Non-inferiority randomized controlled trial comparing CricOid pressure and para-laryngeal pressure in parturients undergoing cesarean delivery: NiCOP trial.

BACKGROUND: Cricoid pressure has been surrounded with controversies regarding its effectiveness. Application of ultrasound-guided para-laryngeal (PL) force has been shown to occlude the esophagus effectively compared with cricoid pressure (CP) in awake patients. We hypothesized that there would be no meaningful difference in the change in antero-posterior esophageal diameter from with application of cricoid or para-laryngeal pressure in parturients undergoing cesarean delivery under general anesthesia. METHODS: In this prospective, randomized, non-inferiority trial, 40 parturients scheduled for elective cesarean delivery under general anesthesia were randomized to receive rapid sequence induction with either cricoid pressure (n = 20) or para-laryngeal pressure (n = 20). The antero-posterior diameter of the esophagus, measured by sonography, was the primary outcome. Visualization of the esophagus, its position in relation to the glottic aperture, esophageal occlusion, percentage of glottic opening (POGO), time to intubation, first pass success rate, overall success rate and adverse events like desaturation or bronchospasm were secondary outcomes. RESULTS: The mean change in anterior-posterior diameter in the CP group was 0.17 ±0.1 cm vs. 0.28 ±0.1 cm in the PL group. The mean difference (CP-para-laryngeal pressure) between the groups was -0.11 (95% CI -0.17 to -0.1) cm. As the upper limit of the 95% CI was lower than the prespecified non-inferiority margin (δ = -0.2), non-inferiority was established (P <0.001]. There was no significant difference in the POGO score (P = 0.818), time to intubation (P =0.55), or intubation attempts (P = 0.99). CONCLUSIONS: Para-laryngeal pressure was non-inferior to CP in occluding the esophagus in parturients undergoing cesarean delivery under general anesthesia and furthermore, no significant deterioration in intubation parameters was seen.

CT coronary angiography as an alternative imaging method to ascertain cardiac output and its correlation with echocardiography.

AIM: To assess the feasibility and accuracy of cardiac output (CO) obtained using a test bolus in patients scanned with single-source prospective-gated cardiac computed tomography (CT), and comparing it with CO obtained from unenhanced two-dimensional (2D) echocardiography using biplane Simpson's method. MATERIALS AND METHODS: In the present study, 100 patients with a mean age of 55 ± 12 years who underwent coronary CT angiography with prospective electrocardiogram (ECG)-gated CT in which the scan delay was evaluated using a test bolus. The time-attenuation curves obtained from the test bolus were used to calculate the CO of the patients. The CO obtained was then compared with that obtained after follow-up 2D echocardiography using biplane modified Simpson method. RESULTS: Linear regression was calculated between the CO and contrast enhancement: CO = -0.16(HUmax) + 7.65. The study showed good correlation between the two methods with r=0.77, p<0.001. On Bland-Altman analysis, no significant difference was noted between the two methods. CONCLUSION: This less researched method for CO estimation appears feasible; however, the clinical usefulness of this parameter is uncertain in absence of further clinical and reference standard validation.

A phase II study of metformin plus pemetrexed and carboplatin in patients with non-squamous non-small cell lung cancer (METALUNG).

