bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Evolution of Transmitted Human Immunodeficiency Virus Drug Resistance in Belgium Between 2013 and 2019
Authors: Mortier Virginie , Debaisieux Laurent , Dessilly Géraldine , Stoffels Karolien , Vaira Dolores , Vancutsem Ellen , Van Laethem Kristel , Vanroye Fien , Verhofstede Chris
Published: April 2022

Background

To assess the prevalence and evolution of transmitted drug resistance (TDR) in Belgium, a total of 3708 baseline human immunodeficiency virus (HIV)-1 polymerase sequences from patients diagnosed between 2013 and 2019 were analyzed.

Methods

Protease and reverse-transcriptase HIV-1 sequences were collected from the 7 national Aids Reference Laboratories. Subtype determination and drug resistance scoring were performed using the Stanford HIV Drug Resistance Database. Trends over time were assessed using linear regression, and the maximum likelihood approach was used for phylogenetic analysis.

Results

A total of 17.9% of the patients showed evidence of TDR resulting in at least low-level resistance to 1 drug (Stanford score  ≥15). If only the high-level mutations (Stanford score ≥60) were considered, TDR prevalence dropped to 6.3%. The majority of observed resistance mutations impacted the sensitivity for nonnucleoside reverse-transcriptase inhibitors (NNRTIs) (11.4%), followed by nucleoside reverse-transcriptase inhibitors (6.2%) and protease inhibitors (2.4%). Multiclass resistance was observed in 2.4%. Clustered onward transmission was evidenced for 257 of 635 patients (40.5%), spread over 25 phylogenetic clusters.

Conclusions

The TDR prevalence remained stable between 2013 and 2019 and is comparable to the prevalence in other Western European countries. The high frequency of NNRTI mutations requires special attention and follow-up. Phylogenetic analysis provided evidence for local clustered onward transmission of some frequently detected mutations.
The value of ultrasound-defined tenosynovitis and synovitis in the prediction of persistent arthritis
Authors: Sahbudin Ilfita , Singh Ruchir , De Pablo Paola , Rankin Elizabeth , Rhodes Benjamin , Justice Elizabeth , Derrett-Smith Emma , Amft Nicole , Narayan Nehal , McGrath Catherine , Baskar Sangeetha , Trickey Jeanette , Maybury Mark , Raza Karim , Filer Andrew
Published: April 2022

Objectives

The value of US-defined tenosynovitis in predicting the persistence of inflammatory arthritis is not well described. In particular, the predictive utility of US-defined tenosynovitis of larger tendons is yet to be reported. We assessed the value of US-defined tenosynovitis alongside US-defined synovitis and clinical and serological variables in predicting persistent arthritis in an inception cohort of DMARD-naïve patients with early arthritis.

Methods

One hundred and fifty DMARD-naïve patients with clinically apparent synovitis of one or more joints and a symptom duration of ≤3 months underwent baseline clinical, laboratory and US (of 19 bilateral joints and 16 bilateral tendon compartments) assessments. Outcomes were classified as persistent or resolving arthritis after 18 months’ follow-up. The predictive value of US-defined tenosynovitis for persistent arthritis was compared with those of US-defined synovitis, and clinical and serological variables.

Results

At 18 months, 99 patients (66%) had developed persistent arthritis and 51 patients (34%) had resolving disease. Multivariate logistic regression analysis showed that US-detected digit flexor tenosynovitis [odds ratio (OR): 6.6, 95% CI: 2.0 , 22.1, P = 0.002] provided independent predictive data for persistence over and above the presence of US-detected joint synovitis and RF antibodies. In the RF/ACPA-negative subcohort, US-defined digit flexor tenosynovitis remained a significant predictive variable (OR: 4.7, 95% CI: 1.4, 15.8, P = 0.012), even after adjusting for US-defined joint synovitis.

Conclusion

US-defined tenosynovitis provided independent predictive data for the development of persistent arthritis. The predictive role of US-defined digit flexor tenosynovitis should be further assessed; investigators should consider including this tendon site as a candidate variable when designing imaging-based predictive algorithms for persistent inflammatory arthritis development.
Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization
Authors: Rodríguez Ruiz Alejandro , van Hoolwerff Marcella , Sprangers Sara , Suchiman Eka , Schoenmaker Ton , Dibbets-Schneider Petra , Bloem Johan L , Nelissen Rob G H H , Freund Christian , Mummery Christine , Everts Vincent , de Vries Teun J , Ramos Yolande F M , Meulenbelt Ingrid
Published: April 2022

Objectives

To study the mechanism by which the readthrough mutation in TNFRSF11B, encoding osteoprotegerin (OPG) with additional 19 amino acids at its C-terminus (OPG-XL), causes the characteristic bidirectional phenotype of subchondral bone turnover accompanied by cartilage mineralization in chondrocalcinosis patients.

Methods

OPG-XL was studied by human induced pluripotent stem cells expressing OPG-XL and two isogenic CRISPR/Cas9-corrected controls in cartilage and bone organoids. Osteoclastogenesis was studied with monocytes from OPG-XL carriers and matched healthy controls followed by gene expression characterization. Dual energy X-ray absorptiometry scans and MRI analyses were used to characterize the phenotype of carriers and non-carriers of the mutation.

