bluuebunny/crossref_metadata_2025 huggingface dataset:
Microvascular Transposition Without Teflon: A Single Institution's 17-Year Experience Treating Trigeminal Neuralgia
Authors: Pines Andrew R , Butterfield Richard J , Turcotte Evelyn L , Garcia Jose O , De Lucia Noel , Algier Emily J , Patel Naresh P , Zimmerman Richard S
Published: March 2021

BACKGROUND

Trigeminal neuralgia (TN) refractory to medical management is often treated with microvascular decompression (MVD) involving the intracranial placement of Teflon. The placement of Teflon is an effective treatment, but does apply distributed pressure to the nerve and has been associated with pain recurrence.

OBJECTIVE

To report the rate of postoperative pain recurrence in TN patients who underwent MVD surgery using a transposition technique with fibrin glue without Teflon.

METHODS

Patients were eligible for our study if they were diagnosed with TN, did not have multiple sclerosis, and had an offending vessel that was identified and transposed with fibrin glue at our institution. All eligible patients were given a follow-up survey. We used a Kaplan-Meier (KM) model to estimate overall pain recurrence.

RESULTS

A total of 102 patients met inclusion criteria, of which 85 (83%) responded to our survey. Overall, 76 (89.4%) participants responded as having no pain recurrence. Approximately 1-yr pain-free KM estimates were 94.1% (n = 83), 5-yr pain-free KM estimates were 94.1% (n = 53), and 10-yr pain-free KM estimates were 83.0% (n = 23).

CONCLUSION

Treatment for TN with an MVD transposition technique using fibrin glue may avoid some cases of pain recurrence. The percentage of patients in our cohort who remained pain free at a maximum of 17 yr follow-up is on the high end of pain-free rates reported by MVD studies using Teflon. These results indicate that a transposition technique that emphasizes removing any compression near the trigeminal nerve root provides long-term pain-free rates for patients with TN.
Management practices and public policy: an overview
Authors: Quinn Simon , Scur Daniela
Published: March 2021

This paper introduces and summarizes this issue of the Oxford Review of Economic Policy, on management practices. We outline key concepts in the empirical study of structured management practices, then summarize each of the eight papers that follows. We conclude by speculating on future directions for research and policy development in this area.
Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia are more frequent in advanced versus early Parkinson’s disease
Authors: Sringean Jirada , Stefani Ambra , Marini Kathrin , Bergmann Melanie , Werkmann Mario , Holzknecht Evi , De Marzi Roberto , Brandauer Elisabeth , Hackner Heinz , Djamshidian Atbin , Stockner Heike , Gaig Carles , Iranzo Alex , Santamaria Joan , Tolosa Eduardo , Seppi Klaus , Poewe Werner , Högl Birgit
Published: March 2021

Study Objectives

To evaluate macro sleep architecture and characterize rapid eye movement (REM) sleep without atonia (RWA) by using the SINBAR excessive electromyographic (EMG) montage including mentalis and upper extremity muscles in early and advanced Parkinson’s disease (PD).

Methods

We recruited 30 patients with early- and advanced-stage of PD according to Movement Disorder Society (MDS) Clinical Diagnostic Criteria. Participants were classified as early-stage PD if they were treatment-naïve or had no motor complications and had been diagnosed with PD within the previous 6 years. Advanced PD was defined as a disease duration equal to or >6 years with or without motor complications.

Results

There was significantly shorter REM sleep latency in early as compared to the advanced stage of PD. We found that the sleep Innsbruck Barcelona (SINBAR) EMG index and tonic EMG activity of the mentalis muscle in advanced-stage PD were significantly higher than in early-stage PD with a trend in phasic EMG activity of the flexor digitorum superficialis muscles. The SINBAR EMG index, tonic and any EMG activity of the mentalis muscle, and phasic EMG activity of flexor digitorum superficialis muscles significantly correlated with disease duration.

Conclusions

This study analyzed RWA using the SINBAR EMG montage in early- and advanced-stage of PD and showed higher RWA in mentalis and flexor digitorum superficialis muscles and SINBAR EMG index in advanced-PD patients compared to patients in the early stage. Also, polysomnography-confirmed REM sleep behavior disorder was more common in advanced versus early-stage patients. Our findings suggest that RWA worsens or is more intense or more frequent with disease progression.
Manipulation of rapid eye movement sleep via orexin and GABAA receptor modulators differentially affects fear extinction in mice: effect of stable versus disrupted circadian rhythm
Authors: Clark Jacob W , Daykin Heather , Metha Jeremy A , Allocca Giancarlo , Hoyer Daniel , Drummond Sean P A , Jacobson Laura H
Published: March 2021