Immune checkpoint inhibitors (ICIs) ± chemotherapy is the standard treatment for driver mutation-negative non-small cell lung cancer (NSCLC). However, accessibility to ICIs in LMICs is limited due to high cost, and platinum-based chemotherapy remains the mainstay of treatment. Metformin has anticancer properties, and studies suggest synergism between metformin and pemetrexed. Based on preclinical evidence, this combination may be more beneficial for STK11-mutated NSCLC, a subgroup, inherently resistant to ICIs. In this Simon two-stage, single-arm phase 2 trial, we investigated metformin with pemetrexed-carboplatin (PC) in patients with treatment-naive stage IV non-squamous NSCLC. The primary outcome was 6-month progression-free survival (PFS) rate. Secondary outcomes were safety, overall survival (OS), overall response rate (ORR), proportion of STK11 mutation, and effect of STK11 mutation on 6-month PFS rate. The study was terminated for futility after interim analysis. The median follow-up was 34.1 months. The 6-month PFS rate was 28% (95% CI 12.4-0.46). The median PFS and OS were 4.5 (95% CI 2.2-6.1) and 7.4 months (95% CI 5.3-15.3), respectively. The ORR was 72%. Gastrointestinal toxicities were the most common. No grade 4/5 toxicities were reported. Targeted sequencing was possible in nine cases. Two patients had STK11 mutation and a poor outcome (PFS < 12 weeks). We could not demonstrate the benefit of metformin with CP in terms of improvement in 6-month PFS rate; however, the combination was safe (CTRI/2019/02/017815).

Performance of Xpert® MTB/RIF and Xpert® Ultra for the diagnosis of tuberculous meningitis in children.

OBJECTIVE: To assess Xpert® MTB/RIF (Xpert) and Xpert® MTB/RIF Ultra (Ultra) performance in diagnosing pediatric tuberculous meningitis (TBM).METHODS: We conducted a study among children with suspected meningoencephalitis in Pune, India. Clinical, radiological, laboratory, and treatment data were analyzed to classify disease as definite, probable, possible or no TBM, using microbiologic or composite reference standards. We tested cerebrospinal fluid (CSF) either using Xpert or Ultra and estimated test performance characteristics.RESULTS: Of 341 participants, 149 (43.7%) were tested using Ultra and 192 (56.3%) with Xpert. Ultra had higher sensitivity (50% vs. 18%), lower specificity (91% vs. 99%), poor positive predictive value (PPV) (13% vs. 75%), and higher negative predictive value (NPV) (99% vs. 93%) than Xpert using the composite reference standard, with similar results by the microbiologic reference standard. Of 10 participants with trace positivity on Ultra, none met clinical TBM definitions.CONCLUSION: This is the first study to report on diagnostic performance of Ultra in pediatric TBM, which showed higher sensitivity and NPV than Xpert. For children presenting with nonspecific clinical features, Ultra is a promising diagnostic test. Further studies are required to define its optimal clinical use, including interpretation of trace positive results.

Validation of an obstetric quality of recovery scoring tool (ObsQoR-11) after elective caesarean delivery in a developing country: a prospective observational study.

BACKGROUND: The obstetric quality of recovery scoring tool (ObsQoR-11) was developed and validated in the United Kingdom for use after elective and emergency caesarean delivery. Quality of recovery scoring tools validated in one country may not be valid in other countries with significant cultural, socio-economic and linguistic variations. The aim of the current study was to validate a Hindi version of the ObsQoR-11. METHODS: In this prospective observational study, 100 parturients who underwent elective caesarean delivery in a tertiary care obstetric referral university hospital in North India were asked to complete a Hindi version of the ObsQoR-11 scoring tool 24 h after surgery. The performance of the Hindi version of ObsQoR-11 was assessed using measures of validity, reliability, and feasibility. RESULTS: The Hindi version of ObsQoR-11 correlated moderately with the global health visual analogue scale (r=0.45, 95% CI 0.27 to 0.59; P <0.0001) and discriminated well between good and poor recovery (mean (SD) score 84.6 (9.4) vs 75.0 (11.2); P <0.0001). The reliability and internal consistency were moderate (Cronbach's alpha=0.66; Spearman-Brown Prophesy Reliability estimate=0.57) with good repeatability (intraclass correlation coefficient 0.85, 95% CI 0.69 to 0.93; P <0.0001) and no floor or ceiling effects. All parturients completed the questionnaire in a (median (IQR) time of completion of 3 (1.5 - 5.5) min). CONCLUSION: The Hindi version of the ObsQoR-11 questionnaire is a promising scoring tool to evaluate quality of recovery after elective caesarean delivery. Further research is needed to evaluate the Hindi tool in other institutions in India as well as in other languages.

