Cholera Dynamics and the Emergence of Pandemic Vibrio cholerae.

Cholera is a severe diarrheal disease caused by the aquatic bacterium Vibrio cholerae. Interestingly, to date, only one major clade has emerged to cause pandemic disease in humans: the clade that encompasses the strains from the O1 and O139 serogroups. In this chapter, we provide a comprehensive perspective on the virulence factors and mobile genetic elements (MGEs) associated with the emergence of pandemic V. cholerae strains and highlight novel findings such as specific genomic background or interactions between MGEs that explain their confined distribution. Finally, we discuss pandemic cholera dynamics contextualizing them within the evolution of the bacterium.

Bilateral Microvascular Submandibular Gland Transfer with Implantation of Wharton's Duct in Superior Conjunctival Fornix: A Vision-Saving Procedure for Severe Dry Eye Disease.

Dry eye can initially cause mild symptoms of irritation and may rapidly progress to corneal scarring and blindness. Tear substitutes can only help for mild cases. With the advancement in microsurgical techniques, an option of transferring vascularized salivary glands has shown positive results. We present a case of a 5-year-old boy with congenital alacrimia with ocular surface damage. Vascularized autologous submandibular gland transfer was considered as a viable option for this patient. We performed the gland transfer in two separate stages for the two eyes (1 year 5 months apart). The patient was evaluated for up to 2 years for the right eye and for 7 months for the left eye. Dry eye workup showed drastic improvement (right > left). Biochemical analysis showed gradual transition to resemble that of natural tears. This procedure can result in significant symptomatic improvement and can be a promising treatment option for cases of severe dry eye.

Volume and Location of the Defect as Predictors of Swallowing Outcome After Glossectomy: Correlation with a Classification.

This study aimed to characterize the swallowing outcomes after glossectomy and analyze factors affecting them. An attempt is made to propose a classification system and corroborate it to the results. This is a cross-sectional study to assess swallowing in carcinoma tongue patients treated surgically with or without reconstruction, followed by adjuvant therapy as indicated. One hundred and six patients were evaluated with videofluoroscopy (VFS). Volume defects were classified as I: less than one-third, II: one-third to half, III: half to two-thirds, IV: two-thirds to total glossectomy. Location was assigned as lateral, tip, and sulcus defects. Predictors were T stage, surgical approach, volume, location, and adjuvant radiotherapy. Chi-square and logistic regression were used for statistical analysis. Defects were Class I, II, III, and IV in 36, 42, 16, and 12 patients, respectively. Adjuvant radiotherapy was given in 40% of cases. Mean evaluation time was 14 months from treatment. On, Functional Oral Intake Scale (FOIS) score, as the Class of the defect increased, the percentage of patients with low scores (poor swallowing outcomes) showed an increasing trend (p < 0.001). Defect volume, T stage, approach, and radiotherapy correlated significantly with an abnormality of all VFS parameters (p < 0.001). On multivariate analysis, defect volume remained an independent predictor for oral parameters; radiotherapy emerged as the only independent predictor for pharyngeal parameters. The incremental volume of the defect is a significant independent predictor of swallowing. Based on this, we propose a classification for glossectomy.

Inhibition of Pseudomonas aeruginosa and Mycobacterium tuberculosis disulfide bond forming enzymes.

In bacteria, disulfide bonds confer stability on many proteins exported to the cell envelope or beyond, including bacterial virulence factors. Thus, proteins involved in disulfide bond formation represent good targets for the development of inhibitors that can act as antibiotics or anti-virulence agents, resulting in the simultaneous inactivation of several types of virulence factors. Here, we present evidence that the disulfide bond forming enzymes, DsbB and VKOR, are required for Pseudomonas aeruginosa pathogenicity and Mycobacterium tuberculosis survival respectively. We also report the results of a HTS of 216,767 compounds tested against P. aeruginosa DsbB1 and M. tuberculosis VKOR using Escherichia coli cells. Since both P. aeruginosa DsbB1 and M. tuberculosis VKOR complement an E. coli dsbB knockout, we screened simultaneously for inhibitors of each complemented E. coli strain expressing a disulfide-bond sensitive ß-galactosidase reported previously. The properties of several inhibitors obtained from these screens suggest they are a starting point for chemical modifications with potential for future antibacterial development.

