bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distal Adding-on Phenomenon in Scoliosis Secondary to Chiari Malformation Type I
Authors: Yin Rui , Qin Xiaodong , Shi Benlong , He Zhong , Qian Bangping , Qiu Yong , Zhu Zezhang 
Published: November 2020

Study Design.
A retrospective study.

Objective.
The aim of this study was to investigate the incidence and risk factors for distal adding-on (AO) phenomenon after posterior spinal fusion (PSF) in scoliosis secondary to Chiari malformation type I (CMS) patients with right major thoracic curve.

Summary of Background Data.
Distal AO phenomenon is a common complication observed in adolescent idiopathic scoliosis (AIS), which is significantly associated with unsatisfactory outcomes. However, few studies specifically focused on the incidence and risk factors of distal AO in CMS.

Methods.
Seventy-eight CMS adolescents were included with a minimum of 2-year follow-up after PSF. patients with distal AO at the final follow-up were divided into AO group and those without were No-AO group. The coronal and sagittal parameters were evaluated preoperatively, immediately after surgery, and at the last follow-up. Clinical outcome was analyzed using the Chicago Chiari Outcome Scale (CCOS).

Results.
Distal AO was observed in 18 of 78 patients (23.1%). Compared with No-AO group, patients with distal AO had significantly lower Risser sign (P = 0.001), more flexibility of lumbar curve (P = 0.021), higher incidence of lowest instrumented vertebra-last substantially touched vertebra (LIV-LSTV) ≤0 (P = 0.001), smaller postoperative Cobb angle of lumbar curve (P < 0.001), and greater correction rate of lumbar curve (P = 0.001). Logistic regression analysis revealed that low Risser sign (Grade 1-2, odds ratio [OR] = 5.7, P = 0.029) and LIV-LSTV ≤0 (OR = 6.4, P = 0.019) were independent risk factors for distal AO. There was no significant difference of CCOS scores between two groups at the final follow-up (P > 0.05 for all).

Conclusion.
The incidence of distal AO was 23.1% in CMS patients after PSF. Patients with low Risser sign and LIV-LSTV ≤0 were high risk factors for distal AO.

Level of Evidence: 3
Rescue Treatment With High-Dose Gaseous Nitric Oxide in Spontaneously Breathing Patients With Severe Coronavirus Disease 2019
Authors: Wiegand Steffen B. , Safaee Fakhr Bijan , Carroll Ryan W. , Zapol Warren M. , Kacmarek Robert M. , Berra Lorenzo 
Published: November 2020

Objectives:
Treatment options are limited for patients with respiratory failure due to coronavirus disease 2019. Conventional oxygen therapy and awake proning are options, but the use of high-flow nasal cannula and continuous positive airway pressure are controversial. There is an urgent need for effective rescue therapies. Our aim is to evaluate the role of inhaled nitric oxide 160 ppm as a possible rescue therapy in nonintubated coronavirus disease 2019 patients.

Design:
Retrospective evaluation of coronavirus disease 2019 patients in respiratory distress receiving nitric oxide gas as rescue therapy.

Setting:
Massachusetts General Hospital, between March 18, 2020, and May 20, 2020, during the local coronavirus disease 2019 surge.

Patients:
Coronavirus disease 2019 patients at high risk for acute hypoxemic respiratory failure with worsening symptoms despite use of supplemental oxygen and/or awake proning.

Interventions:
Patients received nitric oxide at concentrations of 160 ppm for 30 minutes twice per day via a face mask until resolution of symptoms, discharge, intubation, or the transition to comfort measures only.

Measurements and Main Results:
Between March 18, 2020, and May 20, 2020, five patients received nitric oxide inhalation as a rescue therapy for coronavirus disease 2019 at Massachusetts General Hospital. All received at least one dosage. The three patients that received multiple treatments (ranging from five to nine) survived and were discharged home. Maximum methemoglobin concentration after 30 minutes of breathing nitric oxide was 2.0% (1.7–2.3%). Nitrogen dioxide was below 2 ppm. No changes in mean arterial pressure or heart rate were observed during or after nitric oxide treatment. Oxygenation and the respiratory rate remained stable during and after nitric oxide treatments. For two patients, inflammatory marker data were available and demonstrate a reduction or a cessation of escalation after nitric oxide treatment.

