bluuebunny/crossref_metadata_2025 huggingface dataset:
Dronedarone vs. placebo in patients with atrial fibrillation or atrial flutter across a range of renal function: apost hocanalysis of the ATHENA trial
Authors: Vamos Mate , Oldgren Jonas , Nam Gi-Byoung , Lip Gregory Y H , Calkins Hugh , Zhu Jun , Ueng Kwo-Chang , Ludwigs Ulf , Wieloch Mattias , Stewart John , Hohnloser Stefan H
Published: December 2021

Aims

Use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is challenging owing to issues with renal clearance, drug accumulation, and increased proarrhythmic risks. Because CKD is a common comorbidity in patients with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish the efficacy and safety of AAD treatment in patients with CKD.

Methods and results

Dronedarone efficacy and safety in individuals with AF/AFL and varying renal functionality [estimated glomerular filtration rate (eGFR): ≥60, ≥45 and <60, and <45 mL/min] was investigated in a post hoc analysis of ATHENA (NCT00174785), a randomized, double-blind trial of dronedarone vs. placebo in patients with paroxysmal or persistent AF/AFL plus additional cardiovascular (CV) risk factors. Log-rank testing and Cox regression were used to compare the incidence of endpoints between treatments. Overall, 4588 participants were enrolled from the trial. There was no interaction between treatment group and baseline eGFR assessed as a continuous variable (P = 0.743) for the first CV hospitalization or death from any cause (primary outcome). This outcome was lower with dronedarone vs. placebo across a wide range of renal function. First CV hospitalization and first AF/AFL recurrence were both lower in the two least renally impaired subgroups with dronedarone vs. placebo. Treatment emergent adverse events leading to treatment discontinuation were more frequent with dronedarone vs. placebo and occurred more often in patients with severe renal impairment.

Conclusion

Dronedarone is an effective AAD in patients with AF/AFL and CV risk factors across a wide range of renal function.
Changes in balance due to mild lateral ankle sprain measured by parts of the JESS-Score: a case report
Authors: Loudovici-Krug Dana , Kießhauer Susan , Best Norman
Published: December 2021

Background

By chance, one participant of a norm value study concerning the Jenaer-Standing-Stability-Score (JESS-Score) could be measured before and after a lateral ankle sprain (LAS, Grade I). Therefore, a complete comparison of the initial function, the situation after the LAS and even after additional therapy with focus on balance and postural control, was possible.

Case presentation

A 34-year-old woman, working as medical doctor was measured her standing stability by use of the JESS-Score. A few weeks after, she experienced a mild LAS. There was no physical therapy in the first 3 months after the LAS. In the following, the patient received 7 sessions of physical therapy with focus on balance and postural control. The 2 used parts of the stability assessment (JESS-Score: 1—unipedal stance test; 2—target-step-test) changed in the course of time. Before the ankle sprain both tests on balance and postural control reached the standard value and were inconspicuous. There was no medically prescribed therapy due to the LAS, based on the minor complaints. However, after the LAS the number of deviating test items increased and was even 6 weeks and 3 months after the LAS inconsistent. Only after additional physiotherapy, the score result improved to the initial situation again.

Conclusions

It is assumable that LAS is associated with postural deterioration. Therefore, the effect of exercises focussing on postural control and balance after lateral ankle sprain, even if only mild, should be investigated. Some items of the JESS-Score seem to be sensitive for evaluating changes concerning the balance ability.
Single-Step Genomic Analysis Increases the Accuracy of Within-Family Selection in a Clonally Replicated Population ofPinus taedaL.
Authors: Walker Trevor D , Cumbie W Patrick , Isik Fikret
Published: December 2021

The use of genomic markers in forest tree breeding is expected to improve the response to selection, especially within family. To evaluate the potential improvements from genotyping, we analyzed a large Pinus taeda L. clonal population (1,831 cloned individuals) tested in multiple environments. Of the total, 723 clones from five full-sib families were genotyped using 10,337 single-nucleotide polymorphism markers. Single-step models with genomic and pedigree-based relationships produced similar heritability estimates. Breeding value predictions were greatly improved with inclusion of genomic relationships, even when clonal replication was abundant. The improvement was limited to genotyped individuals and attributable to accounting for the Mendelian sampling effect. Reducing clonal replication by omitting data indicated that genotyping improved breeding values similar to clonal replication. Genomic selection predictive ability (masking phenotypes) was greater for stem straightness (0.68) than for growth traits (0.41 to 0.44). Predictive ability for a new full-sibling family was poorer than when full-sibling relationships were present between model training and validation sets. Species that are difficult to propagate clonally can use genotyping to improve within-family selection. Clonal testing combined with genotyping can produce breeding value accuracies adequate to graft selections directly into deployment orchards without progeny testing.
Assessing Health Care Use Trajectories After the Onset of Functional Disability: Application of a Group-Based Trajectory Model
Authors: Ankuda Claire K , Ornstein Katherine A , Kelley Amy S
Published: December 2021

Objectives

While older adults with activity limitations have high levels of health care use, we do not know how this varies over time. We aimed to assess trajectories of Emergency Department (ED) use and hospitalization after the onset of receipt of help with self-care or mobility.

