Revolutionizing cancer treatment in India: Evaluating the unmet need, economics, and a roadmap for project implementation of particle therapy.

INTRODUCTION: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India. METHODOLOGY: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large-scale combined particle (carbon and proton-three room fixed-beam), large-scale proton (one gantry and two fixed-beam), and small-scale proton (one gantry) facility. RESULTS: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30-year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high-income countries (USD 1000 to 3000 per fraction). CONCLUSION: This study indicates that, in the Indian scenario, all particle therapy models are cost-beneficial and feasible, with large-scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India. PLAIN LANGUAGE SUMMARY: In India, the number of eligible patients benefiting from high-precision particle therapy technology is projected to rise till 2040. Despite high upfront costs, our study finds the long-term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high-income countries. Despite challenges, India can succeed with an iterative phased approach.

The long-term impact of acute renal failure after aortic arch replacement for acute type A aortic dissection.

OBJECTIVE: To determine the long-term impact of developing acute renal failure (ARF) on survival after open aortic arch reconstruction for acute type A aortic dissection (ATAAD). METHODS: This was an observational study of consecutive aortic surgeries from 2007 to 2021. Patients with ATAAD were identified via a prospectively maintained institutional database and were stratified by the presence or absence of postoperative ARF (by RIFLE criteria). Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed. RESULTS: A total of 601 patients undergoing open surgery for ATAAD were identified, of which 516 (85.9%) did not develop postoperative ARF, while 85 (14.1%) developed ARF, with a median follow-up time of 4.6 years (1.6, 7.9). Baseline characteristics were similar across each group, except for higher rates of branch vessel malperfusion and lower preoperative ejection fraction in the ARF group. Patients with ARF underwent more total arch replacement and elephant trunk procedures, with longer cardiopulmonary bypass and circulatory arrest times than patients without ARF. ARF was associated with worse short-term outcomes, including increased in-hospital mortality, prolonged mechanical ventilation, higher rates of sepsis, more blood transfusions, and longer length of hospital stay. Unadjusted Kaplan-Meier survival estimates were significantly lower in the ARF group, compared to the group without ARF (p < .001, log-rank test). After multivariable adjustment, the development of postoperative ARF was significantly associated with an increased hazard of death over the study's follow-up time-period (hazard ratio: 2.74, 95% confidence interval: 1.95, 3.86, p < .001). CONCLUSIONS: ARF is a highly morbid postoperative event that may adversely impact long-term survival after aortic surgery.

Endogenous T1ρ cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. METHODS: HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15-20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE --); otherwise, the image was labeled equivocal (LGE + -). RESULTS: In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman's rho = 0.61, p < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE -- slices had lower ECV than LGE + + (p = 0.01). CONCLUSIONS: Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients.

Efficacy and toxicity of SBRT in advanced hepatocellular carcinoma with portal vein tumor thrombosis - a retrospective study.

BACKGROUND: The purpose of this study was to evaluate the outcome of stereotactic body radiation therapy (SBRT) in patients of unresectable hepatocellular carcinoma (HCC ) complicated with portal vein tumor thrombosis (PVTT) who are also unsuitable for other locoregional therapies. MATERIALS AND METHODS: Between May 2018 and January 2020, twenty-nine patients with advanced unresectable HCC s, treated with SBRT, were enrolled in this retrospective audit. Patients of Child status A5-B7 and with healthy liver volume, ≥ 700 ccs were treated. Local control (LC), overall survival (OS), progression-free survival (PFS), PVTT opening rate, and effect of prognostic factors were analyzed. RESULTS: The median tumor diameter was 8.6 cm (5-14), and the median tumor volume was 275 cc (151-1196). The median SBRT dose prescription was 48 Gy in 6 fractions (32-50 Gy in 5-6 fractions). The median follow up was eight months (1-20), 1-year local control, progression-free survival, and overall survival were 95%, 53.4%, and 60%, respectively. Overall rate of grade III toxicity was less than 5%, and the most common toxicity was lymphocytopenia. Tumors of more than 350cc had worse OS and PFS when compared to tumors < 350 cc (median OS and PFS of tumors > 350 cc was 4 months and two months, p = .01 and .003, respectively). A total of fifteen patients progressed with the disease and the median time to progression was two months [1-4]. CONCLUSION: SBRT is safe and provides excellent local control in advanced HCC complicated with PVTT. The out of field failure pattern and time to failure in these patients highlights the need for adjuvant systemic therapy after completion of local treatment. Our data warrant the need for multimodality trials in this patient cohort.

