tbuckley/cabot-search huggingface dataset:
Hyperglycemia Drives Stent Restenosis in STEMI Patients
Authors: Pasquale Mone, Jessica Gambardella, Fabio Minicucci, Angela Lombardi, Ciro Mauro, Gaetano Santulli
Journal: Diabetes Care (2021)

ST-elevation myocardial infarction (STEMI) is one of the leading causes of death and hospitalization worldwide (1). Hyperglycemia (HG) has been shown to adversely affect STEMI clinical outcomes, leading to higher mortality and severe complications (1,2).

The aim of our study was to investigate the impact of HG at hospital admission on the risk of restenosis after primary percutaneous coronary intervention (PCI) for STEMI, comparing normoglycemic subjects (NG group), patients without diabetes mellitus (DM) but with HG (HG-non-DM group), and patients with both HG and DM (HG-DM group). HG was defined by glycemia >140 mg/dL, according to the guidelines of the American Diabetes Association (3). We evaluated STEMI patients referred to the Division of Cardiology of “Antonio Cardarelli” Hospital from February 2008 to February 2016. Inclusion criteria were age >18 years and first STEMI. Exclusion criteria were left ventricular ejection fraction <25% and prior coronary artery bypass grafting. Routine blood analysis, including HbA1c, was obtained at admission. The STEMI culprit lesion was identified and treated via primary PCI, crossed with an angioplasty guidewire followed by stent implantation. All patients were contacted 1 year after the …
Adolescents navigating the COVID-19 pandemic
Authors: Farooq Kazi, Ammara Mushtaq
Journal: The Lancet Child & Adolescent Health (2021)

COVID-19 has disrupted the lives of individuals and families around the world, and the consequences have been multifaceted, reaching beyond the physical to encompass social, emotional, psychological, and financial aspects. Although much research has focused on older individuals in terms of morbidity and mortality, children and adolescents are especially vulnerable to the mental health consequences of the pandemic. Further complicating the issue, prolonged symptoms after initial SARS-CoV-2 infection have recently been brought to attention.
All you need to know about sperm RNAs
Authors: Joana Santiago, Joana V Silva, John Howl, Manuel A S Santos, Margarida Fardilha
Journal: Human Reproduction Update (2021)

Spermatogenesis generates a small and highly specialised type of cell that is apparently incapable of transcription and translation. For many years, this dogma was supported by the assumption that (i) the compact sperm nucleus, resulting from the substitution of histones by protamine during spermatogenesis, renders the genome inaccessible to the transcriptional machinery; and (ii) the loss of most organelles, including endoplasmic reticulum and ribosomes, limits or prevents translational activity. Despite these observations, several types of coding and non-coding RNAs have been identified in human sperm. Their functional roles, particularly during fertilisation and embryonic development, are only now becoming apparent.This review aimed to summarise current knowledge of the origin, types and functional roles of sperm RNAs, and to evaluate the clinical benefits of employing these transcripts as biomarkers of male fertility and reproductive outcomes. The possible contribution of sperm RNAs to intergenerational or transgenerational phenotypic inheritance is also addressed.A comprehensive literature search on PubMed was conducted using the search terms 'sperm' AND 'RNA'. Searches focussed upon articles written in English and published prior to August 2020.The development of more sensitive and accurate RNA technologies, including RNA sequencing, has enabled the identification and characterisation of numerous transcripts in human sperm. Though a majority of these RNAs likely arise during spermatogenesis, other data support an epididymal origin of RNA transmitted to maturing sperm by extracellular vesicles. A minority may also be synthesised by de novo transcription in mature sperm, since a small portion of the sperm genome remains packed by histones. This complex RNA population has important roles in paternal chromatin packaging, sperm maturation and capacitation, fertilisation, early embryogenesis and developmental maintenance. In recent years, additional lines of evidence from animal models support a role for sperm RNAs in intergenerational or transgenerational inheritance, modulating both the genotype and phenotype of progeny. Importantly, several reports indicate that the sperm RNA content of fertile and infertile men differs considerably and is strongly modulated by the environment, lifestyle and pathological states.Transcriptional profiling has considerable potential for the discovery of fertility biomarkers. Understanding the role of sperm transcripts and comparing the sperm RNA fingerprint of fertile and infertile men could help to elucidate the regulatory pathways contributing to male factor infertility. Such data might also provide a molecular explanation for several causes of idiopathic male fertility. Ultimately, transcriptional profiling may be employed to optimise ART procedures and overcome some of the underlying causes of male infertility, ensuring the birth of healthy children.
Lung dendritic cells migrate to the spleen to prime long-lived TCF1 <sup>hi</sup> memory CD8 <sup>+</sup> T cell precursors after influenza infection
Authors: Meagan M. Jenkins, Holly Bachus, Davide Botta, Michael D. Schultz, Alexander F. Rosenberg, Beatriz León, André Ballesteros-Tato
Journal: Science Immunology (2021)

