A prospective health economic evaluation to determine the productivity loss due to premature mortality from oral cancer in India.

INTRODUCTION: India contributes two-thirds of the global mortality due to oral cancer and has a younger population at risk. The societal costs of this premature mortality are barely discussed. METHODS: Using the human capital approach, we aimed to estimate the productivity lost due to premature mortality, valued using individual socioeconomic data, related to oral cancer in India. A bottom-up approach was used to prospectively collect data of 100 consecutive patients with oral cancer treated between 2019 and 2020, with a follow-up of 36 months. RESULTS: The disease-specific survival for early and advanced stage was 85% and 70%, with a median age of 47 years. With 671 years lost prematurely, the loss of productivity was $41 900/early and $96 044/advanced stage. Based on population level rates, the total cost of premature mortality was $5.6 billion, representing 0.18% of GDP. CONCLUSION: India needs to implement tailored strategies to reduce the economic burden from premature mortality.

Areca nut and oral cancer.

INTRODUCTION: The association between areca nut consumption and oral cancer has been a subject of increasing concern in global public health. GLOBAL PERSPECTIVE: Areca nut, often chewed in various forms such as betel quid, is deeply rooted in cultural practices across Asia and other parts of the world. Epidemiological studies consistently reveal a significant correlation between areca nut use and the incidence of oral cancer, emphasizing the need for targeted preventive measures. The complex interplay of areca nut's bioactive compounds, particularly arecoline, with cellular processes, contributes to the initiation and progression of oral carcinogenesis. Mechanistic insights into the genotoxic and cytotoxic effects of its components underscore the urgency for comprehensive public health interventions. PUBLIC HEALTH: Efforts to address this public health challenge involve multidisciplinary approaches, encompassing education, policy implementation, and behavioral interventions. Understanding the socio-cultural factors influencing areca nut consumption is pivotal for designing effective awareness campaigns and cessation programs. CONCLUSION: As oral cancer remains a significant global health burden, unraveling the nuanced relationship between areca nut and its role in oral carcinogenesis is crucial for advancing preventive strategies and mitigating the impact of this modifiable risk factor.

Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer.

Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative. By comprehensively analyzing structure studies in the context of the binding epitope of FasL and various preclinical Fas agonist antibodies, we characterize a highly significant patch of positively charged residue epitope (PPCR) in its cysteine-rich domain 2 of Fas. PPCR engagement is indispensable for superior Fas agonist signaling and CAR-T bystander function in ovarian tumor models. A single-point mutation in FasL or Fas that interferes with the PPCR engagement inhibited apoptotic signaling in tumor cells and T cells. Furthermore, considering that clinical and immunological features of the autoimmune lymphoproliferative syndrome (ALPS) are directly attributed to homozygous mutations in FasL, we reveal differential mechanistic details of FasL/Fas clustering at the PPCR interface compared to described ALPS mutations. As Fas-mediated bystander killing remains vital to the success of CAR-T therapies in tumors, our findings highlight the therapeutic analytical design for potentially effective Fas-targeting strategies using death agonism to improve cancer immunotherapy in ovarian and other solid tumors.

A Comparative Analysis of Phytochemicals, Metal Ions, Volatile Metabolites in Heart Wood, Stem Bark and Leaves of Salix alba L. along with in Vitro Antioxidant, Antacid, Antimicrobial Activities for Sake of Environment Conservation by Substitution of Stem Bark With Leaf.

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.

Quantification of Phytochemicals and Metal Ions as well as the Determination of Volatile Compounds, Antioxidant, Antimicrobial and Antacid Activities of the Mimosa pudica L. Leaf: Exploration of Neglected and Under-Utilized Part.

