Improvement in plan quality after Implementation of clinical goals in a large network of cancer centers.

Clinical Goals (CG) is a tool available in the Varian Eclipse planning system to objectively and visually evaluate the quality of treatment plans based upon user-defined dose-volume parameters. We defined a set of CG for Stereotactic Radiosurgery (SRS) and Intensity-Modulated Radiotherapy (IMRT) based on published data and guidelines and implemented this in a network of cancer centers in India (American Institute of Oncology). A dosimetric study was performed to compare brain SRS and breast IMRT plan quality before and after CG implementation.The CG defined for SRS plans were target V100% ≥ 98%, dose gradient measure (GM) ≤ 0.5 cm, conformity index (CI) 1.0 to 1.2. For breast IMRT plans, CG defined target V100% ≥ 97%, V95% ≥ 95%, V107% ≤ 2%, V105% ≤ 10%, and Dmax ≤ 2.4 Gy. Dose limits to organs-at-risk (OAR) were summarize in supplemental materials. Twenty brain SRS and 10 breast IMRT treatment plans that were previously delivered on patients were selected and re-planned using CG. The pre and postoptimized plan parameters were compared using student t-tests.For brain SRS plans, the V100, GM, and CI for the pre- and post-Clinical-Goals plans were 93.22% ± 7.2% vs 97.96% ± 0.29% (p = 0.009), 0.63 ± 0.16 vs 0.42 ± 0.05 (p < 0.001) and 1.07 ± 0.18 vs 1.06 ± 0.06 (p = 0.79), respectively. There were no differences in max dose to OARs. In breast IMRT plans, the target V107% for pre and postimplemented plans were 16.50% ± 10.98% vs 0.32% ± 0.32%, respectively (p = 0.001). The average target V105% were 44.00% ± 15.72% and 8.69% ± 4.53%, respectively (p < 0.001). No differences were found in the average target V100% (p = 0.128) and V95% (p = 0.205). The average target Dmax were 112.28% ± 1.59% and 109.14% ± 0.73%, respectively (p < 0.001). There were only minor differences in doses to OARs.The implementation of CG in Varian Eclipse significantly improved SRS and IMRT plan quality with enhanced coverage, dose GM, and CI without increased dose to OARs.

Terahertz Spectroscopy: Encoding the Discovery, Instrumentation, and Applications toward Pharmaceutical Prospectives.

Terahertz (THz) spectroscopy is an emerging field for quality control of pharmaceuticals, which uses T-waves for detection. T-waves fall in between infrared and microwave radiations while possessing some of the characteristics of both. THz spectroscopy reveals its existence in between 0.1 and 10 THz. These radiations have the ability to penetrate a broad range of non-conductive materials and it is nonionizing. The first article stating the use of THz radiations was found in late 1960 for the generation of the astronomical images. This review essentially creates attention toward different forms and instrumentation of THz spectroscopy along with the updates for timely and upbeat pharmaceutical applications. The most frequently used technique is THz-TDS which has profoundly privileged applicability for the pharmaceuticals. The existing literature of THz spectroscopy further created albeit interest to explore the applications for future implementation in concern with the pharmaceuticals. The review critically outlines here all the pharmaceutical applications of THz spectroscopy including protein analyses, crystallinity studies, evaluating tablet films and coats, medicinal aging variations, and detection of illicit drugs, along with the advantages over traditional techniques. The other side of THz spectroscopy stating limitations is also studied and taken into the note to present here. This review is a genuine attempt to quote and crucially assess the possible as well as anticipated prospectives for the pharmaceuticals. The present article will further promote the awareness, opportunities, and scientific exploration of this exciting technology as THz spectroscopy.

Solitary Pancreatic Head Metastasis from Ductal Carcinoma of Breast: A Case Report.

Liver, bones, and brain are common sites for breast cancer metastasis. We report here a rare scenario of metastasis to pancreatic head from breast cancer after a disease free interval of 7 years. A 60-year old breast cancer survivor noticed upper abdominal pain for 2 weeks, and her investigations revealed a pancreatic head mass lesion. Computed tomography imaging revealed a solitary pancreatic mass lesion with portal cavernoma formation and a guided biopsy yielded adenocarcinoma on histopathological examination. Immunohistochemistry processing demonstrated estrogen receptor, cytokeratin 7, and GATA 3 positivity which confirmed it to be a metastasis. Therapy was initiated with palbociclib and exemestane. Later, everolimus was started in view of failure of hormonal therapy. The patient is still alive 21 months after diagnosing the recurrence.

Hydrotropic Solubilization in Pharmaceutical Analysis: Origin, Evolution, Cumulative Trend and Precise Applications.