Lung-derived dendritic cells carry influenza antigens to the spleen after egressing the lymph node by an S1P/S1PR-dependent mechanism.
A Phase II Cluster-Crossover Randomized Trial of Fentanyl versus Morphine for Analgosedation in Mechanically Ventilated Patients
Authors: Andrew J. Casamento, Ary Serpa Neto, Marcus Young, Mervin Lawrence, Christina Taplin, Glenn M. Eastwood, Angajendra Ghosh, Rinaldo Bellomo
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. Objectives: To compare the effect of fentanyl versus morphine on patient-centered outcomes in ventilated patients. Methods: We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult ICUs. We compared two continuous infusion regimens (fentanyl versus morphine). One ICU was randomized to the fentanyl-morphine sequence and the other to the morphine-fentanyl sequence. The primary outcome was the number of ventilator-free days at Day 28. Secondary outcomes included, among others, duration of mechanical ventilation in survivors and ICU-free days at Day 28. Measurements and Main Results: Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded because of the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [interquartile range] age, 59 [44-69] years). Median ventilator-free days at Day 28 were 26.1 (20.7-27.3) in the fentanyl versus 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% confidence interval, 0.31 to 1.28], P = 0.001). ICU-free days were greater (P < 0.001) and length of stay in the ICU for survivors shorter (P < 0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group. Conclusions: Among adult patients requiring mechanical ventilation, compared with morphine, fentanyl infusion significantly increased the median number of ventilator-free days at Day 28. The choice of opioid infusion agent may affect clinical outcomes and requires further investigation.
PROGNOSTIC IMPACT OF CASCADE SCREENING FOR FAMILIAL HYPERCHOLESTEROLEMIA ON CARDIOVASCULAR EVENTS
Authors: Hayato Tada, Hirofumi Okada, Akihiro Nomura, Atsushi Nohara, Masakazu Yamagishi, Masayuki Takamura, Masa-aki Kawashiri
Journal: Journal of the American College of Cardiology (2020)
Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure
Authors: Kevin S. Shah, James C. Fang
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve blood glucose control by blocking renal glucose reabsorption with little subsequent risk of hypoglycemia. Consequently, there are decreases in plasma volume, body weight, and blood pressure. Additional putative benefits include improved cardiovascular energetics, decreased systemic inflammation, and less renal dysfunction. Multiple cardiovascular outcome trials in diabetic patients have demonstrated this drug class reduces the risk of adverse cardiovascular events. Reductions in heart failure (HF) hospitalization suggested that SGLT2 inhibitors might prove useful for the primary treatment of HF. Two large subsequent trials studying SGLT2 inhibitors in heart failure with reduced ejection fraction (HFrEF) demonstrated a reduction in cardiovascular mortality, HF hospitalizations, and renal-specific adverse events. This medication class is now recognized as a new pillar of therapy for patients with HFrEF. The cardiovascular and HF community await the results of ongoing trials of SGLT2 inhibition in patients with HF with preserved ejection fraction.
Understanding Metabolic Memory: The Prolonged Influence of Glycemia During the Diabetes Control and Complications Trial (DCCT) on Future Risks of Complications During the Study of the Epidemiology of Diabetes Interventions and Complications (EDIC)
Authors: John M. Lachin, David M. Nathan
Journal: Diabetes Care (2021)

