High-income ZIP codes in New York City demonstrate higher case rates during off-peak COVID-19 waves.

Introduction: Our study explores how New York City (NYC) communities of various socioeconomic strata were uniquely impacted by the COVID-19 pandemic. Methods: New York City ZIP codes were stratified into three bins by median income: high-income, middle-income, and low-income. Case, hospitalization, and death rates obtained from NYCHealth were compared for the period between March 2020 and April 2022. Results: COVID-19 transmission rates among high-income populations during off-peak waves were higher than transmission rates among low-income populations. Hospitalization rates among low-income populations were higher during off-peak waves despite a lower transmission rate. Death rates during both off-peak and peak waves were higher for low-income ZIP codes. Discussion: This study presents evidence that while high-income areas had higher transmission rates during off-peak periods, low-income areas suffered greater adverse outcomes in terms of hospitalization and death rates. The importance of this study is that it focuses on the social inequalities that were amplified by the pandemic.

Accuracy of a Single-Lead ECG Device for Diagnosis of Cardiac Arrhythmias Compared Against Cardiac Electrophysiology Study.

BACKGROUND: Single-lead electrocardiogram (ECG) devices may allow detection and diagnosis of cardiac rhythms. However, data on their accuracy for detecting cardiac arrhythmias beyond atrial fibrillation are limited. We aimed to determine the accuracy of the AliveCor KardiaMobile (AC) (AliveCor Inc, Mountain View, CA, USA) for the diagnosis of arrhythmias against gold standard cardiac electrophysiology study (EPS). METHOD: Patients undergoing clinically indicated EPS underwent simultaneous rhythm recording with an AC, standard 12-lead ECG, and EP catheters for intracardiac electrograms. Rhythms recorded during EPS were classified based on electrogram, 12-lead ECG, and clinical findings. Blinded reviewers provided differential diagnoses for the single-lead AC tracings; a separate reviewer compared diagnoses made between the AC tracings and EPS findings. RESULTS: In 49 patients, 843 cardiac rhythms were captured during 502 AC recordings. Analysis of tracings containing sinus rhythm (n=273) returned an overall accuracy of 92%, with sensitivity and specificity values of 93% and 92%, respectively. Accuracy for tracings per rhythm was atrial fibrillation 91% (n=51); supraventricular tachycardia accuracy was 89% (n=191), ventricular tachycardia 91% (n=198), ventricular fibrillation 98% (n=11), and asystole 100% (n=5). Accuracy for supraventricular ectopy was 93% (n=28) and for premature ventricular complexes was 91% (n=86). Overall accuracy was 94% for solitary rhythms and 93% in tracings from patients with baseline bundle branch block. CONCLUSIONS: When compared against the gold standard EPS diagnosis, the interpretation of arrhythmias recorded by an AliveCor single-lead ECG device had reasonable diagnostic accuracy.

The Current Landscape of Ventricular Tachycardia Trials: A Systematic Review of Registered Studies.

BACKGROUND: Although there are evolving techniques and technologies for treating ventricular tachycardia (VT), the current landscape of clinical trials for managing VT remains understudied. OBJECTIVE: The objective of this study was to provide a systematic characterisation of the interventional management of VT through an analysis of the ClinicalTrials.gov, clinicaltrialsregister.eu, anzctr.org.au and chictr.org.cn databases. METHODS: We queried all phase II to IV interventional trials registered up to November 2023 that enrolled patients with VT. Published, completed but unpublished, terminated, or ongoing trials were included for final analysis. RESULTS: Of the 698 registered studies, 135 were related to VT, with 123 trials included in the final analysis. Among these trials, 25 (20%) have been published, enrolling a median of 35 patients (interquartile range [IQR] 20-132) over a median of 43 months (IQR 19-62). Out of the published trials, 14 (56%) were randomised, and 12 (48%) focused on catheter ablation. Twenty-two (18%) have been completed but remain unpublished, even after a median of 36 months (IQR 15-60). Furthermore, 27 (22%) trials were terminated or withdrawn, with the most common cause being poor enrolment. Currently, 49 (40%) trials are ongoing and novel non-ablative technologies, such as radioablation and autonomic modulation, account for 35% and 8% of ongoing trials, respectively. CONCLUSIONS: Our analysis revealed that many registered trials remain unpublished or incomplete, and randomised controlled trial evidence is limited to only a few studies. Furthermore, many ongoing trials are focused on non-catheter ablation-based strategies. Therefore, larger pragmatic trials are needed to create stronger evidence in the future.

