Lung organoids and other preclinical models of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease affecting over 100 000 people in Europe with an increasing incidence. Available treatments offer only slowing of disease progression and are poorly tolerated by patients leading to cessation of therapy. Lung transplant remains the only cure. Therefore, alternative treatments are urgently required. The pathology of IPF is complex and poorly understood and thus creates a major obstacle to the discovery of novel treatments. Additionally, preclinical assessment of new treatments currently relies upon animal models where disparities with human lung biology often hamper drug development. At a cellular level, IPF is characterized by persistent and abnormal deposition of extracellular matrix by fibroblasts and alveolar epithelial cell injury which is seen as a key event in initiation of disease progression. In-depth investigation of the role of alveolar epithelial cells in health and disease has been impeded due to difficulties in primary cell isolation and culture ex vivo. Novel strategies employing patient-derived induced pluripotent stem cells engineered to produce type 2 alveolar epithelial cells (iAEC2) cultured as three-dimensional organoids have the potential to overcome these hurdles and inform new effective precision treatments for IPF leading to improved survival and quality of life for patients worldwide.

The 100 Citation Classics in the Irish Medical Literature; A Bibliometric Analysis.

Identifying citation classics is a valuable metric of research performance. Ireland has a distinguished history of medical research, although Ireland's top-cited articles are unknown. The SCOPUS database identified all medical and surgical articles published by journals in the Republic of Ireland or Northern Ireland. The 100 top-cited articles were analysed. The most cited article received 240 citations. There is an observed trend of increasing number of authors over time (p<0.05). General medicine and public health are the most common topics. The majority of works originate from Irish institutions. Collaborative research and non-Irish research are poorly represented among the citation classics. The Irish medical literature contains multiple highly cited and influential articles.

Varicocele Embolization: An Assessment of the Quality and Readability of Online Patient Information.

AIMS AND OBJECTIVES: Varicocele embolization is a growing treatment modality owing to the safety, efficacy, and quick return to work following the procedure. The internet is the most dominant source of information for many. We aimed to assess the quality of information accessible by patients considering treatment. MATERIALS AND METHODS: A list of applicable, commonly used searchable terms was generated. Each term was assessed across the five most-used English language search engines to determine the two most commonly used terms. These two terms were then investigated across each search engine, with the first 25 web pages returned by each engine included for analysis. Duplicate web pages, nontext content such as video or audio, and web pages behind paywalls were excluded. Web pages were analyzed for quality and readability using validated tools including DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Secondary features including age, rank, author, and publisher were recorded. RESULTS: The most common applicable terms were "Testicular embolization" (378,300 results) and "Varicocele embolization" (375,800 results). Mean DISCERN quality of information provided by websites is "fair"; Adherence to JAMA Benchmark Criteria was 13.5%. Flesh-Kincaid readability tests demonstrated an average "9th grade" reading level. Scientific journals showed the highest quality scores, but were least up to date with an average web page age of 11.2 years. Web pages produced by "for-profit" organizations were the second most current (average age 2.7 years), but displayed the lowest quality of information scores. CONCLUSION: While quality of online information available to patients is "fair," adherence to JAMA benchmark criteria is poor. "For-profit" organization websites are far more numerous and significantly more up-to-date, yet showed significantly lower quality of information scores. Scientific journals were unsurprisingly of higher quality, yet more challenging for the general public to read. These findings call for the production of high-quality and comprehensible content regarding interventional radiology, where physicians can reliably direct their patients for information.

The accuracy of standard multiple sclerosis MRI brain sequences for the diagnosis of optic neuropathy.

BACKGROUND: Detection of optic neuropathy on MRI has potential implications for the diagnosis and management of Multiple Sclerosis (MS). OBJECTIVE: This study assessed the accuracy of T2 sagittal MRI brain for detection of optic neuropathy, compared to coronal STIR orbit. METHODS AND MATERIALS: Retrospective single-center blinded diagnostic accuracy study of 100 consecutive patients who underwent both T2 sagittal brain and coronal STIR orbit MRI. All were performed on 1.5T scanners. T2 sagittal slice thickness was 4 mm for the first 50 patients (group1) and 3 mm for the second 50 (group2). The MRIs were reviewed in a blinded fashion to determine the presence of optic neuropathy. Coronal STIR orbit sequences were considered the diagnostic reference standard. RESULTS: The sensitivity of T2 sagittal brain imaging for ON was 44% in group 1 and 85% in group 2 (p = 0.007). The specificities were 98% and 97% respectively (p = 0.9). Sensitivity was poorest for evaluation of the intraorbital nerve segment (56% grp1, 69% grp2, p = 0.4). CONCLUSION: T2 sagittal MRI brain has high specificity for the detection of optic neuropathy when compared to coronal STIR orbit. Sensitivity is increased when slice thickness is reduced, but remains poor for evaluation of the intraorbital segment.