The Diabetes Control and Complications Trial (DCCT, 1983-1993) showed that intensive therapy (mean HbA1c 7.2%) compared with conventional therapy (mean HbA1c 9.0%) markedly reduced the risks of retinopathy, nephropathy, and neuropathy, and these reductions in complications were entirely attributable, statistically, to the difference in mean HbA1c levels. The DCCT cohort has been followed in the Epidemiology of Diabetes Interventions and Complications (EDIC) study (1994 to date). Early in EDIC, mean HbA1c levels in the former intensively and conventionally treated groups converged. Nevertheless, the beneficial effects of DCCT intensive versus conventional therapy on microvascular complications not only persisted but increased during EDIC. The differences in complications during EDIC were wholly explained, statistically, by differences between groups in HbA1c levels during DCCT. These observations give rise to the concept of metabolic memory. Subsequent similar findings from the UKPDS gave rise to a similar concept, which they called the legacy effect. In this report, we present the evidence to support metabolic memory as both a biological and epidemiological phenomenon and discuss potential underlying mechanisms. We also compare metabolic memory and the legacy effect and conclude that the two are likely biologically similar, with comparable effects on long-term outcomes. The long-term influence of metabolic memory on the risk of micro- and macrovascular complications supports the implementation of intensive therapy, with the goal of maintaining near-normal levels of glycemia, as early and as long as safely possible in order to limit the risk of complications.
P14.30 Voxelwise analysis of spatial distribution of postoperative ischemia in diffuse glioma
Authors: A T J van der Boog, S David, A M M Steennis, T J Snijders, J W Dankbaar, P A Robe, J J C Verhoeff
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Surgical treatment of diffuse glioma is performed to reduce tumor mass effect and to pave the way for adjuvant (chemo)radiotherapy. As a complication of surgery, ischemic lesions are often found in the postoperative setting. Not only can these lesion induce neurological deficits, but their volume has also been associated with reduced survival time. Prior studies suggest areas with a singular vascular supply to be more prone to postoperative ischemic lesions, although the precise cause is yet unknown. The aim of this study was to explore the volumetric and spatial distributions of postoperative ischemic lesions and their relation to arterial territories in glioma patients. MATERIAL AND METHODS We accessed a retrospective database of 144 adult cases with WHO grade II-IV supratentorial gliomas, who received surgery and postoperative MRI within 3 days in 2012–2014. We identified 93 patients with postoperative ischemia, defined as new confluent diffusion restriction on DWI. Ischemic lesions were manually delineated and spatially normalized to stereotaxic MNI space. Voxel-based analysis (VBA) was performed to compare presence and absence of postoperative ischemia. False positive results were eliminated by family-wise error correction. Areas of ischemia were labeled using an arterial territory map, the Harvard-Oxford cortical and subcortical atlases and the XTRACT white matter atlas. RESULTS Median volume of confluent ischemia was 3.52cc (IQR 2.15–5.94). 23 cases had only ischemic lesion in the left hemisphere, 46 in the right hemisphere and 24 bilateral. Median volume was 3.08cc (IQR 1.35–5.72) in left-sided lesions and 2.47cc (1.01–4.24) in right-sided lesions. Volume of ischemic lesions was not associated with survival after 1, 2 or 5 years. A cluster of 125.18cc was found to be significantly associated with development of postoperative ischemia. 73% of this cluster was situated in the arterial territory of the right middle cerebral artery (MCA), limited by the border of the posterior cerebral artery (PCA), and the watershed area between the right MCA and the right anterior cerebral artery (ACA). Significant areas were located in the frontal lobes, spanning into the right temporo-occipital region, and predominantly included right and left thalamus, caudate nucleus, putamen, pallidum, as well as right temporal gyri and insular cortex, and parts of the right corticospinal tract, longitudinal fasciculi and superior thalamic radiation. CONCLUSION We found slightly more and larger ischemic lesions in the right than left hemisphere after glioma resection. A statistically significant cluster of voxels of postoperative ischemia was found in the territory of the right MCA and watershed area of the right ACA. Exploration of the spatial distribution of these lesions could help elucidate their etiology and form the basis for predicting clinically relevant postoperative ischemia.
Extraction of a large mollusc shell impacted in the cervical esophagus: a twin-grasping approach could be the answer
Authors: Oscar Nogales, Celia Caravaca Gámez, Jon de la Maza, Julia del Río Izquierdo, Javier García-Lledó, Isabel Payeras, Beatriz Merino Rodríguez
Journal: Endoscopy (2021)