RoBétArmé Project: Human-robot collaborative construction system for shotcrete digitization and automation through advanced perception, cognition, mobility and additive manufacturing skills.

The importance of construction automation has grown worldwide, aiming to deliver new machineries for the automation of roads, tunnels, bridges, buildings and earth-work construction. This need is mainly driven by (i) the shortage and rising costs of skilled workers, (ii) the tremendous increased needs for new infrastructures to serve the daily activities and (iii) the immense demand for maintenance of ageing infrastructure. Shotcrete (sprayed concrete) is increasingly becoming popular technology among contractors and builders, as its application is extremely economical and flexible as the growth in construction repairs in developed countries demand excessive automation of concrete placement. Even if shotcrete technology is heavily mechanized, the actual application is still performed manually at a large extend. RoBétArméEuropean project targets the Construction 4.0 transformation of the construction with shotcrete with the adoption of breakthrough technologies such as sensors, augmented reality systems, high-performance computing, additive manufacturing, advanced materials, autonomous robots and simulation systems, technologies that have already been studied and applied so far in Industry 4.0. The paper at hand showcases the development of a novel robotic system with advanced perception, cognition and digitization capabilities for the automation of all phases of shotcrete application. In particular, the challenges and barriers in shotcrete automation are presented and the RoBétArmésuggested solutions are outlined. We introduce a basic conceptual architecture of the system to be developed and we demonstrate the four application scenarios on which the system is designated to operate.

The RoBétArmé European project targets the Construction 4.0 transformation of the construction with shotcrete with the adoption of breakthrough technologies such as sensors, augmented reality systems, high-performance computing, additive manufacturing, advanced materials, autonomous robots and simulation systems, technologies that have already been studied and applied so far in Industry 4.0. This paper showcases a case study on which novel robotic systems will be developed for the automation of shotecrete application. The outcomes of this research can be widely used in other application technologies related to the construction domain.

Gross Hematuria and Lower Urinary Tract Symptoms Associated With Military Burn Pits Exposures in US Veterans Deployed to Iraq and Afghanistan.

OBJECTIVE: The aim of the study is to describe rates of hematuria and other lower urinary tract symptoms, including self-reported cancer rates, among veterans postburn pits emissions exposure during deployment to Iraq and Afghanistan. METHODS: US post-9/11 veterans with burn pits emissions exposure confirmed via DD214 forms in the Burn Pits360.org Registry were sent a modified survey. Data were deidentified and anonymously coded. RESULTS: Twenty-nine percent of the 155 respondents exposed to burn pits self-reported seeing blood in their urine. The average index score of our modified American Urological Association Symptom Index Survey was 12.25 (SD, 7.48). High rates of urinary frequency (84%) and urgency (76%) were self-reported. Bladder, kidney, or lung cancers were self-reported in 3.87%. CONCLUSIONS: US veterans exposed to burn pits are self-reporting hematuria and other lower urinary tract symptoms.

Mortality after catheter ablation of structural heart disease related ventricular tachycardia.

BACKGROUND: There is a paucity of data describing mortality after catheter ablation of ventricular tachycardia (VT). OBJECTIVES: We describe the causes and predictors of cardiac transplant and/or mortality following catheter ablation of structural heart disease (SHD) related VT. METHODS: Over 10-years, 175 SHD patients underwent VT ablation. Clinical characteristics, and outcomes, were compared between patients undergoing transplant and/or dying and those surviving. RESULTS: During 2.8 (IQR 1.9-5.0) years follow-up, 37/175 (21%) patients underwent transplant and/or died following VT ablation. Prior to ablation, these patients were older (70.3 ± 11.1 vs. 62.1 ± 13.9 years, P = 0.001), had lower left ventricular ejection fraction ([LVEF] 30 ± 12% vs. 44 ± 14%, P < 0.001), and were more likely to have failed amiodarone (57% vs. 39%, P = 0.050), compared to those that survived. Predictors of transplant and/or mortality included LVEF≤35% (HR 4.71 [95% CI 2.18-10.18], P < 0.001), age ≥ 65 years (HR 2.18 [95% CI 1.01-4.73], P = 0.047), renal impairment (HR 3.73 [95% CI 1.80-7.74], P < 0.001), amiodarone failure (HR 2.67 [95% CI 1.27-5.63], P = 0.010) and malignancy (HR 3.09 [95% CI 1.03-9.26], P = 0.043). Ventricular arrhythmia free survival at 6-months was lower in the transplant and/or deceased, compared to non-deceased group (62% vs. 78%, P = 0.010), but was not independently associated with transplant and/or mortality. The risk score, MORTALITIES-VA, accurately predicted transplant and/or mortality (AUC: 0.872 [95% CI 0.810-0.934]). CONCLUSIONS: Cardiac transplant and/or mortality after VT ablation occurred in 21% of patients. Independent predictors included LVEF≤35%, age ≥ 65 years, renal impairment, malignancy, and amiodarone failure. The MORTALITIES-VA score may identify patients at high-risk of transplant and/or dying after VT ablation.

