bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of dispatcher-assisted cardiopulmonary resuscitation with initial shockable rhythm and survival after out-of-hospital cardiac arrest
Authors: Goto Yoshikazu , Funada Akira , Maeda Tetsuo , Goto Yumiko
Published: August 2021

Background and importance

Bystander cardiopulmonary resuscitation (CPR) and initial shockable rhythm are crucial predictors of survival after out-of-hospital cardiac arrest (OHCA). However, the relationship between dispatcher-assisted CPR (DA-CPR) and initial shockable rhythm is not completely elucidated.

Objective

To examine the association of DA-CPR with initial shockable rhythm and outcomes.

Design, setting and participants

This nationwide population-based observational study conducted in Japan included 59 688 patients with witnessed OHCA of cardiac origin after excluding those without bystander CPR. Patients were divided into DA-CPR (n = 42 709) and CPR without dispatcher assistance (unassisted CPR, n = 16 979) groups.

Outcome measures and analysis

The primary outcome measure was initial shockable rhythm, and secondary outcome measures were 1-month survival and neurologically intact survival. A Cox proportional hazards model adjusted for collapse-to-first-rhythm-analysis time and multivariable logistic regression models were used after propensity score (PS) matching to compare the incidence of initial shockable rhythm and outcomes, respectively.

Main results

Among all patients (mean age 76.7 years), the rates of initial shockable rhythm, 1-month survival and neurologically intact survival were 20.8, 10.7 and 7.0%, respectively. The incidence of initial shockable rhythm in the DA-CPR group (20.4%, 3462/16 979) was significantly higher than that in the unassisted CPR group (18.5%, 3133/16 979) after PS matching (P < 0.0001). However, no significant differences were found between the two groups with respect to the incidence of initial shockable rhythm in the Cox proportional hazards model [adjusted hazard ratio of DA-CPR for initial shockable rhythm compared with unassisted CPR, 0.99; 95% confidence interval (CI), 0.97–1.02, P = 0.56]. No significant differences were observed in the survival rates in the two groups after PS matching [10.8% (1833/16 979) vs. 10.3% (1752/16 979), P = 0.16] and neurologically intact survival rates [7.3% (1233/16 979) vs. 6.8% (1161/16 979), P = 0.13]. The multivariable logistic regression model showed no significant differences between the groups with regard to survival (adjusted odds ratio of DA-CPR compared with unassisted CPR: 1.00; 95% CI, 0.89–1.13, P = 0.97) and neurologically intact survival (adjusted odds ratio: 1.12; 95% CI, 0.98–1.29, P = 0.14).

Conclusion

DA-CPR after OHCA had the same independent association with the likelihood of initial shockable rhythm and 1-month meaningful outcome as unassisted CPR.
Metabolic regulation of macrophage proliferation and function in atherosclerosis
Authors: Patterson Michael T. , Williams Jesse W.
Published: August 2021

Purpose of review

Macrophage accumulation within atherosclerotic plaque is a primary driver of disease progression. However, recent advances in both phenotypic and functional heterogeneity of these cells have allowed for improved insight into potential regulation of macrophage function within lesions. In this review, we will discuss recent insights on macrophage heterogeneity, lipid processing, metabolism, and proliferation in atherosclerosis. Furthermore, we will identify outstanding questions in the field that are pertinent to future studies.

Recent findings

With the recent development of single-cell RNA sequencing, several studies have highlighted the diverse macrophage populations within plaques, including pro-inflammatory, anti-inflammatory, lipid loaded and tissue resident macrophages. Furthermore, new data has suggested that differential activation of metabolic pathways, including glycolysis and fatty acid oxidation, may play a key role in determining function. Recent works have highlighted that different populations retain varying capacity to undergo proliferation; regulating the proliferation pathway may be highly effective in reducing plaque in advanced lesions.

Macrophage populations within atherosclerosis are highly heterogeneous; differences in cytokine production, lipid handling, metabolism, and proliferation are seen between subpopulations. Understanding the basic cellular mechanisms that drive this heterogeneity will allow for the development of highly specific disease modulating agents to combat atherosclerosis.
Systematic Review and Meta‐analysis of Histological Gastric Biopsy Aspects According to the Updated Sydney System in Children
Authors: Kalach Nicolas , Zrinjka Misak , Bontems Patrick , Kori Michal , Homan Matjaz , Cabral José , Casswall Thomas , Chong Sonny , Cilleruelo Maria Luz , Faraci Simona , Megraud Francis , Papadopoulou Alexandra , Pehlivanoglu Ender , Raymond Josette , Rea Francesca , Maria Rogalidou , Roma Eleftheria , Tavares Marta , Ugras Meltem , Urbonas Vaidotas , Urruzuno Pedro , Gosset Pierre , Creusy Colette , Delebarre Mathilde , Verdun Stephane ,   ESPGHAN‐Helicobacter pylori Special Interest Group (ESPGHAN‐ H. pylori‐SIG)
Published: August 2021

Objectives:

A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori‐positive versus H pylori‐negative children referred for upper gastrointestinal endoscopy.