Dosimetric impact of contrast-enhanced 4d computed tomography for stereotactic body radiation therapy of hepatocelluar carcinoma.

BACKGROUND: A purpose of the study was to investigate the dosimetric impact of contrast media on dose calculation using average 4D contrast-enhanced computed tomography (4D-CECT) and delayed 4D-CT (d4D-CT) images caused by CT simulation contrast agents for stereotactic body radiation therapy (SBRT) of liver cases. MATERIALS AND METHODS: Fifteen patients of liver SBRT treated using the volumetric modulated arc therapy (VMAT) technique were selected retrospectively. 4D-CECT, and d4D-CT were acquired with the Anzai gating system and GE CT. For all patients, gross target volume (GTV) was contoured on the ten phases after rigid registration of both the contrast and delayed scans and merged to generate internal target volume (ITV) on average CT images. Region of interest (ROI) was drawn on contrast images and then copied to the delayed images after rigid registration of two average CT datasets. The treatment plans were generated for contrast enhanced average CT, delayed average CT and contrast enhanced average CT with electron density of the heart overridden. RESULTS: No significant dosimetric difference was observed in plans parameters (mean HU value of the liver, total monitor units, total control points, degree of modulation and average segment area) except mean HU value of the aorta amongst the three arms. All the OARs were evaluated and resulted in statistically insignificant variation (p > 0.05) using one way ANOVA analysis. CONCLUSIONS: Contrast enhanced 4D-CT is advantageous in accurate delineation of tumors and assessing accurate ITV. The treatment plans generated on average 4D-CECT and average d4D-CT have a clinically insignificant effect on dosimetric parameters.

Cubic Nanostructures of Nickel-Cobalt Carbonate Hydroxide Hydrate as a High-Performance Oxygen Evolution Reaction Electrocatalyst in Alkaline and Near-Neutral Media.

Catalyst development for the efficient direction of electrocatalytic water splitting with much less overpotential is crucial for meeting large-scale hydrogen generation. Being highly abundant and cost-effective, 3d transition-metal-based catalysts show promising activities in alkaline conditions. In this work, bimetallic nickel-cobalt carbonate hydroxide hydrate (NiCoCHH) was prepared by a co-precipitation method with varying molar ratios of Ni/Co of 0.5:1, 1:1, and 1.5:1, which were analyzed for oxygen evolution reaction (OER) study in both alkaline (1 M KOH) and near-neutral (1 M NaHCO3) media. For OER in 1 M KOH, NiCoCHH 1:1 required overpotential of just 238 mV at 10 mA cm-2 current density compared to other ratios of 0.5:1 and 1.5:1, which required 290 and 308 mV, respectively. Similarly, in 1 M NaHCO3, NiCoCHH 1:1 required an overpotential of 623 mV to reach 10 mA cm-2. A post-OER study confirmed the formation of NiOOH during OER. The observed faradaic efficiency was nearly 95.21% for the NiCoCHH 1:1 catalyst. A two-electrode setup with NiCoCHH 1:1∥Pt required just 312 mV as an overpotential at 10 mA cm-2. These kinds of comparative studies can be used in other 3d transition-metal-based catalysts for OER in the future.

A prospective comparative dosimetric study between diffusion weighted MRI (DWI) & T2-weighted MRI (T2W) for target delineation and planning in cervical cancer brachytherapy.