A Prospective, Multicentre Randomised Controlled Trial Comparing Catheter Ablation Versus Antiarrhythmic Drugs in Patients With Structural Heart Disease Related Ventricular Tachycardia: The CAAD-VT Trial Protocol.

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.

The Role of Contemporary Wearable and Handheld Devices in the Diagnosis and Management of Cardiac Arrhythmias.

Cardiac arrhythmias are associated with significant morbidity, mortality and economic burden on the health care system. Detection and surveillance of cardiac arrhythmias using medical grade non-invasive methods (electrocardiogram, Holter monitoring) is the accepted standard of care. Whilst their accuracy is excellent, significant limitations remain in terms of accessibility, ease of use, cost, and a suboptimal diagnostic yield (up to ∼50%) which is critically dependent on the duration of monitoring. Contemporary wearable and handheld devices that utilise photoplethysmography and the electrocardiogram present a novel opportunity for remote screening and diagnosis of arrhythmias. They have significant advantages in terms of accessibility and availability with the potential of enhancing the diagnostic yield of episodic arrhythmias. However, there is limited data on the accuracy and diagnostic utility of these devices and their role in therapeutic decision making in clinical practice remains unclear. Evidence is mounting that they may be useful in screening for atrial fibrillation, and anecdotally, for the diagnosis of other brady and tachyarrhythmias. Recently, there has been an explosion of patient uptake of such devices for self-monitoring of arrhythmias. Frequently, the clinician is presented such information for review and comment, which may influence clinical decisions about treatment. Further studies are needed before incorporation of such technologies in routine clinical practice, given the lack of systematic data on their accuracy and utility. Moreover, challenges with regulation of quality standards and privacy remain. This state-of-the-art review summarises the role of novel ambulatory, commercially available, heart rhythm monitors in the diagnosis and management of cardiac arrhythmias and their expanding role in the diagnostic and therapeutic paradigm in cardiology.

Attenuation of Human Growth Hormone-Induced Rash With Graded Dose Challenge.

Adult growth hormone (GH) deficiency is rare and requires replacement with extrinsic/synthetic injection. GH hypersensitivity has been reported; specifically, atopic patients may develop rashes from somatotropin therapy. Allergic and non-allergic skin reactions to recombinant human GH are uncommon and infrequently reported. We describe a graded-dose challenge with intravenous Norditropin® in a 65-year-old atopic adult woman who developed a severe whole-body rash with Norditropin FlexPro® administration on several occasions but was negative on skin-prick testing to Norditropin® percutaneously and intradermally, but the patch testing was positive for gold and nickel. The patient was registered as a direct admission to the emergency room at a university hospital for a rapid antigen coronavirus disease 2019 (COVID-19) testing after having received two COVID-19 vaccinations and re-testing four months after vaccination. She was then directly admitted to a non-COVID-19 intensive care unit with direct bedside supervision by a registered nurse and a physician board certified in internal medicine, allergy/immunology, and pulmonary diseases. The patient brought a Norditropin® pen which our pharmacy team attached to a compatible syringe for dilutions. A graded dose challenge at a final dosage of 0.1 mL was performed and the patient was monitored for allergic and other adverse drug reactions, which did not occur. At the time of writing this case report, the patient has been maintained on Norditropin FlexPro® 0.1 mL and has not experienced any adverse reactions, including recurrent skin eruptions. The case presented is the first to describe a patient who successfully tolerated a graded dose challenge of an adult patient to GH replacement therapy (as Norditropin®) under supervision in an intensive care unit, whereas prior to reporting of this case, a graded dose challenge to GH replacement therapy had only been successfully performed in a child using another formulation of somatotropin (Humatrope®). Hence, this case lends support that graded dose challenge with somatotropin analogs may be considered for patients with isolated GH deficiency such as in the case presented here.