Results

Human OPG-XL carriers relative to sex- and age-matched controls showed, after an initial delay, large active osteoclasts with high number of nuclei. By employing hiPSCs expressing OPG-XL and isogenic CRISPR/Cas9-corrected controls to established cartilage and bone organoids, we demonstrated that expression of OPG-XL resulted in excessive fibrosis in cartilage and high mineralization in bone accompanied by marked downregulation of MGP, encoding matrix Gla protein, and upregulation of DIO2, encoding type 2 deiodinase, gene expression, respectively.

Conclusions

The readthrough mutation at CCAL1 locus in TNFRSF11B identifies an unknown role for OPG-XL in subchondral bone turnover and cartilage mineralization in humans via DIO2 and MGP functions. Previously, OPG-XL was shown to affect binding between RANKL and heparan sulphate (HS) resulting in loss of immobilized OPG-XL. Therefore, effects may be triggered by deficiency in the immobilization of OPG-XL Since the characteristic bidirectional pathophysiology of articular cartilage calcification accompanied by low subchondral bone mineralization is also a hallmark of OA pathophysiology, our results are likely extrapolated to common arthropathies.
MDA5 expression is associated with TGF-β-induced fibrosis: potential mechanism of interstitial lung disease in anti-MDA5 dermatomyositis
Authors: Shen Ning , Zhou Xiaopeng , Jin Xuexiao , Lu Ci , Hu Xiuhua , Zhang Yichi , Jiang Yu , Xu Qin , Xu Xiayan , Liu Minghao , Lu Linrong , Han Yongmei
Published: April 2022

Objectives

This study aimed to investigate the high-resolution CT (HRCT) characteristics of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5 DM-ILD), and to clarify the underlying mechanisms of the clinical phenomenon.

Methods

Clinical data and HRCT patterns were compared between anti-MDA5 DM-ILD (n = 32) and antisynthetase syndrome-associated ILD (ASS-ILD) (n = 29). RNA sequencing of whole-blood samples from the two groups, and in vitro experiments using human embryonic lung fibroblasts (HELFs) were conducted to explore the potential mechanisms of the clinical findings.

Results

The anti-MDA5 DM-ILD subset had a significantly higher incidence of rapidly progressive ILD (RPILD) than ASS-ILD (65.6% vs 37.9%; P = 0.031). The relative percentage of the lung fibrosis HRCT pattern was significantly lower in the anti-MDA5 DM-ILD group, especially the RPILD subgroup (P = 0.013 and 0.003, respectively). RNA sequencing detected the upregulated genes including interferon-induced helicase C domain 1 (encoding MDA5), and a trend towards downregulated expression of TGF-β signalling components in anti-MDA5 DM-ILD. In vitro culture of HELFs revealed that upregulated expression of MDA5 in HELFs was correlated with the downregulated expression of alpha smooth muscle actin, connective tissue growth factor, collagen I and collagen III by suppressing the TGF-β signalling pathway.

Conclusions

Anti-MDA5 DM-ILD patients have significantly less lung fibrosis and elevated MDA5 expression. The upregulated expression of MDA5 has relations with the suppression of the pro-fibrotic function of fibroblasts via the TGF-β signalling pathway, which may partially explain the mechanism of the clinical phenomenon.
Cutaneous Vascular Compromise and Resolution of Skin Barrier Breakdown After Dermal Filler Occlusion—Implementation of Evidence-Based Recommendations Into Real-World Clinical Practice
Authors: Loyal Jameson , Hartman Nina , Fabi Sabrina G. , Butterwick Kimberly J. , Goldman Mitchel P.
Published: April 2022

BACKGROUND

Vascular occlusions that threaten skin integrity, although not an emergency like those that threaten a patient's vision, is an urgent situation. Accurately interpreting physical examination findings is paramount. The use of high-dose, pulsed hyaluronidase is the mainstay of therapy; however, adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and hyperbaric oxygen should be considered.

OBJECTIVE

To provide a review of the literature on the treatment of vascular occlusions threatening skin barrier integrity and develop a step-wise treatment guide.

MATERIALS AND METHODS

The authors searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords.

RESULTS

Twenty-six articles focusing on vascular occlusions threatening the skin barrier were reviewed. The authors collectively agreed on treatments to reverse vascular occlusions and restore the skin barrier. The importance of high-dose, pulsed hyaluronidase was clear. Therapies that lacked evidence such as sodium thiosulfate were also revealed.

CONCLUSION

A vascular occlusion that threatens skin integrity is an urgent matter which requires accurate interpretation of physical examination findings that will help guide intervention. High-dose, pulsed hyaluronidase along with adjunctive measures performed in a step-wise manner is key to an optimal outcome.
Effects of Transcendental Meditation on Blood Pressure
Authors: Schneider Joanne Kraenzle , Reangsing Chuntana , Willis Danny G.
Published: April 2022

Background

The World Health Organization estimates that 1.13 billion people worldwide have hypertension. Although pharmaceutical management of blood pressure is available, there are reasons why people prefer not to take medications including costs, adverse effects, and lack of access. Nonpharmacological healthy lifestyle methods are needed. One alternative method is transcendental meditation (TM).

Objective

The purpose of this study was to quantitatively synthesize the effects of TM on blood pressure. In addition, we examined the moderator effects of participant, methods, and intervention characteristics.

