Research undertaken by staff affiliated to Beaumont Hospital

Recent Submissions

  • The impact of the COVID-19 pandemic on the provision of endovascular thrombectomy for stroke: an Irish perspective.

    Brennan, David; Power, Sarah; O'Hare, Alan; Brennan, Paul; Thornton, John; Brosnan, Conor; Reid, Conor; Crockett, Matthew (2023-02-16)
    Background: The COVID-19 pandemic produced unprecedented challenges to healthcare systems. These challenges were amplified in the setting of endovascular thrombectomy (EVT) for large vessel occlusion strokes given the time-sensitive nature of the procedure. Aims: To assess the impact of the COVID-19 pandemic on service provision at the primary endovascular stroke centre in Ireland. Methods: A retrospective review of the National Thrombectomy Service database was performed. All patients undergoing EVT from 1 January to 31 December inclusive of 2019 to 2021 were included. Patient demographics, functional outcomes and endovascular treatment time metrics were recorded. Results: Data from 2019, 2020 and 2021 were extracted. Three hundred seven thrombectomies were performed in 2019 and 2020; this number increased to 327 in 2021. Median time from arrival to groin puncture for thrombectomy was 64 min in 2019, increasing to 65 min in 2020. In 2021, this decreased to 52 min. Median time taken from groin puncture to first perfusion remained stable from 2019 to 2021 years at 20 min. Total duration of emergency thrombectomies reduced from 32 min in 2019 to 27 min in 2020. This increased to 29 min in 2021. Conclusions: Despite the myriad of challenges presented by the pandemic, service provision at the primary Irish ESC, and the referring hospitals, has proven to be robust. Procedural time metrics were maintained whilst the expected reduction in number of EVTs performed did not materialise, there actually being a significant increase in number of EVTs performed in the pandemic's second year.
  • An observational study of dose dense chemotherapy with lipegfilgrastim support in early breast cancer.

    Rashed, Ahmed; Fitzpatrick, Orla M; Easty, David J; Collins, Dearbhaile; Mallet, Victoria; Milewski, Maciej; Egan, Keith; Grogan, Liam; Hennessy, Bryan T; Morris, Patrick G; et al. (2023-02-20)
    This was a single arm, non-interventional, prospective study. The primary endpoint was to determine the rate of neutropenia defined as ANC of < 1.0 × 109/L, during four cycles of dose dense AC with lipegfilgrastim support. The secondary endpoints were the incidence of febrile neutropenia, (temperature > 38 °C and ANC < 1.0 × 109/L), treatment delays, premature treatment cessation and toxicity.
  • Isavuconazole Treatment of Spinal Cord Invasive Aspergillosis Guided by Cerebrospinal Fluid (1,3)-β-d-Glucan Levels in a Patient with Low Interferon-Gamma and Ulcerative Colitis.

    Reidy, Paul; O'Toole, Aoibhlinn; Caird, John; McNally, Cora; McConkey, Samuel; de Barra, Eoghan; O’Regan, Siobhán; O'Kelly, Brendan (2022-05-25)
    This case highlights the use of (1,3)-beta-d glucan to direct treatment of a cervical spinal cord Aspergillus fumigatus infection in a 22-year-old woman immunocompromised due to steroid and anti-TNF therapy in the context of ulcerative colitis and interferon gamma deficiency. A 4-year treatment course requiring neurosurgical intervention on four occasions and prolonged antifungal therapy, including isavuconazole, resulted in clinical cure with a corresponding decrease in CSF beta-d-glucan to &lt;30 pg/mL. Serum and CSF galactomannan levels were not elevated at any point during the clinical course.
  • An Oncology Urgent Care Clinic for the Management of Immune-Related Adverse Events: A Descriptive Analysis.

