bluuebunny/crossref_metadata_2025 huggingface dataset:
A panel of urinary proteins predicts active lupus nephritis and response to rituximab treatment
Authors: Davies Jennifer C , Carlsson Emil , Midgley Angela , Smith Eve M D , Bruce Ian N , Beresford Michael W , Hedrich Christian M ,   the BILAG-BR and MRC MASTERPLANS Consortia
Published: November 2020

Objectives

∼30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE.

Methods

A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEX® Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment.

Results

Urine levels of transferrin (P <0.005), AGP-1 (P <0.0001), MCP-1 (P <0.001) and sVCAM-1 (P <0.005) were significantly higher in SLE patients when compared with healthy controls. Furthermore, levels of transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 (all P <0.0001) were higher in SLE patients with active LN when compared with patients without active LN. A combination of five urine proteins, namely LPGDS, transferrin, ceruloplasmin, MCP-1 and sVCAM-1 was a good predictor of active LN (AUC 0.898). A combined model of LPGDS, transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12 months (AUC 0.818).

Conclusions

Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.
SECRETARY OF STATE FOR HEALTH v SERVIER LABORATORIES LTD
Authors:   Court of Appeal
Published: November 2020

H1 Patents – European patents - Pharmaceuticals – Generic products – Economic torts – Unlawful means – Strike out application – Necessary elements of the tort – Whether the unlawful means relied upon had to interfere with claimant’s liberty to deal with third party against whom the unlawful act relied upon had been committed – Invalid patents – Proceedings for patent infringement – Interim injunctions – Market entry of third party generic product delayed – Prices thereby maintained – Patent later invalidated – Claim struck out at first instance – Appeal to Court of Appeal
Timing, Distribution, and Relationship Between Nonpsychotic and Subthreshold Psychotic Symptoms Prior to Emergence of a First Episode of Psychosis
Authors: Cupo Lani , McIlwaine Sarah V , Daneault Jean-Gabriel , Malla Ashok K , Iyer Srividya N , Joober Ridha , Shah Jai L
Published: November 2020

Prospective population studies suggest that psychotic syndromes may be an emergent phenomenon—a function of severity and complexity of more common mental health presentations and their nonpsychotic symptoms. Examining the relationship between nonpsychotic and subthreshold psychotic symptoms in individuals who later developed the ultimate outcome of interest, a first episode of psychosis (FEP), could provide valuable data to support or refute this conceptualization of how psychosis develops. We therefore conducted a detailed follow-back study consisting of semistructured interviews with 430 patients and families supplemented by chart reviews in a catchment-based sample of affective and nonaffective FEP. The onset and sequence of 27 pre-onset nonpsychotic (NPS) or subthreshold psychotic (STPS) symptoms was systematically characterized. Differences in proportions were analyzed with z-tests, and correlations were assessed with negative binomial regressions. Both the first psychiatric symptom (86.24% NPS) and the first prodromal symptom (66.51% NPS) were more likely to be NPS than STPS. Patients reporting pre-onset STPS had proportionally more of each NPS than did those without pre-onset STPS. Finally, there was a strong positive correlation between NPS counts (reflecting complexity) and STPS counts (β = 0.34, 95% CI [0.31, 0.38], P < 2 e-16). Prior to a FEP, NPS precede STPS, and greater complexity of NPS is associated with the presence and frequency of STPS. These findings complement recent arguments that the emergence of psychotic illness is better conceptualized as part of a continuum—with implications for understanding pluripotential developmental trajectories and strengthening early intervention paradigms.
The use of traditional medicines among mycetoma patients
Authors: Kunna Ezzan , Yamamoto Taro , Fahal Ahmed
Published: November 2020

Background

Mycetoma patients frequently present with advanced disease, the cause of which is multi-factorial, but the use of traditional medicine modalities has been shown to be an important one. Traditional medicine is an integral part of the Sudanese culture and many mycetoma patients revert to it because it is accessible, cheap and available.

Methods

To confirm this anecdotal observation, the pattern and characteristics of traditional medicine use among a group of mycetoma patients seen at the Mycetoma Research Center in Khartoum, Sudan, were studied.

Results

In this descriptive, cross-sectional, hospital-based study, 389 mycetoma-confirmed patients were included. All of them had used traditional medicine at some stage of their mycetoma treatment. Among them, 66% had first consulted traditional healers for mycetoma treatment. In this study, 58% had consulted religious healers known as fakis, while the majority (72%) of those who consulted specialist healers had consulted herbalists. The most frequent type of traditional medicine received by patients from religious healers was al-azima (31%) and the most common treatment given by the specialist healers was herbal medicine (46%).