Mimosa pudica L. (MP) is well-known plant in traditional medicinal system, especially in India. Unfortunately, leaves of MP are less explored. To determine the food and nutritional value of the neglected part of Mimosa pudica L. (MP), that is MP leaves, phytochemicals and metal ions of MP were quantified by newly developed HPLC and ICPOES-based methods. The content of phytochemicals observed using HPLC analysis for chlorogenic acid, catechin, and epicatechin was 141.823 (±8.171), 666.621 (±11.432), and 293.175 (±12.743) µg/g, respectively. Using GC/MS/MS analysis, fatty acid like oleic acid were identified. In ICP-OES analysis, a significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The observed TPC and TFC for MP leaf extracts was 44.327 (±1.041) mg GAE/ g of wt. and 214.217 (±4.372) mg QCE/ g of wt., respectively. The DPPH assay depicted a strong antioxidant activity of MP leaf extracts with IC50 values of 0.796 (±0.081) mg/mL and a TEAC value of 0.0356 (±0.0003). A significant antacid activity (666 mg MP+400 mg CaCO3 >400 mg CaCO3 ≫666 mg Gelusil) of MP leaves was noticed. The methanolic extract of MP leaves demonstrated anti-microbial activity against Staphylococcus aureus (15±2mm), Pseudomonas aeruginosa (12±2mm) and Escherichia coli (10±2mm). In silico studies confirmed the in vitro results obtained for antioxidant, antiacid, and anti-microbial activities. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the MP leaves. In summary, this study demonstrated the medicinal significance of MP leaves and the conversion of agro-waste or the under-utilized part of MP into pharmaceutical potent materials. Consequently, the present study highlighted that MP leaves alone have medicinal importance with good nutritional utility and possess large promise in the pharma industry along with improving bio-valorization and the environment.

Prognostic Impact of Poor Differentiation of Squamous Cell Carcinoma in Treatment Naïve Node-Negative Early Oral Cancers.

We have conducted this study to understand the impact of poor differentiation (PD), as a sole poor prognostic factor, in early oral cancers. This was a retrospective analysis of a prospectively maintained database of clinically node-negative early T stage OSCC patients operated between 2012 and 2014. Impact of PD on the survival and role of adjuvant therapy in these patients was noted. Out of 1172 patients screened, 280 patients were found to be eligible for the study. 11.4% patients had PDSCC. It was found to be associated with tongue cancers and peri-neural invasion. It had a significant impact on OS and DFS (48.7 months vs 81.4 months, p < 0.00 and 44.6 months vs 73.5 months, p < 0.00 respectively. Hazard ratio for DFS: 4.08. Although patients with PDSCC had better survival with radiotherapy, but this was not statistically significant. Poor differentiation as a stand-alone factor impacts survival in patients with early oral cancer. It may be seen more often in patients with tongue cancer and may have associated PNI. The role of adjuvant therapy in such patients is not clear.

Can Patients Accurately Recall their Preoperative Pain and Functional Scores Following Rotator Cuff Repair and Total Shoulder Arthroplasty?

Objectives: Accurate analysis of preoperative shoulder pain and function is important for understanding treatment efficacy and producing high-quality research. Oftentimes, preoperative patient-reported outcomes (PROs) are missing. Therefore the accuracy of recalled preoperative PROs may be important. We investigate the ability of patients who underwent rotator cuff repair (RCR) or shoulder arthroplasty (TSA) to recall their preoperative PROs. Methods: We identified 145 patients who underwent either RCR or TSA and had preoperative PROs. All patients completed the ASES, SANE, SST, and VAS surveys within 3 months prior to surgery. Patients were contacted between one and four years after surgery and asked to recall their baseline pain and shoulder function prior to surgery. The mean difference was calculated by determining the difference between the mean recalled score and the mean actual score. Intraobserver reliability analysis was performed, comparing recall and actual score for each using the 2-way mixed-effects intraclass correlation coefficient (ICC) model. The ICC values > 0.75 were considered excellent, values between 0.4 and 0.75 were considered moderate, and values of < 0.4 demonstrated a weak agreement. Results: For patients who underwent RCR, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 6.3 (P=0.004), 2.0 (P=0.155), -0.04 (P=0.625) and - 1.0 (P<0.001), respectively. In patients who underwent TSA, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 4.5 (P =0.038), -3.9 (P=0.262), -1.2 (P=0.001) and -1.5 (P<0.001), respectively. ASES, SST, and VAS show moderate reliability, and SANE reliability was weak in both RCR and TSA populations. Patients had a tendency to recall higher pain scores than actual preoperative pain scores. Conclusion: In patients who underwent RCR or TSA, there was too much variability between individual patient's ability to accurately recall preoperative pain and function to reliably use recall data for research purposes.

What Can We Still Learn from Brain Autopsies in COVID-19?

