bluuebunny/crossref_metadata_2025 huggingface dataset:
Peroneus longus intra-tendinous ganglion cyst
Authors: Khoja Yousef Tawfik , Altammami Abdulaziz Fahad , Alattas Mohammed Hashem
Published: June 2022

Ganglion cysts arising from tendons are uncommon lesions with an unknown cause. We present a case report of a 38-year-old female was diagnosed with an intra-tendinous ganglion cyst of the peroneus longus. She complained of right ankle swelling for 1 year and associated with pain. MRI revealed a peroneus longus intra-tendinous ganglion below the lateral malleolus with a thin wall. The ganglion cyst was surgically excised while the structure of the peroneus longus tendon was preserved. The clinical and functional outcomes were satisfactory after 1 year without recurrence.
Vectorial folding of telomere overhang promotes higher accessibility
Authors: Paul Tapas , Opresko Patricia L , Ha Taekjip , Myong Sua
Published: June 2022

Human telomere overhang composed of tandem repeats of TTAGGG folds into G-quadruplex (G4). Unlike in an experimental setting in the test tube in which the entire length is allowed to fold at once, inside the cell, the overhang is expected to fold as it is synthesized directionally (5′ to 3′) and released segmentally by a specialized enzyme, the telomerase. To mimic such vectorial G4 folding process, we employed a superhelicase, Rep-X which can unwind DNA to release the TTAGGG repeats in 5′ to 3′ direction. We demonstrate that the folded conformation achieved by the refolding of full sequence is significantly different from that of the vectorial folding for two to eight TTAGGG repeats. Strikingly, the vectorially folded state leads to a remarkably higher accessibility to complementary C-rich strand and the telomere binding protein POT1, reflecting a less stably folded state resulting from the vectorial folding. Importantly, our study points to an inherent difference between the co-polymerizing and post-polymerized folding of telomere overhang that can impact telomere architecture and downstream processes.
Towards a comprehensive understanding of RNA deamination: synthesis and properties of xanthosine-modified RNA
Authors: Mair Stefan , Erharter Kevin , Renard Eva , Brillet Karl , Brunner Melanie , Lusser Alexandra , Kreutz Christoph , Ennifar Eric , Micura Ronald
Published: June 2022

Nucleobase deamination, such as A-to-I editing, represents an important posttranscriptional modification of RNA. When deamination affects guanosines, a xanthosine (X) containing RNA is generated. However, the biological significance and chemical consequences on RNA are poorly understood. We present a comprehensive study on the preparation and biophysical properties of X-modified RNA. Thermodynamic analyses revealed that base pairing strength is reduced to a level similar to that observed for a G•U replacement. Applying NMR spectroscopy and X-ray crystallography, we demonstrate that X can form distinct wobble geometries with uridine depending on the sequence context. In contrast, X pairing with cytidine occurs either through wobble geometry involving protonated C or in Watson–Crick-like arrangement. This indicates that the different pairing modes are of comparable stability separated by low energetic barriers for switching. Furthermore, we demonstrate that the flexible pairing properties directly affect the recognition of X-modified RNA by reverse transcription enzymes. Primer extension assays and PCR-based sequencing analysis reveal that X is preferentially read as G or A and that the ratio depends on the type of reverse transcriptase. Taken together, our results elucidate important properties of X-modified RNA paving the way for future studies on its biological significance.
ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia
Authors: Lao Linjiang , Bourdeau Isabelle , Gagliardi Lucia , He Xiao , Shi Wei , Hao Bingbing , Tan Minjia , Hu Yan , Peng Junzheng , Coulombe Benoit , Torpy David J , Scott Hamish S , Lacroix Andre , Luo Hongyu , Wu Jiangping
Published: June 2022

ARMC5 is implicated in several pathological conditions, but its function remains unknown. We have previously identified CUL3 and RPB1 (the largest subunit of RNA polymerase II (Pol II) as potential ARMC5-interacting proteins. Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1. ARMC5, CUL3, and RBX1 formed an active E3 specific for RPB1. Armc5 deletion caused a significant reduction in RPB1 ubiquitination and an increase in an accumulation of RPB1, and hence an enlarged Pol II pool in normal tissues and organs. The compromised RPB1 degradation did not cause generalized Pol II stalling nor depressed transcription in the adrenal glands but did result in dysregulation of a subset of genes, with most upregulated. We found RPB1 to be highly expressed in the adrenal nodules from patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) harboring germline ARMC5 mutations. Mutant ARMC5 had altered binding with RPB1. In summary, we discovered that wildtype ARMC5 was part of a novel RPB1-specific E3. ARMC5 mutations resulted in an enlarged Pol II pool, which dysregulated a subset of effector genes. Such an enlarged Pol II pool and gene dysregulation was correlated to adrenal hyperplasia in humans and KO mice.
Identifying ribosome heterogeneity using ribosome profiling
Authors: Alkan Ferhat , Wilkins Oscar G , Hernández-Pérez Santiago , Ramalho Sofia , Silva Joana , Ule Jernej , Faller William J
Published: June 2022