Methods

We searched 19 electronic databases without date restrictions to March 2021 including the gray literature and specific journals for primary studies evaluating TM to reduce blood pressure in adults and written in English. We coded primary studies for 5 categories (source, method, intervention, participant characteristics, and outcomes).

Results

Across 18 primary studies (N = 1207), TM mildly improved systolic blood pressure by −3.3 mm Hg (P = .025) and diastolic blood pressure by −1.8 mm Hg (P = .008) compared with comparison groups, but the effects waned after 3 months. Transcendental meditation reduced systolic blood pressure in samples that were 65 years and older significantly more than in samples that were younger than 65 years (−1.44 vs −9.87, P = .021) but showed no differential effect on diastolic blood pressure.

Conclusions

Transcendental meditation mildly reduced blood pressure, but the effect waned after 3 months. Adults older than 65 years benefited more than younger adults. Transcendental meditation might be recommended as one aspect of a healthy lifestyle.
First Use of a New Extracorporeal Membrane Oxygenation System in COVID19-Associated Adult Respiratory Distress Syndrome: The MobyBox Device
Authors: Kau Miriam , Steltner Jens C. , Lepper Philipp M. , Omlor Albert J. , Mang Sebastian , Misic Jovan , Peivandi Ali A. , Muellenbach Ralf M. , Reyher Christian
Published: April 2022

In late 2020, during the second wave of COVID-19 in Germany, we started using the MobyBox, which is a novel fully pneumatically driven ECMO device, on a regular basis to meet the increasing demand for ECMO therapy. In this case series, we performed a retrospective chart review of seven patients with severe COVID-19-related acute respiratory distress syndrome (ARDS) requiring veno-venous (vv)-ECMO support with the MobyBox. During ECMO treatments we have observed no disadvantages in comparison to conventional ECMO systems. There were no system failures or adverse events directly attributable to the MobyBox system. Our data support that providing vv-ECMO with the MobyBox device is safe and feasible. Furthermore, our findings suggest that the MobyBox device might represent an advantage in terms of biocompatibility. Therefore, more data on this issue is needed to better understand how the pneumatically driven pump affects cellular blood components.
Bivalirudin Versus Unfractionated Heparin in Patients With Cardiogenic Shock Requiring Venoarterial Extracorporeal Membrane Oxygenation
Authors: Uricchio Marissa N. , Ramanan Raj , Esper Stephen A. , Murray Holt , Kaczorowski David J. , D’Aloiso Brandon , Gomez Hernando , Sciortino Christopher , Sanchez Pablo G. , Sappington Penny L. , Rivosecchi Ryan M.
Published: April 2022

This study evaluated differences in efficacy and safety outcomes with bivalirudin compared with unfractionated heparin (UFH) in patients with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA ECMO). We performed a retrospective study at an academic medical center that included patients greater than 18 years of age supported with VA ECMO due to cardiogenic shock from January 2009 to February 2021. The primary endpoint was ECMO-associated thrombotic events normalized to duration of ECMO support. Secondary safety endpoints included major bleeding (per ELSO criteria) and blood product administration. Overall, 143 patients were included in our analysis with 54 having received bivalirudin and 89 having received UFH. Median duration of ECMO support was 92 (interquartile range, 56–172) hours. ECMO-associated thrombotic events per ECMO day were significantly less among those that received bivalirudin (P < 0.001). In adjusted regression, bivalirudin was independently associated with an increased time to thrombosis when compared with UFH (Exp[B] –3.8; 95% confidence interval, 1.7–8.8; P = 0.002). Patients receiving bivalirudin experienced less major bleeding events (P = 0.02) with less total red blood cell and fresh frozen plasma administration (P = 0.04 and P = 0.03, respectively). Bivalirudin is a safe and efficacious alternative to UFH in patients requiring VA ECMO for cardiogenic shock.
Functional constipation in patients with hemorrhoids: a systematic review and meta-analysis
Authors: Kalkdijk Jenneke , Broens Paul , ten Broek Richard , van der Heijden Joost , Trzpis Monika , Pierie Jean Pierre , Klarenbeek Bastiaan
Published: April 2022

Hemorrhoids are common anorectal pathology, with high recurrence rates after surgical treatment. It is hypothesized that high straining forces during paradoxical contractions and inadequate relaxation are causally related to hemorrhoids. This review aimed to assess the coprevalence of functional constipation and dyssynergic defecation in a population with hemorrhoids. Moreover, the effects of rubber band ligation (RBL) were analyzed. Sources included Pubmed, Embase and CENTRAL. Randomized trials, cohort and case-control studies that investigated the prevalence of constipation in patients with hemorrhoids or the prevalence of hemorrhoids in patients with constipation compared to healthy subjects were included. Manometric studies were also eligible. Quality assessment was performed by using the Newcastle Ottawa Quality Assessment Scale. The primary outcome was the prevalence of functional constipation or dyssynergic defecation in patients with hemorrhoids. Nineteen studies were included. Prevalence of constipation was significantly higher in patients with hemorrhoids compared to controls [OR (odds ratio), 2.09; 95% CI (confidence interval), 1.27–3.44]. No significant difference in the prevalence of hemorrhoids between patients with constipation compared to controls was found (OR, 2.37; 95% CI, 0.67–8.44). Anal pressures in patients with hemorrhoids were significantly higher compared to healthy controls in all manometric studies. After RBL, these pressures remained significantly higher in patients with hemorrhoids (P = 0.001). Functional constipation, dyssynergic defecation and higher basal anal pressures are more prevalent in patients with hemorrhoids compared to controls. Improvement of therapy for functional constipation, especially dyssynergic defecation patterns, might lead to better long-term outcomes and reduce recurrence.
An elevated FIB-4 score is not associated with cardiovascular events: a longitudinal analysis from 137 842 patients with and without chronic liver disease
Authors: Loosen Sven , Luedde Mark , Demir Münevver , Luedde Tom , Kostev Karel , Roderburg Christoph
Published: April 2022

