Recent Submissions

  • Development and relative validation of a short food frequency questionnaire for assessing dietary intakes of non-alcoholic fatty liver disease patients.

    Bredin, Carla; Naimimohasses, Sara; Norris, Suzanne; Wright, Ciara; Hancock, Neil; Hart, Kathryn; Moore, J Bernadette (2019-02-25)
    Fifty-five patients completed both the SFFQ and the 4DDD within 30 weeks; 42 (76%) were diagnosed with simple steatosis, whereas 13 (24%) had biopsy-proven steatohepatitis; the majority were overweight or obese, with a median (25th; 75th percentile) BMI of 33.2 kg/m2 (29.3; 36.0). Reported energy intakes were well below EER with a median intake of 73% of requirements, suggesting widespread under-reporting. Significant correlations were observed between sugar (r = 0.408, P = 0.002), fat (r = 0.44, P = 0.001), fruits (r = 0.51, P = 0.0001) and vegetables (r = 0.40, P = 0.0024) measurements by the SFFQ and 4DDD. Bland Altman plots with regression analysis demonstrated broad comparability with the 4DDD for intakes of fat (bias - 13.8 g/day) and sugar (bias  + 12.9 g/day).
  • Endovascular flow-diversion of visceral and renal artery aneurysms using dual-layer braided nitinol carotid stents.

    van Veenendaal, Penelope; Maingard, Julian; Kok, Hong Kuan; Ranatunga, Dinesh; Buckenham, Tim; Chandra, Ronil V; Lee, Michael J; Brooks, Duncan Mark; Asadi, Hamed (2020-06-28)
    Background: Visceral and renal artery aneurysms (VRAAs) are uncommon but are associated with a high mortality rate in the event of rupture. Endovascular treatment is now first line in many centres, but preservation of arterial flow may be difficult in unfavourable anatomy including wide necked aneurysms, parent artery tortuosity and proximity to arterial bifurcations. Endovascular stenting, and in particular flow-diversion, is used in neurovascular intervention to treat intracranial aneurysms but is less often utilised in the treatment of VRAAs. The CASPER stent is a low profile dual-layer braided nitinol stent designed for carotid stenting with embolic protection and flow-diversion properties. We report the novel use of the CASPER stent for the treatment of VRAAs. We present a case series describing the treatment of six patients with VRAAs using the CASPER stent. Results: Six patients with unruptured VRAAs were treated electively. There were three splenic artery aneurysms and three renalartery aneurysms. Aneurysms were treated with the CASPER stent, with or without loose aneurysm coil packing or liquid embolic depending on size and morphology. All stents were successfully deployed with no immediate or periprocedural complications. Four aneurysms completely occluded after serial imaging follow up with one case requiring repeat CASPER stenting for complete occlusion. In one patient a single aneurysm remained patent at last follow up, A single case was complicated by delated splenic infarction and surgical splenectomy.
  • Does CT Reduce the Rate of Negative Laparoscopies for Acute Appendicitis? A Single-Center Retrospective Study.

    Wagner, Pedro de J; Haroon, Muthana; Morarasu, Stefan; Eguare, Emmanuel; Al-Sahaf, Osama (2020-01)
    In surgical practice, surgeons request CT scans to rule out acute appendicitis, even in young patients. We aimed to assess the feasibility of using a CT scan to reduce the rate of negative laparoscopies in patients younger than 40 with equivocal signs of acute appendicitis. Therefore, we conducted a retrospective observational study on the patients admitted with a provisional diagnosis of acute appendicitis. Patients younger than 40 and with the Alvarado score between 3 and 6 were included. These were divided into two groups: those who had or did not have a CT scan. Each group was further subdivided into patients that had a laparoscopy and those that did not. Out of 204 patients included in the study, 16% were included in the CT group, and 84% in the non-CT group. 71.9% of the patients that underwent a CT scan had appendicitis and underwent an appendectomy. Five patients with a normal CT scan had appendectomy due to persistent signs of acute appendicitis. The histopathology of the 23 patients with positive CT was positive, and 3 of the 5 patients with negative CT that underwent appendectomy had positive histology results. The negative appendectomy rate for patients that had preoperative CT is 7.14% compared to 32.4% in patients without preoperative CT. The rate of negative laparoscopy in patients younger than 40 years old that undergo preoperative CT is significantly lower with a p-value of .00667.
  • Technical challenges and potential solutions for rectal and sigmoid tumours following previous radiation for prostate malignancy: A case series.

