Introduction: Oral squamous cell carcinoma (OSCC) the sixth leading cancer worldwide ranks as the most common cancer in males, and the third most common in females in Pakistan.It is influenced by risk factors which are widely consumed in our population.The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that is imperative for cell signalling, growth and differentiation.It is mutated and overexpressed in a variety of cancers, while in OSCC it has been linked to poor patient survival; premalignant to malignant transformation and recurrence.This study investigates the use of EGFR as a prognostic factor for OSCC.Materials and Methods: Premalignant (n=29) and OSCC (n=100) formalin-fixed paraffin-embedded tissues were retrieved from the surgical archives of Aga Khan University Hospital (AKUH).Immunohistochemistry for EGFR overexpression was performed using monoclonal antibody on both groups.EGFR expression was correlated with habits of risk factor consumption, clinicopathologic features and 5-year survival and recurrence.Results: 15/29 premalignant and 67/100 OSCC patients had overexpressed EGFR.The upper/lower lip had the highest EGFR positivity among all premalignant sites of lesion (p=0.041).In OSCC patients, those who had EGFR overexpression had worse 5-year survival (univariate: p=0.048, multivariate: p=0.056) and higher chances of recurrence (univariate: p=0.01, multivariate: p=0.004) as compared to EGFR negative patients.Conclusion: EGFR is a viable candidate for an OSCC prognostic marker since its overexpression leads to poor survival and markedly increases the chances of recurrence.
Bacterial enoyl-acyl carrier protein reductase (ENR) catalyzes an essential step in fatty acid biosynthesis. ENR is an attractive target for narrow-spectrum antibacterial drug discovery because of its essential role in metabolism and its sequence conservation across many bacterial species. In addition, the bacterial ENR sequence and structural organization are distinctly different from those of mammalian fatty acid biosynthesis enzymes. High-throughput screening to identify inhibitors of Escherichia coli ENR yielded four structurally distinct classes of hits. Several members of one of these, the 2-(alkylthio)-4,6-diphenylpyridine-3-carbonitriles ("thiopyridines"), inhibited both purified ENR (50% inhibitory concentration [IC(50)] = 3 to 25 micro M) and the growth of Staphylococcus aureus and Bacillus subtilis (MIC = 1 to 64 micro g/ml). The effect on cell growth is due in part to inhibition of fatty acid biosynthesis as judged by inhibition of incorporation of [(14)C]acetate into fatty acids and by the increased sensitivity of cells that underexpress an ENR-encoding gene (four- to eightfold MIC shift). Synthesis of a variety of compounds in this chemical series revealed a correlation between IC(50) and MIC, and the results provided initial structure-activity relationships. Preliminary structure-activity relationships, potency on purified ENR, and activity on bacterial cells indicate that members of the thiopyridine chemical series are effective fatty acid biosynthesis inhibitors suitable for further antibacterial development.
Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events.
Objective
To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients.
Design, Setting, and Participants
The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents.
Exposures
Tracheal intubation.
Main Outcomes and Measures
The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality.
Results
Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%.
Conclusions and Relevance
In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events—in particular cardiovascular instability—were observed frequently.
Abstract Aim: Cancer of the oral cavity is extremely prevalent in Pakistan. Human papillomavirus (HPV) has been shown to play a role in the development of oral squamous cell carcinoma (OSCC) and may even improve overall and disease‐free survival. The purpose of this study was to determine prevalence and types of HPV in a high risk population and its correlation with overall and disease‐free survival, chewing habits and histologic variables. Material and methods: A total of 140 patients of OSCC, having a long‐term follow‐up, were included in this study. HPV‐general and type‐specific 16 and 18 infection were investigated by means of polymerase chain reaction. Results: Out of 140 patients, HPV was detected in 95 (68%) patients, out of whom, 85 (90%) contained HPV16. HPV positive patients had comparatively prolonged overall survival when compared with HPV‐negative patients, but this difference was not statistically significant ( P = 0.97). HPV presence was also not found to correlate significantly with disease‐free survival ( P = 0.58). The male were significantly correlated [odds ratio (OR) = 2.34; 95% confidence interval (CI) = 1.13–4.84] with the HPV infection. Betel quid chewer were comparatively more prone to HPV positivity (OR = 2; 95% CI = 1.1–4.31). Conclusion: Our study found a high prevalence of HPV16 in OSCC of Pakistani patients with male sex showing significant correlation with HPV infection. However, we did not find a statistically significant favourable association between HPV, survival and histologic variables. Borderline significance of HPV positivity was also seen with betel quid chewing ( P = 0.049).
Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the Pakistani population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. This study investigated the impact of CSC markers expression on overall survival (OS) and disease-free survival (DFS) of OSCC patients. Materials and Methods. Immunohistochemistry was used to evaluate CD44, CD133, L1CAM, and SOX2 expression in a well-characterized cohort of 100 Pakistani patients with primary treatment naïve OSCC. The immunoreactivity for each marker was correlated with patient clinicopathologic characteristics, oral cancer risk chewing habits, and survival. The minimum follow-up time for all patients was five years, and survival estimates were calculated using the Kaplan-Meier method and Cox proportional hazards model. Results. In this cohort of 100 patients, there were 57 males and 43 females. The median OS and DFS time durations observed were 64 and 52.5 months, respectively. Positive expression for CD44, CD133, L1CAM, and SOX2 was observed in 33%, 23%, 41%, and 63% of patients. High CD44 expression correlated with decreased OS (P=0.047) but did not influence DFS. However, CD133, L1CAM, and SOX2 had no effect on either OS or DFS. Tonsils, nodal involvement, and AJCC stage were independent predictors of worse OS and DFS both. Conclusion. Of the CSC markers investigated here, only CD44 was a predictor for poor OS. CD44 was also associated with advanced AJCC and T stages. Interestingly, CD133 was significantly lower in patients who habitually consumed oral cancer risk factors.
Dental caries is one of the most common non-communicable diseases in humans. Various interventions are available for the management, of which microinvasive techniques such as infiltration, sealants, glass ionomers, are novel and convenient. The purpose of this systematic review and meta-analysis was to compare microinvasive techniques with noninvasive or invasive treatment modalities in terms of effectiveness in halting interproximal caries lesion progression radiographically assessed. The review was registered on PROSPERO (CRD42024557636). Three electronic databases, PubMed, Google Scholar and Cochrane Oral Health Group Trial Register, were searched for the randomized controlled trials comparing any of the microinvasive techniques with either non- invasive or invasive treatments for non-cavitated proximal lesions both in primary and permanent teeth. The radiographic lesion progression was set as primary outcome. Rayyan and EndNote X9 were used for screening and full text review respectively. The risk of bias was assessed using Cochrane Risk of Bias tool. We performed analysis with the help of RevMan5.4 and calculated odds ratio and 95% confidence interval for evaluation of efficacy. The quality of evidence was assessed with the help of GRADEpro. A total of 185 studies were recruited after initial search, of which 18 were recruited after screening. Finally, 13 studies were included, and all were split mouth randomized controlled trials comparing various microinvasive techniques with non-invasive techniques. Five of the included trials studied primary teeth in children ranging from 3 to 9 years and seven trials assessed permanent teeth in children and adults ranging from 11 to 45 years while one trial included children having lesions on both primary and permanent teeth. The risk of bias assessment showed that 2 of the included studies had unclear risk of bias whereas 11 were at low risk of bias. Tau2, I2, and Chi-Square tests (0.04, 10% and 7.50 respectively) showed minimum level of heterogeneity. The overall odds ratio (95% confidence interval) of 0.29 (95% CI 0.19–0.38) showed that microinvasive techniques were superior as compared to noninvasive techniques for the management of proximal lesions. The subgroup analysis was also performed for types of dentitions, various microinvasive interventions and levels of caries depth. All showed improved outcomes in case of microinvasive interventions as compared to noninvasive techniques. The publication bias was assessed using forest plot and there was no significant publication bias. The quality of evidence assessed by GRADEpro came out to be moderate. This review concludes that microinvasive techniques are superior to noninvasive interventions for the treatment of non-cavitated proximal lesions in both primary and permanent dentition. However, cost effectiveness, feasibility, durability, and long-term effects of microinvasive techniques need to be explored further.
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