Safety of maintaining elective and emergency surgery during the COVID-19 pandemic with the introduction of a Protected Elective Surgical Unit (PESU): A cross-specialty evaluation of 30-day outcomes in 9,925 patients undergoing surgery in a University Health Board.

Background: The COVID-19 pandemic has caused unprecedented health care challenges mandating surgical service reconfiguration. Within our hospital, emergency and elective streams were separated and self-contained Protected Elective Surgical Units were developed to mitigate against infection-related morbidity. Aims of this study were to determine the risk of COVID-19 transmission and mortality and whether the development of Protected Elective Surgical Units can result in significant reduction in risk. Methods: A retrospective observational study of consecutive patients from 18 specialties undergoing elective or emergency surgery under general, spinal, or epidural anaesthetic over a 12-month study period was undertaken. Primary outcome measures were 30-day postoperative COVID-19 transmission rate and mortality. Secondary adjusted analyses were performed to ascertain hospital and Protected Elective Surgical Unit transmission rates. Results: Between 15 March 2020 and 14 March 2021, 9,925 patients underwent surgery: 6,464 (65.1%) elective, 5,116 (51.5%) female, and median age 57 (39-70). A total of 69.5% of all procedures were performed in Protected Elective Surgical Units. Overall, 30-day postoperative COVID-19 transmission was 2.8% (3.4% emergency vs 1.2% elective P < .001). Protected Elective Surgical Unit postoperative transmission was significantly lower than non-Protected Elective Surgical Unit (0.42% vs 3.2% P < .001), with an adjusted likely in-hospital Protected Elective Surgical Unit transmission of 0.04%. The 30-day all-cause mortality was 1.7% and was 14.6% in COVID-19-positive patients. COVID-19 infection, age > 70, male sex, American Society of Anesthesiologists grade > 2, and emergency surgery were all independently associated with mortality. Conclusion: This study has demonstrated that Protected Elective Surgical Units can facilitate high-volume elective surgical services throughout peaks of the COVID-19 pandemic while minimising viral transmission and mortality. However, mortality risk associated with perioperative COVID-19 infection remains high.

Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias.

Resistance to imatinib (IM) and other tyrosine kinase inhibitors (TKI)s is an increasing problem in leukemias caused by expression of BCR-ABL1. As chronic myeloid leukemia (CML) cell lines expressing BCR-ABL1 utilize an alternative non-homologous end-joining pathway (ALT NHEJ) to repair DNA double-strand breaks (DSB)s, we asked whether this repair pathway is a novel therapeutic target in TKI-resistant disease. Notably, the steady state levels of two ALT NHEJ proteins, poly-(ADP-ribose) polymerase 1 (PARP1) and DNA ligase IIIα, were increased in the BCR-ABL1-positive CML cell line K562 and, to a greater extent, in its imatinib-resistant (IMR) derivative. Incubation of these cell lines with a combination of DNA ligase and PARP inhibitors inhibited ALT NHEJ and selectively decreased survival with the effect being greater in the IMR derivative. Similar results were obtained with TKI-resistant derivatives of two hematopoietic cell lines that had been engineered to stably express BCR-ABL1. Together our results show that the sensitivity of cell lines expressing BCR-ABL1 to the combination of DNA ligase and PARP inhibitors correlates with the steady state levels of PARP1 and DNA ligase IIIα, and ALT NHEJ activity. Importantly, analysis of clinical samples from CML patients confirmed that the expression levels of PARP1 and DNA ligase IIIα correlated with the sensitivity to the DNA repair inhibitor combination. Thus, the expression levels of PARP1 and DNA ligase IIIα serve as biomarkers to identify a subgroup of CML patients who may be candidates for therapies that target the ALT NHEJ pathway when treatment with TKIs has failed.

Patterns of hospital admission with epistaxis for 26,725 patients over an 18-year period in Wales, UK.