    Hannan, Enda; Ryan, Jessica; Toomey, Desmond (2020-07-16)
    Introduction: The aftermath of pelvic radiotherapy for prostate cancer (PC) can pose a significant challenge for surgeons in the management of rectal and sigmoid tumours, resulting in extensive fibrosis and difficult anatomy. Higher rates of ureteric injuries and anastomotic leakage following anterior resection (AR) have been reported with no clear consensus for an optimal approach. We present three cases, each employing a different surgical approach tailored to the individual patient-specific and disease-specific factors. Presentation of case: In each case, the patient had active radiation proctitis. Case 1 was a T3 rectal cancer 9 cm from the anal verge. A non-restorative procedure was performed with a permanent end colostomy, due to the extensive pelvic fibrosis encountered in a comorbid patient. In case 2, a large rectal polyp at 12 cm from the anal verge was managed using transanal minimally invasive surgery (TAMIS) with a covering loop ileostomy. In case 3, an elderly patient with dementia with a malignant sigmoid polyp underwent a segmental resection rather than standard oncological resection, thus avoiding either a stoma or rectal anastomosis in the context of active radiation proctitis. All three patients remain well at follow-up with no evidence of recurrence. Discussion: All three cases demonstrate an individualised approach, taking into account specific factors relating to both patient and disease. In all cases, the presence of active chronic radiation proctitis meant that primary colorectal anastomosis was not safe, thus, alternative approaches were taken. Conclusion: It is essential to tailor treatment according to patient-specific and disease-specific factors.
  • Conservative management of complete traumatic pancreatic body transection; A case report.

    Duggan, W; Hannan, E; Brosnan, C; O'Sullivan, S; Conlon, K (2020-05-21)
    Introduction: Isolated pancreatic body transection secondary to blunt abdominal trauma is a very rare injury associated with poor outcomes. Almost all previously reported cases were managed by emergency distal pancreatectomy, which is associated with high morbidity and mortality. To our knowledge, this is the first reported case of complete transection of the pancreas at the body that was successfully treated by conservative management in an adult patient. Presentation of case: A 19-year-old male was found to have complete transection of the pancreatic body on computed tomography (CT) following blunt force abdominal trauma. Given that he was haemodynamically stable without evidence of haemorrhage or bile leakage on imaging, a trial of conservative management was initiated. He remained well through his admission, gradually improving clinically and biochemically with stable appearances on serial imaging. He remains asymptomatic as of six months since discharge from the hospital and continues to be monitored in the outpatient setting. Discussion: Management of pancreatic trauma with ductal injury has typically been with emergency distal pancreatectomy, which is associated with high morbidity and mortality. The decision to operate should not be purely based on radiological findings, and should take into account clinical status, haemodynamic stability, coexisting injuries and evidence of active haemorrhage or bile leak. Conclusion: In select cases, it is reasonable to trial conservative management in isolated traumatic pancreatic body fracture by means of close clinical observation and serial imaging. This may allow the patient to avoid a high-risk emergency distal pancreatectomy.
  • Initial Assessment of the Percutaneous Electrical Phrenic Nerve Stimulation System in Patients on Mechanical Ventilation.