Sleep disruption, and especially rapid eye movement (REM) sleep disruption, is associated with fear inhibition impairment in animals and humans. The REM sleep-fear inhibition relationship raises concern for individuals with posttraumatic stress disorder (PTSD), whose sleep disturbance is commonly treated with hypnotics that disrupt and/or decrease REM sleep, such as benzodiazepines or “Z-drugs.” Here, we examined the effects of the Z-drug zolpidem, a gamma-aminobutyric acidA (GABAA) receptor positive allosteric modulator, as well as suvorexant, an orexin receptor antagonist (hypnotics which decrease and increase REM sleep, respectively) in the context of circadian disruption in murine models of fear inhibition-related processes (i.e. fear extinction and safety learning). Adult male C57Bl/6J mice completed fear and safety conditioning before undergoing shifts in the light–dark (LD) cycle or maintaining a consistent LD schedule. Fear extinction and recall of conditioned safety were thereafter tested daily. Immediately prior to the onset of the light phase between testing sessions, mice were treated with zolpidem, suvorexant, or vehicle (methylcellulose). Polysomnographic analyses showed the temporal distribution of REM sleep was misaligned during LD cycle-shifts, while REM sleep duration was preserved. Suvorexant increased REM sleep and improved fear extinction rate, relative to zolpidem, which decreased REM sleep. Survival analysis demonstrated LD shifted mice treated with suvorexant were faster to achieve complete extinction than vehicle and zolpidem-treated mice in the LD shifted condition. By contrast, retention of conditioned safety memory was not influenced by either treatment. This study thus provides preclinical evidence for the potential clinical utility of hypnotics which increase REM sleep for fear extinction after PTSD-relevant sleep disturbance.
Expansion of Internal Hyphal Growth in Fusarium Head Blight–Infected Grains Contributes to the Elevated Mycotoxin Production During the Malting Process
Authors: Jin Zhao , Solanki Shyam , Ameen Gazala , Gross Thomas , Poudel Roshan Sharma , Borowicz Pawel , Brueggeman Robert S. , Schwarz Paul
Published: March 2021

Fusarium head blight (FHB) and the occurrence of mycotoxins is the largest food safety threat to malting and brewing grains. Worldwide surveys of commercial beers have reported that the trichothecene mycotoxin deoxynivalenol (DON) is the most frequent contaminant in beer. Although the DON content of grain generally declines during steeping due to its solubilization, Fusarium spp. can continue to grow and produce DON from steeping through the early kilning stage of malting. DON present on malt is largely extracted into beer. The objective of the current study was to localize the growth of Fusarium spp. within FHB-infected kernels by developing an improved method and to associate fungal growth with the production of DON during malting. FHB-infected barley, wheat, rye, and triticale grains that exhibited large increases in the amount of Fusarium Tri5 DNA and trichothecene mycotoxins following malting were screened for hyphal localization. The growth of fungal hyphae associated with grain and malt was imaged by scanning electron microscopy and confocal laser-scanning microscopy assisted with WGA-Alexa Fluor 488 staining, respectively. In barley, hyphae were present on or within the husk, vascular bundle, and pericarp cavities. Following malting, vast hyphal growth was observed not only in these regions but also in the aleurone layer, endosperm, and embryo. Extensive fungal growth was also observed following malting of wheat, rye, and triticale. However, these grains already had an extensive internal presence of Fusarium hyphae in the unmalted grain, thus representing an enhanced chance of fungal expansion during the malting.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Methionine Deprivation Induced Effects on the Growth of PC3 prostate cancer cells
Authors: Diaz Eduardo , Nosal Rebecca , Venkatachalam KV
Published: March 2021

Methionine is a key nutrient required for the synthesis of S‐adenosylmethionine (SAM). SAM is the universal methyl group donor. Methionine gamma lyase deaminase (Mgld) is an enzyme that degrades methionine into alpha‐ketobutyrate and methylthiol. In this study, the Mgld gene was cloned into vectors that expressed Mgld, either in the cytosol or in the nucleus. The prostate cancer cell line, PC3 (ATCC‐CRL1435) was transfected with vectors containing Mgld. The PC3 cells experience cell death when Mgld is expressed in the cytosol or nucleus. In the presence of Proparglycine (PGLY), a Mgld inhibitor, the cells proliferate to a moderate degree. Co‐treatment of the PGLY with the nuclear Mgld caused a slight decrease of cells whereas with cytoplasmic Mgld caused a slight increase. In the cytoplasm, methionine is required for forming cysteine; cysteine in turn is required for glutathione (cells redox agent). Both cysteine and methionine are required for protein synthesis. Therefore, cytosolic dwindling of methionine will hamper protein synthesis and it should, in general, affect the growth of Mgld treated cells when compared to controlled cells. The addition of PGLY alone or in combination with the cytosolic vector increased proliferation, while the addition of PGLY to the nuclear vector caused modest cell death. We conclude that the methylation status of PC3 might be different and it affects the growth in varying degrees depending on the location of the Mgld expression. We speculate that PGLY might affect expressed Mgld and endogenous cytosolic cystathione beta‐synthase activity, resulting in complex cell fate, a hypothesis that needs to be tested further.

Support or Funding Information

NSU Internal grant

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anti‐thrombotic and Anti‐inflammatory Nanoparticle Limits Early Remodeling in Acute Myocardial Infarction
Authors: Grabau Ryan , Chen Junjie , Weinheimer Carla , Kovacs Attila , Pan Hua , Wickline Samuel A.
Published: March 2021

