Comparative Efficacy of Intraoperative Patient State Index vs. Bi-Spectral Index in Patients Undergoing Elective Spine Surgery with Neuromonitoring Under General Anaesthesia: A Randomized Controlled Trial.

Objective: Various electroencephalogram-based monitors have been introduced to objectively quantify anaesthesia depth. However, limited data are available on their comparative clinical efficacy in various surgical procedures. Therefore, we planned this study to compare the relative efficacy of patient state index (PSI) vs. Bi-spectral index (BIS) assessment in patients undergoing elective spine surgery under general anaesthesia. Methods: This prospective, parallel-group, single-center study included patients undergoing major spine surgery with neuromonitoring. Patients were randomized into two groups, i.e., group B (undergoing surgery under BIS monitoring) and group P (undergoing surgery under PSI monitoring). The primary objective was to compare the time to eye opening after stopping anaesthetic drug infusions. Results: The mean propofol dose required for induction in group B was 130.45±26.579, whereas that in group P, it was 139.28±17.86 (P value 0.085). The maintenance doses of propofol and fentanyl required for surgery were also comparable between the groups. Time to eye opening was 12.2±4.973 in group B and 12.93±4.19 in group P, with a P value of 0.2664 (U-statistic-684.50). Conclusion: The intraoperative PSI and BIS had similar clinical efficacy in terms of the dose of propofol required for induction, time of induction, maintenance dose of propofol and fentanyl, time of eye opening, and recovery profile in patients undergoing elective spine surgery under neuromonitoring.

The efficacy of ultrasound-guided upper thoracic erector spinae plane block for postoperative analgesia in proximal shoulder surgery and its effect on phrenic nerve function: A prospective exploratory study.

Background and Aims: The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in shoulder surgery. The current study was conducted to evaluate the same. Material and Methods: Patients scheduled for shoulder surgery under general anesthesia (GA) received ultrasound-guided UT-ESPB. The outcomes measured were diaphragmatic movements, block characteristics, and quality of recovery at 24 h. Results: A total of 43 patients were recruited. The incidence of phrenic nerve palsy was 0%. The sensory level achieved by the maximum number of patients at the end of 30 min was C7-T5 level, and none had a motor block. Forty-two percent of patients did not require rescue analgesia till 24 h postoperative. In the rest of the patients, the mean (SD) duration of analgesia was 724.2 ± 486.80 min, and the mean postoperative requirement of fentanyl was 98.80 ± 47.02 µg. The median pain score (NRS) during rest and movement is 2 to 3 and 3 to 4, respectively. The median quality of recovery score at the end of 24 h after the block was 14 (15-14). Conclusion: The upper thoracic ESPB resulted in a sensory loss from C7-T5 dermatomes without any weakness of the diaphragm and upper limb. However, the block was moderately effective in terms of the total duration of analgesia, postoperative pain scores, analgesic requirement, and quality of recovery in patients undergoing proximal shoulder surgeries under GA. Further studies are required to establish its role due to its poor correlation with sensory spread.

Incidence and Risk Factors for Postoperative Visual Loss after Cardiac Surgical Procedures: A Systematic Review.