A 57-year-old man with a history of bipolar disorder presented to the emergency room with a 48-hour history of aphagia without dyspnea. A chest X-ray revealed a calcium-dense foreign body in the cervical esophagus. Given the long symptom duration, a chest computed tomography scan was performed, ruling out complications ([Fig. 1]). In accordance with European Society of Gastrointestinal Endoscopy recommendations [1], we performed an emergency therapeutic endoscopy within 2 hours after admission.
Effects of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction patients with chronic obstructive pulmonary disease in <scp>EMPHASIS‐HF</scp> and <scp>RALES</scp>
Authors: Su E. Yeoh, Pooja Dewan, Matteo Serenelli, João Pedro Ferreira, Bertram Pitt, Karl Swedberg, Dirk J. van Veldhuisen, Faiez Zannad, Pardeep S. Jhund, John J.V. McMurray
Journal: European Journal of Heart Failure (2021)

Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) individually cause significant morbidity and mortality. Their coexistence is associated with even worse outcomes, partly due to suboptimal heart failure therapy, especially underutilisation of beta-blockers. Our aim was to investigate outcomes in HFrEF patients with and without COPD, and the effects of mineralocorticoid receptor antagonists (MRAs) on outcomes.We studied the effect of MRA therapy in a post-hoc pooled analysis of 4397 HFrEF patients in the RALES and EMPHASIS-HF trials. The primary endpoint was the composite of heart failure hospitalisation or cardiovascular death. A total of 625 (14.2%) of the 4397 patients had COPD. Patients with COPD were older, more often male, and smokers, but less frequently treated with a beta-blocker. In patients with COPD, event rates (per 100 person-years) for the primary endpoint and for all-cause mortality were 25.2 (95% confidence interval 22.1-28.7) and 17.2 (14.9-19.9), respectively, compared with 19.9 (18.8-21.1) and 12.8 (12.0-13.7) in participants without COPD. The risks of all-cause hospitalisation and sudden death were also higher in patients with COPD. The benefit of MRA, compared with placebo, was consistent in patients with or without COPD for all outcomes, e.g. hazard ratio for the primary outcome 0.66 (0.50-0.85) for COPD and 0.65 (0.58-0.73) for no COPD (interaction p = 0.93). MRA-induced hyperkalaemia was less frequent in patients with COPD.In RALES and EMPHASIS-HF, one-in-seven patients with HFrEF had coexisting COPD. HFrEF patients with COPD had worse outcomes than those without. The benefits of MRAs were consistent, regardless of COPD status.
England’s new Office for Health Improvement and Disparities
Authors: Gabriel Scally
Journal: BMJ (2021)

