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Metabolomics has emerged as a critical field in understanding biological processes and disease mechanisms, necessitating advancements in analytical techniques to handle complex biological samples. This review explores the global landscape of metabolomics, with a focus on the use of spectroscopy and spectrometry. Techniques such as UV-Vis and Fourier Transform InfraRed (FTIR) spectroscopy offer fast and cost-effective metabolite tracing but are limited by their sensitivity, particularly for low-abundance metabolites. Nuclear Magnetic Resonance (NMR) spectroscopy, despite being less sensitive than mass spectrometry (MS), provides unparalleled structural information, distinguishing metabolites with similar mass-to-charge ratios. NMR's capability to detect metabolites in the 1-10 µM range highlights its effectiveness in metabolomics. This review categorizes advancements in these techniques, starting with global contributions to spectroscopy, followed by detailed discussions on FTIR strategies for metabolite tracing, and concluding with NMR's qualitative and quantitative applications in metabolomics and disease diagnostics. The review underscores the continuous development in sample preparation and data integration, enhancing the accuracy and applicability of these techniques, positioning NMR and FTIR as essential tools in modern metabolomic research.

Radiographs of 338 clinical cases of cattle and buffalo reported to Teaching Veterinary Clinical Services Complex, Veterinary College, Udgir (M.S.) were studied for recording the incidences of various affections in bovine. All these cases were having the history of tympani (acute/chronic/recurrent). All animals were subjected to lateral plane radiography of reticulo- thoracic region. Out of these cases 27.81% of the cases were interpreted as a foreign body syndrome, of which 21.59% were potential and 6.21% were non-potential foreign bodies. 4.44% of cases showed presence of foreign body in the thoracic region. The incidence of diaphragmatic hernia was recorded in 6.50% of the animals. Further, lung abscess was recorded in 2.94% of the cases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate outcomes of cervical cancer patients treated with abbreviated high dose rate brachytherapy (HDR-BT) that used 2-implants and delivered 4-5 fractions over 7-12 days rather than 21-28 days., Materials and Methods: Patients with stage IB2-IVA cervical cancer, treated with external beam radiation (EBRT) ± chemotherapy followed by abbreviated MR/CT-based HDR-BT were included. The planning aim was to achieve > 70Gy equivalent doses in 2Gy (EQD2 10Gy ) at Point A dose in patients undergoing intracavitary BT (ICBT) and > 85Gy EQD2 10Gy to the HRCTV in intracavitary-interstitial BT (IC-ISBT). The dose constraints to 2 cc of bladder, rectum and sigmoid were restricted to < 90Gy 3 , < 75Gy 3 and < 75Gy EQD2 3Gy respectively., Results: From 2020 to 2022, 245 patients were treated with EBRT followed by MR/CT-based HDR-BT. Median OTT was 57 days. The median HRCTV volume was 35.5cc with higher HRCTV in MR than CT-based (42.3cc vs. 32.8cc). The median dose to Point-A, HRCTV-D90, B2cc, R2cc and S2cc for ICBT was 78.1, 86.2, 87, 70.2 and 70.4Gy respectively. For IC-ISBT cohort, the median dose to HRCTV-D90, B2cc, R2cc, and S2cc was 86.1, 88.6, 70 & 66.7Gy respectively. The 3-years local control, pelvic control, locoregional, disease free and overall survival was 90%, 88%, 83.7%, 75.5% and 85% respectively. Late ≥ grade III gastrointestinal and genitourinary toxicities were 7.3% and 1.6% respectively with marginally higher toxicity in CT based cohort., Conclusion: Accelerated HDR-BT schedule of 2-implants 4-5 fractions is radiobiological iso-effective and clinically safe with comparable oncological outcomes and adverse events., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy., Methods: Between November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment., Results: Sixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as 'target nodal lesions' and the remaining nodes as 'non-target'. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%)., Conclusions: The study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High-dose-rate image guided brachytherapy (IGBT) for cervical cancer leads to improved local control and reduced toxicity and is a critical component of treatment. However, transition to IGBT requires capacity upscaling. An institutional activity mapping and national impact analysis of such a transition were undertaken to understand feasibility., Methods: Between September 2020 and March 2021, activity mapping was conducted in a high-volume centre that triaged cervical cancer patients for brachytherapy into four workflows; A: two-dimensional (2D) X-Ray point A-based intracavitary brachytherapy, B: CT point A-based intracavitary brachytherapy, C: MRI/CT-volume based intracavitary brachytherapy, D: MRI/CT volume-based intracavitary +/- interstitial brachytherapy. Clinical process time mapping was performed, and case scenarios for transition were modelled at the institutional and national levels based on available incidence and infrastructure levels. Treatment capacity changes were calculated, and potential strategies for workflow reorganisation were proposed., Findings: Eighty-four patients were included in the study. The total time taken for the workflows A, B, C, and D were 176 min (57-208), 224 min (74-260), 267 min (101-302), and 348 min (232-383), respectively. The transition from workflow A to D through sequential steps led to 35%, 49%, and 64% loss of treatment capacity in the index institution. Solutions such as 10-hour or 12-hour overlapping shifts increased treatment capacity by 25% and 50% and performing single implants and delivering multiple fractions increased capacity by 100%. Twenty-three Indian states and Union Territories are predicted to be able to transition to advanced workflows. For four Indian states, it may be detrimental considering the current infrastructure level, and eight Indian states lacked brachytherapy access. Further financial investment is required in the latter 12 states for transition to advanced workflows., Interpretation: Our study demonstrates that unplanned transition to IGBT can lead to treatment capacity loss and increase in waiting lists to access treatment. The proposed solutions of workflow reorganisation, using strategies such as single brachytherapy applicator implant and delivering multiple treatment fractions can improve access to treatment for women with cervix cancer in resource-strained and high patient-volume settings. We recommend state-wise solutions for the upscale from conventional 2D workflows to IGBT, subject to the availability of skilled personnel, infrastructure and training. Financial investments may be needed in some states to achieve this goal., Funding: International Atomic Energy Agency (IAEA) supported the salary of VH through project E33042 that focussed on implementation strategies of image guided brachytherapy., Competing Interests: SC received funding and VH received salary from International Atomic Energy Agency (IAEA) [funding as a part of Coordinated Research Project E33042]. SC is a consultant to Kortuc Pharmaceuticals (Japan) and received educational grants from Varian and Elekta. All authors declare no other conflicts of interest., (© 2023 The Author(s).)

Purpose: Brachytherapy (BT) for cervix cancer was listed as a level I priority and reduced number of implants and multiple fractions were recommended during COVID-19 pandemic. We present early clinical outcome of this approach., Methods and Materials: Patients treated with (chemo)radiotherapy and BT with single implant and multiple fractions BT were included. Treatment protocol included 3-5 fractions of 5-8.5 Gy with an aim to achieve point A dose of 70 Gy EQD2 10Gy (or HRCTV dose of >80 Gy EQD2 10Gy ) in those undergoing intracavitary (IC) and HRCTV dose >85 Gy EQD2 10Gy in patients undergoing Intracavitary-Interstitial (IC/IS) whereas maintaining bladder (B2cc), rectum (R2cc), sigmoid (S 2cc) doses of 90, 75, and 75 Gy EQD2 3Gy . Time to event analysis was used to report oncological endpoints. Toxicity was reported using crude proportions., Results: From April 2020 to March, 2021, 64 patients with stage IB2-IV received single implant and multi-fraction BT after external radiation of 45 Gy/25 fractions/5 weeks. Only 76.7% (n = 49) received concurrent chemotherapy. Median overall treatment time (OTT) was 56 days (38-131 days). Overall, 62.5% (n = 40) patients received IC and 37.5% (n = 24) received IC+IS. The median HRCTV was 34.7 cc (IQR 25-41). Median (IQR) point A dose, HRCTV D90, B2cc, R2cc, and S2cc for those undergoing IC was 74 Gy (71-78), 80 Gy (73-84), 86 Gy (82-89), 70 Gy (65-74), 65 Gy (59-73) respectively. For the IC+IS cohort, HRCTV D90, B2cc, R2cc, and