Correlation of Prognostic Markers {CEA, Ca19.9, Neutrophil To Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR)} With Progression Free Survival (PFS) in Advanced/Metastatic Gallbladder Carcinoma.

Gallbladder carcinoma (GBC) is likely to be diagnosed at progressive stages and shows a very poor prognosis. Combination of gemcitabine and cisplatin (GEMCIS) has been widely used as first line palliative chemotherapy. Prognostic significance of inflammatory markers Neutrophil to lymphocyte ratio (NLR) and Platelet to lymphocyte ratio (PLR) in advanced gallbladder carcinoma (GBC) is not well established. MATERIAL: 30 patients who were diagnosed as advanced/ metastatic gallbladder carcinoma with age more than 18 years were included. All patients who were fit to receive chemotherapy was started on gemcitabine 1000mg/m2 and cisplatin 25mg/m2 (GEMCIS) administered intravenously on days 1 and 8 every 3 weeks. The treatment was repeated for a total of 6 cycles or until the occurrence of unacceptable toxicity, loss to follow up, confirmation of disease progression or death. All the patients underwent Contrast enhanced CT scan along with markers NLR, PLR, carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9) at the baseline and at the end of 3 and 6 cycles of chemotherapy and the tumour response was assessed based on Response Evaluation Criteria in Solid Tumours RECIST 1.1 criteria. Progression free survival was calculated from the date of documentation of best response. The response was correlated with markers CEA, CA19.9, NLR and PLR. OBSERVATION: At a cut-off of NLR (>3 ng/ml) and PLR (>190) predicts progression with a sensitivity of 91% and 100% respectively and both with a specificity of 100%. Out of 30 participants 11 (36.7%) had disease progression (p<0.001). Disease progression noted in 8 participants (26.7%) after 3 cycles (P<0.001) and in 3 participants (13.6%) after 6 cycles of chemotherapy (p <0.001). Disease control rate was 63.33%: 01(3.3%) patient with complete response, 07(23.3%) patients with partial response, 11(36.7%) patients with stable disease. Mean progression free survival in participants associated with progressive disease was 11.45±5.54 weeks (p <0.001). Neutrophil to lymphocyte ratio (NLR) >3 (95%CI 7.6-13.6; log rank test P<0.01) and Platelet to lymphocyte ratio (PLR) >190 (95%CI 7.67-8.83; log rank test p<0.001) were significantly associated with worse progression free survival. CONCLUSION: Increased levels of NLR (>3) and PLR (>190) have prognostic value to predict progression free survival (PFS) in advanced gallbladder carcinoma patients on palliative chemotherapy. NLR and PLR can be used as prognostic markers in advanced gallbladder carcinoma.

Synchrotron-based phase-sensitive imaging of leaves grown from magneto-primed seeds of soybean.

Experiments were conducted to study the effects of static magnetic fields (SMFs) on the venation network of soybean leaves using the synchrotron-based X-ray micro-imaging technique. The seeds of soybean (Glycine max, variety JS-335) were pretreated with different SMFs from 50 to 300 mT in steps of 50 mT for 1 h. The phase-contrast images obtained showed that, as the strength of the SMF increased, the area, width of the midrib, area of the midrib and minor vein of the middle leaflets of third trifoliate leaves also increased up to the SMF strength of 200 mT (1 h) and decreased thereafter. Quantification of the major conducting vein also showed the differences in the major and minor vein structures of the soybean leaves as compared with control leaves. Further, the phase-retrieval technique has been applied to make the segmentation process easy and to quantify the major and minor veins in the venation network. The width and area of midrib enhancement by pre-treatment with SMF implies an enhancement in the uptake of water, which in turn causes an increased rate of photosynthesis and stomatal conductance.

Synchrotron X-ray phase contrast imaging of leaf venation in soybean (Glycine max) after exclusion of solar UV (280-400†nm) radiation.