Methods

We used the 2011–2017 National Health Aging Trends Study (NHATS) linked to Medicare claims to identify a cohort of older adults who began to receive help with self-care or mobility in the past year. Primary outcome was the quarterly rates of ED use and/or hospitalization over the 24 months following the onset of receiving help. We fit a Group-Based Trajectory Model to identify the trajectories of ED use or hospitalization and assessed the association of characteristics preceding and concurrent to the onset of help with trajectory group membership.

Results

Among 1,687 NHATS respondents newly receiving help with self-care/mobility, health care use escalated and then immediately fell. We found distinct trajectories of ED use and hospitalization: delayed rise (13.5%), falling (26.2%), and persistent (60.4%). Trajectory group membership was predicted by clinical, economic, and regional characteristics; and the individuals in each group differed in terms of concurrent new illnesses and degree of disability.

Discussion

While activity limitations are a strong predictor of health care use among older adults, trajectories of health care use are heterogeneous. Along with clinical characteristics, potentially modifiable household and regional factors shaped health care trajectories, indicating that addressing these factors could potentially shift health care use patterns.
10-Year Trend of Abdominal Magnetic Resonance Imaging Compared With Abdominal Computed Tomography Scans in Inflammatory Bowel Disease
Authors: Shah Raj , Elangovan Abbinaya , Jordan David W , Katz Jeffry , Cooper Gregory S
Published: December 2021

Background

Patients with inflammatory bowel disease (IBD) frequently undergo multiple computed tomography (CT) examinations. With the widespread availability of magnetic resonance imaging (MRI), it is unclear whether the use of CTs in IBD has declined. We aimed to analyze the trends of CT and MRI use in a large cohort of IBD patients in a 10-year period.

Methods

We retrospectively analyzed adults ≥18 years of age using a de-identified database, IBM Explorys. Patients with ≥1 CT of the abdomen (± pelvis) or MRI of the abdomen (± pelvis) at least 30 days after the diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) were included. We examined the factors associated with patients undergoing multiple CTs (≥5 CTs of the abdomen) and performed a trend analysis from 2010 to 2019.

Results

Among 176 110 CD and 143 460 UC patients, those with ≥1 CT of the abdomen annually increased from 2010 to 2019 with mean annual percentage change of +3.6% for CD and +4.9% for UC. Similarly, annual percentage change for patients with ≥1 MRI (CD: +15.6%; UC: +22.8%) showed a rising trend. There was a 3.8% increase in CD patients receiving ≥5 CTs of the abdomen annually compared with a 2.4% increase among UC patients in the 10-year period. Age ≥50 years, men, African Americans, public insurance payors, body mass index ≥30kg/m2, and smoking history were associated with ≥5 CTs.

Conclusions

There is a considerable increase in the number of CT scans performed in IBD patients. Further studies can explore factors influencing the use of CT and MRI of the abdomen in IBD patients.
Successful redo aortic valve replacement using Perceval for multiple recurrent prosthetic valve dysfunction
Authors: Kakizawa Yumi , Nishi Hiroyuki , Goto Takasumi , Kitahara Mutsunori
Published: December 2021

A 50-year-old man who required aortic valve replacement (AVR) 3 times for severe paravalvular leakage (PVL) was diagnosed with a recurrence of severe PVL. Since the PVL recurred each time because of prosthetic valve detachment from the annulus, a fourth AVR was performed using a self-expanding sutureless valve. Postoperative echocardiography showed no significant PVL. The patient was discharged without any complications and returned to normal work soon after. In cases such as our patient, sutureless AVR could be a powerful alternative to conventional AVR.
Knowledge of surgical management of hyperhidrosis among primary care physicians and the general public
Authors: Lee Andy Chao Hsuan , Ferguson Mark K
Published: December 2021

OBJECTIVES

Our study examined attitudes towards initial management of hyperhidrosis, willingness to seek surgical consultation and knowledge of an appropriate specialty for surgical consultation among primary care physicians and the general public.

METHODS

An online survey was sent to all general medicine and paediatric residents and attending physicians at our academic medical centre. Participants were provided with a clinical scenario of palmar hyperhidrosis and were asked to select among initial management options and preferences for surgical consultation if patients failed non-operative management. To assess the general public’s perspective, workers from Amazon Mechanical Turk were recruited to complete a similar survey.