Neuropathological findings have been published from ∼900 patients who died with or from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, representing less than 0.01% of the close to 6.4 million deaths reported to the World Health Organization 2 years into the coronavirus disease 2019 (COVID-19) pandemic. In this review, we extend our prior work summarizing COVID-19 neuropathology by including information on published autopsies up to June 2022, and neuropathological studies in children, COVID-19 variants, secondary brain infections, ex vivo brain imaging, and autopsies performed in countries outside of the United States or Europe. We also summarize research studies that investigate mechanisms of neuropathogenesis in nonhuman primates and other models. While a pattern of cerebrovascular pathology and microglial-predominant inflammation remains the primary COVID-19-associated neuropathological finding, there is no singular understanding of the mechanisms that underlie neurological symptoms in acute COVID-19 or the post-acute COVID-19 condition. Thus, it is paramount that we incorporate microscopic and molecular findings from brain tissue into what we know about the clinical disease so that we attain best practice guidance and direct research priorities for the study of the neurological morbidity of COVID-19.

Determining the impact of COVID-19 pandemic on adjuvant therapy for oral cancer - A matched-pair analysis.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has hard-pressed the health care systems beyond their capabilities, causing a lack of appropriate cancer treatment delivery. The aim of this study was to assess the impact of pandemic-related restrictions on adjuvant therapy delivery for oral cancer patients during these demanding times. Materials and Methods: Oral cancer patients who were operated on between February and July 2020 and scheduled to receive prescribed adjuvant therapy during the COVID-19-related restrictions (Group I) were included in the study. The data were matched for the length of hospital stay and type of prescribed adjuvant therapy, with a set of patients who were similarly managed 6 months preceding the restrictions (Group II). Demographic and treatment-specific details, including inconveniences faced in procuring prescribed treatment, were obtained. Factors associated with delay in receiving adjuvant therapy were compared using regression models. Results: A total of 116 oral cancer patients were considered for analysis, comprising 69% (n = 80) adjuvant radiotherapy alone and 31% (n = 36) concurrent chemoradiotherapy. The mean hospital stay was 13 days. In Group I, 29.3% (n = 17) of patients were not able to receive any form of their prescribed adjuvant therapy at all, which was 2.43 times higher than Group II (P = 0.038). None of the disease-related factors significantly predicted delay in receiving adjuvant therapy. Of the delay, 76.47% (n = 13) was present during the initial part of the restrictions, with the most common reason being unavailability of appointments (47.1%, n = 8), followed by inability to reach treatment centers (23.5%, n = 4) and redeem reimbursements (23.5%, n = 4). The number of patients who were delayed the start of radiotherapy beyond 8 weeks after surgery was double in Group I (n = 29) than in Group II (n = 15; P = 0.012). Conclusions: This study highlights a small part of the rippling effect the COVID-19 restrictions have on oral cancer management and pragmatic actions may be needed by policymakers to deal with such challenges.

Patients With Mild Osteoarthritis Are Less Likely to Achieve a Clinically Important Improvement in Pain or Function After Anatomic Total Shoulder Arthroplasty.