Conclusions:
Nitric oxide at 160 ppm may be an effective adjuvant rescue therapy for patients with coronavirus disease 2019.
Timing of Tracheostomy for Prolonged Respiratory Wean in Critically Ill Coronavirus Disease 2019 Patients: A Machine Learning Approach
Authors: Takhar Arunjit , Surda Pavol , Ahmad Imran , Amin Nikul , Arora Asit , Camporota Luigi , Denniston Poppy , El-Boghdadly Kariem , Kvassay Miroslav , Macekova Denisa , Munk Michal , Ranford David , Rabcan Jan , Tornari Chysostomos , Wyncoll Duncan , Zaitseva Elena , Hart Nicholas , Tricklebank Stephen 
Published: November 2020

Objectives:
To propose the optimal timing to consider tracheostomy insertion for weaning of mechanically ventilated patients recovering from coronavirus disease 2019 pneumonia. We investigated the relationship between duration of mechanical ventilation prior to tracheostomy insertion and in-hospital mortality. In addition, we present a machine learning approach to facilitate decision-making.

Design:
Prospective cohort study.

Setting:
Guy’s & St Thomas’ Hospital, London, United Kingdom.

Patients:
Consecutive patients admitted with acute respiratory failure secondary to coronavirus disease 2019 requiring mechanical ventilation between March 3, 2020, and May 5, 2020.

Interventions:
Baseline characteristics and temporal trends in markers of disease severity were prospectively recorded. Tracheostomy was performed for anticipated prolonged ventilatory wean when levels of respiratory support were favorable. Decision tree was constructed using C4.5 algorithm, and its classification performance has been evaluated by a leave-one-out cross-validation technique.

Measurements and Main Results:
One-hundred seventy-six patients required mechanical ventilation for acute respiratory failure, of which 87 patients (49.4%) underwent tracheostomy. We identified that optimal timing for tracheostomy insertion is between day 13 and day 17. Presence of fibrosis on CT scan (odds ratio, 13.26; 95% CI [3.61–48.91]; p ≤ 0.0001) and Pao
2:Fio
2 ratio (odds ratio, 0.98; 95% CI [0.95–0.99]; p = 0.008) were independently associated with tracheostomy insertion. Cox multiple regression analysis showed that chronic obstructive pulmonary disease (hazard ratio, 6.56; 95% CI [1.04–41.59]; p = 0.046), ischemic heart disease (hazard ratio, 4.62; 95% CI [1.19–17.87]; p = 0.027), positive end-expiratory pressure (hazard ratio, 1.26; 95% CI [1.02–1.57]; p = 0.034), Pao
2:Fio
2 ratio (hazard ratio, 0.98; 95% CI [0.97–0.99]; p = 0.003), and C-reactive protein (hazard ratio, 1.01; 95% CI [1–1.01]; p = 0.005) were independent late predictors of in-hospital mortality.

Conclusions:
We propose that the optimal window for consideration of tracheostomy for ventilatory weaning is between day 13 and 17. Late predictors of mortality may serve as adverse factors when considering tracheostomy, and our decision tree provides a degree of decision support for clinicians.
A Propensity-Matched Cohort Study of Tocilizumab in Patients With Coronavirus Disease 2019
Authors: Lewis Tyler C. , Adhikari Samrachana , Tatapudi Vasishta , Holub Meredith , Kunichoff Dennis , Troxel Andrea B. , Montgomery Robert A. , Sterman Daniel H. 
Published: November 2020

Objectives:
To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019.

Design:
Observational cohort study of patients hospitalized with coronavirus disease 2019 between March 1, 2020, and April 24, 2020. A propensity-matched (1:1) analysis was used to compare patients who received tocilizumab to controls who did not. Competing risk survival analysis was used to determine the primary outcome of time to mortality, and adjusted log-linear and logistic regression for secondary outcomes.

Setting:
Three hospitals within the NYU Langone Health system in New York.

Patients:
Consecutive adult patients hospitalized with coronavirus disease 2019.

