bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular adverse events in PD-1 and PD-L1 inhibitors
Authors: Young LeAnne , Finnigan Shanda , Streicher Howard , Chen Helen X , Murray James , Sen H Nida , Sharon Elad 
Published: July 2021

BackgroundProgrammed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation. However, less is known about adverse effects of these drugs in the eye.MethodsTwo adverse event databases were retrospectively reviewed. The two databases consisted of a routine adverse event database and a serious adverse event database of expeditiously submitted reports. Patients with any malignancy who had ocular adverse events while on PD-1/PD-L1 inhibitor treatment were included. Patients received nivolumab, pembrolizumab, atezolizumab or durvalumab alone or in combination with other anticancer agents per each trial’s protocol. Databases were queried up to May 19, 2020.ResultsIn the routine adverse event database, 272 adverse events from 213 patients were reported and in the serious adverse event reporting database, 59 ocular adverse events from 47 patients were reported. A lower estimate of the prevalance from the routine adverse event database showed 259/7727 patients on study treatment arms reporting ocular adverse events (3.3% prevalence). Excluding trials that do not report lower grade adverse events to the routine adverse event database results in a higher end estimate of 242/3255 patients on study treatment arms reporting ocular adverse events (7.4% prevalence). Ocular events occurred early after drug initiation (routine database: median 6 weeks, IQR 0–16, serious adverse events database: median 11 weeks, IQR 6–21). The median Common Terminology Criteria for Adverse Events grade was grade 1 (mild) (IQR 1–2) and grade 2 (moderate) (IQR 2–3) for the routine database and the serious adverse events database, respectively. In-depth analysis of the serious adverse event reports revealed varying degrees of clinical workup, with 30/47 patients (64%) receiving ophthalmological evaluation and 16/47 (34%) of patients having to delay or discontinue treatment. However, 16/47 (34%) patients experienced resolution and 14/47 (30%) patients experienced at least some improvement.ConclusionsThis is one of the largest analyses of ocular adverse events in patients treated with PD-1/PD-L1 inhibitors in the USA. We found ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, can be severe enough to cause treatment discontinuation/delay, and may not always be appropriately evaluated by eye specialists. Standardized plans for ophthalmology evaluation and management of ocular toxicities are needed in studies of patients treated with PD-1/PD-L1 inhibitors.
Expression of KLRG1 and CD127 defines distinct CD8+subsets that differentially impact patient outcome in follicular lymphoma
Authors: Wu Hongyan , Tang Xinyi , Kim Hyo Jin , Jalali Shahrzad , Pritchett Joshua C , Villasboas Jose C , Novak Anne J , Yang Zhi-Zhang , Ansell Stephen M 
Published: July 2021

BackgroundCD8+T-lymphocyte subsets defined by killer lectin-like receptor G1 (KLRG1) and CD127 expression have been reported to have an important role in infection, but their role in the setting of lymphoid malignancies, specifically follicular lymphoma (FL), has not been studied.MethodsTo characterize the phenotype of KLRG1/CD127-defined CD8+subsets, surface and intracellular markers were measured by flow cytometry and Cytometry by time of flight (CyTOF), and the transcriptional profile of these cells was determined by CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing). The functional capacity of each subset was determined, as was their impact on overall survival (OS) and event-free survival (EFS) of patients with FL.ResultsWe found that intratumoral CD8+cells in FL are skewed toward effector cell subsets, particularly KLRG+CD127-and KLRG1-CD127-cells over memory cell subsets, such as KLRG1-CD127+and KLRG1+CD127+cells. While effector subsets exhibited increased capacity to produce cytokines/granules when compared with memory subsets, their proliferative capacity and viability were found to be substantially inferior. Clinically, a skewed distribution of intratumoral CD8+T cells favoring effector subtypes was associated with an inferior outcome in patients with FL. Increased numbers of CD127+KLRG1-and CD127+KLRG1+were significantly associated with a favorable OS and EFS, while CD127-KLRG1-correlated with a poor EFS and OS in patients with FL. Furthermore, we demonstrated that interleukin (IL)-15 promotes CD127-KLRG1+cell development in the presence of dendritic cells via a phosphoinositide 3-kinase (PI3K)-dependent mechanism, and treatment of CD8+T cells with a PI3K inhibitor downregulated the transcription factors responsible for CD127-KLRG1+differentiation.ConclusionsTaken together, these results reveal not only a biological and prognostic role for KLRG1/CD127-defined CD8+subsets in FL but also a potential role for PI3K inhibitors to manipulate the differentiation of CD8+T cells, thereby promoting a more effective antitumor immune response.
Night shift work undertaken by women and fertility treatment interact to increase prevalence of urogenital anomalies in children
Authors: Fernandez Renae C , Moore Vivienne M , Willson Kristyn J , Davies Michael 
Published: July 2021