INTRODUCTION: Epistaxis is the one of the most common otorhinolaryngology emergencies. This study examined the age and sex distribution of all patients admitted with epistaxis to National Health Service (NHS) hospitals in Wales, UK, over a period of 18 years and 9 months. METHODS: The Patient Episode Database for Wales was examined for all patient admissions with a diagnosis of epistaxis between April 1991 and December 2009. The age and sex of these patients was recorded and the proportion of the underlying population affected was calculated by comparing admission rates to the population data derived from the 1991 and 2001 national population censuses for Wales. RESULTS: A total of 26,725 patients were admitted to NHS hospitals in Wales with epistaxis over the period studied. The proportion of the population admitted with epistaxis increased from the age of 40 onwards. For all ages except patients in the 10-14 years group, a higher proportion of the male population was admitted with epistaxis than the comparable female population. This discrepancy was most pronounced between the ages of 15 and 49 years, with the female-to-male ratio of hospital admissions with epistaxis being 0.55. These ages (15 and 49 years) approximate the average age of menarche and menopause respectively in the UK. CONCLUSIONS: Women of menstrual age have fewer hospital admissions with epistaxis. This may be due to oestrogens providing protection to the nasal vasculature (as they do to other areas of the vascular tree).

Assessing the accuracy of tympanometric evaluation of external auditory canal volume: a scientific study using an ear canal model.

Tympanometric evaluation is routinely used as part of the complete otological examination. During tympanometric examination, evaluation of middle ear pressure and ear canal volume is undertaken. Little is reported in relation to the accuracy and precision tympanometry evaluates external ear canal volume. This study examines the capability of the tympanometer to accurately evaluate external auditory canal volume in both simple and partially obstructed ear canal models and assesses its capability to be used in studies examining the effectiveness of cerumolytics. An ear canal model was designed using simple laboratory equipment, including a 5 ml calibrated clinical syringe (Becton Dickinson, Spain). The ear canal model was attached to the sensing probe of a Kamplex tympanometer (Interacoustics, Denmark). Three basic trials were undertaken: evaluation of the tympanometer in simple canal volume measurement, evaluation of the tympanometer in assessing canal volume with partial canal occlusion at different positions within the model, and evaluation of the tympanometer in assessing canal volume with varying degrees of canal occlusion. 1,290 individual test scenarios were completed over the three arms of the study. At volumes of 1.4 cm(3) or below, a perfect relationship was noted between the actual and tympanometric volumes in the simple model (Spearman's ρ = 1) with weakening degrees of agreement with increasing volume of the canal. Bland-Altman plotting confirmed the accuracy of this agreement. In the wax substitute models, tympanometry was observed to have a close relationship (Spearman's ρ > 0.99) with the actual volume present with worsening error above a volume of 1.4 cm(3). Bland-Altman plotting and precision calculations provided evidence of accuracy. Size and position of the wax substitute had no statistical effect on results [Wilcoxon rank-sum test (WRST) p > 0.99], nor did degree of partial obstruction (WRST p > 0.99). The Kamplex tympanometer accurately and precisely assesses ear canal volume in the scientific model in both simple and partially occluded wax substitute scenarios up to a volume of 1.4 cm(3). These findings suggest that the Kamplex tympanometer could be used as an effective objective tool in evaluating the efficacy of topical cerumolytics in both laboratory and human models.

Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthma.

BACKGROUND: Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4Ralpha and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum-sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. METHODS: Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. RESULTS: Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC(100) relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05-0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC(100) relative to control (P < 0.05) at nominal b.i.d. doses of 3-100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. CONCLUSION: Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma.

Frequency and management of epistaxis in schools.

STUDY OBJECTIVES: To investigate the frequency and management of epistaxis in schools. STUDY DESIGN: A postal survey of schools. RESULTS: One hundred and fifty-seven questionnaires were posted out to 41 secondary schools (students aged 11-18 years) and to 116 primary schools (students aged four to 11 years). One hundred and twelve completed questionnaires were returned, 32 from secondary schools and 80 from primary schools. Most schools stated that they encountered a nose bleed once per month. The commonest method of treating a nose bleed was to pinch the top of the nose (an ineffective method), although pinching the bottom of the nose was almost as common. Only a minority of primary and secondary schools (37.5 and 25 per cent, respectively) had a policy for dealing with nose bleeds. Despite many respondents reportedly using an ineffective method, only two stated that they did not feel confident in dealing with nose bleeds. CONCLUSION: Nose bleeds in school students are common, and management frequently deviates from recommended guidelines.

External auditory canal exostoses in white water kayakers.