Minimally invasive approaches to the management of anastomotic leakage following restorative rectal cancer resection.

AIM: Management of anastomotic leakage (AL) following rectal resection has evolved with increasing use of less invasive techniques. The aim of this study was to review the management of AL following restorative rectal cancer resection in a tertiary referral centre. METHOD: A retrospective review of a prospectively maintained database was performed. The primary outcome was successful management of AL. The secondary outcome was the impact of AL on oncological outcome. RESULTS: Five hundred and two restorative rectal cancer resections were performed during the study period. The incidence of AL was 9.9% (n = 50). AL occurred more commonly following neoadjuvant chemoradiotherapy (n = 31/252, 12.3%) than in those who did not receive neoadjuvant chemoradiotherapy (n = 19/250, 7.6%; P = 0.107); however, this was not statistically significant. Successful minimally invasive drainage was achieved in 28 patients (56%, radiological n = 24, surgical n = 4). Trans-rectal drainage was the most common drainage method (n = 14). The median duration of drainage was longer in the neoadjuvant group (27 vs 18 days). Surgical intervention was required in 11 patients, with anastomotic takedown and end-colostomy formation was most commonly required. Successful management of AL with drainage (maintenance of the anastomosis without the need for further intervention) was achieved in 26 of the 28 patients. There were no significant differences in overall or disease-free survival when patients with AL were compared with patients without AL (69.4% vs 72.6%, P = 0.99 and 78.7% vs 71.3%, P = 0.45, respectively). CONCLUSION: In selected patients, AL following restorative rectal resection can be effectively controlled using minimally invasive radiological or surgical drainage without the need for further intervention.

Overnight Emergency CT Imaging: A 10-Year Experience at an Irish Tertiary Referral Hospital.

In recent years there has been increased utilisation of computed tomography (CT) imaging in developed countries, however there is a paucity of data regarding the utilisation of CT in the emergency overnight setting. We retrospectively analysed trends in 'overnight' (midnight to 8am) CT utilisation over a ten-year period at a single Irish tertiary referral hospital. Over the study period, we observed a significant increase in the proportion of CT imaging that was carried out overnight. There was no significant variation in the yield of pathological findings over the study period, which remained low (64% of CT studies were normal or had non-critical findings). The multiple factors which have contributed to the increased utilization of overnight emergency CT in recent years, the potential for reporting errors overnight and the implications therein for patient safety warrant consideration.

Preoperative CT in patients with surgically resectable pancreatic adenocarcinoma: does the time interval between CT and surgery affect survival?

PURPOSE: The preoperative imaging-to-surgery time interval (ISI) influences the risk of unexpected progression (UP) found at surgery for pancreatic adenocarcinoma. We aimed to assess whether ISI influences disease recurrence and/or survival. METHODS AND MATERIALS: A single-institution, ethics board-approved retrospective analysis of all patients who underwent attempted resection of pancreatic (PDAC) or periampullary adenocarcinoma (AmpAC) between 1st January 2010 and 31st December 2015 was performed. All patients underwent preoperative abdominal computed tomography (CT). Exclusion criteria were borderline resectable disease and neoadjuvant chemo/radiotherapy. Patients were followed up until 30th June 2016. The population was divided into ISI ≥/<25 days. Kaplan-Meier and Cox regression survival analyses were performed. RESULTS: 239 patients underwent surgical exploration. UP was found in 29 (12.1%) and these patients had longer ISI (median 46 vs. 29 days, p < 0.05). When intention-to-treat analysis was performed, there was no difference in overall survival (OS) between patients with ISI ≥/<25. In those who underwent resection, ISI did not influence disease-free survival (DFS) or OS for PDAC (n = 174). For AmpAC (n = 36), ISI ≥ 25 days was associated with longer OS (p < 0.05) but did not influence DFS. Longer ISI was independently associated with improved OS on regression analysis for AmpAC. CONCLUSION: Performing surgery for resectable pancreatic adenocarcinoma within 25 days of abdominal CT reduces the chance of UP but does not confer a survival benefit. For those who undergo resection of AmpAC, a longer ISI was associated with longer OS. This probably represents a more biologically indolent disease in this cohort.

Ireland's recent contribution to the radiological literature; a bibliometric analysis.

The aim of this study was to identify and analyse all articles published by Irish radiology departments in the medical literature since the year 2000. The PubMed database was searched to identify and review all articles published by radiologists based in the Republic of Ireland or Northern Ireland. Citation counts were then obtained and the top ten most cited articles were identified. There were 781 articles published during the study period. Of these, 558 (71%) were published in radiology journals and the remaining 223 (29%) were published in general medical journals. Abdominal radiology was the most represented sub-specialty (33% of all articles). There was a general trend of increased publications per year. Only 75 (9.6%) of articles were collaborative efforts by more than one radiology department. Irish radiology departments have a considerable research output and this has increased since the year 2000. More collaborative research between Irish radiology departments is encouraged.

