Pd/C-Catalyzed Carbonylative Amidation for the Synthesis of 2-Carboxamidocyclohexane-1,3-diones.

Herein, a first-ever heterogeneous Pd/C-catalyzed single-step tandem approach for the synthesis of 2-carboxamidocyclohexane-1,3-diones via direct carbonylative C-H amidation of cyclohexane-1,3-diones is reported. The reaction progressed under base-, oxidant-, and ligand-free conditions employing oxalic acid as a CO surrogate and sodium azide as a nitrogen precursor in a double-layer vial system.

Assessment of Setup Errors in Gynecological Malignancies Treated With Radiotherapy Using Onboard Imaging.

Introduction  Radiotherapy plays a vital role in the management of gynecological malignancies. However, maintaining patient position poses a challenge during daily radiotherapy treatment of these patients. This study identifies and calculates setup errors in interfraction radiotherapy and optimum clinical target volume-planning target volume (CTV-PTV) margins in patients with gynecological malignancies. Material and methods  A total of 38 patients with gynecological malignancies were included in the study. They were treated with a dose of 50 Gy in 25 fractions for five weeks, followed by brachytherapy. All patients were immobilized using a 4-point thermoplastic cast. Anteroposterior and lateral images were taken thrice weekly for five weeks. Setup verification was done using kilovoltage images obtained using Varian On-board Imager (Varian Medical System, Inc., Palo Alto, CA). Manual matching was done utilizing bony landmarks such as the widest portion of the pelvic brim, anterior border of S1 vertebrae, and pubic symphysis in the X, Y, and Z axes, respectively. Results A total of 1140 images were taken. The individual systematic errors ranged from -0.24 to 0.17 cm (LR), -0.15 to 0.19 cm (AP) and -0.36 to 0.29 cm (CC) while the individual random errors ranged from 0.04 to 0.36 cm (LR), 0.06 to 0.33 cm (AP) and 0.10 to 0.29 cm (CC). The calculated CTV-PTV margins in LR, AP and CC directions were 0.17, 0.18, and 0.25 cm (ICRU-62); 0.28, 0.31 and 0.47 cm in LR, AP and CC directions (Stroom's), and 0.32, 0.36 and 0.55 cm (Van Herk) respectively. Conclusion Based on this study, the calculated CTV-PTV margin is 6 mm in gynecological malignancies, and the present protocol of 7 mm of PTV margin is optimum.

An unconventional iron oxide catalyst for 5-hydroxymethylfurfural oxidation to 2,5-diformylfuran.

Commonly used magnetic iron oxide (γ-Fe2O3) was examined for the first time as an unconventional catalyst for 5-hydroxymethylfurfural (5-HMF) oxidation to 2,5-diformylfuran (DFF). Fascinatingly, the magnetic support showed remarkable catalytic activity for this conversion, especially in nanoscale size (≤50 nm). The developed mild reagent system consisting of γ-Fe2O3 and molecular O2 in xylene solvent delivered DFF with 94% selectivity and 82% conversion at 135 °C for 12 h. A deep inspection of the mechanistic study through IR and XPS analysis revealed a phase transition (γ-Fe2O3 to Fe3O4) during the reaction, and then its reversal to the parent form after catalyst activation. The loss in crystallinity and increase in the particle size of the catalyst after the reaction were explicitly analysed by XRD and TEM studies, respectively. The excellent activity of the catalyst was even noticed by a recyclability test for six cycles. The method avoided the requirement of high-pressure equipment, costly noble and transition metals, and harsh basic environments.

Comparison of Dosimetric Parameters in Dysphagia Aspiration-Related Structures and Clinical Correlation in Head and Neck Cancer Patients Treated With Radiotherapy.