Background

Liver diseases and cardiovascular diseases are closely associated. Noninvasive tests (NITs), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced fibrosis and estimate the risk of liver-related outcomes in patients with chronic liver diseases (CLDs). However, the association of an elevated FIB-4 score with the development of myocardial infarction and/or stroke/transient ischemic attack (TIA) is unknown.

Methods

By using the Disease Analyzer database (IQVIA), which compiles diagnoses, laboratory values as well as basic medical and demographic data of over 7.5 million patients followed in general practices in Germany, we identified 68 921 patients with available lab values for FIB-4 score calculation between 2005 and 2019. Patients with an FIB-4 score of less than 1.3 were matched 1:1 to patients with an FIB-4 score of at least 1.3 by age, sex and yearly consultation frequency.

Results

In regression analysis, the incidence rate ratio (IRR) of myocardial infarction was similar among patients with an FIB-4 score of at least 1.3 compared with patients with a low FIB-4 score of less than 1.3, regardless of whether patients with or without preexisting liver disease were analyzed. Moreover, there was no significant increase in the IRR of stroke/TIA between patients with a high or low FIB-4 score, both in the general population and patients with CLD.

Conclusion

Our study suggests that the FIB-4 score is not associated with cardiovascular events both in the general population as well as in patients with CLD.
Homelessness and Depressive Symptoms
Authors: Maestrelli Luiz Gustavo , Sousa Martins Silva Anderson , de Azevedo-Marques Périco Cintia , Torales Julio , Ventriglio Antonio , Castaldelli-Maia João Maurício
Published: April 2022

The present systematic review aimed to summarize data on the prevalence and treatment of depressive symptoms among homeless people. We referred to the PubMed and Google Scholar databases to identify relevant studies on the topic. Among the 43 included studies, we found great variability in the prevalence of depressive symptoms among homeless people (ranging from 9.9% to 77.5%). Comparative studies among the homeless versus nonhomeless population showed that rates of depressive symptoms are 5 to 14 times higher in the homeless population. Similar differences were also found for suicidal ideation. The lack of research and treatment plans for this specific population further encourages more evidence and special therapeutic intervention. Although little has been found in the literature, a substantial improvement in the quality of life and reduction in depressive symptoms was demonstrated when therapeutic interventions were performed among homeless people (i.e., housing, nursing, access to community care and effective services and supports programs, mindfulness, pharmacological treatment).
Case Report: Acute Posterior Multifocal Placoid Pigment Epitheliopathy after SARS-CoV-2 Vaccination
Authors: Jakirlic Naida , Harris Tiffenie
Published: April 2022

SIGNIFICANCE

Acute posterior multifocal placoid pigment epitheliopathy is an uncommon inflammatory chorioretinopathy that has been reported after vaccination. This is the first reported case, to our knowledge, after vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a healthy adolescent boy.

PURPOSE

This report aimed to inform the eye care community about a possible ocular sequela of SARS-CoV-2 vaccination.

CASE REPORT

A 17-year-old boy presented to a clinic for a second opinion after sudden-onset blind spots in his right eye. His medical history was remarkable for receiving the first dose of the Pfizer-BioNTech SARS-CoV-2 vaccine 2 weeks before symptom onset. He had no history of ocular inflammation, autoimmune disease, or systemic infection. A diagnosis of unilateral acute posterior multifocal placoid pigment epitheliopathy was made based on the presence of typical fundus lesions and noninvasive imaging with fundus autofluorescence, retinal optical coherence tomography, and optical coherence tomography angiography. The diagnosis was further confirmed with fluorescein angiography. The patient developed an anterior vitritis in the right eye 42 days after initial symptom onset. His unilateral intraocular inflammation resolved after a 5-week course of prednisone.

CONCLUSIONS

Acute posterior multifocal placoid pigment epitheliopathy is a self-limited inflammatory condition of the outer retina that usually affects young adults and often does not require treatment. It has been reported to occur after vaccination for influenza, polio, hepatitis B, meningococcus C, and varicella zoster virus. This is the first known case to occur after SARS-CoV-2 vaccination in a healthy adolescent boy.
Rasch-calibrated Intermittent Exotropia Symptom Questionnaire for Children
Authors: Holmes Jonathan M. , Leske David A. , Hercinovic Amra , Hatt Sarah R. , Chandler Danielle L. , Li Zhuokai , Melia B. Michele , Chen Angela M. , Erzurum Sergul Ayse , Crouch Eric R. , Jenewein Erin C. , Kraker Raymond T. , Cotter Susan A.
Published: April 2022

SIGNIFICANCE

A rigorously designed and calibrated symptom questionnaire for childhood intermittent exotropia would be useful for clinical care and for research.

