IgG4-related disease confined to the laryngopharynx: a case report highlighting the complexities in diagnosis for this rare cause of stridor.

This case represents only the 15th reported incidence of IgG4-related disease (IgG4-RD) affecting the laryngopharynx, adding diagnostic and therapeutic data for this rare condition and helping to inform the future management of these patients. A 66-year-old man presented with airway symptoms, and investigations by otolaryngology, cardiology and respiratory teams did not provide a clear diagnosis. Repeat biopsies of the laryngopharynx eventually confirmed a clinicopathological diagnosis of IgG4-RD. Treatment with prednisolone and methotrexate was successful. When infective and malignant causes of adult stridor have been excluded, inflammatory causes should be considered. The diagnosis of IgG4-RD isolated to the laryngopharynx may be delayed when using the widely accepted American College of Rheumatology classification criteria because it excludes upper aerodigestive tract features. IgG4-RD isolated to the laryngopharynx is extremely rare. This means a multidisciplinary approach is vital in ensuring timely diagnosis and treatment. Better diagnostic criteria are also needed.

Utilisation of a smartphone-enabled video otoscope to train novices in otological examination and procedural skills.

OBJECTIVE: The ai/m of this study was to compare the self-reported confidence of novices in using a smartphone-enabled video otoscope, a microscope and loupes for ear examination and external ear canal procedures. METHOD: Medical students (n = 29) undertook a pre-study questionnaire to ascertain their knowledge of techniques for otoscopy and aural microsuction. Participants underwent teaching on ear anatomy, examination and procedural techniques using a microscope, loupes and smartphone-enabled video otoscopes. Confidence and preference using each modality was rated using a Likert-like questionnaire. RESULTS: After teaching, all modalities demonstrated a significant increase in confidence in ear examination (p < 0.0001). Confidence in using the smartphone-enabled otoscope post-teaching was highest (p = 0.015). Overall, the smartphone-enabled video otoscope was the preferred method in all other parameters assessed including learning anatomy or pathology (51.72 per cent) and learning microsuction (65.51 per cent). CONCLUSION: Smartphone-enabled video otoscopes provide an alternative approach to ear examination and aural microsuction that can be undertaken outside of a traditional clinical setting and can be used by novices.

Accuracy of virtual assessment in hand trauma.

A virtual clinic was developed from an existing telemedicine system to manage hand trauma in the Queen Victoria Hospital, East Grinstead, UK, during the first wave of the COVID-19 pandemic. This study evaluates the accuracy of the assessments made and makes comparisons to the traditional face-to-face clinic. The accuracy of assessment was analysed by comparing diagnosis with findings at surgery. One hundred and eighty-nine virtual assessments conducted by telephone with photographic data or by video were compared to 129 face-to-face assessments conducted prior to the pandemic. There was no difference in the accuracy of virtual and face-to-face clinics for patients treated surgically (p=0.27); treatment was correctly predicted for 87% of the virtual group and 78% of the face-to-face group. However, fewer virtual assessments led to a surgical outcome (p=0.0064); 68% of the virtual group had surgical outcomes compared to 82% of the face-to-face group. Most face-to-face assessments were done by a specialty trainee compared to a range of clinicians in the virtual clinic. Accuracy of assessment among trainees was significantly associated with experience for the virtual (p=0.045) but not face-to-face clinics (p=0.94). Virtual assessment by video versus telephone plus photographs were similarly accurate. We conclude that virtual triage serves as a successful alternative to face-to-face appointments. It is robust and succeeds in reducing footfall to the hospital site in line with recent social distancing measures against COVID-19. We have shown that video conferencing triage is no better than telemedicine triage with telephone and photographs.

Respiratory presentations to acute services at a tertiary hospital in South Africa.

BACKGROUND: Respiratory diseases account for >10% of the global burden of disease when measured in disability-adjusted life-years. The burden of chronic respiratory diseases (CRDs) increases as the world's population ages, with a much greater increase in low- to middle-income countries. OBJECTIVES: To characterise and quantify the reasons for acute respiratory presentations to the acute care services at a tertiary hospital in Cape Town, South Africa. METHODS: A cross-sectional descriptive study was conducted. Casualty registers and electronic record databases were reviewed to determine the diagnoses of consecutive patients attending the casualty unit from May 2019 to January 2020. RESULTS: A total of 1 053 individual patients presented with a primary respiratory diagnosis. Fewer than 10% of admissions were from outside the Cape Town metropole, while >60% were from the subdistrict immediately adjacent to the hospital. Of all patients, 8.3% were readmitted at least once within the 9-month study period. Six hundred and forty-three (61.1%) of the patients presented with non-CRDs. The main reasons for presentation in these patients were pulmonary tuberculosis (PTB) (n=224; 21.3%), other infections including lower respiratory tract infections, pneumonia and bronchitis (n=272; 25.8%), and cancer (n=140; 13.3%). Haemoptysis was seen in 9.8% of all patients, mainly explained by post-tuberculosis lung disease (PTLD) (37.9%) and PTB (36.9%). Of the patients, 410 (38.9%) had an underlying CRD, with chronic pulmonary obstructive disease (COPD) being the most common (n=192; 18.2%), followed by PTLD (n=88; 8.5%) and asthma (n=52; 5.1%). CONCLUSIONS: Over a 9-month period, acute respiratory presentations to a tertiary hospital were mainly for primary/secondary level of care indications, highlighting disparity in accessing tertiary services. COPD and PTLD predominated among CRDs, while infections and cancers were common. A high readmission rate was found for several diseases, suggesting the potential for targeted interventions to prevent both admissions and readmissions and reduce acute hospital utilisation costs.