Unexpected Relations of Historical Anthrax Strain.

In 1998, it was claimed that an 80-year-old glass tube intentionally filled with Bacillus anthracis and embedded in a sugar lump as a WWI biological weapon still contained viable spores. Today, genome sequencing of three colonies isolated in 1998 and subjected to phylogenetic analysis surprisingly identified a well-known B. anthracis reference strain isolated in the United States in 1981, pointing to accidental laboratory contamination.IMPORTANCE Next-generation sequencing and subsequent phylogenetic analyses are useful and reliable tools for the classification of recent and historical samples. The reliability of sequences obtained and bioinformatic algorithms has increased in recent years, and research has uncovered the identity of a presumed bioweapon agent as a contaminant.

PROSPER delivery of universal preventive interventions with young adolescents: long-term effects on emerging adult substance misuse and associated risk behaviors.

BACKGROUND: Substance misuse and associated health-risking behaviors are prevalent in emerging adulthood. There is a knowledge gap concerning the post-high school effects of community-based delivery systems for universal preventive interventions implemented during young adolescence. This study reports effects of the PROSPER delivery system through age 19, 7.5 years past baseline. METHODS: A cohort sequential design included 28 public school districts randomly assigned to the PROSPER partnership delivery system or usual-programming conditions. PROSPER community teams implemented a family-focused intervention in 6th grade and a school-based intervention in 7th grade. Outcomes for the age 19, post-high school report included lifetime, current, and frequency of substance misuse, as well as antisocial and health-risking sexual behaviors. Intent-to-treat, multi-level analyses of covariance of point-in-time outcomes were conducted, along with analyses of risk-related moderation of intervention effects. RESULTS: Results showed emerging adults from PROSPER communities reported significantly lower substance misuse across a range of types of substances, with relative reduction rates of up to 41.0%. No significant findings were observed for associated antisocial and health-risking sexual behavior indices; or for lifetime rates of sexually transmitted infections. Risk-related moderation effects were non-significant, suggesting generally comparable outcomes across higher- and lower-risk subgroups of emerging adults. CONCLUSIONS: The PROSPER delivery system for brief universal preventive interventions has potential for public health impact by reducing long-term substance misuse, with positive results extending beyond high school.

PET imaging of subclinical seizure associated with intracranial cavernous malformations.

We present the case of a subclinical seizure identified during positron emission tomography with 18-fluorodeoxyglucose in a patient with cavernous malformations.

The use of ultrasonography and digital mammography in women under 40 years with symptomatic breast cancer: a 7-year Irish experience.

BACKGROUND: Breast cancer in women under 40 years of age is rare and typically presents symptomatically. The optimal imaging modality for this patient group is controversial. Most women undergo ultrasonography with/without mammography. Young women typically have dense breasts, which can obscure the features of malignancy on film mammography, however, initial studies have suggested that digital mammography may have a more accurate diagnostic performance in younger women. Ultrasound generally performs well in this age group, although it is poor at detecting carcinoma in situ (DCIS). AIMS: To evaluate the comparative diagnostic performance of ultrasonography and digital mammography in the initial diagnostic evaluation of women under 40 years of age with symptomatic breast cancer. METHODS: Retrospective review of all women under the age of 40 years managed at our symptomatic breast cancer unit from January 2009 to December 2015. RESULTS: There were 120 patients that met the inclusion criteria for this study. The sensitivity of ultrasonography and digital mammography for breast cancer in this patient group was 95.8 and 87.5 %, respectively. The patients with a false negative mammographic examination were more likely to have dense breasts (p < 0.01). Five patients had a false negative ultrasonographic examination, withal of whom were diagnosed with DCIS detected by mammography. CONCLUSION: This study demonstrates the superior sensitivity of ultrasound for breast cancer in women under the age of 40 years, however, the results show that digital mammography has an important complimentary role in the comprehensive assessment of these patients, particularly in the diagnosis of DCIS.

Minimally Invasive Diagnosis of Secondary Intracranial Lymphoma.

Diffuse large B cell lymphomas (DLBCL) are an aggressive group of non-Hodgkin lymphoid malignancies which have diverse presentation and can have high mortality. Central nervous system relapse is rare but has poor survival. We present the diagnosis of primary mandibular DLBCL and a unique minimally invasive diagnosis of secondary intracranial recurrence. This case highlights the manifold radiological contributions to the diagnosis and management of lymphoma.