    O'Rourke, James; Soták, Michal; Curley, Gerard F; Doolan, Aoife; Henlín, Tomáš; Mullins, Gerard; Tyll, Tomáš; Omlie, William; Ranieri, Marco V (2020-05)
    Objectives: Maintaining diaphragm work using electrical stimulation during mechanical ventilation has been proposed to attenuate ventilator-induced diaphragm dysfunction. This study assessed the safety and feasibility of temporary percutaneous electrical phrenic nerve stimulation on user-specified inspiratory breaths while on mechanical ventilation. Design: Two-center, nonblinded, nonrandomized study. Setting: Hospital ICU. Patients: Twelve patients mechanically ventilated from 48 hours to an expected 7 days. Interventions: Leads were inserted to lie close to the phrenic nerve in the neck region using ultrasound guidance. Two initial patients had left-sided placement only with remaining patients undergoing bilateral lead placement. Percutaneous electrical phrenic nerve stimulation was used for six 2-hour sessions at 8-hour intervals over 48 hours. Measurements and main results: Data collected included lead deployment success, nerve conduction, ventilation variables, work of breathing, electrical stimulation variables, stimulation breath synchrony, and diaphragm thickness measured by ultrasound at baseline, 24, and 48 hours. Primary endpoints included ability to capture the left and/or right phrenic nerves and maintenance of work of breathing within defined limits for 80% of stimulated breaths. Lead insertion was successful in 21 of 22 attempts (95.5%). Analysis of 36,059 stimulated breaths from 10 patients with attempted bilateral lead placement demonstrated a mean inspiratory lag for phrenic nerve stimulation of 23.7 ms (p < 0.001 vs null hypothesis of <88ms). Work of breathing was maintained between 0.2 and 2.0 joules/L 96.8% of the time, exceeding the 80% target. Mean diaphragm thickness increased from baseline by 7.8% at 24 hours (p = 0.022) and 15.0% at 48 hours (p = 0.0001) for patients receiving bilateral stimulation after excluding one patient with pleural effusion. No serious device/procedure-related adverse events were reported. Conclusions: The present study demonstrated the ability to safely and successfully place percutaneous electrical phrenic nerve stimulation leads in patients on mechanical ventilation and the feasibility of using this approach to synchronize electrical stimulation with inspiration while maintaining work of breathing within defined limits.
  • Technical outcome of atlantoaxial transarticular screw fixation without supplementary posterior construct for rheumatoid arthritis.

    Thomas, Philip; Amoo, Michael; Horan, Jack; Husien, Mohammed Ben; Cawley, Derek; Nagaria, Jabir; Bolger, Ciaran (2020-07-11)
    Background: transarticular screw (TAS) fixation without a supplementary posterior construct, even in rheumatoid arthritis (RA) patients, provides sufficient stability with acceptable clinical results. Here, we present our experience with 15 RA patients who underwent atlantoaxial (AA) TAS fixation without utilizing a supplementary posterior fusion. Methods: To treat AA instability, all 15 RA patients underwent C1-C2 TAS fixation without a supplementary posterior construct. Patients were followed for at least 24 months. Pre- and postoperative sagittal measures of C1- C2, C2-C7, and C1-C7 angles, atlanto-dens interval (ADI), posterior atlanto-dens interval (PADI), and adjacent segment (i.e., C2-C3) anterior disc height (ADH) were retrospectively recorded from lateral X-ray imaging. The presence or absence of superior migration of the odontoid (SMO), cervical subaxial subluxation, C1-C2 bony fusion, screw pull-out, and screw breakage were also noted. Results: There was little difference between the pre- and postoperative studies regarding angles measured. Following TAS fixation, the mean ADI shortened, and mean PADI lengthened. There was no difference in the mean measures of C2-C3 ADH. There was no evidence of SMO pre- or postoperatively. Two patients developed anterior subluxation at C5-C6; one of the two also developed anterior subluxation at C2-C3. All patients subsequently showed C1-C2 bony fusion without screw pull-out or breakage. Conclusion: In RA patients who have undergone C1-C2 TAS fixation, eliminating a supplementary posterior fusion resulted in adequate stability.
  • Editorial: Cardiovascular Adjustments and Adaptations to Exercise: From the Athlete to the Patient.

    Crisafulli, Antonio; Piepoli, Massimo F; Thijssen, Dick; Bassareo, Pier Paolo (2020-02-27)
  • Fertility-sparing treatment in early endometrial cancer: current state and future strategies.

    Obermair, Andreas; Baxter, Eva; Brennan, Donal J; McAlpine, Jessica N; Muellerer, Jennifer J; Amant, Frédéric; van Gent, Mignon D J M; Coleman, Robert L; Westin, Shannon N; Yates, Melinda S; et al. (2020-07-08)
    Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14-25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral salpingo-oophorectomy, has excellent survival outcomes, particularly for low-grade endometrioid tumors. However, it leads to permanent loss of fertility among women who wish to preserve their reproductive potential. With current trends of reproductive-age women delaying childbearing, rising EC incidence rates, and a growing epidemic of obesity, particularly in developed countries, research on conservative non-surgical treatment approaches remains a top priority. Fertility-sparing treatment predominantly involves the use of oral progestins and levonorgestrel-releasing intrauterine devices, which have been shown to be feasible and safe in women with early stage EC and minimal or no myometrial invasion. However, data on the efficacy and safety of conservative management strategies are primarily based on retrospective studies. Randomized clinical trials in younger women and high-risk obese patients are currently underway. Here, we have presented a comprehensive review of the current literature on conservative, fertility-sparing approaches, defining the optimal candidates and evaluating tumor characteristics, reproductive and oncologic outcomes, and ongoing clinical trials. We have also summarized current guidelines and recommendations based on the published literature.
  • Determinants of healthcare seeking for childhood illnesses among caregivers of under-five children in urban slums in Malawi: a population-based cross-sectional study.