PURPOSE

The aim of this study was to Rasch-calibrate and evaluate the previously developed Child Intermittent Exotropia Symptom Questionnaire using data gathered as part of a randomized clinical trial.

METHODS

The questionnaire was administered to 386 children aged 3 to 10 years with intermittent exotropia who were enrolled in a randomized clinical trial comparing overminus with nonoverminus spectacles. Participants were followed at 6 and 12 months while on treatment and at 18 months off treatment. Factor analysis determined dimensionality, and Rasch analysis evaluated questionnaire performance. Logit values were converted to 0 (best) to 100 (worst). We evaluated differences in questionnaire scores between treatment groups and time points, and correlations with control scores.

RESULTS

The Child Intermittent Exotropia Symptom Questionnaire was unidimensional. Rasch analysis indicated that there was no notable local dependence and no significant differential item functioning for sex or age. There was suboptimal targeting (mean logit, −1.62), and person separation was somewhat poor (0.95). There were no significant differences in the Child Intermittent Exotropia Symptom score between overminus spectacles and nonoverminus spectacles at 6, 12, and 18 months. Combining data from both treatment groups, there was significant improvement from baseline at all follow-up visits (e.g., mean change from baseline to 12 months, −6.6 points; 95% confidence interval, −8.6 to −4.6). Child Intermittent Exotropia Symptom scores were not correlated with distance or near control scores at 12 months.

CONCLUSIONS

The seven-item Rasch-scored Child Intermittent Exotropia Symptom Questionnaire is limited by suboptimal performance. Future study is needed to determine whether it may be useful for clinical practice and for research.
Case Series: Unusual Presentation of Acanthamoeba Coinfection in the Cornea
Authors: Chuang Yu-Hsun , Wang Ying-Ching , Yen Chu-Yu , Lin Chih-Chung , Chen Chun-Chen
Published: April 2022

SIGNIFICANCE

The cases illustrate Acanthamoeba coinfection with Pseudomonas aeruginosa or microsporidia in the cornea.

PURPOSE

This case series aimed to alert clinicians toward considering Acanthamoeba coinfection in the cornea when unusual presentation such as perineuritis or epitheliitis was observed in clinical images. Increased suspicion of Acanthamoeba coinfection may facilitate early diagnosis and prompt management, eventually leading to good vision outcomes.

CASE SERIES

An 11-year-old boy wearing orthokeratology lens for myopia control complained of pain in the right eye for 1 week. A paracentral corneal ulcer with perineuritis was observed. Culture from corneal tissue revealed P. aeruginosa, and an in vivo confocal microscopic examination showed highly reflective and oval-shaped structures indicating Acanthamoeba coinfection. Corneal lesions gradually improved under 0.02% polyhexamethylene biguanidine, 0.1% propamidine isethionate, and 0.3% ciprofloxacin. At 1 year, the final best-corrected visual acuity was 20/25 with residual paracentral corneal opacity. Another 20-year-old man complained of pain in the right eye for 2 weeks. Multiple raised corneal lesions associated with epitheliitis were found. Moreover, 1% acid-fast staining showed oval-shaped spores, and microsporidia infection was inferred. In addition, polymerase chain reaction results obtained after subjecting the patient to corneal debridement revealed positivity for Acanthamoeba. Polyhexamethylene biguanidine (0.02%) and 0.5% moxifloxacin were prescribed, and the lesions subsided. At a 2-year follow-up, the final best-corrected visual acuity was 20/25.

CONCLUSIONS

Perineuritis in orthokeratology lens wearers and epitheliitis without any predisposing factor are unusual presentations of Acanthamoeba coinfection in the cornea. These corneal findings should arouse the suspicion of coinfection and enable the clinicians to conduct the appropriate workup and initiate adequate treatment. This case series demonstrated that early diagnosis and prompt treatment can improve visual prognosis.
Interocular Phase Disparity Tuning of Binocular Contrast Summation Depends on Carrier Spatial Frequency and Orientation
Authors: Raghunandan Avesh , Boyak Tabytha A.
Published: April 2022

SIGNIFICANCE

Binocular summation is a sensitive metric of binocular integration. As such, characterization of the mechanisms underlying binocular summation is a key step in translating and applying this knowledge to abnormal binocular systems afflicted with strabismus and amblyopia.

PURPOSE

Computational models of binocular summation have advocated the operation of mechanisms sensitive to the interocular phase disparity of first-order carrier gratings. This study investigated if such generalization depended on carrier spatial frequency and orientation.

METHODS

Monocular and binocular contrast detection thresholds were measured in nine observers with normal binocular vision. Stimuli comprised Gabor targets presented with one of three spatial frequencies (1, 3, and 9 cycles per degree [cpd]), two orientations (horizontal and vertical), and five interocular phase disparities (0, ±π/2, ±π radians). Horizontal and vertical fixation disparities were measured for each binocular threshold condition. Binocular summation ratios were computed by dividing the mean monocular detection threshold by the respective binocular detection threshold.

RESULTS

Binocular summation ratio varied significantly with interocular phase disparity for the 1- and 3-cpd horizontal and vertical gratings. Phase dependency was reduced with the 9-cpd horizontal grating and absent for the 9-cpd vertical grating, even though binocular summation ratio exceeded predictions of probability summation. Computational modeling that incorporated the variability of fixation disparity into a vector summation model predicted a reduction in peak binocular summation ratio with increasing carrier spatial frequency but did not account for the reduction of phase sensitivity noted with the 9-cpd stimulus.

