bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review and meta-analysis of breast cancer brain metastasis and primary tumor receptor expression discordance
Authors: Kotecha Rupesh , Tonse Raees , Rubens Muni , McDermott Michael W , Odia Yazmin , Appel Haley , Mehta Minesh P
Published: January 2021

Background

Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or human epidermal growth factor receptor type 2 (HER2) status during the evolutionary course of metastatic breast cancer and the effect of tumor classification subtype switching remain understudied and underappreciated in brain metastasis patients.

Methods

Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic review of series published prior to April 2020 obtained from the Medline database of biopsied or resected breast cancer brain metastasis (BCBM) was performed. Weighted random effects models were used to calculate pooled estimates.

Results

15 full-text articles were included with receptor expression analyses on 1373 patients who underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. Primary tumor receptor expression immunophenotypes were 45.0% ER+, 41.0% ER−, 31.0% PR+, 51.0% PR−, 35% HER2+, and 47.0% HER2−. Corresponding BCBM immunophenotypes were 19.0% ER+, 31.0% ER−, 13.0% PR+, 40.0% PR−, 21.0% HER2+, and 26.0% HER2−. On primary/BCBM comparison, 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%–23.0%) discordant on ER, 23.0% (95% CI: 18.0%–30.0%) discordant on PR, and 12.0% (95% CI: 8.0%–16.0%) discordant on HER2 status. The most common receptor conversions found in BCBM were ER loss 11.0% (95% CI: 8.0%–16.0%), PR loss 15.0% (95% CI: 11.0%–21.0%), and HER2 gain 9.0% (95% CI: 7.0%–11.0%).

Conclusions

BCBM exhibits significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients. Classification patterns need to be analyzed to determine factors predictive of BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.
Association of plasma cell-free DNA with survival in patients with IDH wild-type glioblastoma
Authors: Bagley Stephen J , Till Jacob , Abdalla Aseel , Sangha Hareena K , Yee Stephanie S , Freedman Jake , Black Taylor A , Hussain Jasmin , Binder Zev A , Brem Steven , Desai Arati S , O’Rourke Donald M , Long Qi , Nabavizadeh Seyed Ali , Carpenter Erica L
Published: January 2021

Background

We aimed to determine whether plasma cell-free DNA (cfDNA) concentration is associated with survival in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM).

Methods

Pre-operative and post-chemoradiotherapy blood samples were prospectively collected from patients with newly diagnosed IDH wild-type GBM. Patients underwent surgical resection or biopsy and received adjuvant radiotherapy with concomitant temozolomide. Cell-free DNA (cfDNA) was isolated from plasma and quantified using SYBR Green-based q polymerase chain reaction (qPCR).

Results

Sixty-two patients were enrolled and categorized into high vs. low cfDNA groups relative to the pre-operative median value (25.2 ng/mL, range 5.7–153.0 ng/mL). High pre-operative cfDNA concentration was associated with inferior PFS (median progression-free survival (PFS), 3.4 vs. 7.7 months; log-rank P = .004; hazard ratio [HR], 2.19; 95% CI, 1.26–3.81) and overall survival (OS) (median OS, 8.0 vs. 13.9 months; log-rank P = .01; HR, 2.43; 95% CI, 1.19–4.95). After adjusting for risk factors, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, pre-operative cfDNA remained independently associated with PFS (HR, 2.70; 95% CI, 1.50–4.83; P = .001) and OS (HR, 2.65; 95% CI, 1.25–5.59; P = .01). Post-hoc analysis of change in cfDNA post-chemoradiotherapy compared to pre-surgery (n = 24) showed increasing cfDNA concentration was associated with worse PFS (median, 2.7 vs. 6.0 months; log-rank P = .003; HR, 4.92; 95% CI, 1.53–15.84) and OS (median, 3.9 vs. 19.4 months; log-rank P < .001; HR, 7.77; 95% CI, 2.17–27.76).

Conclusions

cfDNA concentration is a promising prognostic biomarker for patients with IDH wild-type GBM. Plasma cfDNA can be obtained noninvasively and may enable more accurate estimates of survival and effective clinical trial stratification.
Durometry in SSc: The hard facts. A systematic literature review and additional pilot study
Authors: Vanhaecke Amber , Verschuere Sven , Vilela Veronica , Heeman Lise , Cutolo Maurizio , Smith Vanessa
Published: January 2021

Objectives

To investigate the reliability of durometry in systemic sclerosis (SSc), by means of a systematic review and additional pilot study.