The hydrotropy though existing as precisely used scientific approach assisting solubilization for all. It took 66 long years to use the concept in drug analysis since its inception in 1916 and first use for facilitation of drug solubility toward better pharmaceutical analysis in 1982. Considering the unending importance in pharmaceutical sciences and thereby in analysis, it's a necessity to comprehensively outlook the origin, evolution, cumulative trend and precise applications in pharmaceutical analysis. Achieved hereby with chronological and comparative assessment of the studies published pertaining to solubility enhancement of poorly soluble drugs with use of hydrotropic agents alone or in combination for assisting pharmaceutical analysis. The thorough literature searches resulted into 77 references over a span of about 38 years. This comprehensive review critically evaluates existing literature; to our surprise we found Ibuprofen sodium, Lignocaine, Niacinamide and Metformin HCl as atypical hydrotropic agents. We also compared herein mono and mixed approaches which indicated prevalence of mono - hydrotropy over mixed. The possible mechanisms behind solubilization are presented for an additional insight. An essential effort has been made to state arbitrary classification to assist in future applications. The obvious purpose of this study was to collectively evaluate the crucial role of hydrotropic agents in pharmaceutical analyses for better drug delivery. This comprehensive review covers all details since inception to the updates till date which will definitely act as appropriate guideline for pharmaceutical analyst's in need of hydrotropy to assist pharmaceutical analysis for therapies today and tomorrow.

Pharmaceutical Analytical Profile for Novel SGL-2 Inhibitor: Dapagliflozin.

Dapagliflozin (DPG) is a novel drug from class of sodium glucose co-transporter 2 (SGL-2) inhibitors which has been evolved as profound treatment option for the type-2diabetes mellitus (T2DM). Considering the severity of the disease the drug is of crucial significance for the therapy and associated research. As a pharmaceutical dosage form DPG has immense importance as an individual drug and with other antidiabetic drugs as combinations. The drugs existing in combination with DPG are Metformin (MET) and Saxagliptin (SXG). The existence of the Dapagliflozin in combinations further created more interest in reviewing its pharmaceutical, analytical and bio-analytical profile. Such estimations are always in need of precise pharmacological and physicochemical information; hence authors have presented it beforehand. Authors hereby wish to present an essential update pertaining to emergence of gliflozins and DPG. The article further presents a simultaneous and comparative assessment of the analytical investigations published in literature for pharmaceutical estimation to assist future analysis. The thorough literature searches revealed fifty three research papers in total till date. A comprehensive presentation of typical; hyphenated and unique methods used for analysis are outlined effectively. The percentile utilization of analytical approaches since appearance of first publication in 2010 is investigated to report trend in determination. The present review explores the pharmaceutical estimation of DPG to scientifically potentiate analytical research and therapeutic future of DPG as a novel SGL-2 Inhibitor antidiabetic.

Optimal Standardized Uptake Value Threshold for Auto contouring of Gross Tumor Volume using Positron Emission Tomography/Computed Tomography in Patients with Operable Nonsmall-Cell Lung Cancer: Comparison with Pathological Tumor Size.

PURPOSE: Incorporating 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) for gross tumor volume (GTV) delineation is challenging due to varying tumor edge based on the set threshold of the standardized uptake value (SUV). This study aims to determine an optimal SUV threshold that correlates best with the pathological tumor size. MATERIALS AND METHODS: From January 2013 to July 2014, 25 consecutive patients of operable nonsmall-cell lung cancer (NSCLC) who underwent staging18F-FDG-PET/CT before surgical resection were included in the test cohort and 12 patients in the validation cohort. GTVs were delineated on the staging PET/CT by automatic delineation using various percentage threshold of maximum SUV (SUVmax) and absolute SUV. The maximum pathological tumor diameter was then matched with the maximum auto-delineated tumor diameter with varying SUV thresholds. First-order linear regression and Bland-Altman plots were used to obtain an optimal SUV threshold for each patient. Three radiation oncologists with varying degrees of experiences also delineated GTVs with the visual aid of PET/CT to assess interobserver variation in delineation. RESULTS: In the test set, the mean optimal percentage threshold for GTV was SUVmax of 35.6%±18.6% and absolute SUV of 4.35 ± 1.7. In the validation set, the mean optimal percentage threshold SUV and absolute SUV were 36.9 ± 16.9 and 4.1 ± 1.6, respectively. After a combined analysis of all 37 patients, the mean optimal threshold was 36% ± 17.9% and 4.27 ± 1.7, respectively. Using Bland-Altman plots, auto-contouring with 40% SUVmax and SUV 4 was in greater agreement with the pathological tumor diameter. CONCLUSION: Automatic GTV delineation on PETCT in NSCLC with percentage threshold SUV of 40% and absolute SUV of 4 correlated best with pathological tumor size. Auto-contouring using these thresholds will increase the precision of radiotherapy contouring of GTV and will save time.

Transrectal ultrasound-guided prostatic biopsy: midazolam, the ideal analgesic.

