Depth of Invasion, Lymphovascular Invasion, and Perineural Invasion as Predictors of Neck Node Metastasis in Early Oral Cavity Cancers.

Aims: The present study examines the role of demographic and pathological features of primary tumours in predicting neck metastasis in early oral cavity cancers, which has been a matter of debate. Methods: A single-centre, retrospective, institution review was conducted of all the patients presented to our centre from January 2014 to December 2021. Patient characteristics were compared between the two lymph node groups (lymph node positive and lymph node negative) and significant prognostic factors were determined. Results: A total of 462 oral squamous cell carcinoma (OSCC) patients were included, 407 male and 55 female. Tobacco chewing (59.2%) was a major habit with buccal mucosa (49.5%) and tongue (44.8%) as primary sites. The majority of the patient's histology was of SCC (96.8%) with grade II (moderately differentiated, 74.5%). Univariate logistic regression analysis to predict lymph node metastasis showed pT size (< 0.001), LVI (< 0.001), and PNI (< 0.001) as significant tumor characteristics. On multivariate, pT size (OR-1.58, P - 0.0001) and LVI (OR-19.70, P - 0.0001) were reported to be statistically significant to predict lymph node metastasis. Conclusion: Reporting and studying the clinico-pathological features of primary tumors can give vital information in predicting the neck node metastasis in OSCC patients.

The predictive role of neutrophil-to-lymphocyte ratio in the outcomes of patients with sarcomatoid carcinoma of oral cavity.

INTRODUCTION: The aim of the present study was to evaluate the prognostic value of the inflammatory response biomarkers and their impact on survival outcomes in the patients with sarcomatoid carcinoma (SC) of oral cavity, a rare variant of squamous cell carcinoma (SqC). MATERIALS AND METHODS: Seventeen patients diagnosed with SC of oral cavity without metastases treated between Jan 2017 to June 2020 were identified and included in the present study. Pre- and post-operative inflammatory biomarkers and other prognostic markers were evaluated and their impact on disease-free survival (DFS) and overall survival (OS) was studied. RESULTS: Seventeen patients (16 males and one female) were included in the present study with a median age of 42 years (IQR: 26-76 years). With the median follow-up of 15 months, nine of 17 patients had developed recurrence and were succumbed to either locoregional recurrence or distant progression. One-year Kaplan-Meier estimates of DFS and OS were 57% and 58.3% respectively. On univariate analysis, baseline NLR, PLR, and pathological bone/skin involvement were identified to be significant prognostic factors affecting the patient's DFS and OS. On multi-variate analysis, baseline NLR > 3 and pathological bone or skin involvement by tumour were emerged as some independent significant predictors. CONCLUSION: For the first time, the predictive role of inflammatory markers is studied and proven significant affecting patients' survival outcomes. Hence, these inflammatory biomarkers may be considered for routine clinical use as reliable and low-cost prognostic markers to tailor the management of SC of oral cavity.

Dipeptidyl peptidase-IV inhibitory action of Calebin A: An in silico and in vitro analysis.

BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, the enhancers of incretin are used for the treatment of diabetes. The non-glycaemic actions of these drugs (under developmental stage) also proved that repurposing of these molecules may be advantageous for other few complicated disorders like cardiovascular diseases, Parkinson's disease, Alzheimer's disease, etc. OBJECTIVE: The present study was aimed to investigate the DPP-IV inhibitory potential of Calebin-A, one of the constituents of Curcuma longa. MATERIAL AND METHODS: The phytoconstituent was subjected for various in silico studies (using Schrödinger Suite) like, Docking analysis, molecular mechanics combined with generalized Born model and solvent accessibility method (MMGBSA) and Induced fit docking (IFD) after validating the protein using Ramachandran plot. Further, the protein-ligand complex was subjected to molecular dynamic simulation studies for 50 nanoseconds. And finally, the results were confirmed through enzyme inhibition study. RESULTS: Insilico results revealed possible inhibitory binding interactions in the catalytic pocket (importantly Glu205, Glu206 and Tyr 662 etc.) and binding affinity in terms of glide g-score and MMGBSA dG bind values were found to be -6.2 kcal/mol and -98.721 kcal/mol. Further, the inhibitory action towards the enzyme was confirmed by an enzyme inhibition assay, in which it showed dose-dependent inhibition, with maximum % inhibition of 55.9 at 26.3 µM. From molecular dynamic studies (50 nanoseconds), it was understood that Calebin A was found to be stable for about 30 nanoseconds in maintaining inhibitory interactions. CONCLUSION: From the in silico and in vitro analysis, the current research emphasizes the consideration of Calebin A to be as a promising or lead compound for the treatment of several ailments where DPP-IV action is culprit.

Predictors of Weight Loss in Patients With Head and Neck Cancer Receiving Radiation or Concurrent Chemoradiation Treated at a Tertiary Cancer Center.

