bluuebunny/crossref_metadata_2025 huggingface dataset:
PDGFRα/Sca-1 Sorted Mesenchymal Stromal Cells Reduce Liver Injury in Murine Models of Hepatic Ischemia-Reperfusion Injury
Authors: Owen Andrew , Patten Daniel , Vigneswara Vasanthy , Frampton Jon , Newsome Philip N
Published: August 2022

Liver transplantation is an effective therapy, but increasing demand for donor organs has led to the use of marginal donor organs with increased complication rates. Mesenchymal stromal cells (MSC) pleiotropically modulate aberrant immune-mediated responses and represent a potential therapy to target the inflammation seen post-transplant with marginal donor livers. To avoid the confounding effects of xenotransplantation seen in studies with human MSC, a PDGFRα/Sca-1 (PaS) sorted MSC population was used which was analogous to human MSC populations (LNGFR+Thy-1+VCAM-1Hi). PaS MSC are a well-described population that demonstrate MSC properties without evidence of clonal mutation during expansion. We demonstrate their anti-inflammatory properties herein through their suppression of T-lymphocyte proliferation in vitro and secretion of anti-inflammatory cytokines (IL-10 and OPG) after stimulation (P = .004 and P = .003). The MDR2−/− model of biliary injury and hepatic ischemia-reperfusion (HIR) injury models were used to replicate the non-anastomotic biliary complications seen following liver transplantation. Systemic MSC therapy in MDR2−/− mice led to reduced liver injury with an increase in restorative macrophages (5913 ± 333.9 vs 12 597 ± 665.8, P = .002, n = 7) and a change in lymphocyte ratios (3.55 ± 0.37 vs 2.59 ± 0.139, P = .023, n = 17), whereas subcutaneous administration of MSC showed no beneficial effect. MSC also reduced cell death in the HIR model assessed by Periodic acid–Schiff (PAS) staining (91.7% ± 2.8 vs 80.1% ± 4.6, P = .03). Systemically administered quantum dot-labeled MSC were tracked using single-cell resolution CryoViz imaging which demonstrated their sequestration in the lungs alongside retention/redistribution to injured liver tissue. MSC represent a potential novel therapy in marginal organ transplantation which warrants further study.
Methylene blue: a controversial diagnostic acid and medication?
Authors: Bužga Marek , Machytka Evžen , Dvořáčková Eliška , Švagera Zdeněk , Stejskal David , Máca Jan , Král Jan
Published: August 2022

A narrative review of the literature was conducted to determine if the administration of methylene blue (MB) in humans has potential risks. Studies were identified from MEDLINE, Web of Science, Scopus, and Cochrane. MB is a diagnostic substance used during some diagnostic procedures and also a part of the treatment of several diseases including methemoglobinemia, vasoplegic syndrome, fosfamide-induced encephalopathy, and cyanide intoxication, and the detection of leaks or position of parathyroid corpuscles during surgery. Although the use of MB is historically justified, and it ought to be safe, because it originated as a diagnostic material, the basic toxicological characteristics of this substance are unknown. Despite reports of severe adverse effects of MB, which could significantly exceed any possible benefits evaluated for the given indication. Therefore, the clinical use of MB currently represents a controversial problem given the heterogeneity of available data and the lack of preclinical data. This is in conflict with standards of safe use of such substances in human medicinal practice. The toxic effects of the application of MB are dose-dependent and include serious symptoms such as hemolysis, methemoglobinemia, nausea and vomitus, chest pain, dyspnoea, and hypertension. Some countries regard MB as harmful because of the resulting skin irritation and triggering of an adverse inflammatory response. MB induced serotoninergic toxicity clinically manifests as neuromuscular hyperactivity. This review aims to summarize the current understanding concerning the indications for MB administration and define the potential adverse effects of MB.
Legal reasoning and Latin America’s economic development
Authors: Kozolchyk Boris
Published: August 2022

This article discusses how a method of legal reasoning employed first by French and Spanish legislators and judges and, subsequently, by their Latin American successors hindered the economic development of their respective countries.1 It suggests that significant economic development would be possible if legislators helped enact honest, reasonable, and fair versions of successful market practices in a manner consistent with their nations’ or regions’ developmental goals.2 It further suggests that Latin American judges can contribute to the attainment of such goals by adopting a method of reasoning that differs from their present method. The proposed method requires that in disputes caused by the disabling effects of obsolete statutory, case, or customary law on promising new customs and practices, the judge acts as a quasi-legislator. In that capacity, he should carefully consider not only the pivotal facts of the dispute and the applicable law but also his nation’s socio-economic conditions and economic development goals. Then, by placing himself in the archetypal position of a reasonable merchant, always having in mind the interest of his contractual and third-party ‘others’, the judge’s decision should enable Justice Oliver Wendell Holmes Jr.’s ‘prophecies’ of what courts will decide in future cases with similar facts and legal issues.3 Thus, he will also be heeding the advice of the distinguished Mexican legal philosopher Eduardo García Máynez, who urged judges to fill the inevitable obsolete and unfair normative gaps with equitable judicial ‘individual’ norms.4 Finally, in updating practices and correcting injustices, the judges’ methods of reasoning should be guided by a broad definition of good faith adopted by 19th-century German Civil and Commercial Codes as well as by the 20th-century US Uniform Commercial Code (UCC), as will be discussed throughout this article. In essence, it requires that legislators and judges take into account the honesty, reasonableness, and fairness of the new practice before it becomes a binding norm.
Variation in within-host replication kinetics among virus genotypes provides evidence of specialist and generalist infection strategies across three salmonid host species
Authors: Páez David J , McKenney Douglas , Purcell Maureen K , Naish Kerry A , Kurath Gael
Published: August 2022