Claudin-18.

CONTEXT.­: Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target. OBJECTIVES.­: To evaluate claudin-18 expression in intestinal metaplasia, dysplasia, and adenocarcinoma of the distal esophagus/gastroesophageal junction and stomach and to evaluate claudin-18 expression in gastric and nongastric neuroendocrine tumors as a marker of gastric origin. DESIGN.­: Samples included gastroesophageal junction with intestinal metaplasia (n = 40), dysplasia (n = 54), and adenocarcinoma (n = 20) and stomach with intestinal metaplasia (n = 79), dysplasia (n = 43), and adenocarcinoma (n = 25). Additionally, gastric (n = 40) and nongastric (n = 322) neuroendocrine tumors were included. Claudin-18 expression was evaluated for any staining as positive and by meeting clinical trial inclusion criteria (≥2+ intensity in ≥50% of tumor). RESULTS.­: Claudin-18 staining was not significantly different across dysplasia categories in the gastroesophageal junction (P = .11) or stomach (P = .12). The rate of positive staining was higher in gastroesophageal junction than stomach for intestinal metaplasia (37 of 40 [92.5%] versus 37 of 79 [46.8%]; P < .001) and high-grade dysplasia (33 of 38 [86.8%] versus 9 of 16 [56.3%]; P = .03). Intestinal metaplasia showed staining in 7 of 37 autoimmune gastritis samples (18.9%) compared with 30 of 42 samples without autoimmune gastritis (71.4%) (P < .001). Adenocarcinoma showed similar staining in gastroesophageal junction (15 of 20; 75.0%) and stomach (17 of 25; 68.0%) (P = .85). Eighty percent (32 of 40) of gastric neuroendocrine tumors were positive for claudin-18 expression, with 57.5% (23 of 40) meeting clinical trial inclusion criteria. Comparatively, 0.62% (2 of 322) of nongastric neuroendocrine tumors showed staining (P < .001). CONCLUSIONS.­: Claudin-18 staining was similar in intestinal metaplasia, dysplasia, and adenocarcinoma. Claudin-18 was negative in most cases of intestinal metaplasia in autoimmune gastritis, indicating that intestinal metaplasia in this setting may differ from other forms. Claudin-18 was sensitive and specific for gastric origin in neuroendocrine tumors.

Evaluation of tumor mutational burden in small early hepatocellular carcinoma and progressed hepatocellular carcinoma.

While researchers know that tumor mutational burden (TMB) is low in hepatocellular carcinoma (HCC), prior studies have not investigated TMB in cirrhosis, small early HCC and progressed HCC. HCC (n = 18) and cirrhosis (n = 6) cases were identified. TMB was determined by a 1.7 megabase, 409-gene next-generation sequencing panel. TMB values were defined as the number of nonsynonymous variants per megabase of sequence. There was no significant difference between cirrhosis versus small early HCC or between cohorts when stratified by size, early versus progressed, differentiation or morphology. There was a significant difference between cirrhosis and small early HCC versus progressed HCC (p = 0.045), suggesting TMB may be related to HCC progression. TMB similarities in small early HCC and background cirrhosis suggest TMB is not a useful tool for diagnosing small early HCC. Additional study is needed to address TMB in histological and molecular subsets of HCC.

A qualitative study of community pharmacists' perceptions of their role in primary mental health care in New Zealand.

OBJECTIVES: Mental illness is an important public health issue internationally. As people with mild-to-moderate illness are usually cared for in primary health care, pharmacists are well placed to play an important role. The study objectives were to explore community pharmacists' perceptions of their role in primary mental health care and the barriers and facilitators to the provision of care in New Zealand. METHODS: Fifteen face-to-face, semi-structured interviews were undertaken with practising pharmacists nationally. Interviews were audio-taped and transcribed verbatim. Data were analysed iteratively using an inductive thematic approach. KEY FINDINGS: Support offered to patients with mild-to-moderate mental illness ranged from solely dispensing to providing more holistic, patient-centred care. Three key themes were identified with the potential to influence whether participants were willing and able to support patients. These were pharmacists' beliefs about their role in primary mental health care, their perception of patients' needs and the environmental context in which they were practising. The connection to the local community and the philosophy of the business owner were contexts that strongly influenced the support provided. CONCLUSIONS: Community pharmacists have a valuable contribution and role to play in supporting primary mental health care extending well beyond medicines supply and the provision of advice about medicines. Advocacy roles including health system navigation and much broader social support are also possible. The philosophy of the business owner and the actual impact this has on a pharmacist's practice and the time available to support patients is likely to be influential.