On 1 October, Public Health England, an executive agency of the UK's Department of Health and Social Care (DHSC), will disappear.Two new organisations will replace it-the Office for Health Improvement and Disparities (to be part of the DHSC) and the UK Health Security Agency (a new executive agency of the DHSC). 1 2 What makes these changes notable and concerning is not just the timing, but the disappearance of the words "public health" and the arrival of the phrase "health disparities" (rather than the established term "health inequalities") in the title of the organisation dealing with non-communicable disease.These changes can only reinforce the perception that the government regards activity in the realm of public health as part of an undesirable "nanny state."Provenance and peer review: Commissioned; not externally
Assessment of Prevalence of Adolescent Patient Portal Account Access by Guardians
Authors: Wui Ip, Samuel Yang, Jacob Parker, Austin Powell, James Xie, Keith Morse, Rachael C. Aikens, Jennifer Lee, Manjot Gill, Shravani Vundavalli, Yungui Huang, Jeannie Huang, Jonathan H. Chen, Jeffrey Hoffman, Cynthia Kuelbs, Natalie Pageler
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Patient portals can be configured to allow confidential communication for adolescents' sensitive health care information. Guardian access of adolescent patient portal accounts could compromise adolescents' confidentiality. <h3>Objective</h3> To estimate the prevalence of guardian access to adolescent patient portals at 3 academic children's hospitals. <h3>Design, Setting, and Participants</h3> A cross-sectional study to estimate the prevalence of guardian access to adolescent patient portal accounts was conducted at 3 academic children's hospitals. Adolescent patients (aged 13-18 years) with access to their patient portal account with at least 1 outbound message from their portal during the study period were included. A rule-based natural language processing algorithm was used to analyze all portal messages from June 1, 2014, to February 28, 2020, and identify any message sent by guardians. The sensitivity and specificity of the algorithm at each institution was estimated through manual review of a stratified subsample of patient accounts. The overall proportion of accounts with guardian access was estimated after correcting for the sensitivity and specificity of the natural language processing algorithm. <h3>Exposures</h3> Use of patient portal. <h3>Main Outcome and Measures</h3> Percentage of adolescent portal accounts indicating guardian access. <h3>Results</h3> A total of 3429 eligible adolescent accounts containing 25 642 messages across 3 institutions were analyzed. A total of 1797 adolescents (52%) were female and mean (SD) age was 15.6 (1.6) years. The percentage of adolescent portal accounts with apparent guardian access ranged from 52% to 57% across the 3 institutions. After correcting for the sensitivity and specificity of the algorithm based on manual review of 200 accounts per institution, an estimated 64% (95% CI, 59%-69%) to 76% (95% CI, 73%-88%) of accounts with outbound messages were accessed by guardians across the 3 institutions. <h3>Conclusions and Relevance</h3> In this study, more than half of adolescent accounts with outbound messages were estimated to have been accessed by guardians at least once. These findings have implications for health systems intending to rely on separate adolescent accounts to protect adolescent confidentiality.
Darshan Kumar Suri
Authors: Raman Suri
Journal: BMJ (2021)

Darshan Kumar Suri arrived at London’s Heathrow airport on 14 October 1969 with only three pounds in his pocket. The British government were recruiting doctors from the Commonwealth and Darshan answered the call. He was leaving behind an offer to work in the Indian army, but a new life beckoned abroad.

From humble beginnings Darshan overcame the odds to lead and excel in his chosen fields. As well as being a gifted physician, he went on to become a professor, medical leader, hospital board member, medicolegal adviser, magistrate, and philanthropist. Later pioneers like Darshan who came from India would be labelled the “three pounds in my pocket” generation. They rightfully earned their place in British social history, and their life stories have been an inspiration to so many.

Darshan worked at a time of much cultural transformation within the NHS during the 1970s and 80s. His sociable nature meant he was able to integrate himself and enjoy his work …
P-140 A phase I study of biweekly abraxane in combination with oxaliplatin and oral S-1/leucovorin as first line treatment for advanced gastric, pancreatic and biliary tract cancers
Authors: H. Tsai, S. Yang, C. Hsiao, H. Kao, Y. Shan, Y. Lin, C. Yen, J. Du, C. Hsu, I. Wu, L. Chen
Journal: Annals of Oncology (2021)