Survival of Trial-Like and Non-Trial-Like Patients With Immunotherapy in Advanced Hepatocellular Carcinoma in Real World: A Collaborative Multicenter Indian Study (IMHEP).

PURPOSE: Immune checkpoint inhibitors (ICIs) is the initial line of management in advanced hepatocellular carcinoma (HCC), but survivals in the real world are not known. MATERIALS AND METHODS: A retrospective study of patients with advanced HCC receiving ICIs (as first-line therapy or as later lines of therapy) across 11 Indian institutions was conducted. Patients were divided into either cohort 1 (trial-like receiving ICI as first-line therapy), with a Child Pugh score (CTP) of ≤6, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1, and no VP4 (main portal vein thrombosis [MPVT]) or cohort 2 (trial unlike) who did not satisfy at least one of the above criteria. The primary end point was 12-month overall survival (OS). RESULTS: Between January 2017 and January 2022, 133 patient data were analyzed. The presence of MPVT was seen in 33 patients (25%). The ICIs used were atezolizumab-bevacizumab, nivolumab, and pembrolizumab in 89 (66%), 44 (33%), and one (1%) patients, respectively. With a median follow-up of 13.8 months, the 12-month OS for the entire cohort was 33.4% (95% CI, 23.6 to 43.2). Patients in cohort 1 (n = 31) had a significantly improved OS compared with patients in cohort 2 (n = 102; 12-month OS, 57.9% [95% CI, 38.5 to 77.3] v 24% [95% CI, 13.4 to 34.6]; P = .005). Patients with CTP A as compared with CTP B (9.7 v 4.3 months; P < .001) and an ECOG PS of 0/1 as compared with a PS of ≥2 (8.7 v 7.2 months; P = .04) and without MPVT (9.4 v 4.0; P < .001) had superior survivals. CONCLUSION: Patients with advanced HCC in the real world, trial-like have survivals in consonance with trial data, whereas patients with features excluding them from trials, such as main portal vein thrombosis, poor ECOG PS, and child Pugh B status, have markedly inferior survivals, despite good tolerance to immunotherapy.

Comparative Evaluation of Debris Extrusion, Remaining Dentin Thickness and Fracture Resistance of Endodontically Treated Teeth Using Rotary and Reciprocating Endodontic File Systems: An In Vitro Study.

BACKGROUND: Preventing the apical extrusion of debris during instrumentation is of paramount importance to reduce the occurrence of flare-ups in endodontically treated teeth. Furthermore, an essential requirement for the longevity and strength of an endodontically treated tooth and its ability to resist fracture is the preservation of residual dentin thickness during instrumentation. The aim of this study was to compare the amount of debris extrusion, remaining dentin thickness at the coronal third, middle third, apical third, and the fracture resistance of the teeth using rotary (TruNatomy; Dentsply Sirona, Charlotte, NC) and reciprocating (WaveOne Gold; Dentsply Sirona) endodontic file systems. METHODS: An in vitro study included 52 single-rooted, oval canal shaped teeth that underwent exploration and initial cleaning with a no. 15 K-file. The prepared canals were then randomly assigned to two groups: Group I, with instrumentation with the TruNatomy rotary file (n=26) and Group II, with instrumentation with the WaveOne Gold reciprocating file. Parameters like debris extrusion, remaining dentin thickness, and fracture resistance were evaluated in both the groups. Analysis was performed using a paired t-test for the assessment of difference between groups and one-way ANOVA test followed by the post-hoc Tukey test for difference between the coronal, middle and apical third for each study group. RESULTS: The results revealed no significant difference (t=0.454, p=0.652) between the TruNatomy rotary file and WaveOne Gold reciprocating file in apical extrusion of debris after their use in root canal therapy. For the remaining dentin thickness, a significant difference was present between the TruNatomy rotary file and WaveOne Gold reciprocating rotary file at the coronal (t=5.766, p<0.0001) and middle (t=3.690, p=0.001) levels. The mean fracture resistance was significantly more (t=15.877, p<0.0001) with the TruNatomy rotary file compared to the WaveOne Gold reciprocating rotary file. CONCLUSION: The TruNatomy rotary file system outperformed the WaveOne Gold reciprocating file system in terms of maintaining the remaining dentin thickness and providing improved fracture resistance. Nevertheless, debris extruded apically was comparable between the TruNatomy rotary file system and the WaveOne Gold reciprocating file system.