Pediatric COVID toes and fingers.

The emergence of the coronavirus disease 2019 (COVID-19) worldwide pandemic has been associated with a new constellation of cutaneous features in children. Among the unusual dermatologic presentations are the so-called COVID toes, inflammatory nodules of the feet and toes, sometimes involving the hands and fingers. These lesions mimic acral pernio, the synonym being chilblains. Unlike adult patients with COVID toes, children are less likely to manifest symptomatic COVID-19. Although a few studies have found some linkage to COVID-19 through the serum IgA or IgG severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, other studies have no demonstrable linkage suggesting that barefoot children in cold weather develop such lesions. It appears that the chilblain-like lesions related to the period of the COVID-19 pandemic may reflect a brisk immune response portending a good prognosis and perhaps some form of innate immunity. The possible need to screen for coagulopathy is unclear, but this has been suggested in one report. Until we fully understand the pattern of immune response to COVID-19, questions may persist as to how disease manifestations are linked to SARS-CoV-2 exposures.

Random and combinatorial mutagenesis for improved total production of secretory target protein in Escherichia coli.

Signal peptides and secretory carrier proteins are commonly used to secrete heterologous recombinant protein in Gram-negative bacteria. The Escherichia coli osmotically-inducible protein Y (OsmY) is a carrier protein that secretes a target protein extracellularly, and we have previously applied it in the Bacterial Extracellular Protein Secretion System (BENNY) to accelerate directed evolution. In this study, we reported the first application of random and combinatorial mutagenesis on a carrier protein to enhance total secretory target protein production. After one round of random mutagenesis followed by combining the mutations found, OsmY(M3) (L6P, V43A, S154R, V191E) was identified as the best carrier protein. OsmY(M3) produced 3.1 ± 0.3 fold and 2.9 ± 0.8 fold more secretory Tfu0937 ß-glucosidase than its wildtype counterpart in E. coli strains BL21(DE3) and C41(DE3), respectively. OsmY(M3) also produced more secretory Tfu0937 at different cultivation temperatures (37 °C, 30 °C and 25 °C) compared to the wildtype. Subcellular fractionation of the expressed protein confirmed the essential role of OsmY in protein secretion. Up to 80.8 ± 12.2% of total soluble protein was secreted after 15 h of cultivation. When fused to a red fluorescent protein or a lipase from Bacillus subtillis, OsmY(M3) also produced more secretory protein compared to the wildtype. In this study, OsmY(M3) variant improved the extracellular production of three proteins originating from diverse organisms and with diverse properties, clearly demonstrating its wide-ranging applications. The use of random and combinatorial mutagenesis on the carrier protein demonstrated in this work can also be further extended to evolve other signal peptides or carrier proteins for secretory protein production in E. coli.

Influenza Vaccination Quality Improvement as a Model for COVID-19 Prophylaxis.

INTRODUCTION: Many comparisons have been made on the effect and impact of COVID-19 on influenza pandemics of history. Therefore, it is reasonable to infer that the strategies utilized by healthcare providers to improve influenza vaccination rates can similarly be applied to the administration of a COVID-19 vaccine. The purpose of this study was to determine the rationale of low influenza vaccination rates in an urban allergy clinic and how to improve patient education and knowledge regarding the importance of influenza vaccination. A three-year comparison of interventions is presented as well as its application to future COVID-19 vaccinations. METHODS: This study was performed at an outpatient allergy and clinical immunology practice (MSBI) with hospital affiliation in New York City, New York. A quality improvement medical committee was formed to optimize influenza vaccination rates to greater than 71% and established standardized protocols regarding patient intake workflows, vaccine counseling, and documentation. Patient records from four providers were used for this study to compare pre-and post-intervention rates. RESULTS: 984 patients met inclusion criteria, with a normal distribution of ages (18-80), race, and sex. Average vaccination rates prior to the intervention were 9.25-13.60%. The average vaccination rate after the intervention was 91.34%. DISCUSSION: The MSBI quality improvement study identified key areas to address in improving influenza vaccination rates. Vaccine hesitancy, public misinformation, and ambivalence surrounding vaccination with egg allergies or during a subcutaneous immunotherapy injection were all topics addressed during the 2018-2019 intervention year. Additional attention was also put toward provider education and standardization of documentation. Shared decision making and intensive education/outreach efforts are needed by physicians and patients alike to overcome vaccine hesitancy. In comparing this to upcoming COVID-19 vaccine challenges, similar barriers will likely also need to be addressed. Greater research is needed to understand patient motivations regarding hesitancy specific to the COVID-19 vaccine. CONCLUSION: As evidenced in the yearly battle with influenza and now the COVID-19 pandemic, it has become essential to identify and implement multi-level strategies to maximize vaccination rates, especially amid a global pandemic. With COVID-19 vaccines reaching emergency approval stages, it is important for healthcare providers to start creating workflows and strategies to address patient inquiries. The influenza vaccination quality improvement project presented here can be used as a guideline for future evaluations of COVID-19 vaccination efforts.

