Photodynamic therapy in head and neck carcinomas: clinical and in vitro studies.

Despite the advances in diagnostic and therapeutic techniques, the outcome and survival of patients suffering from head and neck cancer has remained poor, primarily due to late detection, and the tendency of the disease to develop loco-regional metastasis. A key to its control is early detection and treatment and prevention of recurrence and metastasis. Tumour metastases can be considered as complex multi-step molecular events which involve the interplay between several processes including changes in cell survival, adhesion, proteolysis, and angiogenesis. Based on these considerations, a positive correlation between tumour invasiveness and expression/suppression of these processes would be expected. Photodynamic Therapy (PDT) is a novel treatment modality for a variety of malignant tumours, including head and neck cancer. The technique is based on the combination of a photosensitive drug and visible light to disrupt cell function and induce cytotoxicity, but there is little agreement on its efficacy. Furthermore, PDT is indicated for early tumour without metastases, yet it is crucial to determine its influence on the metastasis process. The aims of the study were: (i) to explore, using an in vitro model, the influence of PDT, alone or in combination with either chemotherapy or small molecules, on cell toxicity, expression of a5(31 and avp6 integrins and epidermal growth factor receptor (EGFR), production of matrix metalloproteinases, MMP-2, MMP-9 and MMP-13, urokinase plasminogen activator (uPA) and vascular endothelial growth factor (VEGF) (ii) to clinically evaluate the potential of PDT as a tool for head and neck cancer treatment (iii) to clinically evaluate the ability of an optical system, based on fluorescence and elastic scattering spectroscopy, to distinguish between normal, potentially malignant and malignant tissues and to develop an applicable algorithm that can be used as a standard for the subsequent analysis of "unknown" lesions (iv) to monitor the sensitiser photobleaching during PDT in patients with superficial basal cell carcinoma (BCC), and compare this to clinical outcome. It was found that, using a series of human oral squamous cell carcinoma cell lines, a marked decrease of tumour invasion and migration is evident after PDT this was associated with the downregulation of MMP-9, -2 and -13, uPA and VEGF. Moreover, this migratory inhibition was further enhanced when PDT was combined with either cisplatin chemotherapy or tyrosine kinase inhibitors. Clinically, a complete response with excellent cosmetic results was achieved on patients treated with PDT. Both fluorescence and elastic scattering spectroscopy have shown a great potential to both non-invasively identify dysplastic changes at an early stage and to be used as a screening tool for the detection of subsequent primary lesions. This thesis has demonstrated that, PDT and its related optical system together are able to detect, treat and reduce invasion and metastasis of head and neck carcinoma

Improving Outpatient Follow-Up After Hospitalization

Introduction: Hospital readmission is costly, in both patient quality of life and healthcare expenditures. Timely post-discharge follow-up has shown to reduce preventable readmissions. Efforts should be aimed at improving coordination of follow-ups. The aim of this quality improvement project was to increase post-hospital discharge follow-up by 20% for academic primary care patients admitted to a local tertiary care hospital by June 2020. This QI project was conducted at St. John Medical Center and the OU Internal Medicine Clinic utilizing Plan-Do-Study-Act methodology (PDSA). Patients admitted to OU inpatient teams who also designated OU Internal Medicine as their PCP were included in the study. An EMR query was utilized to measure follow-ups completed within 14 days of discharge. A process map was made, showing intervention points. Gap Analysis/Scatter Diagram was used to show points of largest impact. Methods: PDSA #1: Senior residents were given access to AllScripts (the clinic EMR scheduling program) to directly schedule patient follow-up appointments within 14 days of discharge. Follow-up appointments were included in patients’ discharge paperwork.    PDSA #2: Prior to discharge, patients were screened by care managers for a follow-up home visit. If appropriate, a multidisciplinary team of providers conducted an onsite follow-up visit within 14 days of discharge. Results: After PDSA #1: Residents surveyed after the first PDSA cycle admitted feeling overwhelmed with additional tasks and inconsistently scheduled appointments in AllScripts. In addition, EMR review demonstrated a high no-show rate for patients with follow-up appointments. Due to these results, we sought alternative options. After PDSA #2: Three patients were visited in their homes for an onsite 14-day follow-up appointment. Unfortunately, this process was put on hold given the COVID outbreak. At baseline, 31.6% of patients discharged from the hospital attended post-discharge follow-up visit within 14 days. This percentage declined to 29.2% after our interventions. Conclusion: The low rate of hospital discharge appointments within two weeks of discharge indicates that many patients are lacking crucial follow-up care. This project found that having residents enter appointments directly into AllScripts and performing home visits within 14 days of discharge made no difference in the overall rate of successful post-discharge follow-up visits. Weaknesses of this study include but are not limited to the gap of data between July 2019 and March 2020 and the small number of home visits that were performed. This project confirms the concern that unless new approaches to significant post-discharge follow-up barriers are considered, increasing the percentage of successful follow-up appointments will remain a difficult task