Consensus guidelines for the management of HR-positive HER2/neu negative early breast cancer in India, SAARC region and other LMIC by DELPHI survey method.

BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

Comparison of two different volumes of 0.5%, ropivacaine used in ultrasound-guided adductor canal block after knee arthroplasty: A randomized, blinded, controlled noninferiority trial.

Background and Aims: The aim of this study was to establish noninferiority of 10 mL of 0.5% ropivacaine as compared to 20 mL of 0.5% ropivacaine; for choosing right dose in adductor canal block (ACB) after knee arthroplasty (KA), this trial was conducted. Material and Methods: Forty patients undergoing bilateral KA with postoperative ultrasound-aided ACB were randomized: Group A patients received 20 mL 0.5% ropivacaine in the right limb and 10 mL 0.5% ropivacaine in the left limb. Group B patients received 10 mL of 0.5% ropivacaine in the right limb and 20 mL of 0.5% ropivacaine in the left limb. Catheter is positioned for intermittent boluses every 12-h up to 48 h. Results: In the final analysis (excluding six patients) based on split-body design between Group I (comprising 34 limbs which received 20 mL of 0.5% ropivacaine) and Group II (comprising 34 limbs which received 10 mL of 0.5% ropivacaine), baseline demographic data were collected. Length of the limb from anterior superior iliac spine (ASIS) to the base of the patella was comparable between two groups: Group I (in cm; 149 ± 1.63) versus Group II (in cm; 149.5 ± 1.51) (P = 0.49, 95% CI of - 1.98 to 0.98). Primary outcomes, that is, quadriceps muscle strength, show a significant difference (P < 0.025) at various timeline. Secondary outcome pain scores and degree of knee flexion at various time intervals showed no significant difference. There was zero incidence of fall of the patient and no significant complication due to catheter was reported leading to discontinuation of catheter use in both groups. Conclusion: 10 mL of 0.5% ropivacaine is noninferior to 20 mL of 0.5% ropivacaine in providing postoperative analgesia with preserved quadriceps muscle strength.

Comparison of adductor canal block with femoral nerve block for post-operative pain relief after bilateral total knee arthroplasty: A non-randomised controlled trial.

BACKGROUND AND AIMS: Pain perception and pain threshold vary from one individual to another and also differ in the right and left limbs leading to an inter-cerebral pain variability bias and inter-patient pain variability bias. To date, data comparing adductor canal block (ACB) with femoral nerve block (FNB) in the same patient who underwent bilateral total knee arthroplasty (TKA) remain limited. METHODS: We performed a prospective, non-randomised, controlled study. Patients scheduled for bilateral TKA with central neuraxial anaesthesia received every 12-hourly intermittent boluses of 15 mL of ropivacaine 0.5% in two different peripheral nerve blocks (ACB and FNB) in either of the lower limbs postoperatively. The primary outcome was to assess postoperative VAS score, and the secondary outcomes were muscle strength of the quadriceps muscle and degree of flexion at the knee joint. RESULTS: Among the 80 patients assessed for eligibility, 72 patients were enroled, and 69 were included in the final analysis. VAS scores after the two blocks during rest at 30 minutes, 6 hours, 12 hours and 48 hours post-operatively had no significant difference. VAS scores during rest at 24 hours and on doing exercise at 24 hours and 48 hours showed a significant difference. Quadriceps muscle strength and degree of flexion of knee at 24 hours and 48 hours post-operatively did show a significant difference in favour of the ACB over FNB. CONCLUSION: ACB provides equivalent analgesia in comparison with FNB at rest and during passive exercise up to 48 hours post-operatively. ACB significantly preserved motor power of quadriceps muscles when compared with FNB with no added complications.