Conclusion

Traditional medicine can lead to a delay in seeking medical care and serious complications. Collaboration with traditional healers, and training and educating them to refer mycetoma patients to specialised centres is vital to ensure that they receive proper treatment in a timely and efficient manner.
Assessment of adherence to anti-tuberculosis treatment and predictors for non-adherence among the caregivers of children with tuberculosis
Authors: Laghari Madeeha , Talpur Bandeh Ali , Sulaiman Syed Azhar Syed , Khan Amer Hayat , Bhatti Zohra
Published: November 2020

Background

Information on the extent of patient medication adherence and the use of interventions to advance adherence are scarce in clinical practice. This study aimed to assess medication adherence and risk factors for non-adherence among the caregivers of children with tuberculosis (TB).

Methods

This prospective study was conducted among the caregivers of 443 child TB patients registered during the study. Caregivers of children were queried using a structured questionnaire consisting of sociodemographic and socio-economic factors and the role of healthcare workers during the treatment course. Risk factors for non-adherence were estimated using a logistic regression model.

Results

In multivariate analysis, the independent variables that had a statistically significant positive association with non-adherence were male sex (adjusted odds ratio [AOR] 5.870 [95% confidence interval {CI} 1.99 to 17.29]), age ≥45 y (AOR 5.627 [95% CI 1.88 to 16.82]), caregivers with no formal education (AOR 3.905 [95% CI 1.29 to 11.79]), financial barriers (AOR 30.297 [95% CI 6.13 to 149.54]), insufficient counselling by healthcare workers (AOR 5.319 [95% CI 1.62 to 17.42]), insufficient counselling by health professionals (AOR 4.117 [95% CI 1.05 to 16.05]) and unfriendly attitude and poor support from healthcare professionals (AOR 11.150 [95% CI 1.91 to 65.10]).

Conclusions

Treatment adherence in the present study was 86% using the Morisky Green Levine Medication Adherence Scale and 90.7% using the visual analogue scale tool. Predictors of non-adherence need to be a focus and caregivers should be given complete knowledge about the importance of adherence to TB treatment.
Activity of the Novel Fungicide Mefentrifluconazole Against Colletotrichum scovillei
Authors: Gao Yangyang , Liu Yang , He Lifei , Zhu Jiamei , Wu Buhua , Liu Feng , Mu Wei
Published: November 2020

The prevalence and destructiveness of anthracnose, caused by Colletotrichum scovillei, in pepper production regions seriously affects pepper yield and quality. Mefentrifluconazole, the first of the isopropanol-azole subgroup of triazole fungicides, was introduced for the control of pepper anthracnose. However, the growth characteristics of pepper fruit and rapid spread of anthracnose suggest that the fungicide application method must be optimized to enhance fungicide efficacy. The sensitivity of C. scovillei to mefentrifluconazole was determined by mycelial growth and germ tube elongation assays using 157 single-spore isolates with mean 50% effective concentration values of 0.462 ± 0.138 and 0.359 ± 0.263 mg/liter, respectively. The in vivo data also showed that mefentrifluconazole had favorable protective and curative effects against pepper anthracnose. Mefentrifluconazole significantly affected C. scovillei infection on pepper by reducing appressorium formation and sporulation, shriveling spores and germ tubes, and causing the abnormal development of appressoria and conidiophores. Mefentrifluconazole could move acropetally, horizontally, and basipetally in pepper plants. Compared with a knapsack sprayer, mefentrifluconazole applied by mist sprayer exhibited significantly better activity against pepper anthracnose. Additionally, as the spray volume increased from 45 to 150 liters/ha, the control efficacy of mefentrifluconazole first increased and then tended to be steady, with an optimal spray volume of 90 liters/ha. The difference in disease control efficacy was related to the deposition and droplet distribution of mefentrifluconazole on the pepper fruit. These results provide scientific guidance for the application of mefentrifluconazole in pepper fields and improved fungicide utilization.
Magnetic sphincter augmentation device placement for treatment of gastroesophageal reflux
Authors: Laird Jason
Published: November 2020

Gastroesophageal reflux disease typically is treated with lifestyle modifications and proton pump inhibitors (PPIs). Surgery is effective in treating the symptoms associated with gastroesophageal reflux, but common procedures involve invasive techniques that can leave the patient unable to belch or vomit. Research has raised concerns regarding the long-term use of PPIs, leaving few treatment options for patients with refractory reflux symptoms. The magnetic sphincter augmentation device demonstrates similar efficacy to existing antireflux procedures, avoids complex surgery techniques, and preserves normal physiologic functions at the lower esophageal sphincter. This device is a safe and effective alternative to more invasive procedures for patients whose GERD does not respond to medical management.
Recognizing and treating child overweight and obesity
Authors: Cooper Christen Cupples , Mandel Ellen D.
Published: November 2020

Primary care providers can help prevent and address child overweight and obesity, conditions that can affect children's present and future health as well as their psychologic, emotional, and social well-being. This article describes approaches to preventing, identifying, and addressing overweight and obesity using empathetic, practical, family-focused recommendations and actions.
Percutaneous Fixation of Pediatric Fractures of the Proximal Phalanx Neck: A Novel Technique
Authors: Pientka William F. , Cheng Jonathan
Published: November 2020

Introduction:

Proximal phalanx neck fractures occur almost exclusively in children. Fractures of the proximal phalanx neck can be difficult to treat nonoperatively given the anatomic location and associated extrinsic forces. A divergent or crossed pin configuration is often utilized for the stabilization of these fractures.