CONCLUSIONS

Binocular summation magnitude is less dependent on interocular phase disparities for carrier spatial frequencies that exceed 3 cpd, especially with vertical gratings. Although vergence variability due to fixation disparities contributes to the overall reduction in binocular summation magnitude with increasing carrier spatial frequency, it does not provide a complete account for the lack of interocular phase disparity tuning noted with high grating spatial frequencies.
Early Hypocalcemia in Pediatric Major Trauma
Authors: Gimelraikh Yulia , Berant Ron , Stein Michael , Berzon Baruch , Epstein Danny , Samuel Nir
Published: April 2022

Objective

Early hypocalcemia (EH) is common in adult major trauma patients and has been associated with coagulopathy, shock, increased transfusion requirements, and mortality. The incidence of EH in pediatric severe trauma has not been investigated. We aimed to explore the incidence of EH among severely injured children.

Methods

We conducted a retrospective cohort study at a tertiary children's hospital and a level 1 pediatric trauma center. We extracted the medical records of all pediatric major trauma patients, defined as an age less than 18 years and an Injury Severity Score (ISS) greater than 15, admitted after trauma team activation from January 2010 to December 2020.

The primary outcome was the presence of EH. Patients were classified into 3 groups: severe hypocalcemia (ionized calcium [iCa] <1 mmol/L), hypocalcemia (1 < iCa < 1.16 mmol/L), and normal calcium (iCa ≥1.16 mmol/L).

Results

During the study period, 5126 children were hospitalized because of trauma. One hundred eleven children met the inclusion criteria. The median age was 11 years (interquartile range [IQR], 4–15), and 78.4% (87) were male. The median ISS was 21 (IQR, 17–27).

Hypocalcemia was found in 19.8% (22) and severe hypocalcemia in 2.7% (3) of the patients.

Although not statistically significant, hypocalcemic pediatric trauma patients had higher ISS (25.5 [IQR, 17–29] vs 21 [IQR, 17–26], P = 0.39), lower Glasgow Coma Scale (11 [IQR, 3–15] vs 13 [IQR, 7–15], P = 0.24), a more prolonged hospital stay (8 days [IQR, 2–16] vs 6 days [IQR, 3–13], P = 0.36), a more frequent need for blood products (27.3% vs 20.2%, P = 0.74), and higher mortality rates (9.1% vs 1.1%, P = 0.18) compared with normocalcemic patients.

Conclusions

Our data suggest that in the setting of major trauma, EH is less frequent in children than previously reported in adults. Our preliminary data suggest that pediatric patients with EH may be at risk of increased morbidity and mortality compared with children with normal admission iCa requiring further studies.
Mandibular Distraction in Neonatal Pierre Robin Sequence: Is Immediate Extubation Both Feasible and Safe?
Authors: Payne Samuel H. , Brady Colin M. , Mercury Oblaise A. , Soldanska Magdalena , Hush Stefanie E. , Xiang Yijin , Williams Joseph K.
Published: April 2022

Background:

The timing of extubation following placement of mandibular distractors in the setting of Pierre Robin sequence is variable across institutional algorithms. Postoperative maintenance of intubation allows for an improvement in airway dimension and tongue positioning before extubation, theoretically decreasing the impact of postoperative airway edema. Maintenance of intubation, however, is not without risk. The authors analyze their institutional experience with neonatal mandibular distraction followed by immediate extubation to assess feasibility and safety profiles.

Methods:

A 4-year retrospective review of patients diagnosed with Pierre Robin sequence who underwent mandibular distraction within the first 3 months of life was performed. Patients intubated preoperatively were excluded.

Results:

Fifty-two patients met inclusion criteria. Thirty-eight patients (73 percent) were extubated immediately, whereas 14 patients (27 percent) remained intubated. No differences between these groups were found when comorbidities, cleft pathology, preoperative respiratory support, or grade of view on direct laryngoscopy were analyzed. Case duration greater than 120 minutes, operation start time after 3 pm, and the subjective designation of a difficult airway by the anesthesiologist were associated with maintaining intubation (p < 0.05). Eight patients (21 percent) in the extubated group required an increase in respiratory support in the postoperative interval. Four of these patients (11 percent) required reintubation. Increased postoperative respiratory support was more likely in patients with certain comorbidities and higher preoperative respiratory support requirements (p < 0.05).

Conclusions:

The authors’ data suggest that immediate extubation following neonatal mandibular distraction is feasible in patients who are not intubated preoperatively. Careful consideration should be given to patients who require significant respiratory support preoperatively and in those with certain comorbidities.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Secondary Alveolar Bone Grafting in Patients with Cleft Lip and Palate: A Step-by-Step Video Series
Authors: Murali Srinisha P. , Denadai Rafael , Chou Pang-Yun , Chang Chun-Shin , Lo Lun-Jou
Published: April 2022