Oral Health-related Quality of Life among Psychiatric In- and Outpatients Diagnosed with Different Disorders in Indore, Central India.

AIM: To assess oral health-related quality of life among psychiatric patients. MATERIALS AND METHODS: A total of 400 inpatients and outpatients reporting to the Department of Psychiatry was taken as the final sample. Subjects diagnosed with mental illness and on medication for at least 1 year, who were able to respond to the pro forma and oral health impact profile (OHIP) questionnaire, were included. A guided, self-administered structured questionnaire was designed to include sociodemographic characteristics and short form of the OHIP-14 consisting of 14 items covering 7 domains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability and handicap. It was used to assess the impact of oral conditions on well-being and quality of life. The data collected were subjected to statistical analysis using SPSS IBM version 20.0. RESULTS: The highest mean OHIP score for the disorders was seen among the patients diagnosed with schizophrenia for functional limitation (2.73 ± 1.194), 2.91 ± 1.111 for psychological discomfort, 2.67 ± 1.203 was recorded for physical disability, 2.79 ± 1.156 was the mean score for psychological disability followed by a score of 2.87 ± 1.172 for social disability. The highest mean score for the handicap domain was recorded for schizophrenia patients (2.73 ± 1.241) whereas for physical pain, a mean score of 3.01 ± 1.261 was recorded for patients diagnosed with bipolar disorder. CONCLUSION: Based on the findings of the study, it can be stated that the psychiatrists should pay attention to the dental anxiety concerns of the patients and encourage them to visit oral health professionals. CLINICAL SIGNIFICANCE: The study highlights the importance of incorporating dental health education to psychiatric rehabilitation programs.

In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-emulsifying Drug System.

BACKGROUND: Carvedilol (CD), a non-selective beta-blocker, is indicated for the management of mild to moderate congestive heart failure. After oral administration, CD is rapidly absorbed with an absolute bioavailability of 18-25% because of low solubility and extensive first-pass metabolism. OBJECTIVE: The present investigation focused on enhanced oral delivery of CD using supersaturated self-emulsifying drug delivery (SEDDS) system. METHODS: Optimized SEDDS consisted of a blend of Oleic acid and Labrafil-M2125 as an oil-phase, Cremophor-RH40, polyethylene glycol-400 and HPMC-E5 as a surfactant, co-surfactant and supersaturation promoter respectively. Formulations were characterized for physical characteristics, invitro release in simulated and biorelevant dissolution media, intestinal permeability and bioavailability studies in Wistar rats. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized formulation. RESULTS: DSC and XRD, SEM studies showed that the drug was in amorphous form, and droplets were spherical in shape. Dissolution studies clearly showed distinct CD release in compendial and biorelevant dissolution media. The results from permeability and in-vivo studies depicted 2.2-folds and 3.2-folds increase in permeability and bioavailability, respectively from supersaturated SEDDS in comparison with control. CONCLUSION: The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral supply of CD. Lay Summary: Carvedilol (CD) is a non-selective antihypertensive drug with poor oral bioavailability. Previously, various lipid delivery systems were reported with enhanced oral delivery. We developed suprsaturable SEDDS formulation with immediate onset of action. SEDDS formulation was developed and optimized as per the established protocols. The optimized SEDDS formulation was stable over three months and converted to solid and supersaturated SEDDS. The results from permeability and in-vivo studies demonstrated an enhancement in permeability and bioavailability from supersaturated SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral administration of CD.

A Study to Evaluate the Effect of Hyperbaric Oxygen on Osseointegration of Root-form Endosseous Titanium Dental Implants: An In Vivo Study.