BACKGROUND: The severity of glenohumeral osteoarthritis (OA) as demonstrated by preoperative radiographs and patient-reported pain plays an important role in the indication for anatomic total shoulder arthroplasty (aTSA). In hip and knee research, data about the effect of the severity of preoperative radiographic OA on the outcome of total joint arthroplasty have been mixed. For shoulder replacement, we are unsure of the effects of radiographic severity on outcomes. QUESTIONS/PURPOSES: This study investigated whether the preoperative radiographic severity of glenohumeral OA is associated with improvement in pain and function after aTSA. We asked, (1) does the severity of glenohumeral OA correlate with improvement in patient-reported outcomes after TSA (delta American Shoulder and Elbow Surgeons score [postoperative-preoperative], delta Single Assessment Numeric Evaluation, delta Simple Shoulder Test, and delta VAS)? (2) Is having mild osteoarthritis associated with not meeting the minimum clinically important differences in preoperative and postoperative American Shoulder and Elbow Surgeons scores? METHODS: An institutional query of patients who underwent aTSA for OA was performed between January 2015 and December 2018. A total of 1035 patients were eligible; however, only patients with adequate preoperative radiographs and patient-reported outcome measures collected preoperatively and at a minimum of 2 years postoperatively were included. Patients with proximal humerus fractures, inflammatory arthropathy, cuff tear arthropathy, prior ipsilateral rotator cuff repair, brachial plexus injury or neuromuscular disorder, workers compensation, periprosthetic joint infection, or revision surgery within 2 years were excluded. Patient characteristics, comorbidities, and prior shoulder surgery were recorded. The severity of OA was classified based on the modified Samilson-Prieto and Walch classification. The association between Samilson-Prieto grade and patient-reported outcome measures (American Shoulder and Elbow Surgeons Score, Single Assessment Numeric Evaluation, Simple Shoulder Test, and VAS score) was evaluated. Radiographic characteristics, patient demographics, comorbidities, and prior surgery were also evaluated for the potential risk of not achieving improvement in the minimum clinically important difference (16.1) with respect to the American Shoulder and Elbow Surgeons score. The American Shoulder and Elbow Surgeons score is scored 0 to 100, with higher scores representing less pain and better function. A total of 206 patients (20% of those eligible) with a mean follow-up of 2.3 years were included. Twenty-three patients had Samilson-Prieto Grade I, 38 had Grade II, 57 had Grade III, and 88 had Grade IV. RESULTS: There were no differences in improvements (delta) between the groups and between patient-reported outcome scores (American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation, Simple Shoulder Test, and VAS). Compared with patients with more severe osteoarthritis (Samilson-Prieto Grades II, III, and IV), a higher proportion of patients with less severe osteoarthritis (Grade I) did not exceed the minimum clinical important difference for the American Shoulder and Elbow Surgeons score (22% [five of 23] versus 4% [seven of 183]; odds ratio 0.14 [95% confidence interval 0.04 to 0.520]; p = 0.006). CONCLUSION: The improvement in patient-reported outcome measure scores was similar regardless of radiographic severity after aTSA. Surgeons should use caution when recommending surgery to patients with less severe OA because a higher percentage did not improve, based on the minimum clinically important difference. LEVEL OF EVIDENCE: Level III, therapeutic study.

Status and Determinants of Early Detection of Oral Premalignant and Malignant Lesions in India.

It has been over four decades since the launch of the National Cancer Control Programme in India, yet the cancer screening rates for oral cancer remain unremarkable. Moreover, India is bracing a large burden of oral cancer with poor survival rates. An effective public health programme implementation relies on a multitude of factors related to cost-effective evidence-based interventions, the healthcare delivery system, public health human resource management, community behaviour, partnership with stakeholders, identifying opportunities and political commitment. In this context, we discuss the various challenges in the early detection of oral premalignant and malignant lesions and potential solutions.

Structural investigation of Ayurveda Lauha (Iron) Bhasma.

In Ayurveda, 'Lauha' (Iron) Bhasma is primarily used to cure diseases related to iron deficiency in humans. It is produced from purified raw metallic iron using a combination of multi-step traditional preparation processes described in the Ayurveda literature. Here, we present the results of structural investigation performed on the medicinal grade 'Lauha' Bhasma using various X-ray based techniques. Our results indicate that after several rounds of heating and cooling in specific conditions following the Ayurvedic preparation procedure, metallic iron eventually converts to a natural iron-oxide mineral belonging to the magnetite group. Scanning electron microscopy (SEM) and X-ray standing wave assisted fluorescence measurements carried out on powdered Bhasma specimen reveal that the magnetite micro-particles in the Bhasma specimen are usually present in the form of agglomerates of nano-particles. We anticipate that the Ayurvedic Lauha Bhasma has great potential for noninvasive localized target killing of cancer cells, particularly in sensitive parts of the human body such as the brain, spinal cord, and lungs, via necrosis by application of an alternating external magnetic field or photo electron generation through X-rays.

Factors associated with functional improvement after posteriorly augmented total shoulder arthroplasty.