Acute myocardial infarction (AMI) is a life‐threatening medical condition. Based on the statistics updated in 2017, there is a person experiencing myocardial infarction every 40 seconds. For AMI patients, majority of them miss the treatment window for rescuing significant amounts of viable myocardium. However, infarction size can expand for weeks after the initial AMI, which provides an opportunity to prevent ventricular remodeling (progressive chamber enlargement) as well as improve healing process. AMI associated secondary ischemia further induces endothelial damage, elevated propagulation status, inflammation, and extracellular collagen degradation. Accordingly, the objective of this study is to reduce early ventricular remodeling by preventing microvascular thrombosis and reducing inflammation simultaneously with PPACK (phenylalanine‐proline‐arginine chloromethylketone) perfluorocarbon (PFC) nanoparticles (NP). Benefits of delivery PPACK by PFC NP are 1) enabling formation of anticoagulation surface specifically in the damaged vessels where thrombin is activated in order to preserve vascular integrity and limit inflammation induced by thrombin signaling and 2) minimum systemic exposure to avoid the risk of bleeding. Fluorescence microscopic images demonstrated the delivery of PFC NPs to the area at risk and remain there 24 hours after the i.v. injection (n=10) (Fig. A). For all 32 mice underwent closed‐chest ischemia (LAD occlusion) for 90 min followed by 24 hrs reperfusion. Before and 24 hrs after ischemic reperfusion injury, echocardiography was performed (VEVO 2200). The results (Fig. B) demonstrated that PPACK NP treated mice exhibited marked preservation of cardiac functional parameters as early as 24 hours after ischemia as compared to control mice according to changes in contractile metrics: 1) ΔEDV%: 40%±21% vs 77%±38% for treated vs control (p=0.02) and 2) ΔESV%: 118%±43% vs 216%±108%, for treated vs control (p=0.02) (n=16/group). To better understand the therapeutic mechanism, transcriptome profile has been evaluated by using RNASeq on normal zones and border zones of AMI mice with (n=5) or without (n=4) PPACK PFC NP treatment. The results demonstrated that in the border zone after 24 hours reperfusion, PPACK PFC NP treatment attenuated inflammatory NF‐kB signaling, and reduced NF‐kB dependent proteases (MMP 8, 9, 25), which were ~2 times higher in control group (Fig C). Moreover, numerous collagen transcripts, including Col1, 5, 6, 11, 16, and 24, were significantly elevated in the treatment group (Fig D), offering protective effects in AMI. These results demonstrate that PPACK PFC nanoparticle treatment may enhance healing in AMI and preserve cardiac microarchitecture.

Support or Funding Information

R01 DK102691R01 AR067491R01 HL073646‐08

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Clinical presentation, imaging findings, and arthroscopic features in skeletally immature and mature adolescent hip patients: a comparative double-cohort retrospective study
Authors: Schallmo Michael , Marquez-Lara Alejandro , Luo Tianyi David , Stone Austin V. , Mannava Sandeep , Sharma Aman , Howse Elizabeth A. , Stubbs Allston J.
Published: March 2021

The purpose of this study was to evaluate differences in clinical presentation and extent of surgery required based on skeletal maturity between two cohorts of adolescent hip arthroscopy patients. We hypothesized that skeletal immaturity would be associated with a lower frequency of pincer impingement and a decreased need for surgical acetabuloplasty. A database of 1481 hip arthroscopies performed by a single orthopaedic surgeon between 2008 and 2016 was queried. Patients ≤18 years of age with femoroacetabular impingement were divided into two groups based on Risser score: Risser 1–4 (skeletally immature) or Risser 5 (skeletally mature). Groups were compared with respect to presentation, diagnosis, and arthroscopic procedures performed. Eighty-eight skeletally immature and 49 skeletally mature patients were included. Mixed impingement was more common in skeletally mature patients than immature (67.3% vs. 48.9%, P = 0.037). Skeletal maturity was associated with a significantly increased probability of undergoing acetabuloplasty (odds ratio = 4.6, 95% confidence interval 1.4–15.5; P = 0.014). Extent of chondral degeneration was similar between groups. Our findings support the hypothesis that skeletally immature hips undergo acetabuloplasty less frequently and demonstrate similar chondromalacia compared with a skeletally mature cohort. These results suggest that arthroscopic treatment for impingement-associated hip pain may be a reasonable option to consider for symptomatic skeletally immature patients who have completed a structured course of nonoperative treatment. Additional longitudinal outcomes data are needed to clarify the natural history of impingement-associated hip pain in younger populations and whether hip arthroscopy delays progression of osteoarthritis in these patients.
Proximal femoral changes related to obesity: an analysis of slipped capital femoral epiphysis pathoanatomy
Authors: Winston Travis W. , Landau Andrew J. , Hosseinzadeh Pooya
Published: March 2021

Recent research has revealed the importance of the femoral epiphyseal tubercle and cupping height in the stability of the physis and its association with capital femoral slippage. To better understand the connection between the pathogenesis of slipped capital femoral epiphysis and obesity, we performed a retrospective analysis of proximal femur and acetabular anatomies using computed tomography (CT) scans in the hips of normal weight and obese pediatric patients. We measured morphologic characteristics of the proximal femur and acetabulum in developing hips of 31 obese adolescent patients and age-matched and sex-matched control group using pelvic CT scans. Measurements included physeal diameter, tubercle height, width, and volume, cupping height, acetabular rotation and inclination, and metaphyseal bone density. Measurements were performed on true coronal and sagittal views through the center of the epiphysis using previously described and validated techniques. Statistical analysis was performed to compare the measurements between obese and nonobese adolescents. The epiphyseal tubercle volume and average cupping size were similar between the two groups. Acetabular inclination and metaphyseal bone density were significantly different between the cohorts. Metaphyseal bone density was lower among obese patients. Obesity does not appear to cause morphologic changes to the capital femoral physis, though it is associated with a decreased metaphyseal bone mineral density which could indicate physeal instability. This could suggest increased metabolic activity in the metaphyseal bone in obese adolescents. Therefore, metabolic factors associated with obesity, rather than anatomical changes, may be responsible for physeal instability seen in obese adolescents.
Femoral osteotomy is not recommended for children aged 2–3 years with Tönnis grade III developmental dysplasia of the hip
Authors: Duan Jiahua , Yuan Huajiao , Hu Xinyue , Lou Yue , Zheng Pengfei
Published: March 2021