Introduction Chemoradiotherapy plays a major role in the treatment of head and neck cancer (HNC). Persistent dysphagia following primary chemoradiotherapy for head and neck cancers can have a devastating effect on a patient's quality of life. Many studies have shown that the dosimetric sparing of critical structures which were included in swallowing such as the pharyngeal constrictor muscle and larynx can provide improved functional outcomes and better quality of life. However, there are no current randomized studies confirming the benefits of such swallowing-sparing strategies. The aim is to evaluate late dysphagia after chemoradiotherapy for head and neck cancer and to examine its correlation with clinical and dosimetric parameters. Materials and methods The period of this prospective study was from November 2018 to March 2020. Patients were divided randomly in 1:1 ratio into two groups, group 1 and group 2, each with 25 patients. Group 1 was planned by three-dimensional conformal radiotherapy (3D-CRT) technique and group 2 was planned by intensity-modulated radiotherapy technique (IMRT) technique. Treatment was delivered after approval of radiotherapy plan. To evaluate the dose to dysphagia aspiration-related structures (DARS), these structures were contoured and dose-volume histograms were generated. Various dosimetric parameters of DARS were evaluated. Swallowing status was clinically evaluated based on the Radiation Therapy Oncology Group and the Common Terminology Criteria for Adverse Events, version 5. Results A significant advantage was seen with intensity-modulated radiotherapy technique (IMRT) in comparison to three-dimensional conformal radiotherapy (3D-CRT) in terms of mean dose delivered to the pharyngeal constrictor muscles (66.03 Gy vs 68.77 Gy, p=0.003). The mean dose delivered to the combined dysphagia/aspiration-related structures (DARS) was statistically significantly lower in IMRT compared to 3D-CRT (66.15 Gy vs. 70.09 Gy, p<0.001). Other dose-volumes were also reduced in IMRT group (V30: {98.64% vs. 99.88%, p=0.05}; V50: {90.49% vs. 99.02%, p=0.0002}; V60: {83.92% vs. 95.04, p=0.0002}; D50: {70 Gy vs. 71.16 Gy, p=0.001); and D80: {61.18 Gy vs. 67.39 Gy, p=0.01}. Futhermore, the clinical worsening of dysphagia was less common in IMRT group (48% vs. 80%, p=0.039). Conclusion IMRT can reduce the high-dose volumes received by the DARS receiving high doses by sparing these structures through optimization. This may provide a significant additional benefit that could improve dysphagia and hence the quality of life of patients with head and neck cancer.

Comparison of Dosimetric Parameters and Clinical Outcomes in Inversely Planned Intensity-Modulated Radiotherapy (IMRT) and Field-in-Field Forward Planned IMRT for the Treatment of Breast Cancer.