OBJECTIVE: In this study, the presence and severity of external auditory canal exostoses (EACE) in a group of white water kayakers related to the duration and intensity of kayaking and the number of ear infections reported were identified. DESIGN: A community-based volunteer cross-sectional study was completed with 92 kayakers (69 men, 23 women; mean (SD) age 29.3 (8.72) years) and 65 control volunteers (37 men, 28 women; mean (SD) age 36.9 (14.9) years). After exclusions, 269 individual ears were examined (154 kayakers and 115 controls). Participants completed a questionnaire and underwent otoscopic examination. Main outcome measures were the presence and severity of EACE, the duration and frequency of kayaking and self-reported ear infections. Exclusion criteria included other cold-water exposure, known ear pathology or poor visualisation of the auditory canal. RESULTS: The findings demonstrated that 69.5% of kayaker ears and 1.7% of the control group were found to have EACE. Severity of EACE was significantly associated with the duration (p<0.01) and frequency (p<0.05) of kayaking with 90.6% of kayakers that had participated for more than 10 years having evidence of EACE. A significant relationship also existed between the number of self-reported ear infections and the severity of EACE (p<0.01). CONCLUSION: There is a positive relationship between the duration and frequency of white water kayaking and the presence and severity of EACE and associated ear infections.

Allergen dose dependency of the early- and late-phase cutaneous response in the cynomolgus monkey.

BACKGROUND: Cutaneous administration of allergen provides a means to confirm an allergic status, investigate the pathogenesis of allergic diseases, and/or provide a mechanism to evaluate the benefit of new potential therapeutics. OBJECTIVE: Studies were performed to characterize the allergen-induced cutaneous early- and late-phase response (EPR and LPR) in the cynomolgus monkey. METHODS: Following intradermal injections of Ascaris suum allergen, the cutaneous weal and flare EPR was measured 15 min post-injection, and skin biopsies were collected at 8-24 h to determine the optimal time of LPR occurrence. Biopsies were analysed for epidermal and dermal inflammatory changes. RESULTS: The EPR was dose related with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100 allergen dilution. In contrast, the threshold dose required for a reproducible LPR was much greater requiring a dilution of 6 : 100, suggesting independent mechanisms for the EPR and LPR. The LPR 20 h post-allergen injection induced an inflammatory response in the upper and deep dermis. The response was characterized by a moderate perivascular to diffuse inflammation consisting of mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis, P<0.001; deep dermis, P=0.02). CONCLUSION: Collectively, the results indicate the dose dependency of the EPR and LPR. Furthermore, our observations indicate the value of the LPR response in the cynomolgus monkey to evaluate new therapeutics for the treatment of allergic diseases such as atopic dermatitis.

The incidence and aetiology of epistaxis in infants: a population-based study.

OBJECTIVE: To estimate the incidence and describe the aetiology of epistaxis in infants. DESIGN: Population-based study including a retrospective hospital admission database analysis and a postal questionnaire to clinicians. SETTING: Wales, United Kingdom. METHODS: Cases of epistaxis over a 6-year period (1999-2004) were identified from the Patient Episode Dataset for Wales (PEDW) and validated using clinical information to calculate the population-based incidence and ascertain the causes of epistaxis in infants in Wales. RESULTS: 36 confirmed cases were identified over the 6-year period giving an estimated annual incidence of epistaxis of 19.3 (95% CI 14.0 to 26.7) per 100,000 infants. The median age at admission was 12 weeks (interquartile range 4-33) (min 1 week, max 49 weeks). 23 of the infants had a recognised cause for their epistaxis (trauma (five), coagulation disorder (four), congenital anomaly (two), acute rhinitis or coryza (11), abusive smothering event (one)). No cause for the epistaxis was identified for 13 cases. Coagulation disorder was excluded in seven of these 13 infants but in the other six no attempt was made to exclude this disorder. Child abuse was suspected but excluded in four of the 13 cases. CONCLUSION: Hospital admission for epistaxis is a rare event. In the majority of cases in this study a simple explanation was available and proven physical abuse was rare. A bleeding disorder should always be considered and, if additional evidence suggests physical abuse, this must be excluded.

Does tonsillectomy lead to improved outcomes over and above the effect of time? A longitudinal study.

