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Abstract In 2016, a new, improved and modern intensive care unit was constructed at Kamuzu Central Hospital in Lilongwe, Malawi. Having been operational for about 4 years, there has not been a systematic audit to gauge its performance. Therefore, this quantitative retrospective cohort study aimed at investigating the performance of the intensive care unit at Kamuzu Central Hospital in Lilongwe, Malawi. We analysed the patterns of admission through 250 clinical cases and their respective outcomes spanning from 1st January 2019 to 31st December 2019 using STATA. Descriptive and inferential statistics were computed. We also had a follow-up discussion with the Head of the unit to better understand the unit’s functioning. Out of the 250 admissions, we evaluated 249 case files. About 30.8% of all patients were referred from the main operating theatre, and 20.7% from the casualty (emergency medicine). Head injury (26.7%) and peritonitis (15.7%) were the commonest causes of admission. The overall mortality was 52.2% with more females (57.5%) dying than males (47.9%). Head injury and peritonitis had the highest contribution to the mortality accounting for 25.3% and 16.9% of all deaths respectively. In conclusion, despite the new unit registering an improved performance compared to the old unit’s 2012 mortality of 60.9%, the current mortality rate of 52.2% generally reflects a suboptimal performance. The intensive care unit is still grappling with a number of challenges that need immediate attention including few working beds, shortage of critical care specialists and nursing staff and lack of standard admission criteria.

Background: In adults, the solitary lateral cystic neck mass remains a diagnostic challenge with little solid material to target for cytology and few clues on imaging modalities to suggest underlying malignancy. Method: This study was a retrospective review of patients presenting with a lateral cystic neck mass to a tertiary academic head and neck centre over a 10-year period. Results: A total of 25 of 157 cystic lesions were subsequently malignant on paraffin section histopathology, with the youngest patient being 42 years. In the age cohort over 40 years, 30 per cent of males and 10 per cent of females were diagnosed with malignancy. The ipsilateral palatine tonsil was the most common primary site (50 per cent). A total of 85 per cent of cases demonstrated integrated human papillomavirus infection. Age, male sex and alcohol were significant risk factors on univariate analysis. Ultrasound-guided fine needle aspiration cytology and magnetic resonance imaging represented the most accurate pre-open biopsy tests. Conclusion: The authors of this study advocate for a risk-stratified, evidence-based workup in patients with solitary lateral cystic neck mass in order to optimise timely diagnosis. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has caused unprecedented disruption to the routine operations of healthcare services across the world. As the potential duration of the pandemic remains uncertain, the need to develop strategies to continue urgent elective services has received increasing attention. A solution adopted in the Kent, Sussex and Surrey area of England has been to create COVID-19-protected cancer hubs. The Queen Victoria Hospital is the designated hub for head and neck cancer services in the area. We report on the evolution of the head and neck cancer care pathway and standard operating protocols put in place and how these have combined both national guidelines and local problem solving. It is hoped that our experience can help guide other centres as they re-establish head and neck cancer services during the ongoing pandemic., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

A rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) incidence has occurred throughout the developed world, where it has been attributed to an increasing impact of human papillomavirus (HPV) on disease etiology. This report presents the findings of a multicenter cross-sectional retrospective study aimed at determining the proportion of HPV-positive and HPV-negative OPSCC within the United Kingdom. Archival tumor tissue blocks from 1,602 patients previously diagnosed with OPSCC (2002-2011) were collated from 11 centers. HPV status was determined with three validated commercial tests to provide valid data for 1,474 cases in total. Corresponding national incidence data from the same decade were obtained from UK Cancer registries. The overall proportion of HPV + OPSCC between 2002 and 2011 was 51.8% [95% confidence interval (CI), 49.3-54.4], and this remained unchanged throughout the decade [unadjusted RR = 1.00 (95% CI, 0.99-1.02)]. However, over the same period, the incidence of OPSCC in the broader UK population underwent a 2-fold increase [age-standardized rate 2002: 2.1 (95% CI, 1.9-2.2); 2011: 4.1 (95% CI, 4.0-4.3)]. Although the number of OPSCCs diagnosed within the United Kingdom from 2002 to 2011 nearly doubled, the proportion of HPV + cases remained static at approximately 50%. Our results argue that the rapidly increasing incidence of OPSCC in the United Kingdom cannot be solely attributable to the influence of HPV. The parallel increase in HPV + and HPV - cases we documented warrants further investigation, so that appropriate future prevention strategies for both types of disease can be implemented. Cancer Res; 76(22); 6598-606. ©2016 AACR., (©2016 American Association for Cancer Research.)

Objective: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC., Methods: Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases., Results: A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort., Conclusions: Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Craniosynostosis is defined as premature fusion of the cranial suture lines and is part of a syndrome in 15% to 40% of the patients. There is limited literature available regarding these children's ability to smell. Most of them will undergo numerous surgical procedures, some of which may alter their sense of smell, potentially leading to significant social as well as safety implications. Ethical approval was obtained for this pilot study. Children with syndromic craniosynostosis were recruited and underwent anterior rhinoscopy, prior to performing a smell test utilizing the Sensonic pediatric Smell wheel. The results were compared to an age-matched control group. Eight children with syndromic craniosynostosis participated in the study. Of a possible total score of 11, their mean average score was 6.6 and the median was 6. In comparison, the mean average score for the control group was 7.5 and the median was 7. Although the study group was small, this pilot study demonstrates that children with syndromic craniosynostosis have a similar ability to identify smells to an age-matched cohort. Further research can now be undertaken to see whether or not midface advancement procedures affect these children's sense of smell.