Theory of the evolution of pathogen specialization suggests that a specialist pathogen gains high fitness in one host, but this comes with fitness loss in other hosts. By contrast, a generalist pathogen does not achieve high fitness in any host, but gains ecological fitness by exploiting different hosts, and has higher fitness than specialists in nonspecialized hosts. As a result, specialist pathogens are predicted to have greater variation in fitness across hosts, and generalists would have lower fitness variation across hosts. We test these hypotheses by measuring pathogen replicative fitness as within-host viral loads from the onset of infection to the beginning of virus clearance, using the rhabdovirus infectious hematopoietic necrosis virus (IHNV) in salmonid fish. Based on field prevalence and virulence studies, the IHNV subgroups UP, MD, and L are specialists, causing infection and mortality in sockeye salmon, steelhead, and Chinook salmon juveniles, respectively. The UC subgroup evolved naturally from a UP ancestor and is a generalist infecting all three host species but without causing severe disease. We show that the specialist subgroups had the highest peak and mean viral loads in the hosts in which they are specialized, and they had low viral loads in nonspecialized hosts, resulting in large variation in viral load across hosts. Viral kinetics show that the mechanisms of specialization involve the ability to both maximize early virus replication and avoid clearance at later times, with different mechanisms of specialization evident in different host–virus combinations. Additional nuances in the data included different fitness levels for nonspecialist interactions, reflecting different trade-offs for specialist viruses in other hosts. The generalist UC subgroup reached intermediate viral loads in all hosts and showed the smallest variation in fitness across hosts. The evolution of the UC generalist from an ancestral UP sockeye specialist was associated with fitness increases in steelhead and Chinook salmon, but only slight decreases in fitness in sockeye salmon, consistent with low- or no-cost generalism. Our results support major elements of the specialist–generalist theory, providing evidence of a specialist–generalist continuum in a vertebrate pathogen. These results also quantify within-host replicative fitness trade-offs resulting from the natural evolution of specialist and generalist virus lineages in multi-host ecosystems
Seasonal Transcriptome Profiling of Susceptible and Tolerant Citrus Cultivars to Citrus Huanglongbing
Authors: Ribeiro Camila , Xu Jin , Hendrich Connor , Pandey Sheo Shankar , Yu Qibin , Gmitter Frederick G. , Wang Nian
Published: August 2022

Citrus huanglongbing (HLB) caused by ‘ Candidatus Liberibacter asiaticus’ (CLas) is the most devastating citrus disease worldwide. Most commercial citrus cultivars are susceptible to HLB, with a few more tolerant exceptions such as ‘LB8-9’ Sugar Belle mandarin. Transcriptomic analyses have been widely used to investigate the potential mechanisms for disease susceptibility, resistance, or tolerance. Previous transcriptomic studies related to HLB mostly focused on single time point data collection. We hypothesize that changes in day length and temperature throughout the seasons have profound effects on citrus−CLas interactions. Here, we conducted RNA-seq analyses on HLB-susceptible Valencia sweet orange and HLB-tolerant mandarin ‘LB8-9’ in winter, spring, summer, and fall. Significant variations in differentially expressed genes (DEGs) related to HLB were observed among the four seasons. For both cultivars, the highest number of DEGs were found in the spring. CLas infection stimulates the expression of immune-related genes such as NBS-LRR, RLK, RLCK, CDPK, MAPK pathway, reactive oxygen species (ROS), and PR genes in both cultivars, consistent with the model that HLB is a pathogen-triggered immune disease. HLB-positive mandarin ‘LB8-9’ trees contained higher concentrations of maltose and sucrose, which are known to scavenge ROS. In addition, mandarin ‘LB8-9’ showed higher expression of genes involved in phloem regeneration, which might contribute to its HLB tolerance. This study shed light on the pathogenicity mechanism of the HLB pathosystem and the tolerance mechanism against HLB, providing valuable insights into HLB management.
Breastfeeding on Injectable Opioid Agonist Therapy: A Case Report
Authors: Patricelli Charissa J. , Gouin Isabelle J. , Gordon Shanlea , Carter Nicole , Albert Arianne , Paquette Vanessa , Stewart Karly , George Shawn , Urbanoski Karen
Published: August 2022

Background

Injectable opioid agonist therapy (iOAT) is the highest-intensity treatment currently available in Canada for individuals with severe opioid use disorder. However, there is limited data on iOAT administration in the perinatal period, with no research, practice guidelines, or known reports of breastfeeding on iOAT. This article presents the first known case of an individual breastfeeding on iOAT.