The hydraulic efficiency of a leaf depends on its vascular structure as this is responsible for transport activities. To investigate the effect of exclusion of UVAB and UVB radiation from the solar spectrum on the micro-structure of leaves of soybean (Glycine max, variety JS-335), a field experiment was conducted using synchrotron-based phase contrast imaging (PCI). Plants were grown in specially designed UV exclusion chambers, and wrapped with filters that excluded UVB (280-315 nm) or UVAB (280-400 nm), or transmitted all the ambient solar UV (280-400 nm) radiation (filter control). Qualitative observation of high-resolution X-ray PCI images obtained at 10 keV has shown the differences in major and minor vein structures of the leaves. The mid-rib width of the middle leaflet of third trifoliate leaves, for all treatments, were obtained using quantitative image analysis. The width of the mid-rib of the middle leaflet of third trifoliate leaves of UVB excluded plants was found to be more compared to leaves of filter control plants, which are exposed to ambient UV. The mid-rib or the main conducting vein transports water and sugars to the whole plant; therefore, mid-rib enhancement by the exclusion of solar UV radiation possibly implies enhancement in the leaf area which in turn causes an increased rate of photosynthesis.

Expression of Neuron-Specific Enolase and Other Neuroendocrine Markers is Correlated with Prognosis and Response to Therapy in Non-Hodgkin Lymphoma.

Objective Non-Hodgkin lymphoma (NHL) is a common hematological malignancy. There is very little known about the expression of neuroendocrine immunohistochemical markers and their clinical significance in NHL due to the paucity of studies. Our objective was to study the expression of neuroendocrine immunohistochemical markers in NHL and correlate with clinical parameters. Materials and Methods All cases diagnosed as NHL on morphology and immunohistochemistry (World Health Organization, 2016 classification) were included in the study. Immunohistochemistry for neuron-specific enolase (NSE), synaptophysin, and chromogranin A was performed. The results were correlated with clinical parameters and response to chemotherapy. Results A total of 66 cases were included in the study with a male-to-female ratio of 3.1:1. The most frequent subtypes observed were diffuse large B-cell lymphoma not otherwise specified and follicular lymphoma. Among the neuroendocrine markers, positivity was observed only for NSE, whereas the other markers were uniformly negative. It was positive in both B- and T-cell lymphomas and in many different subtypes. No relation with the age and sex of the patients was observed. However, NSE-positive cases, more frequently, presented in the advanced stage as compared with NSE negative (61 vs. 38%). All NSE-positive cases showed remission with chemotherapy. Conclusion Among the neuroendocrine immunohistochemical markers, positivity was observed only for NSE. This isolated positivity suggests cross-binding of NSE antibodies with some other isoenzyme of NSE. NSE positivity was associated with higher stage and better response to therapy. Despite this apparent paradox, it is recommended that NSE should be part of routine immunohistochemical panel for NHL.

A Comparative Study of Osteoarthritis Knee Arthroscopy versus Intra-Articular Platelet Rich Plasma Injection: A Randomised Study.

Introduction: Osteoarthritis (OA) is estimated to be the fourth leading cause of disability in the general population. It probably is the most common disease of joints in adults throughout the world. Knee OA accounts for more than 80% of the disease's total burden and as per an estimate in US population, it affects at least 19% of adults aged 45 years and older. This was a randomised study aimed to evaluate the efficacy of platelet rich plasma (PRP) as a treatment modality for osteoarthritis knee in comparison to arthroscopic management. Materials and methods: This study was conducted from 2018 to 2020 at a tertiary care teaching hospital, under reference number ELMC&H/RCELL2019/39. A total of 70 patients of osteoarthritis knee with grade 2-3 according to the Kellgren-Lawrence classification were selected using computer generated random number among them 35 patients were subjected to arthroscopy (Group II) and 35 were administered platelet rich plasma injection (Group I) and evaluated at 3, 6 and 9 months of follow-up. Both the groups were assessed and scored with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analog Pain Scale (VAS) to compare pre-treatment and post-treatment values. As all the patients in the sample was followed-up, resulting into no loss of subjects. Result: Overall, percentage reduction in VAS score at 3 months, 6 months, and 9 months was 24.45±9.09, 18.45±11.60 and 8.29±14.19%, respectively in Group I and 18.96±5.85, 7.33±8.60 and 3.20±7.39%, respectively in Group II. A statistically significant difference between two groups was observed at 3- and 6-months' time intervals only (p<0.05). Overall, percentage reduction in WOMAC score at 3 months, 6 months and 9 months was 24.03±11.41, 17.45±9.24, and 9.49±9.80%, respectively in Group I and 11.27±5.73, 5.70±4.78, and -0.13±5.06%, respectively in Group II. At all the three-time intervals, the difference between two groups was significant statistically (p<0.001). Conclusion: This study suggested that both PRP as well as arthroscopy provide a reduction in WOMAC and VAS scores for pain among cases of knee osteoarthritis. Most effective reduction is observed at three months follow-up which thereafter tends to diminish. Of the two modalities, PRP seemed to have an edge over arthroscopic debridement, however, this efficacy was more pronounced for Kellgren-Lawrence Grade 2 as compared to Grade 3.