Tracheal Allotransplantation-Lessons Learned.

Reconstruction of long tracheal defects still proves to be a challenge. Free fasciocutaneous flaps with cartilaginous struts or an allotransplant trachea have been reported but not been widely performed. This article reports with the experience of using a tracheal allotransplant in such a defect. A 43-year-old lady presented with adenoid cystic carcinoma involving the entire trachea from subglottic area up to the carina, leading to a life-threatening airway occlusion. After preliminary stenting, allotransplant trachea obtained from a brain-dead individual was revascularized in the forearm of the patient after mechanical decellularization to reduce the immune load and fulfil the need for immunosuppression in the background of active cancer. Subsequently, the trachea and larynx were resected. The vascularized neotrachea was transferred successfully into the neck. The patient did well initially but succumbed to a fatal hemorrhage due to innominate vein aneurysmal rupture on the 22nd day after the transplant. The technical details of resection, fabrication of the neotrachea, its transfer, and the lessons learnt in this tracheal allotransplant are described.

Validation of the eighth edition AJCC staging system in early T1 to T2 oral squamous cell carcinoma.

BACKGROUND: To validate the newly proposed American Joint Committee on Cancer (AJCC) eighth edition staging in early T1 and T2 oral cavity cancers and its effect in predicting tumour control. METHODS: Retrospective analysis of treatment outcomes of 441 T1 to T2 oral squamous cell carcinoma (OSCC). Overall survival (OS), disease-specific survival (DSS), and tumour control were calculated and compared between the AJCC 7 and 8 staging systems. RESULTS: The 5-year OS was 78% and 61% for T1 and T2 tumours, respetively (P < 0.001) (AJCC 7) vs 87% and 67% (P < 0.001) (AJCC 8). The 5-year DSS was 78% and 61% for T1 and T2, respectively (P < 0.001) (AJCC 7) vs 89% and 71% (P < 0.001) (AJCC 8). For stages I and II tumours the 5-year OS was 81% and 76%, respectively (P < 0.302) (AJCC 7) vs 87% and 73% (P < 0.017) (AJCC 8). The 5-year DSS was 83% and 82% (P < 0.222) vs 89% and 77% (P < 0.016). With the AJCC eighth edition the 5-year local, regional, and distant control rates for T1 vs T2 tumours were 85% vs 74% (P = 0.003), 95% vs 77% (P = 0.001), and 95% vs 80% (P = 0.014), respectively. CONCLUSION: The AJCC 8th staging system provided for more accurate prediction of OS, DSS, and disease control in early oral cavity cancers.

Geographic Inequities in Coverage of Maternal and Child health Services in Haryana State of India.

Introduction India aims to achieve universal health coverage, with a focus on equitable delivery of services. There is significant evidence on extent of inequities by income status, gender and caste. In this paper, we report geographic inequities in coverage of reproductive, maternal and child health (MCH) services in Haryana state of India. Methods Cross-sectional data on utilization of maternal, child health and family planning services were collected from 12,191 women who had delivered a child in the last one year, 10314 women with 12-23 months old child, and 45864 eligible couples across all districts in Haryana state. Service coverage was assessed based on eight indicators - 6 for maternal health, one for child health and one for family planning. Inter- and intra-district inequalities were compared based on four and three indicators respectively. Results Difference in coverage of full ante-natal care, full immunization and contraceptive prevalence rate between districts performing best and worst was found to be 54%, 65% and 63% respectively. More than one-thirds of the sub-centres (SCs) in Panchkula, Ambala, Gurgaon and Mewat districts had their ante-natal care coverage less than 50% of the respective district average. Similarly, a significant proportion of SCs in Mewat, Panipat and Hisar districts had full immunization rate below 50% of the district average. Conclusion Widespread inter- and intra-district inequities in utilization of MCH services exist. A comprehensive geographical targeting to identify poor performing districts, community development blocks and SCs could result in significant equity gains, besides contributing to quick achievement of sustainable development goals.