The objective of this study was to compare outcomes following open reduction with and without femoral shortening when treating patients aged 2–3 years with Tönnis grade III developmental dysplasia of the hip (DDH). In this prospective study, 78 patients (6 boys and 72 girls; mean age: 27.8 months; age range: 24–35 months) with Tönnis grade III DDH at our hospital from January 2014 to August 2017 were included. There were 34 hips in the without femoral shortening group and 44 hips in the femoral shortening group. Clinical outcomes were rated using the modified McKay criteria, and the hips were graded using the Severin score. Avascular necrosis (AVN) and redislocation were assessed. Mean follow-up was 26.5 months (range 17–32 months). In the without femoral shortening group (n = 34), there were five patients with AVN (14.7%), and 30 scored excellent and 4 scored good results per the modified McKay criteria. Further, 28 excellent and six good results were obtained using the Severin scale; no patient had redislocation. In the femoral shortening group(n = 44), there were seven patients with AVN (15.9%), and 38 scored excellent and six scored good results per the modified McKay criteria. Further, 31 excellent and 13 good results were obtained using the Severin scale; no patient had redislocation. Additionally, there were no statistically significant differences based on Modified McKay criteria, Severin score and AVN rate. Femoral shortening is not required for children aged 2–3 years with Tönnis grade III DDH.
The efficacy of two-hole tension band plates in the treatment of lower extremity limb length discrepancy
Authors: Ozdemir Erdi , Cetik Riza Mert , Ayvaz Mehmet , Yilmaz Guney
Published: March 2021

The main purpose of our study was to investigate the efficacy of dual two-hole tension band plates in the treatment of lower extremity limb length discrepancy (LLD). We retrospectively reviewed patients who underwent epiphysiodesis utilizing dual two-hole tension band plates due to lower extremity LLD between January 2012 and June 2018. The efficacy of epiphysiodesis was defined as the inhibited percentage of the expected growth of the physis between two time intervals and was calculated between 0–6 months and 6–18 months as the primary outcome. The relationship of efficacy of epiphysiodesis with time intervals, bone segments, physeal coverage percentage by the screws, age and interscrew angle and physeal health was also assessed. A total of 11 patients’ 17 bone segments (9 femurs and 8 tibias) with a mean age of 8.7 ± 2.3 were included. The mean efficacy of the epiphysiodesis in the first 6 months for femurs was 23 ± 20 % (range, 0–53%) and for tibias was 21 ± 19 % (range, 0–53%); between 6 and 18 months it was 27 ± 19 % (range, 0–56%) for femurs and 15 ± 19 % (range, 0–50%) for tibias. In the first 6 months, physeal coverage percentage by the screws (r = 0.503, P = 0.04) and age (r = −0.534, P = 0.027) had a strong correlation with the epiphysiodesis efficacy. Dual two-hole tension band plating has variable efficacy in the treatment of LLD. Age and physeal coverage percentage by the screws could be related to epiphysiodesis efficacy.
Characteristics of Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Comparison With Influenza in Children Admitted to U.K. PICUs
Authors: Kanthimathinathan Hari Krishnan , Buckley Hannah , Lamming Caroline , Davis Peter , Ramnarayan Padmanabhan , Feltbower Richard , Draper Elizabeth S.
Published: March 2021

Objectives:

Severe acute respiratory syndrome coronavirus-2 affects adults disproportionately more than children. A small proportion of children with severe acute respiratory syndrome coronavirus-2 required admission to a PICU. We describe the nationwide U.K. PICU experience of severe acute respiratory syndrome coronavirus-2 infection during the first wave of the pandemic and compare this with the critical care course of the 2019 influenza cohort.

Design:

Prospective nationwide cohort study of characteristics of severe acute respiratory syndrome coronavirus-2–positive children. Data collection utilized routine Pediatric Intensive Care Audit Network and severe acute respiratory syndrome coronavirus-2–specific data.

Setting:

All U.K. PICUs.

Patients:

Children less than 18 years old, admitted to U.K. PICUs between March 14, 2020, and June 13, 2020, and a positive severe acute respiratory syndrome coronavirus-2 polymerase chain reaction. Children admitted to U.K. PICUs in 2019 with influenza provided comparison.

Interventions:

None.

Measurements and Main Results:

We identified 76 PICU admissions among 73 children with a positive severe acute respiratory syndrome coronavirus-2 polymerase chain reaction test. Prevalence of PICU admissions per million was 5.2 for children versus 260 for adults. Ten children (14%) were identified on routine screening. Seventeen children (23%) had pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Seventeen (23%) had coinfections. Invasive ventilation was required in seven of 17 children (41%) with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 versus 38 of 56 other severe acute respiratory syndrome coronavirus-2 positive children (68%), with 77% requiring vasoactive support versus 43%, respectively. Seven children (10%) died. In comparison with influenza children, severe acute respiratory syndrome coronavirus-2 children were older (median [interquartile range]: 10 [1–13] vs 3 yr [1–8 yr]), more often Black or Asian (52% v 18%), higher weight z score (0.29 [–0.80 to 1.62] vs –0.41 [–1.37 to 0.63]), and higher deprivation index (3.3 [–1 to 6.3] vs 1.2 [–1.8 to 4.4]). Comorbidities, frequency of organ supports, and length of stay were similar.