    Tackett, Sean; Myers, Samantha; Brahmer, Julie R; Browner, Ilene S; Ettinger, David S; Forde, Patrick M; Hales, Russell K; Hann, Christine L; Lam, Vincent K; Marrone, Kristen A; et al. (2022-06-17)
    Introduction: With the increasing use of immune checkpoint inhibitors (ICI) for cancer, there is a growing burden on the healthcare system to provide care for the toxicities associated with these agents. Herein, we aim to identify and describe the distribution of encounters seen in an urgent care setting for immune-related adverse events (irAEs) and the clinical outcomes from irAE management. Methods: Patient demographics, disease characteristics, and treatment data were collected retrospectively from encounters at an oncology Urgent Care Clinic (UCC) from a single tertiary center for upper aerodigestive malignancies from 1 July 2018 to 30 June 2019. Data were summarized using descriptive statistics with odds ratios for associations between patient features and hospitalization after UCC evaluation. Results: We identified 494 encounters from 289 individual patients over the study period. A history of ICI therapy was noted in 34% (n = 170/494) of encounters and 29 encounters (29/170, 17%) were confirmed and treated as irAEs. For those treated for irAEs, the majority (n = 19/29; 66%) were discharged home. Having an irAE was associated with an increased risk of hospitalization compared to non-irAEs (OR 5.66; 95% CI 2.15-14.89; p &lt; 0.001). Conclusion: In this single institution experience, the majority of UCC encounters for confirmed irAEs were safely managed within the UCC. In ICI-treated patients, having an irAE was associated with an increased risk of hospitalization versus non-irAEs.
  • Spectrum of Phenotypic, Genetic, and Functional Characteristics in Patients With Epilepsy With Pathogenic Variants.

    Schwarz, Niklas; Seiffert, Simone; Pendziwiat, Manuela; Rademacher, Annika Verena; Brünger, Tobias; Hedrich, Ulrike B S; Augustijn, Paul B; Baier, Hartmut; Bayat, Allan; Bisulli, Francesca; et al. (2022-03-21)
    KCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyze the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.
  • Test-retest reliability of arterial spin labelling for cerebral blood flow in older adults with small vessel disease.

    Binnie, Lauren R; Pauls, Mathilde M H; Benjamin, Philip; Dhillon, Mohani-Preet K; Betteridge, Shai; Clarke, Brian; Ghatala, Rita; Hainsworth, Fearghal A H; Howe, Franklyn A; Khan, Usman; et al. (2022-01-26)
    Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter. Here we quantified test–retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days). Test–retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM). We conclude that pCASL has high test–retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.
  • The cost of cancer care: how far would you go for a trial?

    Fitzpatrick, Orla; Murphy, Catherine; Duignan, Erica; Egan, Keith; Hennessy, Bryan T; Grogan, Liam; Murphy, Adrian; Breathnach, Oscar S; Naidoo, Jarushka; Morris, Patrick G (2022-01-17)
    Background: Clinical trials are often considered the gold standard in cancer care. However, patients face barriers in trial participation including distances to cancer centres and personal costs including changing employment status, cost of medications, inpatient admissions, and parking tariffs. Aim: Our aim was to compare the distances patients travelled for clinical trials compared to those receiving standard systemic anticancer therapy (SACT). We also investigated the additional costs associated with this. Methods: This was a retrospective review of electronic patient medical records. The distance from the patients' home address to Beaumont was calculated as a one-way journey in kilometres. Patients attending for clinical trials were compared to those receiving standard of care SACT. Results: A total of 271 patients receiving standard SACT over a 5-day period and 111 patients enrolled on 24 clinical trials were included. The median one-way distance travelled by patients enrolled in clinical trials was 41.4 km, compared to 14 km in those patients' receiving standard of care SACT. The median estimated cost was €13 vs €4.20 for those enrolled on clinical trials compared to those receiving standard of care treatment, respectively. Conclusion: Patients enrolled on clinical trials often travel more than twice as far to receive their anti-cancer treatment compared to those receiving standard of care SACT and incur an increased cost of travel expenses.
  • Bilateral patellar tendon rupture following low-energy trauma in a young patient without predisposing risk factors.

    Murphy, Suzanne M; McAleese, Timothy; Elghobashy, Osama; Walsh, James (2022-04-30)
    We describe the case of a 25 year old male who presented with a bilateral patellar tendon ruptures without any of the identified risk factors for tendon injuries. Our patient is the youngest adult reported to date with confirmed bilateral, unprovoked, patellar tendon ruptures. We accompany our case with an up-to-date literature review on this topic. A degree of clinical suspicion is required for emergency room physicians as well as orthopaedic surgeons assessing such patients to avoid missing bilateral injuries. Point of care ultrasound may be utilised when there is doubt regarding the diagnosis. Prompt surgical management and a specific rehabilitation programme are both required to ensure maximum recovery of these patients.
  • Ultraviolet disinfection robots to improve hospital cleaning: Real promise or just a gimmick?