"Deep Extrinsic Muscle Involvement" Is a Fallacy in the American Joint Committee on Cancer's Seventh Edition of Tumor Staging of Oral Cavity Cancers.

PURPOSE: The seventh edition of tumor staging by the American Joint Committee on Cancer (AJCC) includes extrinsic muscle involvement to define stage T4a tongue carcinomas. The anatomic location of extrinsic muscles predisposes them to early involvement even in superficial tumors. The purpose of this study was to expose a fallacy in this staging system for extrinsic muscle involvement. MATERIALS AND METHODS: This was a prospective cohort study of 87 patients with oral tongue squamous cell carcinoma. Magnetic resonance imaging (MRI) parameters were 1) the distance of the extrinsic muscles from the surface measured on the normal side in millimeters (range, mean, and standard deviation); 2) maximum transverse, craniocaudal, and anteroposterior tumor dimensions (range, mean, and standard deviation); and 3) tumor involvement of the muscles recorded on the involved side for the number and percentage of each muscle involved. Histopathologic depth of invasion also was recorded. RESULTS: Sixty-seven patients were men and 20 were women (age range, 18 to 74 yr; mean age, 51 yr). The mean distances of the most superficial part of the muscle to the normal surface at MRI for the genioglossus (anteroventral), hyoglossus, and styloglossus were 3.98, 2.13 and 0.66 mm, respectively. The patterns of extrinsic muscle involvement showed hyoglossus, styloglossus, and genioglossus involvement in 79 (90.8%), 58 (66.76%), and 31 (35.6%), respectively. In patients with a pathologic depth of invasion shallower than 10 mm, involvement of the hyoglossus, styloglossus, and genioglossus was seen in 80, 35, and 15%, respectively. CONCLUSION: The extrinsic muscles of the tongue are not deep. Even superficial thin tumors can involve these muscles. The eighth edition of tumor staging by the AJCC, which includes tumor thickness in the staging system, is in the process of being implemented. The present study justifies the removal of extrinsic muscle involvement in defining stage T4 of the oral cavity.

Factors Affecting Survival in Surgically Salvaged Locoregional Recurrences of Squamous Cell Carcinoma of the Tongue.

PURPOSE: To determine the factors affecting outcomes in surgically salvaged, locoregionally recurrent squamous cell carcinoma of the tongue (SCCT). MATERIALS AND METHODS: In a retrospective cohort of patients who underwent successful salvage of locoregionally recurrent SCCT, we performed this observational analytical study to determine survival and its determinants. Details extracted from our database were patient characteristics (age, gender, tobacco use), treatment characteristics, and characteristics of recurrent disease (stage and adverse pathologic features [APFs] such as grade, perineural invasion, and lymphovascular invasion). Overall survival (OS) curves were plotted using the Kaplan-Meier method. A Cox proportional hazards model was used to determine the impact of patient, disease, and treatment characteristics on OS. RESULTS: Of 52 patients with locoregional recurrences of surgically treated SCCT, 25 (48.1%) underwent surgical salvage with curative intent. The median overall OS for this cohort was 26 months. Factors predictive of worse OS were previous adjuvant therapy (P = .016) and increasing APFs in recurrent tumor histology (P = .008). Lymphovascular invasion in recurrent tumor histology and patients with a disease-free interval of less than 6 months showed worse survival (P = .008 and P = .058, respectively). CONCLUSIONS: Among patients with locoregional recurrence, the number who are eligible for curative-intent surgical salvage is small. Those who received previous adjuvant therapy and those with increasing APFs in recurrent tumors had poor outcomes despite attempts at surgical salvage, particularly patients with early recurrence.

Interdisciplinary Telemedicine in the Management of Dysphagia in Head and Neck.