Case summary

We present a case of a pregnant 32-year-old woman from Canada with severe opioid use disorder, who stabilized with iOAT and chose to breastfeed her infant. She presented to hospital at 38 + 6 gestation in labor, unstable in her substance use disorder despite multiple interventions and was initiated on iOAT (intravenous hydromorphone) shortly after delivery. Before initiation of breastfeeding the infant was admitted to the neonatal intensive care unit for monitoring. On day 9 of life the infant received breastmilk for the first time, and was discharged from neonatal intensive care unit on day 12 of life with no clinical evidence of sedation or respiratory depression. The infant maintained mixed feeding and at 58 days of life was discharged in the mother and father’s care, a healthy infant with stable vitals.

Discussion

This case suggests positive infant and maternal health and social outcomes for breastfeeding on iOAT. Further research on perinatal iOAT use and the pharmacokinetics of high-dose hydromorphone in breastmilk is required to inform clinical practice guidelines to safely support individuals and their infants who are impacted by substance use.
High-risk Coronary Plaque Regression in Cash-based Contingency Management Intervention Among Cocaine Users With HIV-associated Subclinical Coronary Atherosclerosis
Authors: Lai Hong , Bluemke David A. , Fishman Elliot K. , Gerstenblith Gary , Celentano David D. , Treisman Glenn , Foster Parker , Mandler Raul , Khalsa Jag , Chen Shaoguang , Bhatia Sandeepan , Kolossváry Márton , Lai Shenghan
Published: August 2022

Background

Cocaine use exacerbates human immunodeficiency virus (HIV)–associated subclinical coronary atherosclerosis. We investigated whether cocaine abstinence or reduced use achieved with contingency management (CM) intervention would retard high-risk coronary plaque progression among cocaine users with HIV and subclinical coronary atherosclerosis.

Methods

Between March 2014 and August 2017, 76 cocaine users with HIV and coronary plaques were enrolled in a study designed to decrease cocaine use and determine whether doing so impacted progression of subclinical coronary atherosclerosis as measured by coronary artery computed tomography examinations. Of the 76, 7 did not complete the study, resulting in 69 participants. A 12-month cash-based CM intervention was implemented to promote cocaine abstinence or reduced cocaine use. Generalized estimating equation approach was used to perform longitudinal data analyses.

Findings

During the 12-month CM, all 69 participants reduced cocaine use, and of these, 25 (36%; 95% confidence interval, 25%–49%) achieved cocaine abstinence. After adjusting for potential confounding factors, generalized estimating equation analyses showed that (1) endothelin-1 (ET-1) levels, a proinflammatory biomarker for endothelial dysfunction, at the 6-month and 12-month visits were significantly lower compared with baseline ET-1 (P = 0.001 and P < 0.001, respectively), and (2) low-attenuation noncalcified coronary plaque volume, a predictor for myocardial infarction, at 12-month visit was significantly lower compared with baseline low-attenuation noncalcified coronary plaque volume (P < 0.05).

Conclusions

The findings of this study have not only demonstrated that CM is effective in achieving a sustained reduction in cocaine use, but also provided compelling evidence that reduction in cocaine use leads to quantifiable cardiovascular health benefits, including concurrent decrease in high-risk plaque burden and ET-1, among cocaine users with HIV-associated coronary atherosclerosis.
Comminuted Olecranon Fractures (Mayo IIB): Is Dynamic Tension Band Wiring Enough?
Authors: Esper Garrett W. , Herbosa Christopher G. , Moses Michael J. , Egol Kenneth A.
Published: August 2022

Objectives:

To compare the efficacy and outcomes of dynamic tension band wiring (TBW) and plate and screw (PS) fixation of comminuted (Mayo Type IIB) olecranon fractures.

Design:

Retrospective cohort.

Setting:

Academic medical center.

Patients/Participants:

Forty-one patients with Mayo type IIB (OTA/AO 2U1C) olecranon fractures were involved in the study.

Intervention:

Patients with tensile Mayo type IIB olecranon fractures between August 2012 and November 2020 treated by a single surgeon with either TBW or PS fixation were reviewed for demographics, radiographic/surgical details, and clinical/functional outcomes. Descriptive fracture data included proximal olecranon fragment size and the presence of joint impaction at surgery.

Main Outcome Measurements:

The main outcome measurements were Mayo Elbow Performance Score, elbow range of motion, patient-reported pain, and complications.

Results:

The mean follow-up was 38 months. Fractures healed for all patients in both groups. No differences in clinical outcomes, functional outcomes, elbow range of motion, or complications were seen between fixation groups. There was no difference in proximal fragment size between the 2 groups. Fractures with articular impaction requiring elevation and grafting demonstrated no difference in clinical or functional outcomes when compared with those that did not have any impaction. However, patients with impacted articular fractures treated with TBW had a higher rate of implant removal (25% vs. 0%, P = 0.05) when compared with those treated with PS.