ObjectiveTo investigate the role of maternal night shift work in occurrence of urogenital anomalies in offspring, considering a possible interaction with mode of conception.MethodsA population-based cohort comprising births in South Australia (1986–2002) was produced via linkage of fertility clinic records, perinatal and birth defects data. This study concerned first births to women in paid employment (n=98 103). Potential exposure to night shift was imputed by applying a job-exposure matrix to recorded occupation. Associations were examined using logistic regression, first for nurses and other night shift workers separately, then combined. An interaction term for night shift work and mode of conception was included in all models, while adjusting for covariates.ResultsAssociations were similar for nurses and other night shift workers, although only statistically significant for the former when considered separately. A multiplicative interaction was supported: for natural conceptions, maternal night shift work was not associated with offspring urogenital anomalies (OR=0.99, 95% CI 0.84 to 1.15); where a birth arose from fertility treatment, urogenital anomalies were significantly higher among births to all night shift workers compared with day workers (OR=2.07, 95% CI 1.20 to 3.55). This was not due to differences in the type of fertility treatment received.ConclusionsWomen in occupations that probably involved night shift did not have offspring with increased prevalence of urogenital anomalies if they conceived naturally. When night shift workers conceived with fertility treatment, the prevalence of urogenital anomalies was elevated. Possibly these women had the greatest exposure to night shift work, or least tolerance for this work schedule, or heightened sensitivity to hormonal aspects of fertility treatment.
Safeguarding teenagers in a sexual health service during the COVID-19 pandemic
Authors: Bekaert Sarah , Azzopardi Liz 
Published: July 2021

ObjectivesThe first aim was to examine how the COVID-19 restrictions on movement impacted on teenagers’ access to a local sexual health service (SHS). The second aim was to audit whether safeguarding assessments were carried out for those accessing the service remotely.MethodsApril–September 2020 consultation numbers for teenagers aged 17 years and under were compared with the 2019 equivalent. Service safeguarding assessment standards were reviewed for teenagers receiving telephone consultations for the first 6 months of lockdown, April–September 2020.ResultsThere was a reduction in contact with the service of 100% for those aged 13 years and younger, 52% for those aged 14 and 15 years and 31% for those aged 16 and 17 years for the compared months. A safeguarding assessment was either carried out by the service or accounted for by a partner community practitioner for all contacts with the service by young people 15 years or younger. 96% of safeguarding assessments were carried out for those aged 16–17 years.ConclusionsThere was a reduction in consultations for all age groups examined in the 6 months following lockdown. This adds to the evidence that restrictions during lockdown are barriers to young people accessing SHSs. For those who did have a consultation, safeguarding assessments were consistently carried out. Nevertheless, due to reduced contact overall, it is likely that some safeguarding issues remain undisclosed. Multiagency safeguarding networks and telephone consultations with a low threshold for promoting an in-person consultation facilitated access to the SHS and a robust safeguarding pathway during the constraints of the COVID-19 pandemic.
Six-week behaviour change intervention to reduce sedentary behaviour in people with chronic obstructive pulmonary disease: a randomised controlled trial
Authors: Cheng Sonia Wing Mei , Alison Jennifer , Stamatakis Emmanuel , Dennis Sarah , McNamara Renae , Spencer Lissa , McKeough Zoe 
Published: July 2021

IntroductionThis study aimed to determine whether a 6-week behaviour change intervention was more effective than a sham intervention for reducing sedentary behaviour (SB) in people with chronic obstructive pulmonary disease (COPD).MethodsPeople with stable COPD on the waitlist for entry into pulmonary rehabilitation were recruited to this multicentre trial with randomisation (independent, concealed allocation) to either an intervention group or sham group, assessor blinding and intention-to-treat (ITT) analysis. The behaviour change intervention consisted of once weekly sessions for 6 weeks with a physiotherapist to reduce SB through education, guided goals setting and real-time feedback on SB. The sham intervention consisted of once weekly phone calls for 6 weeks to monitor health status. SB was measured continuously over 7 days using thigh-worn accelerometry (activPAL3 micro). The primary outcome was time spent in SB. Participants with at least 4 days of ≥10 hours waking wear time were included in the ITT analysis and those who reported achieving ≥70% of goals to reduce SB or who completed all sham calls were included in a per-protocol analysis.Results70 participants were recruited and 65 completed the study (mean±SD age 74±9 years, mean FEV1 55%±19% predicted, 49% male). At 6 weeks, no between-group differences in time spent in SB were observed in the ITT analysis (mean difference 5 min/day, 95% CI −38 to 48) or per-protocol analysis (−16 min/day, 95% CI −80 to 48).DiscussionA 6-week behaviour change intervention did not reduce time in SB compared with a sham intervention in people with stable moderate-to-severe COPD prior to pulmonary rehabilitation.
Homens da Montanha: Cristãos Novos e a Ocupação do Interior Brasileiro
Authors: Tonello Levy Daniela 
Published: July 2021