The study considered the feasibility and impact of interdisciplinary telemedicine discussions in the management of post-treatment dysphagia in patients with head and neck tumors. This is a retrospective analysis of patients with persistent dysphagia after treatment for head and neck pathology, at an institute in India. The cases were discussed in the telemedicine meeting conducted between host institute and a second unit in the United States. A monthly meeting was organized, using an internet-based video conference system. The ongoing swallowing problems and management were presented, and through discussions, a plan for further management was formulated and carried out. The Functional Oral Intake Scale (FOIS) was measured before and after the implementation of the plan. Twenty-six patients were discussed, out of which, 22 were head and neck malignancies. The recommendations concurred with that of the host unit in 18, differed for three and additive in five patients. The pre-treatment mean FOIS was 1.46 with a standard deviation of 0.989 and post-treatment mean improved to 3.92 with a standard deviation of 1.809 (p < 0.0001). The present study supports the success of an interdisciplinary telemedicine meeting to manage difficult cases of dysphagia in head and neck. The outcome in terms of the FOIS score improved significantly after implementing them. In addition to the direct patient benefits, the meeting helped to facilitate interdepartmental collaboration between two units treating similar sets of patients across the globe, in specialized clinical areas like dysphagia management.

Outcomes following pharyngeal reconstruction in total laryngectomy - Institutional experience and review of literature.

BACKGROUND: Pharyngeal reconstruction is a challenging aspect of reconstruction after resections for head-and-neck cancer. The goals of reconstruction are to restore the continuity of the pharyngeal passage to enable oral alimentation and rehabilitation of speech wherever possible. This study was performed to determine the outcomes following pharyngeal reconstruction in total laryngectomy (TL) using different reconstructive options and to determine the predictors of pharyngocutaneous fistula (PCF) and swallowing dysfunction. MATERIALS AND METHODS: Retrospective analysis of patient data between 2003 and 2010 of patients undergoing TL with partial or total pharyngectomy. Demographic and treatment details were collected and analysed. Univariate analysis was performed to determine predictors of PCF and swallowing dysfunction. RESULTS: Fifty-seven patients underwent pharyngeal reconstruction following TL, 31 of whom had received prior treatment. Following tumour resection, 31 patients had circumferential defects and 26 patients had partial pharyngeal defects. The flaps used include pectoralis major myocutaneous flap (n = 29), anterolateral thigh flap (n = 8), gastric pull-up (n = 13) and free jejunal flap (n = 7). PCF was seen in 20 patients, of which 15 (75%) were managed conservatively and 5 required another surgery. At last follow-up, 99 patients (68%) were on full oral alimentation. Tracheo-oesophageal puncture and prosthesis insertion was done in 20 patients, of whom 17 (85%) developed satisfactory speech. Partial pharyngeal defects were associated with a higher risk of PCF on univariate analysis (P = 0.006) but were not significant on multivariate analysis. Post-operative swallowing dysfunction was significantly higher with hypopharyngeal involvement by tumour (P = 0.003). CONCLUSION: Pharyngeal reconstruction in TL is feasible with good results. Majority of the patients swallow and regain acceptable swallowing function within 3 months.

Cost of delivering secondary-level health care services through public sector district hospitals in India.

BACKGROUND & OBJECTIVES: Despite an impetus for strengthening public sector district hospitals for provision of secondary health care in India, there is lack of robust evidence on cost of services provided through these district hospitals. In this study, an attempt was made to determine the unit cost of an outpatient visit consultation, inpatient bed-day of hospitalization, surgical procedure and overall per-capita cost of providing secondary care through district hospitals. METHODS: Economic costing of five randomly selected district hospitals in two north Indian States - Haryana and Punjab, was undertaken. Cost analysis was done using a health system perspective and employing bottom-up costing methodology. Quantity of all resources - capital or recurrent, used for delivering services was measured and valued. Median unit costs were estimated along with their 95 per cent confidence intervals. Sensitivity analysis was undertaken to assess the effect of uncertainties in prices and other assumptions; and to generalize the findings for Indian set-up. RESULTS: The overall annual cost of delivering secondary-level health care services through a public sector district hospital in north India was ' 11,44,13,282 [US Dollars (USD) 2,103,185]. Human resources accounted for 53 per cent of the overall cost. The unit cost of an inpatient bed-day, surgical procedure and outpatient consultation was ' 844 (USD 15.5), ' 3481 (USD 64) and ' 170 (USD 3.1), respectively. With the current set of resource allocation, per-capita cost of providing health care through district hospitals in north India was ' 139 (USD 2.5). INTERPRETATION & CONCLUSIONS: The estimates obtained in our study can be used for Fiscal planning of scaling up secondary-level health services. Further, these may be particularly useful for future research such as benefit-incidence analysis, cost-effectiveness analysis and national health accounts including disease-specific accounts in India.