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa.

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SAgovernment announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes.

The single-use rhinolaryngoscope: an evaluation and cost comparison.

BACKGROUND: This study investigated whether the single-use rhinolaryngoscope is clinically and economically comparable to the conventional reusable rhinolaryngoscope within a tertiary otolaryngology centre in the UK. METHODS: A non-blinded, prospective and single-arm evaluation was carried out over a 5-day period, in which micro-costing was used to compare single-use rhinolaryngoscopes with reusable rhinolaryngoscopes. RESULTS: Overall, 68 per cent of the investigators perceived the single-use rhinolaryngoscope to be 'good' or 'very good', while 85 per cent believed the single-use rhinolaryngoscope could replace the reusable rhinolaryngoscope (n = 59). The incremental costs of reusable rhinolaryngoscope eyepieces and videoscopes in the out-patient clinic, when compared to single-use rhinolaryngoscopes, were £30 and £11, respectively. The incremental costs of reusable rhinolaryngoscope eyepieces and videoscopes in the acute surgical assessment unit, when compared to single-use rhinolaryngoscopes, were -£4 and -£73, respectively. CONCLUSION: The single-use rhinolaryngoscope provides a clinically comparable, and potentially cost-minimising, alternative to the reusable rhinolaryngoscope for use in the acute surgical assessment unit of our hospital.

Transoral robotic surgery for the benefit of patients with head and neck cancer of unknown primary: our experience at St George's University Hospital, London.

INTRODUCTION: Head and neck carcinoma of unknown primary represents 1-5% of all head and neck cancers and presents a diagnostic and therapeutic dilemma. In approximately 40% of cases, a primary tumour location remains unknown despite investigation. With advancements in our understanding of the role of high-risk human papilloma virus in head and neck cancer, transoral robotic surgery presents an option for diagnosis and therapy. MATERIALS AND METHODS: This is a retrospective case series from a single centre. Case notes were reviewed for 28 patients who had transoral robotic surgery for head and neck carcinoma of unknown primary between May 2015 and July 2019. RESULTS: Transoral robotic surgery identified an oropharyngeal primary tumour in 19 of 28 (67.8%) patients. All oropharyngeal primaries were p16 positive. The base of tongue identification rate was 63.2%. Median length of inpatient stay postoperatively was 1.0 day. Normal oral intake resumed within 48 hours in 96% (27/28) of patients. Three patients (10.3%) suffered minor postoperative bleeds that were all managed conservatively. DISCUSSION: The base of tongue primary identification rate (63.2%) in this series is consistent with that previously reported (43-63%; 95% confidence interval). Primary tumour identification rate if a patient is p16 positive is 86.3% (19/22), with 100% of these being oropharyngeal. We suggest future investigation into p16 status as a means of stratifying patients with head and neck carcinoma of unknown primary for transoral robotic surgery. CONCLUSION: Transoral robotic base of tongue mucosectomy (or lingual tonsillectomy) is a promising technique that offers a high yield of positive identification for the primary tumour. It is well tolerated with minimal associated morbidity. Our findings are comparable with those in the current literature.

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SA government announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes

Guide Field Reconnection: Exhaust Structure and Heating.

Magnetospheric Multiscale observations are used to probe the structure and temperature profile of a guide field reconnection exhaust ~100 ion inertial lengths downstream from the X-line in the Earth's magnetosheath. Asymmetric Hall electric and magnetic field signatures were detected, together with a density cavity confined near 1 edge of the exhaust and containing electron flow toward the X-line. Electron holes were also detected both on the cavity edge and at the Hall magnetic field reversal. Predominantly parallel ion and electron heating was observed in the main exhaust, but within the cavity, electron cooling and enhanced parallel ion heating were found. This is explained in terms of the parallel electric field, which inhibits electron mixing within the cavity on newly reconnected field lines but accelerates ions. Consequently, guide field reconnection causes inhomogeneous changes in ion and electron temperature across the exhaust.