Conclusions:

Comminuted Mayo IIB olecranon fractures are amenable to TBW or plate construct, with similar clinical and functional outcomes. The presence of articular impaction is associated with a greater need for implant removal.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Injury Pattern Recognition and Surgical Technique of Pilon Fracture Reduction With Posterior Tibial Tendon Incarceration
Authors: Labrum Joseph T. , Gallagher Bethany , Boyce Robert H.
Published: August 2022

Pilon fractures occur over a broad spectrum of injury severity and soft-tissue compromise. This article will review a distinct pilon injury variant characterized by posterior tibial tendon incarceration in posteromedial pilon fracture propagation. This injury pattern is vital to recognize preoperatively because failure to mobilize the entrapped posterior tibial tendon (PTT) will result in fracture malreduction and postoperative loss of PTT excursion. In addition, the authors’ preferred surgical technique for PTT mobilization and anatomic fracture reduction is described.
Deciphering diffuse glioma immune microenvironment as a key to improving immunotherapy results
Authors: Picca Alberto , Finocchiaro Gaetano
Published: August 2022

Purpose of review

Immunotherapeutic approaches have yet to demonstrate their clinical efficacy in diffuse gliomas. Evidence is mounting that the central nervous system is subject to immune surveillance, but brain tumours manage to escape due to factors intrinsic to their tumoral immune microenvironment (TME). This review aims to discuss the recently characterized molecular bases of the glioma TME and the potentially actionable targets to improve immunotherapeutic results in these hard-to-treat cancers.

Recent findings

Single-cell studies defined the composition of the glioma immune TME and its peculiarities compared with other solid cancers. In isocitrate dehydrogenase (IDH) wildtype gliomas, the TME is enriched in myeloid cells (monocyte-derived macrophages and resident microglia) with mainly immunosuppressive functions. Lymphocytes can infiltrate the glioma TME, but are exposed to multiple immunomodulating signals that render them in a state of deep exhaustion. IDH mutant gliomas produce the oncometabolite D-2-hydroxyglutarate with negative effects on leukocyte recruitment and function, resulting in the induction of an ‘immune-desert’ TME.

Several molecular pathways have been recently identified in the induction of an ‘immune-hostile’ microenvironment in diffuse gliomas, unravelling potential vulnerabilities to targeted immunotherapies.
Age-Related Changes in Intraocular Pressure: Japan Ningen Dock Study
Authors: Terauchi Ryo , Wada Takashi , Fukai Kota , Tatemichi Masayuki , Ogawa Shumpei , Noro Takahiko , Ito Kyoko , Kato Tomohiro , Kato Kiminori , Nakano Tadashi
Published: August 2022

Précis:

The analysis of intraocular pressure by age using a mega database showed a consistent age-related intraocular pressure decrease.

Purpose:

To clarify the association between age and intraocular pressure (IOP), the IOP value by age was assessed using a large IOP database.

Materials and Methods:

This cross-sectional study was conducted among 103 health checkup institutions registered to the Japan Society of Ningen Dock, and included participants who underwent annual health checkups between April 2014 and March 2015. The inclusion criteria were as follows: complete data for IOP in eyes, body mass index, waist circumference, blood pressure, hemoglobin A1c, and a self-administered health questionnaire. A total of 655,818 participants were enrolled. The mean age was 51.5±10.5 years (range, 20–96 y), and 40.1% were women. IOP was measured using a noncontact tonometer. Multiple linear regression analysis was conducted to explore factors associated with IOP, including age, and analyses stratified by age group: <40, 40–69, and ≥70 years.

Results:

A consistent negative association between IOP and age [β=−0.353 (95% confidence interval: −0.360–−0.346)] was observed. In the age groups of <40 and ≥70 years, the age-related IOP decline was more pronounced [β=−0.502 (95% CI: −0.566 to –0.439); β=−0.674 (95% CI: −0.753 to –0.595)], with it being 14.21±2.95 and 11.18±2.52 mm Hg in the 20–24 and 90–96 year age groups, respectively. The middle-aged (aged 40–69 y) population showed gradual decline [β=−0.313 (95% CI: −0.323 to –0.303)].

Conclusion:

Age was strongly and negatively associated with IOP. The magnitude of IOP decline across lifespans was ∼3 mmHg. Age-related decreases in IOP were nonlinear and phasic.
Topical Steroid-Induced Cushing’s Syndrome in a Newborn Following Goniotomy for Glaucoma
Authors: Choudhary Sandeep , Singh Ashok Kumar , Gupta Kajree , Pandav Surinder S. , Kaushik Sushmita
Published: August 2022

Iatrogenic Cushing’s syndrome is a life-threatening condition which requires an early diagnosis multidisciplinary approach. Despite reports of iatrogenic Cushing’s syndrome following nasal or inhaled steroids, its development after topical betamethasone eye drops for a short duration is a less frequently reported or anticipated condition. We describe a 6-week-old infant who developed exogenous Cushing’s syndrome following topical steroids after bilateral goniotomy for newborn glaucoma. The child was kept under observation and managed with a physiological dose of hydrocortisone. Parental counselling regarding the proper method of eye drop instillation and signs of steroid toxicity is of vital importance in all cases of pediatric ocular surgeries, especially where bilateral surgeries are undertaken.
Liver directed stereotactic body radiotherapy can be reliably delivered to selected patients without internal fiducial markers- a case series
Authors: Fu Hsiao-Ju , Chen Po-Yueh , Yang Hsin-Yi , Tsang Yuk-Wah , Lee Cheng-Yen
Published: August 2022