    Lungu, Edgar Arnold; Darker, Catherine; Biesma, Regien (2020-01-17)
    Background: There is considerable evidence that health systems, in so far as they ensure access to healthcare, promote population health even independent of other determinants. Access to child health services remains integral to improving child health outcomes. Cognisant that improvements in child health have been unevenly distributed, it is imperative that health services and research focus on the disadvantaged groups. Children residing in urban slums are known to face a health disadvantage that is masked by the common view of an urban health advantage. Granted increasing urbanisation rates and proliferation of urban slums resulting from urban poverty, the health of under-five children in slums remains a public health imperative in Malawi. We explored determinants of healthcare-seeking from a biomedical health provider for childhood symptoms of fever, cough with fast breathing and diarrhoea in three urban slums of Lilongwe, Malawi. Methods: This was a population-based cross-sectional study involving 543 caregivers of under-five children. Data on childhood morbidity and healthcare seeking in three months period were collected using face-to-face interviews guided by a validated questionnaire. Data were entered in CS-Pro 5.0 and analysed in SPSS version 20 using descriptive statistics and logistic regression analyses. Results: 61% of caregivers sought healthcare albeit 53% of them sought healthcare late. Public health facilities constituted the most frequently used health providers. Healthcare was more likely to be sought: for younger than older under-five children (AOR = 0.54; 95% CI: 0.30-0.99); when illness was perceived to be severe (AOR = 2.40; 95% CI: 1.34-4.30); when the presenting symptom was fever (AOR = 1.77; 95% CI: 1.10-2.86). Home management of childhood illness was negatively associated with care-seeking (AOR = 0.54; 95% CI: 0.36-0.81) and timely care-seeking (AOR = 0.44; 95% CI: 0.2-0.74). Caregivers with good knowledge of child danger signs were less likely to seek care timely (AOR = 0.57; 95% CI: 0.33-0.99). Conclusions: Even in the context of geographical proximity to healthcare services, caregivers in urban slums may not seek healthcare or when they do so the majority may not undertake timely healthcare care seeking. Factors related to the child, the type of illness, and the caregiver are central to the healthcare decision making dynamics. Improving access to under-five child health services therefore requires considering multiple factors.
  • Letter to the editor: HIV in women in the World Health Organization (WHO) European Region.

    Aebi-Popp, Karoline; Mulcahy, Fiona; Gilleece, Yvonne; On Behalf Of Wave (2020-01-30)
  • Transcutaneous bilirubinometry during and after phototherapy in preterm infants: a prospective observational study.

    Raba, Ali Ahmed; O'Sullivan, Anne; Miletin, Jan (2020-07-16)
    Objective: To examine the accuracy of transcutaneous bilirubinometry (TCB) measurements during and after phototherapy (PT) in preterm infants. Design: Prospective observational cohort study. Setting: Level III neonatal centre. Patients: Preterm infants (from 23+0 to 36+6 weeks of gestation) born between June 2017 and May 2018 requiring PT. Interventions: TCB was measured from an exposed area of the skin (the sternum; TCBU) and the covered area of the skin under the nappy (the bony part of the upper outer quadrant of the buttock; TCBC) within an hour of obtaining total serum bilirubin (TSB). Main outcome measures: Correlation and agreement between TCB (TCBU and TCBC) and TSB during and after PT. Results: We have enrolled 196 preterm infants. There was a significant correlation between TSB and TCB during PT (r=0.72, 95% CI 0.66 to 0.77 in covered area; r=0.75, 95% CI 0.70 to 0.80 in uncovered area) and after PT (r=0.87, 95% CI 0.83 to 0.91). TCB underestimated TSB level during PT, with a mean TCBC-TSB difference of -25±43 (95% agreement limits of 62 to -112) and a mean TCBU-TSB difference of -48±46 (95% agreement limits of 45 to -140). The agreement between TCB and TSB after cessation of PT improved, with TCB underestimating TSB by a mean TCB-TSB difference of -10±31 (95% agreement limits of 52 to -72). Conclusion: TCB measurements correlated strongly with TSB levels during and after PT. However, there was a wide and clinically relevant disagreement between TCB and TSB measurements during the PT phase, improving significantly after PT.
  • Time taken from primary care referral to a specialist centre diagnosis of idiopathic pulmonary fibrosis: an opportunity to improve patient outcomes?