RESULTS

The majority of primary care physicians (31/53; 58%) would prescribe topical aluminium chloride for palmar hyperhidrosis, whereas 28 of 53 (53%) would refer such patients to dermatology. Twenty-three of 53 (43%) physicians would refer such patients to surgery if conservative management failed: 18 (78%) to plastic surgery, 4 (17%) to general surgery and none to thoracic surgery. The majority of workers (130/205; 63.4%) would seek primary care treatment for palmar hyperhidrosis. Over half (113/205; 55%) would seek surgical consultation if conservative management failed: 65 (58%) general surgery and 15 (13%) neurosurgery, with only 8 (7%) selecting thoracic surgery.

CONCLUSIONS

Neither primary care physicians nor the general public recognize the role of thoracic surgeons in managing primary focal hyperhidrosis when medical management fails. Education of physicians and the public may mitigate this knowledge gap.
Differential Potency of Venlafaxine, Paroxetine, and Atomoxetine to Inhibit Serotonin and Norepinephrine Reuptake in Patients With Major Depressive Disorder
Authors: Aldosary Fahad , Norris Sandhaya , Tremblay Philippe , James Jonathan S , Ritchie James C , Blier Pierre
Published: December 2021

Background

Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter (NET) remained to be determined. Paroxetine is generally considered as a selective 5-HT reuptake inhibitor but exhibits some affinity for NET. Atomoxetine is a NET inhibitor but also has some affinity for the 5-HT reuptake transporter (SERT).

Methods

This study examined the effects of forced titration of venlafaxine from 75 to 300 mg/d, paroxetine from 20 to 50 mg/d, or atomoxetine from 25 to 80 mg/d in 32 patients with major depressive disorder. Inhibition of SERT was estimated using the depletion of whole-blood 5-HT. Inhibition of NET was assessed using the attenuation of the systolic blood pressure produced by i.v. injections of tyramine.

Results

All 3 medications significantly reduced 5-HT levels at the initiating regimens: venlafaxine and paroxetine by approximately 60% and atomoxetine by 16%. The 3 subsequent regimens of venlafaxine and paroxetine reduced 5-HT levels by over 90%, but the highest dose of atomoxetine only reached a 40% inhibition. Atomoxetine dose dependently inhibited the tyramine pressor response from the lowest dose, venlafaxine from 225 mg/d, and paroxetine left it unaltered throughout.

Conclusion

These results confirm that venlafaxine and paroxetine are potent SERT inhibitors over their usual therapeutic range but that venlafaxine starts inhibiting NET only at 225 mg/d, whereas paroxetine remains selective for SERT up to 50 mg/d. Atomoxetine dose dependently inhibits NET from a low dose but does not inhibit SERT to a clinically relevant degree.
A Criterion for Decomposabilty in QYBE
Authors: Camp-Mora Sergio , Sastriques Raúl
Published: December 2021

In this paper, set theoretic solutions of the Quantum Yang–Baxter Equations are considered. Etingof et al. [ 8] defined the structure group for non-degenerate solutions and gave some properties of this group. In particular, they provided a criterion for decomposability of involutive solutions based on the transitivity of the structure group. In that paper, the diagonal permutation $T$ is also introduced. It is known that this permutation is trivial exactly when the solution is square free. Rump [ 12] proved that these solutions are decomposable except in the trivial case. Later, Ramirez and Vendramin [ 11] gave some criteria for decomposability related with the diagonal permutation $T$. In this paper it was proven that an involutive solution is decomposable when the number of symbols of the solution and the order of the diagonal permutation $T$ are coprime.
Estimating the effects of race and social vulnerability on hospital admission and mortality from COVID-19
Authors: Landman Joshua M , Steger-May Karen , Joynt Maddox Karen E , Hammond Gmerice , Gupta Aditi , Rauseo Adriana M , Zhao Min , Foraker Randi E
Published: December 2021

Objective

To estimate the risk of hospital admission and mortality from COVID-19 to patients and measure the association of race and area-level social vulnerability with those outcomes.

Materials and Methods

Using patient records collected at a multisite hospital system from April 2020 to October 2020, the risk of hospital admission and the risk of mortality were estimated for patients who tested positive for COVID-19 and were admitted to the hospital for COVID-19, respectively, using generalized estimating equations while controlling for patient race, patient area-level social vulnerability, and time course of the pandemic.

Results

Black individuals were 3.57 as likely (95% CI, 3.18–4.00) to be hospitalized than White people, and patients living in the most disadvantaged areas were 2.61 times as likely (95% CI, 2.26–3.02) to be hospitalized than those living in the least disadvantaged areas. While Black patients had lower raw mortality than White patients, mortality was similar after controlling for comorbidities and social vulnerability.