Judeus Sefaraditas, descendentes dos convertidos em 1497, foram os pioneiros na descoberta do ouro e diamantes na América portuguesa. A instituição do Tribunal do Santo Ofício da Inquisição, trouxe drásticas consequências para a vida Ibérica, que a longo prazo arruinaram o comércio português, fazendo emigrar do Reino os mais prestigiosos elementos, prejudicando por muitos anos a produção nacional, destruindo famílias e negócios. A cultura judaica, florescente na Península Ibérica até o século XV, apagou-se, e Portugal submergiu nas trevas da ignorância. Em São Paulo, os cristãos novos estiveram entre os desbravadores do sertão brasileiro, ultrapassando os limites do Tratado de Tordesilhas. Os habitantes da então inóspita Vila de São Paulo de Piratininga eram considerados inimigos da Espanha, por suas incursões ao sertão em busca de oportunidades econômicas. No interior, lutaram contra às Missões jesuíticas, a vida selvagem, fome, sede e finalmente se tornaram os primeiros a encontrar ouro no Brasil. Foram os primeiros a abrir estradas e fundar as vilas do ouro. Um marrano, Garcia Rodrigues Paes, foi o responsável pela construção do “Caminho do comércio” que encurtava a distância entre o Rio de janeiro, principal porto e a Vila de Ouro Preto. Os sefaraditas acreditavam estar seguros, nas montanhas e no interior do Brasil, mas a Inquisição formou uma rede de espiões encarregados de espionar e prender os cristãos novos.
Abstract 186: Reduction Of High density lipoprotein Cholesterol After Successfull Dietary Intervention Is Not Accompanied By A Change In Reverse Cholesterol Transport
Authors: Poledne Rudolf 
Published: July 2021

Substitution of dietary saturated fat by unsaturated fat and the reduction of dietary cholesterol intake leads to a decrease of LDL cholesterol concentration accompanied usually by a decrease of HDL cholesterol.

Method: 18 young male volunteers were fed for 4 weeks either a high cholesterol saturated fat diet or low cholesterol and unsaturated fat diet in crossover design. At the end of both experimental periods, the lipoprotein concentration was determined. In addition, the reverse cholesterol transport from
14
C cholesterol labeled macrophages in tissue cultures was analyzed. Reverse cholesterol transport was calculated as the percentage of radioactivity released from pre-labeled cells to incubation media with serum of each individuals.

Results: Highly significant decrease of LDL cholesterol after the unsaturated fat diet was accompanied by a significant decrease of the HDL cholesterol from 1.25 mmol/l to 1.05 mmol/l. Reverse cholesterol transport did not significantly change when the data of high cholesterol saturated fat diet (9.97 ± 1.45) and low cholesterol unsaturated fat diet (9.53 ± 1.41) were compared. There was no correlation between data of the decrease of HDL cholesterol concentration and change in reverse cholesterol transport.
Conclusion: We conclude that dietary treatment by hypocholesterolemic diet accompanied by a reduction of HDL cholesterol does not lead to the decrease in reverse cholesterol transport.
Abstract 1541: Atypical Atrioventricular Nodal Reentrant Tachycardia with Anterior Retrograde Slow Pathway: Incidence, Electrophysiological Characteristics and Effect of Slow Pathway Ablation
Authors: Otomo Kiyoshi , Nagata Yasutoshi , Taniguchi Hiroshi , Uno Kikuya , Iesaka Yoshito 
Published: July 2021