    Diab-El Schahawi, Magda; Zingg, Walter; Vos, Margreet; Humphreys, Hilary; Lopez-Cerero, Lorena; Fueszl, Astrid; Zahar, Jean Ralph; Presterl, Elisabeth (2021-02-12)
    The global COVID-19 pandemic due to the novel coronavirus SARS-CoV-2 has challenged the availability of traditional surface disinfectants. It has also stimulated the production of ultraviolet-disinfection robots by companies and institutions. These robots are increasingly advocated as a simple solution for the immediate disinfection of rooms and spaces of all surfaces in one process and as such they seem attractive to hospital management, also because of automation and apparent cost savings by reducing cleaning staff. Yet, there true potential in the hospital setting needs to be carefully evaluated. Presently, disinfection robots do not replace routine (manual) cleaning but may complement it. Further design adjustments of hospitals and devices are needed to overcome the issue of shadowing and free the movement of robots in the hospital environment. They might in the future provide validated, reproducible and documented disinfection processes. Further technical developments and clinical trials in a variety of hospitals are warranted to overcome the current limitations and to find ways to integrate this novel technology in to the hospitals of to-day and the future.
  • Distance Management of Spinal Disorders During the COVID-19 Pandemic and Beyond: Evidence-Based Patient and Clinician Guides From the Global Spine Care Initiative.

    Haldeman, Scott; Nordin, Margareta; Tavares, Patricia; Mullerpatan, Rajani; Kopansky-Giles, Deborah; Setlhare, Vincent; Chou, Roger; Hurwitz, Eric; Treanor, Caroline; Hartvigsen, Jan; et al. (2021-02-17)
    Abstract: Background The COVID-19 pandemic has greatly limited patients' access to care for spine-related symptoms and disorders. However, physical distancing between clinicians and patients with spine-related symptoms is not solely limited to restrictions imposed by pandemic-related lockdowns. In most low- and middle-income countries, as well as many underserved marginalized communities in high-income countries, there is little to no access to clinicians trained in evidence-based care for people experiencing spinal pain. Objective The aim of this study is to describe the development and present the components of evidence-based patient and clinician guides for the management of spinal disorders where in-person care is not available. Methods Ultimately, two sets of guides were developed (one for patients and one for clinicians) by extracting information from the published Global Spine Care Initiative (GSCI) papers. An international, interprofessional team of 29 participants from 10 countries on 4 continents participated. The team included practitioners in family medicine, neurology, physiatry, rheumatology, psychology, chiropractic, physical therapy, and yoga, as well as epidemiologists, research methodologists, and laypeople. The participants were invited to review, edit, and comment on the guides in an open iterative consensus process. Results The Patient Guide is a simple 2-step process. The first step describes the nature of the symptoms or concerns. The second step provides information that a patient can use when considering self-care, determining whether to contact a clinician, or considering seeking emergency care. The Clinician Guide is a 5-step process: (1) Obtain and document patient demographics, location of primary clinical symptoms, and psychosocial information. (2) Review the symptoms noted in the patient guide. (3) Determine the GSCI classification of the patient’s spine-related complaints. (4) Ask additional questions to determine the GSCI subclassification of the symptom pattern. (5) Consider appropriate treatment interventions. Conclusions The Patient and Clinician Guides are designed to be sufficiently clear to be useful to all patients and clinicians, irrespective of their location, education, professional qualifications, and experience. However, they are comprehensive enough to provide guidance on the management of all spine-related symptoms or disorders, including triage for serious and specific diseases. They are consistent with widely accepted evidence-based clinical practice guidelines. They also allow for adequate documentation and medical record keeping. These guides should be of value during periods of government-mandated physical or social distancing due to infectious diseases, such as during the COVID-19 pandemic. They should also be of value in underserved communities in high-, middle-, and low-income countries where there is a dearth of accessible trained spine care clinicians. These guides have the potential to reduce the overutilization of unnecessary and expensive interventions while empowering patients to self-manage uncomplicated spinal pain with the assistance of their clinician, either through direct in-person consultation or via telehealth communication.
  • Solitary Plasmacytoma Management and Outcomes