Methods:

The Prisma method was used to perform a systematic review and meta‐analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle‐Ottawa Scale, and a meta‐regression analysis was done. The study was registered on the PROSPERO platform.

Results:

Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta‐analysis concerning 5990 H pylori‐infected and 17,782 uninfected children.

H pylori‐positive versus H pylori‐negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta‐regression analysis showed that H pylori‐positive versus H pylori‐negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence.

Conclusions:

H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.
Local Anesthetic Systemic Toxicity during Labor, Birth, and Immediate Postpartum
Authors: Mock Nicole D. , Griggs Kellie M. , Mileto Lisa A.
Published: August 2021

Local anesthetic systemic toxicity (LAST) is a life-threatening event caused by elevated local anesthetic plasma concentration. It is often unrecognized or misdiagnosed. Peripartum women are at increased risk for toxicity due to pregnancy-related physiological changes. Rising serum drug levels can cause cellular level impairment of mitochondria and voltage-gated ion channels leading to a cascade of symptoms that can end in cardiac arrest. Local anesthetic systemic toxicity can mimic other maternal pathologies but may be considered if local anesthetics have been used. Published treatment guidelines for this event include lipid emulsion which is approved for use in pregnant women. We review LAST in the maternity care setting, published treatment protocols, management of maternity patients with toxicity, and recommendations to increase awareness among maternity care clinicians for this medical emergency.
Best Fit Orientation
Authors: Torres Dulce A. , Jeske Lee , Marzinski Sara J. , Oleson Renee , Hook Mary L.
Published: August 2021

The premature turnover of newly licensed registered nurses is a costly problem prompting leaders to consider new orientation approaches. This article describes the “Best Fit Orientation”—an innovative approach for onboarding newly licensed registered nurses. It features centralized hiring, individualized orientation on diverse units, and realistic job preview tenets promoting self-evaluation, change management, relationship building, and “best fit” unit selection. Positive evaluations, high retention, and minimal added costs make this program very attractive.
Histopathological Findings in a Fatal Case of Paraquat Poisoning
Authors: Moar Jacob Joseph , Hill Lawrence
Published: August 2021

Fatal paraquat ingestion presents many interesting pathological findings for the forensic pathologist. The majority of prior research regarding paraquat poisoning has focused on the lung and liver, this article is further directed to and presents some of the histopathological findings present in the brain. Typical macroscopic and histopathological findings of paraquat poisoning were identified in the liver and lungs. The brain was found to be edematous with widening of the centrum semiovale, whereas histologically, it was found that there was extravasation of erythrocytes into the surrounding Virchow-Robin spaces, a finding normally associated with blunt force head injury and, therefore, commonly interpreted by forensic pathologists as a cortical contusion hemorrhage.
When the Hidden Issue of Elder Abuse Leads to Death
Authors: Mazzotti Maria Carla , Fais Paolo , Amadasi Alberto , Pelletti Guido , Giovannini Elena , Giorgetti Arianna , Pelotti Susi
Published: August 2021

It is well known that elder neglect entails a number of physical and psychological consequences, as well as being an independent risk factor for death. In the present study, we describe 5 forensic cases of death of older adults where the diagnosis of neglect only emerged postmortem through the combination of the scene investigation, the often-scarce circumstantial data, and the autopsy findings. The gathering of this information allowed the presence of risk factors—not previously assessed or reported—to be identified. Nevertheless, complete medical information was lacking both for the isolation of the victims with their caregivers and for the absence of every social and health support in self-neglect. More research is needed also in the forensic pathology field with standardized methods to contribute to prevention strategies and to avoid that victims of elder neglect remain hidden also after death.
Permanent Unilateral Vision Loss From Allergic Fungal Sinusitis
Authors: O'Donnell Erin P. , Kane Ann E.
Published: August 2021

In the absence of trauma, sudden unilateral painless visual loss is an uncommon condition in the pediatric population requiring emergent medical evaluation. In the acute care setting, clinicians face the challenge of accurately assessing the patient and determining the initial diagnostic workup. A careful history alone helps guide diagnosis with sudden visual loss that is unilateral and persistent. Several neuro-ophthalmological conditions that present with these characteristics include retinal artery or vein occlusion, diseases affecting the cavernous sinus or orbital apex region, and optic neuropathy. Simple eye examination techniques have crucial diagnostic value in helping localize the disease process, determining the level of urgency, and need for timely intervention. Here we present an adolescent patient with nontraumatic, acute unilateral visual loss who had concerning ophthalmological examination findings and was subsequently diagnosed with optic neuropathy secondary to allergic fungal sinusitis.
Lifestyle Interventions in the Treatment of Obsessive-Compulsive and Related Disorders: A Systematic Review
Authors: Brierley Mary-Ellen E. , Thompson Emma M. , Albertella Lucy , Fontenelle Leonardo F.
Published: August 2021

Objective

Lifestyle medicine is increasingly important in psychiatry for its efficacy as a transdiagnostic treatment, its preventative potential, and its increased tolerability compared with first-line strategies. Although the impact of lifestyle medicine is strong across many psychiatric illnesses, our understanding of the effectiveness of lifestyle interventions in treating obsessive-compulsive and related disorders (OCRDs) is minimal. We aimed to conduct a systematic review examining the effect of lifestyle interventions (targeting diet, exercise, sleep, stress management, and tobacco/alcohol use) on OCRD symptoms.