BACKGROUND: Atypical AV nodal reentrant tachycardias (AVNRT) usually exhibit earliest retrograde atrial activation (ERAA) at the right posteroseptum (Rt-PS) or proximal coronary sinus (PCS). However, previous studies have shown that atypical AVNRT could rarely exhibit ERAA at the right anteroseptum (Rt-AS). The purpose of this study was to elucidate the incidence, characteristics and effect of slow pathway (SP) ablation in atypical AVNRT with an anterior retrograde SP.
METHODS: The electrophysiological and ablation data were reviewed in 360 AVNRTs induced in 340 consecutive patients. Atypical AVNRT was differentiated from typical form by a longer H-A interval during ventricular pacing at the tachycardia cycle length (TCL) (HAp: =/>70ms), and evidences for a lower common pathway (LCP), including second-degree AV block without tachycardia interruption, HAp longer than the HA interval during tachycardia (HAt). Atypical AVNRTs were classified into two types; the posterior type with ERAA at the Rt-PS or PCS; and anterior type with ERAA at the Rt-AS.
RESULTS: In a total of 360 AVNRTs, there were 300 typical (83%) and 60 atypical forms (17%). Among the 60 atypical forms, 51 (14%) were classified into the posterior type, while the remaining 9 (3%) were classified into the anterior type. The anterior type of atypical AVNRT (TCL: 322+/−37ms) exhibited ERAA at the Rt-AS during the tachycardia and ventricular pacing, shorter A-H interval (162+/−39ms), longer HAt (167+/−40 ms), longer HAp (184+/−53ms), and evidences for a LCP, including a second-degree AV block during the tachycardia (n=4) and HAt being shorter than the H-Ap (n=9). All posterior types of atypical AVNRT were rendered non-inducible after an ablation to the ERAA site. In anterior type, the conventional SP ablation at the Rt-PS did not eliminate any of the 9 tachycardias; however, ablations at the right midseptum eliminated 7 (78%) of the 9 anterior types of atypical AVNRT.
CONCLUSION: Atypical AVNRT with an anterior retrograde SP was observed in 3% of all AVNRTs. Conventional Rt-PS ablation was ineffective; and the midseptal ablation was modestly effective in this entity. The tachycardia circuit of the anterior type might be deviated to more anterior part of the Koch’s triangle than that of the posterior type.
Abstract 2138: Fontan Fenestration Closure Has No Effect On Exercise Capacity But Improves The Ventilatory Response To Exercise
Authors: Meadows Jeffery , Lang Peter , Marx Gerald , Curran Tracy , Sheehan Julie , Rhodes Jonathan 
Published: July 2021

Introduction: For patients undergoing Fontan procedures for palliation of single ventricle physiology the addition of a fenestration to the procedure, which permits intracardiac right-to-left shunting, mitigates perioperative morbidity. While some fenestrations may close spontaneously, many remain patent and subject patients to arterial hypoxemia and risk for paradoxical emboli. For this reason fenestration closure is routinely performed post-operatively in the cardiac catheterization laboratory. Fenestration closure typically results in improved arterial oxygenation, but decreased cardiac index. We assessed the hypothesis that sum effect of these physiologic changes would have not improve exercise capacity.
Methods: Nineteen consecutive patients, age 4.8–46 (median 10) years underwent pre and post-fenestration closure exercise testing with expiratory gas analysis.
Results: Prior to fenestration closure, peak oxygen consumption (VO2) was low. Arterial desaturation was present at rest and worsened with exercise. The ventilatory response to exercise was excessive, characterized by elevation of the minute ventilation vs. CO2 production slope (VE/VCO2 slope) and a low end tidal pCO2 at the ventilatory anaerobic threshold (pETCO2). Following fenestration closure, arterial saturation (at rest and at peak exercise) improved significantly. However, there was no change in VO2, heart rate, or oxygen pulse at peak exercise. In contrast, ventilatory abnormalities improved considerably. The VE/VCO2 slope fell 25% and pETCO2 rose from 27.9+/−4.2 to 34.1+/−3.2 mmHg.
Conclusion: Elective Fontan fenestration closure does not improve peak VO2. However, the reduction in right-to-left intracardiac shunting improves arterial oxygen saturation during exercise and reduces the patient’s need to ventilate during exercise. These changes may reduce the Fontan patient’s perception of dyspnea during exercise.

Pre and Post-Fenestration Exercise Data
Abstract 2373: Diet Plus Pravastatin Treatment Reduces The Risk Of Cardiovascular Disease And Total Mortality In Patients With Metabolic Syndrome: Sub-analysis From A Large-scale Primary Prevention Trial With Pravastatin (MEGA Study)
Authors: Matsushima Teruhiko , Koseki Susumu , Nakamura Haruo 
Published: July 2021

Background: The metabolic syndrome is related to an increased risk of cardiovascular disease (CVD), as reported by numerous studies. In this analysis, we investigated the relationship between the metabolic syndrome (MetSyn) and CVD risk in hypercholesterolemic patients and the effect of pravastatin treatment in the MEGA Study population.