BACKGROUND: Posteriorly augmented glenoid components in anatomic total shoulder arthroplasty (TSA) address posterior glenoid bone loss with inconsistent results. The purpose of this study was to identify preoperative and postoperative factors that impact range of motion (ROM) and function after augmented TSA in patients with type B2 or B3 glenoid morphology. METHODS: This was a retrospective review of all patients who underwent TSA with a step-type augmentation performed by a single surgeon between 2009 and 2018. Patients with Walch type B2 or B3 glenoids were included. Outcomes included forward elevation (FE), external rotation (ER), internal rotation (IR), Single Assessment Numeric Evaluation (SANE) score, and visual analog scale pain score. Preoperative imaging was reviewed to assess glenoid retroversion and posterior humeral head subluxation relative to the scapular body and midglenoid face. Postoperative measurements included glenoid retroversion, subluxation relative to the scapular body, subluxation relative to the central glenoid peg, and center-peg osteolysis. Measurements were performed by investigators blinded to ROM and functional outcome scores. RESULTS: Fifty patients (mean age, 68.1 ± 8.0 years) with a mean follow-up period of 42.0 months (range, 24-106 months) were included. Glenoid morphology included type B2 glenoids in 41 patients and type B3 glenoids in 9. One patient had center-peg osteolysis, and 1 patient had glenoid component loosening. Average preoperative FE, ER, and IR were 110°, 21°, and S1, respectively. Average postoperative FE, ER, and IR were 155°, 42°, and L1, respectively. The mean postoperative visual analog scale score was 0.5 ± 0.8, and the mean SANE score was 94.5 ± 5.6. Type B3 glenoids were associated with better postoperative IR compared with type B2 glenoids (T10 vs. L1, P = .024), with no other differences in ROM between the glenoid types. Preoperative glenoid retroversion did not significantly impact postoperative ROM. Postoperative glenoid component retroversion and residual posterior subluxation relative to the scapular body or glenoid face did not correlate with ROM in any plane. However, posterior subluxation relative to the glenoid face was moderately associated with lower SANE scores (r = -0.448, P = .006). CONCLUSION: Patients achieved excellent functional outcomes and pain improvement after TSA with an augmented glenoid component. Postoperative ROM and function showed no clinically important associations with preoperative or postoperative glenoid retroversion or humeral head subluxation in our cohort of posteriorly augmented TSAs, except for worse functional scores with increased humeral head subluxation in relation to the glenoid surface.

Multiparametric analysis of carotid body tumours: a pictorial essay.

Carotid body tumours (CBT), also called carotid body paraganglioma, are highly vascular and histologically portray paraganglion cells. They are typically found at the carotid bifurcation and result in the splaying of the internal and external carotid arteries (ICA and ECA). Recent literature supports the role of chronic hypoxia in the etiology of CBT. This pictorial essay discusses how CBT is an uncommon etiology for common clinical problems such as transient ischemic attacks. It also discusses imaging techniques to precisely map out the tumour for surgical resection using advanced imaging modalities and techniques.

Impact of Changes in Treatment Paradigms on Survival in Oral Squamous Carcinoma-a Population-Level Study.

There have been notable improvements in the treatment of oral cancers. The objective of this study was to see whether these improvements have translated into survival benefits at the population level from the SEER database. This is a retrospective study using the SEER 19 Custom database which included patients diagnosed with oral cancer between January 1, 1995, and December 31, 2015. The overall stage, age, sex, and treatment modalities were the covariates. For analysis, the patients were divided into four cohorts as per their year of diagnosis-cohort I included patients who were diagnosed between 1995 and 2000 (n = 3873), cohort II between 2001 and 2005 (n = 5881), cohort III between 2006 and 2010 (n = 6233), and cohort IV between 2011 and 2015 (n = 12567). Patients undergoing surgery with adjuvant therapy have increased significantly across cohorts and there is a significant fall in patients undergoing non-surgical treatment. Pairwise comparison by the Mantel-Cox test showed that cohort IV had significantly improved median overall survival (OS) and disease-specific survival (DSS) as compared to other cohorts and there was a significant impact of treatment modality on OS and DSS, especially in cohorts III and IV (p<0.001). Though geographical variations in the presentation and habits limit the generalization of these results, this study demonstrates that the changes and improvements in treatment paradigms incorporating level I evidence and surgical techniques have translated into improved survival outcomes at the population level. We recommend further studies on the local population to lend further credence to our observation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01790-0.

Bacterial chitinases: genetics, engineering and applications.