AIM: To evaluate the difference between GTVBT (Gross Tumor Volume at Brachytherapy) and HR CTV (High Risk Clinical Tumor Volume) delineated with DWI and T2W MRI. To evaluate doses to organs at risk and targets from plans generated using T2W and DWI. BACKGROUND: Functional imaging with DWI can improve cervical tumor distinction as it is more sensitive than T2W MRI even in detecting parametrial invasion. This study does a dosimetric comparison between a T2W and DWI based plan. METHODS: Fifty carcinoma cervix patients were subjected to MRI based brachytherapy. T2W and a diffusion weighted sequence were acquired. Target delineation and brachytherapy planning was done on both T2W and DWI. Standard DVH parameters were recorded and the treatment was given using the plan generated from T2W images. RESULTS: GTVBT and HRCTV contours on DWI were different when compared with T2W. Mean GTVBT volume on T2W and DWI was 5.25 and 5.23, respectively (p value 0.8). Mean HRCTV on T2W and DWI was 28.3 and 27 cc, respectively (p value 0.003). Planning on the above volumes resulted in a superior coverage in terms of HRCTV D90 and D100 for DWI based plan, HRCTV D90 - 735.1 and 741 cGy for T2W and DWI, respectively (p value 0.006), HRCTV D100 - 441.05 and 444.5 for T2W and DWI plans, respectively (p value = 0.006). Doses to the OAR were not significantly increased. CONCLUSION: GEC ESTRO based contouring guidelines cover all the functionally abnormal areas on DWI. DWI should only be used as a supplement to T2W for contouring target volumes.

Change of telomerase activity in peripheral blood of patients with head and neck squamous cell carcinoma pre and post curative treatment.

BACKGROUND: There is no clinically applicable tumor marker for head and neck cancers. Telomerase is detected in approximately 90% of all malignant tumors, it may predict poor or favorable outcomes, thus being both a highly attractive biomarker and a target for the development of molecular-based cancer diagnostics, prognostics, and therapeutics. AIM: Primary aim was to detect a change of telomerase activity before and after curative treatment. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma, stage I-IVB treated with a curative intent, performance status 0-2 and malignancy at one primary site were included in the study. Telomerase levels were tested in tissue biopsy. Plasma telomerase levels were tested at baseline, 5 days and at 3 months after treatment using ELISA. RESULTS: Raised plasma telomerase activity was seen in all the patients with cancer at baseline. The mean plasma telomerase level at baseline was 861.4522 ng/ml, at 5 days after completion of curative treatment was 928.92 ng/ml and at 3 months of follow up was 898.87 ng/ml. The mean tissue biopsy telomerase level was 19768.53 ng/mg. There was a significant increase in baseline telomerase levels in cancer patients compared to normals (volunteers) (t = -3.52, p = 0.001).There was a significant increase in plasma levels of telomerase at 3 months compared to baseline values (z = -1.98, p = 0.04). The increase in telomerase level did not correlate with the response of the treatment. CONCLUSION: In patients with head and neck squamous cell carcinomas treated with a curative intent, the change in levels of telomerase correlates neither with the disease status nor with prognostic factors.

Dosimetric comparison of dynamic conformal arc integrated with segment shape optimization and variable dose rate versus volumetric modulated arc therapy for liver SBRT.