Introduction Radiotherapy has been an important component of the multimodality approach to breast cancer treatment. Newer techniques like three-dimensional radiotherapy had led to better dose distribution over the target volume, with tissue inhomogeneity corrections. To improve the uniformity in dose distribution, a newer technique of intensity modulation was developed, namely, intensity-modulated radiotherapy (IMRT). The present study was designed to compare inverse planned IMRT (IP IMRT) and field-in-field forward planned IMRT (FP IMRT) in patients with breast cancer receiving post-modified radical mastectomy (MRM) adjuvant radiotherapy in terms of dosimetric parameters and clinical outcomes. Materials and methods Fifty patients with breast cancer who have undergone MRM and need adjuvant radiotherapy were randomly assigned in a 1:1 ratio into two groups (25 each) of IP IMRT and FP IMRT techniques. The prescribed dose was 50 Gy in 25 fractions over five weeks. In IP IMRT, five to seven tangential beams were used for the chest wall, nodal volumes were placed at suitable angles with beam optimization, and calculation was carried out by the analytical anisotropic algorithm. For FP IMRT, two opposing tangential fields were created in such a way to achieve uniform dose distribution to the planning target volume (PTV), minimizing hot spot regions, and limiting dose to the ipsilateral lung and contralateral breast. Multiple subfields were manually designed to boost the area not included in the dose cloud. The dosimetric parameters were compared for PTV, lungs, heart, left anterior descending coronary artery (LAD), opposite breast, and esophagus. Results The dosimetric parameters in terms of PTV are better for IP IMRT plans compared to FP IMRT plans (V95%: 92.3% vs 75.2%, p = 0.0001; D90%: 47.4 Gy vs 42.9 Gy, p = 0.0001; D95%: 44.9 Gy vs 37.1, p = 0.0004). The ipsilateral lung (V10Gy: 71.9% vs 41%, p = 0.00001; V20Gy: 42.14% vs 36.35%, p = 0.03; V40Gy: 17.31% vs 26.95%, p = 0.00004; Dmean: 20.91 Gy vs 17.88 Gy, p = 0.01) and contralateral lung (V5Gy: 31.8% vs 0.1%, p < 0.00001; V10Gy: 6.2% vs 0.08%, p = 0.0001) received statistically significant lesser doses in terms of low dose parameters in FP IMRT. In the heart, the dosimetric parameter V5 was significantly lower for FP IMRT (61.7% vs 9.7%, p = 0.00001) along with Dmean (10.92 Gy vs 4.01 Gy, p = 0.001). Similarly, LAD parameters showed comparable high dose volumes (V40Gy: 21.02% vs 16.26%; p = 0.29) in both groups and a trend toward reduction in mean dose (17.1% vs 9.2%; p = 0.05) in FP IMRT group, although low dose volumes were higher in IP IMRT group. In contralateral breast, doses in smaller volumes were better for FP IMRT plans (V0.5Gy: 59.7% vs 43.8%, p = 0.01; V0.6Gy: 54.07% vs 37.6%, p = 0.007; V1Gy: 40.9% vs 22.1%, p = 0.001; V2Gy: 28.7% vs 9.4%, p = 0.00003; V5Gy: 12.07% vs 4.2%, p = 0.0001). In esophagus, statistically significant lower doses were seen only in terms of Dmean (10.29 Gy vs 5.1 Gy; p = 0.03) with FP IMRT. No significant difference in terms of skin reactions and dysphagia was seen in both the groups. Conclusion Both IP IMRT and FP IMRT techniques have advantages and disadvantages, and the superiority of one technique over another cannot be established in this study. The decision for choosing one technique over another can also be based on various patient-related factors weighing the risk of loco-regional recurrences to that of manifesting radiation-induced sequelae.

Pd-Catalysed Decarbonylation Free Approach to Carbonylative Esterification of 5-HMF to Its Aryl Esters Synthesis Using Aryl Halides and Oxalic Acid as C1 Source.

A decarbonylation free, polystyrene-supported, Pd (Pd@PS)-catalysed carbonylative esterification of the hydroxy group of 5-hydroxymethyl furfural (5-HMF) to its corresponding aryl esters has been developed. The use of Pd@PS, oxalic acid as CO source, and aryl halides was first explored for the aryl ester of 5-HMF synthesis. Here, we investigated the vital role of a polystyrene support to avoid the commonly known decarbonylation of 5-HMF. The reaction exhibits vast substrate scope with comparably good yield and catalyst recyclability.

Palladium-catalyzed ortho-halogen-induced deoxygenative approach of alkyl aryl ketones to 2-vinylbenzoic acids.

The 2-vinylbenzoic acids have wide applications in the field of polymer chemistry and are key precursors for the synthesis of important bioactive molecules. Herein, an ortho-halogen-induced deoxygenative approach for the generation of 2-vinylbenzoic acids from alkyl aryl ketones by palladium catalysis is discovered and explored. This approach requires no base or stoichiometric additives and can be carried out through a simple one-step process. Furthermore, the present reaction is scalable up to one-gram scale. The commercially available palladium on carbon (5 wt%) was used as a heterogeneous catalyst and showed excellent recyclability (<5 times) without significant loss in catalytic activity. Pleasingly, under our optimized conditions, the alpha alkyl substituted 2-iodoacetophenones exhibit good diastereoselectivity and predominantly (E)-2-vinylbenzoic acids were obtained with good to excellent yields.

Polystyrene-Supported Palladium (Pd@PS)-Catalyzed Carbonylative Annulation of Aryl Iodides Using Oxalic Acid as a Sustainable CO Source for the Synthesis of 2-Aryl Quinazolinones.