Conclusions:

This nationwide study confirms that PICU admissions with severe acute respiratory syndrome coronavirus-2 infections were infrequent. We have reported similarities and differences in sociodemographic characteristics, organ support interventions, and outcomes of children affected by severe acute respiratory syndrome coronavirus-2 compared with influenza.
Differences in Family Involvement in the Bedside Care of Patients in the ICU Based on Self-Identified Race
Authors: Nunez Eduardo R. , Villa Gianluca , McFadden Rory , Palmisciano Amy , Lanini Iacopo , O’Mahony Sean , Curtis J. Randall , Levy Mitchell M. , Amass Timothy
Published: March 2021

Objectives:

Being a caregiver for a patient in the ICU can place emotional burden on families and engaging families in caregiving can reduce psychological distress. Our goal was to observe support methods used by families in the ICU and identify differences between race/ethnicity.

Design:

A secondary analysis of a multicenter before-and-after clinical trial.

Setting:

Three hospitals in Chicago, Providence, and Florence, Italy.

Participants:

Family members of patients admitted to the ICU.

Interventions:

In the primary study, an intervention was designed to engage families in seven domains that were based on the five physical senses (taste, touch, sight, smell, and sound), personal care, and spiritual care of the patient. During the control phase, nursing staff observed and recorded if they witnessed families participating in support methods unprompted.

MEASUREMENTS AND MAIN RESULTS:

We compared the use of support methods among families from different races, categorized by race as either White, Black, or other using generalized estimating equation population-averaged logistic regression analysis. A total of 133 patients and 226 family members were enrolled in the control arm of the primary study, with patients being 71.2% White, 17% Black, and 11.8% other. Compared with Whites, families who identified their race Black or other may be more likely to participate in support methods that included personal care, touch, or spiritual care. Families who identified as Black may also be more likely to incorporate audio or sound. There were no differences in the categories of sight, smell, or taste.

Conclusions:

Our study identifies racial differences in the use of bedside support methods in the ICU. Guiding families in a culturally congruent and open-minded manner may have the potential to decrease family distress and improve the experience for families in the ICU.
Emerging systemic antitarget treatment for differentiated thyroid carcinoma
Authors: Basté Neus , Mora Mireia , Grau Juan José
Published: March 2021

Purpose of review

We review the new systemic treatment strategies for differentiated thyroid carcinoma, as well as the acquaintance of its molecular biology.

Recent findings

Multiple kinase inhibitor drugs have become the standard therapy for thyroid cancer, albeit several adverse effects. In the last few years, new molecules have raised with an overall safety profile. Most of them, are considered targeted therapies directed toward driven-molecules alterations, such as neurotrophic tyrosine kinase receptor (NTRK) inhibitors for NTRK-fusion thyroid cancer and rearranged during transfection (RET) inhibitors for RET-fusion thyroid cancer. Recently, promising outcomes and safety data have been presented. Furthermore, other novel strategies for advanced thyroid carcinoma are currently investigated in clinical trials.

The ability to provide precision medicine to patients in routine clinical settings depends on the availability of molecular profiling test at their cancer centers. The impossibility to perform molecular characterization could turn out to be a diagnostic and treatment limitation for some patients.

The treatment of advanced differentiated thyroid carcinoma has undergone rapid evolution in the last decade. An emerging treatment era is coming. From now to then, we will need to face the different types of diagnostic tools for molecular characterization, their interpretation and, finally the access to targeted therapies.
COVID-19 and supportive cancer care: key issues and opportunities
Authors: Ashbury Fredrick D.
Published: March 2021

Purpose of review

The disruption to people's lives, including financial impacts, morbidity and loss of life caused by the Coronavirus disease (COVID-19) pandemic requires a dramatic transformation of cancer care delivery, including supportive care. This paper focuses on issues of supportive care in the context of the pandemic, and the extent to which these issues will impact supportive cancer care post-COVID-19.

Recent findings

Cancer care, including supportive care delivery, has had to be dramatically altered during the COVID-19 pandemic, including reallocation of human resources, repurposing of existing physical space, amplified use of telehealth and other remote patient monitoring technologies, changes to treatment and follow-up care patient schedules, among others. These changes have resulted in psychosocial sequelae for cancer patients (including anxiety, stress, loss of control), financial toxicity, and risk of disengagement from treatment and follow-up care.

COVID-19 has seriously disrupted cancer treatment and supportive care for patients and survivors. This paper highlights implications for clinical practice during and post-COVID-19, including the durability of practice adaptations and opportunities for research into mechanisms to support supportive care post the pandemic, including the advancement of eHealth technologies and alternative models of care that integrate community resources, primary care and allied health disciplines.
Dexmedetomidine vs. total intravenous anaesthesia in paediatric emergence delirium
Authors: Petre Maria-Alexandra , Levin David N. , Englesakis Marina , Maynes Jason T. , Pechlivanoglou Petros , Aoyama Kazuyoshi
Published: March 2021

BACKGROUND

Emergence delirium is a common complication in paediatric anaesthesia associated with significant morbidity. Total intravenous anaesthesia (TIVA) and intra-operative dexmedetomidine as an adjuvant to sevoflurane anaesthesia can both reduce the incidence of emergence delirium compared with sevoflurane alone, but no studies have directly compared their relative efficacy.