PURPOSE: The aim is a dosimetric comparison of dynamic conformal arc integrated with the segment shape optimization and variable dose rate (DCA_SSO_VDR) versus VMAT for liver SBRT and interaction of various treatment plan quality indices with PTV and degree of modulation (DoM) for both techniques. MATERIAL: Twenty-five patients of liver SBRT treated using the VMAT technique were selected. DCA_SSO_VDR treatment plans were also generated for all patients in Monaco TPS using the same objective constraint template and treatment planning parameters as used for the VMAT technique. For comparison purpose, organs at risk (OARs) doses and treatment plans quality indices, such as maximum dose of PTV (Dmax%), mean dose of PTV (Dmean%), maximum dose at 2 cm in any direction from the PTV (D2cm%), total monitor units (MU's), gradient index R50%, degree of modulation (DoM), conformity index (CI), homogeneity index (HI), and healthy tissue mean dose (HTMD), were compared. RESULTS: Significant dosimetric differences were observed in several OARs doses and lowered in VMAT plans. The D2cm%, R50%, CI, HI and HTMD are dosimetrically inferior in DCA_SSO_VDR plans. The higher DoM results in poor dose gradient and better dose gradient for DCA_SSO_VDR and VMAT treatment plans, respectively. CONCLUSIONS: For liver SBRT, DCA_SSO_VDR treatment plans are neither dosimetrically superior nor better alternative to the VMAT delivery technique. A reduction of 69.75% MU was observed in DCA_SSO_VDR treatment plans. For the large size of PTV and high DoM, DCA_SSO_VDR treatment plans result in poorer quality.

Feasibility of 4D CT simulation with synchronized intravenous contrast injection in hepatocellular carcinoma.

BACKGROUND: Delivering Stereotactic Body Radiotherapy (SBRT) for Hepatocellular Carcinoma (HCC) is challenging mainly for two reasons: first, motion of the liver occurs in six degrees of freedom and, second, delineation of the tumor is difficult owing to a similar density of HCC to that of the adjoining healthy liver tissue in a non-contrast CT scan. To overcome both these challenges simultaneously, we performed a feasibility study to synchronize intravenous contrast to obtain an arterial and a delayed phase 4D CT. MATERIALS AND METHODS: We included seven HCC patients of planned for SBRT. 4D CT simulation was performed with synchronized intravenous contrast based on the formula TSCAN DELAY = T peak - (L0/Detector Coverage × Cine Duration in Seconds). This was followed by a delayed 4D CT scan. RESULTS: We found that, with our protocol, it is feasible to obtain a 4DCT with an arterial and a delayed phase making it comparable to a diagnostic multi-phase CT. The peak HU of the 4D scan and diagnostic CT were similar (mean peak HU 134.2 vs 143.1, p value = 0.58 N.S). Whereas in comparison with a non-contrast CT a significant rise in the peak HU was seen (mean peak 134.2 vs 61.4 p value = .00003). CONCLUSION: A synchronized contrast 4D CT simulation for HCC is safe and feasible. It results in good contrast enhancement comparable to a diagnostic 3D contrast CT scan.

Survival analysis in association with GST gene polymorphism and Treatment outcomes of Gemcitabine and Cisplatin/Carboplatin-based chemotherapy among patients with Gallbladder Carcinoma.

PURPOSE: Majority of the gallbladder cancer (GBC) cases are diagnosed at an advanced stage where chemotherapy alone (or in combination with other treatment methods) is mainly opted as therapeutic approach. However, success or failure of this approach largely depends on the interindividual genetic differences. Careful consideration on the genetic association could assist in the evaluation of patient's treatment response and survival rate. Hence, the present study aims to investigate the survival of patients with GBC and their treatment response to gemcitabine and cisplatin/carboplatin-based chemotherapy in association with Glutathione S-transferase (GSTs) gene polymorphism. MATERIAL AND METHODS: A total of 216 histologically confirmed cases of gallbladder cancer were recruited. A total of 180 patients were treated with gemcitabine and cisplatin/carboplatin-based chemotherapy. GSTM1, GSTT1, and GSTP1 genotypes were determined by multiplex PCR and by PCR restriction fragment length polymorphism (PCR-RFLP), respectively. The influence of genetic polymorphism on overall survival was analyzed by Kaplan-Meier method, survival rate difference was analyzed by log-rank test, and hazard ratio for mortality outcomes was estimated using Cox regression method. RESULTS: GBC patients having genotype GSTP1 (AG + GG) showed poor 3-year survival rate of 0.8% compared to 10.9% of GSTP1 (AA) genotype (χ2 = 6.456, P = 0.011). The multivariate Cox regression results showed that the death risk was significantly higher in GSTP1 (AG + GG) genotype (HR = 3.858, P = 0.050). We found no association of GSTM1 and GSTT1 gene polymorphism with the survival; however, the combined genotypes of GSM1/GSTP1, GSTT1/GSTP1, and GSTM1/GSTT1/GSTP1 were associated with survival (P = 0.053, 0.006, and 0.058, respectively). Increased death hazard was noted by the genotype combinations of GSTM1+/GSTP1AG + GG (HR = 3.484, P = 0.024), GSTM1-/GSTP1AG + GG (HR = 2.721, P = 0.014), GSTT1+/GSTP1AG + GG (HR = 20.690, P = 0.001), and GSTT1-/GSTP1AA (HR = 26.111, P < 0.0001). Our findings indicate that chemotherapy treatment response of GSTP1 (AG + GG) has 1.62-fold increased risk for progression compared to GSTP1 (AA) genotype (p = 0.018); however, none of the genotypes showed association with overall survival and death risk after chemotherapeutic treatment. CONCLUSION: We found that the presence of GSTP1 (AG + GG) genotype showed survival disadvantage and poor treatment outcomes in response to gemcitabine and cisplatin/carboplatin-based chemotherapy. This could serve as biomarker, and future research in pharmacogenomics will definitely pave the way for the development of better treatment approach for GBC.