Unlabelled: Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1) (MVA-NP-M1) or pandemic H1N1 HA (MVA-pdmH1HA). The MVA vaccine uptake and expression, and T and B cell responses were analyzed. MVA-vectored vaccines were highly efficient infecting NALT and vaccine antigens were highly expressed by B cells. MVA-NP-M1 elicited T cell response with greater numbers of IFNγ-producing CD4+ T cells and tissue-resident memory T cells than controls. MVA-pdmH1HA induced cross-reactive anti-HA antibodies to a number of influenza subtypes, in an age-dependent manner. The cross-reactive antibodies include anti-avian H5N1 and mainly target HA2 domain., Conclusion: MVA vaccines are efficient in infecting NALT and the vaccine antigen is highly expressed by B cells. MVA vaccines expressing conserved influenza antigens induce cross-reactive T and B cell responses in human NALT in vitro, suggesting the potential as mucosal vaccines for broader immunity against influenza., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: 2009 H1N1 pandemic influenza (A(H1N1)pdm09) virus infected large numbers of people worldwide. Recent studies suggest infection with A(H1N1)pdm09 virus elicited cross-reactive anti-hemagglutinin (HA) memory B cell response to conserved regions of HA. However, the breadth and magnitude of cross-reactive immunity in children and adults following A(H1N1)pdm09 infection are unknown., Methods: We investigated serum anti-HA immunity to a number of group-1 and -2 viruses in children and adults using hemagglutination inhibition (HAI), enzyme-linked immunosorbent assay and virus neutralization assay., Results: Applying hemagglutination inhibition (HAI) titers ⩾40 against A(H1N1)pdm09 as threshold of sero-positivity, we observed significantly higher levels of anti-HA antibodies to a number of virus subtypes, including those neutralizing H5N1, in subjects with HAI titer ⩾40 than those with HAI <40. Adults demonstrated broader and stronger cross-reactive anti-HA antibodies than children, including cross-reactive anti-HA1 and -HA2 antibodies. By comparison, individuals with serologic evidence of recent exposure to seasonal H1N1 or H3N2 did not show such broad cross-reactive immunity., Conclusion: Our results suggest individuals exposed to A(H1N1)pdm09 virus developed a broad and age-associated cross-reactive anti-HA immunity which may have important implications for future vaccination strategies to enable protection against a broader range of influenza viruses., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition., (©2014 American Association for Cancer Research.)

Extended vertical hemilaryngectomy and reconstruction with a neovascularised tracheal autograft is a two-stage procedure for advanced unilateral tumours of the larynx. The purpose of this study was to review our early experience of this technique by reporting our clinical outcomes and highlighting some key learning points. Patients were identified from the Liverpool Head and Neck Cancer electronic database. Case notes were reviewed for demographic data, tumour stage, treatment, complications and outcomes. Eleven patients (all males) were identified. The mean age of the cohort was 58.2 years (range 37-78 years). The overall average follow-up period was 41.5 months (range 14 days-75 months). Of the 11 cases, 3 had completed stage 1 only. The most common complications following stage 1 procedure are related to the surgical neck wound (36% of cases). Of the remaining eight patients who completed the first two surgical stages, closure of tracheostomy stoma was possible in seven; all seven subsequently resumed a normal oral diet. All these patients have subsequently remained free of disease at latest follow-up. There were two cases of post-operative pneumonia and one case of radial forearm free-flap failure. In contrast, only one case of post-operative pneumonia was recorded following the stage 2 procedure. In total, three patients in this cohort were dead at follow-up. This technique has a role in the management of a select group of fit patients presenting with unilateral tumours of the glottis and who are otherwise destined for a total laryngectomy. Whilst the technique is complex, we have shown that its introduction is possible in a suitably specialised and motivated surgical unit.

Over 25 years ago Francis reported an association between blood transfusion and worsened cancer prognosis. Subsequently there has been much debate over whether there is in fact such an association, and if so, what is its underlying mechanism. Allogeneic blood transfusion is the most frequent allo-transplantation procedure performed on a routine basis with no prior HLA-typing. 50% of the recipients of unprocessed red cells and platelets become allo-immunised. It is our proposition that as result of normal physiological ageing and metabolic processes (with depletion of ATP and reduction of active membrane processes), there is leaching of biologically active substances from the cells into stored blood products. These leached bioactive substances have immuno-modulatory effects, which may in part explain the increased likelihood of postoperative sepsis and adult respiratory distress syndrome in transfusion recipients. They also promote cell growth and angiogenesis and may therefore have a direct effect on tumour growth. We provide evidence to support a possible hypothesis which could explain much of the conflicting clinical and experimental evidence.