bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticoagulation Therapy in Patients With Coronavirus Disease 2019: Results From a Multicenter International Prospective Registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019 [HOPE-COVID19])
Authors: Santoro Francesco , Núñez-Gil Ivan J. , Viana-Llamas María C. , Maroun Eid Charbel , Romero Rodolfo , Fernández Rozas Inmaculada , Aparisi Alvaro , Becerra-Muñoz Victor Manuel , García Aguado Marcos , Huang Jia , Maltese Ludovica , Cerrato Enrico , Alfonso-Rodriguez Emilio , Castro Mejía Alex Fernando , Marin Francisco , Raposeiras Roubin Sergio , Pepe Martino , Moreno Munguia Victor H. , Feltes Gisela , Navas Jesus Varas , Cortese Bernardo , Buzón Luis , Liebetrau Cristoph , Ramos-Martinez Raquel , Fernandez-Ortiz Antonio , Estrada Vicente , Brunetti Natale Daniele
Published: April 2021

OBJECTIVES:

No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival.

DESIGN:

Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019).

SETTING:

Hospitalized patients with coronavirus disease 2019.

PATIENTS:

Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients.

INTERVENTIONS:

Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient.

MEASUREMENTS AND MAIN RESULTS:

Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox’ analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49–0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49–0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51–1.01) in noninvasive ventilation.

CONCLUSIONS:

Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation.
Clinical consequences of asymptomatic cytomegalovirus in treated human immunodeficency virus infection
Authors: Schnittman Samuel R. , Hunt Peter W.
Published: April 2021

Purpose of review

Despite antiretroviral therapy (ART)-mediated viral suppression, people with human immunodeficiency virus (HIV) (PWH) have increased morbidity and mortality. Immune activation and inflammation persist on ART and predict these complications. Over 90% of PWH have cytomegalovirus (CMV) co-infection, and CMV is considered a plausible contributor to this persistent immune activation.

Recent findings

A detailed understanding of the link between CMV and multimorbidity is needed, particularly as research moves toward identifying potential targeted therapeutics to attenuate inflammation-mediated morbidity and mortality in treated HIV. We review the literature on the association between CMV and immune activation as well as multiple end-organ complications including cardiovascular disease, venous thromboembolic disease, metabolic complications, gastrointestinal dysfunction, central nervous system involvement, birth sex-related differences, and the relation to the HIV reservoir. We conclude with a discussion of ongoing therapeutic efforts to target CMV.

As CMV is a plausible driver of multiple comorbidities through persistent immune activation in treated HIV, future research is needed and planned to address its causal role as well as to test novel therapeutics in this setting.
Heart Valve Critical Pathway and Heart Valve Clinic: Novel Benchmarks for Modern Management of Valvular Heart Disease
Authors: Pavone Natalia , Burzotta Francesco , Bruno Piergiorgio , Spalletta Claudio , Farina Piero , Cammertoni Federico , Nesta Marialisa , Chiariello Giovanni A. , Grandinetti Maria , De Belvis Antonio G. , Marzetti Emanuele , Angeletti Carmen , Pasquini Annalisa , Mazza Andrea , Iafrancesco Mauro , Trani Carlo , Lombardo Antonella , Massetti Massimo
Published: April 2021

The growing burden of valvular heart disease in Western countries represents a challenge for the daily clinical practice, especially in the light of the ever-increasing number of therapeutic options. The Euro Heart Survey showed that, among elderly subjects with severe, symptomatic valve dysfunction, surgery is denied for 33% of patients with aortic stenosis and for 50% of patients with mitral regurgitation. Current management (from diagnosis to follow-up) is often fragmented in multiple—sometimes unnecessary—steps. Such a “patchy” approach may translate into a suboptimal management, especially in the geriatric population. New healthcare models exist that can coordinate care, reduce fragmentation, limit costs and, ultimately, improve outcomes: the clinical pathways.
Changes in Intraocular Pressure During Hemodialysis: A Meta-analysis
Authors: Chen Szu-Han , Lu Da-Wen , Ku Wan-Chen , Chuang Lan-Hsin , Ferng Shyang-Hwa , Chen Yi-Ju , Lu Yi-Hsuan , Chai Pony Yee-Chee
Published: April 2021

Précis:

Acetate dialysate causes elevation of intradialytic intraocular pressure (IOP) and contributed to the rise of IOP in the early years of hemodialysis (HD). Glaucoma, narrow-angle, or impaired aqueous outflow is another moderator causing a rise of intradialytic IOP.

Purpose:

Severe IOP elevation during HD has been described in many case reports. However, the results of primary studies are conflicting. This meta-analysis examined the impact of HD on IOP and explored the potential moderators.

Methods:

Medline, PubMed, Embase, Web of Science, and Cochrane were systematically searched. Before-after studies reporting the change of IOP during HD were included. Intradialytic IOP changes were calculated based on 4 different definitions: highest-baseline, lowest-baseline, max-baseline, and end-baseline IOP difference. Standardized mean difference (SMD) was pooled using the random-effects model.