Intervention:
Tocilizumab 400-mg IV once in addition to standard of care or standard of care alone.

Measurements and Main Results:
Data from 3,580 severe acute respiratory syndrome coronavirus 2 positive qualifying hospitalized patients were included, of whom 497 (13.9%) were treated with tocilizumab. In the analysis of tocilizumab-treated patients and matched controls, fewer tocilizumab-treated patients died (145/497, 29.2%) than did controls (211/497, 42.4%). In the adjusted competing risk regression model, tocilizumab therapy was associated with improved survival relative to controls (hazard ratio = 0.24, 95% CI = 0.18–0.33, p < 0.001). Tocilizumab-treated patients and controls had similar adjusted time to discharge from hospital (hazard ratio = 0.96, 95% CI = 0.78–1.17, p = 0.67). However, they had longer adjusted ICU length of stay (rate ratio = 3.1, 95% CI = 2.5–3.7, p < 0.001) and a higher adjusted infection rate (odds ratio = 4.18, 95% CI = 2.72–6.52, p < 0.001) than controls.

Conclusions:
Tocilizumab therapy was associated with significantly improved survival in coronavirus disease 2019 patients. This survival benefit was associated with increased ICU length of stay and increased infection rate, even as more patients in the tocilizumab group were rescued from rapid death. A prospective, randomized, placebo-controlled trial is needed to confirm these findings.
Procalcitonin Exerts a Mediator Role in Septic Shock Through the Calcitonin Gene-Related Peptide Receptor
Authors: Baranowsky Anke , Appelt Jessika , Kleber Christian , Lange Tobias , Ludewig Peter , Jahn Denise , Pandey Puja , Keller Daniela , Rose Thomas , Schetler Daniela , Braumüller Sonja , Huber-Lang Markus , Tsitsilonis Serafeim , Yorgan Timur , Frosch Karl-Heinz , Amling Michael , Schinke Thorsten , Keller Johannes 
Published: November 2020

OBJECTIVES:
Clinically, procalcitonin represents the most widely used biomarker of sepsis worldwide with unclear pathophysiologic significance to date. Pharmacologically, procalcitonin was shown to signal through both calcitonin receptor and calcitonin gene-related peptide receptor in vitro, yet the identity of its biologically relevant receptor remains unknown.

DESIGN:
Prospective randomized animal investigations and in vitro human blood studies.

SETTING:
Research laboratory of a university hospital.

SUBJECTS:
C57BL/6J mice and patients with post-traumatic sepsis.

INTERVENTIONS:
Procalcitonin-deficient mice were used to decipher a potential mediator role in experimental septic shock and identify the relevant receptor for procalcitonin. Cecal ligation and puncture and endotoxemia models were employed to investigate septic shock. Disease progression was evaluated through survival analysis, histology, proteome profiling, gene expression, and flow cytometry. Mechanistic studies were performed with cultured macrophages, dendritic cells, and gamma delta T cells. Main findings were confirmed in serum samples of patients with post-traumatic sepsis.

MEASUREMENTS AND MAIN RESULTS:
Procalcitonin-deficient mice are protected from septic shock and show decreased pulmonary inflammation. Mechanistically, procalcitonin potentiates proinflammatory cytokine expression in innate immune cells, required for interleukin-17A expression in gamma delta T cells. In patients with post-traumatic sepsis, procalcitonin positively correlates with systemic interleukin-17A levels. In mice with endotoxemia, immunoneutralization of interleukin-17A inhibits the deleterious effect of procalcitonin on disease outcome. Although calcitonin receptor expression is irrelevant for disease progression, the nonpeptide calcitonin gene-related peptide receptor antagonist olcegepant, a prototype of currently introduced antimigraine drugs, inhibits procalcitonin signaling and increases survival time in septic shock.