    Comerford, C; McKey, S; Wallace, N; McArdle, O; Faul, C; Glavey, S; Sargent, J; Thornton, P; Murphy, P T; Quinn, J (2019-06-17)
    Solitary plasmacytoma (SP) is a rare malignant tumour characterised by a localised collection of neoplastic plasma cells. SP is closely related to multiple myeloma (MM) which, in contrast, is characterised by widespread plasma cell neoplasia with systemic features including hypercalcaemia, bone disease, anaemia and/or renal impairment. SPs can manifest as a solitary bone plasmacytoma (SBP) or less commonly as a soft tissue mass i.e. solitary extramedullary plasmacytoma (SEP). SP is far less common than MM (~5% of plasma cell malignancies) and therefore there is a lack of high-quality data guiding management1. Like MM, SP is more common in males but has a lower median age of onset. SBP most commonly affects the axial skeleton 1,2, particularly the vertebrae, with SBP accounting for ~30% of malignant spinal bone tumours1. Less common sites of SBP include the ribs, clavicle and scapulae2. SEP (ratio approximately 10:1) are much less common than SBP1,3 and are most frequently seen in the upper respiratory tract and less commonly in the lower respiratory tract, gastrointestinal tract and rarely in sites such as breast and pituitary gland3. Five year overall survival(OS) following a diagnosis of SP is variable with reported ranges of 40-85%4.
  • Reply to Blot and to Inoue

    McElvaney, Oliver J; McEvoy, Natalie L; McElvaney, Noel G; Curley, Gerard F; Royal College of Surgeons in Ireland Dublin, Ireland and. Beaumont Hospital Dublin, Ireland. (the American Thoracic Society, 2021-09-21)
    Reply to Blot et al. and to Inoue et al. From the Authors: We thank Blot and colleagues for their interest in our article and for raising an important question regarding the suitability of IL-6 as a therapeutic target in coronavirus disease (COVID-19). In their correspondence, Blot and colleagues provide data on IL-6 levels measured in patients with a diagnosis of COVID-19 versus non–COVID-19 pneumonia. Although we believe the data presented by Blot and colleagues are valid, we suggest that the IL-6 levels depicted are, by virtue of sample timing, processing methodology, and patient severity of disease, not comparable to ours and should be interpreted in context.
  • CSF Rhinorrhea After Endonasal Intervention to the Skull Base (CRANIAL) - Part 2: Impact of COVID-19.

    CRANIAL Consortium (World Neurosurg ., 2021-01-11)
    Abstract Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised regarding the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, especially during endonasal neurosurgical operations. The Pituitary Society has produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the effects of COVID-19.
  • Novel case of a scleroderma-mimicking syndrome associated with gastrointestinal stromal tumour.

    Butt, Zaran Ahmad; Ng, Wan Lin; Osman, Kamal; Howard, Donough (2021-03-04)
    We report a case of a 54-year-old man who developed an atypical systemic syndrome involving Raynaud's phenomenon, pulmonary fibrosis and skin thickening. These features were initially suggestive of newly diagnosed scleroderma. However, he displayed atypical clinical features of same, antinuclear antibody was negative and symptoms were refractory to various immunosuppressive therapies. CT imaging revealed a gastric mass, which later proved to be a gastrointestinal stromal tumour (GIST). Resection of the GIST leads to minimal symptomatic improvement. Surveillance imaging 1 year later revealed metastatic deposits. He was subsequently initiated on imatinib therapy, which led to a rapid improvement in fibrotic changes within weeks. While there have been previous descriptions of paraneoplastic fibrotic disorders, this is the first description of a scleroderma mimic in the setting of a GIST. It highlights an important potential overlap in the pathogenesis of these disease processes and the potential efficacy of tyrosine kinase inhibitors for scleroderma-like fibrotic disorders.
  • Development of a Novel Weighted Ranking Method for Immunohistochemical Quantification of a Heterogeneously Expressed Protein in Gastro-Esophageal Cancers.