Results:

Fifty-three studies involving 1903 participants and 2845 eyes were included. Overall data pooling showed no significant rise in intradialytic IOP. However, subgroup analysis showed an intradialytic IOP rise before 1986 (SMD: 0.593; 95% confidence interval: 0.169-1.018; max-baseline IOP difference as representative; most studies using acetate dialysate), no change between 1986 and 2005 (using both acetate and bicarbonate), and a decline after 2005 (SMD: −0.222; 95% confidence interval: −0.382 to −0.063; entirely using bicarbonate). Multivariable meta-regression showed only the type of dialysate, but not publication year or other potential factors, as a significant moderator. Glaucoma was found to be another significant moderator independent of the dialysate effect in bivariate meta-regression.

Conclusions:

IOP elevation in the early years of HD with the use of acetate dialysate is less of a clinical problem following its substitution with bicarbonate dialysate. However, physicians should still be cautious of potential IOP changes in the HD population with glaucoma.
Effects of Functional Foot Orthoses and Taping Interventions on Pain, Function, and Plantar Pressure for Adult Hallux Valgus: A Literature Review
Authors: Glasoe Ward M. , Allen Mary K. , Harris Joseph R. , Higgins Madeline M. , Jewett Susan M. , Rucker Michael J.
Published: April 2021

Introduction

No recent review of the literature has investigated the effects of dynamic weight-bearing interventions for hallux valgus (HV) deformity, nor has research identified a preferred conservative treatment. This review studied the effectiveness of functional foot orthoses or taping in adults seeking care for HV. The outcomes examined were pain, function, and change in plantar pressures.

Materials and Methods

The literature was searched up to February 1, 2019, to identify relevant studies that treated adult HV with functional foot orthoses or taping and reported outcomes of pain, function, or the redistribution of plantar pressures. Pain and function were evaluated with a standardized mean difference effect size calculation; change in plantar pressures attributed to interventions was reported descriptively.

Results

Seven studies were identified for review. Five studies reported improved (pooled effect size, ≥0.89) pain or function outcomes for up to 6 months. Two studies that reported only plantar pressure measurements identified reduced loading under the first metatarsophalangeal joint.

Conclusions

Treatment with functional foot orthoses and taping reduced pain and function impairments in patients with HV over the short term (6 months), with no adverse outcomes reported. Although the actual mechanism is unknown, studies reporting plantar pressures indicate that load is transferred away from the area of deformity. Foot orthoses were identified as the preferred treatment, with tape considered an option for clinical assessment or temporary pain relief. Because of the progressive nature of deformity, the impairments, although improved with treatment (pooled effect size, ≥0.89), may not necessarily be lasting.
Describing Frequencies of Lower-Limb Apophyseal Injuries in Children and Adolescents: A Systematic Review
Authors: Haines Mitchell , Pirlo Larissa , Bowles Kelly-Ann , Williams Cylie M.
Published: April 2021

Objective:

To describe the frequency with which children are affected by lower-limb apophyseal injuries, and subgroups at greater risk.

Design:

Systematic review.

Setting:

N/A.

Participants:

N/A.

Interventions:

N/A.

Main Outcome Measures:

Systematic review of Medline OVID, PsycINFO, Cinahl, and PubMed from inception until February 21st, 2020. Articles reporting prevalence and/or incidence of an apophyseal injury (eg, calcaneal apophysitis) or its eponym (Severs or Sever disease). Per person data relating to the incidence or prevalence. Subgroup comparisons were made between sex groups and between activity participant groups.

Results:

There was wide variation in measurement approaches and follow-up timeframes with the majority of studies reporting on traction apophysitis of the tibial tubercle (Osgood–Schlatter disease). This condition had a point prevalence of 10% in the general population of children between the ages of 12 and 15 years, whereas the lifetime incidence has been reported as 13%. Point prevalence was higher among those who participated in sport compared with those who did not {relative risk [95% confidence interval (CI): 1.98 (1.31-2.99)]}, whereas lifetime incidence was higher among those who participated in sport at the age of 13 years compared with those who did not [relative risk (95% CI): 4.63 (2.31-9.26)]. Other apophyseal injuries did not report enough data to permit comparisons.

Conclusion:

Sports participation is likely to substantially increase the frequency of traction apophysitis of the tibial tubercle. Further research is required with standardized approaches to compare frequencies between different apophyseal injuries and subgroups of interest.
The effect of fluoxetine on morning blood pressure surge in patients with ischemic stroke: a prospective preliminary clinical study
Authors: He Yitao , Deng Jian , Zhang Yaqing , Cai Zhili , Zhang Hui , Guo Yi
Published: April 2021

Objective

Our study aimed to evaluate the effect of fluoxetine on morning blood pressure surge (MBPS) in patients with ischemic stroke.