ABSTRACT: Postoperative visual loss (POVL) is an infrequent yet consequential complication that can follow cardiac surgical interventions. This systematic review aims to provide a comprehensive analysis of the incidence of POVL after cardiac surgery and to delineate the associated risk factors. A comprehensive search was conducted in major medical databases for relevant studies published up to September 2022. Eligible studies reporting on the incidence of POVL and identifying risk factors in patients undergoing cardiac surgery were included. Data extraction was performed independently by two reviewers. The pooled incidence rates and the identified risk factors were synthesized qualitatively. POVL after cardiac surgery has an overall incidence of 0.015%, that is, 15 cases per 100,000 cardiac surgical procedures. Risk factors for POVL include patient characteristics (advanced age, diabetes, hypertension, and preexisting ocular conditions), procedural factors (prolonged surgery duration, cardiopulmonary bypass time, and aortic cross-clamping), anesthetic considerations (hypotension, blood pressure fluctuations, and specific techniques), and postoperative complications (stroke, hypotension, and systemic hypoperfusion). Ischemic optic neuropathy (ION) is an uncommon complication, associated with factors like prolonged cardiopulmonary bypass, low hematocrit levels, excessive body weight gain, specific medications, hypothermia, anemia, raised intraocular pressure, and micro-embolization. Diabetic patients with severe postoperative anemia are at increased risk for anterior ischemic optic neuropathy (AION). Posterior ischemic optic neuropathy (PION) can occur with factors like hypertension, postoperative edema, prolonged mechanical ventilation, micro-embolization, inflammation, hemodilution, and hypothermia.While the overall incidence of POVL postcardiac surgery remains modest, its potential impact is substantial, necessitating meticulous consideration of modifiable risk factors. Notably, prolonged surgical duration, intraoperative hypotension, anemia, and reduced hematocrit levels remain salient contributors. Vigilance is indispensable to promptly detect this infrequent yet visually debilitating phenomenon in the context of postcardiac surgical care.

Recent Developments in the Study of the Microenvironment of Cancer and Drug Delivery.

Cancer is characterized by disrupted molecular variables caused by cells that deviate from regular signal transduction. The uncontrolled segment of such cancerous cells annihilates most of the tissues that contact them. Gene therapy, immunotherapy, and nanotechnology advancements have resulted in novel strategies for anticancer drug delivery. Furthermore, diverse dispersion of nanoparticles in normal stroma cells adversely affects the healthy cells and disrupts the crosstalk of tumour stroma. It can contribute to cancer cell progression inhibition and, conversely, to acquired resistance, enabling cancer cell metastasis and proliferation. The tumour's microenvironment is critical in controlling the dispersion and physiological activities of nano-chemotherapeutics which is one of the targeted drug therapy. As it is one of the methods of treating cancer that involves the use of medications or other substances to specifically target and kill off certain subsets of malignant cells. A targeted therapy may be administered alone or in addition to more conventional methods of care like surgery, chemotherapy, or radiation treatment. The tumour microenvironment, stromatogenesis, barriers and advancement in the drug delivery system across tumour tissue are summarised in this review.

Effect of intraoperative alveolar recruitment maneuver on intraoperative oxygenation and postoperative pulmonary function tests in patients undergoing robotic-assisted hysterectomy: a single-blind randomized study.

BACKGROUND: Robotic-Assisted Hysterectomies (RAH) require Trendelenburg positioning and pneumoperitoneum, which further accentuate alteration in respiratory mechanics induced by general anesthesia. The role of Recruitment Maneuver (RM) as a lung-protective strategy during intraoperative surgical settings has not been much studied. We planned this study to evaluate the effect of RM on perioperative oxygenation and postoperative spirometry using PaO2/FiO2 and FEV1/FVC, respectively in patients undergoing RAH. METHODS: Sixty-six ASA I‒II female patients scheduled for elective RAH were randomized into group R (recruitment maneuver, n = 33) or group C (control, n = 33). Portable spirometry was done one day before surgery. Patients were induced with general anesthesia, and mechanical ventilation started with volume control mode, with Tidal Volume (TV) of 6-8 mL.kg-1, Respiratory Rate (RR) of 12 min, inspiratory-expiratory ratio (I: E ratio) of 1:2, FiO2 of 0.4, and Positive End-Expiratory Pressure (PEEP) of 5 cmH2O. Patients in group R received recruitment maneuvers of 30 cmH2O every 30 minutes following tracheal intubation. The primary objectives were comparison of oxygenation and ventilation between two groups intraoperatively and portable spirometry postoperatively. Postoperative pulmonary complications, like desaturation, pulmonary edema, pneumonia, were monitored. RESULTS: Patients who received RM had significantly higher PaO2 (mmHg) (203.2+-24.3 vs. 167.8+-27.3, p < 0.001) at T2 (30 min after the pneumoperitoneum). However, there was no significant difference in portable spirometry between the groups in the postoperative period (FVC, 1.40 ± 0.5 L vs. 1.32 ± 0.46 L, p = 0.55). CONCLUSION: This study concluded that intraoperative recruitment did not prevent deterioration of postoperative spirometry values; however, it led to improved oxygenation intraoperatively.