    Richards, Cathy E; Sheehan, Katherine M; Kay, Elaine W; Hedner, Charlotta; Borg, David; Fay, Joanna; O'Grady, Anthony; Hill, Arnold D K; Jirström, Karin; Hopkins, Ann M (2021-03-13)
    High expression of Junctional Adhesion Molecule-A (JAM-A) has been linked with poor prognosis in several cancers, including breast cancers overexpressing the human epidermal growth factor receptor-2 (HER2). Furthermore, JAM-A expression has been linked with regulating that of HER2, and associated with the development of resistance to HER2-targeted therapies in breast cancer patients. The purpose of this study was to establish a potential relationship between JAM-A and HER2 in HER2-overexpressing gastro-esophageal (GE) cancers. Interrogation of gene expression datasets revealed that high JAM-A mRNA expression was associated with poorer survival in HER2-positive gastric cancer patients. However, high intra-tumoral heterogeneity of JAM-A protein expression was noted upon immunohistochemical scoring of a GE cancer tissue microarray (TMA), precluding a simple confirmation of any relationship between JAM-A and HER2 at protein level. However, in a test-set of 25 full-face GE cancer tissue sections, a novel weighted ranking system proved effective in capturing JAM-A intra-tumoral heterogeneity and confirming statistically significant correlations between JAM-A/HER2 expression. Given the growing importance of immunohistochemistry in stratifying cancer patients for the receipt of new targeted therapies, this may sound a cautionary note against over-relying on cancer TMAs in biomarker discovery studies of heterogeneously expressed proteins. It also highlights a timely need to develop validated mechanisms of capturing intra-tumoral heterogeneity to aid in future biomarker/therapeutic target development for the benefit of cancer patients.
  • Effect of routinely assessing and addressing depression and diabetes distress using patient-reported outcome measures in improving outcomes among adults with type 2 diabetes: a systematic review protocol.

    McMorrow, Rita; Hunter, Barbara; Hendrieckx, Christel; Kwasnicka, Dominika; Cussen, Leanne; Ho, Felicia Ching Siew; Speight, Jane; Emery, Jon; Manski-Nankervis, Jo-Anne (2021-03-15)
    Introduction: Type 2 diabetes is a global health priority. People with diabetes are more likely to experience mental health problems relative to people without diabetes. Diabetes guidelines recommend assessment of depression and diabetes distress during diabetes care. This systematic review will examine the effect of routinely assessing and addressing depression and diabetes distress using patient-reported outcome measures in improving outcomes among adults with type 2 diabetes. Methods and analysis: MEDLINE, Embase, CINAHL Complete, PsycInfo, The Cochrane Library and Cochrane Central Register of Controlled Trials will be searched using a prespecified strategy using a prespecified Population, Intervention, Comparator, Outcomes, Setting and study design strategy. The date range of the search of all databases will be from inception to 3 August 2020. Randomised controlled trials, interrupted time-series studies, prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies published in peer-reviewed journals in the English language will be included. Two review authors will independently screen abstracts and full texts with disagreements resolved by a third reviewer, if required, using Covidence software. Two reviewers will undertake risk of bias assessment using checklists appropriate to study design. Data will be extracted using prespecified template. A narrative synthesis will be conducted, with a meta-analysis, if appropriate.
  • Resistance to Cell Death in Mucinous Colorectal Cancer-A Review.

    O'Connell, Emer; Reynolds, Ian Sean; McNamara, Deborah A; Burke, John P; Prehn, Jochen (2021-03-19)
    Mucinous colorectal cancer (CRC) is estimated to occur in approximately 10-15% of CRC cases and is characterized by abundant extracellular mucin. Mucinous CRC is frequently associated with resistance to apoptosis. Inferior prognosis is observed in mucinous CRC, particularly in rectal cancer and metastatic cases. Mucins are heavily glycosylated secretory or transmembrane proteins that participate in protection of the colonic epithelium. MUC2 overexpression is a hallmark of mucinous CRCs. Mucinous CRC is associated with KRAS and BRAF mutation, microsatellite instability and the CpG island methylator phenotype. Mutations of the APC gene and p53 mutations which are characteristic non-mucinous colorectal adenocarcinoma are less common in mucinous CRC. Both physical and anti-apoptotic properties of mucin provide mechanisms for resistance to cell death. Mucin glycoproteins are associated with decreased expression of pro-apoptotic proteins, increased expression of anti-apoptotic proteins and increased cell survival signaling. The role for BCL-2 proteins, including BCL-XL, in preventing apoptosis in mucinous CRC has been explored to a limited extent. Additional mechanisms opposing cell death include altered death receptor expression and altered mutation rates in genes responsible for chemotherapy resistance. The roles of alternate cell death programs including necroptosis and pyroptosis are not well understood in mucinous CRC. While the presence of MUC2 is associated with an immunosuppressive environment, the tumor immune environment of mucinous CRC and the role of immune-mediated tumor cell death likewise require further investigation. Improved understanding of cell death mechanisms in mucinous CRC may allow modification of currently used regimens and facilitate targeted treatment.
  • Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