Discussion

Our findings point to potent correlates of race and socioeconomic status, including resource distribution, employment, and shared living spaces, that may be associated with inequitable burden of disease across patients of different races.

Conclusions

Public health and policy interventions should address these social factors when responding to the next pandemic.
Mapping the Use of Open Source Research in UN Human Rights Investigations
Authors: Murray Daragh , McDermott Yvonne , Koenig K Alexa
Published: December 2021

Open source information, particularly digital open source information that is publicly available on the internet, plays an increasingly central role in the landscape of human rights investigations. This article provides a thorough analysis of how open source information is used in practice by UN human rights fact-finding missions, commissions of inquiry and other official human rights investigations. Combining data from semi-structured interviews carried out with investigators with specific experience in open source human rights investigations with a review of reports and other primary and secondary sources, it examines the utility of open source information to UN human rights investigative bodies. It posits that open source research can offer tremendous benefits in planning investigations, supplying lead evidence, and providing direct evidence of violations, thereby overcoming some of the access barriers that investigators face, and potentially giving voice to a wider range of perspectives. On the other hand, this article argues that open source investigations should be approached with a clear eye to their challenges and possible pitfalls. These include the gaps of open source information and the potential to silence already-marginalized communities through open source investigations, as well as the resource-intensive nature of these investigations, the danger that open source information can affect witnesses’ perceptions, and the risks posed by online disinformation. As open source research is likely to comprise an important component of the human rights investigator’s toolbox in the future, this article argues in favour of the institutional buy-in, resourcing, and methodological rigour that it deserves.
Growing judicial support for a ‘Formstein’ defence in English patent litigation
Authors: Pendock Bethany , Kakkaiyadi Krishna , Taylor Sarah
Published: December 2021

Facebook Ireland Limited v Voxer IP LLC [2021] EWHC 1377 (Pat), 26 May 2021

The English Patents Court has considered the effects of a Formstein defence in the context of an infringement argument based on the doctrine of equivalents and has opined that a successful Formstein defence should result in a finding of non-infringement rather than a finding that the patent is invalid.
A novel method for skin marking in radiotherapy: first clinical use of temporary organic tattoo seal
Authors: Goto Masaaki , Oshiro Yoshiko , Tamaki Yoshio , Ishida Toshiki , Kato Yuichi , Shinoda Kazuya , Sakurai Hideyuki
Published: December 2021

An oil-based pen is widely used as a skin marker for identification of the isocenter and computed tomography (CT)-coordinate origin during radiotherapy. However, use of this pen has some disadvantages, including color loss and color migration. To address these problems, we have developed use of a temporary fashion tattoo (Inkbox) for skin marking. The utility and feasibility of Inkbox as an alternative to an oil-based pen were evaluated in this study. The study included patients from two centers who required skin marking for radiotherapy performed between December 2020 and March 2021. Skin markings were made with an oil-based pen or with Inkbox. The durability was recorded during daily irradiation. Skin markings with Inkbox were made in 32 patients. The total number of skin markings was 94: 64 with Inkbox and 30 with an oil-based pen. A questionnaire survey to evaluate each method was conducted among patients after radiotherapy. The median durations of marking were 16 and 4 days with Inkbox and an oil-based pen, respectively (p-value < 0.001). The survey showed that Inkbox had less impact on the daily lives of patients, including reduced color migration to clothes and less concern about disappearance of the marking. There were no adverse cutaneous side effects with Inkbox. The duration of marking with Inkbox is about 16 days, with little impact on daily life. These findings suggest that Inkbox is a potentially useful method of skin marking in radiotherapy.
Scarless total thyroidectomy via transoral endoscopic vestibular approach: initial case series in a developing Asian country
Authors: Yap Ralph Victor , Villamor Jr Manuel
Published: December 2021

Conventional open thyroidectomy may leave a visible scar postoperatively and can lead to impaired quality of life. Since 2016, the transoral endoscopic thyroidectomy via vestibular approach (TOETVA) has gained popularity due to being a true ‘scarless’ procedure. However, minimally invasive thyroidectomy has not been widely adopted in the Philippines yet. From August 2019 to December 2019, nine patients (mean thyroid nodule size of 3.1 cm) underwent TOETVA with one open conversion due to adherent papillary cancer. Majority had a blood loss of <100 ml, whereas mean operative time was 149.8 ± 20.5 minutes. Five patients developed hypocalcemia (three transient), whereas two patients reported transient lower lip numbness. TOETVA is a safe and feasible novel procedure for both benign and malignant thyroid diseases. Care must be taken in selecting patients who opt for TOETVA, and that surgeons should reassess their limitations before implementing this technique in their surgical practice.
Appendicitis and ganglioneuroma—an unusual co-existence
Authors: Koullouros Michalis , Candler Sarah , Smith Caroline , Olakkengil Santosh
Published: December 2021