Methods

Literature was systematically reviewed according to the PRISMA guidelines to identify all original studies assessing the reliability of durometry in SSc. Additionally, in the pilot study, intra-rater reliability was evaluated in a first cohort of 74 SSc patients (61 female, 13 LSSc/53 LcSSc/8 DcSSc). In a second separate set of 30 SSc patients (21 female, 4 LSSc/20 LcSSc/6 DcSSc), intra- and inter-rater reliability were evaluated.

Results

Only two unique records identified through the systematic review were qualified to generate conclusions. Regarding intra-rater reliability, Kissin reported excellent intra-class correlation coefficient values (ICC, 0.86–0.94) for measurements at nine skin sites in two DcSSc patients. Merkel and Kissin described, both in five DcSSc patients, good to excellent inter-rater reliability (ICC, 0.82–0.96 and 0.61–0.85) for measurements at respectively, six and nine skin sites. In our pilot study, ICC for intra-rater reliability at 17 standardized skin sites were excellent in both cohorts, ranging 0.93–0.99 and 0.78–0.98, respectively. ICC for inter-rater reliability at 17 standardized skin sites were good to excellent 0.63–0.93, except for the feet (0.48 and 0.52).

Conclusion

The preliminary findings in the literature are supported by our pilot study in which we have attested the reliability of durometry in SSc patients. However, prior to including durometry as an (additional) outcome measure in SSc clinical trials, its validation status in the assessment of skin fibrosis needs to be completely attested.
Mind-wandering Is Accompanied by Both Local Sleep and Enhanced Processes of Spatial Attention Allocation
Authors: Wienke Christian , Bartsch Mandy V , Vogelgesang Lena , Reichert Christoph , Hinrichs Hermann , Heinze Hans-Jochen , Dürschmid Stefan
Published: January 2021

Mind-wandering (MW) is a subjective, cognitive phenomenon, in which thoughts move away from the task toward an internal train of thoughts, possibly during phases of neuronal sleep-like activity (local sleep, LS). MW decreases cortical processing of external stimuli and is assumed to decouple attention from the external world. Here, we directly tested how indicators of LS, cortical processing, and attentional selection change in a pop-out visual search task during phases of MW. Participants’ brain activity was recorded using magnetoencephalography, MW was assessed via self-report using randomly interspersed probes. As expected, the performance decreased under MW. Consistent with the occurrence of LS, MW was accompanied by a decrease in high-frequency activity (HFA, 80–150 Hz) and an increase in slow wave activity (SWA, 1–6 Hz). In contrast, visual attentional selection as indexed by the N2pc component was enhanced during MW with the N2pc amplitude being directly linked to participants’ performance. This observation clearly contradicts accounts of attentional decoupling that would predict a decrease in attention-related responses to external stimuli during MW. Together, our results suggest that MW occurs during phases of LS with processes of attentional target selection being upregulated, potentially to compensate for the mental distraction during MW.
COVID-19: Knowledge of Mode of Spread and Preventive Practices among College Adolescents in Nigeria
Authors: Aronu Ann E , Chinawa Awoere T , Ossai Edmund N , Onukwuli Vivian O , Chinawa Josephat M
Published: January 2021

Background

Corona virus pandemic (COVID 19) has emerged as the single most important topical issue and poses a challenge to medicine. Adolescent school children are exposed to a varying degree.

Objectives

The study is aimed to determine the knowledge of the mode of spread and preventive practices among college adolescents attending six secondary schools in Enugu metropolis.

Methodology

This was a cross-sectional study carried out in 6 secondary schools among 500 college adolescents. A pretested, interviewer-administered questionnaire was used for data collection.