Recent studies have revealed multiple mechanisms that can lead to heterogeneity in ribosomal composition. This heterogeneity can lead to preferential translation of specific panels of mRNAs, and is defined in large part by the ribosomal protein (RP) content, amongst other things. However, it is currently unknown to what extent ribosomal composition is heterogeneous across tissues, which is compounded by a lack of tools available to study it. Here we present dripARF, a method for detecting differential RP incorporation into the ribosome using Ribosome Profiling (Ribo-seq) data. We combine the ‘waste’ rRNA fragment data generated in Ribo-seq with the known 3D structure of the human ribosome to predict differences in the composition of ribosomes in the material being studied. We have validated this approach using publicly available data, and have revealed a potential role for eS25/RPS25 in development. Our results indicate that ribosome heterogeneity can be detected in Ribo-seq data, providing a new method to study this phenomenon. Furthermore, with dripARF, previously published Ribo-seq data provides a wealth of new information, allowing the identification of RPs of interest in many disease and normal contexts. dripARF is available as part of the ARF R package and can be accessed through https://github.com/fallerlab/ARF.
TBX2 acts as a potent transcriptional silencer of tumour suppressor genes through interaction with the CoREST complex to sustain the proliferation of breast cancers
Authors: McIntyre Alexander J , Angel Charlotte Z , Smith James S , Templeman Amy , Beattie Katherine , Beattie Shannon , Ormrod Alice , Devlin Eadaoin , McGreevy Charles , Bothwell Chloe , Eddie Sharon L , Buckley Niamh E , Williams Rich , Mullan Paul B
Published: June 2022

Chromosome 17q23 amplification occurs in 20% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6. Previously we found that TBX2 cooperates with the PRC2 complex to repress several TSGs, and that PRC2 inhibition restored NDRG1 expression to impede cellular proliferation. Here, we now identify CoREST proteins, LSD1 and ZNF217, as novel interactors of TBX2. Genetic or pharmacological targeting of CoREST emulated TBX2 loss, inducing NDRG1 expression and abolishing breast cancer growth in vitro and in vivo. Furthermore, we uncover that TBX2/CoREST targeting of NDRG1 is achieved by recruitment of TBX2 to the NDRG1 promoter by Sp1, the abolishment of which resulted in NDRG1 upregulation and diminished cancer cell proliferation. Through ChIP-seq we reveal that 30% of TBX2-bound promoters are shared with ZNF217 and identify novel targets repressed by TBX2/CoREST; of these targets a lncRNA, LINC00111, behaves as a negative regulator of cell proliferation. Overall, these data indicate that inhibition of CoREST proteins represents a promising therapeutic intervention for TBX2-addicted breast tumours.
Real-world Antimicrobial Stewardship Experience in a Large Academic Medical Center: Using Statistical and Machine Learning Approaches to Identify Intervention “Hotspots” in an Antibiotic Audit and Feedback Program
Authors: Goodman Katherine E , Heil Emily L , Claeys Kimberly C , Banoub Mary , Bork Jacqueline T
Published: June 2022

Background

Prospective audit with feedback (PAF) is an impactful strategy for antimicrobial stewardship program (ASP) activities. However, because PAF requires reviewing large numbers of antimicrobial orders on a case-by-case basis, PAF programs are highly resource intensive. The current study aimed to identify predictors of ASP intervention (ie, feedback) and to build models to identify orders that can be safely bypassed from review, to make PAF programs more efficient.

Methods

We performed a retrospective cross-sectional study of inpatient antimicrobial orders reviewed by the University of Maryland Medical Center’s PAF program between 2017 and 2019. We evaluated the relationship between antimicrobial and patient characteristics with ASP intervention using multivariable logistic regression models. Separately, we built prediction models for ASP intervention using statistical and machine learning approaches and evaluated performance on held-out data.

Results

Across 17 503 PAF reviews, 4219 (24%) resulted in intervention. In adjusted analyses, a clinical pharmacist on the ordering unit or receipt of an infectious disease consult were associated with 17% and 56% lower intervention odds, respectively (adjusted odds ratios [aORs], 0.83 and 0.44; P ≤ .001 for both). Fluoroquinolones had the highest adjusted intervention odds (aOR, 3.22 [95% confidence interval, 2.63–3.96]). A machine learning classifier (C-statistic 0.76) reduced reviews by 49% while achieving 78% sensitivity. A “workflow simplified” regression model that restricted to antimicrobial class and clinical indication variables, 2 strong machine learning–identified predictors, reduced reviews by one-third while achieving 81% sensitivity.

Conclusions

Prediction models substantially reduced PAF review caseloads while maintaining high sensitivities. Our results and approach may offer a blueprint for other ASPs.
Severe Libman–Sacks endocarditis complicating antiphospholipid syndrome: a retrospective analysis of 23 operated cases
Authors: Chalvon Nellie Bourse , Costedoat-Chalumeau Nathalie , Pennaforte Jean-Loup , Servettaz Amelie , Boulagnon Rombi Camille , Gavand Pierre-Edouard , Lekieffre Maud , Le Guern Veronique , Morel Nathalie , Cohen Aubart Fleur , Haroche Julien , Mathian Alexis , Collet Jean-Philippe , Piette Jean-Charles , Amoura Zahir , Orquevaux Pauline
Published: June 2022

Objective

Data on severe heart valve disease (HVD), including Libman–Sacks endocarditis, associated with SLE and/or APS requiring valvular surgery are scarce. We thus conducted a retrospective study, aimed at describing and clarifying clinical, laboratory, echocardiographic, histopathological and evolutional features of SLE and/or APS patients with severe associated-HVD.

Methods

An observational retrospective multicentric analysis of 23 adults with SLE and/or APS and HVD between 1996 and 2019 and available histopathological report evaluating long-term follow-up.