Tumor motion and the lack of tissue-tumor contrast have been challenging parts of liver directed stereotactic body radiotherapy (SBRT). In this study, we investigated the possibility of liver directed SBRT without internal fiducials using breath hold technique and diaphragm matching technique. 134 volumetric images of 13 consecutive patients with either primary or metastatic liver tumors who underwent expiratory breath hold SBRT were compared and analyzed. Reproducibility of diaphragm position between fractions relative to bone was evaluated on image registration software. At median follow-up time of 13 months, 1-year and 2-year local control rates of index lesions were 90% and 72%, respectively. In comparison to diaphragm matching, a greater margin is required for bone matching technique for that 19 out of 67 (28%) of all interfractional SI offsets were more than 6mm, whereas 6 out of 67 (9%) intrafractional SI exceeded 6mm. Despite the small study size, our study showed that breath hold SBRT without internal hepatic fiducial is a valid approach for selected patients.
Addressing telehealth education in a family nurse practitioner program through simulation-based learning
Authors: Berrier Faith , Hellier Susan
Published: August 2022

Telehealth usage increased because of the COVID-19 pandemic. Health care agencies responded by increasing existing platforms and implementing new telehealth platforms. Despite the demand, health care providers may have had little training in the telehealth care delivery model in the workplace or embedded in school. Based on educational theory, evidence, and best practice, the authors crafted a learning module that focused on telehealth medical skills followed by a summative standardized patient simulation. This article describes the development, implementation, and evaluation of the learning module and the summative simulation assessment. The learning module and the simulation provided a teaching strategy that resulted in an objective measurement of student clinical performance, which may be elusive in a traditional face-to-face practicum. Additionally, the simulation-based learning resulted in increased student satisfaction with simulation and increased self-confidence to apply the information in the clinical setting.
Radiologic Features in Cochlear Implant Candidates: A Prospective Study Comparing Candidates Carrying the p.Pro51Ser Mutation in Coagulation Factor C Homology With Noncarriers
Authors: Beerten Anneleen , Bosmans Helena , Lauwers Meindert , Vermeulen Helene , Janssens de Varebeke Sebastien Pierre
Published: August 2022

Background

DFNA9 is a form of autosomal progressive sensorineural hearing loss, caused by more than 30 variants in the COCH gene. p.Pro51Ser (p.P51S) variant is characterized by late-onset functional deterioration toward bilateral severe hearing loss and vestibulopathy. Focal sclerosis on computed tomography (CT) and T2-weighted magnetic resonance imaging (MRI) signal loss of semicircular canals are presumably radiologic biomarkers of advanced otovestibular deterioration.

Objectives

The aim of this study was to investigate whether these biomarkers are more frequent in cochlear implant candidates carrying the p.P51S mutation versus noncarriers. Second, the correlation between the hearing and vestibular function and carrier status was studied. Finally, the relationship between the presence of these radiologic features and the degree of hearing and vestibular deterioration was investigated.

Methods

A prospective cohort study was performed on 38 candidates for cochlear implantation in a tertiary referral center. Patients underwent pure tone audiometry, videonystagmography, video head impulse tests and vestibular-evoked myogenic potentials. In addition, three dizziness questionnaires were used. All subjects were administered CT, MRI, and molecular genetic analysis.

Results

Sixteen of 38 patients were carriers of the p.P51S COCH mutation. Radiologic lesions were almost exclusively observed in carriers. MRI was more sensitive in showing lesions than CT. Furthermore, p.P51S carriers showed significantly lower function on most vestibular tests, including questionnaires, than noncarriers. Patients with imaging abnormalities showed more pronounced vestibulopathy.

Conclusion

The present study supplements previous data that endorse the hypothesis that focal sclerosis of semicircular canals are biomarkers of advanced vestibular deterioration, especially in DFNA9.
Targeted Mutational Profiling Reveals Clonal Relationships in Metachronous Occurrence of Classic Hodgkin and Mediastinal Large B-Cell Lymphomas
Authors: Singh Kunwar , Lezama Lhara S. , Kurzer Jason , Oak Jean , Schultz Liora M. , Walkush Ann , Cheng Tse-Chang , Chen Everett H. , May William A. , Chang Cheryl , Link Michael P. , Advani Ranjana H. , Suarez Carlos J. , Natkunam Yasodha
Published: August 2022

Classic Hodgkin lymphoma (CHL) patients may infrequently present with a prior or recurrent disease with discordant histology resembling non-Hodgkin lymphomas. These include primary mediastinal large B-cell lymphoma (PMBL), diffuse large B-cell lymphoma (DLBCL), or mediastinal gray-zone lymphoma (MGZL). Such patients are often refractory to standard therapy and their diagnosis is hampered by significant morphologic and immunophenotypic overlap and insufficient molecular data. Among 509 CHL patients seen at an academic medical center, 6 patients had a prior or subsequent diagnosis different from CHL. Paired tissue samples were evaluated by targeted mutational analysis using a 164-gene panel. Our findings show multiple shared variants indicative of a clonal relationship between the CHL and the PMBL, DLBCL, or MGZL diagnoses. Most frequent mutated genes included TNFAIP3 (4 of 6, 66.7%), STAT6 (3 or 6, 50%), ARID1A (3 of 6, 50%), and XPO1 (3 of 5, 60%). Three patients showed the same oncogenic variant within the XPO1 gene (E571K), and mutations in TNFAIP3 and B2M were observed in 2 of the 5 patients with shared variants. In addition, differences in the mutation profile between the lymphoma pairs were also observed, which could represent clonal evolution. Mutational profiling could be of benefit in patients with recurrent/refractory disease with discordant histology, where the clonal relationship could be helpful to inform and guide therapeutic decisions. These findings provide further evidence of a true biological continuum surrounding CHL, PMBL, DLBCL, and MGZL and shed light on underlying genetic events and their clinical impact.
Dataset for the Reporting of Merkel Cell Carcinoma
Authors: Busam Klaus J. , Judge Meagan J. , Bichakjian Christopher K. , Coit Daniel , Kutzner Heinz , Requena Luis , Scolyer Richard A. , Stefanato Catherine M. , Wood Benjamin A. , Walsh Noreen M.
Published: August 2022