Methods

A total of 30 patients with acute ischemic stroke, 15 in the control group and 15 in the treatment group, were enrolled. Two patients in the control group and one in the treatment group were lost during follow-up. The patients in the treatment group were treated with fluoxetine (20 mg per day for 3 months) based on the treatments in the control group. Baseline characteristics, Patient Health Questionnaire 9 (PHQ-9) items scale score, mean blood pressure and MBPS were evaluated before and after treatment, and the correlation between the improvements of PHQ-9 scale score and MBPS was also analyzed.

Results

The mean SBP and the systolic and diastolic MBPS in the treatment group were significantly lower than that in the control group after 3 months of treatment (P = 0.024, P = 0.022, P = 0.001, respectively). Besides, the improvement of PHQ-9 scale score was significantly higher in the treatment group than in the control group (P = 0.049). There was no significant correlation between the improvement of systolic or diastolic MBPS and the improvement of PHQ-9 scale score in the treatment group (P = 0.289 and P = 0.206, respectively).

Conclusion

Fluoxetine might improve MBPS in patients with ischemic stroke.
The Effectiveness of Common Cannabis Products for Treatment of Nausea
Authors: Stith Sarah S. , Li Xiaoxue , Orozco Joaquin , Lopez Victoria , Brockelman Franco , Keeling Keenan , Hall Branden , Vigil Jacob M.
Published: April 2021

Goals:

We measure for the first time how a wide range of cannabis products affect nausea intensity in actual time.

Background:

Even though the Cannabis plant has been used to treat nausea for millennia, few studies have measured real-time effects of common and commercially available cannabis-based products.

Study:

Using the Releaf App, 886 people completed 2220 cannabis self-administration sessions intended to treat nausea between June 6, 2016 and July 8, 2019. They recorded the characteristics of self-administered cannabis products and baseline symptom intensity levels before tracking real-time changes in the intensity of their nausea.

Results:

By 1 hour postconsumption, 96.4% of people had experienced symptom relief with an average symptom intensity reduction of −3.85 points on a 0 to 10 visual analog scale (SD=2.45, d=1.85, P<0.001). Symptom relief was statistically significant at 5 minutes and increased with time. Among product characteristics, flower and concentrates yielded the strongest, yet similar results; products labeled as Cannabis indica underperformed those labeled as Cannabis sativa or hybrid; and joints were associated with greater symptom relief than pipes or vaporizers. In sessions using flower, higher tetrahydrocannbinol and lower cannabidiol were generally associated with greater symptom relief (eg, within 5 min).

Conclusions:

The findings suggest that the vast majority of patients self-selecting into cannabis use for treatment of nausea likely experience relief within a relative short duration of time, but the level of antiemetic effect varies with the characteristics of the cannabis products consumed in vivo. Future research should focus on longer term symptom relief, including nausea-free intervals and dosing frequency; the risks of consumption of medical cannabis, especially among high-risk populations, such as pregnant women and children; and potential interactions between cannabis, conventional antiemetics, other medications, food, tobacco, alcohol, and street drugs among specific patient populations.
Gastric Peroral Endoscopic Myotomy
Authors: Reja Mishal , Mishra Avantika , Tyberg Amy , Andalib Iman , Martínez Guadalupe M. , Zamarripa Felipe , Gaidhane Monica , Nieto Jose , Kahaleh Michel
Published: April 2021

Introduction:

Gastric peroral endoscopic pyloromyotomy (G-POEM) is a novel option for patients with gastroparesis. It involves submucosal tunneling across the pylorus, followed by pyloromyotomy, and subsequent closure of the endoscopic tunnel. The aim of this study was to determine the learning curve for G-POEM.

Methods:

Consecutive patients undergoing G-POEM by a single operator were included from a prospective registry over 2 years. Demographics, procedure info, postprocedure follow-up data, and adverse events were collected. Nonlinear regression and cumulative sum control chart analyses were conducted for the learning curve. Clinical outcomes were improvement in Gastroparesis Cardinal Symptom Index score and gastric emptying scintigraphy.

Results:

Thirty-six patients were included (16.7% M, mean age 46 y). The majority had idiopathic gastroparesis (n=16, 44%), with the remaining having diabetes (n=5, 17%), postsurgical (n=10, 28%), or other (n=4, 11%). Technical success was achieved in 35 of 36 (97%). There was a significant reduction in the total Gastroparesis Cardinal Symptom Index score (2.09 units, P<0.00001) and a significant reduction in postoperative gastric emptying scintigraphy (82.44 mins, P<0.00001). Mean follow-up was 15 months (SD, 1.05). Median procedure time was 60.5 minutes (range, 35 to 136). Cumulative sum control chart shows 60-minute procedure was achieved at the 18th procedure. Procedure durations further reduced with consequent procedures with the last 3 being 45 minutes, thus demonstrating continued improvement with ongoing experience (nonlinear regression P<0.0001).