Methods

We systematically searched four electronic databases for published randomized controlled trials reporting on lifestyle interventions for OCRDs. We qualitatively synthesized results of eligible studies and calculated mean changes in symptom severity from baseline to end point and standardized between-group effect sizes.

Results

We identified 33 eligible studies. Poor efficacy was noted across a number of rigorous dietary supplement interventions with some promising data in four (of six) studies regarding N-acetylcysteine for trichotillomania, skin picking, and obsessive-compulsive disorder. Stress management interventions, generally characterized by high risk of bias, reported mild effectiveness with greater effects noted for mind-body exercises (yoga) for obsessive-compulsive disorder. Greater improvements may be achieved when lifestyle intervention is adjunct to first-line treatments and delivered by facilitators.

Conclusions

Diet (particularly N-acetylcysteine) and stress management interventions seem promising avenues for OCRDs treatment. We present an action plan to move the lifestyle interventions for OCRDs field forward. Further high-quality lifestyle interventions are required to improve the certainty of findings and to inform clinical treatment guidelines.

Review Registration Number: CRD42020151407.
Dispositional Optimism and All-Cause Mortality in Older Adults: A Cohort Study
Authors: Craig Heather Jayne , Ryan Joanne , Freak-Poli Rosanne , Owen Alice , McNeil John , Woods Robyn , Ward Stephanie , Britt Carlene , Gasevic Danijela
Published: August 2021

Objective

Optimism is modifiable and may be associated with healthy aging. We aim to investigate whether dispositional optimism is associated with all-cause mortality in adults 70 years and older.

Methods

Between 2010 and 2014, older adults free of serious cardiovascular disease and dementia were recruited through primary care physicians and enrolled in the Aspirin Reducing Events in the Elderly (ASPREE) clinical trial. Australian ASPREE participants were invited to participate in the ASPREE Longitudinal Study of Older Persons (ALSOP) that was running in parallel to ASPREE. Optimism was assessed at baseline using the Life Orientation Test—Revised. The association between optimism, divided into quartiles, and all-cause mortality was assessed using Cox proportional hazards models.

Results

A total of 11,701 participants (mean [standard deviation] age = 75.1 [4.24] years; 46.6% men) returned the ALSOP Social questionnaire and completed the Life Orientation Test—Revised. During a median follow-up of 4.7 years, 469 deaths occurred. The fully adjusted model was not significant (hazard ratio = 0.78, 95% confidence interval = 0.58–1.06). There was evidence that age was an effect modifier of the association between optimism and longevity. Higher optimism was associated with lower mortality risk in the oldest individuals only (77+ years; hazard ratio = 0.61, 95% confidence interval = 0.39–0.96).

Conclusions

We observed no independent relationship between optimism and all-cause mortality in the total sample, although optimism seemed to be associated with lower risk among the oldest old (adults 77 years and older).
Prenatal Maternal Bereavement and Its Association With Intellectual Disability in the Offspring
Authors: Su Xiujuan , Yu Yongfu , Meng Lulu , Duan Tony , Zhao Yan , László Krisztina D. , Valdimarsdóttir Unnur Anna , Hua Jing , Li Jiong
Published: August 2021

Objective

This study aimed to examine the association of a mother’s loss of a close relative before or during pregnancy with intellectual disability (ID) in the offspring.

Methods

We performed a nationwide population-based cohort study based on Danish national registries. All live-born singletons born in Denmark during the 1978–2016 period (n = 2,216,601) were followed up starting from birth to 38 years of age. Log-linear Poisson regression was used to estimate the association between maternal bereavement (the death of an older child, a partner, or a parent 1 year before or during pregnancy) and the risk of ID in the offspring.

Results

Maternal bereavement during or before pregnancy was associated with an increased risk of ID (incidence rate ratio [IRR] = 1.15; 95% confidence interval [CI] = 1.04–1.28). The risk of ID was increased by 27% when maternal bereavement occurred during pregnancy (IRR = 1.27; 95% CI = 1.08–1.49). When stratifying on the child’s sex, we also observed an increased risk of ID associated with maternal bereavement during pregnancy both for male (IRR = 1.25; 95% CI = 1.02–1.53) and for female (IRR = 1.31; 95% CI = 1.02–1.69), respectively. The IRRs for unnatural death of a relative were also elevated (IRR = 1.22; 95% CI = 0.91–1.64) in general, although the difference was not statistically significant.