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics.

Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs' potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.

Yield of residues produced in 6Li reaction on Ta: A comparative analysis for 183Os.

The present work reports an analysis of the production yield of residues from the 6Li ＋ 181Ta reaction in a low-energy regime. The experimental yield of 183gOs, 183mOs, 182Os, 183Re, 183Ta, 182m2Ta, and 180Ta have been measured in the 27-43 MeV energy window and compared with equilibrium and pre-equilibrium model calculations under the framework of the nuclear reaction model code, EMPIRE-3.2.2. The maximum yield measured for 183gOs is 80.5 ± 14.9 MBq/C at 40.2 MeV energy in a 2.3 mg/cm2 thick Ta target corresponding to a cross-section of 360.1 ± 34.4 mb from the 181Ta(6Li,4n)183Os reaction and that for 183Re is 1.36 ± 0.4 MBq/C at 42.75 MeV in a 2.4 mg/cm2 thick target. The model estimations agree well with the experimental yields of 183gOs and 183Re. The possible production of stable residues has been estimated using the model-predicted cross-section in the studied energy range. A comparison of production yields of 183m,gOs from 6Li- and 7Li-induced reaction on Ta demonstrates the 6Li reaction as a better candidate. Thick target yields have been evaluated for Os and Re isotopes.

Clinical and Radiological Outcomes of Patients With Anterior Acetabulum Fractures Treated by the Modified Stoppa Approach.