Conclusion:

Endoscopists experienced in G-POEM are expected to achieve a reduction in procedure time over successive cases, with efficiency reached at 60.5 minutes and a learning rate of 18 cases with continuing improvement.
Exercise Medicine in the Management of Pancreatic Cancer
Authors: Luo Hao , Galvão Daniel A. , Newton Robert U. , Lopez Pedro , Tang Colin , Fairman Ciaran M. , Spry Nigel , Taaffe Dennis R.
Published: April 2021

The aim of this study was to examine the health-related effects of exercise in patients with pancreatic cancer (PanCa) through a systematic review of current evidence. Studies were obtained through searching PubMed, Web of Science, PsycINFO, Embase, CINAHL Plus, and Cochrane Library databases with additional hand searches. All intervention-based studies were included if it involved (1) adult patients with PanCa, (2) exercise training, and (3) findings in quality of life, cancer-related fatigue, psychological distress, and physical function. The review protocol was registered in PROSPERO: CRD42020154684. Seven trials described in 9 publications were included consisting of 201 patients with early-stage and advanced PanCa. Participants were required to perform supervised and/or home-based, low- to moderate-intensity resistance and/or aerobic exercise for 12 to 35 weeks or duration of neoadjuvant therapy. There were no exercise-related adverse events with a reported retention rate of 71% to 90% and exercise attendance of 64% to 96%. The programs were consistently associated with improvements in cancer-related fatigue, psychological distress, and physical function, with mixed effects on quality of life. Exercise training seems to be safe and feasible and may have a beneficial effect on various physical and psychological outcomes in patients with PanCa. Further work with rigorous study designs is required to consolidate and advance current findings.
Clinical Care Strategies That Support Parents of Children With Complex Chronic Conditions*
Authors: Bogetz Jori F. , Revette Anna , DeCourcey Danielle D.
Published: April 2021

OBJECTIVES:

Children with complex chronic conditions often receive inpatient and end-of-life care in the ICU, yet little is known about the clinical care strategies that best support this unique group of parents. This study aimed to elucidate supportive clinical care strategies identified by bereaved parents of children with complex chronic conditions.

DESIGN:

Qualitative analysis of 21 open-response items from the cross-sectional “Survey of Caring for Children with Complex Chronic Conditions” querying communication, decision-making, and end-of-life experiences.

SETTING:

Large tertiary care children’s hospital.

PATIENTS:

Parents of children with complex chronic conditions who received care at a large academic institution and died between 2006 and 2015.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

An iterative multistage thematic analysis of responses was used to identify key themes pertaining to clinical care strategies that support parents of children with complex chronic conditions. Open-ended responses were analyzed from 110 of 114 (96%) of survey respondents. The majority of parents had children with congenital/chromosomal complex chronic conditions who died 3.9 years (interquartile range, 2.2–6.7 yr) prior to their parents’ study participation. Although informational themes related to clear honest communication, consistent messaging, and enhanced care coordination were identified, parents emphasized the relational aspects of clinical care including inclusivity of their expertise about their child’s needs, recognition of their unique experience as parents, and maintenance of connection with clinicians through bereavement.

CONCLUSIONS:

Clinical care strategies that support parents of children with complex chronic conditions reflect the unique needs of this group of children. Relational strategies such as including parents as experts in their child’s care were paramount to parents of children with complex chronic conditions throughout their child’s medical journey and at end of life.
Age-Specific Dose Regimens of Dexmedetomidine for Pediatric Patients in Intensive Care Following Elective Surgery: A Phase 3, Multicenter, Open-Label Clinical Trial in Japan
Authors: Takeuchi Mamoru , Nemoto Shintaro , Suzuki Yasuyuki , Takahashi Naoki , Takenaka Nobuko , Takata Ami , Kobayashi Mihoko
Published: April 2021

OBJECTIVES:

To demonstrate the efficacy, safety, and pharmacokinetics of dexmedetomidine as a potential sedative for pediatric surgery patients in the ICU.

DESIGN:

Phase 3, multicenter, open-label study.

SETTING:

This study included 61 patients at 13 tertiary hospitals in Japan.

PATIENTS:

Pediatric patients (≥ 45 wk corrected gestational age to < 17 yr) undergoing intensive care treatment with mechanical ventilation requiring greater than 6 hours estimated duration of sedation following elective cardiac surgery.

INTERVENTIONS:

Dexmedetomidine was IV administered without a loading dose at age-specific dose regimens 0.2–1.4 (< 6 yr) and 0.2–1.0 µg/kg/hr (≥ 6 yr). The primary endpoint was the percentage of patients who did not require a rescue sedative (midazolam) infusion during mechanical ventilation or for the first 24 hours of a greater than 24 hours ventilation following the commencement of dexmedetomidine administration.