    Nguyen, Thanh N; Haussen, Diogo C; Qureshi, Muhammad M; Yamagami, Hiroshi; Fujinaka, Toshiyuki; Mansour, Ossama Y; Abdalkader, Mohamad; Frankel, Michael; Qiu, Zhongming; Taylor, Allan; et al. (2021-03-26)
    Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
  • Acute complicated appendicitis caused by an ingested toothpick - A case report.

    Lloyd, A J; Abd Elwahab, S M; Boland, M R; Elfadul, A; Hill, A D K; Power, C (2022-02-25)
    Introduction and importance: Acute appendicitis is one of the most common presentations to the emergency department, particularly in young adults. A combination of clinical suspicion, inflammatory blood markers and imaging modalities such as ultrasound and CT are used for its definitive diagnosis. Early detection and intervention are paramount to reduce morbidity and mortality. Laparoscopic appendicectomy is the current gold standard in the management of appendicitis, especially if complicated according to EAES guidelines. There are few documented cases in the literature of acute appendicitis secondary to foreign body ingestion. On account of this, there are currently no guidelines for its management. Our literature review highlights the importance of surgical management of foreign body acute appendicitis. Case presentation: This case report describes the rare presentation of acute complicated appendicitis caused by an ingested toothpick in a 64 year old woman. The patient was admitted with a 3 day history of lower abdominal pain, localizing to the right iliac fossa with raised inflammatory markers. CT imaging reported acute complicated appendicitis. Laparoscopic appendicectomy was performed during which a toothpick was seen protruding through the appendiceal wall. Post operatively the patient was treated with IV antibiotics for 5 days prior to discharge. Clinical discussion: Due to the rare nature of foreign body appendicitis there are no specific guidelines on the respective surgical approach. A literature review showed that in the setting of foreign body appendicitis, surgical intervention is paramount with no scope for conservative management.
  • Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer.

    Mezynski, M Janusz; Farrelly, Angela M; Cremona, Mattia; Carr, Aoife; Morgan, Clare; Workman, Julie; Armstrong, Paul; McAuley, Jennifer; Madden, Stephen; Fay, Joanna; et al. (2021-05-01)
    Background: Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in overcoming trastuzumab resistance is unclear. Methods: Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients. A panel of gastric cell lines (N87, OE19, ESO26, SNU16, KATOIII) were profiled for anti-proliferative response to the PI3K inhibitor copanlisib and the MEK1/2 inhibitor refametinib alone and in combination with anti-HER2 therapies. Results: Patients with HER2-positive GC had significantly poorer overall survival compared to HER2-negative patients (15.9 months vs. 35.7 months). Mutations in PIK3CA were only identified in HER2-negative tumours, while ERBB-family mutations were identified in HER2-positive and HER2-negative tumours. Copanlisib had anti-proliferative effects in 4/5 cell lines, with IC50s ranging from 23.4 (N87) to 93.8 nM (SNU16). All HER2-positive cell lines except SNU16 were sensitive to lapatinib (IC50s 0.04 µM-1.5 µM). OE19 cells were resistant to trastuzumab. The combination of lapatinib and copanlisib was synergistic in ESO-26 and OE-19 cells (ED50: 0.83 ± 0.19 and 0.88 ± 0.13, respectively) and additive in NCI-N87 cells (ED50:1.01 ± 0.55). The combination of copanlisib and trastuzumab significantly improved growth inhibition compared to either therapy alone in NCI-N87, ESO26 and OE19 cells (p < 0.05). Conclusions: PI3K or MEK inhibition alone or in combination with anti-HER2 therapy may represent an improved treatment strategy for some patients with HER2-positive GC, and warrants further investigation in a clinical trial setting.

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