Effect of intraoperative alveolar recruitment maneuver on intraoperative oxygenation and postoperative pulmonary function tests in patients undergoing robotic-assisted hysterectomy: a single-blind randomized study

Abstract Background Robotic-Assisted Hysterectomies (RAH) require Trendelenburg positioning and pneumoperitoneum, which further accentuate alteration in respiratory mechanics induced by general anesthesia. The role of Recruitment Maneuver (RM) as a lung-protective strategy during intraoperative surgical settings has not been much studied. We planned this study to evaluate the effect of RM on perioperative oxygenation and postoperative spirometry using PaO2/FiO2 and FEV1/FVC, respectively in patients undergoing RAH. Methods Sixty-six ASA I‒II female patients scheduled for elective RAH were randomized into group R (recruitment maneuver, n = 33) or group C (control, n = 33). Portable spirometry was done one day before surgery. Patients were induced with general anesthesia, and mechanical ventilation started with volume control mode, with Tidal Volume (TV) of 6-8 mL.kg−1, Respiratory Rate (RR) of 12 min, inspiratory-expiratory ratio (I: E ratio) of 1:2, FiO2 of 0.4, and Positive End-Expiratory Pressure (PEEP) of 5 cmH2O. Patients in group R received recruitment maneuvers of 30 cmH2O every 30 minutes following tracheal intubation. The primary objectives were comparison of oxygenation and ventilation between two groups intraoperatively and portable spirometry postoperatively. Postoperative pulmonary complications, like desaturation, pulmonary edema, pneumonia, were monitored. Results Patients who received RM had significantly higher PaO2 (mmHg) (203.2+-24.3 vs. 167.8+-27.3, p < 0.001) at T2 (30 min after the pneumoperitoneum). However, there was no significant difference in portable spirometry between the groups in the postoperative period (FVC, 1.40 ± 0.5 L vs. 1.32 ± 0.46 L, p= 0.55). Conclusion This study concluded that intraoperative recruitment did not prevent deterioration of postoperative spirometry values; however, it led to improved oxygenation intraoperatively.

Optimal level of bispectral index for conscious sedation in awake fiberoptic nasotracheal intubation.

BACKGROUND: Bispectral index (BIS) has been in practice as an objective tool to measure the depth of conscious sedation. The data on adequate levels for awake fiberoptic nasotracheal intubation (AFNI) is however scarce. We aimed to obtain an optimal level of BIS required for achieving the adequate conscious sedation in AFNI procedure. METHODS: In a prospective, observational, outcome assessor blinded cohort trial, 94 consecutive patients with anticipated difficult intubation and undergoing AFNI for any elective surgery were enrolled. The topical anesthesia and sedation were induced with lidocaine and dexmedetomidine, while keeping the patient awake. The sedation levels were targeted to BIS ≤90 and Ramsay sedation score (RSS)≥2 to attempt intubation. Propofol bolus were administered if patients get agitated. The primary outcome was "Stable BIS", the lowest BIS at which intubation could be feasibly performed. A receiver operator characteristic curve, Youden index, and correlation analysis were used. RESULTS: The optimal criterion for BIS was obtained as ≤86 (AUC: 0.80, sensitivity 88.30%, specificity 61.45%, Youden index 49.74). The stable BIS ranged from 80 to 88, while RSS varied from 1 to 3. The BIS and RSS correlated significantly (r: 0.83). The stable BIS was independent of any baseline characteristics. Six patients had transient untoward events, none requiring any intervention. CONCLUSION: BIS serves as an effective objective tool for titrating the depth of conscious sedation. We advocate a BIS range of 80-86 for feasibly performing the AFNI procedure.