OBJECTIVE: To determine the effect of tonsillectomy on morbidity in patients listed for tonsillectomy. DESIGN: Questionnaire survey of 257 children and 159 adults who had been listed for tonsillectomy. The cohort studied had experienced delays of greater than 12 months between being listed for tonsillectomy and undergoing surgery. They had responded to an earlier questionnaire in 2003 regarding morbidity experienced while waiting for surgery. The same questionnaire was presented to them again in 2005. Morbidity experienced in 2003 was compared to that experienced in 2005 in subjects who had and had not proceeded to surgery in the interval. RESULTS: Forty-seven per cent of the cohort had undergone tonsillectomy. The questionnaire response rate was 48 per cent. Respondents reported less morbidity in 2005 than in 2003, whether or not they had had surgery. Respondents who had undergone tonsillectomy reported significantly greater reductions in morbidity than those who had not. Five per cent of children who had undergone tonsillectomy experienced at least three short episodes of tonsillitis in the six months before the questionnaire, compared with 35 per cent of those who had not undergone tonsillectomy (p < 0.001). CONCLUSIONS: The morbidity reported by patients suffering from chronic, untreated tonsillitis decreases with time. Tonsillectomy produces significantly greater reductions in morbidity than time alone.

Value of head and neck cancer incidence data on UK cancer registry websites: a comparison.

We evaluated the relative usefulness of data on head and neck cancer available on the websites of cancer registries in the United Kingdom. Data were analysed to determine the accuracy and completeness of essential information related to the incidence of head and neck cancer. We found that 16 per cent (2/11) of the registries had some cancer data but none relating to head and neck cancer patients. Seventy-five per cent (9/12) of the registries had selected data on head and neck cancer, but 33 per cent (3/9) of these pooled the various head and neck cancers into a single group. The remainder of registries offering data [66 per cent (6/9)] had a variety of ways of grouping and presenting the various types of head and neck cancer. The overall value and usefulness of head and neck cancer information on these websites were limited, especially when all the sites were considered together. The cancer registries collectively possess an extremely important asset of immense value to both the medical profession and, possibly, patients with cancer. The accessibility of this data and the overall experience of those seeking information on this subject could be improved. However, this would require significant thought, collaboration and agreement between each registry, which would involve significant extra investment.

Morbidity in patients waiting for tonsillectomy in Cardiff: a cross-sectional study.

OBJECTIVE: Our aim was to determine the morbidity of patients awaiting tonsillectomy. DESIGN: The study comprised a questionnaire survey of 379 children and 278 adults waiting over 12 months for tonsillectomy. OUTCOME MEASURES: These comprised frequency of infection, sickness absence and continuing desire for surgery. RESULTS: Response rates were 70 per cent (children) and 60 per cent (adults). Morbidity was similar in adults and children, and in those waiting more or less than two years. In the six months prior to the study, 86 per cent of children and 83 per cent of adults had had tonsillitis. Sixty per cent of children and 50 per cent of adults had had three or more episodes. Sixty-two per cent of children and 59 per cent of adults had had at least one long episode of tonsillitis, and 29 per cent of children and 24 per cent of adults had had more than three long episodes. Eighty-nine per cent of children had missed school at least once, compared with 71 per cent of adults missing work at least once (p = 0.01). The frequency of infection was significantly associated with patients' desire for surgery (p < 0.001). CONCLUSIONS: Patients awaiting tonsillectomy experience considerable morbidity. This study does not support the hypothesis that untreated patients will 'outgrow' their condition.

Instrumentation and patient characteristics that influence postoperative haemorrhage rates following tonsil and adenoid surgery.

OBJECTIVES: To investigate the effect of the type instrumentation used and the age and gender characteristics of patients on postoperative haemorrhage rates following tonsil and adenoid surgery. DESIGN: A retrospective analysis of 13 593 procedures was performed from The Patient Episode Database for Wales between 1 January 1999 and 31 March 2004. SETTING: National health policy changes created four periods of different instrument usage (reusable, single-use with diathermy, single-use alone, specified single-use with diathermy). These and the age and gender distribution of the patients were examined against four categories of postoperative haemorrhage. MAIN OUTCOME MEASURES: Postoperative haemorrhage rates were expressed as the number of complications per operations performed. Primary postoperative haemorrhage that occurred during the initial admission either required a return to theatre [R1] or was managed conservatively [N1]; secondary postoperative haemorrhage that required a return to hospital either returned to theatre [R2] or was managed conservatively [N2], were compared. RESULTS: Primary haemorrhage with return to theatre doubled, from the baseline rate with reusable instruments, from 0.6% (CI 0.5-0.8) to 1.2% (CI 0.7-1.9) when single-use instruments were introduced and remained high at 1.4% (CI 0.9-2.1) after the withdrawal of single-use diathermy. This haemorrhage rate returned to the baseline rate (0.6% CI 0.3-1.0) when specified single-use instruments were introduced. None of the other haemorrhage rates changed significantly throughout the four observation periods. Adenotonsillectomy and tonsillectomy patients have different age and gender patterns. In a univariate analysis, males over the age of 12 years were twice as likely to have haemorrhage with return to theatre than girls of the same age, 3.8% (CI 3.0-4.7) versus 1.7% (CI 1.4-2.1). CONCLUSIONS: A significant rise in serious postoperative primary haemorrhage but not secondary haemorrhage was seen following the initial introduction of single-use instruments that reverted to baseline with the introduction of specified single-use instruments. Diathermy does not appear to have affected the haemorrhage rates. There is a distinct age and gender pattern for tonsil and adenoid surgery and risk of postoperative haemorrhage. The use of arbitrary divisions of age may be misleading in studies that examine post-tonsillectomy haemorrhage.