CONCLUSIONS:
Our experimental data suggest that procalcitonin exerts a moderate but harmful effect on disease progression in experimental septic shock. In addition, the study points towards the calcitonin gene-related peptide receptor as relevant for procalcitonin signaling and suggests a potential therapeutic application for calcitonin gene-related peptide receptor inhibitors in sepsis, which warrants further clinical investigation.
An Appraisal of Electrodiagnostic Studies in Stiff Person Syndrome
Authors: Li Yuebing , Thakore Nimish 
Published: November 2020

Abstract
A literature review was performed on the use of electrodiagnostic (EDX) tests including nerve conduction study, electromyography, exteroceptive reflex, blink reflex, and late response in the evaluation of patients with stiff person syndrome (SPS). A web survey was conducted to report the extent of EDX testing usage in the evaluation of SPS among laboratories accredited by the American Academy of Neuromuscular and Electrodiagnostic Medicine. Coactivation of selected agonist and antagonist muscles was performed in 5 healthy subjects to determine its specificity for SPS. Observation of continuous motor unit activity on electromyography and elicitation of exteroceptive reflexes by electric stimulation are informative in assisting a diagnosis of SPS, but further studies focusing on their sensitivities in diagnosing SPS and specificities in differentiating SPS from other movement disorders are needed. The value of EDX testing in SPS lies in ruling out other neuromuscular disorders.
A Pharmacoepidemiologic Approach to Evaluate Real-world Effectiveness of Hormonal Contraceptives in the Presence of Drug–drug Interactions
Authors: Sarayani Amir , Brown Joshua D. , Goodin Amie J. , Squires Patrick , Pham Phuong , Cicali Brian , Henriksen Carl , Schmidt Stephan , Winterstein Almut G. 
Published: November 2020

Background:
Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates.

Methods:
We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC’s effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12–48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting.

Results:
We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person–years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2).

Conclusions:
OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug–drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.
Eighty-micron flap femtosecond-assisted LASIK for the correction of myopia and myopic astigmatism
Authors: Bages-Rousselon Yunuen , Pinkus Denisse , Rivas Miguel , Butron Karla , Robledo Nora , Chayet Arturo 
Published: November 2020

Purpose:
To evaluate the safety and efficacy of 80-μm flap femtosecond laser–assisted LASIK and the early clinical and refractive outcomes in the correction of myopia and myopic astigmatism.

Setting:
Private practice, outpatient.

Design:
Prospective study.

Methods:
Patients who underwent femtosecond-assisted LASIK between February and April 2018 were included. Inclusion criteria were myopia from −1.00 to −8.00 diopters (D) and astigmatism up to −3.00 D and no previous surgeries. All patients were tested preoperatively and on day 1 and month 3 for uncorrected distance visual acuity (UDVA), manifest refraction, corrected distance visual acuity (CDVA), intraocular pressure (IOP), slitlamp and dilated fundus examination, Schirmer I test with anesthesia, and ocular surface disease index questionnaire. The FEMTO LDV Z8 was used for flap construction and the Wavelight Allegretto 400 excimer for refractive treatment. Flap thickness was measured at week 1 with anterior segment optical coherence tomography (AS-OCT).

Results:
Eighty-two eyes were included. Logarithm of the minimum angle of resolution UDVA was 1.28 ± 0.53 preoperatively, 0.02 ± 0.05 at day 1, and 0.14 ± 0.127 at month 3. There was no loss of CDVA lines. The mean flap thickness measured at 1 week with AS-OCT was 73 ± 6.7 µm.

Conclusions:
The use of ultrathin flaps, just below Bowman's layer, with the Ziemer LDV Z8 femtosecond laser was possible, safe, reliable, and reproducible. Eighty-micron flaps allowed for excellent vision on 1 day post-LASIK and might be a good alternative to maintain an appropriate percentage of tissue altered, especially when attempting greater corrections or larger treatment zones.
Human hematopoiesis: aging and leukemogenic risk
Authors: Adelman Emmalee R. , Figueroa Maria E. 
Published: November 2020

Purpose of review
Our understanding of the effects of aging on human hematopoiesis has advanced significantly in recent years, yet the full ramifications of these findings are not fully understood. This review summarizes these findings and discusses their implication as they relate to malignant hematopoiesis.