Conclusions

Our findings suggest that prenatal stress due to maternal loss of a close relative may increase the risk of offspring’s ID of both sexes, in particular when the loss happened during pregnancy.
Recalled Neighborhood Environments, Parental Control, and Cytokine-Mediated Response to Viral Challenge
Authors: Corallo Kelsey L. , Lyle Sarah M. , Murphy Michael L. M. , vanDellen Michelle R. , Ehrlich Katherine B.
Published: August 2021

Objective

Neighborhood risk in childhood is associated with poor health across the life span. However, many people who are reared in risky neighborhoods remain healthy in adulthood. In the context of high-risk neighborhoods, parenting practices that are controlling might promote better physical health outcomes later in life. The current study used a viral challenge paradigm to examine whether parental control throughout childhood moderated the association between recalled neighborhood risk and cytokine-mediated cold susceptibility.

Methods

A sample of 209 healthy adults completed questionnaires to assess recalled neighborhood risk and parental control over the first 15 years of life, were exposed to a common cold virus, and were quarantined for 6 days. Researchers assessed nasal proinflammatory cytokine production and objective markers of illness. Participants were diagnosed with a clinical cold if they met the infection and objective illness criteria.

Results

A significant Neighborhood Risk by Parental Control interaction emerged to predict proinflammatory cytokine production. Furthermore, parental control moderated the cytokine-mediated association between neighborhood risk and cold diagnosis (index = −0.073, 95% confidence interval [CI] = −0.170 to −0.016), likelihood of infection (index = −0.071, 95% CI = −0.172 to −0.015), and meeting the objective symptom criteria (index = −0.074, 95% CI = −0.195 to −0.005). Specifically, there was a negative association between neighborhood risk and objective cold diagnosis and infection status at higher levels of parental control, but a nonsignificant association at lower levels of parental control.

Conclusions

Findings suggest that the degree to which recalled neighborhood risk is related to adult health varies as a function of parental control throughout childhood.
Sustained Attention Deficits in Adults With Juvenile-Onset Type 1 Diabetes Mellitus
Authors: Zou Wenjing , He Jing , Liu Yuzhuo , Zhu Jiang , Liu Fang , Xie Yuting , Li Chuting , Du Hongyu , Huang Fansu , Zhou Zhiguang , Li Xia , Zhu Xiongzhao
Published: August 2021

Objective

This study aimed to investigate whether patients with juvenile-onset type 1 diabetes mellitus (T1DM) have poorer sustained attention than their counterparts with adult-onset T1DM, and whether there is a relationship between diabetes-related variables and sustained attention.

Methods

This study included 76 participants with juvenile-onset T1DM, 68 participants with adult-onset T1DM, and 85 healthy controls (HCs). All participants completed the Sustained Attention to Response Task, Beck Depression Inventory-II, and the Chinese version of the Wechsler Adult Intelligence Scale.

Results

The juvenile-onset group showed more omission errors (p = .007) than the adult-onset group and shorter reaction time (p = .005) than HCs, whereas the adult-onset group showed no significant differences compared with HCs. Hierarchical linear regression analysis revealed that the age of onset was associated with omission errors in T1DM participants (β = −0.275, t = −2.002, p = .047). In the juvenile-onset group, the omission error rate were associated with the history of severe hypoglycemia (β = 0.225, t = 1.996, p = .050), whereas reaction time was associated with the age of onset (β = −0.251, t = −2.271, p = .026). Fasting blood glucose levels were significantly associated with reaction time in both the juvenile-onset and adult-onset groups (β = −0.236, t = −2.117, p = .038, and β = 0.259, t = 2.041, p = .046, respectively).

Conclusions

Adults with juvenile-onset T1DM have sustained attention deficits in contrast to their adult-onset counterparts, suggesting that the disease adversely affects the developing brain. Both the history of severe hypoglycemia and fasting blood glucose levels are factors associated with sustained attention impairment. Early diagnosis and treatment in juvenile patients are required to prevent the detrimental effects of diabetes.
A Longitudinal Evaluation of Goal-Striving Stress and Sleep Duration Among African Americans in the Jackson Heart Study
Authors: Cain-Shields Loretta R. , Johnson Dayna A. , Glover LáShauntá , Sims Mario
Published: August 2021

Objective

The purposes of this study were to assess the association between changes in goal-striving stress (GSS) and changes in sleep duration in African Americans (AAs) and to determine if the association varies by sex, age, and/or educational attainment.

Methods

We completed a longitudinal analysis using examination 1 (2000–2004, n = 5306) and examination 3 (2009–2013, n = 3819) data from the Jackson Heart Study, with a final sample of 3500. Changes in GSS and changes in sleep duration were calculated by subtracting examination 1 GSS from examination 3 GSS. Mean differences (β [standard error]) between changes in GSS and changes in sleep duration were assessed using linear regression models that adjusted for length of follow-up, sociodemographics, health behaviors/risk factors, and stressors.