OBJECTIVE

The study objective was to compare the effects of TIVA and dexmedetomidine on the incidence of paediatric emergence delirium.

STUDY DESIGN

The current study is a systematic review and network meta-analysis (NMA) of randomised controlled trials.

DATA SOURCES

We conducted a systematic search of 12 databases including Medline (Ovid) and Web of Science (Clarivate Analytics) from their respective inception to December 2020.

ELIGIBILITY

Inclusion criteria were randomised controlled trials of paediatric patients undergoing general anaesthesia using sevoflurane, sevoflurane with dexmedetomidine or TIVA. Data were extracted by two reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and analysed using NMA methodology. Risk ratios and 95% credible intervals (CrI) were calculated for all outcomes [emergence delirium, postoperative nausea and vomiting (PONV), and time to emergence and extubation]. The protocol was registered with PROSPERO (CRD42018091237).

RESULTS

The systematic review returned 66 eligible studies comprising 5257 patients with crude median emergence delirium incidences of 12.8, 9.1 and 40% in the dexmedetomidine with sevoflurane, TIVA and sevoflurane alone groups, respectively. NMA indicated that compared with TIVA, sevoflurane with adjuvant dexmedetomidine decreased the incidence of emergence delirium without statistical difference (risk ratio 0.88, 95% CrI 0.61 to 1.20, low quality of evidence), but resulted in a higher incidence of PONV (risk ratio: 2.3, 95% CrI 1.1 to 5.6, low quality of evidence).

CONCLUSION

Clinical judgement, considering the patient's risk factors for the development of clinically significant outcomes such as emergence delirium and PONV, should be used when choosing between TIVA and sevoflurane with adjuvant dexmedetomidine. These findings are limited by the low quality of evidence (conditional recommendation).
The use of high flow nasal oxygen in a patient with Duchenne muscular dystrophy with severe restrictive lung disease requiring dental extractions: a case report
Authors: Desjardins Danielle , Zuo Leila W.
Published: March 2021

Presentation:

A 22-year-old man with Duchenne muscular dystrophy (DMD) presented for removal of impacted third molars in his baseline health status. Comorbidities included decreased mobility, restrictive lung disease [forced vital capacity (FVC) 35% at baseline], adrenal insufficiency, and obstructive sleep apnea.

Anesthetic challenge:

General anesthetics are problematic in this population. The airway is typically compromised by macroglossia. Patients have reduced functional residual capacity, so time to desaturation after induction is reduced; in patients with FVC<50% there is high risk of postoperative pulmonary complications. Those with FVC<30% face further increased risk. The use of depolarizing neuromuscular blockade is contraindicated due to the risk of hyperkalemia. Residual nondepolarizing neuromuscular blockade could compromise postoperative pulmonary status further. Controversy remains regarding use of inhaled anesthetics, but they are generally avoided given the risk of rhabdomyolysis. In addition, DMD patients often have cardiomyopathy, further complicating management. The overall challenge was to avoid general anesthetics in this patient.

How it was done:

After a full discussion with the patient and family, we decided sedation with local anesthetic was the safest anesthetic plan. As a safeguard, inhaled anesthetics were removed, the machine was flushed, and filters were placed in the circuit; a Glidescope was available. We proceeded with moderate sedation with propofol and dexmedetomidine infusions. Given his reduced pulmonary function and need for oral access, the patient was placed on high-flow nasal cannula to provide supplemental oxygen and provide positive end-expiratory pressure. Opioids were kept to a minimum: 50 mcg fentanyl was given with local anesthetic injection. The anesthetic and dental teams talked the patient through his discomfort for much of the procedure. Music of the patient’s choosing was played. Overall the patient did well with a combination of sedation, local anesthesia, and coaching by the surgery and anesthesia teams. He was discharged same day without noted complications of anesthesia.

Conclusion:

Preparation for this apparently “simple” case in a complex patient was key to our success. By addressing the known pulmonary changes in DMD, we employed high-flow nasal cannula in a dental surgery—a new use for this device. By using all the tools available to us as anesthesiologists we were able to avoid an intubation and the possibility of a prolonged hospital stay for our patient.
Scoring Endoscopy in Pediatric Inflammatory Bowel Disease
Authors: Norsa Lorenzo , Ferrari Alberto , Arrigo Serena , Bramuzzo Matteo , Deganello Saccomani Marco , Di Nardo Giovanni , Illiceto Maria Teresa , Miele Erasmo , Paci Monica , Romano Claudio , Romeo Erminia , Daperno Marco , Oliva Salvatore ,   Endoscopy group of the Italian society of pediatric Gastroenterology Hepatology and Nutrition (SIGENP)
Published: March 2021

Objectives and study:

There is a large interobserver variability in evaluating mucosal lesions of inflammatory bowel disease (IBD), especially in pediatric patients. This multicenter prospective observational study aims to evaluate interobserver agreement (IOA) among pediatric endoscopists in assigning validated IBD endoscopic scores in children.