Secondary alveolar bone grafting is one of the key surgical procedures performed to restore dental arch continuity and facilitate tooth eruption in patients with cleft lip and palate. Harvest of cancellous bone graft from the iliac crest has become the gold standard; however. there is no consensus regarding the ideal technique. An optimal bone harvest technique must be aimed at producing minimal donor-site morbidity and patient discomfort. The success of the bone grafting procedure depends largely on the surgical technique. To restore cleft alveolar defects, one must be able to conceptualize the different underlying aspects of the problem to perform an effective surgical repair. It is important for surgeons-in-service to adopt newer techniques that significantly enhance the overall outcome. This article describes two techniques of iliac bone harvest and the principles involved in execution of the alveolar bone grafting procedure. The accompanying four-part video series depicts the bone harvest, flap design, dissection of the recipient cleft alveolus, and bone grafting in a step-by-step manner.
An Evidence-Based Theory of Psychological Adjustment to Long-Term Physical Health Conditions: Applications in Clinical Practice
Authors: Carroll Susan , Moon Zoe , Hudson Joanna , Hulme Katrin , Moss-Morris Rona
Published: April 2022

Objective

Around 30% of people with long-term physical health conditions (LTCs) experience comorbid anxiety and depression. For many, comorbid distress is linked to difficulties adjusting to the challenges of the LTC. The aims of this article are to present a transdiagnostic theoretical model of adjustment to LTCs (TMA-LTC), demonstrate the application of this model in clinical practice, and highlight the distinguishing features of treating LTC-related distress compared with treating primary anxiety and/or depression.

Methods

A systematic review (k = 21) was conducted to collate preexisting evidence-based models of adjustment across LTCs. Models of adjustment for a range of LTCs were extracted and synthesized into a new preliminary TMA-LTC. Two expert consensus meetings were held, where experts rated the relevance and importance of all concepts within the models.

Results

The TMA-LTC proposes that acute critical events or ongoing illness stressors can disrupt emotional equilibrium, and that whether a person returns to equilibrium and achieves good psychological adjustment depends on a number of cognitive and behavioral factors, as well as their interpersonal, intrapersonal, environmental, and illness-specific contexts. A case study is presented to demonstrate the clinical application of this model in treating illness-related distress, highlighting how it overcomes roadblocks that may be encountered when working primarily within traditional mental health paradigms.

Conclusions

As an empirically and clinically informed model, TMA-LTC provides a useful guide for assessment, formulation, and treatment in the context of psychological adjustment to LTCs. Future studies are needed to test treatments that have been developed based on TMA-LTC.
The Influence of Emotion Regulation on the Association Between Depression and Heart Rate Variability in Cardiac Patients
Authors: Mura Francesca , Patron Elisabetta , Messerotti Benvenuti Simone , Gentili Claudio , Ponchia Andrea , Palomba Daniela
Published: April 2022

Objective

Poor vagally mediated heart rate variability (vmHRV) is a mechanism linking depression to coronary heart disease (CHD). Reduced vmHRV is also considered an index of emotion dysregulation—the frequent use of maladaptive emotion regulation strategies, one of the most important being expressive suppression—which is a key component of depression. Therefore, this study aimed to investigate the moderating role of expressive suppression in the relation between depression and vmHRV in patients with CHD.

Methods

The sample included 235 patients with CHD (mean [standard deviation] age = 61.6 [9.8] years; 12% women) admitted to cardiac rehabilitation after a cardiac intervention. The Beck Depression Inventory-II was administered to assess depressive symptoms. Emotion regulation strategies based on either expressive suppression or cognitive reappraisal were assessed through the Emotion Regulation Questionnaire. Resting electrocardiographic recordings were collected for 5 minutes to compute HRV indices.

Results

Expressive suppression moderated the relation between depressive symptoms and vmHRV (b = −0.03, p = .012). Patients with lower expressive suppression scores showed no association between depressive symptoms and vmHRV (b = −0.00, p = .94), whereas those with higher expressive suppression scores showed a significant negative association between depressive symptoms and vmHRV (b = −0.05, p = .015).

Conclusions

The use of expressive suppression is likely to potentiate the relation between depressive symptoms and poor vmHRV, which could increase the cardiac risk in these patients. Targeting emotion regulation skills in cardiac rehabilitation programs may be useful for reducing the impact of depression in cardiac patients.
Nocardia albiluteola sp. nov., a novel lignin-degrading actinobacterium isolated from rhizosphere soil of pumpkin
Authors: Shan Qiqi , Han Chuang , Zhao Junwei , Yu Bing , Jiang Mengqi , Liu Ting , Wang Xiangjing , Xiang Wensheng
Published: April 2022

A novel lignin-degrading actinobacterium, designated NEAU-G5T, was isolated from pumpkin rhizosphere soil collected from field in Mudanjiang, Heilongjiang Province, northeast China, and characterized using polyphasic approach. The prior 16S rRNA gene sequence similarities and phylogenic analysis showed that strain NEAU-G5T exhibited close phylogenetic relatedness to

Nocardia miyunensis

NBRC 108239T (98.82 %),

Nocardia nova

NBRC 15556T (98.75 %),

Nocardia jiangxiensis

NBRC 101359T (98.68 %) and

Nocardia macrotermitis

RB20T (98.61 %). Morphological and chemotaxonomic characteristics indicated that strain NEAU-G5T could be assigned to the genus

Nocardia

. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, an unidentified phospholipid and an unidentified lipid. The predominant menaquinone was MK-8(H4, ω-cycl). The major fatty acids (>10 %) were identified as C16 : 0, C18 : 1
 ω9c, 10-methyl C18 : 0 and C18 : 0. Mycolic acids were present. The genomic DNA G+C content of strain NEAU-G5T was 68 mol%. Moreover, based on digital DNA–DNA hybridization and average nucleotide identity values, strain NEAU-G5T could be differentiated from its reference strains. In addition, an azure B plate decolorization test and genomic analysis indicated that strain NEAU-G5T had the ability to degrade lignin. On the basis of polyphasic characteristics, strain NEAU-G5T represents a novel species of the genus