Results

Twenty-three individuals (20 females, median age 37 [range 17–76] years) were included. All had APS (thrombotic in 22, with an arterial phenotype in 15 and with catastrophic APS [CAPS] in six), and 11 (47%) had SLE. Systemic underlying disease had been diagnosed prior to HVD in 12 (52%). In 10 patients (43%), HVD was complicated by cerebral stroke prior to surgery. Twenty patients (87%) had only one pathological valve, the mitral valve in 18 patients (78%). Valvular thickening (n = 19) and valvular regurgitation (n = 19) were the most frequently reported lesions. Fifteen (62%) patients underwent mechanical valve replacement, six (26%) conservative valve repair (five were later re-operated after a median time of 1 [0–4] year), and two (9%) underwent biological valve replacement. Nine patients (39%) presented early-onset post-operative complications, including three CAPS immediately after surgery and one death. After surgery, 18 patients (78%) had normal postoperative valvular function, but almost half of the patients (43%) had post-operative neurological sequelae (median follow-up of 6 [2–20] years).

Conclusion

Severe HVD leading to surgery was strongly associated with thrombotic APS, especially arterial phenotypes. Half of the reported patients presented cerebral stroke complicating the HVD. Valvular surgery carried a significant risk of CAPS.
Pathogenesis of Plasmopara viticola Depending on Resistance Mediated by Rpv3_1, and Rpv10 and Rpv3_3, and by the Vitality of Leaf Tissue
Authors: Marie Juraschek Lena , Matera Christiane , Steiner Ulrike , Oerke Erich-Christian
Published: June 2022

Grapevine cultivars vary in their resistance to Plasmopara viticola, causal agent of downy mildew. Genes from various Vitis species confer pathogen resistance (Rpv), resulting in reduced compatibility of the host–pathogen interaction and partial disease resistance that may become apparent at different stages of pathogenesis. This study describes the pathogenesis of P. viticola on the partially resistant cultivars Regent (Rpv3-1) and Solaris (Rpv3-3, Rpv10) as compared with the susceptible cultivar Mueller-Thurgau using various microscopic techniques, visual disease rating as well as qPCR. Host plant resistance had no effect on the initial steps of pathogenesis outside the host plant cells (zoospore attachment, formation of substomatal vesicle) and became detectable only after the formation of primary haustoria. The restricted compatibility resulted in reductions in haustorium size and in the number of secondary haustoria and was associated with callose depositions around haustoria and stomatal guard cells, collapsed mesophyll cells (hypersensitive reaction), and additional production of an amorphous substance in the intercellular space of cultivar Solaris. Resistance mechanisms reduced the efficiency of P. viticola haustoria and largely restricted tissue colonization to the spongy parenchyma; resistance of cultivar Solaris having thicker leaves was more effective than that of cultivar Regent. Despite of the effects of resistance genes, P. viticola was able to complete its life cycle by forming sporangiophores with sporangia through the stomata on both resistant cultivars indicating partial resistance. Differences in the pathogenesis on detached and attached grapevine leaves highlighted the impact of host tissue vitality on both resistance and susceptibility to the biotrophic pathogen.
May-Thurner Syndrome and Lymphedema Reconstruction
Authors: Gupta Rohun , Mathijs Emily , Hart Justin , Bates John , Powers Jeremy , Chaiyasate Kongkrit
Published: June 2022

Background:

May-Thurner syndrome (MTS) is an anatomical variant that results in compression of the left common iliac vein by the right common iliac artery. Although often asymptomatic, lower extremity swelling/edema, deep venous thrombosis, post-thrombotic syndrome, and eventual lymphedema (due to long-standing venous obstruction) can develop. The clinical management of patients presenting for lymphedema surgery with concomitant or undiagnosed MTS is not well described.

Methods:

This review investigates two patients who were evaluated for unilateral lower extremity lymphedema, both of whom were subsequently diagnosed with MTS. Standard imaging (including lymphoscintigraphy, indocyanine green lymphangiography, and magnetic resonance venography) were performed to identify proximal venous obstruction. Treatment was accomplished using vascular surgical management, including stenting of the iliac vein before lymphedema reconstruction with vascularized lymph node transfer and multiple lymphovenous bypass.

Results:

Both patients we examined in this review had improvement of lymphedema with vascular surgical management. Literature review reveals that MTS has an incidence as high as 20% in the population, although commonly unidentified due to lack of symptomatology.

Conclusions:

There are no studies documenting the incidence of MTS in patients referred for lymphedema surgical management. Routine studies should be obtained to screen for proximal venous obstruction in patients presenting for surgical management of lower extremity lymphedema. Additional research is needed regarding the approach to managing patients with both MTS and lymphedema. Careful observational and prospective studies may elucidate the appropriate time interval between venous stenting and lymphedema microsurgical reconstruction.
Adolescent Occupational Exposures Reported to United States Poison Centers, 2011–2020
Authors: Lam Angela H. , Leonard James B. , Klein-Schwartz Wendy
Published: June 2022

Objective

The aim of this study was to perform an updated description of adolescent occupational exposures reported to the US poison centers.

Methods

We performed a descriptive analysis of adolescents aged 13 to 19 years with unintentional occupational exposures from 2011 to 2020 using the National Poison Data System. A clinically significant occupational poisoning (CSOP) case is defined as exposures with moderate effect, major effect, or death. Differences in substance categories between younger (13 to 17 years) and older (18 to 19 years) adolescents with CSOP were compared.

Results

There were 14,374 adolescent occupational exposures. There were 2151 CSOPs. The most common substance categories associated with CSOP were household cleaners (22.3%), chemicals (20.8%), industrial cleaners (14.2%), fumes/gases/vapors (10.8%), and hydrocarbons (5.9%). Categories of exposures were similar across age groups.