Ganglioneuromas are benign, fully differentiated mature tumours related to neuronal tissues and usually seen in the gastrointestinal tract, retroperitoneum and mediastinum. The few cases of appendiceal ganglioneuromas that were previously described in the literature belong to the paediatric population and were associated with genetic mutations and syndromes. We present a unique case of an Aboriginal Australian adult with acute appendicitis and concurrent ganglioneuroma diagnosed using histopathology and immunohistochemistry using Neu-N, S100 and Sox-10. The patient had no history of any of the syndromes associated with ganglioneuromatosis and had no other relevant family history.
Cytosolic fumarase acts as a metabolic fail-safe for both high and low temperature acclimation ofArabidopsis thaliana
Authors: Saunders Helena A , Calzadilla Pablo I , Schwartz Jean-Marc , Johnson Giles N
Published: December 2021

Plants acclimate their photosynthetic capacity (Pmax) in response to changing environmental conditions. In Arabidopsis thaliana, photosynthetic acclimation to cold requires the accumulation of the organic acid fumarate, catalysed by a cytosolically localized fumarase, FUM2. However, the role of this accumulation is currently unknown. Here, we use an integrated experimental and modelling approach to examine the role of FUM2 and fumarate across the physiological temperature range. We have studied three genotypes: Col-0; a fum2 mutant in a Col-0 background; and C24, an accession with reduced FUM2 expression. While low temperature causes an increase in Pmax in the Col-0 plants, this parameter decreases following exposure of plants to 30 °C for 7 d. Plants in which fumarate accumulation is partially (C24) or completely (fum2) abolished show a reduced acclimation of Pmax across the physiological temperature range (i.e. Pmax changes less in response to changing temperature). To understand the role of fumarate accumulation, we have adapted a reliability engineering technique, Failure Mode and Effect Analysis (FMEA), to formalize a rigorous approach for ranking metabolites according to the potential risk that they pose to the metabolic system. FMEA identifies fumarate as a low-risk metabolite, while its precursor, malate, is shown to be high risk and liable to cause system instability. We propose that the role of FUM2 is to provide a fail-safe in order to control malate concentration, maintaining system stability in a changing environment. We suggest that FMEA is a technique that is not only useful in understanding plant metabolism but can also be used to study reliability in other systems and synthetic pathways.
Quantification of radiation-induced DNA double strand break repair foci to evaluate and predict biological responses to ionizing radiation
Authors: Penninckx Sébastien , Pariset Eloise , Cekanaviciute Egle , Costes Sylvain V
Published: December 2021

Radiation-induced foci (RIF) are nuclear puncta visualized by immunostaining of proteins that regulate DNA double-strand break (DSB) repair after exposure to ionizing radiation. RIF are a standard metric for measuring DSB formation and repair in clinical, environmental and space radiobiology. The time course and dose dependence of their formation has great potential to predict in vivo responses to ionizing radiation, predisposition to cancer and probability of adverse reactions to radiotherapy. However, increasing complexity of experimentally and therapeutically setups (charged particle, FLASH …) is associated with several confounding factors that must be taken into account when interpreting RIF values. In this review, we discuss the spatiotemporal characteristics of RIF development after irradiation, addressing the common confounding factors, including cell proliferation and foci merging. We also describe the relevant endpoints and mathematical models that enable accurate biological interpretation of RIF formation and resolution. Finally, we discuss the use of RIF as a biomarker for quantification and prediction of in vivo radiation responses, including important caveats relating to the choice of the biological endpoint and the detection method. This review intends to help scientific community design radiobiology experiments using RIF as a key metric and to provide suggestions for their biological interpretation.
Characterization of the consensus mucosal microbiome of colorectal cancer
Authors: Zhao Lan , Grimes Susan M , Greer Stephanie U , Kubit Matthew , Lee HoJoon , Nadauld Lincoln D , Ji Hanlee P
Published: December 2021