Accurate and complete pathology reports are critical for the optimal management of cancer patients. Protocols for the pathologic reporting of Merkel cell carcinoma (MCC) have been developed independently by the Royal College of Pathologists (UK) and the College of American Pathologists. In this study, data elements for pathologic reporting of MCC were analyzed by an international panel of pathologists and clinicians with the aim of developing a common, internationally agreed upon dataset useful for clinical practice. The International Collaboration on Cancer Reporting expert review panel developed a protocol containing “core” (required) and “noncore” (recommended) elements. Core elements were defined as those that had evidentiary support and were unanimously agreed upon by the review panel as essential for the clinical management, staging, and/or assessment of prognosis in patients with MCC. Noncore elements were those considered to be clinical of interest, but with lesser degrees of supportive evidence or nonactionable implications. Ten core data elements for pathology reports on primary MCC were defined. Development and agreement on this evidence-based protocol at an international level was accomplished in a timely and efficient manner. The template developed for melanoma reporting was used as a structural base for this initiative. It is applicable to, and may facilitate the development of, protocols for other tumor types. Widespread utilization of an internationally agreed upon structured pathology dataset for MCC can be expected to lead to improved patient management. It should also facilitate collaborative clinical research.
Characteristics of Pediatric Nasal Foreign Body Cases That Required Multiple Removal Procedures
Authors: Kawaguchi Risa , Matsui Satoshi , Hayashi Takuro , Takei Hirokazu , Tanizawa Naoko , Ohnishi Yasuhiro , Sameshima Tomohiro , Miyawaki Kousuke , Yoshii Takuma Henry , Tanaka Ryojiro
Published: August 2022

Objectives

Removal of nasal foreign bodies in children should be completed as few numbers of times as possible to reduce the burden on the child. This study aimed to reveal the characteristics of pediatric nasal foreign body cases that required multiple removal procedure and to investigate the appropriate removal method for each shape of foreign body.

Methods

We retrospectively reviewed patients who visited a pediatric emergency department because of nasal foreign body from November 1, 2018, to October 31, 2020. We compared the characteristics of patients, foreign bodies, and treatment between the success and failure groups in the first removal procedure. Moreover, we described the detail of patients in the failure group. We also showed final successful removal methods according to the shape of the foreign bodies.

Results

We included 104 children in our analysis. Between the success and failure groups in the first removal procedure, there was no statistically significant difference in the characteristics of patients and foreign bodies but a significant difference in the removal method (P < 0.001). In the failure groups, the most frequent number of times required for removal is 2 and the most common methods in the first removal procedure was the parent's kiss, most of which were performed on spherical foreign bodies in younger children, Finally, only 7 cases (6.7%) failed to remove the foreign body. According to the shape of the foreign bodies, the percentage of forceps and clamps used for successful removal was high in every shape.

Conclusions

There was a significant difference in the removal method between the success and failure groups in the first removal procedure, but finally, most foreign bodies were removed by emergency physicians. Therefore, further research is needed to determine the appropriate removal method for each patient and foreign body.
Proinflammatory and cardiovascular biomarkers are associated with echocardiographic abnormalities in children with HIV taking antiretroviral therapy
Authors: Majonga Edith D. , Yindom Louis-Marie , Hameiri-Bowen Dan , Mayini Justin , Rehman Andrea M. , Kaski Juan P. , Mujuru Hilda A. , Rowland-Jones Sarah L. , Ferrand Rashida A.
Published: August 2022

Objectives:

Children with perinatally acquired HIV (PHIV) and taking antiretroviral therapy (ART) have a high prevalence of subclinical cardiac disease. We hypothesized that cardiac disease may be a consequence of dysregulated systemic immune activation driven by HIV infection. We examined cardiovascular and proinflammatory biomarkers and their association with echocardiographic abnormalities in children with PHIV.

Design:

Cross-sectional analysis of soluble biomarkers from a prospective cohort of children aged 6–16 years with PHIV and age-matched HIV-uninfected comparison group.

Methods:

Cryopreserved plasma samples were used to measure seven soluble biomarkers using multiplex bead assay (Luminex). Multivariable logistic regression assessed how biomarker levels related to cardiac abnormalities.

Results:

A total of 406 children participated in this study (195 PHIV and 211 HIV-uninfected). Mean [standard deviation (SD)] ages of PHIV and HIV-uninfected participants were 10.7 (2.6) and 10.8 (2.8) years, respectively. Plasma levels of CRP, TNF-α, ST2, VCAM-1 and GDF-15 were significantly higher in the PHIV group compared with uninfected control (P < 0.001). Among children with PHIV, with one-unit representing one SD in biomarker level, a one-unit increase in CRP and GDF-15, was associated with increased odds of having left ventricular (LV) diastolic dysfunction [adjusted odds ratio (aOR), 1.49 (1.02–2.18; P < 0.040)] and [aOR 1.71 (1.18–2.53; P = 0.006)], respectively. Each one unit increase in GDF-15 was associated with increased odds of LV hypertrophy [aOR 1.84 (95% CI 1.10–3.10; P < 0.021)].