Results

Majority of the respondents, 98.4% were aware of COVID-19. Although, a higher proportion of the respondents, 52.0% were aware COVID-19 could be transmitted through contact with infected persons, only a minor proportion of them, 42.4% had a good knowledge of the mode of spread of COVID-19. However, a high proportion of the respondents, 69.2% practiced good preventive measures against COVID-19. Also, respondents whose parents were self-employed were 1.4 times more likely to have good knowledge of the mode of spread of COVID-19 when compared with those whose parents were on paid employment [adjusted odd ratio (AOR) = 1.4, 95% confidence interval (CI): 0.9–2.0]. The respondents whose fathers have attained tertiary education were 1.6 times more likely to have good preventive practices against COVID-19 when compared with those who had secondary school and below (AOR = 1.6, 95% CI: 1.04–2.5).

Conclusion

Though college adolescents were aware of COVID-19, not a significant proportion practiced good preventive measures against COVID-19. Knowledge of mode of spread and preventive practices were significantly enhanced by fathers’ educational status and being a female adolescent child.
Designing transmissible viral vaccines for evolutionary robustness and maximum efficiency
Authors: Layman Nathan C , Tuschhoff Beth M , Nuismer Scott L
Published: January 2021

The danger posed by emerging infectious diseases necessitates the development of new tools that can mitigate the risk of animal pathogens spilling over into the human population. One promising approach is the development of recombinant viral vaccines that are transmissible, and thus capable of self-dissemination through hard to reach populations of wild animals. Indeed, mathematical models demonstrate that transmissible vaccines can greatly reduce the effort required to control the spread of zoonotic pathogens in their animal reservoirs, thereby limiting the chances of human infection. A key challenge facing these new vaccines, however, is the inevitability of evolutionary change resulting from their ability to self-replicate and generate extended chains of transmission. Further, carrying immunogenic transgenes is often costly, in terms of metabolic burden, increased competition with the pathogen, or due to unintended interactions with the viral host regulatory network. As a result, natural selection is expected to favor vaccine strains that down-regulate or delete these transgenes resulting in increased rates of transmission and reduced efficacy against the target pathogen. In addition, efficacy and evolutionary stability will often be at odds; as when longer, more efficacious antigens experience faster rates of evolutionary decay. Here, we ask how such trade-offs influence the overall performance of transmissible vaccines. We find that evolutionary instability can substantially reduce performance, even for vaccine candidates with the ideal combination of efficacy and transmission. However, we find that, at least in some cases, vaccine stability and overall performance can be improved by the inclusion of a second, redundant antigen. Overall, our results suggest that the successful application of recombinant transmissible vaccines will require consideration of evolutionary dynamics and epistatic effects, as well as basic measurements of epidemiological features.
The Impact of 2 Weight-Based Standard Parenteral Nutrition Formulations Compared With One Standard Formulation on the Incidence of Hyperglycemia and Hypernatremia in Low Birth-Weight Preterm Infants
Authors: Garner Sandra S. , Cox Toby H. , Safirstein Julie , Groat Erna K. , Breznak Katherine , Taylor Sarah N.
Published: January 2021

Background:

Standardized parenteral nutrition (PN) formulations are used in at-risk neonates to provide nutrition immediately following birth. However, evidence for the optimal formulation(s) to maximize growth while reducing the risks of glucose and electrolyte abnormalities is limited.

Purpose:

The purpose of this study was to compare the rates of hypernatremia and hyperglycemia with 2 weight-based standardized PN formulations versus one standard PN in low birth-weight preterm neonates.

Methods:

This was a single-center observational study of infants less than 1800 g birth weight and less than 37 weeks' gestation who received standardized PN in the first 48 hours of life. Patients in the weight-based PN group were compared with a historical group of patients receiving single standard PN. Rates of hypernatremia and hyperglycemia were compared by χ2 analysis.

Results:

There was a nonsignificant (P = .147) reduction in hypernatremia in the weight-based PN group (9 of 87; 10.3%) compared with the single PN group (16 of 89; 18.0%). However, hyperglycemia was significantly more frequent in the weight-based group than in the single PN group (24.1% vs 12.4%, P = .035).

Implications for Practice:

The 2 weight-based PN standardized formulations studied did not significantly decrease the incidence of hypernatremia or hyperglycemia.