Chemotherapy-Induced Nausea and Vomiting: Pathogenesis, Recommendations, and New Trends.

The significant physical and emotional effects of chemotherapy-induced nausea and vomiting (CINV) are experienced by cancer patients. Severe symptoms decrease the patient's quality of life and potentially deters further treatment. The five main forms of CINV (i.e., acute, delayed, anticipatory, breakthrough, and refractory) require different treatment regimens, which often include 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids. Despite a significant amount of research and development of antiemetic agents, management of CINV remains a great challenge with many needs waiting to be adequately addressed, such as controlling non-acute CINV, developing appropriate CINV treatment protocols for multiple-day chemotherapy patients, and providing options for those prone to CINV despite treatment. Further research is required to optimize CINV management for these patients.

Effect of pneumoperitoneum on intracranial pressure during supratentorial craniotomy: a case report.

Laparoscopic surgery has become the method of choice for many procedures previously performed by open techniques. However, its use in patients with a potentially decreased intracranial compliance warrants caution. We report a case of combined glioma excision and laparoscopic cholecystectomy procedures with evaluation of the effects of pneumoperitoneum on ICP and operative field. The clinical implications, safety and recommendations of conducting laparoscopic surgeries in neurosurgical patients are discussed. Performing pneumoperitoneum in patients with marginal intracranial compliance needs interdisciplinary discussions and ICP monitoring is mandatory.

Nanoindentation and scratch studies on magnetron sputtered Ti thin films.

Ti thin films sputter deposited on D9 steel at two different temperatures were studied for their mechanical behavior under static and sliding contact conditions using nanoindentation and scratch tests. The film hardness measured at the surface of the coatings exhibited a value of 2.5 GPa, for both conditions. From the scratch test, it is understood that coatings deposited at 200 degrees C substrate temperature showed superior adhesion strength. Critical load to failure for these coatings was evaluated at 2 N.

Microstructural studies of nanocomposite thin films of Ni/CrN prepared by reactive magnetron sputtering.

Synthesis and characterization of nanocomposites of Ni/CrN thin films prepared by DC magnetron sputtering from a target of 50 wt.%Ni-50 wt.%Cr is investigated. The films prepared as a function of nitrogen flow rate and substrate temperature showed that the films contained Ni and CrN phases with crystallite sizes in the nanometer range. Measurement of nanomechanical properties of the composite films exhibited a significant decrease in the values of hardness and Young's modulus than those of pure CrN films.

Change in biventricular function after cone reconstruction of Ebstein's anomaly: an echocardiographic study.

Aims: The Cone reconstruction in Ebstein's anomaly (EA) aims to reduce tricuspid valve regurgitation (TR) and reposition the valve to the anatomic annulus, but post-operative progress of ventricular function is poorly understood. This study evaluated biventricular function after Cone reconstruction using echocardiographic techniques. Methods and results: A retrospective study assessing longitudinal change was conducted from 2009 to 2014. All symptomatic patients with EA and severe TR undergoing surgery were included. Transthoracic advanced echocardiography was performed pre- and post-operatively (at short-term (<30 days) and mid-term). Conventional and longitudinal 2D strain parameters were measured for left ventricle (LV) and right ventricle (RV). Paired analyses were compared using Wilcoxon Matched-pairs signed rank test. From the 38 patients operated for EA, the echocardiographic data of 17 patients, aged 15 (1-57 years) at operation could be analysed. Median follow up was 6 months (8 days-54 months). The tricuspid annular plane systolic excursion (26.42 ± 5.79 mm vs. 8.75 ± 3.18 mm, P < 0.001), RV fractional area change (FAC) (45.00 ± 8.13% vs. 35.46 ± 5.76%, P = 0.038) and LV 2D peak systolic strain were significantly reduced post-operatively (-20.49 ± 2.79 vs. -17.73 ± 2.76, P = 0.041), with a trend to later recovery for LV 2D strain. There was no evidence of systolic mechanical dys-synchrony before or after operation. Conclusion: Although clinical outcome of Cone reconstruction for EA remains excellent, acute post-operative changes leads to reduction of myocardial function of both ventricles, with a trend to later recovery for LV. Continuing impairment of RV function is multifactorial but may reflect intrinsic myocardial deficiency.