Introduction Acetabular fractures are intra-articular fractures involving the lower extremity's weight-bearing dome. These fractures require an anatomical reduction of the fracture fragments. This aim can be accomplished by the selection of an appropriate surgical approach. This study aimed to analyze the clinical and radiological outcomes of patients with fractures in the anterior part of the acetabulum who were treated by the modified Stoppa approach. Methods This prospective observational study was conducted from April 2022 to September 2023. The inclusion criteria were: (i) age between 18 and 70 years, (ii) displaced acetabular fracture (displacement > 3 mm), (iii) within three weeks of trauma (iv) acetabular fractures with involvement of anterior column. Exclusion criteria included: (i) patients with visceral injuries requiring colostomy, (ii) pathological fracture, (iii) open fractures of the acetabulum, and (iv) neglected fracture (more than three weeks). Intraoperative data regarding surgical time, amount of blood loss, and incidence of intraoperative complications were recorded. In the postoperative period, anteroposterior X-ray and Judet views of the pelvis X-ray were obtained. Matta criteria were used to judge the quality of Fracture reduction and fixation. All the patients to be included in this study had undergone a minimum follow-up duration of six months. At the last follow-up, an assessment of the functional outcome of the affected hip by Merle d'Aubigné Hip Score and Harris Hip Score was done. Results Twenty-four patients were included in the study. The mean patient age was 36.08±11.65 years. Eighteen patients were male (75%) and six patients were female in this study. All acetabular fractures were due to high-energy trauma: road traffic accidents in 22 cases (91%) and fall from height in two cases (9%). According to Judet & Letournel's classification, there were 13 T-type fractures, five transverse fractures, and six associated both column fractures. The mean duration of surgery was 152.08 ±29.19 minutes, and the mean intraoperative blood loss was 277.08±85.95 ml. Intraoperatively one unit of blood transfusion was done in most cases. There were intraoperative complications of rent in the external iliac vein in two patients. Postoperative X-rays showed anatomical reduction in 17 cases, imperfect reduction in five cases, and poor reduction in two cases. Functional outcome of the hip by Merle d'Aubigné Hip Score was very good in 15, good in four, fair in three, and poor in two patients. Similar functional outcomes were obtained with the Harris Hip Score. Conclusion The results of the current study demonstrated that the modified Stoppa approach allows good visualization of the pelvic brim, quadrilateral surface, and posterior column. Lesser experienced orthopedic surgeons should utilize this approach to get good radiological and functional outcomes.

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders.

Stem cells' self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells' self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.

Is Regular Probiotic Practice Safe for Management of Sepsis?

For decades, the gut has been thought to play an important role in sepsis pathogenesis. Sepsis is a serious life-threatening, chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit patients. Probiotics have dual roles in polymicrobial sepsis i.e. probiotics may induce sepsis in many cases and may prevent its prognosis in many cases. Experimental evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor, interleukin-10 (IL-10), IL-6, etc., in septicemia. In addition, probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in septicemia. On contrary, probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced inflammation. Importantly, in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing it. This review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.

Higher order genes interaction in DNA repair and cytokine genes polymorphism and risk to lung cancer in North Indians.

Context: Lung cancer pathological process involves cumulative effects exerted by gene polymorphism(s), epigenetic modifications, and alterations in DNA repair machinery. Further, DNA damage due to oxidative stress, chronic inflammation, and the interplay between genetic and environmental factors is also an etiologic milieu of this malignant disease. Aims: The present study aims to assess the prognostic value of DNA repair, cytokines, and GST gene polymorphism in lung cancer patients who had not received any neoadjuvant therapy. Materials and Methods: In this case-control study, 127 cases and 120 controls were enrolled. DNA from the blood samples of both patients and controls was used to genotype XRCC1Arg399Gln, XPDLys751Gln, and interleukin-1 (IL-1ß) genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism method, whereas multiplex PCR was performed to genotype GSTT1 and GSTM1. Results: Binary logistic regression analysis showed that XRCC1Arg399Gln-mutant genotype (Gln/Gln, odds ratio [OR] = 4.6, 95% confidence interval [CI]: 2.2-9.6) and GSTT1 null (OR = 2.7, 95% CI: 1.6-4.5) were linked to cancer susceptibility. Generalized multidimensional reduction analysis of higher order gene-gene interaction using cross-validation testing (CVT) accuracy showed that GSTT1 (CVT 0.62, P = 0.001), XPD751 and IL-1ß (CVT 0.6, P = 0.001), and XRCC1399, XPD751, and interleukin-1 receptor antagonists (IL-1RN) (CVT 0.98, P = 0.001) were single-, two-, and three-factor best model predicted, respectively, for lung cancer risk. Classification and regression tree analysis results showed that terminal nodes which contain XRCC1399-mutant genotype (AA) had increased the risk to lung cancer. Conclusion: The present study demonstrated that XRCC1399 (Gln/Gln), GSTT1, and IL-1RN allele I, I/II served as the risk genotypes. These genes could serve as the biomarkers to predict lung cancer risk.

Is hepatocellular carcinoma complicated with portal vein tumor thrombosis potentially curable by radiotherapy in the form of stereotactic body radiation therapy?