Purpose:

We present a surgical technique with a single Kirschner (K-wire) placed axially along the affected finger, with a hyperextension reduction maneuver, to reduce and fixate proximal phalanx neck fractures in children and adolescents.

Methods:

We performed a retrospective review of all pediatric proximal phalanx neck fractures treated by a single surgeon. Demographic data, as well as clinical and radiographic outcomes were recorded. We then directly compared axial pinning [14 patients; average age 6.63 y (9 mo to 17 y)] with nonoperative treatment [28 patients; average age 8.03 y (9 mo to 16 y)], and open treatment [8 patients; average age 8.13 y (1 to 14 y)].

Results:

Patients who underwent closed reduction and axial pinning had significantly improved final coronal alignment compared with nonoperative treatment. Compared with fractures which required open reduction, closed reduction with axial pinning resulted in significantly shorter surgical duration and time to radiographic healing. The final range of motion showed no difference between intervention types, as all patients regained full range of motion.

Conclusions:

We find this axial pinning technique to be simpler and faster than divergent pin fixation, with no significant differences in time to radiographic healing, time to full activity, final proximal interphalangeal active flexion or extension, loss of reduction, or radiographic parameters.

Level of Evidence:

Level III—Therapeutic.
Notable response of a young adult with recurrent glioblastoma multiforme to vincristine-irinotecan-temozolomide and bevacizumab
Authors: Papageorgiou Georgios I. , Tsakatikas Sergios A. , Fioretzaki Rodanthi G. , Kosmas Christos
Published: November 2020

Glioblastoma multiforme is a malignant central nervous system (CNS) disease with dismal prognosis. Current treatment modalities only offer modest activity and usually of short duration, so there is an urgent need for the conduct of clinical trials exploring new treatment options and modalities. The vincristine-irinotecan-temozolomide and bevacizumab (VITb) regimen is an option of special interest, as it has produced encouraging results in young patients with various relapsed/refractory childhood and adolescence solid tumors, with an acceptable toxicity profile. With the current report, we present the case of a young male patient who was treated for GBM in second relapse at out institution, after previous surgical attempts and two radiotherapy sessions in conjunction with temozolomide and experienced a major and long-lasting response, weaned off steroids, to the VITb regimen followed by bevacizumab maintenance. The above case is discussed in the context of the existing literature regarding available evidence of synergy between the drugs used and the activity of certain components of the combination (i.e. combination of temozolomide-irinotecan ± vincristine, or bevacizumab-irinotecan in GBM) or the complete VITb regimen in other pediatric/adolescence solid tumors and the few cases reported with GBM.
Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis
Authors: Grossestreuer Anne V. , Moskowitz Ari , Andersen Lars W. , Holmberg Mathias J. , Konacki Varun , Berg Katherine M. , Chase Maureen , Cocchi Michael N. , Donnino Michael W.
Published: November 2020

Objectives:

Patients who experience sepsis often have long-term effects that may impact health-related quality of life. This study aimed to investigate whether the combination of ascorbic acid, corticosteroids, and thiamine compared with placebo improves health-related quality of life in patients with septic shock.

Design:

Secondary analysis of the Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis randomized controlled trial (NCT03389555).

Setting:

Thirteen tertiary-care hospitals in the United States.

Patients:

Patients who were enrolled in Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis, survived to 90 days post enrollment and were able to be contacted by telephone.

Interventions:

Patients were randomly assigned to parenteral ascorbic acid (1,500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days or placebo.

Measurements and Main Results:

One hundred seventeen patients (59%) survived to 90 days and were administered the Short Form 36 questionnaire; of these, 72 (62%) completed the Short Form 36 (38 [53%] in the intervention group, 34 [47%] in placebo). Sixty-six (92%) completed all survey questions (36 [95%] in the intervention group, 30 [88%] in placebo). There was no significant difference in overall Short Form 36 score between intervention and placebo group (median score: 39.4 [interquartile range, 31.2–45.4] vs 43.2 [37.0–46.7], respectively, p = 0.18). We found no statistically significant difference between the two groups in any of the other health-related quality of life domains used.

Conclusions:

We found no difference in the health-related quality of life in patients with septic shock treated with a combination of ascorbic acid, corticosteroids, and thiamine compared to placebo.
COVID-19 antibody development fueled by HIV-1 broadly neutralizing antibody research
Authors: Mendoza Pilar , Lorenzi Julio C.C. , Gaebler Christian
Published: November 2020

Purpose of review

The coronavirus disease 2019 (COVID-19) pandemic has caught the world unprepared, with no prevention or treatment strategies in place. In addition to the efforts to develop an effective vaccine, alternative approaches are essential to control this pandemic, which will most likely require multiple readily available solutions. Among them, monoclonal anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been isolated by multiple laboratories in record time facilitated by techniques that were first pioneered for HIV-1 antibody discovery. Here, we summarize how lessons learned from anti-HIV-1 antibody discovery have provided fundamental knowledge for the rapid development of anti-SARS-CoV-2 antibodies.