Practical consensus recommendation on when to do BRCA testing.

BRCA-mutation associated breast cancer and to future cancer risks and sensitivity to systemic therapies. Now that rapid genetic testing for BRCA1 and BRCA2 mutations is available, BRCA mutation status can be considered when making treatment and prevention decisions for BRCA testing, BRCA mutation carriers with breast cancer. Expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

Growing Teratoma Syndrome.

Growing teratoma syndrome, a disease characterized by presence of benign metastasis increasing in size and number after chemotherapy, is infrequent occurrence. Being unfamiliar with the disease entity, many oncologists misinterpret it as disease progression. Though the exact etio-pathognesis of the disease is still unidentified, but clinical characteristics are well defined. Being a chemo and radio-resistant disease, surgery offers only cure. We present a case of ovarian immature teratoma, who after chemotherapy presented with increased tumor size. Resected specimen confirms the diagnosis of mature teratoma leading to recognition of GTS. Surgery resulted in cure.

Disseminated histoplasmosis with reactive haemophagocytosis presenting as PUO in an immunocompetent host.

Disseminated histoplasmosis (DH) with reactive haemophagocytosis has been described in literature mainly in immunocompromised hosts. Only sporadic case reports exist in immunocompetent hosts. Here, we present a rare case of DH with reactive haemophagocytosis in an immunocompetent host presenting as PUO.

Chemotherapy-induced palmer planter erythrodysesthesia.

We report a case of palmar plantar erythrodysesthesia (PPE) in a case of acute lymphoblastic leukemia treated with VALP regime. The treating physician must be aware of this uncommon complication of chemotherapeutic agents to avoid unnecessary investigations.

A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model.

HIV-1 reverse transcriptase (RT) is a key enzyme involved in the replication of the virus and is a potential target for therapeutic intervention following infection. Several drugs that inhibit the enzyme from acting have been discovered. These include nucleoside-analogue inhibitors such as AZT (zidovudine), ddI and ddC, and non-nucleoside inhibitors such as nevirapine and delavirdine. All of them, however have been found to be of limited clinical utility because the RT becomes rapidly resistant to them on account of point mutations in the enzyme. One way to partly overcome this limitation is to design an inhibitor that has interactions mainly with the backbone and the conserved residues of RT. Using a rational drug-design approach based on the high resolution X-ray crystal structure of the RT-nevirapine complex (1), and the specific design principles of peptides containing dehydro-Alanine (deltaAla) generated by our theoretical calculations, we present here the design of a peptide inhibitor of RT. Energy minimization and molecular modeling of the interaction of the designed pentapeptide with the nevirapine-binding site indicate that the inhibitor has 60% of its interactions with the conserved regions of RT as compared to 30% in the case of nevirapine, thus making it much less sensitive to mutations in the enzyme.

A proteinase K inhibitor using alpha,beta-unsaturated (dehydro) residues: a presumptive model.

Enzymes of the subtilisin family, of which proteinase K is a member, have been studied extensively on account of their numerous biological applications. Specific inhibitors of the proteinases are of immense importance in regulating their activity so as to protect the cells against uncontrolled proteolysis. Using the specific design principles of peptides containing dehydro-Alanine (deltaAla), generated by our theoretical calculations, we present here the design of an inhibitor of proteinase K. Energy minimization and molecular modeling of the interaction of the designed tetrapeptide with the recognition site of proteinase K indicate that it is an effective inhibitor.