Results

In the fully adjusted models, the increase in GSS from examination 1 to examination 3 was associated with a decrease in sleep duration (in minutes) from examination 1 to examination 3 in the overall cohort (β = −7.72 [2.44], p < .002), in high school graduates (β = −21.23 [5.63], p < .001), and in college graduates (β = −7.57 [3.75], p = .044) but not in those with less than a high school education (β = 1.49 [8.35], p = .86) or those who attended college but did not graduate (β = 0.44 [4.94], p = .93).

Conclusions

Changes in GSS were inversely associated with changes in sleep duration over a mean period of 8 years in AA subgroups. Interventions that reduce stress related to goal striving should be considered to help improve sleep health in AAs.
Brief Report: Yield of Repeat Tuberculin Skin Testing for People Living With HIV in Brazil
Authors: Chaisson Lelia H. , Saraceni Valeria , Cohn Silvia , Cavalcante Solange C. , Chaisson Richard E. , Durovni Betina , Golub Jonathan E.
Published: August 2021

Objectives:

In Brazil, annual tuberculin skin tests (TSTs) are recommended for people living with HIV (PLWH) with CD4 >350, with tuberculosis preventive therapy provided on test conversion. We aimed to determine the yield of repeat TSTs for PLWH.

Design:

Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT) to prevent tuberculosis (TB).

Methods:

We analyzed data from newly registered PLWH with negative baseline TST results. We calculated the number of TST conversions after 1 and/or 2 years among patients eligible for follow-up TSTs, the proportion of converters initiating IPT, and incidence of TB/death.

Results:

Among 1770 PLWH with a negative baseline TST, 679 (38%) were female and median age was 36 years (IQR 29–43). Eighty-six (5%) developed TB or died within 1 year. Among 1684 eligible for a follow-up 1-year TST, 582 (35%) were tested and 53 (9%) were positive. Forty-nine converters (92%) started IPT. Of 529 patients with a negative 1-year TST, 7 (1%) developed TB or died over the following year. Of 522 patients eligible for a 2-year TST, 158 (30%) were tested and 13 (8%) were positive. Ten converters (77%) started IPT. Of 1102 patients who did not receive a 1-year TST, 33 (3%) developed TB or died. Of the 1069 patients eligible for a 2-year TST, 259 (24%) were tested and 34 (13%) were positive. Thirty converters (88%) started IPT.

Conclusions:

In this cohort of PLWH in Brazil, TST conversion was high among those retested, but only 48% received a follow-up TST within 2 years.
Radiopaque Recreations of Lung Pathologies From Clinical Computed Tomography Images Using Potassium Iodide Inkjet 3-dimensional Printing
Authors: Wang Jia , Falkson Samuel R. , Guo H. Henry
Published: August 2021

Purpose:

The purpose of this study was to develop a 3-dimensional (3D) printing method to create computed tomography (CT) realistic phantoms of lung cancer nodules and lung parenchymal disease from clinical CT images.

Materials and Methods:

Low-density paper was used as substrate material for inkjet printing with potassium iodide solution to reproduce phantoms that mimic the CT attenuation of lung parenchyma. The relationship between grayscale values and the corresponding CT numbers of prints was first established through the derivation of exponential fitted equation from scanning data. Next, chest CTs from patients with early-stage lung cancer and coronavirus disease 2019 (COVID-19) pneumonia were chosen for 3D printing. CT images of original lung nodule and the 3D-printed nodule phantom were compared based on pixel-to-pixel correlation and radiomic features.

Results:

CT images of part-solid lung cancer and 3D-printed nodule phantom showed both high visual similarity and quantitative correlation. R
2 values from linear regressions of pixel-to-pixel correlations between 5 sets of patient and 3D-printed image pairs were 0.92, 0.94, 0.86, 0.85, and 0.83, respectively. Comparison of radiomic measures between clinical CT and printed models demonstrated 6.1% median difference, with 25th and 75th percentile range at 2.4% and 15.2% absolute difference, respectively. The densities and parenchymal morphologies from COVID-19 pneumonia CT images were well reproduced in the 3D-printed phantom scans.

Conclusion:

The 3D printing method presented in this work facilitates creation of CT-realistic reproductions of lung cancer and parenchymal disease from individual patient scans with microbiological and pathology confirmation.
Immunoscore Signatures in Surgical Specimens and Tumor-Infiltrating Lymphocytes in Pretreatment Biopsy Predict Treatment Efficacy and Survival in Esophageal Cancer
Authors: Noma Toshiki , Makino Tomoki , Ohshima Kenji , Sugimura Keijiro , Miyata Hiroshi , Honma Keiichiro , Yamashita Kotaro , Saito Takuro , Tanaka Koji , Yamamoto Kazuyoshi , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Nakajima Kiyokazu , Morii Eiichi , Eguchi Hidetoshi , Doki Yuichiro
Published: August 2021

Objectives:

Tumor-infiltrating lymphocytes (TILs) have long been recognized as playing an important role in tumor immune microenvironment. Lately, the Immunoscore (IS) has been proposed as a new method of quantifying the number of TILs in association with patient survival in several cancer types.