Dysbioisis is an imbalance of an organ's microbiome and plays a role in colorectal cancer pathogenesis. Characterizing the bacteria in the microenvironment of a cancer through genome sequencing has advantages compared to culture-based profiling. However, there are notable technical and analytical challenges in characterizing universal features of tumor microbiomes. Colorectal tumors demonstrate microbiome variation among different studies and across individual patients. To address these issues, we conducted a computational study to determine a consensus microbiome for colorectal cancer, analyzing 924 tumors from eight independent RNA-Seq data sets. A standardized meta-transcriptomic analysis pipeline was established with quality control metrics. Microbiome profiles across different cohorts were compared and recurrently altered microbial shifts specific to colorectal cancer were determined. We identified cancer-specific set of 114 microbial species associated with tumors that were found among all investigated studies. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were among the four most abundant phyla for the colorectal cancer microbiome. Member species of Clostridia were depleted and Fusobacterium nucleatum was one of the most enriched bacterial species in tumors. Associations between the consensus species and specific immune cell types were noted. Our results are available as a web data resource for other researchers to explore (https://crc-microbiome.stanford.edu).
OLOGRAM-MODL: mining enrichedn-wise combinations of genomic features with Monte Carlo and dictionary learning
Authors: Ferré Quentin , Capponi Cécile , Puthier Denis
Published: December 2021

Most epigenetic marks, such as Transcriptional Regulators or histone marks, are biological objects known to work together in n-wise complexes. A suitable way to infer such functional associations between them is to study the overlaps of the corresponding genomic regions. However, the problem of the statistical significance of n-wise overlaps of genomic features is seldom tackled, which prevent rigorous studies of n-wise interactions. We introduce OLOGRAM-MODL, which considers overlaps between n ≥ 2 sets of genomic regions, and computes their statistical mutual enrichment by Monte Carlo fitting of a Negative Binomial distribution, resulting in more resolutive P-values. An optional machine learning method is proposed to find complexes of interest, using a new itemset mining algorithm based on dictionary learning which is resistant to noise inherent to biological assays. The overall approach is implemented through an easy-to-use CLI interface for workflow integration, and a visual tree-based representation of the results suited for explicability. The viability of the method is experimentally studied using both artificial and biological data. This approach is accessible through the command line interface of the pygtftk toolkit, available on Bioconda and from https://github.com/dputhier/pygtftk
Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline
Authors: Mohile Nimish A , Messersmith Hans , Gatson Na Tosha N , Hottinger Andreas F , Lassman Andrew B , Morton Jordan , Ney Douglas , Nghiemphu Phioanh Leia , Olar Adriana , Olson Jeffery , Perry James , Portnow Jana , Schiff David , Shannon Anne , Shih Helen A , Strowd Roy , van den Bent Martin , Ziu Mateo , Blakeley Jaishri
Published: December 2021

Purpose

To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults.

Methods

ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature.

Results

Fifty-nine randomized trials focusing on therapeutic management were identified.

Recommendations

Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMTpromoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.
The Epistemology of Debunking Argumentation
Authors: Egeland Jonathan
Published: December 2021

There is an ever-growing literature on what exactly the condition or criterion is that enables some (but not all) debunking arguments to undermine our beliefs. In this paper, I develop a novel schema for debunking argumentation, arguing that debunking arguments generally have a simple and valid form, but that whether or not they are sound depends on the particular aetiological explanation which the debunker provides in order to motivate acceptance of the individual premises. The schema has three unique features: (1) it satisfies important desiderata for what any acceptable account of debunking would have to look like; (2) it is consistent with the inductively supported claim that there is no special debunking principle; and (3) it coheres with the plausible claim that what makes debunking arguments unique is that they rely on so-called genealogies for the justification of their premises.
Characterizing heat mitigation strategies utilized by beef processors in the United States
Authors: Davis Melissa K , Engle Terry E , Cadaret Caitlin N , Cramer M Caitlin , Bigler Libby J , Wagner John J , Edwards-Callaway Lily N
Published: December 2021

During lairage at slaughter plants, cattle can be exposed to extreme heat conditions from pen densities and holding pen microclimates. While research outlining heat mitigation strategies used in other sectors of the beef supply chain is available, there is no published data on the use of heat mitigation strategies at slaughter plants. The objective of this study was to characterize short-term heat mitigation strategies used by commercial beef slaughter plants in the United States. Twenty-one beef slaughter plants, representing an estimated 60% of beef slaughter in the United States, were included in the study. All plants indicated use of at least one heat mitigation strategy, and five of them used more than one type. Sprinklers/misters were the most commonly used heat mitigation type (n = 17, 81%), and fans were the least common type (n = 4, 19%). Shade usage was present in several plants (n = 7, 33%), ranging from barn style roofs to shade cloths. Respondents indicated that they believed heat mitigation strategies provide benefits both to cattle well-being and meat quality outcomes. Future research should focus on the effectiveness of these techniques in improving animal well-being and quality outcomes in the slaughter plant environment and protocols for optimum implementation.
Adding Insult to Injury: Levator Ani Avulsion in Women With Obstetric Anal Sphincter Injuries
Authors: Heliker Bhumy Davé , Kenton Kimberly , Leader-Cramer Alix , Brown Oluwateniola , Bochenska Katarzyna , Geynisman-Tan Julia , Mueller Margaret , Lewicky-Gaupp Christina
Published: December 2021