Redefining the importance of polylactide-co-glycolide acid (PLGA) in drug delivery.

The limitations of non-biodegradable polymers have paved the way for biodegradable polymers in the pharmaceutical and biomedical sciences over the years. Poly (lactic-co-glycolic acid) (PLGA), also known as "Smart polymer", is one of the most successfully developed biodegradable polymers due to its favorable properties, such as biodegradability, biocompatibility, controllable drug release profile, and ability to alter surface with targeting agents for diagnosis and treatment. The release behavior of drugs from PLGA delivery devices is influenced by the physicochemical properties of PLGA. In this review, the current state of the art of PLGA, its synthesis, physicochemical properties, and degradation are discussed to enunciate the boundaries of future research in terms of its applicability with the optimized design in today's modern age. The fundamental objective of this review is to highlight the significance of PLGA as a polymer in the field of cancer, cardiovascular diseases, neurological disorders, dentistry, orthopedics, vaccine therapy, theranostics and lastly emerging epidemic diseases like COVID-19. Furthermore, the coverage of recent PLGA-based drug delivery systems including nanosystems, microsystems, scaffolds, hydrogels, etc. has been summarized. Overall, this review aims to disseminate the PLGA-driven revolution of the drug delivery arena in the pharmaceutical and biomedical industry and bridge the lacunae between material research, preclinical experimentation, and clinical reality.

Dose-dense Paclitaxel and Carboplatin as Neoadjuvant Chemotherapy for Stage IIB/IIIA Non-small Cell Lung Cancer - A Phase II trial.

AIMS: The approach to potentially resectable non-small cell lung cancer (NSCLC) remains controversial. There is a benefit of neoadjuvant chemotherapy (NACT), but the ideal regimen is unknown. We evaluated the efficacy and safety of dose-dense NACT in potentially resectable NSCLC in this phase II trial. MATERIALS AND METHODS: Paclitaxel at 80 mg/m2 on days 1, 8 and 15 with AUC-6 carboplatin on day 1, 3 weekly for four cycles was evaluated as NACT. Patients with Eastern Cooperative Oncology Group performance status 0-2, stage IIB and IIIA (with only non-bulky N2 nodes) were included. The primary end point was the objective response rate. Secondary end points included toxicity, progression-free survival, recurrence-free survival, complete resection rate and overall survival. The relative dose intensity (RDI) was calculated to define tolerability (CTRI/2016/05/006916). RESULTS: In total, 37 patients were enrolled (median age 55 years). Most (78.8%) were smokers. Most patients had adenocarcinoma (57.6%) and stage IIIA disease (81.0%) according to the seventh American Joint Committee on Cancer staging system. Seventy-eight per cent of patients completed four cycles. The objective response rate was 75.6% with a complete response in 10.8%. The mean RDI of paclitaxel was 88.61%, with 68.0% of patients able to maintain an RDI ≥85.0%. In total, 187 toxicity events were recorded (120 grade 1, 64 grade 2 and three grade 3 events). Common toxicities were peripheral neuropathy (20.3%), myalgia (19.8%), nausea (15.7%) and neutropenia (10.2%). There were no treatment-related deaths. Seventeen patients underwent surgery (lobectomy 82.4%). After a median follow-up of 47 months (95% confidence interval 27-50.7 months), the median progression-free survival was 9.6 months (7.4-17.4) and overall survival was 29.2 months (16.0-37.2). CONCLUSION: Dose-dense paclitaxel-carboplatin is feasible, safe and efficacious and should be evaluated further in potentially resectable NSCLC.

Effect of cervical lesion centered access cavity restored with short glass fibre reinforced resin composites on fracture resistance in human mandibular premolars- an in vitro study.