Methods: The MetSyn was defined according to modified National Cholesterol Education Program (NCEP) criteria, namely, the presence of three or more risk factors: 1)obesity (body mass index ≥25 kg/m
2
), 2)hypertriglyceridemia (≥150 mg/dL), 3)low HDL cholesterol (<40 mg/dL in men and <50 mg/dL in women), 4)hypertension (SBP≥130 mmHg and/or DBP≥85 mmHg), 5)hyperglycemia (fasting glucose ≥100 mg/dL). The risk of CVD and total mortality was compared in patients with and without MetSyn. The effect of pravastatin plus diet therapy in the patients with MetSyn was compared to those without MetSyn, and moreover these comparisons were conducted in two groups, divided according to their LDL cholesterol levels (cut point: 156.9 mg/dL).

Results: A total of 2,636 (33.7%) of the 7,832 hypercholesterolemic patients enrolled in MEGA had MetSyn. A 1.9 times higher incidence of CVD was found in the patients with, compared to those without, MetSyn. The risk of CVD in patients with MetSyn was very similar to that in patients with high LDL cholesterol (≥156.9 mg/dL) and with low LDL cholesterol (<156.9 mg/dL). Notably, a 36% significant risk reduction for CVD and 50% risk reduction for total mortality were observed in the patients with MetSyn treated with pravastatin plus diet treatment compared to diet therapy alone. Moreover, the greatest CVD risk reduction was observed in the high LDL-C group with MetSyn compared to those without MetSyn (Hazard ratio 0.44 vs. 0.56, respectively, interaction p=0.07).
Conclusion: Metabolic syndrome increases the risk of CVD regardless of the presence or absence of hypercholesterolemia. Diet plus pravastatin treatment is effective for the prevention of CVD for patients with hypercholesterolemia and MetSyn.
Abstract 2685: Assessment of Myocardial Perfusion With Stress-Contrast Echocardiography in Diabetics
Authors: Aggeli Constadina , Giannopoulos Georgios , Roussakis Georgios , Christoforatou Euaggelia , Marinos Georgios , Ioakeimidis Nikolaos , Kokkinakis Christos , Stefanadis Christodoulos 
Published: July 2021

Background and purpose: The combination of myocardial contrast echocardiography with dobutamine-atropine stress echocardiography has shown promising results in the diagnostic approach of coronary heart disease (CHD). However, its diagnostic value in specific patient populations has not been clearly specified. The aim of the present study was to assess the value of stress contrast echocardiography (SCE) in diagnosing significant coronary heart disease in diabetic versus non-diabetic patients.
Methods: 127 individuals (60 males, 62±9.8 years old) with no known history of CHD, among which 59 patients with Type 2 diabetes mellitus, were submitted to stress echocardiography (four-stage dobutamine protocol 10 – 40 mcg/kg/min, with use of atropine as required to reach 90% of age-adjusted target heart rate), combined with intravenous contrast use to perform myocardial contrast echocardiography. New or worsening wall motion abnormalities during stress or reversible perfusion defects in >2 contiguous segments were considered as signs of ischemia. Significant CHD was defined as >50% stenosis in a major epicardial artery on coronary angiography (CAG).

Results: Among the 68 non-diabetic subjects and the 59 diabetics, 58 (85.3%) and 45 (76.3%) were found to have significant CHD on CAG, respectively. There were no significant differences as regards to age, sex and other major risk factors between diabetics and non-diabetics. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in the total of 127 patients were 92%, 63%, 91%, 65% and 87%, respectively. These diagnostic parameters in non-diabetic vs. diabetic subjects were 93% vs. 91% (p=
NS
), 90% vs. 43% (p<0.01), 98% vs. 84% (p<0.05) and 69% vs. 60% (p=
NS
).

Conclusions: Stress contrast echocardiography is an exceptionally reliable technique for CHD diagnosis. However, our findings suggest that in diabetic patients it appears to exhibit inferior specificity and PPV compared to non-diabetics. A possible explanation could be that microcirculation abnormalities, which are common in diabetes, may cause appearance of signs of ischemia (wall-motion abnormalities and/or perfusion defects) on SCE, without presence of angiographically significant CHD.