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27:462–467)

Obstetric anal sphincter injuries (OASIS) and levator ani avulsion (LA) are 2 of the more widely studied neuromuscular birth injuries. Although they may occur together, sometimes they do not.
Video Head Impulse Test in Darkness, Without Visual Fixation: A Study on Healthy Subjects
Authors: Pérez-Vázquez Paz , Franco-Gutiérrez Virginia
Published: December 2021

Objective:

The head impulse test (HIT) is triggered by the vestibulo-ocular reflex (VOR), complemented by the optokinetic and pursuit systems. This study aimed to evaluate the possibility of individualizing the VOR contribution to the HIT.

Design:

Thirty-six healthy individuals (19 males, 17 females; age 21–64 years, mean 39 years) underwent horizontal video HIT (vHIT). This was first conducted in darkness, without visual fixation, and then visually tracked.

Results:

Seventy percent of the impulses delivered ocular responses opposite to the direction of the head, matching its velocity to a point where quick anticompensatory eye movements (SQEM) stopped the response (SQEM mean latency 58.21 ms, interquartile range 50–67 ms). Of these, 75% recaptured the head velocity after culmination. Thirty percent of the responses completed a bell-shaped curve. The completed bell-shaped curve gains and instantaneous gains (at 40, 60, and 80 ms) before SQEM were equivalent for both paradigms. Females completed more bell-shaped traces (42%) than males (15%); p = 0.01. The SQEM latency was longer (62.81 versus 55.71 ms, p < 0.01), and the time to recapture the bell-shaped curve was shorter (77.51 versus 92.52 ms, p < 0.01) in females than in males. The gains were comparable between sexes in both paradigms.

Conclusions:

The VOR effect can be localized in the first 70 ms of the vHIT response. In addition, other influences may take place in estimating the vHIT responses. The study of these influences might provide useful information that can be applied to patient management.
Inclusion of Older Adults Who Experience Homelessness in Laboratory-Based Audiology Research: a Feasibility Study
Authors: Shen Jing , Weller Bridget E. , Perales Jeanette Calvario
Published: December 2021

Objectives:

The objective of this study was to recruit older adults who experience homelessness into a feasibility study on laboratory-based audiology research.

Design:

Using best practices for recruiting individuals who experience homelessness into research, we aimed to recruit 25 participants over the course of six months. The protocol included hearing health history and hearing test. Individuals were also referred to services if needed and requested.

Results:

Among the 11 study participants recruited, almost half of the individuals did not meet the inclusion criteria due to severe hearing loss, neurological disorders, and difficulty staying alert.

Conclusions:

We identified a few barriers to including older adults who experience homelessness in laboratory-based audiology research and discussed potential strategies. Our findings provide lessons for future audiology research on including a population of individuals who may be vulnerable to health disparity and often omitted from research.
Comparison of the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter in term nulliparous women with borderline oligohydramnios
Authors: Zhang Yongqing , Chen Luping , Yan Guohui , Zhou Menglin , Chen Zhengyun , Liang Zhaoxia , Chen Danqing
Published: December 2021

Backgrounds:

At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios.

Methods:

We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups.

Results:

The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6% [84/141], P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57–2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8% [11/141], P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7% [1/141], P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96–22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07–2.14), body mass index (BMI) >30 kg/m2 (aOR: 2.98, 95% CI: 1.10–8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12–5.50).

Conclusions:

Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m2, large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.
Antibody-drug conjugates in HER2-positive breast cancer
Authors: Li Lixi , Zhang Di , Liu Binliang , Lv Dan , Zhai Jingtong , Guan Xiuwen , Yi Zongbi , Ma Fei
Published: December 2021

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
Risk of Malignant Transformation Arising From Giant Congenital Melanocytic Nevi: A 20-year Single-center Study
Authors: Kim Ji-Young , Jeon Ji Hui , Choi Tae Hyun , Kim Byung Jun
Published: December 2021

BACKGROUND

Although giant congenital melanocytic nevus (GCMN) is regarded as premalignant, the incidence and risk factors of malignant transformation are controversial.

OBJECTIVE

This study aimed to share the authors’ surgical experience with GCMNs and provide data on their demographics, malignant transformation, and prognosis.

METHODS

This single-center, consecutive study included 152 patients with GCMN who visited this center from March 2000 to February 2020. Their medical documentation was reviewed retrospectively, and the nevi were classified according to the size as follows: Group 1, 10 to 19.9 cm (n = 45); Group 2, 20 to 39.9 cm (n = 62); and Group 3, ≥40 cm (n = 45).

