estimate the concentrations of apolipoprotein E and α-synuclein. Pathway analysis was done to establish a possible role of these two proteins in various pathways in these two dopamine dictated diseases.

Results: Apolipoprotein E and α-synuclein CSF concentrations have an inverse correlation along the entire dopaminergic clinical spectrum. Pathway analysis convincingly establishes a plausible hypothesis for their co-regulation in the pathogenesis of Parkinson's disease and schizophrenia. Each protein by itself or as a combination has encouraging sensitivity and specificity values of more than 55%.

Conclusion: The dynamic variation of these two proteins along the spectrum is ideal for them to be pursued as pharmacotherapeutic biomarkers in CSF to monitor pharmacological efficacy in Parkinson's disease and schizophrenia.
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http://dx.doi.org/10.2147/NDT.S205550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650621PMC
July 2019

Continuous wound infiltration of local anaesthetics for acute postoperative pain - A revisit.

Indian J Anaesth 2019 Jun;63(6):425-427

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India E-mail:

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http://dx.doi.org/10.4103/ija.IJA_425_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573056PMC
June 2019

Changes in blood pressure, blood sugar, and quality of life in patients undergoing pheochromocytoma surgery: a prospective cohort study.

Indian J Urol 2019 Jan-Mar;35(1):34-40

Department of Urology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Pheochromocytoma surgery is associated with significant hemodynamic and metabolic changes that require post-operative monitoring. We prospectively evaluated the trends of blood pressure, blood sugar, body mass index (BMI), and quality of life (QoL) changes in a cohort of patients undergoing pheochromocytoma surgery to determine the minimum duration of monitoring and assess factors that could predict these changes.

Materials And Methods: Consecutive patients undergoing surgery for pheochromocytoma over a 20-month period were included in this ethics review board-approved, prospective cohort study. Blood pressure and sugar levels were serially monitored using a fixed protocol in the perioperative period and subsequently at 3 months after surgery. BMI and QoL (using World Health Organization Quality of Life [WHOQOL-BREF] questionnaire) were recorded at baseline and 3 months. Changes were compared and assessed for the predictive factors.

Results: Twenty-six patients undergoing 31 procedures were included in the study of whom 8 (30%) developed hypotension and 4 (15%) developed hypoglycemia after surgery. All hypotension episodes occurred within 6 hours of surgery. However, while 3 of the 4 patients who developed hypoglycemia manifest in the first 4 h after surgery, one occurred after 12 h. Occurrence of hypotension correlated with preoperative 24-h urinary vanillylmandelic acid (VMA) levels ( = 0.02) and the total daily dose of prazosin ( = 0.04). Out of 21 hypertensive patients, 7 (33%) had persistent hypertension (HTN) at 3 months and this was associated with age ( = 0.04) and diabetes mellitus (DM) at presentation ( = 0.04). Among six diabetic patients, 1 (16%) had persistent DM. There was significant increase in the BMI ( < 0.0001) and in WHOQOL-BREF scores postoperatively.

Conclusions: Hypotension occurs in 30% patients and hypoglycemia in 15% after pheochromocytoma surgery. Hypotension occurs immediately but hypoglycemia may manifest upto 12h after surgery. Older, diabetic patients are more likely to have persistent HTN. Surgery results in increase in BMI and improvement in QoL.
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http://dx.doi.org/10.4103/iju.IJU_190_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334590PMC
January 2019

Compression with the ultrasound probe to prevent malposition of central venous catheter in the ipsilateral internal jugular vein during axillary vein cannulation.

J Clin Ultrasound 2019 Feb 25;47(2):95-96. Epub 2018 Nov 25.

Department of Anaesthesiology, Pain Medicine, and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/jcu.22666DOI Listing
February 2019

Ultrasonography and Seldinger's technique: Using the best of both worlds for difficult radial artery cannulation!

J Anaesthesiol Clin Pharmacol 2018 Jul-Sep;34(3):420-421

Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/joacp.JOACP_15_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194826PMC
November 2018

Bougie-associated bronchial injury complicated by a nephropleural fistula after percutaneous nephrolithotomy: a tale of two complications.

BMJ Case Rep 2018 Apr 17;2018. Epub 2018 Apr 17.

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, Delhi, India.

We present a case of bronchial injury following bougie-assisted endotracheal intubation in a patient with difficult airway scheduled to undergo right percutaneous nephrolithotomy under general anaesthesia. The patient developed pleuritic pain along with right pleural effusion on the third postoperative day which was diagnosed by the anaesthesiologist who was following up the patient for airway trauma-associated complications. However, the patient was diagnosed to have a nephropleural fistula, a rare complication of supracostal access to percutaneous nephrolithotomy, which was managed successfully.
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http://dx.doi.org/10.1136/bcr-2017-223969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905817PMC
April 2018
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