Implications for Research:

Future studies to determine optimal standardized PN to provide early nutrition in high-risk neonates are warranted.
Deep Gluteal Space, Peripheral Compartment, and Peritrochanteric Disorders
Authors: Perez Carro Luis , Gómez-Hoyos Juan , Fernandez Escajadillo Natalia , Miguel Santos Hugo , Saenz Navarro Ivan , Sabetian Layazali Payam , Alfonso Fernandez Ana
Published: January 2021

Deep gluteal syndrome is an underdiagnosed entity characterized by pain and/or dysesthesias in the buttock area, hip, or posterior thigh and/or radicular pain due to a nondiscogenic sciatic nerve entrapment in the subgluteal space. The whole sciatic nerve trajectory in the deep gluteal space can be addressed by an endoscopic surgical technique, allowing treatment of diverse causes of sciatic nerve entrapment. Endoscopic decompression of the sciatic nerve appears useful in improving function and diminishing hip pain in sciatic nerve entrapments within the subgluteal space. Greater trochanteric pain syndrome has expanded to include a number of disorders, including trochanteric bursitis, tears of the gluteus medius and minimus, and external coxa saltans. This article reviews known and new etiologies of deep gluteal syndrome, assesses the role of orthopedic surgeons in the diagnosis and treatment of sciatic nerve entrapments in the subgluteal, and reviews the present understanding of the lesions that comprise greater trochanteric pain syndrome.
A New Technique for Patient Registration During Navigated Total Hip Arthroplasty
Authors: Oragui Emeka , Du-Moulin Will , Adie Sam , Molnar Robert , Harris Laura
Published: January 2021

Background:

This study describes a new technique of computer navigation for total hip arthroplasty (THA) that uses a customized perspex board to register the coronal plane of a patient in the lateral position. Cup placement is then referenced to the coronal plane.

Purposes:

This paper looks at the outcome of this technique.

Materials and Methods:

Seventeen patients who underwent a total of 18 THA were included. During surgery, the patient was placed in a lateral decubitus position and care taken to ensure the patient was secured perpendicular to the table. The coronal plane was registered using a customized perspex board aligned with the long axis of the operating table. The intraoperative target for acetabular cup placement was 20-degree anteversion and 40-degree inclination with respect to the coronal plane. Radiographs were taken 6 weeks postoperatively.

Results:

The mean cup angle of anteversion was larger in the postoperative method (M=22.83, SD=4.436) than in the intraoperative method (M=22.39, SD=4.629). A 1-sample t test indicated the difference between means was not statistically significant. The mean cup angle of inclination was larger in the intraoperative method (M=44.83, SD=3.400) than in the postoperative method (M=41.56, SD=4.693). A 1-sample t test indicated the difference between means was significant although still within the prescribed safe zones.

Conclusion:

Using a customized perspex board to register the patient and targeting cup placement to a safe zone referenced to the coronal plane result in optimal cup placement when assessed by postoperative radiographs. This avoids the need to turn the patient after registration and obviates the effect of pelvic tilt on cup placement.

Level of Evidence:

Level IV—case series.
Tibia Tubercle Distalization Osteotomy: A Surgical Technique
Authors: DiBartola Alex C. , Magnussen Robert A. , Perez Althea A. , Fitzpatrick Sean , Smith Scott , Flanigan David C.
Published: January 2021

Patella alta increases the risk of recurrent patellar instability. The complex movement of the patellofemoral joint may be altered in a growing number of ways to address various conditions that contribute to patellar instability. We describe a tibial tubercle distalization procedure for the management of patella alta in the setting of recurrent patellar instability.
Posterolateral Tibial Plateau Depression Fracture Reduction and Fixation: A Novel Approach
Authors: Fletcher Jason , Bateman Edward
Published: January 2021

Introduction:

Reduction and fixation of pure depression fractures of the posterolateral tibial plateau are technically challenging. Surgical approach and exposure are complicated by the presence of the fibular head and important ligamentous, and neurovascular structures. Current lateral-based plate options may also leave the elevated articular surface unsupported and risk subsequent collapse.

Materials and Methods:

We present a case of a 37-year-old female rugby player with acute isolated posterolateral tibial plateau depression fracture. We utilized a novel surgical strategy that included a standard anterolateral approach, indirect reduction of the depressed articular surface using a targeted lateral tibial plateau osteotomy, and fixation with anterolateral periarticular and 1/3 tubular plate used in “blade” manner. The reduction was confirmed by fluoroscopy and arthroscopy. Fixation was augmented by femoral strut allograft to fill subsequent defect.