A laboratory and clinical evaluation of single-use instruments for tonsil and adenoid surgery.

OBJECTIVES: To compare the quality and consistency of single-use adenotonsillectomy instruments available in the UK with reusable instruments and examine their performance in a clinical setting. DESIGN: A laboratory assessment of each reusable instrument created a detailed specification for the respective single-use equivalent. A surveillance system monitored the performance of a selected set of specified single-use instruments. SETTING: Single-use instruments were withdrawn shortly after their introduction in 2001. Persisting concerns from the Spongiform Encephalopathy Advisory Committee led to an investigation into the feasibility of continuing to use such instruments. MAIN OUTCOME MEASURES: The numbers of instruments from each set judged as unacceptable or as good as the original. The number and cause of instrument failure during clinical surveillance. RESULTS: Between 40% and 93% of the instruments on each set were as good as the original and between 0% and 40% of the instruments were unacceptable from six sets of steel and one set of polymer instruments. 4151 procedures were monitored between 1 February 2003 and 31 March 2004 using a total of 41 376 instruments. Problems were reported with 335 (0.8%) instruments, 46% attributable to instrument design, 14% to poor design control and 13% to instruments escaping quality control systems. Following correction of the faults, between 1 January 2004 and 31 March 2004 the problem rate fell to 0.4%. CONCLUSIONS: High quality single-use instruments for tonsil and adenoid surgery are available in the UK. Some companies offered inferior instruments not fit for their purpose. The procurement, introduction and subsequent clinical approval of single-use instruments requires a radically different approach to that currently applied to the purchase of reusable surgical equipment. Careful monitoring of their introduction is essential.

Inhibition of stem cell factor reduces pulmonary cytokine levels during allergic airway responses.

Stem cell factor (SCF) has a significant role in the inflammation and activation of allergic airway responses. When monoclonal anti-SCF was administered intratracheally during allergen challenge there was a significant alteration of eosinophil accumulation and airway hyperreactivity (AHR). Anti-SCF treatment also attenuated pulmonary cytokine and chemokine levels. In particular, there was an antibody dose-dependent decrease in interleukin (IL)-5 and tumour necrosis factor (TNF)-alpha. There was also a significant reduction of CCL2 and CCL5, which correlated with the reduction in AHR. Mice treated with anti-SCF demonstrated a significant decrease in pulmonary gob-5 gene expression, which has been shown to correlate to goblet cell hyperplasia/metaplasia relating to airway mucus production. Blocking SCF-mediated activation within the airway using a monoclonal antibody indicates that this cytokine may represent a viable target for therapeutic intervention that could affect multiple aspects of allergen-induced immunopathology.

Risk-adjusted comparative audit. Is Possum applicable to head and neck surgery?

Possum (the physiological and operative severity score for the enumeration of mortality) is used in many surgical specialities for comparative audit. We investigated its validity in relation to head and neck surgery by retrospectively scoring 301 operative interventions. We also applied the P-Possum (Portsmouth Possum) equation for mortality. We compared our observed with the predicted outcomes. We introduced two new variables, radiotherapy and previous surgery to the operative site, to test their association with outcome. We found that Possum is valid for morbidity but predicts more accurately for high-risk than for low-risk groups. Neither Possum or P-Possum accurately predicts mortality. Radiotherapy and previous surgery were both significant for the development of postoperative complications (P = 0.002, P = 0.007 respectively) and are worthy of inclusion in a Possum score for head and neck surgery.