AIM: To evaluate the effect of hyperbaric oxygen (HBO) therapy on the osseointegration of dental implants by resonance frequency analysis. MATERIALS AND METHODS: Six rabbits of age 2 to 2 and 1/2 years, weight approximately 2 kg were selected and tagged 1-6. For all the animals' right femur was selected as a control group (R) and left femur as test group (L). Initially, implants of dimensions 3.75×8mm (Adin Touareg) were placed in the right femur. Implant stability quotient (ISQ) values were recorded using OSSTELL ISQ at the time of surgery (R0), after one month (R1), and the end of the second month (R2). After two months of uneventful healing, implants were placed on the left femur of all the six rabbits and three were grouped as 2S (subjected to 2 HBO sessions at the weekly interval) and other three as 4S (subjected to 4 HBO sessions at weekly interval for a month). At the time of surgery (L0), end of one month (L1) and two months (L2), ISQ values were recorded and subjected to statistical analysis. The total duration of the study was 4 months from 3 March 2013 to 03 July 2013. RESULTS: The data were statistically analyzed using t-test and analysis of variance (ANOVA) F. On the comparison between the control group (R) and test groups (2S and 4S) ISQ values for test groups were more which was highly statistically significant (p <0.001). Among the two test groups 4S group has more ISQ values compared to 2S (p <0.001). CONCLUSION: This study indicated that HBO therapy has a promotive effect on the rate of osseointegration of dental implants. CLINICAL SIGNIFICANCE: Study opens new scope for further in vivo research in utilizing hyperbaric oxygen therapy (HBOT) in implant surgeries, maxillofacial trauma cases and irradiated patients to hasten or improve osseointegration.

The Pre-Conception and Pre-Natal Diagnostic Techniques Act and its implication on advancement of ultrasound in anaesthesiology; time to change mindsets rather than laws.

Ultrasonography (USG) has a continuously expanding role in anaesthesiology, critical care and pain management and has enhanced and refined patient care. The Pre-Conception and Pre-Natal Diagnostic Techniques (PCPNDT) Act was established to counter the persistent problem of female foeticide in India. This unique problem which seems to be rooted in our social structure has indirectly impeded the evolution of USG as a widespread tool in medicine in our country. This brief review is aimed at highlighting the expanding role of USG in anaesthesia practice and training, nuances of the PCPNDT act and its implications on the growth and management of ultrasound technology in anaesthesia, in India.

Is There a Limitation of RECIST Criteria in Prediction of Pathological Response, in Head and Neck Cancers, to Postinduction Chemotherapy?

This study studied the coorelation between radiological response to induction chemotherapy and acheivement of pCR or near pCR. It was a retrospective analysis in which all patients who received NACT from 2008 till april 2012 were subjected to inclusion criteria. Coorelation analysis was performed between CR + PR and acheivement of pCR or near pCR. Twenty four patients were identified.The primary site of tumor was oral cavity in 19 patients (79.2%), maxilla in 2 patients (4.2%), laryngopharynx in 2 patients (4.2%) and oropharynx in 1 patient (4.2%). The clinical stage was stage IVA in 16 patients ( 66.7%) and IVB in 8 patients (33.3%). The overall response rates ie a combination of CR and PR was seen in 11patients (45.8%). The pCR was seen in 15 patients (62.5%) and rest had near pCR. There was no linear coorelation between radiological size decrement and tumor response. On coorelation analysis the spearman correlation coefficent was -0.039 (P = 0.857). This suggest that presently used radiological response criterias for response assesment in head and neck cancers severly limit our ability to identify patients who would have pCR or near pCR.

Stage IV lung cancer: Is cure possible?

Reporting a case, 53 years old male with stage IV Nonsamall cell lung cancer in view of cytologically proven malignant pleural effusion. Usually the management of stage IV lung cancer is with palliative intent where the patient receives palliative chemotherapy along with palliative radiotherapy and surgery if required. Most of the data on curative management of oligometastatic non-small cell lung cancer includes patient with adrenal metastasis and some reports with brain metastasis. There is scarce literature on the surgical management of stage IV lung cancer with pleural effusion.