Characterization of a Carbapenem-Hydrolyzing Enzyme, PoxB, in Pseudomonas aeruginosa PAO1.

Pseudomonas aeruginosa is an opportunistic pathogen often associated with severe and life-threatening infections that are highly impervious to treatment. This microbe readily exhibits intrinsic and acquired resistance to varied antimicrobial drugs. Resistance to penicillin-like compounds is commonplace and provided by the chromosomal AmpC ß-lactamase. A second, chromosomally encoded ß-lactamase, PoxB, has previously been reported in P. aeruginosa. In the present work, the contribution of this class D enzyme was investigated using a series of clean in-frame ampC, poxB, and oprD deletions, as well as complementation by expression under the control of an inducible promoter. While poxB deletions failed to alter ß-lactam sensitivities, expression of poxB in ampC-deficient backgrounds decreased susceptibility to both meropenem and doripenem but had no effect on imipenem, penicillin, and cephalosporin MICs. However, when expressed in an ampCpoxB-deficient background, that additionally lacked the outer membrane porin-encoding gene oprD, PoxB significantly increased the imipenem as well as the meropenem and doripenem MICs. Like other class D carbapenem-hydrolyzing ß-lactamases, PoxB was only poorly inhibited by class A enzyme inhibitors, but a novel non-ß-lactam compound, avibactam, was a slightly better inhibitor of PoxB activity. In vitro susceptibility testing with a clinical concentration of avibactam, however, failed to reduce PoxB activity against the carbapenems. In addition, poxB was found to be cotranscribed with an upstream open reading frame, poxA, which itself was shown to encode a 32-kDa protein of yet unknown function.

Deep sequencing analyses expands the Pseudomonas aeruginosa AmpR regulon to include small RNA-mediated regulation of iron acquisition, heat shock and oxidative stress response.

Pathogenicity of Pseudomonas aeruginosa, a major cause of many acute and chronic human infections, is determined by tightly regulated expression of multiple virulence factors. Quorum sensing (QS) controls expression of many of these pathogenic determinants. Previous microarray studies have shown that the AmpC ß-lactamase regulator AmpR, a member of the LysR family of transcription factors, also controls non-ß-lactam resistance and multiple virulence mechanisms. Using RNA-Seq and complementary assays, this study further expands the AmpR regulon to include diverse processes such as oxidative stress, heat shock and iron uptake. Importantly, AmpR affects many of these phenotypes, in part, by regulating expression of non-coding RNAs such as rgP32, asRgsA, asPrrF1 and rgRsmZ. AmpR positively regulates expression of the major QS regulators LasR, RhlR and MvfR, and genes of the Pseudomonas quinolone system. Chromatin immunoprecipitation (ChIP)-Seq and ChIP-quantitative real-time polymerase chain reaction studies show that AmpR binds to the ampC promoter both in the absence and presence of ß-lactams. In addition, AmpR directly binds the lasR promoter, encoding the QS master regulator. Comparison of the AmpR-binding sequences from the transcriptome and ChIP-Seq analyses identified an AT-rich consensus-binding motif. This study further attests to the role of AmpR in regulating virulence and physiological processes in P. aeruginosa.

A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence.

Pseudomonas aeruginosa is a metabolically versatile bacterium that is found in a wide range of biotic and abiotic habitats. It is a major human opportunistic pathogen causing numerous acute and chronic infections. The critical traits contributing to the pathogenic potential of P. aeruginosa are the production of a myriad of virulence factors, formation of biofilms and antibiotic resistance. Expression of these traits is under stringent regulation, and it responds to largely unidentified environmental signals. This review is focused on providing a global picture of virulence gene regulation in P. aeruginosa. In addition to key regulatory pathways that control the transition from acute to chronic infection phenotypes, some regulators have been identified that modulate multiple virulence mechanisms. Despite of a propensity for chaotic behaviour, no chaotic motifs were readily observed in the P. aeruginosa virulence regulatory network. Having a 'birds-eye' view of the regulatory cascades provides the forum opportunities to pose questions, formulate hypotheses and evaluate theories in elucidating P. aeruginosa pathogenesis. Understanding the mechanisms involved in making P. aeruginosa a successful pathogen is essential in helping devise control strategies.