Methods:

Fifteen videos of follow‐up ileocolonoscopies in children with IBD were recorded and selected as cases. Eleven pediatric endoscopists from different centers blindly evaluated all videos and calculated scores: either Ulcerative Colitis Endoscopic Index of Severity (UCEIS) or Simple Endoscopic Score for Crohn Disease (SES‐CD). Scores from all reviewers were compared in order to calculate IOA for general videos and specific sections. Scores from an expert adult reader were used to calculate possible reviewer's characteristics affecting scores’ reliability.

Results:

Intraclass correlation was 0.298 (95% confidence interval [CI]: 0.13–0.55) for ulcerative colitis (UC) and 0.266 (0.11–0.52) for Crohn disease (CD). When a disease activity categorization was adopted (remission, mild, moderate, severe activity) Fleiss kappa coefficient was 0.408 (0.29–0.53) for UC and 0.552 (0.43–0.73) for CD. When stratified by item, vascular pattern of UC was the most reliable item IC: 0.624 (0.321–0.854). In multivariable analysis, none of the reviewer's characteristics affected the readers’ errors.

Conclusions:

This multicenter study shows low agreement among pediatric endoscopists in evaluating endoscopic scores in children with IBD. By using disease activity categorization, agreement slightly increased, mostly for CD. All readers showed a low‐grade concordance with the expert adult gastroenterologist's evaluations. Future‐specific training programs should be considered to increase IOA in using IBD endoscopic activity scores.
Long‐Term Results of Laparoscopic Adjustable Gastric Banding in French adolescents
Authors: Yska Hemmo A.F. , Khen‐Dunlop Naziha , Lacaille Florence , Dabbas Myriam
Published: March 2021

Objectives:

To investigate the long‐term follow‐up (FU) and effectivity of laparoscopic adjustable gastric banding (LAGB) in a French adolescent cohort.

Methods:

We retrospectively analyzed the results of LAGB at our institution. We collected information on FU, adjustable gastric banding (AGB) status, weight‐related parameters, and comorbidity at multiple timepoints.

Results:

Fifty‐six patients (77% female) with a mean age of 16.5 years and a mean body mass index (BMI) of 45 kg/m2 underwent LAGB over a period of 12 years. The mean postpediatric FU was 23 months. FU decreased progressively from 96% at 3 years to 54% and 29% at 6 and 9 years, respectively. The loss to FU was 39% at last contact. AGB was removed in 17 patients (30%) and 12 patients (21%) underwent a second bariatric procedure. Mean BMI decreased by 11 kg/m2 at last contact (P < 0.001). The prevalence of most comorbidities also decreased significantly after 3 years. The mean excess weight loss (to reach a BMI of 25 kg/m2) was 47% during the first year postsurgery and further increased to 55% at last contact.

Conclusion:

Overall, AGB resulted in significant weight loss; however, the increase in heterogeneity suggests that LAGB is more effective in some individuals than in others in the long‐term. This study confirmed that LAGB is a valuable bariatric procedure in adolescents, either as a long term‐term efficient or bridging method that would be replaced at the time of transition to adult care. The importance of a standardized long‐term follow‐up should always be emphasized.
Peginterferon Alfa‐2a (40KD) Plus Lamivudine or Entecavir in Children With Immune‐Tolerant Chronic Hepatitis B
Authors: Mieli‐Vergani Giorgina , Bansal Sanjay , Daniel James F. , Kansu Aydan , Kelly Deirdre , Martin Carmen , Tizzard Sarah , Wirth Stefan , Zhou Julian , Vergani Diego
Published: March 2021

Objective:

Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune‐tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune‐tolerant CHB.

Methods:

Fifty‐nine children aged 3 to <18 years hepatitis B e antigen‐positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa‐2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post‐treatment in the antiviral therapy group or at the end of observation in the control group.

Results:

Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune‐tolerant CHB. At 24 weeks post‐treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment‐related adverse events were reported, and no patients discontinued treatment because of adverse events.

Conclusions:

The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune‐tolerant CHB.
International trauma care: initial European approaches during the COVID 19 pandemic
Authors: Chesser Tim J.S. , Handley Robert , Kloos Johannes , De Wachter Gerrit , Putzeys Guy , Gómez-Vallejo Jesús , Sánchez-Pérez Coral , Chana-Rodríguez Francisco , Raggini Filippo , Pari Carlotta , Paderni Stefania , Contini Achille , Belluati MD Alberto , Daskalakis Ioannis , Sperelakis Ioannis , Kostakos Athanasios , Tosounidis Theodoros H. , Halvachizadeh MD Sascha , Pape MD Hans-Christoph , Bouillon Bertil , de Bruin Berend-Jan , Ponsen Keesjan J.
Published: March 2021

The world was not prepared for the global of pandemic in early 2020 with the arrival of COVID 19. Europe has some of the most developed health care systems in the world and this article explains the initial response to the pandemic from an orthopaedic and trauma viewpoint from 8 nations. Italy reported the first cluster in February, which then rapidly spread around the continent, requiring a rapid reorganization of services. The reports highlight how elective surgery was universally stopped, surgical services were reconfigured, and new practices, such as the widespread use of telemedicine, may well become permanent. It also emphasizes how the pandemic has re-educated us on the importance of a consistent and central approach to deal with a global health crisis, and how medical services need to remain flexible and responsive to new ways of working.
Effects of Covid-19 on orthopaedic trauma services: early experiences in South Africa and Israel
Authors: Maqungo Sithombo , Duma Mlekeleli , Laubscher Maritz , Davidson Amit , Bala Miklosh , Weil Yoram A.
Published: March 2021