MEASUREMENTS AND MAIN RESULTS:

Overall, 47 of the 61 patients (77.0%) did not require rescue midazolam. Adverse events were reported in 53 patients (86.9%). Frequently observed adverse events were hypotension (47.5%), bradycardia (31.1%), and respiratory depression (26.2%). Most of these adverse events were mild, a few moderate, and none severe. Although serious adverse events occurred in four patients, including one cardiac tamponade resulting in the withdrawal of dexmedetomidine, none of the adverse events resulted in mortality or were directly related to dexmedetomidine. The plasma dexmedetomidine concentration generally reached the target concentration of 0.3–1.25 ng/mL at 1–2 hours prior to completion of administration or immediately prior to the commencement of tapering.

CONCLUSIONS:

The age-specific dose regimens of dexmedetomidine without an initial loading dose achieved an adequate sedation level during mechanical ventilation and caused no clinically significant adverse events in the intensive care pediatric patients. These effects were achieved within the therapeutic range of dexmedetomidine plasma concentration and were accompanied by minimal effects on hemodynamics and respiration.
Circulating microRNA signatures that predict liver fibrosis progression in patients with HIV-1/hepatitis C virus coinfections
Authors: Franco Sandra , Buccione Daniela , Tural Cristina , Martinez Miguel Angel
Published: April 2021

Objective:

The lack of available biomarkers for diagnosing and predicting different stages of liver disease with a noninvasive strategy is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific microRNAs (miRNAs) may be significantly altered in patients with liver injury, including those with HIV type 1 (HIV-1) infections.

Design/methods:

Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 patients with HIV-1/hepatitis C virus (HCV) coinfections that did not exhibit liver fibrosis at the time of sampling.

Results:

A total of 1065 different miRNAs were identified. After a mean of 10.3 years, 26 out of the 46 patients developed liver fibrosis (stage F2–4) and 20 remained without signs of liver fibrosis (stage F0–1). We identified a signature of seven miRNAs: 100–5p, 192–5p, 99a-5p, 122–5p, 125b-2–3p, 1246 and 194–5p, which were highly correlated with progression to liver fibrosis. These seven miRNAs detected liver fibrosis progression with an area under the curve (AUC) of 0.910–0.806. Two miRNAs, 100–5p and 192–5p, which displayed the best AUC values, yielded a sensitivity of 88% and a specificity of 85% for detecting liver fibrosis progression.

Conclusion:

Our results demonstrated that circulating miRNA levels had potential in predicting liver fibrosis progression before the clinical detection of liver fibrosis or significant clinical signs, such as elevated liver transaminases or platelets. Thus, our results might facilitate predictions of liver injury progression in patients with HIV-1-infections.
Automated Pathology Detection and Patient Triage in Routinely Acquired Head Computed Tomography Scans
Authors: Finck Tom , Schinz David , Grundl Lioba , Eisawy Rami , Yigitsoy Mehmet , Moosbauer Julia , Pfister Franz , Wiestler Benedikt
Published: April 2021

Objectives

Anomaly detection systems can potentially uncover the entire spectrum of pathologies through deviations from a learned norm, meaningfully supporting the radiologist's workflow. We aim to report on the utility of a weakly supervised machine learning (ML) tool to detect pathologies in head computed tomography (CT) and adequately triage patients in an unselected patient cohort.

Materials and Methods

All patients having undergone a head CT at a tertiary care hospital in March 2020 were eligible for retrospective analysis. Only the first scan of each patient was included. Anomaly detection was performed using a weakly supervised ML technique. Anomalous findings were displayed on voxel-level and pooled to an anomaly score ranging from 0 to 1. Thresholds for this score classified patients into the 3 classes: “normal,” “pathological,” or “inconclusive.” Expert-validated radiological reports with multiclass pathology labels were considered as ground truth. Test assessment was performed with receiver operator characteristics analysis; inconclusive results were pooled to “pathological” predictions for accuracy measurements. External validity was tested in a publicly available external data set (CQ500).

Results

During the investigation period, 297 patients were referred for head CT of which 248 could be included. Definite ratings into normal/pathological were feasible in 167 patients (67.3%); 81 scans (32.7%) remained inconclusive. The area under the curve to differentiate normal from pathological scans was 0.95 (95% confidence interval, 0.92–0.98) for the study data set and 0.87 (95% confidence interval, 0.81–0.94) in external validation. The negative predictive value to exclude pathology if a scan was classified as “normal” was 100% (25/25), and the positive predictive value was 97.6% (137/141). Sensitivity and specificity were 100% and 86%, respectively. In patients with inconclusive ratings, pathologies were found in 26 (63%) of 41 cases.

Conclusions

Our study provides the first clinical evaluation of a weakly supervised anomaly detection system for brain imaging. In an unselected, consecutive patient cohort, definite classification into normal/diseased was feasible in approximately two thirds of scans, going along with an excellent diagnostic accuracy and perfect negative predictive value for excluding pathology. Moreover, anomaly heat maps provide important guidance toward pathology interpretation, also in cases with inconclusive ratings.
Evaluation of the Diagnostic Performance of Positron Emission Tomography/Magnetic Resonance for the Diagnosis of Liver Metastases
Authors: Zhang Caiyuan , O'Shea Aileen , Parente Chiara Anna , Amorim Barbara Juarez , Caravan Peter , Ferrone Christina R. , Blaszkowsky Lawrence S. , Soricelli Andrea , Salvatore Marco , Groshar David , Bernstine Hanna , Domachevsky Liran , Canamaque Lina Garcia , Umutlu Lale , Ken Herrmann , Catana Ciprian , Mahmood Umar , Catalano Onofrio Antonio
Published: April 2021

Objective

The aim of this study was to compare the performance of positron emission tomography (PET)/magnetic resonance (MR) versus stand-alone PET and stand-alone magnetic resonance imaging (MRI) in the detection and characterization of suspected liver metastases.