Solution structure, glycan specificity and of phenol oxidase inhibitory activity of Anopheles C-type lectins CTL4 and CTLMA2.

Malaria, the world's most devastating parasitic disease, is transmitted between humans by mosquitoes of the Anopheles genus. An. gambiae is the principal malaria vector in Sub-Saharan Africa. The C-type lectins CTL4 and CTLMA2 cooperatively influence Plasmodium infection in the malaria vector Anopheles. Here we report the purification and biochemical characterization of CTL4 and CTLMA2 from An. gambiae and An. albimanus. CTL4 and CTLMA2 are known to form a disulfide-bridged heterodimer via an N-terminal tri-cysteine CXCXC motif. We demonstrate in vitro that CTL4 and CTLMA2 intermolecular disulfide formation is promiscuous within this motif. Furthermore, CTL4 and CTLMA2 form higher oligomeric states at physiological pH. Both lectins bind specific sugars, including glycosaminoglycan motifs with ß1-3/ß1-4 linkages between glucose, galactose and their respective hexosamines. Small-angle x-ray scattering data supports a compact heterodimer between the CTL domains. Recombinant CTL4/CTLMA2 is found to function in vivo, reversing the enhancement of phenol oxidase activity in dsCTL4-treated mosquitoes. We propose these molecular features underline a common function for CTL4/CTLMA2 in mosquitoes, with species and strain-specific variation in degrees of activity in response to Plasmodium infection.

Unusual clinical presentations of choriocarcinoma: A systematic review of case reports.

Choriocarcinoma (CC) is a highly malignant tumor originating in the trophoblastic tissue. The clinical presentation of CC is so much varied that every case may be one of its kinds and thus can be a diagnostic challenge. Numerous case reports have been published in various journals regarding the unusual clinical presentations of this cancer. Therefore, we conducted a systematic review of all case reports in English language on gestational CC published in PubMed-indexed journals from 1998 to 2015. The main aim was to provide a summary and critical analysis of all the data and evidence published regarding the atypical clinical presentations of CC in recent years. In total, 121 case reports pertaining to unusual clinical manifestations of gestational CC were analyzed. The age of patients in whom cases were reported ranged from 17 to 67 years, and the time period between the index pregnancy and development of CC varied from 4 weeks to as long as 25 years. Cardiopulmonary complaints (20.66%) followed by gastrointestinal (18.43%) and central nervous system manifestations (17.67%) were found to be the most common. Through this review, the authors have made an attempt to discuss various manifestations with which a patient with gestational CC can present to clinician so that early diagnosis and timely management can be initiated, thus improving clinical prognosis.

Patient's knowledge and perception of preanesthesia check-up in rural India.

BACKGROUND: Preanesthesia assessment is an important aspect of patient care. If a patient shows lack of interest during preanesthesia check-up or tries to rush through, it may result in incomplete history and general physical examination, compromising patient care. AIM: The aim of this study was to assess the knowledge of patients presenting for elective surgery to Tertiary Care Hospital in Rural India regarding value and importance of preanesthesia check-up. SETTINGS AND DESIGN: This observational study was conducted in a Tertiary Care Teaching Hospital in Rural India. 1000 patients posted for elective surgery coming to preadmission anesthesia consultation (PAC) clinic over a period of 3 months were included in this study. METHODS: Patients were asked to fill a questionnaire consisting of 15 questions before start of preanesthesia assessment. Each question was provided with multiple possible choices, out of which patient had to choose the most appropriate according to him/her. Scoring was done, with each question answered correctly being given 1 mark while incorrect answer was awarded 0 marks. STATISTICAL ANALYSIS: Data were expressed as frequencies and percentage. Correlations studies were performed by unpaired t-test and one-way analysis of variance. RESULTS: About 27.4% of patients knew that they had come to PAC clinic for preanesthesia assessment, the rest were not clear. Similarly, only 18.1% knew that only anesthesiologist can perform a preanesthesia examination. 16.5% patients said that they would discuss their fears or queries regarding anesthesia in PAC clinic while 58.6% said that they would share such feelings with the surgeon in ward. CONCLUSION: Patients had insufficient knowledge about preanesthesia assessment and its role in improving the outcome of surgery.