    Brereton, Christopher J; Wallis, Timothy; Casey, Michelle; Fox, Lynn; Pontopiddan, Katarina; Laws, Diane; Graves, Jennifer; Titmuss, Vanessa; Kearney, Sarah; Evans, Sian; et al. (2020-07-20)
    For patients with IPF, length of time in healthcare systems prior to review in an ILD clinic reflects disease severity and may impact upon patient outcome
  • Clinical supervision in oncology: A narrative review.

    Hession, Natalie; Habenicht, Andrea (2020-05-26)
    The aim of this narrative literature review is to (a) review all empirical studies of clinical supervision (CS) in oncology and to (b) highlight some CS practice issues distinctive to cancer care. This review identified empirical studies related to qualified professionals and published in English since 1995 that connected to CS and oncology. A total of 15 studies were identified with the majority as small scale, exploratory and qualitative. Psychologists were predominantly utilised as facilitators of the CS with varied sample sizes ranging from 5-230 participants. The studies were grouped into three main categories; the impact of supervision on staff, impact of supervision on professional care/development and impact of supervision in existential exploration. This review highlighted the positive impact of CS while demonstrating the need for more methodologically sound programmes of research into CS in cancer settings so detailed models of effective supervision can develop and thereby inform practice.
  • Resuscitation for Cardiac Arrest and Postcardiac Arrest Care.

    Lin, Yan-Ren; Exadaktylos, Aristomenis K; Ng, Kee-Chong; Ryan, John M (2020-05-27)
  • Targeting IgG Autoantibodies for Improved Cytotoxicity of Bactericidal Permeability Increasing Protein in Cystic Fibrosis.

    McQuillan, Karen; Gargoum, Fatma; Murphy, Mark P; McElvaney, Oliver J; McElvaney, Noel G; Reeves, Emer P (2020-07-17)
    In people with cystic fibrosis (PWCF), inflammation with concurrent infection occurs from a young age and significantly influences lung disease progression. Studies indicate that neutrophils are important effector cells in the pathogenesis of CF and in the development of anti-neutrophil cytoplasmic autoantibodies (ANCA). ANCA specific for bactericidal permeability increasing protein (BPI-ANCA) are detected in people with CF, and correlate with infection with Pseudomonas aeruginosa. The aim of this study was to determine the signaling mechanism leading to increased BPI release by CF neutrophils, while identifying IgG class BPI-ANCA in CF airways samples as the cause for impaired antimicrobial activity of BPI against P. aeruginosa. Plasma and/or bronchoalveolar lavage fluid (BAL) was collected from PWCF (n = 40), CF receiving ivacaftor therapy (n = 10), non-CF patient cohorts (n = 7) and healthy controls (n = 38). Plasma and BAL BPI and BPI-ANCA were measured by ELISA and GTP-bound Rac2 detected using an in vitro assay. The antibacterial effect of all treatments tested was determined by colony forming units enumeration. Levels of BPI are significantly increased in plasma (p = 0.007) and BALF (p < 0.0001) of PWCF. The signaling mechanism leading to increased degranulation and exocytosis of BPI by CF neutrophils (p = 0.02) involved enhancement of Rac2 GTP-loading (p = 0.03). The full-length BPI protein was detectable in all CF BAL samples and patients displayed ANCA with BPI specificity. IgG class autoantibodies were purified from CF BAL complexed to BPI (n=5), with IgG autoantibody cross-linking of antigen preventing BPI induced P. aeruginosa killing (p < 0.0001). Results indicate that the immune-mediated diminished antimicrobial defense, attributed to anti-BPI-IgG, necessitates the formation of a drug/immune complex intermediate that can maintain cytotoxic effects of BPI towards Gram-negative pathogens, with the potential to transform the current treatment of CF airways disease.
  • Sacubitril-Valsartan in a routine community population: attention to volume status critical to achieving target dose.