An efficient and convenient strategy for the synthesis of diversely substituted quinazolinones from o-carbamoyl/cyano aniline and aryl iodides using oxalic acid as a CO source under polystyrene supported palladium (Pd@PS) nanoparticles (NPs) catalyzed conditions has been developed. In this study, oxalic acid has been employed as safe, economic, environmentally benign, sustainable and bench-stable, solid CO surrogate under Double-Layer-Vial (DLV) system for the synthesis of 2-aryl quinazolinones. This methodology does not require any special high-pressure equipment like autoclaves, microwaves, etc. Moreover, a simple procedure for catalyst preparation, catalyst recyclability, easy handling of reaction, additive and base-free generation of CO, excellent to good yields and vast substrate scope are the additional features of developed protocol.

Hypervalent Iodine(III)-Mediated Counteranion Controlled Intramolecular Annulation of Exocyclic ß-Enaminone to Carbazolone and Imidazo[1,2-a]pyridine Synthesis.

A highly efficient and flexible protocol for intramolecular annulation of exocyclic ß-enaminones has been disclosed for the synthesis of carbazolones and imidazo[1,2-a]pyridines through a counter-anion-controlled free-radical mechanism promoted by hypervalent iodine(III). The cooperative behavior of HTIB and AgSbF6 plays a crucial role in the intramolecular annulation process through C-C and C-N bond formation to give the desired products. The mechanistic insights suggest that the two competitive reactions involved in the system are guided by the nature of the counteranion, which determines the formation of the final products. A wide variety of carbazolones and imidazo[1,2-a]pyridine molecules have been prepared and isolated in good to excellent yields.

An assessment of variation in macular volume and RNFL thickness in myopes using OCT and their significance for early diagnosis of primary open-angle glaucoma.

PURPOSE: An assessment of variation in Macular Volume and RNFL Thickness in myopes using OCT, and their significance for early diagnosis of Primary Open Angle Glaucoma(POAG). MATERIALS AND METHOD: Total of 122 eyes of 61 Indian Myopic subjects of both sex and various age groups underwent retinal nerve fiber layer thickness, macular volume in 6mm analysis by Rtvue Avanti SD-OCT, Optovue Technology V6.1.1,after taking due consent from ethical committee. Subjects were divided into two groups based on their refractive error, Group A <6 D and Group B >6D. The results were evaluated to determine the above mentioned measurements and their variation with myopic refractive error. RESULTS: The RNFL thickness in four Quadrants and an inner circle were taken. The mean thickness in inner circle in both groups were 101.48µm (SD±13.34 µm) and 92.38 µm (SD±11.99µm) respectively, which was statistically significant. The difference was also significant in superior, nasal and inferior quadrant. Statistically the difference was not significant in temporal quadrant. The macular volume was calculated in 6mm diameter. The mean value in Group A was 7.82mm3±0.54 mm 3. The mean value in Group B was 7.44mm3±0.98mm3. The statistical analysis showed the difference between the two groups is statistically significant. CONCLUSION: RNFL thickness is an established way to diagnose open angle glaucoma in preperimetric stage. Macular Volume is also found to be co-related with the risk. Myopes are known to be at higher risk to develop POAG. Hence, measurement of RNFL thickness by OCT should be made a mandatory investigation in High Myopes.

Esophageal Ascariasis with Retrosternal Chest Discomfort.

Ascariasis is one of the most well known helminthic parasite affecting humans. Esophageal asacariasis is extremely rare. We present a case of esophageal ascariasis manifesting as retrosternal chest discomfort.

Brain metastasis from esophageal carcinoma.

Esophageal carcinoma rarely metastasizes to brain. In our center, among 504 cases of esophageal cancer registered for treatment during a 15-year (1990-2005) period, brain metastasis from esophageal carcinoma was detected in only 1 case. An unusual case of esophageal carcinoma that presented with brain metastasis is reported here.