Conclusions

This study found that, despite a reduction in the number of adolescent occupational exposures, CSOPs persist.
Altered Mental Distress Among Employees From Different Occupational Groups and Industries During the COVID-19 Pandemic in Germany
Authors: Casjens Swaantje , Taeger Dirk , Brüning Thomas , Behrens Thomas
Published: June 2022

Objective

Mental distress of employees from the financial, public transport, public service, and industrial sector was examined in a cross-sectional study during the second COVID-19 (coronavirus disease 2019) wave in Germany and retrospectively at its beginning.

Methods

Mental distress in terms of anxiety and depression symptoms was assessed with the Patient Health Questionnaire-4. High and potential occupational SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection risk (OSIR) was defined based on job information from 1545 non–health care workers.

Results

The risks for more severe mental distress symptoms increased threefold and twofold, respectively, among employees with high and potential OSIR compared with employees without OSIR. Mental distress severity differed by the extent of work-privacy conflicts, perceived job protection, interactions with colleagues, and overcommitment.

Conclusions

Reducing COVID-19 exposure through workplace protective measures, strengthening interactions among colleagues, and supporting employees with work-privacy conflicts could help better protect employees' mental health.
Non-diabetic ketoacidosis secondary to primary hyperthyroidism
Authors: Al-Mashdali Abdulrahman F. , Gul Mohammadshah , Umer Waseem , Omar Abeer , Jones Akhnuwkh
Published: June 2022

Introduction:

There are variable complications of hyperthyroidism, including atrial fibrillation, heart failure, osteoporosis, and thyroid storm. One infrequent complication of hyperthyroidism is non-diabetic ketoacidosis (NDKA). To the best of our knowledge, our case is the third report of NDKA related to thyrotoxicosis.

Patient concern:

We describe a case of a 41-year-old African lady with no past medical history presented to our hospital with severe abdominal pain and vomiting for three weeks. This was associated with decreased appetite and weight loss.

Diagnosis:

Laboratory findings were significant for high anion gap metabolic acidosis, positive ketones in the urine, and high serum B-hydroxybutyrate. The blood glucose readings and HbA1c were within normal limits. Also, serum lactic acid and salicylate levels were within the normal range. The diagnosis of NDKA was made. Later, the thyroid functions test (TFT) confirmed the diagnosis of primary hyperthyroidism.

Intervention and outcomes:

The patient was managed initially with intravenous fluid and antiemetics. Then, she was started on propranolol and carbimazole. After which, her symptoms improved dramatically, and the metabolic acidosis (with serum ketones) were corrected within a few days of starting anti-thyroid medications.

Conclusion:

Despite its rarity, NDKA can be associated with severe thyrotoxicosis. Vigorous intravenous hydration and anti-thyroid medication are the mainstay treatment. TFT should be requested in a patient with unexplained NDKA
Sacubitril/Valsartan for heart failure
Authors: Dai Wenqin , Luo Jinlan , Huang Xianli
Published: June 2022

Background:

Sacubitril–valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF). However, the effects of sacubitril–valsartan have never been systematically evaluated. Therefore, we performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of sacubitril–valsartan in patients with HF.

Methods:

We selected 8 databases, including PubMed, the Web of Science, Embase, Cochrane Library, the Chinese National Knowledge Infrastructure, the Chinese Science Journal Database, Wanfang Data, and the Chinese Biomedical Literature Database. The search time was from database establishment to March 2022. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. Two reviewers will assess the risk of bias of the included studies by the “Risk of Bias Assessment Tool” of the Cochrane Handbook for randomized controlled trials. Statistical analysis will be performed with Review Manager software 5.3.

Results:

A synthesis of current evidence of sacubitril–valsartan for treating HF will be provided in this protocol.

Conclusion:

The results of this study will provide a theoretical basis for the clinical use of sacubitril–valsartan to treat HF.
The first survey on patient needs for remote monitoring of cardiac implantable electronic device in South Korea
Authors: Hwang You Mi , Kim Ji-Hoon
Published: June 2022

Background/Aims:

Studies showed that remote device monitoring reduced unnecessary outpatient visits and increased patient satisfaction. As there was no local research on remote monitoring (RM) in Korea, there was a lack of evidence for policy or insurance standards due to the lack of domestic data despite high demand by domestic arrhythmia experts. To establish the basis for patient satisfaction, economic efficiency, and safety of wireless monitoring, a survey-based study was planned.

Methods:

This was a single-university hospital survey. The satisfaction index was evaluated using a questionnaire to investigate patient satisfaction in outpatient clinics, economic efficiency (measured as home-to-clinic time, waiting time, and actual clinic time), and demand for RM in patients with implantable cardiac devices. The questionnaire was adopted and modified from the Survey on Telehealth Patient Experience by Bas-Villalobos, 2006 (modified Korean version 2.0 by You Mi Hwang, 2020).

Results:

Surveys were answered by 171 patients. The mean age of these patients was 71.2 ± 12.4 years. Based on the survey, home to clinic time was usually less than one h, mean waiting time in the hospital until clinic time ranged 42.6 ± 24.5 minutes, and mean clinic time ranged 3.1 ± 1.7 minutes. Based on the survey, patients favored RM over hospital visits with cardiac implantable electronic device follow-up mainly because of long travel times from home to clinic.

Conclusion:

Based on the survey results, there is a clear need for RM in patients who have cardiac implantable electronic devices.
Trends in emergency department visits due to back pain and spine surgeries during the COVID-19 pandemic in Finland
Authors: Jäntti Saara , Ponkilainen Ville , Mäntymäki Heikki , Uimonen Mikko , Kuitunen Ilari , Mattila Ville M.
Published: June 2022

We aim to report the incidences of ED visits due to back pain, hospitalizations, and urgent spine surgeries during the first and second waves of COVID-19 in Finland. The number of emergency department visits and hospitalizations due to back pain as well as urgent spine surgeries in the adult population was collected from hospital discharge registers for the years 2017 through 2019 (reference years) and 2020.