Conclusion:

Children with PHIV had higher levels of proinflammatory and cardiovascular biomarkers compared with HIV-uninfected children. Increased CRP and GDF-15 were associated with cardiac abnormalities in children with PHIV.
The Orbital Bones Protect the Globe From Sharp Periorbital Trauma Injuries
Authors: Nemet Arie Y.
Published: August 2022

Background:

The bones of the orbit hold the globe and periocular structures and protect it and other periocular contents. This has been shown in blowout orbital fractures, as well as in high-energy injuries to the periorbital region. However, there is little information regarding how the orbital bones protect the globe after periorbital trauma from sharp objects.

Objectives:

This study reports 4 cases of traumatic injury from sharp objects to the periorbital area and eyelids to demonstrate the protective features of the orbital bones.

Results:

The anatomy of the periorbital bones clearly protected the globe from direct trauma in all the 4 cases.

Conclusions:

There was no harm to the orbit or visual impairment after the successful treatment with definitive surgery.
Safe Region of Craniotomy to Access the Cerebellopontine Region by Retrosigmoid Approach: A Radiological and Anatomical Study
Authors: Cheng Ye , Song Yiming , Wei Yukui , Geng Haoming , Wu Xiaolong , Li Mingchu , Liang Jiantao , Song Gang
Published: August 2022

Accurately positioning the sigmoid sinus (SS), transverse sinus (TS), and vertebral artery (VA) is significantly important during the retrosigmoid (RS) approach. This study aimed to use emissary vein and digastric point as landmarks in high-resolution computer topographic image to locate the SS, TS, and VA to help surgeons to avoid injuring these vascular structures during RS craniotomy. Computed topographic (CT) angiography images of 107 individuals were included, the measurement was performed on coronal, sagittal, and axis planes after the multiplanar reformation. Distance from the emissary vein and digastric point to the posterior boundary of the SS, inferior boundary of the TS were measured by CT angiography preoperatively and in the skull intraoperatively. The VA was also located by emissary vein and digastric point. No significant difference was identified between the distances measured in the CT and skull. Our findings provide anatomical information for locating the boundary of the SS, TS, and V3–VA based on the fixed bony landmarks. Verified by skull measurement, high-resolution CT scan is a cost-effective and reliable tool for identifying the location of the arteries and sinus, which could be widely used to guarantee the safety of RS approach craniectomy.
Behavioral, Learning Skills, and Visual Improvement in Crouzon Syndrome Patient Following Late Posterior Vault Distraction Osteogenesis
Authors: Raposo-Amaral Cassio E. , Menezes Priscila T. , Gil André , Raposo-Amaral Cesar A. , Ghizoni Enrico
Published: August 2022

Background:

It is well accepted among craniofacial surgeons that surgery does not improve mental status but does prevent worsening or deterioration of cognitive and mental function. In this report, we describe significant improvement in behavioral, learning skills and visual acuity for a Crouzon patient who underwent late posteriorvault distraction osteogenesis.

Methods:

A 9-year-old Crouzon patient was referred to our hospital, presenting severe intracranial hypertension. The patient had previously undergone a strip craniectomy in early infancy at another medical institution, but there was no subsequent follow-up. Magnetic resonance imaging showed Chiari type I malformation and fundoscopy revealed papilledema. At the time of referral, the patient was not attending a regular school, had not acquired reading skills, was unable to concentrate, and could not accomplish school-related tasks that were standard for children in his age group.

Results:

The patient underwent posterior vault distraction osteogenesis and showed concentration improvement and acquisition of fluent reading skills. Chiari type I malformation resolved as well as papilledema. visual acuity improved at Snellen test preoperatively from 20/200 to 20/60 at postoperative test. Ventricle size remained unchanged subsequent to performance of the posterior cranial vault distraction. The occipital veins were less visible upon clinical examination and less pronounced when palpated, and the bruit had completely disappeared.

Conclusion:

Late posterior vault distraction osteogenesis can improve behavioral, learning skills and visual acuity as shown in this 9-year-old Crouzon patient.
Professional Coaching and Surgeon Well-being
Authors: Dyrbye Liselotte N. , Gill Priscilla R. , Satele Daniel V. , West Colin P.
Published: August 2022

Objective:

To determine if individualized professional coaching reduces burnout, improves quality of life, and increases resilience among surgeons.

Background:

Burnout is common among surgeons and associated with suboptimal patient care and personal consequences.

Methods:

A randomized controlled trial of 80 surgeons evaluating the impact of 6 monthly professional coaching sessions on burnout (Maslach Burnout Inventory), quality of life (single-item linear analog scale), and resilience (Connor-Davidson Resilience Scale) immediately postintervention and 6 months later. Participants randomized to the control group subsequently received 6 professional coaching sessions during months 6 to 12 (delayed intervention).