Results:

Postoperative progress was uncomplicated. At a 3-month review, the fracture was united and the patient had a full range of knee motion and function.

Conclusions:

This article presents a technique for reduction and stabilization of posterolateral articular impaction fractures while minimizing potential neurovascular and soft tissue complications.
Rectus Femoris-based Muscle Pedicle Bone Graft for Osteonecrosis of Femoral Head: A New Surgical Technique
Authors: Krishna Anant , Kumar Manoj , Yadav Rajeev , Mehta Rohan , Arora Sumit
Published: January 2021

The pre-collapse and pre-degenerative stages of osteonecrosis of femoral head in young adults are preferably treated by a femoral head preservation operation with the objective to delay or possibly avert the further necrosis, collapse and degeneration of the hip joint. To salvage the early stages of the disease, several muscle pedicle bone grafting (MPBG) procedures based on Quadratus Femoris, Tensor Fasciae Latae, and Sartorius muscles have been described in the literature. To overcome the limitations of these procedures, the authors describe here a much simpler and safer MPBG based on the straight head of the Rectus Femoris with distal transposition of its origin along with anterior inferior iliac spineto the head-neck junction. To the best of our knowledge, MPBG based on Rectus Femoris has not been reported in the currently available literature on osteonecrosis of femoral head. Surgical technique with emphasis on protection of the posterior retinacular vessels, post-operative care and expected outcome is presented.
Static Spacer Construction Using Carbon Fiber Rods in 2-stage Revision for Periprosthetic Knee Infection: A Novel Technique and Indications
Authors: Scott Brandon , Levins James , Mariorenzi Michael , Marcaccio Steven , Cohen Eric
Published: January 2021

Background:

Traditionally, 2-stage exchange arthroplasty is preferred to eradicate chronic periprosthetic joint infections after total knee arthroplasty. However, for cases with significant bone destruction and/or soft tissue damage, the risk of knee instability increases with this technique, leading to a number of complications such as tibiofemoral dislocation, wound healing complications, extensor mechanism rupture, or failure of extensor mechanism repair. Intramedullary fixator rods reinforcing static spacers have been utilized to provide improved stability, but persistent infections were still prevalent. Antibiotic static spacers with intramedullary fixator rods coated with antibiotic cement can lower these reinfection rates.

Surgical Technique:

The surgical sequence requires removal of the infected prosthesis and placement of a carbon fiber rod and nonarticulating antibiotic spacer. This remains in situ for ~6 to 12 weeks while the patient receives systemic antibiotic treatment. Following confirmation of successful treatment, the antibiotic spacer and carbon fiber rod are removed, and revision arthroplasty is performed in a standard manner.

Results:

After a minimum of 1-year follow-up, no recurrent infections were diagnosed, 1 patient suffered a complication requiring expedited antibiotic spacer removal, and 1 patient expired in this cohort.

Conclusions:

This technique represents an effective method of providing stability of the knee and delivering adequate antibiosis in patients with knee periprosthetic joint infections in the setting of extensor mechanism disruption and severe bone loss.
Transcranial Doppler Versus CT-Angiography for Detection of Cerebral Vasospasm in Relation to Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Prospective Single-Center Cohort Study
Authors: van der Harst J. Joep , Luijckx Gert-Jan. R. , Elting Jan Willem J. , Bokkers Reinoud P.H. , van den Bergh Walter M. , Eshghi Omid S. , Metzemaekers Jan D.M. , Groen Rob J.M. , Mazuri Aryan , van Dijk J. Marc C. , Uyttenboogaart Maarten
Published: January 2021

Objectives:

Cerebral vasospasm in the first 2 weeks after aneurysmal subarachnoid hemorrhage is recognized as a major predictor of delayed cerebral ischemia. The routine screening for cerebral vasospasm with either transcranial Doppler or CT angiography has been advocated, although its diagnostic value has not yet been determined. Our study investigated the diagnostic accuracy of detecting vasospasm by transcranial Doppler and CT angiography for the prediction of delayed cerebral ischemia and functional outcome. Additionally, agreement between transcranial Doppler and CT angiography was determined.