PURPOSE: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal. Despite best treatment and care, the patients with this malignancy only showed 2.7-4 months of overall survival. It is debatable whether liver transplantation helps PVTT sufferers. The effectiveness of radiation therapy in treating HCC patients with PVTT should not be undervalued. By limiting the high dosage region to a small planning target volume, stereotactic radiation delivery has shifted toward hypofractionation, limiting the radiation exposure to healthy organs and tissues. Stereotactic body radiotherapy (SBRT) has a local control rate of 75-100%, depending on the treatment. The major limitation in SBRT for hepatocellular carcinoma with PVTT is the paucity of prospective evidence for longer periods beyond the first two years after treatment. More prospective studies/randomized clinical trials with a longer follow-up, larger sample size, and adequate statistical power are the dire need of the present situation to ascertain the curative effect of SBRT as primary therapy for advanced HCC with PVTT. CONCLUSION: SBRT can improve survival, particularly for patients receiving multidisciplinary treatment. This review sums up our most current understanding of how radiation therapy, notably SBRT, can be used to treat hepatocellular carcinoma when combined with PVTT. Recent research has led us to believe that irradiation in the form of SBRT may cure hepatocellular carcinoma complicated by PVTT.

Metabolic Pathways, Enzymes, and Metabolites: Opportunities in Cancer Therapy.

Metabolic reprogramming enables cancer cells to proliferate and produce tumor biomass under a nutrient-deficient microenvironment and the stress of metabolic waste. A cancer cell adeptly undergoes a variety of adaptations in metabolic pathways and differential expression of metabolic enzyme genes. Metabolic adaptation is mainly determined by the physiological demands of the cancer cell of origin and the host tissue. Numerous metabolic regulators that assist cancer cell proliferation include uncontrolled anabolism/catabolism of glucose metabolism, fatty acids, amino acids metabolism, nucleotide metabolism, tumor suppressor genes, microRNAs, and many regulatory enzymes and genes. Using this paradigm, we review the current understanding of metabolic reprogramming in tumors and discuss the new strategies of cancer metabolomics that can be tapped into for cancer therapeutics.

Comparison of treatment response in cervical carcinoma patients infected with human papillomavirus 16 and human papillomavirus 18 who are treated with chemoradiation.

OBJECTIVES: The primary objective of this study was to compare the treatment response of cervical carcinoma patients infected with human papillomavirus (HPV) 16 and HPV 18 who are treated with chemoradiation. MATERIALS AND METHODS: Ninety-six biopsy-proven cervical cancer patients, suitable for curative treatment with definitive radio-chemotherapy with International Federation of Gynecology and Obstetrics Stage IB2-IIIB, were included in this prospective study. HPV testing was done using TRUPCR® HPV 16 and 18 real-time polymerase chain reaction kit. All the patients received a dose of 83-90 Gy total equieffective dose to the high risk clinical target volume(HRCTV) using tele- and brachytherapy. RESULTS: Of the 96 patients, 79 (82.3%) patients were positive for HPV DNA. Seventy-three patients showed HPV genotype 16 positivity and six patients were positive for genotype 18. The response was correlated with HPV genotype. There was a statistically significant increase in complete radiological response in HPV 16 compared to HPV 18 and negative groups at 3 months, 80.8%, 50%, and 52.9%, respectively (χ2 = 36.5, P < 0.001). There was also a statistically significant increase in clinical response at 3 months in HPV 16 group compared to HPV 18 and negative groups, 87.5%, 50%, and 50%, respectively (χ2 = 29.9, P < 0.001). The age, volume of the disease, overall treatment time, average hemoglobin level, and the number of blood transfusions did not have any correlation. CONCLUSION: HPV genotype 16 positivity shows higher complete response in cervical carcinoma patients treated with definitive chemoradiation compared to HPV 18 genotype. Further HPV genotyping could potentially help stratify cervical cancer patients for more effective therapeutic regimens.