Prioritising action on occupational carcinogens in Europe: a socioeconomic and health impact assessment.

BACKGROUND: Work-related cancer is an important public health issue with a large financial impact on society. The key European legislative instrument is the Carcinogens and Mutagens Directive (2004/37/EC). In preparation for updating the Directive, the European Commission commissioned a study to provide a socioeconomic, health and environmental impact assessment. METHODS: The evaluation was undertaken for 25 preselected hazardous substances or mixtures. Estimates were made of the number of cases of cancer attributable to workplace exposure, both currently and in the future, with and without any regulatory interventions, and these data were used to estimate the financial health costs and benefits. RESULTS: It was estimated that if no action is taken there will be >700 000 attributable cancer deaths over the next 60 years for the substances assessed. However, there are only seven substances where the data suggest a clear benefit in terms of avoided cancer cases from introducing a binding limit at the levels considered. Overall, the costs of the proposed interventions were very high (up to [euro ]34 000 million) and the associated monetised health benefits were mostly less than the compliance costs. CONCLUSIONS: The strongest cases for the introduction of a limit value are for: respirable crystalline silica, hexavalent chromium, and hardwood dust.

Perioperative complications of esophagectomy: Postneoadjuvant treatment versus primary surgery - Our experience and review of literature.

AIMS: : To compare perioperative complications in esophagectomy after neoadjuvant therapy v/s primary surgery. SETTINGS AND DESIGN: : Retrospective analysis of perioperative complications in a prospectively maintained data base of patients who underwent esophagectomy as Primary surgery or after neoadjuvant therapy was done. METHODS AND MATERIAL: : 238 cases of esophagectomies performed for esophageal carcinoma were analysed and compared, out of which 125(52.5%) were given neoadjuvant therapy followed by surgery and 113(47.5%) underwent primary surgery. Surgical procedure was standard for both the groups. All the cases were analysed for perioperative complications. STATISTICAL ANALYSIS USED: : Data was analysed using Open Epi soft ware. Association between the two study group was assessed with Chi square test. RESULTS: : On comparison, both the groups were comparable in demographic profile and type of surgery performed. However, tumour stage was higher for cases who received neoadjuvant therapy as expected. On analysis there was no significant difference in overall morbidity and 30 days mortality. CONCLUSIONS: : Neoadjuvant Chemo/chemoradiotherapy is a feasible option in esophageal carcinoma without increase in incidence of peri operative morbidity or mortality.

Importance of repeat tissue biopsy and tissue-based epidermal growth factor receptor T790M testing in progressed nonsmall cell lung carcinoma patients upon negative plasma genotyping for selection of third-generation tyrosine kinase inhibitor therapy: A case study.

Resistance to 1st or 2nd generation epidermal growth factor receptor (EGFR) - tyrosine kinases (TKIs) develops predominantly due to an acquired mutation, EGFR T790M. Third-generation EGFR-TKIs have demonstrated potent activity against TKI resistance mediated by EGFR T790M. Thus, it become critical to identify T790M mutation on disease progression. Analysis of tumor tissue biopsy material is considered as gold standard for mutation detection. However, lung re-biopsy in a progressed patient involves several challenges - access to tumor, patient's willingness, safety, cost. Minimally invasive plasma circulating tumor DNA (ctDNA) evolved as an alternative for detection of EGFR T790M mutation when tumor genotyping is not feasible. Although a positive T790M result from ctDNA analysis is actionable, caution should be exercised in interpreting negative plasma results. A negative result may imply the absence of a mutation or merely that a patient's tumor is not shedding ctDNA at detectable levels, thus necessitating a confirmatory tissue biopsy to rule out a false negative plasma result. In this case report, we described a 78-year-old female who underwent a reflexed tumor biopsy and tissue based testing upon negative plasma genotyping. Our case report exhibited the importance to follow proposed T790M plasma testing algorithm to screen eligible patients for 3rd generation TKI therapy.

Complete pathological response in rectal cancer after neoadjuvant therapy - case report

A fifty-four year old woman underwent colonoscopy due to symptoms of altered bowel habit and weight loss. There was a malignant looking lesion at her rectosigmoid junction [Fig. 1a] which was confirmed histologically to be a moderately differentiated adenocarcinoma. Although the blood results were normal, her CT scan and MRI [Fig 2a] showed an apple core lesion at rectosigmoid junction which was deemed to be Stage IIIC (T4aN2aM0)

Observations of Hall Reconnection Physics Far Downstream of the X Line.