AIM: The aim of this study was to evaluate the fracture resistance of cervical lesion centered access cavity restored with short glass fibre reinforced resin materials in human mandibular premolars. MATERIALS AND METHODS: Sixty freshly extracted human mandibular premolars were collected and assigned to positive control group (G1- Intact teeth) and other experimental groups (G2, G3. G4, G5, G6), Traditional Access Cavity(TAC) and Cervical Lesion Centered Access Cavity(CLCAC). Following endodontic therapy, samples were grouped accordingly, G2-CLCAC without restoration (Negative Control), G3-CLCAC restored with conventional nano-hybrid composite (Tetric-N-Ceram), G4-TAC restored with short glass fibre reinforced resin composite (Ever-X Posterior), G5-CLCAC restored with short glass fibre reinforced resin composite (Ever-X Posterior), G6- CLCAC restored with individually formed unidirectional fibre-reinforced post (Everstick post) and short glass fibre-reinforced resin composite (Ever-X Posterior). The samples were thermocycled (35 °C/28s, 15 °C/2s, 35 °C/28s, 45 °C/2s/10,000 cycles) and cyclically fatigued(2,50,000 cycles/15-30N/2 Hz) and then subsequently loaded to failure. The mean load to fracture (Newtons) were statistically analyzed using one-way ANOVA and Tukey's post HOC test and failure mode analysis was also done. RESULTS: The mean fracture resistance of the CLCAC design restored with fibre reinforced materials was higher when compared to the TAC design but the difference was not statistically significant. The negative control group (CLCAC without restoration) showed significantly the least fracture resistance (P < 0.05) when compared to all the other groups except for group 3 (CLCAC restored with conventional composites). CONCLUSIONS: Within the limitations of the study, it can be concluded that short glass fibre reinforced resin composites improved the fracture resistance of endodontically treated mandibular premolars irrespective of the type of access cavity designs. Favourable fractures were seen more in cervical lesion centered access cavity restored with short glass fibre reinforced composite materials. Nevertheless, the applicability of this design in multirooted teeth, canal cleanliness efficacy, and long term clinical performance are yet to be explored to complement this new access design.

Unhealthy alcohol use independently associated with unfavorable TB treatment outcomes among Indian men.

BACKGROUND: Approximately 10% of incident TB cases worldwide are attributable to alcohol. However, evidence associating alcohol with unfavorable TB treatment outcomes is weak.METHODS: We prospectively evaluated men (≥18 years) with pulmonary TB in India for up to 24 months to investigate the association between alcohol use and treatment outcomes. Unhealthy alcohol use was defined as a score of ≥4 on the Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scale at entry. Unfavorable TB treatment outcomes included failure, recurrence, and all-cause mortality, analyzed as composite and independent endpoints.RESULTS: Among 751 men, we identified unhealthy alcohol use in 302 (40%). Median age was 39 years (IQR 28-50); 415 (55%) were underweight (defined as a body mass index [BMI] <18.5 kg/m²); and 198 (26%) experienced an unfavorable outcome. Unhealthy alcohol use was an independent risk factor for the composite unfavorable outcome (adjusted incidence rate ratio [aIRR] 1.47, 95% CI 1.05-2.06; P = 0.03) and death (aIRR 1.90, 95% CI 1.08-3.34; P = 0.03), specifically. We found significant interaction between AUDIT-C and BMI; underweight men with unhealthy alcohol use had increased risk of unfavorable outcomes (aIRR 2.22, 95% CI 1.44-3.44; P < 0.001) compared to men with BMI ≥18.5 kg/m² and AUDIT-C <4.CONCLUSION: Unhealthy alcohol use was independently associated with unfavorable TB treatment outcomes, highlighting the need for integrating effective alcohol interventions into TB care.

COVID-19 with severe acute respiratory distress in a pregnant woman leading to preterm caesarean section: A case report.