Materials and Methods

This multi-institutional retrospective performance study was approved by the institutional review boards and was Health Insurance Portability and Accountability Act compliant, with waiver of informed consent. Seventy-nine patients with confirmed solid extrahepatic malignancies who underwent upper abdominal PET/MR between February 2017 and June 2018 were included. Where focal hepatic lesions were identified, the likelihood of a diagnosis of a liver metastasis was defined on an ordinal scale for MRI, PET, and PET/MRI by 3 readers: 1 nuclear medicine physician and 2 radiologists. The number of lesions per patient, lesion size, and involved hepatic segments were recorded. Proof of metastases was based on histopathologic correlation or clinical/imaging follow-up. Diagnostic performance was assessed using sensitivity, specificity, positive and negative predictive values, and receiver operator characteristic curve analysis.

Results

A total of 79 patients (53 years, interquartile range, 50–68; 43 men) were included. PET/MR had a sensitivity of 95%, specificity of 97%, positive predictive value of 97%, and negative predictive value of 95%. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI were 88%, 98%, 98%, and 90% and for PET were 83%, 97%, 97%, and 86%, respectively. The areas under the curve for PET/MRI, MRI, and PET were 95%, 92%, and 92%, respectively.

Conclusions

Contrast-enhanced PET/MR has a higher sensitivity and negative predictive value than either PET or MRI alone in the setting of suspected liver metastases. Fewer lesions were characterized as indeterminate by PET/MR in comparison with PET and MRI. This superior performance could potentially impact treatment and management decisions for patients with suspected liver metastases.
An 11-year Institutional Review of Nipple-Areolar Complex Tattooing for Breast Reconstruction
Authors: Weissler Jason M. , Kuruoglu Doga , Curiel Daniel , Alsayed Ahmed , Dudakovic Amela , Harless Christin A. , Nguyen Minh-Doan T.
Published: April 2021

Background

Nipple-areolar complex (NAC) tattooing remains a simple and safe procedure, which complements breast reconstruction. This study reviews 11 years of NAC tattooing to identify risk factors for tattoo-related complications.

Methods

Patients undergoing NAC tattooing from January 2009 to March 2020 were reviewed. Patient information, reconstructive, and tattoo procedural details were analyzed. Tattoo-related breast infections, defined as breast redness requiring antibiotic therapy within 30 days after tattoo, were captured. Patients with reactive breast redness during the first 2 postprocedural days were excluded.

Results

Overall, 539 patients (949 breasts) were included. Implant-based reconstruction (IBR) was performed in 73.6% of breasts (n = 698), whereas 26.4% (n = 251) underwent autologous-based reconstruction (ABR). Acellular-dermal matrix was used in 547 breasts (57.6%). There as a 13.7% (n = 130) of breasts that underwent pretattoo radiation. There was a 65.3% (n = 456) of breasts that underwent subpectoral IBR, whereas 34.7% (n = 242) breasts underwent prepectoral IBR. Tattoo-related infection rate was 2.2% (n = 21 breasts). Mean time to infection was 6.5 ± 5.3 days. There was a 85.7% (n = 18) of infections that occurred in IBR patients, one third occurring in radiated patients. There was a 95.2% (n = 20) of infections that were treated with oral antibiotics only. One explantation was performed after failed intravenous antibiotics. On multivariable analysis, radiation history (odds ratio, 4.1, P = 0.007) and prepectoral IBR (odds ratio, 2.8, P = 0.036) were independent predictors of tattoo-related infection. Among irradiated breasts, breasts with IBR had greater odds of developing tattoo-related infection versus breasts with ABR (P = 0.025).