BACKGROUND: Radiation therapy (RT) has remained the mainstay treatment approach for head and neck cancers. Weight loss due to tumor or tumor-related factors remains a major health issue among head and neck cancer patients. METHODS: A total of 357 patients were identified for the study. Possible weight-loss predictors were determined in the patients undergoing RT based on the patient demographics, tumor site, and treatment characteristics. RESULTS: The mean age of patients was 52 years, whereas the median age was 51 years (range, 18-87). Two hundred and thirteen (66%) patients had oral cavity cancers, 43 (14%) had oropharyngeal cancer, 26 (8%) had hypopharyngeal cancer, 13 (6%) had larynx cancer, and 19 (6%) had other site involvement. A total of 192 patients received 3-dimensional conformal radiation therapy (3DCRT), whereas 127 patients received intensity modulated radiation therapy-image guided radiation therapy (IMRT-IGRT), 212 (66%) received concurrent chemotherapy, and 107 (34%) patients did not receive concurrent chemotherapy. A total of 127 (40%) of the patients gained weight during the first week of RT; on the other hand, maximum weight loss among patients was occurred during the third and fourth weeks of RT. CONCLUSION: Analysis by logistic regression determined there is significant weight loss (>10%) in patients receiving radical RT as compared with adjuvant RT. Better outcomes were observed in patients receiving RT by IMRT-IGRT technique as compared with 3DCRT technique.

The Blood Brain Barrier and its Role in Alzheimer's Therapy: An Overview.

BACKGROUND: Alzheimer's disease (AD) is the most frequent age related neurodegenerative disorder. It represents 70% of all dementia. Millions of people have been affected by AD worldwide. It is a complex illness characterized pathologically by accumulation of protein aggregates of amyloid and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein. AD requires drugs that can circumvent the blood-brain barrier (BBB) which is not a simple physical barrier between blood and brain, but acts as an iron curtain, allowing only selective molecules to enter the brain. Unfortunately, this dynamic barrier restricts transport of drugs to the brain; due to which, currently very few drugs are available for AD treatment. OBJECTIVE: The present review focuses mainly on strategies used for administration of drug to the CNS by-passing BBB for the treatment of AD. RESULTS: Many studies have proved to be effective in overcoming BBB and targeting drugs to CNS by using different strategies. Here we have discussed some of the most important drug permeability and drug targeting approaches. CONCLUSION: In conclusion, concentrating solely in development of drug discovery programs is not enough but it is important to maintain balance between the drug discovery and drug delivery systems that are more specific and effective in targeting CNS of AD patients.

Status Epilepticus: An Overview.

Status epilepticus (SE) is an emergency situation, where immediate and effective treatment is required in least possible time as it is associated with neuronal damage, systemic complications, substantial morbidity and mortality depending on status type, duration, age and etiology. In the past few years, morbidity and mortality rate were improved, probably may be due to aggressive use of anti-epileptic drugs in emergency situations. Present literature gives an overview of the conditions leading to SE and its management guidelines in hospital and out of hospital setting emphasizing on the available drug therapies.

A pharmacological overview of lamotrigine for the treatment of epilepsy.

INTRODUCTION: Epilepsy is one of the most common neurological disorders, affecting about 2% of the population worldwide. Lamotrigine (LTG) is a second generation anti-epileptic drug (AED) with broad spectrum of activity, a favourable side-effect profile, simpler dosing than earlier drugs and efficacious in diverse epilepsy syndromes. Areas covered: The present review focuses on pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of LTG and its effect on cognition, psychiatry, quality of life, women and pregnancy along with effect of enzyme inducing and enzyme inhibiting drugs over LTG and their effect on serum level fluctuations by collecting data from various studies over the years until 2016. Expert commentary: Results from various studies and clinical trials indicate that LTG possessed a favourable profile of anticonvulsant activity and good tolerability as a monotherapy/or add-on therapy in children and adult patients against several types of seizures and syndromes. It has wide clinical dose range with favourable pharmacokinetic properties making it an excellent therapeutic option in epilepsy.

A novel vesicular transdermal delivery of nifedipine - preparation, characterization and in vitro/in-vivo evaluation.

Nifedipine is a calcium channel blocker extensively used in the treatment of anginal and hypertension. On oral administration it undergoes extensive first pass metabolism, which outweighs its absorbance through gastrointestinal tract (GIT) and bioavailability of the drug in systemic circulation. As an alternative to oral route transdermal route of drug delivery was developed. In the present investigation, proniosomes are prepared by varying the ratio of span-40, lecithin, aqueous phase and polymer. Formulation containing span-40, lecithin, isopropyl alcohol, 0.1% glycerol (5:5:4) and HPMC (2%) showed smaller vesicle size, high entrapment efficiency. The niosomal formation after hydration and their surface morphology of optimized formulation was studied by Motic and transmission electron microscopy. FTIR and differential scanning calorimetry studies were performed to unravel and understand the solid state properties of the drug and chemical interaction with formulation excipients. The ex-vivo Franz-diffusion studies were carried out in pH 6.8 using rat skin and the results showed better permeability of niosomes with good steady state flux and enhancement ratio suggesting the potential of proniosomal carriers for improved transdermal delivery of nifedipine. Skin irritation studies for 7 days, showed that the drug when formulated as proniosomes to be non-irritant with no erythemia development compared to pure drug. From the bio-distribution studies, the vesicles prepared with hydroxy propyl methyl cellulose with span-40 was found to be ideal batch as the concentration of drug at target site was higher.

A review on novel vesicular drug delivery: proniosomes.

Nanotechnology has brought a revolution in the field of science, which has subsequently lead to development of novel dosage forms such as niosomes, liposomes and proniosomes. Proniosomes overcome the demerits involved with niosomal and liposomal drug delivery systems. Proniosomes are liquid crystalline compact niosome hybrids which upon hydration form niosomes. They help in reducing physical stability problems involved with niosomes such as leaking, fusion, aggregation and provide convenience in dosing, distribution, transportation and storage showing improved results than conventional niosomes. This review focuses on different aspects of proniosome such as preparation, characterization, drug release, applications, merits, demerits, present scenario in market and future trends.