We report the case of a 25-year-old pregnant woman, parity one, at 34 + 2 weeks of gestation, with a body mass index of 41 kg/m2 but no other comorbidities. There was a family history of COVID-19 among her one-year-old son, husband, brother, father and mother. She was admitted with chest pain and a nasopharyngeal swap positive for COVID-19. Due to the severity of the infection, a multidisciplinary team of anaesthesiologists, intensivists, obstetricians, neonatologists, and infectious disease specialists recommended delivery by caesarean section at 35 + 0 weeks of gestation, with combined spinal and epidural anaesthesia. Three days after delivery, the patient developed severe acute respiratory distress syndrome (ARDS) and was intubated for 25 days. The neonate was observed in the neonatal intensive care unit and no vertical transmission occurred. This case highlights the importance of the timing of delivery, the need for extended postpartum observation and a beneficial effect of inhaled nitric oxide after delivery for women with COVID-19.

Endodontic management of pulp canal obliteration using a new single-tooth template: A case series.

Background: Guided Endodontics is suggested as a reliable method for management of teeth with pulp canal obliteration (PCO). The guide used for this usually involves multiple teeth to gain stability but is bulky. It is therefore suboptimal to be used along with rubber dam. Aim: To describe the use of a minimized single-tooth guide template in three patients with radiographic evidence of PCO. Design: The template was designed and fabricated using the cone-beam computed tomography (CBCT) scan and a surface scan image of the involved teeth. In all three patients, the root canals were successfully negotiated within 15 minutes, with the template involving only the tooth in focus or with neighboring half of the teeth. The operator stabilized the template if required. Conclusions: This case series shows clinically that successful outcome can be obtained during guided endodontics with the use of a single-tooth template in previously traumatized anterior teeth with PCO.

Quantification of adsorbed and dangling citrate ions on gold nanoparticle surface using thermogravimetric analysis.

A novel approach involving thermo-gravimetricanalysis (TGA) for the quantification of citrate ions present on the surface of gold nanoparticles has been reported. TGA study was carried out on AuNPs in response to parameters such as concentration of tri-sodium citrate and pH of gold nanoparticles depicting that the number of citrate ion present on gold nanoparticles is highly pH dependent. In general, the citrate ions were observed to be higher in alkaline conditions contradicting earlier beliefs. These results also underline the significance of TGA as a novel tool for quantification of citrate molecules present on gold nanoparticle surface. Thus, the present approach not only provides with an insight into mechanistic details of gold nanoparticle synthesis but also opens the usage of TGA for understanding the nano range association of molecules.

Delays and barriers to early treatment initiation for childhood tuberculosis in India.

BACKGROUND: India accounts for 27% of global childhood tuberculosis (TB) burden. Understanding barriers to early diagnosis and treatment in children may improve care and outcomes.METHODS: A cross-sectional study was performed among 89 children initiated on anti-TB treatment from a public hospital in Pune during 2016, using a structured questionnaire and hospital records. Health care providers (HCPs) were defined as medical personnel consulted about the child's TB symptoms. Time-to-treatment initiation (TTI) was defined as the number of days between onset of TB symptoms and anti-TB treatment initiation. Based on Revised National TB Control Programme recommendations, delayed TTI was defined as >28 days.RESULTS: Sixty-seven (75%) of 89 enrolled children had significant TTI delays (median 51 days, interquartile range [IQR] 27-86). Sixty-six (74%) children visited 1-8 HCPs in the private sector before approaching the public sector. The median HCP delay was 28 days (IQR 10-75). Bacille Calmette-Guérin vaccination (aOR 10.96, P = 0.04) and loss of appetite (aOR 4.44, P = 0.04) were associated with delayed TTI.CONCLUSION: The majority of the children had TTI delays due to delays by HCPs in the private sector. Strengthening HCP competency in TB symptom screening and encouraging early referrals are crucial for rapid scaling up of early treatment initiation in childhood TB.