QSAR based model for discriminating EGFR inhibitors and non-inhibitors using Random forest.

BACKGROUND: Epidermal Growth Factor Receptor (EGFR) is a well-characterized cancer drug target. In the past, several QSAR models have been developed for predicting inhibition activity of molecules against EGFR. These models are useful to a limited set of molecules for a particular class like quinazoline-derivatives. In this study, an attempt has been made to develop prediction models on a large set of molecules (~3500 molecules) that include diverse scaffolds like quinazoline, pyrimidine, quinoline and indole. RESULTS: We train, test and validate our classification models on a dataset called EGFR10 that contains 508 inhibitors (having inhibition activity IC50 less than 10 nM) and 2997 non-inhibitors. Our Random forest based model achieved maximum MCC 0.49 with accuracy 83.7% on a validation set using 881 PubChem fingerprints. In this study, frequency-based feature selection technique has been used to identify best fingerprints. It was observed that PubChem fingerprints FP380 (C(~O) (~O)), FP579 (O = C-C-C-C), FP388 (C(:C) (:N) (:N)) and FP 816 (ClC1CC(Br)CCC1) are more frequent in the inhibitors in comparison to non-inhibitors. In addition, we created different datasets namely EGFR100 containing inhibitors having IC50 < 100 nM and EGFR1000 containing inhibitors having IC50 < 1000 nM. We trained, test and validate our models on datasets EGFR100 and EGFR1000 datasets and achieved and maximum MCC 0.58 and 0.71 respectively. In addition, models were developed for predicting quinazoline and pyrimidine based EGFR inhibitors. CONCLUSIONS: In summary, models have been developed on a large set of molecules of various classes for discriminating EGFR inhibitors and non-inhibitors. These highly accurate prediction models can be used to design and discover novel EGFR inhibitors. In order to provide service to the scientific community, a web server/standalone EGFRpred also has been developed ( http://crdd.osdd.net/oscadd/egfrpred/ ).

The Combined use of Diode LASER & Conscious Sedation in the Excision of Pyogenic Granuloma in A Nine-Year-Old Patient.

This case report is to comprehensively review N2O/ O2 inhalational sedation in the context of conscious sedation for treating a nine-year-old patient with pyogenic granuloma. The excision was carried out by the use of diode laser. The six month postoperative follow up showed complete resolution of the lesion and increased patient acceptance for the future treatment. The use of laser minimizes the pain during the surgery and postoperatively and suturing was not required. Therefore this case report emphasizes the use of combined treatment modalities to increase patient comfort and to obtain a better function and aesthetics of the oral cavity.

Designing of peptides with desired half-life in intestine-like environment.

BACKGROUND: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life. RESULTS: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides. CONCLUSION: In summary, this study describes a web server 'HLP' that has been developed for assisting scientific community for predicting intestinal half-life of peptides and to design mutant peptides with better half-life and physicochemical properties. HLP models were trained using a dataset of peptides whose half-lives have been determined experimentally in crude intestinal proteases preparation. Thus, HLP server will help in designing peptides possessing the potential to be administered via oral route (http://www.imtech.res.in/raghava/hlp/).

QSAR-based models for designing quinazoline/imidazothiazoles/pyrazolopyrimidines based inhibitors against wild and mutant EGFR.