Design:

Prospective diagnostic accuracy study.

Settings:

Neurocritical care unit and neurosurgical ward at a tertiary academic medical center.

Patients:

Between 2013 and 2016, 59 consenting patients were included.

Intervention:

Patients undergo both transcranial Doppler and CT angiography for detection of cerebral vasospasm on days 5 and 10 after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia was defined as secondary neurologic deterioration, not explained otherwise. Unfavorable outcome was defined modified Rankin Scale > 2 at 6 months.

Measurements and Main Results:

On transcranial Doppler, cerebral vasospasm was observed in 26 patients (45%). On CT angiography, vasospasm was observed in 54 patients (95%). The agreement between transcranial Doppler and CT angiography was 0.47. Delayed cerebral ischemia occurred in 16 patients (27%); unfavorable outcome in 12 patients (20%). Transcranial Doppler predicted delayed cerebral ischemia with a sensitivity of 0.44 (day 5) and 0.50 (day 10), with a specificity of 0.67 (day 5) and 0.57 (day 10). CT angiography predicted delayed cerebral ischemia with a sensitivity of 0.81 (day 5 and 10) and with a specificity of 0.070 (day 5) and 0.00 (day 10). The highest accuracy for predicting unfavorable outcome was on day 5 (0.61 for transcranial Doppler vs 0.27 for CT angiography).

Conclusion:

The diagnostic accuracy of both CT angiography and transcranial Doppler for detection of cerebral vasospasm as well as prediction of delayed cerebral ischemia and functional outcome is limited. The agreement between CT angiography and transcranial Doppler is low.
CHORIOCAPILLARIS FLOW IMPAIRMENT IN TYPE 3 MACULAR NEOVASCULARIZATION
Authors: Le Hoang Mai , Souied Eric H. , Querques Giuseppe , Colantuono Donato , Borrelli Enrico , Sacconi Riccardo , Amoroso Francesca , Capuano Vittorio , Jung Camille , Miere Alexandra
Published: January 2021

Purpose:

To quantitatively analyze choriocapillaris alterations using swept-source optical coherence tomography angiography in eyes presenting with Type 3 macular neovascularization (MNV) and to compare these alterations with eyes presenting with intermediate AMD (iAMD).

Methods:

Macular 3 × 3-mm swept-source optical coherence tomography angiography scans were retrospectively analyzed in eyes with Type 3 MNV and in eyes with iAMD. The choriocapillaris en face slabs were extracted from the swept-source optical coherence tomography angiography device after manual segmentation. En face choriocapillaris flow images were compensated with en face choriocapillaris structure images, followed by the Phansalkar local thresholding method using a window radius of 4 and 8 pixels. The percentage of flow deficits (FD%), the number, size, and total area of FDs were computed for comparison. A secondary analysis was performed in the four corners of the image to include equidistant regions in all eyes.

Results:

Twenty-six Type 3 MNV eyes of 21 patients and 26 iAMD eyes of 17 patients were included. Compared with iAMD eyes, eyes with Type 3 MNV displayed a higher FD% (41.37% ± 14.74 vs. 19.80% ± 9.63 using radius 4 pixels [P < 0.001]; 45.24% ± 11.9 vs. 26.63% ± 8.96 using radius 8 pixels [P < 0.001]). The average size of FDs was significantly larger in Type 3 MNV eyes compared with iAMD eyes (P < 0.001), whereas the number of FDs was significantly lower in Type 3 MNV compared with iAMD eyes (P < 0.001).

Conclusion:

Type 3 MNV eyes present with increased choriocapillaris flow impairment compared with iAMD eyes. Reduced choriocapillaris perfusion may contribute to Type 3 MNV development and pathogenesis.
Tuberculosis in Children Hospitalized in a Low-burden Country
Authors: Cogo Haude , Caseris Marion , Lachaume Noémie , Cointe Aurélie , Faye Albert , Pommelet Virginie
Published: January 2021

Background:

In high-income countries, few pediatric studies have described the clinical expression of tuberculosis (TB) according to age, and their results are discordant. Patients <2 years of age are usually considered to be at higher risk for severe disease than older children. Our aim was to better describe pediatric TB disease severity in a low-incidence country.