Conclusions

Although tattoo-related infections were uncommon, previous radiation and prepectoral IBR were both found to be independent predictors of tattoo-related breast infection. There is a role for preprocedural prophylactic antibiotics in these patients to mitigate infectious risk.
Single individual structural variant detection uncovers widespread hemizygosity in molluscs
Authors: Calcino Andrew D. , Kenny Nathan J. , Gerdol Marco
Published: April 2021

The advent of complete genomic sequencing has opened a window into genomic phenomena obscured by fragmented assemblies. A good example of these is the existence of hemizygous regions of autosomal chromosomes, which can result in marked differences in gene content between individuals within species. While these hemizygous regions, and presence/absence variation of genes that can result, are well known in plants, firm evidence has only recently emerged for their existence in metazoans. Here, we use recently published, complete genomes from wild-caught molluscs to investigate the prevalence of hemizygosity across a well-known and ecologically important clade. We show that hemizygous regions are widespread in mollusc genomes, not clustered in individual chromosomes, and often contain genes linked to transposition, DNA repair and stress response. With targeted investigations of
HSP70-12
and
C1qDC
, we also show how individual gene families are distributed within pan-genomes. This work suggests that extensive pan-genomes are widespread across the conchiferan Mollusca, and represent useful tools for genomic evolution, allowing the maintenance of additional genetic diversity within the population. As genomic sequencing and re-sequencing becomes more routine, the prevalence of hemizygosity, and its impact on selection and adaptation, are key targets for research across the tree of life.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Digging into bivalve miRNAomes: between conservation and innovation
Authors: Rosani Umberto , Bortoletto Enrico , Bai Chang-Ming , Novoa Beatriz , Figueras Antonio , Venier Paola , Fromm Bastian
Published: April 2021

Bivalves are a diverse mollusc group of economic and ecological importance. An evident resilience to pollution, parasites and extreme environments makes some bivalve species important models for studying adaptation and immunity. Despite substantial progress in sequencing projects of bivalves, information on non-coding genes and gene-regulatory aspects is still lacking. Here, we review the current repertoire of bivalve microRNAs (miRNAs), important regulators of gene expression in Metazoa. We exploited available short non-coding RNA (sncRNA) data for
Pinctada martensii, Crassostrea gigas, Corbicula fluminea, Tegillarca granosa
and
Ruditapes philippinarum
, and we produced new sncRNA data for two additional bivalves, the Mediterranean mussel
Mytilus galloprovincialis
and the blood clam
Scapharca broughtonii
. We found substantial heterogeneity and incorrect annotations of miRNAs; hence, we reannotated conserved miRNA families using recently established criteria for
bona fide
microRNA annotation. We found 106 miRNA families missing in the previously published bivalve datasets and 89 and 87 miRNA complements were identified in the two additional species. The overall results provide a homogeneous and evolutionarily consistent picture of miRNAs in bivalves and enable future comparative studies. The identification of two bivalve-specific miRNA families sheds further light on the complexity of transcription and its regulation in bivalve molluscs.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Controlling the pandemic during the SARS-CoV-2 vaccination rollout: a modeling study
Authors: Viana João , van Dorp Christiaan H. , Nunes Ana , Gomes Manuel C. , van Boven Michiel , Kretzschmar Mirjam E. , Veldhoen Marc , Rozhnova Ganna
Published: April 2021

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point control of COVID-19 would be achieved for each scenario.
Microsampling for monitoring gentamicin in neonates
Authors: Parker Suzanne L. , Irwin Adam D. , Hosking Francine , August Deanne , Schoenmaker Brittany , Pandey Saurabh , Wallis Steven C. , Lipman Jeffrey , Roberts Jason A. , Davies Mark W
Published: April 2021

Gentamicin is recommended as first-line treatment of neonatal sepsis. The use of gentamicin is associated with toxicity which complicates neonatal dosing and necessitates therapeutic drug monitoring (TDM).

In a proof-of-concept investigation, we sought to compare (1) gentamicin concentrations obtained using volumetric absorptive microsampling (VAMS) to standard TDM plasma samples, and (2) the time taken to report results obtained using VAMS compared to standard TDM by the local hospital chemical pathology service.

The difference between gentamicin concentrations obtained from plasma collected for routine clinical care and calculated plasma concentrations, based on samples collected in whole blood using VAMS, was −18.0% and −0.4% for two patients. The research laboratory reported results within the time taken for the routine chemical pathology laboratory to report results. This proof-of-concept study demonstrates that the use of microsampling for TDM by pathology services can fulfil the requirements of providing an accurate gentamicin concentration in a timely manner.
Advance requests for MAiD in dementia: Policy recommendations emerging from a mixed-methods study of the views of the Canadian public and MAiD practitioners
Authors: Byram Adrian C. , Wiebe Ellen R. , Trembley-Huet Sabrina , Reiner Peter B.
Published: April 2021

Background

The Canadian public has repeatedly expressed its desire for advance requests for Medical Assistance in Dying (MAiD) after dementia diagnosis, yet MAiD practitioners’ willingness to accede to such advance requests is unknown. This study explores the extent and nature of any gap between the public’s desire for, and practitioners’ willingness to provide MAiD, and identifies policies to ameliorate such a gap.

Methods

Two complementary mixed-method surveys gathered data from convenience samples of 83 Canadian adults and 103 MAiD practitioners. The public survey asked participants which of five specific circumstances commonly encountered in dementia they would include in their advance requests. The practitioner survey queried the validation level participants would require before providing MAiD in each specific circumstance. Participants’ reasons were probed using thematic analysis of open-ended questions.