This study was conducted at three large Finnish hospitals. The monthly incidence with 95% confidence intervals (CI) of emergency department visits and hospitalizations due to back pain and spine surgeries in the three participating hospitals were calculated and compared by incidence rate ratios (IRR).

Visits to ED due to back pain decreased during the pandemic. The incidence of ED visits due to back pain was similar in February (IRR 0.95, CI: 0.82-1.10), but a decrease was seen after lockdown began (March IRR 0.67, CI: 0.57-0.78; April IRR 0.65, CI: 0.56-0.76) compared to the reference years. A second decrease in visits was seen after regional restrictions were implemented in October (IRR 0.88, CI: 0.76-1.02). The most common diagnoses were non-specific back pain, lumbar disk herniation, and back contusion. Incidence of non-specific back pain decreased during the lockdown (March IRR 0.65, CI: 0.55-0.78) and regional restrictions (October IRR 0.83, CI: 0.70-0.98), whereas the rates of other diagnoses remained unchanged, and incidences of hospitalizations and urgent spine surgeries remained stable.

A clear decrease in ED visits due to back pain was seen during the first and second waves of the pandemic. This decrease was mainly the result of patients with non-specific back pain avoiding visits to the ED. The incidence of specific back pain, hospitalizations, and urgent spine surgeries remained unchanged during the pandemic.
Toward Better Understanding of Pediatric Feeding Disorder: A Proposed Framework for Patient Characterization
Authors: Sharp William G. , Silverman Alan , Arvedson Joan C. , Bandstra Nancy F. , Clawson Elizabeth , Berry Rashelle C. , McElhanon Barbara O. , Kozlowski Alison M. , Katz Mitchell , Volkert Valerie M. , Goday Praveen S. , Lukens Colleen T.
Published: June 2022

To establish a foundation for methodologically sound research on the epidemiology, assessment, and treatment of pediatric feeding disorder (PFD), a 28-member multidisciplinary panel with equal representation from medicine, nutrition, feeding skill, and psychology from seven national feeding programs convened to develop a case report form (CRF). This process relied upon recent advances in defining PFD, a review of the extant literature, expert consensus regarding best practices, and review of current patient characterization templates at participating institutions. The resultant PFD CRF involves patient characterization in four domains (ie, medical, nutrition, feeding skill, and psychosocial) and identifies the primary features of a feeding disorder based on PFD diagnostic criteria. A corresponding protocol provides guidance for completing the assessment process across the four domains. The PFD CRF promotes a standard procedure to support patient characterization, enhance methodological rigor, and provide a useful clinical tool for providers and researchers working with these disorders.
Effectiveness of Cryotherapy on Cancer Therapy–Induced Oral Mucositis
Authors: Lee Chai-Chun , Kuo Shu-Fen , Chang Wen-Pei , Guo Shu-Liu , Huang Tsai-Wei
Published: June 2022

Background

Oral mucositis (OM) considerably affects the experience of patients with cancer during treatment. This study investigated the effects of cryotherapy on cancer therapy–induced OM.

Objective

This study aimed to systematically appraise evidence on whether cryotherapy can reduce the incidence and severity of OM.

Methods

We conducted an umbrella review to examine the effect of cryotherapy on cancer-related OM. The primary outcome was the incidence and severity of OM. We performed a subgroup analysis including solid cancers and hematological malignancies.

Results

Five meta-analyses were included. Cryotherapy could more effectively reduce the incidence of severe OM (risk ratio [RR], 0.37; 95% prediction interval [PI], 0.22–0.64). In the subgroup analyses of solid cancers or hematological malignancies, cryotherapy significantly reduced the incidence of grades 2 to 4 OM in patients with solid cancers (RR, 0.51; 95% PI, 0.34–0.78 and RR, 0.52; 95% PI, 0.36–0.74). However, no significant difference was observed in the incidence of OM in patients with hematological malignancies regarding any grade or grade 3 or 4 OM. Moreover, cryotherapy did not significantly reduce the OM duration (mean difference, −0.13; 95% PI, −20.89 to 20.63; mean difference, −2.99, 95% PI, −8.10 to 2.12).

Conclusion

Cryotherapy can reduce the incidence of severe OM induced by chemotherapy or radiotherapy.

Implication for Practice

We recommend the inclusion of this safe, simple, and convenient intervention in chemotherapy or radiotherapy plans. Additional clinical trials are warranted to extend the limited evidence on the effectiveness of cryotherapy in reducing the severity and duration of OM.
Neoadjuvant Radiation in High-Grade Soft-Tissue Sarcomas
Authors: Boxberg Melanie , Langer Rupert , Woertler Klaus , Knebel Carolin , Rechl Hans , von Eisenhart-Rothe Rüdiger , Weichert Wilko , Combs Stephanie E. , Hadjamu Miriam , Röper Barbara , Specht Katja
Published: June 2022