Methods:

In 300 preoperatively untreated esophageal cancer (EC) patients who underwent curative resection at two different institutes, immunohistochemical staining using CD3 and CD8 antibodies was performed to evaluate IS, as objectively scored by auto-counted TILs in the tumor core and invasive margin. In addition, in pre-neoadjuvant chemotherapy (pre-NAC) endoscopic biopsies of a different cohort of 146 EC patients who received NAC, CD3, and CD8 were immunostained to evaluate TIL density.

Results:

In all cases, the IS-high (score 3–4) group tended to have better survival [5-year overall survival (OS) of the IS-high vs low group: 77.6 vs 65.8%, P = 0.0722] than the IS-low (score 1–2) group. This trend was more remarkable in cStage II–IV patients (70.2 vs 54.5%, P = 0.0208) and multivariate analysis of OS further identified IS (hazard ratio 2.07, P = 0.0043) to be an independent prognostic variable. In preNAC biopsies, NAC-responders had higher densities than non-responders of both CD3+ (P = 0.0106) and CD8+ cells (P = 0.0729) and, particularly CD3+ cell density was found to be an independent prognostic factor (hazard ratio 1.75, P = 0.0169).

Conclusions:

The IS signature in surgical specimens and TIL density in preNAC- biopsies could be predictive markers of clinical outcomes in EC patients.
Hepatocellular Adenoma Risk Factors of Hemorrhage: Size Is Not the Only Concern!
Authors: Julien Céline , Le-Bail Brigitte , Ouazzani Touhami Kevin , Frulio Nora , Blanc Jean-Frédéric , Adam Jean-Philippe , Laurent Christophe , Balabaud Charles , Bioulac-Sage Paulette , Chiche Laurence
Published: August 2021

Objective:

Our aim was to determine independent risk factors of clinical bleeding of hepatocellular adenoma (HCA) to define a better management strategy.

Summary Background Data:

HCA is a rare benign liver tumor with severe complications: malignant transformation that is rare (5%–8%) and more often, hemorrhage (20%–27%). To date, only size > 5 cm and histological subtype (possibly sonic hedgehog) are associated with bleeding, but these criteria are not clearly established.

Methods:

We retrospectively collected data from a cohort of 268 patients with HCA managed in our tertiary center, from 1984 to 2020 and focused on clinical bleeding. Hemorrhage was considered severe when it required intensive care and moderate when bleeding symptoms required a hospitalization. We included 261 patients, of whom 130 (49.8%) had multiple HCAs or liver adenomatosis. All surgical specimen and liver biopsy were reviewed by an experienced liver pathologist and reclassified in the light of the current immunohistochemistry. Mean duration of follow-up was 93.3 months (range 1–363). We analyzed type, frequency, consequences of bleeding, and risk factors among clinical data and HCA characteristics.

Results:

Eighty-three HCA (31.8%) were hemorrhagic. There were 4 pregnant women with 1 newborn death. One patient died before treatment. Surgery was performed in 78 (94.0%) patients. Mortality was nil and severe complications occurred in 11.5%. Multivariate analysis identified size (OR 1.02 [1.01–1.02], P < 0.001), shHCA (OR 21.02 [5.05–87.52], P < 0.001), b-catenin mutation on exon 7/8 (OR 6.47 [1.78–23.55], P = 0.0046), chronic alcohol consumption (OR 9.16 [2.47–34.01], P < 0.001) as independent risk factors of clinical bleeding.

Conclusions:

This series, focused on the hemorrhagic risk of HCA, shows that size, but rather more molecular subtype is determinant in the natural history of HCA.
Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death
Authors: Czigany Zoltan , Pratschke Johann , Froněk Jiří , Guba Markus , Schöning Wenzel , Raptis Dimitri Aristotle , Andrassy Joachim , Kramer Matthijs , Strnad Pavel , Tolba Rene Hany , Liu Wenjia , Keller Theresa , Miller Hannah , Pavicevic Sandra , Uluk Deniz , Kocik Matej , Lurje Isabella , Trautwein Christian , Mehrabi Arianeb , Popescu Irinel , Vondran Florian Wolfgang Rudolf , Ju Cynthia , Tacke Frank , Neumann Ulf Peter , Lurje Georg
Published: August 2021

Objective:

The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD).

Background:

HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT).

Methods:

Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD).

Results:

Demographics were equally distributed between both groups [donor age: 72 (IQR: 59–78) years, recipient age: 62 (IQR: 55–65) years, labMELD: 15 (IQR: 9–25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221–828) vs 796 (IQR: 477–1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12–56) vs 52 (IQR: 35–98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4–8) vs 8 (IQR: 5–18) days, P = 0.045; 20 (IQR: 16–27) vs 36 (IQR: 23–62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314).