S2cc was 84 Gy (78-89 Gy), 89 Gy (86-92), 70 Gy (67-74), 68 Gy (59-76). At a median follow-up of 16 months (5-27) the 2-year local control, pelvic control, cause specific and overall survival was 88%, 85.3%, 92.2%, and 81.3% respectively. Late gastrointestinal and genitourinary grade ≥III toxicities were 14% and 1.5% each., Conclusions: Abbreviated BT outcomes are encouraging for oncological outcomes despite delays in overall treatment time and omission of chemotherapy. Further mature follow up is needed., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: In patients with recurrent or metastatic cervical cancer, the median survival time is 13 to 24 months based on the choice of palliative systemic chemotherapy. Evolving evidence suggests that the addition of radiation may lead to improved survival., Methods and Materials: Consecutive patients treated with radiation with or without systemic chemotherapy for oligometastatic or oligorecurrent disease within the period from 2017 to 2020 were included. All patients received systemic chemotherapy consultation and radiation to relapsed or metastatic sites. Progression-free survival (PFS) was determined as the period between diagnosis of relapse or metastasis and the last progression of the disease. Overall survival (OS) was defined as the time between the date of diagnosis of relapse or metastasis and follow-up or death. The effect of various prognostic and predictive factors was estimated using the Kaplan-Meier method and log-rank test., Results: Fifty-eight consecutive patients were included. The median time to relapse was 18 months (8-205 months). At the time of first relapse, 34.4% of patients (n = 20) had locoregional relapse, 32.8% (n = 19) had distant nodal metastases, and 32.8% (n = 19) had visceral metastases. The relapse was within previously irradiated portals in 34.5% (n = 20), out of field in 50% (n = 29), and both in 15.5% (n = 9) of patients. Overall, 56% of patients (n = 33) received systemic chemotherapy. The radiation therapy dose in equivalent doses of 2 Gy at the time of retreatment was 44 Gy (31-68 Gy). The median PFS and OS from the date of first relapse were 16 (12-19) and 28 months (2-108), respectively. Grade ≥3 toxicity was observed in 19% of patients. No patient- or treatment-related factor was identified as predictive of OS on univariate analysis., Conclusions: The use of potentially radical doses of radiation, including reirradiation at locoregional or distant oligorelapse or metastasis, is associated with encouraging PFS and OS in patients with cervical cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Reirradiation (re-RT) is a suitable and potentially curative treatment option for in-field locoregional recurrences in gynecological malignancies. Lack of clear guidelines on prescription, dose-response relationship, and clinical outcomes limits its clinical use. This clinical narrative describes the methodology for integration of deformable image registration (DIR) for cumulative dose assessment in the setting of re-RT for gynecologic malignancies, using the tools available within a commercial treatment planning system., Methods and Materials: Four patients who received re-RT for locoregional recurrence or second cancer within previously irradiated areas for a gynecologic primary were identified. Patient-specific DIR for deformable dose mapping and accumulation was retrospectively performed using intensity-based algorithm provided by the Varian Medical Systems Velocity AI version 4.1. Cumulative equivalent doses in 2 Gy fractions (EQD2) delivered to overlapping targets and organs at risk were generated and compared with the physically summated doses. For both approaches, brachytherapy (BT) component was physically summated in cases where the BT applicator caused significant anatomic distortion., Results: The mean maximum cumulative overlapping target dose was 119.4 Gy 10 (range, 84.7 Gy10-144.9 Gy 10 ). The mean cumulative doses received by 2 cm 3 of bladder, rectum, sigmoid, and bowel were 114.6 Gy 3 (101.1-133.4 Gy 3 ), 98.7 Gy 3 (67-136.2 Gy 3 ), 92.5 Gy 3 (70.4-107 Gy 3 ), and 89.9 Gy 3 (81.1-102.8 Gy 3 ) , respectively. In the setting of in-field nodal recurrence, DIR-based dose summation was associated with lower cumulative organs at risk doses than those estimated with physical summation, except in one case with a higher bowel dose. In cases where re-RT was given for local recurrence/second