Recent findings

Research laboratories that successfully identified potent broadly neutralizing antibodies against HIV-1 have harnessed their antibody discovery techniques to isolate novel potent anti-SARS-CoV-2 antibodies, which have efficacy in animal models. These antibodies represent promising clinical candidates for treatment or prevention of COVID-19.

Passive transfer of antibodies is a promising approach when the elicitation of protective immune responses is difficult, as in the case of HIV-1 infection. Antibodies can also play a significant role in post-exposure prophylaxis, in high-risk populations that may not mount robust immune responses after vaccination, and in therapy. We provide a review of the recent approaches used for anti-SARS-CoV-2 antibody discovery and upcoming challenges in the field.
Bisphosphonate use and the risk of atypical fractures
Authors: Bose Debdipta , Gogtay Nithya J.
Published: November 2020

Bisphosphonates (BPs) have been in the market for the past 40 years and proven beneficial especially for patients with osteoporosis and prevention of hypercalcemic in malignancy. However, their long-term use raises safety concerns like Atypical femoral fracture and Osteonecrosis of the Jaw whose pathophysiology still remains unclear. Atypical femoral fracture is more commonly seen among BP users with at least six years of therapy and concomitant use of drugs such as glucocorticoids. The most common treatment for atypical femoral fracture is to withdraw the therapy with monitoring of bone resorption markers but the definitive treatment is intramedullary nail fixation where necessary. Hence, physicians must be vigilant to rarer and long-term BP-reported adverse effects and understand the evidence around the use of these drugs including drug free holidays. A structured benefit-risk assessment should be made for every individual patient including communicating the risk of these rare side effects.
POSITION OF IN-THE-BAG POSTERIOR CHAMBER INTRAOCULAR LENSES RELATIVE TO THE LIMBUS
Authors: Vingopoulos Filippos , Nair Archana , See Craig W. , Iyengar Nishanth , Haberman Ilyse , Sperber Laurence , Lazzaro Douglas R. , Singh Rishi , Ho Allen , Gupta Omesh , Sharma Sumit , Modi Yasha
Published: November 2020

Purpose:

To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning.

Methods:

This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus.

Results:

A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position.

Conclusion:

True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.
CLINICOPATHOLOGIC CORRELATION OF PRERETINAL TISSUES IN MYOPIC TRACTION MACULOPATHY
Authors: Russell Jonathan F. , Naranjo Andrea , Dubovy Sander R. , Smiddy William E.
Published: November 2020

Purpose:

To evaluate histopathologic features of preretinal tissues removed from eyes with myopic traction maculopathy (MTM).

Methods:

We retrospectively studied preretinal tissue specimens from eyes with MTM removed during pars plana vitrectomy. A control group of six idiopathic epiretinal membranes was studied for comparison.

Results:

Six MTM specimens were studied histopathologically. Outer retinal schisis-like thickening was present in 100% of preoperative optical coherence tomography images; four of the six eyes had subfoveal neurosensory retinal detachment. Postoperative optical coherence tomography images demonstrated complete resolution of the schisis-like appearance in all eyes; a full-thickness macular hole occurred in two of the six eyes. Histopathologic examination disclosed fibrocellular tissue that was strongly positive for glial fibrillary acidic protein, weak to moderately positive for cytokeratin, and weakly positive for smooth muscle actin and CD68. There were no apparent histopathologic or immunohistochemical differences between preretinal tissues from eyes with MTM and idiopathic epiretinal membranes from control eyes.

Conclusion:

The outer retinal schisis-like thickening, commonly associated with subretinal fluid, that characterizes MTM is associated with preretinal tissues that are histopathologically indistinguishable from idiopathic epiretinal membranes. These findings suggest that anteroposterior traction caused by axial elongation rather than a uniquely abnormal cellular process is the etiologic mechanism of MTM.
Long-term trajectories of chronic musculoskeletal pain: a 21-year prospective cohort latent class analysis
Authors: Aili Katarina , Campbell Paul , Michaleff Zoe A. , Strauss Vicky Y. , Jordan Kelvin P. , Bremander Ann , Croft Peter , Bergman Stefan
Published: November 2020