In this study, we sought to determine the prognostic value of both the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) score and the histologic parameters viable tumor, coagulative necrosis, hyalinization/fibrosis, and infarction in patients (n=64) with localized, nonmetastatic high-grade soft-tissue sarcomas after preoperative radiomonotherapy. A standardized macroscopic workup for pretreated surgical specimen including evaluation of a whole section of high-grade soft tissue sarcomas in the largest diameter, was used. Association with overall survival and disease-free survival was assessed. Limb salvage could be accomplished in 98.4% of patients. Overall, 90.6% tumors had negative resection margins. The median postoperative tumor diameter was 9 cm. Undifferentiated pleomorphic sarcoma (42.2%) and myxofibrosarcoma (17.2%) were the most common diagnoses. In all, 9.4% of patients had local recurrence despite clear resection margins, and 50% had distant metastases. Morphologic mapping suggests an overall heterogenous intratumoral response to radiotherapy, with significant differences among histologic subtypes. Complete regression (0% vital tumor cells) was not seen. Categorizing the results according to the proposed EORTC-STBSG 5-tier response score, <1% viable tumor cells were seen in 3.1%, ≥1% to <10% viable tumor cells in 20.4%, ≥10% to <50% viable tumor cells in 35.9% and ≥50% viable tumor cells in 40.6% of cases. Mean values for viable tumor cells were 40% (range: 1% to 100%), coagulative necrosis 5% (0% to 60%), hyalinization/fibrosis 25% (0% to 90%) and infarction 15% (0% to 79%). Hyalinization/fibrosis was a significant independent prognostic factor for overall survival (hazard ratio=4.4; P=0.047), while the other histologic parameters including the EORTC-STBSG score were not prognostic.
Outcomes for Children With Pulmonary Hypertension Undergoing Tracheostomy Placement: A Multi-Institutional Analysis*
Authors: Perez Jennifer M. , Melvin Patrice R. , Berry Jay G. , Mullen Mary P. , Graham Robert J.
Published: June 2022

OBJECTIVES:

To describe epidemiology, interventions, outcomes, and the health services experience for a cohort of children with pulmonary hypertension (PH) who underwent tracheostomy placement and to identify risk factors for inhospital mortality and 30-day readmissions.

DESIGN:

Retrospective cohort study of the Pediatric Health Information System database.

SETTING:

Thirty-seven freestanding U.S. children’s hospitals.

PATIENTS:

Patients 31 days to 21 years old who were discharged from the hospital between January 1, 2009, and December 31, 2017, with a diagnosis of primary or secondary PH, and who underwent tracheostomy placement. Outcomes were examined over a 2-year period from the time of discharge from the index encounter.

INTERVENTIONS:

None.

MEASUREMENTS and MAIN RESULTS:

There were 793 patients with PH who underwent tracheostomy placement. The overall inhospital mortality rate was 23.7%. Secondary PH due to congenital heart disease (CHD) was significantly associated with overall inhospital mortality (adjusted odds ratio [OR], 2.36; 95% CI, 1.38–4.04). The rate of 30-day readmissions for patients over the 2-year follow-up period was 33.3%. Tracheostomy during the index encounter and the diagnosis of secondary PH due to CHD were significantly associated with lower rates of 30-day readmissions (adjusted OR, 0.34; 95% CI, 0.19–0.61; and adjusted OR, 0.43; 95% CI, 0.24–0.77, respectively).

CONCLUSIONS:

In the context of expanding utilization of tracheostomy and long-term ventilation, children with PH are among the highest risk cohorts for extended and repeated hospitalization and death. Tracheostomy placement during the index encounter was associated with fewer 30-day readmissions over the 2-year follow-up period. Further understanding of which subgroups may benefit from earlier intervention and which subgroups are at highest risk may offer important clinical insight when considering optimal timing of tracheostomy and may enhance informed decision-making for all stakeholders.
Favorable Transverse Maxillary Development after Covering the Lateral Raw Surfaces with Buccal Fat Flaps in Modified Furlow Palatoplasty: A Three-Dimensional Imaging–Assisted Long-Term Comparative Outcome Study
Authors: Lo Chi-Chin , Denadai Rafael , Lin Hsiu-Hsia , Pai Betty Chien-Jung , Chu Yu-Ying , Lo Lun-Jou , Chou Pang-Yun
Published: June 2022

Background:

The pedicled buccal fat flap has recently been applied to cover the lateral raw surfaces during palatoplasty as an attempt to mitigate scar-induced transverse maxillary constriction during growth, but with no formal long-term comparative analysis. This three-dimensional imaging–assisted study assessed its impact on posterior transverse maxillary development.

Methods:

Cone beam computed tomographic scans from patients with unilateral cleft lip, alveolus, and palate who received buccal fat flap (buccal fat group; n = 22) or Surgicel (Surgicel group; n = 32) for covering lateral raw surfaces during modified Furlow palatoplasty at 9 to 10 months of age and had reached the age of 9 years were retrieved for analysis. Patients with unilateral cleft lip and alveolus (nonpalatoplasty group; n = 24) were also included for comparison. Using three-dimensional maxillary image models, linear (U6T-MSP and U6J-MSP) and area measurements were calculated for cleft and noncleft posterior maxillary sides and for total posterior transverse maxillary dimension.

Results:

The buccal fat group had significantly (all p < 0.05) wider dimensions compared with the Surgicel group for all transverse maxillary measurements on both the cleft and noncleft sides, except for U6J-MSP and posterior palatal area parameters on the cleft side (p > 0.05). The buccal fat group had significantly (all p < 0.05) wider total transverse maxillary dimensions compared with the Surgicel and nonpalatoplasty groups.

