The molecular characteristics of recurrent/metastatic HPV-positive head and neck squamous cell carcinoma:A systematic review of the literature

Objectives: About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV-positive HNSCC as well as novel molecular biomarkers. Design: A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV-positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence-based Medicine and quality was assessed using the Newcastle-Ottawa Scale criteria. Results and Conclusions: The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.</p

A mixed methods comparative evaluation of a low cost otoscope (Arclight) with a traditional device in twenty-one clinicians

According to the World Health Organisation estimate, the global burden of illness from chronic ear infection affects about 4% of the world population (up to 330 million) with ear discharge and 60% of whom (up to 200 million) suffer from significant hearing impairment.1 Alarmingly, over 90% of the burden of chronic ear infections is borne by low‐ and middle‐income countries (LMICs).PostprintPeer reviewe

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Recurrent respiratory distress and cardiopulmonary arrest caused by megaoesophagus secondary to achalasia

INTRODUCTION: Respiratory distress and arrest from tracheal compression secondary to megaoesophagus are rare complications of achalasia. We present the case of a man with end-stage achalasia who required oesophagectomy to prevent recurrent life-threatening tracheal compression and respiratory arrest. A literature review is also presented. PRESENTATION OF CASE: A 40-year old man presented with post-prandial stridor which resolved spontaneously, later being diagnosed with achalasia. He underwent pneumatic dilatation year later, intended as definitive treatment. Despite intervention, the patient had developed megaoesophagus. One month later he presented with tracheal compression and cardiorespiratory arrest but was successfully resuscitated. He subsequently underwent elective oesophagectomy. DISCUSSION: Over 40 case reports of achalasia presenting with stridor have been published. However, only three cases (all female, age range, 35–79 years old) of cardiac, respiratory or cardiorespiratory arrest have been published. The definitive treatments received by these patients were botulinum toxin injections, open Heller cardiomyotomy with Dor fundoplication and pneumatic dilatation. None of these patients suffered recurrent respiratory distress following definitive treatment. The patient currently reported was unique as he suffered cardiorespiratory arrest following an intended definitive treatment, pneumatic dilatation. As such oesophagectomy was considered the greatest risk-reduction intervention. CONCLUSION: Oesophagectomy should be considered for patients with end-stage achalasia and mega-oesophagus causing respiratory compromise to avoid potential fatal complications such as tracheal compression and subsequent respiratory arrest

Patient satisfaction on drainless outpatient parotidectomy

Background: Parotidectomy is commonly performed as an inpatient procedure due to drain insertion. However recent evidence suggests that drainless outpatient parotidectomy is a safe option with comparable postoperative complication and hospital readmission rates to inpatient parotidectomies. Objective: Patient satisfaction on outpatient parotidectomy is unclear and this study aims to report patients’ perspective and satisfaction on drainless outpatient parotidectomy.Design, participants and outcome measures: Anonymous Core questionnaire for the assessment of Patient Satisfaction’ (COPS) for general Day care(COPS-D) questionnaire survey was completed by patients who underwent drainless same day parotidectomy at Ninewells Hospital, Dundee from June2018 to October 2020. Patient satisfaction on different aspects of their outpatient parotidectomy journey (e.g. pre-admission, admission on ward, in-theatre experience, nursing care, pain control and overall satisfaction) were scored using a five-point Likert scale. Results: A total of 31 drainless outpatient parotidectomies were performed and 28patients completed the patient satisfaction survey. The majority of patients were highly satisfied (i.e. scored 5/5) with their preadmission visit (79.5%), admission on the ward (84.5%), operating room experience (96.4%), nursing care (83.9%), medical care (87.5%),information received (75.0%), autonomy (79.8%) and discharge and aftercare (61.9%). Despite preferring drainless parotidectomy, 16/28(57.1%) patients either stayed for less than 23 hours or preferred to stay overnight in the hospital for non-surgical reasons. Conclusion: Outpatient parotidectomy is well received by patients and the majority preferred drainless parotidectomy over inpatient parotidectomy with drains. Careful consideration should be given when selecting patients for day case parotidectomy