RESULTS

Seven malignancies were found (4.6%; 4 melanomas, 2 rhabdomyosarcomas [RMS], and 1 malignant peripheral nerve sheath tumor [MPNST]). The risk increased according to the nevus size (2.2% in Group 1, 3.2% in Group 2, and 8.9% in Group 3) but the difference was not statistically significant (p = .3305).

CONCLUSION

Malignant transformation from GCMN cannot be ignored. It can include transformation into melanoma, RMS, and MPNST. Early surgical resection and regular follow-up should be performed in patients with nevi ≥10 cm.
Postmarket Safety Surveillance of Delayed Complications for Recent FDA-Approved Hyaluronic Acid Dermal Fillers
Authors: Cohen Joel L. , Hicks Jessica , Nogueira Alessandra , Lane Vanessa , Andriopoulos Bill
Published: December 2021

OBJECTIVE

To review postmarketing data for delayed (≥14 days post-treatment) adverse events (AEs) of interest (inflammatory and noninflammatory nodules, hypersensitivity, granulomas) for newer hyaluronic acid (HA) fillers FDA-approved within the last 5 years (2016–2020).

METHODS

Reports from the Manufacturer and User Facility Device Experience (MAUDE) database were extracted for HAREF, HADEF, HAKYS, HAVER, HAVLR, HAVOB, HARH2, HARH3, and HARH4 from January 2016 to January 2021. Keywords from event narratives were used to identify and categorize AEs and then verified through inclusion/exclusion criteria. Percentages are based on the total combined events of interest to provide an overall perspective of the events reported during the search period.

RESULTS

Of 585 MAUDE reports, there were 195 (33.3%) delayed AEs of interest. Of those, 71.8% were nodules (42.1% inflammatory and 29.7% noninflammatory), 21.5% hypersensitivity, and 6.7% granulomas. The combined total events of interest, ordered by frequency reported, were HAVLR (74.4%), HAVOB (12.3%), HADEF (5.1%), HARH4 (3.6%), HAREF (2.6%), and HARH2 (2.1%), with no reports for HARH3, HAVER, and HAKYS.

CONCLUSION

Although delayed nodules and inflammatory events are rare, reports for these events were extracted from the MAUDE database from 2016 to 2020 for HAVLR, HAVOB, HADEF, HARH4, HAREF, and HARH2 (most to least frequent).
Comparison of Sodium–Glucose Cotransporter 2 Inhibitors and Glucagon-like Peptide Receptor Agonists for Atrial Fibrillation in Type 2 Diabetes Mellitus: Systematic Review With Network Meta-analysis of Randomized Controlled Trials
Authors: Li Wenjie , Chen Xingqing , Xie Xiangqi , Xu Min , Xu Lingling , Liu Peiying , Luo Bihui
Published: December 2021

Atrial fibrillation (AF) is a major public health concern with a rising prevalence. Although sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown the respective favorable effects on reducing the occurrence of AF/atrial flutter (AFL), comparative protective AF/AFL effects between above 2 novel antidiabetic agents remain unavailable. Thus, we aimed to evaluate the comparative efficacy of SGLT2is and GLP-1RAs in reducing the risk of AF/AFL in patients with type 2 diabetes and estimate relative rankings of interventions. PubMed, Embase, and ClinicalTrials.gov were searched up to December 1, 2020. All available randomized controlled trials comparing SGLT2is and GLP-1RAs with one another or placebo in patients with type 2 diabetes were included. Pooled results were shown as risk ratios (RRs) with 95% confidence intervals (CIs). We used a frequentist network meta-analysis to evaluate the outcomes of interests. Thirty-six randomized controlled trials including 85,701 participants with type 2 diabetes were identified. Compared with placebo, both SGLT2is (RR: 0.82, 95% CI, 0.68–0.99) and GLP-1RAs (RR: 0.86, 95% CI, 0.76–0.97; RR long-acting ones: 0.87, 95% CI, 0.76–0.99; RR short-acting ones: 0.72, 95% CI, 0.45–1.14) significantly reduced AF/AFL risk. No significant difference between SGLT2is and GLP-1RAs was noted (RR: 0.95, 95% CI, 0.76–1.2). Compared with placebo, results from the analysis showed an RR of 0.72 (95% CI, 0.45–1.14) for short-acting GLP-1RAs and 0.87 (95% CI, 0.76–0.99) for long-acting GLP-1RAs in reducing the risk of AF/AFL. Compared with placebo, both SGLT2is and GLP-1RAs possessed favorable effects on reducing the risk of AF/AFL. However, no difference was observed when comparisons were made between them. In addition, long-acting ones may confer a more pronounced AF/AFL reduction benefit compared with placebo.