    Pharithi, Rebabonye B; Ferre-Vallverdu, Maria; Maisel, Alan S; O'Connell, Eoin; Walshe, Myra; Sweeney, Claire; Barton, James; McDonald, Kathrine; O'Hare, Daniel; Watson, Chris; et al. (2020-01-05)
    This is a retrospective single-centre review of patients switched from angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to sacubitril-valsartan between May 2016 and August 2018. Baseline and follow-up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril-valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril-valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril-valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD.
  • Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database.

    Nguengang Wakap, Stéphanie; Lambert, Deborah M; Olry, Annie; Rodwell, Charlotte; Gueydan, Charlotte; Lanneau, Valérie; Murphy, Daniel; Le Cam, Yann; Rath, Ana (2019-09-16)
    Rare diseases, an emerging global public health priority, require an evidence-based estimate of the global point prevalence to inform public policy. We used the publicly available epidemiological data in the Orphanet database to calculate such a prevalence estimate. Overall, Orphanet contains information on 6172 unique rare diseases; 71.9% of which are genetic and 69.9% which are exclusively pediatric onset. Global point prevalence was calculated using rare disease prevalence data for predefined geographic regions from the 'Orphanet Epidemiological file' ( Of the 5304 diseases defined by point prevalence, 84.5% of those analysed have a point prevalence of <1/1 000 000. However 77.3-80.7% of the population burden of rare diseases is attributable to the 4.2% (n = 149) diseases in the most common prevalence range (1-5 per 10 000). Consequently national definitions of 'Rare Diseases' (ranging from prevalence of 5 to 80 per 100 000) represent a variable number of rare disease patients despite sharing the majority of rare disease in their scope. Our analysis yields a conservative, evidence-based estimate for the population prevalence of rare diseases of 3.5-5.9%, which equates to 263-446 million persons affected globally at any point in time. This figure is derived from data from 67.6% of the prevalent rare diseases; using the European definition of 5 per 10 000; and excluding rare cancers, infectious diseases, and poisonings. Future registry research and the implementation of rare disease codification in healthcare systems will further refine the estimates.
  • Novel clinical and genetic insight into CXorf56-associated intellectual disability.

    Rocha, Maria Eugenia; Silveira, Tainá Regina Damaceno; Sasaki, Erina; Sás, Daíse Moreno; Lourenço, Charles Marques; Kandaswamy, Krishna K; Beetz, Christian; Rolfs, Arndt; Bauer, Peter; Reardon, Willie; et al. (2019-12-10)
    Intellectual disability (ID) is one of most frequent reasons for genetic consultation. The complex molecular anatomy of ID ranges from complete chromosomal imbalances to single nucleotide variant changes occurring de novo, with thousands of genes identified. This extreme genetic heterogeneity challenges the molecular diagnosis, which mostly requires a genomic approach. CXorf56 is largely uncharacterized and was recently proposed as a candidate ID gene based on findings in a single Dutch family. Here, we describe nine cases (six males and three females) from three unrelated families. Exome sequencing and combined database analyses, identified family-specific CXorf56 variants (NM_022101.3:c.498_503del, p.(Glu167_Glu168del) and c.303_304delCTinsACCC, p.(Phe101Leufs*20)) that segregated with the ID phenotype. These variants are presumably leading to loss-of-function, which is the proposed disease mechanism. Clinically, CXorf56-related disease is a slowly progressive neurological disorder. The phenotype is more severe in hemizygote males, but might also manifests in heterozygote females, which showed skewed X-inactivation patterns in blood. Male patients might present previously unreported neurological features such as epilepsy, abnormal gait, tremor, and clonus, which extends the clinical spectrum of the disorder. In conclusion, we confirm the causative role of variants in CXorf56 for an X-linked form of intellectual disability with additional neurological features. The gene should be considered for molecular diagnostics of patients with ID, specifically when family history is suggestive of X-linked inheritance. Further work is needed to understand the role of this gene in neurodevelopment and intellectual disability.
  • The dilemma of the duplicated cystic duct: a case report.

    Harding, Tim; Hannan, Enda; Brosnan, Conor; Duggan, William; Ryan, David; Stafford, Anthony; Maguire, Donal (2020-06-19)

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