Our knowledge of the prevalence, impact, and outcomes of chronic pain in the general population is predominantly based on studies over relatively short periods of time. The aim of this study was to identify and describe trajectories of the chronic pain status over a period of 21 years. Self-reported population data (n = 1858) from 5 timepoints were analyzed. Pain was categorized by: no chronic pain (NCP), chronic regional pain (CRP), and chronic widespread pain (CWP). Latent class growth analysis was performed for identification of trajectories and logistic regression analysis for identification of predictors for pain prognosis. Five trajectories were identified: (1) persistent NCP (57%), (2) migrating from NCP to CRP or CWP (5%), (3) persistent CRP or migration between CRP and NCP (22%), (4) migration from CRP to CWP (10%), and (5) persistent CWP (6%). Age, sleeping problems, poor vitality, and physical function at baseline were associated with pain progression from NCP. Female gender, seeking care for pain, lack of social support, poor physical function, vitality, and mental health predicted poor pain prognosis among those with CRP. In conclusion, chronic pain was common in the population including 6% reporting persistent CWP, although the majority persistently reported NCP. Most people had stable pain status, but some had ongoing change in pain status over time including people who improved from chronic pain. It was possible to identify clinically relevant factors, characterizing trajectories of chronic pain development, that can be useful for identifying individuals at risk and potential targets for intervention.
Screening and diagnostic tools for complex regional pain syndrome: a systematic review
Authors: Mesaroli Giulia , Hundert Amos , Birnie Kathryn A. , Campbell Fiona , Stinson Jennifer
Published: November 2020

Complex regional pain syndrome (CRPS) is a severely painful condition that presents with a constellation of symptoms. The understanding of the pathophysiology of CRPS has evolved over time, as have the diagnostic criteria. Our primary objective was to identify screening and diagnostic tools for CRPS and summarize their feasibility, measurement properties, and study quality. A secondary objective was to identify screening and diagnostic tools used for CRPS in pediatric populations (0-21 years of age). A systematic review of English articles in electronic databases (PsycINFO, MEDLINE, Embase, CINAHL, CENTRAL, and Web of Science) was conducted with the aid of a librarian in November 2018 and updated in July 2020. Studies were included if the tool was a screening or diagnostic tool, the tool included self-report or physical examination, and the primary objective of the study was to evaluate the measurement properties or feasibility of use. For each study, data were extracted for quality indicators using the QUADAS-2 tool. No screening tools were identified. Four diagnostic tools were identified: the Veldman criteria, International Association for the Study of Pain criteria, Budapest Criteria, and Budapest Research Criteria. There are no diagnostic tools validated for use in pediatric CRPS. Because there are no extant screening tools for CRPS, all people with suspected disease should undergo rapid diagnostic assessment by a clinician. For adults, the Budapest Criteria are the preferred diagnostic tool. Future research is recommended to develop a diagnostic tool for pediatric populations and screening tools for both pediatric and adults.
Performance Characteristics, Intra‐ and Inter‐operator Agreement of Transient Elastography in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Mandelia Chetan , Kabbany Mohammad Nasser , Worley Sarah , Conjeevaram Selvakumar Praveen Kumar
Published: November 2020

Background and Aims:

Transient elastography (TE) is a valuable tool in assessment of hepatic steatosis and fibrosis using liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), respectively. Although widely used in adults, little is known about performance characteristics and reproducibility of TE (using Fibroscan device) in evaluation of pediatric nonalcoholic fatty liver disease (NAFLD).

Methods:

We prospectively recruited children with NAFLD. Three consecutive Fibroscan examinations were performed during the same visit—twice by a single expert operator and once by a different novice operator. Intra and inter‐operator agreement was calculated using concordance correlation coefficient (CCC). Failure was defined as inability to obtain 10 valid measurements and examination was considered unreliable if LSM interquartile range/median was greater 30%.

Results:

Fifty‐one children (34 boys; median age 15 years) were recruited. Failure rates for expert and novice operator were 10% (5/51) and 12% (6/51) while unreliable readings were obtained in 2% (1/46) and 4% (2/45) of patients, respectively. Patients with failed/unreliable measurements were significantly more obese (median BMI 46.2 vs 33.1 kg/m2, P = 0.002) compared with those with reliable measurements. The intra‐operator agreement was almost perfect for LSM and substantial for CAP values (CCC = 0.85 and 0.73, respectively). Inter‐operator agreement was substantial for LSM and moderate for CAP values (CCC = 0.76 and 0.58, respectively). The inter‐operator agreement in LSM did not vary significantly over time but showed an inverse correlation with BMI and CAP.

Conclusion:

Our study demonstrated that use of TE in assessment of hepatic fibrosis and steatosis in children with NAFLD is highly reliable with low failure rate and highly reproducible with high intra‐ and inter‐operator reproducibility.
Use of Wise Device Technology to Measure Adherence to Hydroxyurea Therapy in Youth With Sickle Cell Disease
Authors: Ingerski Lisa M. , Loew Megan , Porter Jerlym S. , Su Yin , Zhang Hui , Hankins Jane S. , Wang Winfred C.
Published: November 2020