Detection of serum cross-reactive antibodies and memory response to SARS-CoV-2 in pre-pandemic and post-COVID-19 convalescent samples

Background A notable feature of COVID-19 is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-SARS-CoV-2 antibodies. Methods We investigated the presence of cross-reactive anti-SARS-CoV-2 IgG antibodies (to spike(S)1, S1-receptor-binding receptor (S1-RBD) and nucleocapsid protein(NP)), by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralisation assay, in pre-pandemic sera collected from children(n=50) and adults(n=45), and compared with serum samples from convalescent COVID-19 patients(n=16). Results A significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD and NP antigens, and the anti-S1 and -S1-RBD antibody levels correlated with anti-HCoV-HKU1 and -OC43 S1 antibody titers in pre-pandemic samples(p<0.001). There were marked increases of anti-HCoV-HKU1 and -OC43 S1 (but not anti-NL63 and -229E S-RBD) antibody titres in serum samples from convalescent COVID-19 patients(p<0.001), indicating an activation of cross-reactive immunological memory to β-coronavirus spike. Conclusions We demonstrated cross-reactive anti-SARS-CoV-2 antibodies in pre-pandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses

The future of medical diagnostics: Review paper

While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation. Their accuracy, expressed as sensitivity and specificity, are reported in a number of studies suggests that they have a potential for cost effective, real-time, in situ diagnosis. We review the Third Scientific Meeting of the Head and Neck Optical Diagnostics Society held in Congress Innsbruck, Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual Scientific Meeting was held in association with the International Photodynamic Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The aim was to enhance the interdisciplinary aspects of optical diagnostics and other photodynamic applications. The meeting included 2 sections: oral communication sessions running in parallel to the IPA programme and poster presentation sessions combined with the IPA and EPPM posters sessions. © 2011 Jerjes et al; licensee BioMed Central Ltd

Oral squamous cell cancer: early detection and the role of alcohol and smoking

Objective: Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. Data sources: A web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, alcohol consumption, genetic polymorphisms, tobacco smoking and prevention. The search was restricted to articles published in English, with no publication date restriction (last update 2010). Review Methods: In this review article, we approach the factors for a cytologic diagnosis during OSCC development and the markers used in modern diagnostic technologies as well. We also reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Results: The interaction of smoking and alcohol significantly increases the risk for aero-digestive cancers. The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease. Conclusion: Published scientific data show promising pathways for the future development of more effective prognosis. There is a clear need for new prognostic indicators, which could be used in diagnostics and, therefore a better selection of the most effective treatment can be achieved

Some New Evidence on Concentration and Profitability in Pakistan's Large-Scale Manufacturing Industries

The purpose of this paper is to estimate the extent of industrial concen¬tration in the major manufacturing industries and to analyse its effects on some standard behavioural aspects of oligopoly. Basically, it tests the hypothesis that excessive control of a market removes the pressure on monopolists to keep prices down to their competitive levels and thus generates excessive or 'monopoly profits'. Such behaviour by the oligopolist can be further split into a price-behavioural effect and a production effect [2]. According to the former, prices tend to be sticky as the oligopolist can effectively control output to influence market price. The production effect, on the other hand, implies that during a slowdown in economic activity, there is greater curtailment of output and a smaller reduction in price of products produced by more concentrated industries (henceforth referred to as MCIs). This tendency of a monopolist to restrict output and charge higher prices is generally described as one of the static alloca-tive effects of monopolistic competition and has welfare implications, in that, it leads to a sub-optimal allocation of resources.1 For a developing country (LDC) like Pakistan, where there is an acute shortage of manufactured goods, this restriction has obvious drawbacks