Results:

At the conclusion of professional coaching in the immediate intervention group, the rate of overall burnout decreased by 2.5% in the intervention arm compared with an increase of 2.5% in the control arm [delta: −5.0%, 95% confidence interval (CI): −8.6%, −1.4%; P=0.007]. Resilience scores improved by 1.9 points in the intervention arm compared with a decrease of 0.2 points in the control arm (delta: 2.2 points; 95% CI: 0.07, 4.30; P=0.04). Six months after completion of the coaching period, burnout had returned to near baseline levels while resilience continued to improve among the immediate intervention group. The delayed intervention group experienced improvements in burnout during their coaching experience relative to the immediate intervention group during their postintervention period (18.2% decrease vs 2.9% increase, delta: −21.1%, 95% CI: −24.9%, −17.3%; P<0.001).

Conclusions:

Professional coaching over 6 months improved burnout and resilience among surgeons, with reductions in improvement over the ensuing 6 months.
Women Leadership in Liver Transplantation—Results of an International Survey
Authors: de Rosner – van Rosmalen Marieke , Adelmann Dieter , Berlakovich Gabriela A. , Francoz Claire , Selzner Nazia , Berenguer Marina , Watt Kymberly D. , Man Nancy Kwan , Burra Patrizia , Pai Sher-Lu
Published: August 2022

Background.

The International Liver Transplantation Society (ILTS) has placed a strong focus on achieving gender equality and equity in liver transplant (LT). We aimed to understand gender distribution in leadership positions among LT physicians around the world and within ILTS.

Methods.

In 2019, the ILTS Equality, Diversity, and Inclusion Committee distributed a survey to obtain granular data on gender and characteristics of transplant physicians as well as those in leadership positions in each center. Additionally, data were collected on the gender composition of the ILTS membership, council, chairpersons, and committees and from the United Network for Organ Sharing.

Results.

Data were collected from 243 transplant centers. Thirty-two (13.2%) had at least 1 woman as the director of LT, chief of transplant surgery, or chief of transplant hepatology. Of the 243 centers, 133 reported the age and gender of the leadership personnel. Women physicians comprised 152 of the 833 transplant surgeons (18.2%) and 298 of the 935 hepatologists (31.9%). Among the 1331 ILTS physician members, 588 (44.2%) provided gender information in their member profiles, and 155 (26.3%) identified themselves as women. Of the 26 ILTS leadership positions, 7 (26.9%) were held by women.

Conclusions.

This analysis of worldwide gender distribution in the LT physician workforce showed notable gender disparity in LT leadership around the globe and within the ILTS. These data provide a launching point for promoting and achieving gender equality and equity in LT.
Paul Jozef Crutzen. 3 December 1933—28 January 2021
Authors: Müller Rolf
Published: August 2022

Paul J. Crutzen was both a warm-hearted person and a brilliant scientist. His research interests were broad, encompassing topics of relevance in the mesosphere, the stratosphere and the troposphere. He made fundamental scientific contributions to a wide range of topics in the science of all these atmospheric regions. For example, he first described the NO

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-driven ozone loss cycle in the stratosphere, he contributed key ideas on how to explain the ‘ozone hole’ and he made fundamental discoveries on the impact of biomass-burning on the atmosphere. Understanding and combating the origins of air pollution and climate change were driving motivations for his life's work. Further, he pioneered the concept that is known as ‘nuclear winter’, he initiated the resumption of discussion on geoengineering, and coined the term ‘Anthropocene’. In 1995, together with Mario J. Molina and F. Sherwood Rowland (ForMemRS 2004), Paul was awarded the Nobel Prize in chemistry for ground-breaking work ‘in atmospheric chemistry, particularly concerning the formation and decomposition of ozone’. With all this focus on science, he did not forget the importance of private life, regarding both his family and his colleagues and students. Finally, Paul's work had a profound influence not only on the scientific world, but also on different aspects of environmental politics throughout many countries. His works on the impact of human activities on the atmosphere and climate have been influential in the past and are influential today. They provide a beacon of knowledge for the next generations of scientists and environmental policymakers.
Effects of parental drought on offspring fitness vary among populations of a crop wild relative
Authors: Matesanz Silvia , Ramos-Muñoz Marina , Rubio Teso María Luisa , Iriondo José María
Published: August 2022

Transgenerational plasticity is a form of non-genetic inheritance that can reduce or enhance offspring fitness depending on parental stress. Yet, the adaptive value of such parental environmental effects and whether their expression varies among populations remain largely unknown. We used self-fertilized lines from climatically distinct populations of the crop wild relative
Lupinus angustifolius.
In the parental generation, full-siblings were grown in two contrasting watering environments. Then, to robustly separate the within-generation and transgenerational response to drought, we reciprocally assigned the offspring of parents to the same experimental treatments. We measured key functional traits and assessed lifetime reproductive fitness. Offspring of drought-stressed parents produced less reproductive biomass, but a similar number of lighter seeds, in dry soil compared to offspring of genetically identical, well-watered parents, an effect not mediated by differences in seed provisioning. Importantly, while the offspring of parents grown in the favourable environment responded to drought by slightly increasing individual seed mass, the pattern of plasticity of the offspring of drought-grown parents showed the opposite direction, and the negative effects of parental drought on seed mass were more pronounced in populations from cooler and moist habitats. Overall, our results show that parental effects may override immediate adaptive responses to drought and provide evidence of population-level variation in the expression of transgenerational plasticity.