South Africa and Israel have significantly different health systems. As South Africa is geographically 500 times as large and has a population nearly 7 times as large as the state of Israel, major differences in the challenges and subsequent handling of the pandemic between these countries were to be expected. South Africa's challenges included being under-resourced, particularly related to trauma, and severe and radical measures had to be undertaken that included extended strict lockdowns, bans on alcohol sales, and cancellation of the majority of the elective surgery during this initial period of the pandemic. Although Israel is much smaller and thereby theoretically easier to control, a complex political situation created difficulties and delays in controlling the pandemic after the initial response, leading to a second wave and additional lockdown. Although massively engaged initially, the Israeli trauma systems had continued functioning almost normally throughout the COVID-19 crisis.
Variability in the Hemodynamic Response to Fluid Bolus in Pediatric Septic Shock
Authors: Ranjit Suchitra , Natraj Rajeswari , Kissoon Niranjan , Thiagarajan Ravi R. , Ramakrishnan Balasubramaniam , Monge García M. Ignacio
Published: March 2021

OBJECTIVES:

Fluid boluses are commonly administered to improve the cardiac output and tissue oxygen delivery in pediatric septic shock. The objective of this study is to evaluate the effect of an early fluid bolus administered to children with septic shock on the cardiac index and mean arterial pressure, as well as on the hemodynamic response and its relationship with outcome.

Design, Setting, Patients, and Interventions:

We prospectively collected hemodynamic data from children with septic shock presenting to the emergency department or the PICU who received a fluid bolus (10 mL/kg of Ringers Lactate over 30 min). A clinically significant response in cardiac index-responder and mean arterial pressure-responder was both defined as an increase of greater than or equal to 10% 10 minutes after fluid bolus.

MEASUREMENTS AND MAIN RESULTS:

Forty-two children with septic shock, 1 month to 16 years old, median Pediatric Risk of Mortality-III of 13 (interquartile range, 9–19), of whom 66% were hypotensive and received fluid bolus within the first hour of shock recognition. Cardiac index- and mean arterial pressure-responsiveness rates were 31% and 38%, respectively. We failed to identify any association between cardiac index and mean arterial pressure changes (r = 0.203; p = 0.196). Cardiac function was similar in mean arterial pressure- and cardiac index-responders and nonresponders. Mean arterial pressure-responders increased systolic, diastolic, and perfusion pressures (mean arterial pressure – central venous pressure) after fluid bolus due to higher indexed systemic vascular resistance and arterial elastance index. Mean arterial pressure-nonresponders required greater vasoactive-inotrope support and had higher mortality.

CONCLUSIONS:

The hemodynamic response to fluid bolus in pediatric septic shock was variable and unpredictable. We failed to find a relationship between mean arterial pressure and cardiac index changes. The adverse effects of fluid bolus extended beyond fluid overload and, in some cases, was associated with reduced mean arterial pressure, perfusion pressures and higher vasoactive support. Mean arterial pressure-nonresponders had increased mortality. The response to the initial fluid bolus may be helpful to understand each patient’s individualized physiologic response and guide continued hemodynamic management.
Of mice, microglia, and (wo)men: a case series and mechanistic investigation of hydroxychloroquine for complex regional pain syndrome
Authors: Haight Elena S. , Johnson Emily M. , Carroll Ian R. , Tawfik Vivianne L.
Published: March 2021

Introduction:

Complex regional pain syndrome (CRPS) is a condition that occurs after minor trauma characterized by sensory, trophic, and motor changes. Although preclinical studies have demonstrated that CRPS may be driven in part by autoinflammation, clinical use of immune-modulating drugs in CRPS is limited. Hydroxychloroquine (HCQ) is a disease-modifying antirheumatic drug used to treat malaria and autoimmune disorders that may provide benefit in CRPS.

Objectives:

To describe the use of HCQ in patients with refractory CRPS and investigate possible mechanisms of benefit in a mouse model of CRPS.

Methods:

We initiated HCQ therapy in 7 female patients with refractory CRPS undergoing treatment at the Stanford Pain Management Center. We subsequently undertook studies in the mouse tibial fracture–casting model of CRPS to identify mechanisms underlying symptom reduction. We evaluated behavior using mechanical allodynia and spinal cord autoinflammation by immunohistochemistry and enzyme-linked immunosorbent assay.

Results:

We treated 7 female patients with chronic, refractory CRPS with HCQ 200 mg twice daily for 2 months, followed by 200 mg daily thereafter. Two patients stopped HCQ secondary to lack of response or side effects. Overall, HCQ significantly improved average numerical rating scale pain from 6.8 ± 1.1 before HCQ to 3.8 ± 1.9 after HCQ treatment. In the tibial fracture–casting mouse model of CRPS, we observed reductions in allodynia, paw edema, and warmth following daily HCQ treatment starting at 3 weeks after injury. Spinal cord dorsal horn microglial activation and cytokine levels were also reduced by HCQ treatment.

Conclusion:

Together, these preclinical and clinical results suggest that HCQ may benefit patients with CRPS at least in part by modulating autoinflammation and support further investigation into the use of HCQ for CRPS.