OBJECTIVES: Patients with raised serum prostate-specific antigen and/or an abnormal-feeling prostate were subjected to transrectal ultrasound-guided prostatic biopsy to rule out any prostatic malignancy. There are many methods for pain relief and to treat discomfort during the procedure but we compared the efficacy of intravenous (IV) midazolam for pain control. PATIENTS AND METHODS: This was a prospective study of 50 patients. All patients underwent a ten quadrant biopsy. The patients were divided into two groups: group 1 (study group) which included 25 patients who used 1 ml of IV midazolam and group 2 (control group) which included 25 patients who did not use IV midazolam. RESULTS: In group 1, of 25 patients only 1 patient had mild pain (VAS 2) during and after the procedure. In group 2, of 25 patients, 15 patients had pain during the procedure. CONCLUSION: Midazolam is a benzodiazepine derivative with an anxiolytic, sedative, amnestic and hypnotic action. Our study shows that using midazolam is a very simple technique which gives excellent analgesia and no other analgesia was required. No monitoring was needed, there was a very low incidence of complications and it did not require any technical expertise.

Systemic chemotherapy and short-course radiation in metastatic rectal cancers: A feasible paradigm in unresectable and potentially resectable cancers.

BACKGROUND: The optimal use and sequencing of short-course radiotherapy (SCRT) in metastatic rectal cancers (mRCs) are not well established. MATERIALS AND METHODS: We retrospectively reviewed the records of mRC patients receiving SCRT followed by palliative chemotherapy between January 1, 2013, and December 31, 2016, in Tata Memorial Hospital. Patients were classified as having "potentially resectable" disease (local and metastatic) or "unresectable" disease at baseline based on prespecified criteria. RESULTS: A total of 105 consecutive patients were available for analysis. The median age of patients was 48 years (range: 16-62 years), and 57.1% were male patients. Signet ring histology was seen in 13.3% of patients. The most common site of metastases was liver limited (29.5%), nonloco-regional nodes (12.4%), and lung limited metastases (9.5%). Chemotherapeutic regimens administered were capecitabine-oxaliplatin (70.5%), modified 5 fluorouracil (5 FU)-leucovorin-irinotecan-oxaliplatin (10.5%), and modified 5 FU-leucovorin-irinotecan (8.6%). Targeted therapy accompanying chemotherapy was administered in 27.6% of patients. About 42.1% of patients with potentially resectable disease and 11.1% with the unresectable disease at baseline underwent curative-intent resection of the primary and address of metastatic sites. With a median follow-up 18.2 months, median overall survival (OS) was 15.7 months (95% confidence interval: 10.42-20.99). Patients classified as potentially resectable had a median OS of 32.62 months while patients initially classified as unresectable had a median OS of 13.04 months (P = 0.016). The presence of signet ring morphology predicted for inferior mOS (P = 0.021). CONCLUSIONS: SCRT followed by systemic therapy in mRC is a feasible, efficacious paradigm for maximizing palliation, and achieving objective responses. The classification of patients based on resectability was predictive of actual resection rates as well as outcomes. Signet ring mRC show inferior outcomes in this cohort of patients.

Cinnamaldehyde, Cinnamic Acid, and Cinnamyl Alcohol, the Bioactives of Cinnamomum cassia Exhibit HDAC8 Inhibitory Activity: An In vitro and In silico Study.

BACKGROUND: The altered expression of histone deacetylase family member 8 (HDAC8) has been found to be linked with various cancers, thereby making its selective inhibition a potential strategy in cancer therapy. Recently, plant secondary metabolites, particularly phenolic compounds, have been shown to possess HDAC inhibitory activity. OBJECTIVE: In the present work, we have evaluated the potential of cinnamaldehyde (CAL), cinnamic acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro and in silico. MATERIALS AND METHODS: HDAC8 inhibitory activity of ACE and cinnamon bioactives was determined in vitro using HDAC8 inhibitor screening kit. Trichostatin A (TSA), a well-known anti-cancer agent and HDAC inhibitor, was used as a positive control. In silico studies included molecular descriptor Analysis molecular docking absorption, distribution, metabolism, excretion, and toxicity prediction, density function theory calculation and synthetic accessibility program. RESULTS: Pharmacoinformatics studies implicated that ACE and its Bioactives (CAL, CA, and CALC) exhibited comparable activity with that of TSA. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals along with binding energy of cinnamon bioactives were comparable with that of TSA. Molecular docking results suggested that all the ligands maintained two hydrogen bond interactions within the active site of HDAC8. Finally, the synthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. CONCLUSION: It was evident from both the experimental and computational data that cinnamon bioactives exhibited significant HDAC8 inhibitory activity, thereby suggesting their potential therapeutic implications against cancer. SUMMARY: Pharmacoinformatics studies revealed that cinnamon bioactives bound to the active site of HDAC8 enzyme in a way similar to that of TSAThe molecular descriptors of cinnamon compounds successfully correlated with TSA values. The binding interactions and energies were also found to be close to TSASynthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. Abbreviations used: ACE: Aqueous Cinnamon Extract; DFT: Density Function Theory; CAL: Cinnamaldehyde; CA: Cinnamic Acid; CALC: Cinnamyl Alcohol; MW: Molecular Weight; ROTBs: Rotatable Bonds; ROF: Lipinski's Rule of Five; TSA: Trichostatin A; PDB: Protein Data Bank; RMSD: Root Mean Square Deviation; HBA: Hydrogen Bond Acceptor; HBD: Hydrogen Bond Donor; ADMET: Absorption, Distribution, Metabolism, Excretion and Toxicity; FO: Frontier Orbital; HOMOs: Highest Occupied Molecular Orbitals; LUMOs: Lowest Unoccupied Molecular Orbitals; BE: Binding Energy.