Chitinases are a group of enzymes that catalyze chitin hydrolysis and are present in all domains of life. Chitinases belong to different glycosyl hydrolase families with great diversity in their sequences. Microorganisms such as bacteria and fungi produce chitinases for nutrition, and energy, and to parasitize the chitinous hosts. But chitinases from bacteria are of special interest due to their ubiquitous nature and ability to perform under extreme conditions. Chitinases produced by bacteria have been explored for their use in agriculture and industry. In agriculture, their main role is to control chitin-containing insect pests, fungal pathogens, and nematodes. In the seafood industry, they found their role in the management of processing wastes which are mainly chitinous substances. Chitinases are also used to synthesize low molecular weight chitooligomers which are proven bioactive compounds with activities such as anti-tumour, antimicrobial, and immunity modulation. Considering their importance in ecology and biotechnological applications, several bacterial chitinases have been studied in the last two decades. Despite their potential, bacterial chitinases have a few limitations such as low production and lack of secretion systems which make the wild-type enzymes unfit for their applications in industries and other allied sectors. This review is an attempt to collate significant works in bacterial chitinases and their application in various industries and the employment of various tools and techniques for improvement to meet industrial requirements.

Incidence and impact of skip metastasis in the neck in early oral cancer: Reality or a myth?

OBJECTIVES: Varying evidence exists surrounding skip metastasis in clinically node-negative oral cancer. We aim to report its incidence, identify factors predicting its presence, and determine survival outcomes to possibly decide "adequacy" of neck dissection for this select group. METHODS: A review of audit records (clinical and pathologic) was undertaken to identify early stage (cT1/T2 cN0) oral squamous carcinoma patients operated between January 2016 and December 2020. Skip metastasis was defined as presence of nodal metastases distant from the primary tumour and at a lower level without metastases at levels above this. The factors predicting its presence were determined using chi-square and multivariate tests. Survival analysis was performed using Kaplan-Meier and regression hazard models. RESULTS: Occult metastasis rate was 17.9 % among 761 patients, with 47.1 % travelling to level I. Skip metastasis at level III was seen in 1.2 % and level IV was 0.3 %. Presence of PNI predicted the presence of skip metastasis at level III (p = 0.041, OR-0.241, 95 %CI 0.062-0.942) and no significant factors were identified for level IV. The 5-year disease-free survival was significantly reduced with isolated level IV metastasis (50 % vs 79.6 %, p = 0.017). Isolated occult metastasis at level Ia was in 0.3 %, all from tongue cancers. Their presence did not impact the 5-year overall survival (100 % vs 90.7 %, p = 0.628) and disease-specific survival (100 % vs 92.5 %, p = 0.675). CONCLUSION: The negligible incidence of skip metastasis to level IV in a clinically node negative neck suggests that clearance up to level III might be adequate in a large majority of patients.

Regression Derived Staging Model to Predict Overall and Disease Specific Survival in Patients With Major Salivary Gland Carcinomas With Independent External Validation.

PURPOSE: The current American Joint Cancer Committee (AJCC) staging system for salivary gland tumors does not include histology and grade in its classification despite their proven prognostic importance. We planned to analyze if a modified staging system integrating these two factors into the staging improves prognostic performance and then validate it externally. MATERIALS AND METHODS: From SEER database (2000-2018), patients with major salivary gland carcinoma who underwent surgical resection between 2004 and 2015 were analyzed. Histologies were recoded into two groups based on grade and type of histology into "Low Aggression" and "High aggression" groups. Cox proportional hazards model was used to identify predictor variables for overall survival and disease-specific survival and models were generated based on least absolute shrinkage and selection operator regression. Model performance was evaluated by Akaike Information Criterion, concordance index and calibration plot. The best model chosen was externally validated from our hospital database of patients who underwent surgery for salivary gland tumor between January 1, 2012 to December 31, 2019. RESULTS: Six thousand two hundred forty-six patients were analyzed with a median follow up of 58 months. Age > 65 years, male sex, metastatic disease, Histological Stratification, Grade of tumor, AJCC stage and Primary Site were the significant factors influencing overall survival and disease-specific survival. By least absolute shrinkage and selection operator regression method, Correlation analysis and Interaction testing by multiple regression, AJCC stage and Histological Risk stratification were used for generating four models, out of which the best model was selected by Akaike Information Criterion, C index and calibration plot. This model was then externally validated in our hospital database of 269 patients. CONCLUSION: We propose an externally validated modified salivary gland staging system that incorporates histology and grade of tumor for improved hazard discrimination among patient subgroups.