Conclusion:

Covering the lateral raw surfaces with buccal fat flaps resulted in less posterior transverse maxillary constriction compared with the Surgicel-based covering procedure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Safety and Pharmacokinetics of Intravenous 10-1074 and VRC01LS in Young Children
Authors: Capparelli Edmund V. , Ajibola Gbolahan , Maswabi Kenneth , Holme Molly P. , Bennett Kara , Powis Kathleen M. , Moyo Sikhulile , Mohammed Terence , Maphorisa Comfort , Hughes Michael D. , Seaton Kelly E. , Tomaras Georgia D. , Mosher Shad , Taylor Alison , O’Connell Sarah , Narpala Sandeep , Mcdermott Adrian , Caskey Marina , Gama Lucio , Lockman Shahin , Jean-Philippe Patrick , Makhema Joseph , Kuritzkes Daniel R. , Lichterfeld Mathias , Shapiro Roger L. ,   for the Tatelo Study Team
Published: June 2022

Background:

Broadly neutralizing monoclonal antibodies (bNAbs) suppress HIV-1 RNA and may deplete residual viral reservoirs. We evaluated the safety and pharmacokinetics (PK) of dual intravenous VRC01LS and 10-1074 in very early-treated children with HIV-1 on suppressive antiretroviral treatment (ART).

Setting:

Botswana.

Methods:

Children with HIV-1 (median age 3.1 years) on ART from <7 days old were enrolled. In phase A, 6 children received 10-1074 (30 mg/kg at day 0, 28, and 56) and 6 children received VRC01LS (30 mg/kg at day 0, 10 mg/kg at days 28 and 56) by intravenous infusion. In phase B, 6 children received the 2 bNAbs combined (with higher VRC01LS maintenance dose, 15 mg/kg) every 4 weeks for 32 weeks with PK evaluations over 8 weeks. Population PK models were developed to predict steady-state concentrations.

Results:

BNAb infusions were well tolerated. There were no infusion reactions nor any bNAb-related grade 3 or 4 events. The median (range) first dose Cmax and trough (day 28) combined from both phases were 1405 (876–1999) μg/mL and 133 (84–319) μg/mL for 10-1074 and 776 (559–846) μg/mL and 230 (158–294) μg/mL for VRC01LS. No large differences in bNAb clearances were observed when given in combination. The estimated VRC01LS half-life was shorter than in adults. Predicted steady-state troughs [median (90% prediction interval)] were 261 (95–565) and 266 (191–366) μg/mL for 10-1074 and VRC01LS, respectively, when given in combination.

Conclusions:

10-1074 and VRC01LS were safe and well-tolerated among children receiving ART. Troughs exceeded minimal targets with every 4-week administration of 10-1074 at 30 mg/kg and VRC01LS at 15 mg/kg.
Moving Beyond the LGBTQIA+ Acronym
Authors: McEwing Evan , Black Terrie , Zolobczuk Joseph , Dursun Umut
Published: June 2022

Purpose

The LGBTQIA+ communities experience distinct health disparities and inequities in health outcomes. Healthcare providers must be conscious of these factors to facilitate optimal, person-centered care. This narrative briefly covers health disparities in the LGBTQIA+ community and posits strategies to promote inclusive care.

Methods

Current literature and clinical best practices from several authoritative sources on LGBTQIA+-specific issues and gender-affirming care were reviewed. Sources included several LGBTQIA+-specific healthcare organizations, national healthcare provider organizations, and federal agency policy statements. Inclusive terminology and healthcare practices are included.

Results

Healthcare providers must educate themselves on caring for gender- and sexual orientation-diverse populations to optimize the health status of these communities. It is essential that providers examine their own potential biases and maintain an openness to learning about LGBTQIA+ communities.

Conclusions

Healthcare providers have a responsibility to not only understand issues specific to LGBTQIA+ individuals but also advocate for these groups. As nurses, we must continue to support public health policies that seek to end disparities and ensure health equity for all.

Clinical Relevance to the Practice of Rehabilitation Nursing

Rehabilitation nurses are caring for more diverse populations than ever before and must understand how to provide compassionate, individualized care. Although this article focuses on the LGBTQIA+ community, the principles discussed are applicable across all populations.
Tandem use of gastroesophageal resuscitative occlusion of the aorta followed by resuscitative endovascular balloon occlusion of the aorta in a lethal liver laceration model
Authors: Tiba Mohamad Hakam , McCracken Brendan M. , Greer Nicholas L. , Cramer Traci A. , Colmenero Mahmood Carmen I. , Priambada Putra Ketut B. , Plott Jeffery S. , Shih Albert J. , Wang Stewart C. , Eliason Jonathan L. , Ward Kevin R.
Published: June 2022

BACKGROUND

Gastroesophageal resuscitative occlusion of the aorta (GROA) has been shown effective in creating zone II aortic occlusion capable of temporarily improving survival in animal models of lethal noncompressible torso hemorrhage. In this study, tandem application of GROA transitioning to resuscitative endovascular balloon occlusion of the aorta (REBOA) is explored to demonstrate feasibility as a potential point-of-injury bridge to more advanced care, using a swine model of lethal abdominal hemorrhage.

METHODS

Swine (n = 19) were anesthetized, instrumented, and subjected to a combination of controlled and uncontrolled hemorrhage from a grade-V liver laceration. Animals were designated as intervention (n = 9; GROA to REBOA) or control (n = 10), for 60 minutes. Following intervention, devices were deactivated, and animals received blood and crystalloid resuscitation. Animals were monitored for 4 hours.