Nocardia

, with the name Nocardia albiluteola sp. nov. The type strain is NEAU-G5T (=CCTCC AA 2021018T=DSM 110547T).
From elimination to suppression: genomic epidemiology of a large Delta SARS-CoV-2 outbreak in Aotearoa New Zealand
Authors: Jelley Lauren , Douglas Jordan , Ren Xiaoyun , Winter David , McNeill Andrea , Huang Sue , French Nigel , Welch David , Hadfield James , de Ligt Joep , Geoghegan Jemma L
Published: April 2022

New Zealand’s COVID-19 elimination strategy heavily relied on the use of genomics to inform contact tracing, linking cases to the border and to clusters during community outbreaks. In August 2021, New Zealand entered its second nationwide lockdown after the detection of a single community case with no immediately apparent epidemiological link to the border. This incursion resulted in the largest outbreak seen in New Zealand caused by the Delta Variant of Concern. Here we generated 3806 high quality SARS-CoV-2 genomes from cases reported in New Zealand between 17 August and 1 December 2021, representing 43% of reported cases. We detected wide geographical spread coupled with undetected community transmission, characterised by the apparent extinction and reappearance of genomically linked clusters. We also identified the emergence, and near replacement, of genomes possessing a 10-nucleotide frameshift deletion that caused the likely truncation of accessory protein ORF7a. By early October, New Zealand moved from elimination to suppression and the role of genomics changed markedly from being used to track and trace, towards population-level surveillance.
Evaluation of patient-specific cell free DNA assays for monitoring of minimal residual disease in solid tumors
Authors: Akolkar Dadasaheb , Patil Darshana , Puranik Sneha , Puranik Swapnil , Nandre Pratiksha Sunil , Sabale Karishma Raosaheb , Apurwa Sachin , Bodke Harshal , Shrivastava Navin , Datta Vineet , Schuster Stefan , John Jinumary , Srinivasan Ajay , Datar Rajan
Published: April 2022

Real time monitoring of disease status is an essential part of cancer management. The low sensitivity and specificity of serum markers and the constraints and risks associated with radiological scans prompt the need for accurate non-invasive means to monitor minimal residual disease (MRD) in solid tumors. In this study we describe MRD evaluation via profiling of patient-specific gene variants in cell free tumor DNA (i.e., ctMRD). We evaluate the feasibility of this approach for real time monitoring of tumor load dynamics in response to anticancer treatments. We prioritized 162 hot spot mutations for designing ctMRD assays based on literature review. These ctMRD assays were evaluated in 436 plasma specimens with a median of 6 (range 3-18) longitudinal evaluations in a cohort of 48 patients with various solid tumors. In patients with partial radiological response (PR), Mutant Allele Fraction (MAF) showed high correlation (84%) with radiological response and tumor volume (cm3) compared to conventional CA markers (53%). Total plasma ctDNA level was significantly higher in patients with 2-5 metastatic sites compared with single metastatic site (P = 0.04) and discriminated patients with stable disease (SD) and progressive disease (PD) from patients with partial response (PR) (P =0.01and P = 0.04, respectively). Collectively, the present study shows that changes in mutation burden evaluated using patient specific ctMRD assays is a highly sensitive approach for monitoring of therapy response.
Talking on handsfree and handheld cellphones while driving in association with handheld phone bans
Authors: Benedetti Marco H. , Li Li , Shen Sijun , Kinnear Neale , Delgado M. Kit , Zhu Motao
Published: April 2022

Introduction

Concurrent use of a cellphone while driving impairs driving abilities, and studies of policy effectiveness in reducing distracted driving have yielded mixed results. Furthermore, few studies have considered how hands-free phone use associates with handheld phone bans. It is not clear whether hand-held phone bans dissuade some drivers from using the phone while driving completely, or whether it simply promotes a shift to hands-free use. The present study estimates the association between handheld phone policies and self-reported talking on handsfree and handheld cellphones while driving.

Methods

Our data consisted of 16,067 respondents to annual administrations of the Traffic Safety Culture Index from 2012-2017. Our primary exposure variable was handheld phone policy, and our primary outcome variables were self-reported talking on any phone, self-reported talking on a handheld phone, and self-reported talking on a hands-free phone while driving. We estimated adjusted prevalence ratios of the outcomes associated with handheld phone bans via modified Poisson regression.

Results

Drivers in states with handheld bans were 13% less likely to self-report talking on any type of cellphone (handheld or handsfree) while driving. When broken down by cellphone type, drivers in states with handheld bans were 38% less likely to self-report talking on a handheld phone and 10% more likely to self-report talking on a hands-free phone while driving.

Conclusions

Handheld phone bans were associated with more self-reported talking on hands-free phones and less talking on handheld phones, consistent with a substitution hypothesis. Handheld bans were also associated with less talking on any phone while driving, supporting a net safety benefit.

Practical Applications

In the absence of a national ban on handheld phone use while driving, our study supports state handheld phone bans to deter distracted driving and improve traffic safety.