Lymphogranuloma venereum (LGV) of the anorectum: evaluation of clinicopathological associations and the utility of a novel RNA in-situ hybridisation stain.

AIMS: Recent studies from multiple global regions have reported a resurgence of lymphogranuloma venereum (LGV) proctitis, which is caused by Chlamydia trachomatis (CT). LGV proctitis is histologically indistinguishable from other forms of sexually transmitted proctitis and is difficult to differentiate from inflammatory bowel disease. While immunohistochemical stains are available for syphilis, there is no commonly available stain for the tissue identification of CT. MATERIALS AND METHODS: From 200 positive CT nucleic acid tests (NAT) from anorectal swabs, we identified 12 patients with biopsies collected from the distal colorectum or anus within 90 days of the positive NAT. We collected basic demographic information and tabulated clinical and histological findings. We examined the performance of a novel RNA in-situ hybridisation (ISH) stain targeting CT 23s rRNA on these 12 cases and 10 controls from the anorectum. RESULTS: All 12 patients were male; nine were HIV+, two had concurrent gonococcal infection, one had concurrent syphilis and one had cytomegalovirus co-infection. The majority of biopsies (11 of 12) showed mild or moderate acute inflammation, had a prominent lymphoplasmacytic infiltrate (eight of 11) and lacked marked crypt distortion (10 of 10). The RNA ISH stain was positive in 10 of 12 cases (sensitivity 83%). One case showed equivocal staining. No controls showed definitive positive staining (specificity 100%). One had equivocal staining. CONCLUSION: Our series showed that anorectal LGV had similar histological findings to those of prior STI proctitis series predominantly comprised of syphilis. The novel RNA ISH stain was sensitive and specific and may show utility in differentiating types of STI proctitis.

Cell polarity (the 'four lines') distinguishes gastric dysplasia from epithelial changes in reactive gastropathy.

AIMS: Gastric dysplasia is a risk factor for synchronous and subsequent gastric carcinoma. Distinguishing gastric dysplasia from reactive changes is subject to interobserver disagreement and is a frequent reason for expert consultation. We previously used assessment of surface cell polarity (the 'four lines') as a key feature to decrease equivocal diagnoses in Barrett oesophagus. In the current study, we examined for the presence or absence of the four lines in gastric dysplasia and reactive gastropathy. MATERIALS AND METHODS: The study includes all (n = 91) in-house biopsies with at least gastric dysplasia from the surgical pathology archives of two academic institutions during a 5-year period from 2008 to 2012. A reactive gastropathy group (n = 60) was created for comparison. RESULTS: The dysplasia/neoplasia group was comprised of 14 biopsies of gastric foveolar-type dysplasia, 59 of intestinal-type dysplasia, 14 with dysplasia in fundic gland polyps, three pyloric gland adenomas and one oxyntic gland adenoma. Loss of surface cell polarity was seen in all 88 dysplasia cases with evaluable surface epithelium. All 57 reactive gastropathy cases with evaluable surface epithelium showed intact surface cell polarity except in focal areas directly adjacent to erosions in 17 cases, where the thin wisp of residual surface mucin could not be appreciated on haematoxylin and eosin. CONCLUSION: Surface cell polarity (the four lines) was lost in all gastric dysplasia biopsies with evaluable surface epithelium and maintained in all biopsies of reactive gastropathy. Caution should be taken in using this feature adjacent to erosions in reactive gastropathy.