RESULTS

Injury resulted in onset of class IV shock in all animals with a mean arterial pressure (SD) of 24.5 (4.11) mm Hg at the start of intervention. Nine of 10 controls died during the intervention period with a median (interquartile) survival time of 8.5 (9.25) minutes. All animals receiving the intervention survived both the 60-minute intervention period demonstrating a significant survival improvement (p = 0.0007). Transition from GROA to REBOA was successful in all animals with a transition time ranging from 30 to 90 seconds. Mean arterial pressure significantly improved in animals receiving GROA to REBOA for the duration of intervention, regardless of the method of aortic occlusion, with a range of 70.9 (16.04) mm Hg to 101.1 (15.3) mm Hg. Additional hemodynamics, metrics of shock, and oxygenation remained stable during intervention.

CONCLUSION

Less invasive technologies such as GROA may present an opportunity to control noncompressible torso hemorrhage more rapidly, with a subsequent transition to more advanced care such as REBOA.
Noninvasive assessment of intracranial pressure using subharmonic-aided pressure estimation: An experimental study in canines
Authors: Zheng Shuai , Zhang Yanfen , Cheng Linggang , Wang Hongbin , Li Rui , Chen Zhiguang , Zhang Yukang , He Wen , Zhang Wei
Published: June 2022

BACKGROUND

Intracranial hypertension is a common clinicopathological syndrome in neurosurgery, and a timely understanding of the intracranial pressure (ICP) may help guide clinical treatment. We aimed to investigate the correlation between subharmonic contrast-enhanced ultrasound (SHCEUS) parameters and ICP in experimental canines.

METHODS

A dynamic model of ICP change from 11 mm Hg to 50 mm Hg was established in experimental canines by placing a latex balloon into the epidural space and injecting saline into the balloon. In addition, a pressure sensor was placed in the brain parenchyma to record the changes in ICP. When the ICP stabilized after each increase, subharmonic-aided pressure estimation (SHAPE) technology was performed to obtain the SHCEUS parameters, including the basal venous and adjacent intracranial arterial subharmonic amplitude and SHAPE gradient (subharmonic amplitude in the intracranial artery minus that in the basal vein). The correlation between these parameters and ICP was analyzed.

RESULTS

The subharmonic amplitude of the basal vein was negatively correlated with the ICP (r = −0.798), and the SHAPE gradient was positively correlated with the ICP (r = 0.628). According to the guidelines for ICP monitoring in patients with traumatic brain injury, we defined 20 mm Hg, 25 mm Hg, and 30 mm Hg as the cutoff ICP levels. The area under the receiver operating characteristic curve of the basal venous subharmonic amplitude for diagnosing intracranial hypertension ≥20 mm Hg, ≥25 mm Hg, and ≥30 mm Hg was 0.867 (95% confidence interval [CI], 0.750–0.943), 0.884 (95% CI, 0.770–0.954), and 0.875 (95% CI, 0.759–0.948), respectively. The area under the receiver operating characteristic curve of the SHAPE gradient for diagnosing intracranial hypertension ≥20 mm Hg, ≥25 mm Hg, and ≥30 mm Hg was 0.839 (95% CI, 0.716–0.924), 0.842 (95% CI, 0.720–0.926), and 0.794 (95% CI, 0.665–0.890), respectively.

CONCLUSION

SHCEUS parameters are correlated with ICP. The SHAPE technique can assist in evaluating ICP changes in canines, which provides a new idea and method for evaluating ICP.
Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy
Authors: Lawson Michael A. , Holle Lori A. , Dow Nathan E. , Hennig Grant , de Laat Bas , Moore Hunter B. , Moore Ernest E. , Cohen Mitchell J. , Bouchard Beth A. , Freeman Kalev , Wolberg Alisa S.
Published: June 2022

BACKGROUND

Trauma patients with abnormal fibrinolysis have increased morbidity and mortality. Knowledge of mechanisms differentiating fibrinolytic phenotypes is important to optimize treatment. We hypothesized that subjects with abnormal fibrinolysis identified by whole blood viscoelastometry can also be distinguished by plasma thrombin generation, clot structure, fibrin formation, and plasmin generation measurements.

METHODS

Platelet-poor plasma (PPP) from an observational cross-sectional trauma cohort with fibrinolysis shutdown (% lysis at 30 minutes [LY30] < 0.9, n = 11) or hyperfibrinolysis (LY30 > 3%, n = 9) defined by whole blood thromboelastography were studied. Noninjured control subjects provided comparative samples. Thrombin generation, fibrin structure and formation, and plasmin generation were measured by fluorescence, confocal microscopy, turbidity, and a fluorescence-calibrated plasmin assay, respectively, in the absence/presence of tissue factor or tissue plasminogen activator (tPA).

RESULTS

Whereas spontaneous thrombin generation was not detected in PPP from control subjects, PPP from hyperfibrinolysis or shutdown patients demonstrated spontaneous thrombin generation, and the lag time was shorter in hyperfibrinolysis versus shutdown. Addition of tissue factor masked this difference but revealed increased thrombin generation in hyperfibrinolysis samples. Compared with shutdown, hyperfibrinolysis PPP formed denser fibrin networks. In the absence of tPA, the fibrin formation rate was faster in shutdown than hyperfibrinolysis, but hyperfibrinolysis clots lysed spontaneously; these differences were masked by addition of tPA. Tissue plasminogen activator–stimulated plasmin generation was similar in hyperfibrinolysis and shutdown samples. Differences in LY30, fibrin structure, and lysis correlated with pH.

CONCLUSION

This exploratory study using PPP-based assays identified differences in thrombin generation, fibrin formation and structure, and lysis in hyperfibrinolysis and shutdown subgroups. These groups did not differ in their ability to promote tPA-triggered plasmin generation. The ability to characterize these activities in PPP facilitates studies to identify mechanisms that promote adverse outcomes in trauma.

LEVEL OF EVIDENCE

Prognostic/Epidemiological; Level III.