Conclusion:

This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.
Mortality in Congenital Diaphragmatic Hernia
Authors: Gupta Vikas S. , Harting Matthew T. , Lally Pamela A. , Miller Charles C. , Hirschl Ronald B. , Davis Carl F. , Dassinger MelvinIII S. , Buchmiller Terry L. , Van Meurs Krisa P. , Yoder Bradley A. , Stewart Michael J. , Lally Kevin P. ,   for the Congenital Diaphragmatic Hernia Study Group
Published: August 2021

Objective:

To determine if risk-adjusted survival of patients with CDH has improved over the last 25 years within centers that are long-term, consistent participants in the CDH Study Group (CDHSG).

Summary Background Data:

The CDHSG is a multicenter collaboration focused on evaluation of infants with CDH. Despite advances in pediatric surgical and intensive care, CDH mortality has appeared to plateau. Herein, we studied CDH mortality rates amongst long-term contributors to the CDHSG.

Methods:

We divided registry data into 5-year intervals, with Era 1 (E1) beginning in 1995, and analyzed multiple variables (operative strategy, defect size, and mortality) to assess evolution of disease characteristics and severity over time. For mortality analyses, patients were risk stratified using a validated prediction score based on 5-minute Apgar (Apgar5) and birth weight. A risk-adjusted, observed to expected (O:E) mortality model was created using E1 as a reference.

Results:

5203 patients from 23 centers with >22years of participation were included. Birth weight, Apgar5, diaphragmatic agenesis, and repair rate were unchanged over time (all P > 0.05). In E5 compared to E1, minimally invasive and patch repair were more prevalent, and timing of diaphragmatic repair was later (all P < 0.01). Overall mortality decreased over time: E1 (30.7%), E2 (30.3%), E3 (28.7%), E4 (26.0%), E5 (25.8%) (P = 0.03). Risk-adjusted mortality showed a significant improvement in E5 compared to E1 (OR 0.78, 95% CI 0.62-0.98; P = 0.03). O:E mortality improved over time, with the greatest improvement in E5.

Conclusions:

Risk-adjusted and observed-to-expected CDH mortality have improved over time.
Outcomes of Esophagogastric Cancer Surgery During Eight Years of Surgical Auditing by the Dutch Upper Gastrointestinal Cancer Audit (DUCA)
Authors: Voeten Daan M. , Busweiler Linde A. D. , van der Werf Leonie R. , Wijnhoven Bas P. L. , Verhoeven Rob H. A. , van Sandick Johanna W. , van Hillegersberg Richard , van Berge Henegouwen Mark I.
Published: August 2021

Objective:

To evaluate changes in treatment and outcomes of esophagogastric cancer surgery after introduction of the DUCA. In addition, the presence of risk-averse behavior was assessed.

Summary of Background Data:

Clinical auditing is seen as an important quality improvement tool; however, its long-term efficacy remains largely unknown. In addition, critics claim that enhancements result from risk-averse behavior rather than positive effects of auditing.

Methods:

DUCA data were used from registration start (1-1-2011) until 31-12-2018. Trends in patient, tumor, hospital and treatment characteristics were univariably assessed. Trends in short-term outcomes were investigated using multilevel multivariable logistic regression. Presence of risk aversion was described by the corrected proportion of patients undergoing surgery, using data from the Netherlands Cancer Registry. To evaluate the impact of centralization on time trends identified, the association between hospital volume and outcomes was investigated.

Results:

This study included 6172 patients with esophageal and 3,690 with gastric cancer who underwent surgery. Pathological outcomes (lymph node yield, radicality) improved and futile surgery decreased over the years. In-hospital/30-day mortality decreased for esophagectomy (4.2% to 2.5%) and for gastrectomy (7.1% to 4.3%). Reinterventions, (minor) complications and readmissions increased. Risk aversion appeared absent. Between 2011-2018, annual median hospital volumes increased from 38 to 53 for esophagectomy and from 14 to 29 for gastrectomy. Higher hospital volumes were associated with several improved outcomes measures.

Conclusions:

During 8 years of auditing, outcomes improved, with no signs of risk-averse behavior. These improvements occurred in parallel with centralization. Feedback on postoperative complications remains the focus of the DUCA.
Survival Benefit Associated With Resection of Locally Advanced Pancreatic Cancer After Upfront FOLFIRINOX Versus FOLFIRINOX Only
Authors: Brada Lilly J. H. , Daamen Lois A. , Magermans Lisa G. , Walma Marieke S. , Latifi Diba , van Dam Ronald M. , de Hingh Ignace H. , Liem Mike S. L. , de Meijer Vincent E. , Patijn Gijs A. , Festen Sebastiaan , Stommel Martijn W. J. , Bosscha Koop , Polée Marco B. , Nio Yung C. , Wessels Frank J. , de Vries Jan J. J. , van Lienden Krijn P. , Bruijnen Rutger C. , Busch Olivier R. , Koerkamp Bas Groot , van Eijck Casper , Molenaar Quintus I. , Wilmink Hanneke J. W. , van Santvoort Hjalmar C. , Besselink Marc G.
Published: August 2021

Objective:

This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without resection).