Predictors of mortality in patients of poisonous snake bite: Experience from a tertiary care hospital in Central India.

BACKGROUND AND AIMS: This study was undertaken, to assess the clinical parameters in patients of poisonous snakebite, complications which occurred in them, their outcome and to evaluate various clinical predictors of mortality. MATERIALS AND METHODS: Four hundred and thirty-two patients of snake bite were admitted, of which 172 did not show any signs of envenomation and excluded. Two hundred and sixty patients had signs of local or systemic envenomation and included. Complete clinical examination, blood counts, kidney function tests, serum electrolytes, coagulation profile was done in all patients. All received tetanus toxoid and anti-snake venom (ASV). Appropriate supportive treatment was given. Clinical and laboratory parameters were compared between patients who were discharged (Group A) and those who expired (Group B). All data analysis was performed by using stata software version 10 [StataCorp LP, Texas, USA] and SPSS version 11 [SPSS Inc, Chicago, USA]. RESULTS: Out of 260 patients, 58 died and 202 survived. Mean age was 34.97 ± 14.07 years. One hundred and eighty-six (71.5%) patients were from rural areas and 74 (28.5%) from urban. 63.4% of bites occurred during rainy season. One hundred and ninety-seven (75.8%) had bite on lower limb and 62 (23.8%) on upper limbs. All 260 patients (100%) had pain at site of bite, local swelling in 252 (96.9%) and blackening of skin, blebs in 18 (6.9%). Seventy-seven (29.6%) had bleeding tendencies. Ptosis was present in all the 65 patients with signs of neuroparalysis. Eighty (30.8%) patients had acute renal failure. The mean duration of stay in survivors was 7.50 + 4.13 days and in non-survivors it was 3.45 + 3.02 days. Out of 58 who died 18 (31%) patients, succumbed within 24 hrs. On multivariate analysis, significant predictors o mortality were bleeding tendency (P = 0.013), mean PTTK (sec) (P = 0.047), respiratory failure (P = 0.045), shock (P = 0.013), mean ASV dose (cc) (P < 0.001). CONCLUSIONS: Mortality in patients with snake bite can be predicted by simple variables like presence of bleeding tendencies, respiratory failure, and shock. These parameters can help the doctors at peripheral health centers to predict outcome, so that such high risk cases can be referred to higher centers for expertise management without wasting time.

Clinical predictors of acute kidney injury following snake bite envenomation.

BACKGROUND: Snake bite envenomation is a major public health concern in developing countries. Acute kidney injury (AKI) is as important cause of mortality in patients with vasculotoxic snake bite. AIMS: This study was to evaluate the clinical profile of snake bite patients and to determine the predictors of developing AKI following snake bite. MATERIALS AND METHODS: Two hundred and eighty-one patients with snake envenomation were included. Eighty-seven patients developed AKI (Group A) and 194 (Group B) did not. History, examination findings and investigations results were recorded and compared between the two groups. RESULTS: In group A, 61 (70.11%) patients were male and in group B, 117 (60.30%) patients were male. Out of 281 patients, 232 had cellulitis, 113 had bleeding tendencies, 87 had oliguria, 76 had neuroparalysis, and 23 had hypotension at presentation. After multivariate analysis, bite to hospital time (P = 0.016), hypotension (P = 0.000), albuminuria (P = 0.000), bleeding time (P = 0.000), prothrombin time (P = 0.000), hemoglobin (P = 0.000) and total bilirubin (P = 0.010) were significant independent predictors of AKI. CONCLUSIONS: AKI developed in 30.96% of patients with snake bite, leading to mortality in 39.08% patients. Factors associated with AKI are bite to hospital time, hypotension, albuminuria, prolonged bleeding time, prolonged prothrombin time, low hemoglobin and a high total bilirubin.