Late onset systemic sclerosis with seronegativity: a rare presentation of an uncommon disease.

Systemic sclerosis (SSc) is an uncommon connective tissue disorder characterized by multisystem involvement with fibrosis of skin and internal organs. Antibody formation is one of the hallmarks of SSc. Antinuclear antibodies (ANA) are positive in 97% of patients with SSc. We report a rare case where the patient was negative for ANA, Anti-topoisomerase I, Anti-centromere and Anti-RNA polymerase III antibodies.

Exploiting dispersion of higher-order-modes using M-type fiber for application in mid-infrared supercontinuum generation.

M-type fibers have the exceptional property that the higher-order LP0n modes are core-confined and easily excited, while the LP01 and other modes are confined to a high-index ring surrounding the core, so they are not easily excited. This has profound consequences for mid-infrared supercontinuum sources, where the high zero-dispersion wavelength of chalcogenide and ZBLAN fibers means that exotic pump sources have so far been necessary. We show here that in chalcogenide and ZBLAN M-type fibers the lower ZDW of the core-confined higher-order LP02 mode can be in the range of 2 to 3 µm (around 1.55 µm), while the fiber still has a large core diameter and thus supports high average power. This will allow established pump laser technology to be used in future high-power mid-infrared supercontinuum sources.

Respiratory health status is associated with treatment outcomes in pulmonary tuberculosis.

The association between respiratory impairment and tuberculosis (TB) treatment outcomes is not clear. We prospectively evaluated respiratory health status, measured using the Saint George's Respiratory Questionnaire (SGRQ), in a cohort of new adult pulmonary TB cases during and up to 18 months following treatment in India. Associations between total SGRQ scores and poor treatment outcomes of failure, recurrence and all-cause death were measured using multivariable Poisson regression. We enrolled 455 participants contributing 619 person-years at risk; 39 failed treatment, 23 had recurrence and 16 died. The median age was 38 years (interquartile range 26-49); 147 (32%) ever smoked. SGRQ scores at treatment initiation were predictive of death during treatment (14% higher risk per 4-point increase in baseline SGRQ scores, 95%CI 2-28, P = 0.01). Improvement in SGRQ scores during treatment was associated with a lower risk of failure (1% lower risk for every per cent improvement during treatment, 95%CI 1-2, P = 0.05). Clinically relevant worsening in SGRQ scores following successful treatment was associated with a higher risk of recurrence (15% higher risk per 4-point increase scores, 95%CI 4-27, P = 0.004). Impaired respiratory health status was associated with poor TB treatment outcomes. The SGRQ may be used to monitor treatment response and predict the risk of death in pulmonary TB. .

The incidence of immunofluorescence patterns and specific autoantibodies observed in autoimmune patients in a tertiary care centre.

Summary: Objectives: Testing for antinuclear antibodies (ANA) facilitates the diagnosis of autoimmune diseases (ADs). Here, we report an incidence of ANA positivity and its patterns by indirect immunofluorescence (IIF) and specific autoantibodies through immunodot assay. Methods: Sera from 993 patients presenting with various ADs were tested by IIF and immunodot assay. Results: ANAs were detected in 39.7%, of which speckled pattern was predominantly observed (50.8%). 56.8% of samples were positive on the immunodot assay with SSA Ro 60 antibody being the most prevalent (30.7%). Discussion: A significant correlation (p minor 0.0001) was observed between patterns and auto-antibodies. Coarse speckled (CS) and homogeneous were overly represented by antibodies SSA Ro 60 (13%) and nucleosomes (5.8%) respectively. Mi-2, PL-7, PL-12, and SP-100 were the rarest autoantibodies specificities found. Conclusions: The presence of a particular IIF pattern is predictive of a specific autoantibody in the sample. Association of IIF patterns and specific autoantibody are relevant for a more accurate diagnosis of disease.