Background:

Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking.

Methods:

Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015–December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS.

Results:

Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months, P < 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS [Hazard Ratio (HR) 0.344, 95% confidence interval (0.222–0.534), P < 0.01], with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%, P < 0.01).

Conclusions:

Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.
Protective effects of Dimethyl malonate on neuroinflammation and blood-brain barrier after ischemic stroke
Authors: Zhang Zhen , Lu Zhengfang , Liu Chang , Man Jiang , Li Xiang , Cui Kefei , Lu Hong , Wang Jianping
Published: August 2021

Objectives

After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain.

Methods

We used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins.

Results

DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment.

Conclusions

DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB.
A critical review of life cycle assessment studies of woody biomass conversion to sugars
Authors: Ryan Niamh , Yaseneva Polina
Published: August 2021

Woody biomass could potentially become a viable raw material for the future sustainable chemical industry. For this, a suitable regulatory framework must exist, that would create favourable economic conditions for wood biorefineries. Such policies must be developed on the basis of scientific evidence—in this case, data supporting the environmental advantages of the bio-based feedstocks to the chemical industry. The most suitable methodology for comprehensive evaluation of environmental performance of technologies is life cycle assessment (LCA). In this review, the available LCA studies of woody biomass fractionation and conversion to bulk chemical feedstocks are critically evaluated. It has been revealed that the majority of the openly available studies do not contain transparent inventory data and, therefore, cannot be verified or re-used; studies containing inventory data are reported in this review. The lack of inventory data also prevents comparison between studies of the same processes performed with different evaluation methods or using different system boundaries. Recommendations are proposed on how to overcome issues of commercial data sensitivity by using black-box modelling when reporting environmental information. From several comparable LCA studies, it has been concluded that today the most environmentally favourable technology for wood biomass fractionation is organosolv.

This article is part of the theme issue ‘Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 1)’.
Phylogenetic analysis of molecular pathways in Tregs Suppressor Function
Authors: Mickael Michel-Edwar , Kubick Norwin , Klimovich Pavel , Bieńkowska Irmina , Bhaumik Suniti , Horbańczuk Jarosław Olav , Sacharczuk Mariusz , Basu Rajatava
Published: August 2021

Treg-mediated suppression of conventional T cells is a fundamental step in regulating the adaptive immune response. It is known that Treg first appeared in vertebrates. However, little is known about the of major suppression pathways mediated by Tregs. We employed artificial intelligence text mining system to highlight the suppression pathways currently known to be utilized by Tregs. Our system identified various pathways mediated by CTLA4, calcium signaling, NfkB and NFAT. We simultaneously employed detailed phylogenetic analysis including multiple sequence alignment, phylogenetic tree building, ancestral sequence reconstruction, neutrality tests and positive selection test to investigate the evolution of Treg mediated pathways. We found that CTLA4 first appeared in vertebrates possibly arising from an IGV containing protein in cartilaginous fish. Conversely, we found that Tregs repurposed ancient pathways such as Calcineurin and CAMP Response Element Modulator. Interestingly, these two pathways were highly conserved between vertebrates and lower invertebrates indicating conservation of function. Taken together, our research indicate that Tregs developed its regulatory systems through evolution in vertebrates as well as reusing conserved ancient regulatory systems that are related to the innate immune system.
Hypertension drives microbial translocation and shifts in the fecal microbiome of non-human primates
Authors: Vemuri Ravichandra , Ruggiero Alistaire , Whitfield Jordyn B. , Dugan Greg O. , Cline J. Mark , Block Masha R. , Guo Hao , Kavanagh Kylie
Published: August 2021

Accumulating evidence indicates a link between gut barrier dysfunction and hypertension. However, it is unclear whether hypertension dictates gut barrier dysfunction or vice versa and whether the gut microbiome plays a role. To better understand this relationship, first, we cross-sectionally examined hypertension and other cardio-metabolic risk factors and gut barrier function in a population of 150 nonhuman primates. Interestingly, the animals with hypertension showed evidence of gut barrier dysfunction (i.e., translocation of microbes through the gut wall), as indicated by higher plasma levels of lipopolysaccharide-binding protein (LBP)-1, compared to normotensive animals. Further, plasma LBP-1 levels were strongly correlated with diastolic blood pressure, independent of age and other health markers, suggesting specificity of the effect of hypertension on microbial translocation. In a subsequent longitudinal study (analysis at baseline, 12 and 27 months), hypertensive animals had higher plasma levels of LBP-1 at all the time points and greater bacterial gene expression in mesenteric lymph nodes compared to normotensive animals, confirming microbe translocation. Concomitantly, we identified distinct dysbiosis in the gut microbial signature of hypertensive versus normotensive animals at 12 and 27 months. These results suggest that hypertension drives microbial translocation in the gut and eventually unhealthy shifts in the gut microbiome, possibly contributing to poor health outcomes, providing further impetus for the management of hypertension.

Graphical Abstract