Despite broad support for hydroxyurea (HU) therapy, suboptimal adherence is reported for youth with sickle cell disease. Valid adherence measurement is crucial to understanding the relationship between medication behavior, disease response, and patient-centered health outcomes. The current pilot study examined the feasibility of the Wise electronic device for longitudinal HU adherence measurement in a sample of 36 youths prescribed HU. The study also explored the association between HU adherence, as measured by the Wise device, with other adherence measures (ie, family report, lab values, pill count, and medication possession ratio). A measure of family-reported acceptability was also completed. Overall, results supported the feasibility of the Wise device (rate of consent=82%, device use=75%, device failure=3%) for HU adherence measurement and most families rated their experience using their device positively (favorable responses ranged from 67% to 100%). Associations between HU adherence, as measured by the Wise device, and other adherence measures were not significant. Overall, the feasibility was supported. The Wise device allows longitudinal measurement of adherence with HU from initiation as a young child (ie, with liquid formulations) through adolescence and provides a novel means of adherence measurement for both clinical and research use.
Infantile Pyknocytosis in a Premature Dichorionic Diamniotic Twin
Authors: Spoorenberg Mandy E. , Wachters-Hagedoorn Renate E. , van Wijk Richard , de Kok Jacques B.
Published: November 2020

Infantile pyknocytosis is a rare and self-limiting cause of hemolytic anemia in neonates. It can result in severe anemia and hyperbilirubinemia. The pathogenesis is unknown: a genetic origin has been discussed; however, based on the current literature it is not clear which genetic mutations should be considered. We present a case of a premature twin, in whom genetic screening was performed. Genetic mutations in 46 genes associated with hereditary hemolytic anemia and dyserythropoietic anemia were tested. No mutations were found. In infantile pyknocytosis, a genetic defect in these genes is unlikely.
MEF2D-BCL9 B-Lymphoblastic Leukemia Blast Morphology Does Not Always Mimic Mature B-Cell Leukemia
Authors: Baek Hee Jo , Choi Yoon Jung , Kim Bo Ram , Lee Jun Hyung , Shin Myung-Geun , Kook Hoon
Published: November 2020

MEF2D (myocyte enhancer factor 2D)-rearranged acute lymphoblastic leukemia (ALL) has recently been documented by transcriptome sequencing in B-cell precursor ALL. It is associated with older age of onset (median: 14 y), and characterized by very early relapse and poorer outcomes than other B-cell precursor ALL groups. According to report by Suzuki and colleagues, all 4 cases of MEF2D-BCL9-fusion ALL among 59 children with relapsed or primary refractory ALL had leukemic blasts morphologically mimicking mature B-cell leukemia cells. However, we display morphologically different blast populations in 2 patients with MEF2D-BCL9-rearranged ALL. Mature B-cell leukemia—like morphology would aid the detection of MEF2D-BCL9 fusion, but not all cases might have typical morphology.
Cortactin Expression is a Novel Biomarker for Risk Stratification of T-Cell Acute Lymphoblastic Leukemia
Authors: Aref Salah , Fawzy Enas , Darwish Ahmad , Aref Mohamed , Agdar Mohamed Al
Published: November 2020

The role of cortactin in T-cell acute lymphoblastic leukemia (T-ALL) tissue infiltration has been previously reported. However, its impact on patients’ responsiveness to therapy and patient’s outcome was not previously addressed. This study was conducted on 60 T-ALL pediatric patients at diagnosis and 10 nonleukemic controls. Cortactin and HS1 expressions were identified by real-time polymerase chain reaction. Cortactin and HS1 expression were significantly higher in T-All patients as compared with controls as well as postinduction levels (P≤0.001 for both). The high cortactin expression was significantly associated with high peripheral white cell counts (P≤0.001), blood blast cells (P≤0.001) and central nervous system (CNS) infiltration (P≤0.001), and early precursor T-ALL subtype (P≤0.001) as compared with the remaining groups. The induction of remission response was significantly higher in T-ALL patients with lower cortactin expression levels as compared with T-ALL patients with higher one (P≤0.001). The high cortactin and HS1 expressions were significantly predictors of CNS infiltrations (hazard ratios [HR]: 1.051, confidence interval [CI]: 1.02-1.13, P=0.04 and HR: 1.87, CI: 1.23-2.091, P=0.002, respectively) and bone marrow relapse (HR: 1.43, CI: 1.18-1.92, P=0.004 and HR: 1.07, CI: 1.01-1.24, P=0.002, respectively). Furthermore, high cortactin expression levels were associated with shorter B-ALL patients’ overall survival as compared with those with lower cortactin levels (P=0.002). In conclusion, high expression of cortactin and/or HS1 at diagnosis is a bad prognostic marker of T-ALL patients’ outcome. Moreover, cortactin and/or HS1 expression could be used as a biomarker for refining risk stratification of T-ALL.
Use of a prospective risk analysis method to improve the safety of healthcare workers in oncology hospitals during the COVID-19 spread among cancer patients
Authors: Ouasrhir Abdelali , Rabie Rahhali , Boukhatem Noureddine
Published: November 2020

Background:

Because of their vulnerability, cancer patients were exposed to viral infections and especially by the spread of the COVID-19, the coronavirus pandemic. According to published scientific data, the coronavirus was spread by sneezing, coughing, or the contact of the eyes, nose, and mouth through contaminated spaces. For these reasons, the oncology center's staff needs more protection and more precaution. A multidisciplinary hospital team was assembled to define critical failures linked to cancer patient process in hospital and proposed different actions to secure them and improve this process.