Overexpression of EGFR is responsible for causing a number of cancers, including lung cancer as it activates various downstream signaling pathways. Thus, it is important to control EGFR function in order to treat the cancer patients. It is well established that inhibiting ATP binding within the EGFR kinase domain regulates its function. The existing quinazoline derivative based drugs used for treating lung cancer that inhibits the wild type of EGFR. In this study, we have made a systematic attempt to develop QSAR models for designing quinazoline derivatives that could inhibit wild EGFR and imidazothiazoles/pyrazolopyrimidines derivatives against mutant EGFR. In this study, three types of prediction methods have been developed to design inhibitors against EGFR (wild, mutant and both). First, we developed models for predicting inhibitors against wild type EGFR by training and testing on dataset containing 128 quinazoline based inhibitors. This dataset was divided into two subsets called wild_train and wild_valid containing 103 and 25 inhibitors respectively. The models were trained and tested on wild_train dataset while performance was evaluated on the wild_valid called validation dataset. We achieved a maximum correlation between predicted and experimentally determined inhibition (IC50) of 0.90 on validation dataset. Secondly, we developed models for predicting inhibitors against mutant EGFR (L858R) on mutant_train, and mutant_valid dataset and achieved a maximum correlation between 0.834 to 0.850 on these datasets. Finally, an integrated hybrid model has been developed on a dataset containing wild and mutant inhibitors and got maximum correlation between 0.761 to 0.850 on different datasets. In order to promote open source drug discovery, we developed a webserver for designing inhibitors against wild and mutant EGFR along with providing standalone (http://osddlinux.osdd.net/) and Galaxy (http://osddlinux.osdd.net:8001) version of software. We hope our webserver (http://crdd.osdd.net/oscadd/ntegfr/) will play a vital role in designing new anticancer drugs.

Designing of promiscuous inhibitors against pancreatic cancer cell lines.

Pancreatic cancer remains the most devastating disease with worst prognosis. There is a pressing need to accelerate the drug discovery process to identify new effective drug candidates against pancreatic cancer. We have developed QSAR models for predicting promiscuous inhibitors using the pharmacological data. Our models achieved maximum Pearson correlation coefficient of 0.86, when evaluated on 10-fold cross-validation. Our models have also successfully validated the drug-to-oncogene relationship and further we used these models to screen FDA approved drugs and tested them in vitro. We have integrated these models in a webserver named as DiPCell, which will be useful for screening and designing novel promiscuous drug molecules. We have also identified the most and least effective drugs for pancreatic cancer cell lines. On the other side, we have identified resistant pancreatic cancer cell lines, which need investigative scanner on them to put light on resistant mechanism in pancreatic cancer.

Hmrbase: a database of hormones and their receptors.

BACKGROUND: Hormones are signaling molecules that play vital roles in various life processes, like growth and differentiation, physiology, and reproduction. These molecules are mostly secreted by endocrine glands, and transported to target organs through the bloodstream. Deficient, or excessive, levels of hormones are associated with several diseases such as cancer, osteoporosis, diabetes etc. Thus, it is important to collect and compile information about hormones and their receptors. DESCRIPTION: This manuscript describes a database called Hmrbase which has been developed for managing information about hormones and their receptors. It is a highly curated database for which information has been collected from the literature and the public databases. The current version of Hmrbase contains comprehensive information about approximately 2000 hormones, e.g., about their function, source organism, receptors, mature sequences, structures etc. Hmrbase also contains information about approximately 3000 hormone receptors, in terms of amino acid sequences, subcellular localizations, ligands, and post-translational modifications etc. One of the major features of this database is that it provides data about approximately 4100 hormone-receptor pairs. A number of online tools have been integrated into the database, to provide the facilities like keyword search, structure-based search, mapping of a given peptide(s) on the hormone/receptor sequence, sequence similarity search. This database also provides a number of external links to other resources/databases in order to help in the retrieving of further related information. CONCLUSION: Owing to the high impact of endocrine research in the biomedical sciences, the Hmrbase could become a leading data portal for researchers. The salient features of Hmrbase are hormone-receptor pair-related information, mapping of peptide stretches on the protein sequences of hormones and receptors, Pfam domain annotations, categorical browsing options, online data submission, DrugPedia linkage etc. Hmrbase is available online for public from http://crdd.osdd.net/raghava/hmrbase/.