primary, variation in sigmoid doses was observed between the 2 dose-summation strategies across all 3 cases, but it was inconsistent with bladder, rectum, or the bowel., Conclusions: DIR-based dose accumulation can be used to guide re-RT planning and can provide clinically relevant information, especially in cases with nodal recurrences. Registration of BT data sets remain challenging and requires an individualized assessment when applying these algorithms to clinical practice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The Radiation Therapy Oncology Group (RTOG) under NRG Oncology recently published updated contouring guidelines for intensity modulated radiation therapy in postoperative treatment for endometrial and cervical cancer. The present study was designed to evaluate the implications of newly published guidelines., Methods and Materials: We recruited 300 patients in a phase 3 randomized controlled trial of adjuvant chemoradiation therapy for cervical cancer (NCT01279135) to understand patterns of relapse. For those patients with pelvic relapse, we imported radiation therapy structure sets, treatment plans, and diagnostic images at relapse on the treatment planning system. We performed rigid registration with treatment planning images that contained the delineated planning target volume and radiation dose information. We delineated gross tumor volume at time of relapse on the diagnostic scans and superimposed it on the radiation therapy treatment scans. We categorized the site of pelvic relapse as "within field of old RTOG/[Postoperative Adjuvant Radiation in Cervical Cancer (PARCER)] target delineation guidelines" or "within field of new NRG/RTOG guidelines," or both, and compared proportions of recurrences contained within the 2 guidelines. We consider a P value of <.05 statistically significant. Additionally, we generated intensity modulated radiation therapy treatment plans based on the new guidelines for a limited set of patients to see if these new guidelines increased the organ at risk doses., Results: Most common form of relapse was distant metastasis (15%). Pelvic relapse rate in our study was 8%. Overall, 9 out of 19 relapses were encompassed in the contouring guidelines of the old RTOG/ Postoperative Adjuvant Radiation in Cervical Cancer (PARCER) trial, and 12 out of 19 were encompassed within the new RTOG 2021 contouring guidelines. This corresponded to a further 1% reduction in local relapses (P = .007). Dose to rectum was marginally increased with the new contouring, with no difference in other organs at risk. Salvage treatment was offered in 25 out of 60 patients who relapsed. Patients who received local treatment after relapse had a mean survival after relapse of 27.2 months compared with 8 months among those who received supportive care alone., Conclusions: Our study supports the use of newly published NRG/RTOG contouring guidelines in patients with cervical cancer who have undergone hysterectomy. Further data are needed to ascertain if anterior extension of the clinical target volume is needed as in the Postoperative Adjuvant Radiation in Cervical Cancer trial., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: In locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS)., Methods and Analysis: Radiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years., Ethics and Dissemination: The trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained., Trial Registration Number: The trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A significantly strengthened Revised National Tuberculosis Control Programme (RNTCP) is currently operational in India. In this case-based commentary, we describe the plight of a patient who developed extensive drug-resistant tuberculosis (XDR-TB) despite having received treatment under the RNTCP for a long period. Our aim is to analyse the programmatic management of tuberculosis in India by highlighting and discussing various issues related to the treatment received by the patient. Further, the article explores whether there is a need to incorporate an ethical element into the RNTCP as it stands today.

A fifty year old female presented with cough, breathlessness and chest pain of eighteen months duration. She presented as a case of a non-resolving consolidation. Video bronchoscopy revealed a bronchial foreign body. This case is being reported here, to underline the role of bronchoscopy in a case of a non resolving consolidation.