Methods:

According to a risk management tool (Failures Modes Effect and Criticality Analysis), the cancer patient process was mapped in many steps. During the videoconference brainstorming, many ideas were expressed and were classified into an Ishikawa diagram. The criticality indices were calculated from the severity, the occurrence, and the detection probability.

Results:

The cancer patient process has been described; 20 failures have been identified with 8029 points of the sum of critical indices. The new organization of the cancer patient process, the program of training of administrative staff and security agents of hospitals, wearing the protective resources were reduced to the criticality index of 6615 points, a mean of factor reduction of 1291, and the standard deviation was 5007.75.

Conclusion:

Modification of cancer patient process in oncology center resulted in an important risk reduction as shown by risk analysis. Our study illustrates the usefulness of risk analysis methods in the healthcare system. A systematic use of risk analysis was needed to improve the safety of high-risk activities in healthcare processes.
Krukenberg Tumor of Ovary During Pregnancy: Learning From A Mistake
Authors: Jha Shilpy , Mitra Suvradeep , Patra Susama , Sethi Pruthwiraj , Jena Saubhagya K.
Published: November 2020

Sertoli-Leydig cell tumor of the ovary with heterologous differentiation is a relatively uncommon tumor that occurs in females of variable age range. Krukenberg tumor (KT) is a relatively more common tumor of the ovary although only a few cases of KT occur during pregnancy making it an equally uncommon tumor in this setting. We received a unilateral ovarian mass in a 25-yr-old primigravida which we reported as Sertoli-Leydig cell tumor with heterologous (intestinal) differentiation based on its clinical and histomorphologic features. However, on further investigation, a gastric mass was found which was a signet-ring cell adenocarcinoma. We rectified our diagnosis of ovarian mass as KT. We retrospectively analyzed the reasons for our mistake and concluded that the rarity coupled with the nonclassic clinical features and histomorphology of KT during pregnancy pose challenges to the correct diagnosis. This report highlights the diagnostic challenges faced by us along with the ways to circumvent them in the future.
When Is Primary Metacarpal Corrective Osteotomy Recommended in Patients with Flatt Type IV Radial Polydactyly?
Authors: Hong Seok Woo , Kim Jihyeung , Oh Sohee , Lee Min Ho , Baek Goo Hyun
Published: November 2020

Background:

The aim of this study was to determine when primary metacarpal corrective osteotomy is recommended in patients with Flatt type IV radial polydactyly.

Methods:

A total of 78 patients with Flatt type IV radial polydactyly were included. The authors performed metacarpal osteotomy if the angulation of the metacarpophalangeal joint was not correctable by the intraoperative radial stress test. The authors measured the metacarpal deviation angle of the thumb in simple posteroanterior radiographs. The clinical outcomes were assessed using Japanese Society for Surgery of the Hand evaluation total score and the metacarpal deviation angle correction angle. These outcomes were compared between the patients who underwent metacarpal osteotomy and those who did not. Of the patients who did not undergo metacarpal osteotomy, the relationships between preoperative metacarpal deviation angle and the metacarpal deviation angle correction angle were formulated using segmented linear regression analysis.

Results:

There were no significant differences in the demographic features and the value of preoperative metacarpal deviation angle between the two groups. However, the metacarpal deviation angle correction angle and Japanese Society for Surgery of the Hand evaluation total score were significantly higher in the patients who underwent metacarpal osteotomy. The segmented linear regression analysis demonstrated a breakpoint, indicating that the soft-tissue procedure alone does not sufficiently correct the metacarpal deviation angle. For the postoperative metacarpal deviation angle to be 5 degrees, the preoperative metacarpal deviation angle was calculated as 10.8 degrees.

Conclusion:

If the preoperative metacarpal deviation angle is greater than 10.8 degrees, metacarpal osteotomy can be considered even in patients with correctable metacarpophalangeal joint by intraoperative radial stress test.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
A Roadmap for Navigating Occupational Exposures for Surgeons: A Special Consideration for the Pregnant Surgeon
Authors: Landford Wilmina N. , Stewart Talia , Abousy Mya , Ngaage Ledibabari M. , Kambouris Adrienne , Slezak Sheri
Published: November 2020

Surgeons are exposed to occupational hazards daily. Risks include chemical, biological, and physical hazards that place providers at risk of serious harm. Departmental policies or written guides to help pregnant surgeons navigate the hospital are lacking. In response to the scarcity in the literature, the authors have summarized current guidelines and recommendations to aid surgeons in making an informed decision. In addition, the authors present a brief narrative of the impact of these exposures during pregnancy and methods of transmission and, where relevant, include specialties that are at risk of these exposures.
Lean Management and Breakthrough Performance Improvement in Health Care
Authors: Ahn Christie , Rundall Thomas G. , Shortell Stephen M. , Blodgett Janet C. , Reponen Elina
Published: November 2020

Background and Objectives:

Lean management in health care organizations attempts to empower staff to generate continuous improvement through incremental but regular improvements in work processes. However, because of the increasing pressure on health care organizations to substantially improve quality of care and patient outcomes while containing costs in the relatively short term, many health care leaders are looking for ways to achieve large breakthrough improvements in their organization's performance. The objective of this research is to understand whether and how Lean management can be used to achieve breakthrough improvements in performance.