New Names for Old Tumors.

OBJECTIVES: Previous studies described "clear cell" hepatocellular carcinoma (HCC), although definitions have varied. New clear cell subtypes of HCC have been proposed, including chromophobe (C-HCC), steatohepatitic (SH-HCC), and steatotic (S-HCC), and this study assessed the utility and clinical-pathologic profile of these subtypes. METHODS: Current histologic definitions, including 3 separate proposed definitions for SH-HCC, were applied to tumors previously characterized as clear cell HCC. Histologic and clinical variables were analyzed. RESULTS: Of 66 HCCs, 51 (77%) were classified using modern definitions, including 34 SH-HCCs, 15 S-HCCs, and 2 C-HCCs. Compared with the most permissive SH-HCC definition, the other 2 definitions designated 30 and 25 SH-HCCs (-12% and -26% cases, respectively). Unsurprisingly, S-HCC and SH-HCC were associated with steatotic clear cells (P < .0001). S-HCC was also more typically early type and low grade (P = .0017). The remaining unclassified clear cell HCCs were associated with flocculent (rather than steatotic or optically clear) cytoplasm (P < .0001) but otherwise demonstrated no discrete clinical-pathologic profile. CONCLUSIONS: Current definitions could be used to reclassify the majority of "clear cell" HCCs. The subtypes are significantly correlated with a few variables, suggesting valid differences of the subtypes, although additional study is warranted, particularly to standardize the definition of SH-HCC.

Quantitative Analysis of Intramucosal Mast Cells in Irritable Bowel Syndrome: A Comparison With Inflammatory Bowel Disease in Remission.

GOAL: We aimed to study the density of intramucosal mast cells in histologically normal colonic mucosa biopsied from patients with a clinical diagnosis of irritable bowel syndrome (IBS). BACKGROUND: Mast cell activation has been thought to implicate in the pathogenesis of inflammatory bowel disease (IBD). Whether it serves a role in the pathogenesis of IBS remains controversial. STUDY: A total of 127 colonoscopic mucosal biopsies were immunohistochemically stained, including 51 IBS, 66 IBD, and 10 normal control samples. Intact mast cells were quantified in 3 high power fields (HPF) in areas showing the highest density. RESULTS: CD117 was sensitive in detecting mast cells in colonic mucosa. The mast cell counts in all biopsies ranged from 2 to 60 per HPF (mean=17.5±7.2). The density of intramucosal mast cells were similar among IBS, IBD and normal control groups (P=0.6733). IBD in remission versus IBS (17.1±8.0 vs. 18.1±7.0; P=0.4804), Crohn disease versus ulcerative colitis (17.1±10.4 vs. 17.2±5.2; P=0.9463), IBS with diarrhea versus without diarrhea (19.5±6.3 vs. 16.8±6.9; P=0.1404). Forty biopsies (31.5%) showing ≥20 mast cells per HPF appeared to equally distribute among various disease groups (P=0.7283). CONCLUSIONS: There is no significant difference in the number of intramucosal mast cells between IBS and IBD that show normal colonic biopsies. In IBS patients, the number of intramucosal mast cell does not correlate with symptoms. The mast cell count (≥20/HPF) is not a reliable criterion for the diagnosis of IBS or for the distinction between patients with IBS and those with IBD in remission.

Low-Grade Appendiceal Mucinous Neoplasms: A Single Institution Experience of 64 Cases With Clinical Follow-up and Correlation With the Current (Eighth Edition) AJCC Staging.

Background. In this single-institution study, we applied the current (eighth edition) American Joint Committee on Cancer pathologic staging criteria to 64 low-grade mucinous neoplasms of the appendix (LAMNs), examined their histopathologic features, and studied the patients' clinical outcomes. Design. Sixty-four LAMNs, with a median follow-up of 52 months, were reviewed. Results. The distribution of pathologic stages was pTis (n = 39), pT3 (n = 1), pT4a (n = 5), pT4aM1a (n = 8), and pT4aM1b (n = 11). Recurrence was observed in only 2 patients (both with pT4aM1b disease), one of whom died of disease. All remaining patients were disease-free after a median clinical follow-up of 60 months. Conclusions. Our study confirms that pTis LAMNs have an excellent prognosis and suggests that pT4a and pT4aM1a LAMNs may also have a low risk of developing progressive disease.