Results

On average, 77% of public participants indicated they definitely or probably would include each of the five specific circumstances in their advance requests for MAiD. As validation level decreased from patient consent to patient assent, family assent, or advance request alone, the magnitude of the gap between the public’s desire and practitioners’ willingness increased. The practitioners’ qualitative data contained many practical insights from which emerged seven policy recommendations to ameliorate this gap and increase the likelihood of honouring patient requests.

Interpretation

The study provides evidence of a gap between public desire for, and practitioner willingness to provide MAiD in dementia. The policy recommendations are relevant to consideration of legislation for advance requests for MAiD.
Body Clock: Matching Personalized Multimorbidity and Fast Aging Using Information Entropy
Authors: Salimi Shabnam , Vehtari Aki , Salive Marcel , Ferrucci Luigi
Published: April 2021

With aging, most older adults are at risk of having more than two diseases, conventionally defined as multimorbidity. We determined body organ disease number (BODN) as a new multimorbidity index. We measured the degree to which each disease level, from mild to severe, predicts longitudinal BODN uncoupled from chronological age. We determined Body Clock using global disease levels burden from all systems predicting longitudinal BODN for each individual, which is a proxy of the personalized rate of biological aging. Change in Body Clock predicts late-life age-related outcomes and can be used for geriatric clinics and clinical trials for precision medicine.
Pandemic effect on body composition. Single center analysis of 2.771 cases
Authors: Braga Fabrício , Zagury Roberto , Perroni Cristiane , Domecg Victor Hugo
Published: April 2021

Background

The COVID-19 pandemic has led to a dramatic increase in the levels of sedentary lifestyle and unhealthy dietary habits. A worsening in populational obesity levels and body composition (BC) is strongly awaited but so far not documented.

Objective

To compare BC profile measured by bioelectrical impedance analysis (BIA) between pre-pandemic (P1-03/15th/2017 to 03/16th/2020) and pandemic (P2-3/17th/2020 to 3/10th/2021) period of time.

Materials and Methods

BIA were grouped according to the time it was performed. Two comparisons were done: an independent sample comparison (ISC) and a paired sample comparison (PSC) considering patients with at least one BIA in P1 and P2. Age, height, gender, weight, body mass index (BMI), body fat mass (BFM), free fat mass (FFM), skeletal muscle mass (SMM), percentage of body fat (PBF), visceral fat area (VFA) were compared. Statistical significance level was defined for a p value<0.05.

Results and Discussion

A total of 3.358 BIA were performed, and 2.771 and 112 were selected for IS and PS, respectively. In ISC, despite an unchanged weight, BFM, FFM, PBF and VFA increased and SSM decreased on P2(p<0.015 for all). A multivariated linear regression model using PBF as dependent variable showed P2 as an independent predictor (β=0.38 95%CI 0.19 to 0.56). In the PSC, PBF also increased from P1 to P2 (p=0.015). To our knowledge this is the first documentation of worsening BC after pandemic. Health authorities should be alert for this phenomenon and their clinical consequences in the days to come.
Risk heterogeneity in compartmental HIV transmission models of ART as prevention in Sub-Saharan Africa: A scoping review
Authors: Knight Jesse , Kaul Rupert , Mishra Sharmistha
Published: April 2021

Background

Transmission models provide complementary evidence to clinical trials about the potential population-level incidence reduction attributable to ART (ART prevention impact). Different modelling assumptions about risk heterogeneity may influence projected ART prevention impacts. We sought to review representations of risk heterogeneity in compartmental HIV transmission models applied to project ART prevention impacts in Sub-Saharan Africa.

Methods

We systematically reviewed studies published before January 2020 that used non-linear compartmental models of sexual HIV transmission to simulate ART prevention impacts in Sub-Saharan Africa. We summarized data on model structure/assumptions (factors) related to risk and intervention heterogeneity, and explored multivariate ecological associations of ART prevention impacts with modelled factors.

Results

Of 1384 search hits, 94 studies were included. 64 studies considered sexual activity stratification and 39 modelled at least one key population. 21 studies modelled faster/slower ART cascade transitions (HIV diagnosis, ART initiation, or cessation) by risk group, including 8 with faster and 4 with slower cascade transitions among key populations versus the wider population. In ecological analysis of 125 scenarios from 40 studies (subset without combination intervention), scenarios with risk heterogeneity that included turnover of higher risk groups were associated with smaller ART prevention benefits. Modelled differences in ART cascade across risk groups also influenced the projected ART benefits, including: ART prioritized to key populations was associated with larger ART prevention benefits. Of note, zero of these 125 scenarios considered lower ART coverage among key populations.

Conclusion

Among compartmental transmission models applied to project ART prevention impacts in Sub-Saharan Africa, representations of risk heterogeneity and projected impacts varied considerably. Inclusion/exclusion of risk heterogeneity with turnover, and intervention heterogeneity across risk groups could influence the projected impacts of ART scale-up. These findings highlight a need to capture risk heterogeneity with turnover and cascade heterogenetiy when projecting ART prevention impacts.