Methods:

This study used grounded theory and content analysis of in-depth, semistructured interviews with 10 nationally recognized experts in the use of Lean management in health care organizations. The 10 participants constitute a purposive sample of experts with in-depth understanding of the strengths and limitations of Lean management in health care organizations.

Results:

Two out of 10 participants defined breakthrough improvement as a major change in a performance metric; 2 participants defined it as a fundamental redesign in a process or service; the remaining 6 participants defined breakthrough improvement as having both these characteristics. The extent to which participants believed Lean was an effective means for achieving breakthrough improvement in performance was related to how they defined breakthrough improvement. The 2 participants who defined breakthrough improvement as a significant change in a performance metric believed Lean methods alone were sufficient. The 2 participants who defined breakthrough improvement to be a fundamental redesign tended not to view Lean alone as an effective approach. Rather, they, and the 6 participants who defined breakthrough improvement as having both change-in-metric and process redesign characteristics, viewed human-centered design thinking as the primary or important complementary approach to achieving breakthrough improvement. Participants identified resources, culture change, and leadership commitment beyond what would be required to achieve incremental improvement as the main facilitators and barriers to achieving breakthrough improvements.

Conclusion:

This research reveals some differences in experts' definitions of breakthrough improvement, and illuminates the value of human-centered design thinking, alone or as a complement to Lean management, in achieving breakthrough improvement in health care organizations. Most of our expert participants agreed that supplementing Lean management methods with the contributions of innovation design and investing significant resources, strengthening the organizational culture to support the necessary changes, and providing stronger leadership commitment to the effort are important facilitators for achieving breakthroughs in organizational performance.
Air temperature and diet influence body composition and water turnover in zoo-living African elephants (Loxodonta africana)
Authors: Pontzer Herman , Rimbach Rebecca , Paltan Jenny , Ivory Erin L. , Kendall Corinne J.
Published: November 2020

African elephants, the largest land animal, face particular physiological challenges in captivity and the wild. Captive elephants can become over- or under-conditioned with inadequate exercise and diet management. Few studies have quantified body composition or water turnover in elephants, and none to date have examined longitudinal responses to changes in diet or air temperature. Using the stable isotope deuterium oxide (2H2O), we investigated changes in body mass, estimated fat-free mass (FFM, including fat-free gut content) and body fat in response to a multi-year intervention that reduced dietary energy density for adult African elephants housed at the North Carolina Zoo. We also examined the relationship between air temperature and water turnover. Deuterium dilution and depletion rates were assayed via blood samples and used to calculate body composition and water turnover in two male and three female African elephants at six intervals over a 3-year period. Within the first year after the dietary intervention, there was an increase in overall body mass, a reduction in body fat percentage and an increase in FFM. However, final values of both body fat percentage and FFM were similar to initial values. Water turnover (males: 359 ± 9 l d−1; females: 241 ± 28 l d−1) was consistent with the allometric scaling of water use in other terrestrial mammals. Water turnover increased with outdoor air temperature. Our study highlights the physiological water dependence of elephants and shows that individuals have to drink every 2–3 days to avoid critical water loss of approximately 10% body mass in hot conditions.
The birth environment of planetary systems
Authors: Parker Richard J.
Published: November 2020

Star and planet formation are inextricably linked. In the earliest phases of the collapse of a protostar, a disc forms around the young star and such discs are observed for the first several million years of a star’s life. It is within these circumstellar, or protoplanetary, discs that the first stages of planet formation occur. Recent observations from the Atacama large millimetre array (ALMA) suggest that planet formation may already be underway after only 1 Myr of a star’s life. However, stars do not form in isolation; they form from the collapse and fragmentation of giant molecular clouds several parsecs in size. This results in young stars forming in groups—often referred to as ‘clusters’. In these star-forming regions, the stellar density is much higher than the location of the Sun and other stars in the Galactic disc that host exoplanets. As such, the environment where stars form has the potential to influence the planet formation process. In star-forming regions, protoplanetary discs can be truncated or destroyed by interactions with passing stars, as well as photoevaporation from the radiation fields of very massive stars. Once formed, the planets themselves can have their orbits altered by dynamical encounters—either directly from passing stars or through secondary effects such as the Kozai–Lidov mechanism. In this contribution, I review the different processes that can affect planet formation and stability in star-forming regions. I discuss each process in light of the typical range of stellar densities observed for star-forming regions. I finish by discussing these effects in the context of theories for the birth environment of the Solar System.