Structural and functional characterization of Pseudomonas aeruginosa global regulator AmpR.

Pseudomonas aeruginosa is a dreaded pathogen in many clinical settings. Its inherent and acquired antibiotic resistance thwarts therapy. In particular, derepression of the AmpC ß-lactamase is a common mechanism of ß-lactam resistance among clinical isolates. The inducible expression of ampC is controlled by the global LysR-type transcriptional regulator (LTTR) AmpR. In the present study, we investigated the genetic and structural elements that are important for ampC induction. Specifically, the ampC (PampC) and ampR (PampR) promoters and the AmpR protein were characterized. The transcription start sites (TSSs) of the divergent transcripts were mapped using 5' rapid amplification of cDNA ends-PCR (RACE-PCR), and strong σ(54) and σ(70) consensus sequences were identified at PampR and PampC, respectively. Sigma factor RpoN was found to negatively regulate ampR expression, possibly through promoter blocking. Deletion mapping revealed that the minimal PampC extends 98 bp upstream of the TSS. Gel shifts using membrane fractions showed that AmpR binds to PampC in vitro whereas in vivo binding was demonstrated using chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR). Additionally, site-directed mutagenesis of the AmpR helix-turn-helix (HTH) motif identified residues critical for binding and function (Ser38 and Lys42) and critical for function but not binding (His39). Amino acids Gly102 and Asp135, previously implicated in the repression state of AmpR in the enterobacteria, were also shown to play a structural role in P. aeruginosa AmpR. Alkaline phosphatase fusion and shaving experiments suggest that AmpR is likely to be membrane associated. Lastly, an in vivo cross-linking study shows that AmpR dimerizes. In conclusion, a potential membrane-associated AmpR dimer regulates ampC expression by direct binding.

Oral Management of Patients Undergoing Head and Neck Cancer Treatment.

Oral cancer accounts for around 30 percent of all cancers in India. These cancers are usually managed either by surgery, radiotherapy, chemotherapy or a combination of these modalities. Dental oncologists play an integral part in the multidisciplinary team, including surgeons, radiation and medical oncologists, nurses, physician assistants, nutritionists, psychologists and social workers to efficiently manage cancer patients. Oral complications associated with cancer therapy can range from minor mucositis or infections to severely debilitating conditions such as osteonecrosis of jaws, which can disrupt the ongoing cancer therapy and jeopardize the overall quality of life of the patient. This highlights the primary role of a dentist in the efficient identification and management of potential oral foci of infection and subsequent prevention of the onset of these complications. This necessitates accurate, evidence-based knowledge and extensive training of dental oncologists to provide state-of-the-art management strategies. This article aims to review oral management before, during and after therapy in patients undergoing treatment for cancers affecting the head and neck region.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

OBJECTIVES: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Improving accuracy in nodal staging of oral cancer: Proposal of a new system.

BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery±adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

Propeller flaps in the closure of free fibula flap donor site skin defects.

The free fibula is a versatile and commonly used free flap in microvascular reconstruction. It allows for reconstruction of both bone and soft tissue defects. In head and neck reconstruction, the skin paddle harvested along with the flap allows for the reconstruction of skin or oral mucosal defects. After skin paddle harvest, the donor site can be closed primarily or with skin grafts. Grafting the donor area is the common method used. However, this could lead to delayed healing because of the poor graft over the area of peroneal tendons. Propeller flaps have been extensively reported for closure of leg skin defects. We report a series of 10 patients in whom we used a local propeller flap for the closure of the fibula flap skin donor site. The donor defects could be satisfactorily closed without the need of a skin graft in 9 patients. This method is simple, reliable, and suitable for closing small to medium defects.