Observations made using the Wind spacecraft of Hall magnetic fields in solar wind reconnection exhausts are presented. These observations are consistent with the generation of Hall fields by a narrow ion inertial scale current layer near the separatrix, which is confirmed with an appropriately scaled particle-in-cell simulation that shows excellent agreement with observations. The Hall fields are observed thousands of ion inertial lengths downstream from the reconnection X line, indicating that narrow regions of kinetic dynamics can persist extremely far downstream.

Ion-scale secondary flux ropes generated by magnetopause reconnection as resolved by MMS.

New Magnetospheric Multiscale (MMS) observations of small-scale (~7 ion inertial length radius) flux transfer events (FTEs) at the dayside magnetopause are reported. The 10 km MMS tetrahedron size enables their structure and properties to be calculated using a variety of multispacecraft techniques, allowing them to be identified as flux ropes, whose flux content is small (~22 kWb). The current density, calculated using plasma and magnetic field measurements independently, is found to be filamentary. Intercomparison of the plasma moments with electric and magnetic field measurements reveals structured non-frozen-in ion behavior. The data are further compared with a particle-in-cell simulation. It is concluded that these small-scale flux ropes, which are not seen to be growing, represent a distinct class of FTE which is generated on the magnetopause by secondary reconnection.

A phase 1 study of intermittently administered pazopanib in combination with continuous daily dosing of lapatinib in patients with solid tumors.

PURPOSE: Preclinically, pazopanib/lapatinib combination acted synergistically to suppress the activity of multiple tyrosine kinases, including VEGFR-1, 2, 3, PDGFR and c-kit (pazopanib), HER1/EGFR and HER2 (lapatinib), and several other tyrosine kinases including c-Met through, plausibly, network inhibition effects. Clinically, continuous dosing of pazopanib/lapatinib combination was associated with a higher response rate than with lapatinib monotherapy, with poor tolerance. We explored multiple intermittent dose levels of pazopanib combined with continuous daily dosing of lapatinib in patients with solid tumors. METHODS: The present study used a phase 1, modified 3 + 3, dose-escalation design to evaluate the safety and tolerability of the combination of orally received pazopanib once every other day with continuous daily dosing of lapatinib for 28 days. In the expansion phase, tumor response was evaluated in patients with specific genetic alterations (HER2 amplification, HER2 mutation, c-Met amplification, c-Met mutation, and EGFR mutation). RESULTS: Twenty-four patients were treated. The most common drug-related adverse events were fatigue 7/24 (29%), skin rash 5/21 (21%), and diarrhea 3/24 (17%), with 4/24 (16%) patients experiencing grade ≥3 drug-related adverse events. Escalation to the FDA-approved dose (800 mg daily for pazopanib and 1500 mg every day for lapatinib) was not feasible due to toxicities. Pazopanib 200 mg every other day + lapatinib 500 mg daily was considered the maximum tolerated dose (MTD). No tumor response was observed, including in patients with the specific molecular genetic alterations tested. CONCLUSION: Every other day dosing of pazopanib combined with daily lapatinib was tolerated at the established MTD, but no complete or partial tumor responses were observed at these dose levels.

A comparison of total intravenous anaesthesia using propofol with sevoflurane or desflurane in ambulatory surgery: systematic review and meta-analysis.

With the popularity of ambulatory surgery ever increasing, we carried out a systematic review and meta-analysis to determine whether the type of anaesthesia used had any bearing on patient outcomes. Total intravenous propofol anaesthesia was compared with two of the newer inhalational agents, sevoflurane and desflurane. In total, 18 trials were identified; only trials where nitrous oxide was administered to, or omitted from, both groups were included. A total of 1621 patients were randomly assigned to either propofol (685 patients) or inhalational anaesthesia (936 patients). If surgical causes of unplanned admissions were excluded, there was no difference in unplanned admission to hospital between propofol and inhalational anaesthesia (1.0% vs 2.9%, respectively; p = 0.13). The incidence of postoperative nausea and vomiting was lower with propofol than with inhalational agents (13.8% vs 29.2%, respectively; p < 0.001). However, no difference was noted in post-discharge nausea and vomiting (23.9% vs 20.8%, respectively; p = 0.26). Length of hospital stay was shorter with propofol, but the difference was only 14 min on average. The use of propofol was also more expensive, with a mean (95% CI) difference of £6.72 (£5.13-£8.31 (€8.16 (€6.23-€10.09); $11.29 ($8.62-$13.96))) per patient-anaesthetic episode (p < 0.001). Therefore, based on the published evidence to date, maintenance of anaesthesia using propofol appeared to have no bearing on the incidence of unplanned admission to hospital and was more expensive, but was associated with a decreased incidence of early postoperative nausea and vomiting compared with sevoflurane or desflurane in patients undergoing ambulatory surgery.