Recent findings
With human aging there is an impaired immune response, loss of hematopoietic stem cell (HSC) function, increase in clonal hematopoiesis, and higher frequency of myeloid malignancies. Although murine models have implicated abnormalities in DNA damage repair, autophagy, metabolism, and epigenetics, studies in primary human specimens are more limited. The development of age-related clonal hematopoiesis and the risk associated with this is one of the major findings in the field of recent years. This is accompanied by changes in bone marrow stem and progenitor composition, changes in the epigenetic program of stem cells and an inflammatory milieu in the bone marrow. The precise consequences of these changes for the development of age-related malignancies are still unclear.

Summary
Advances in the field have begun to reveal the mechanisms driving human HSC loss of function with age. It will be critical to delineate between normal and malignant aging in order to better prevent age-associated myeloid malignancies.
Current understanding of human megakaryocytic-erythroid progenitors and their fate determinants
Authors: Kwon Nayoung , Thompson Evrett N. , Mayday Madeline Y. , Scanlon Vanessa , Lu Yi-Chien , Krause Diane S. 
Published: November 2020

Purpose of review
This review focuses on our current understanding of fate decisions in bipotent megakaryocyte-erythroid progenitors (MEPs). Although extensive research has been carried out over decades, our understanding of how MEP commit to the erythroid versus megakaryocyte fate remains unclear.

Recent findings
We discuss the isolation of primary human MEP, and focus on gene expression patterns, epigenetics, transcription factors and extrinsic factors that have been implicated in MEP fate determination. We conclude with an overview of the open debates in the field of MEP biology.

Summary
Understanding MEP fate is important because defects in megakaryocyte and erythrocyte development lead to disease states such as anaemia, thrombocytopenia and leukaemia. MEP also represent a model system for studying fundamental principles underlying cell fate decisions of bipotent and pluripotent progenitors, such that discoveries in MEP are broadly applicable to stem/progenitor cell biology.
Current evidence for focal therapy and partial gland ablation for organ-confined prostate cancer: systematic review of literature published in the last 2 years
Authors: Kayano Paulo Priante , Klotz Laurence 
Published: November 2020

Purpose of review
The shift in the diagnostic algorithm for prostate cancer to early imaging with mpMRI has resulted in many patients being diagnosed with small volume, apparently unilateral, clinically significant cancers. In these patients, a minimally invasive, nonmorbid intervention is appealing. The aim of this study was to review data reported within the last 2 years on focal therapy and partial gland ablation for organ-confined prostate cancer.

Recent findings
High-intensity focal ultrasound, focal cryotherapy, photodynamic therapy, irreversible electroporation and focal laser ablation, have been used as treatment modalities for localized prostate cancer treatment. The reported oncologic outcomes vary widely and makes comparisons challenging. All the focal therapies report low rates of complications, and high rates of continence and erectile function preservation. The most common adverse events are hematuria, urinary retention and urinary tract infections. During this period, the initial results of several new technologies including MRI-guided transurethral ultrasound ablation were published.

Summary
Focal therapy and partial gland ablation for organ-confined prostate cancer is an option for patients with intermediate-risk disease because of its low complication profile and preservation of QOL. Trials comparing the outcome of different focal therapy technologies have not been carried out, and the existing evidence does not point to one approach being clearly superior to others. Long-term oncologic outcome is lacking. Despite this, for men with unilateral intermediate-risk prostate cancer whose disease is often relatively indolent, focal therapy is an appealing option.
An Exploratory Study of Bullying Directed Toward Clinical Nursing Faculty
Authors: El Ghaziri Mazen , Simons Shellie , Taylor Rosemary 
Published: November 2020

Background
Clinical education is an integral component of nursing education and relies heavily on clinical nursing faculty (CNF). However, there are not enough nurses seeking CNF positions to meet the current demand of the nursing workforce.

Purpose
The purpose of this study was to examine the prevalence and impact of workplace bullying directed toward CNF.

Methods
For this exploratory cross-sectional study, a web-based survey was distributed to CNF working in New England states.

Results
A total of 76 participant responses were analyzed. Eighteen percent of the participants met the criteria for being either occasionally or frequently bullied. Nursing staff in the clinical agencies and colleagues and administrators in the nursing program where CNF teach were identified as the most frequent perpetrators.

Conclusions
Understanding the prevalence and impact of bullying of CNF helps inform the development of strategies to support and retain these essential members of the nursing education workforce.