Methods:

All children (<18 years of age) admitted with TB disease to the Robert Debré University Hospital, Paris, between 1992 and 2015 were included. Patients were classified by the severity of TB disease based on the original classification of Wiseman et al. Risk factors associated with severity were analyzed.

Results:

We included 304 patients with a median age of 9.9 years (interquartile range 3.3–13.3) and a male to female ratio of 1.04. Overall, 280/304 (92%) were classified: 168/304 (55%) were classified as showing severe TB and 112/304 (37%) as showing non-severe TB. Central nervous system disease was more frequent among patients <2 years of age than patients 2–17 years of age (5/54; 9% vs. 5/229; 2% P = 0.024). An age of ≥10 years (P = 0.001) and being born abroad (P = 0.011) were both associated with disease severity in univariate analysis. In multivariate analysis, diagnosis through symptom-based screening was independently associated with severity (odds ratio 7.1, 95% confidence interval: 3.9–12.9, P < 0.0001).

Conclusions:

This description of the clinical spectrum of pediatric TB in a low-burden setting demonstrates that adolescents are the group most at risk of experiencing severe TB.
ART Initiation for Infants Diagnosed With HIV Through Point of Care and Conventional Polymerase Chain Reaction Testing in Kenya: A Case Series
Authors: Wexler Catherine , Maloba May , Goggin Kathy , Kale Shadrack Babu , Maosa Nicodemus , Muchoki Elizabeth , Brown Melinda , Gautney Brad , Finocchario-Kessler Sarah
Published: January 2021

We sought to understand the sequence of testing and treatment among nine infants offered both conventional and point-of-care testing and diagnosed as HIV-positive by 6 months of age in Kenya. One infant received per protocol testing and treatment. Patient-level (late presentation and disengagement), provider-level (reluctance and error/oversight) and system-level (stock outs, errors) challenges delayed diagnosis and treatment. Early point-of-care testing can streamline testing; however, challenges mitigate benefits.
Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092
Authors: Owor Maxensia , Tierney Camlin , Ziemba Lauren , Browning Renee , Moye John , Graham Bobbie , Reding Christina , Costello Diane , Norman Jennifer , Wiesner Lubbe , Hughes Emma , Whalen Meghan E. , Purdue Lynette , Mmbaga Blandina Theophil , Kamthunzi Portia , Kawalazira Rachel , Nathoo Kusum , Bradford Sarah , Coletti Anne , Aweeka Francesca. , Musoke Philippa
Published: January 2021

Background:

Severe acute malnutrition (SAM) may alter the pharmacokinetics (PK), efficacy, and safety of antiretroviral therapy. The phase IV study, IMPAACT P1092, compared PK, safety, and tolerability of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in children with and without SAM.

Materials and methods:

Children living with HIV 6 to <36 months of age with or without World Health Organization (WHO)-defined SAM received ZDV, 3TC, and LPV/r syrup for 48 weeks according to WHO weight band dosing. Intensive PK sampling was performed at weeks 1, 12, and 24. Plasma drug concentrations were measured using liquid chromatography tandem mass spectrometry. Steady-state mean area under the curve (AUC0–12h) and clearance (CL/F) for each drug were compared. Grade ≥3 adverse events were compared between cohorts.

Results:

Fifty-two children were enrolled across 5 sites in Africa with 44% (23/52) female, median age 19 months (Q1, Q3: 13, 25). Twenty-five children had SAM with entry median weight-for-height Z-score (WHZ) −3.4 (IQR −4.0, −3.0) and 27 non-SAM had median WHZ −1.0 (IQR −1.8, −0.1). No significant differences in mean AUC0–12h or CL/F were observed (P ≥ 0.09) except for lower 3TC AUC0–12h (GMR, 0.60; 95% CI, 0.4–1.0; P = 0.047) at week 12, higher ZDV AUC0–12h (GMR, 1.52; 1.2–2.0; P = 0.003) at week 24 in the SAM cohort compared with non-SAM cohort. Treatment-related grade ≥3 events did not differ significantly between cohorts (24.0% vs. 25.9%).

Conclusion:

PK and safety findings for ZDV, 3TC, and LPV/r support current WHO weight band dosing of syrup formulations in children with SAM.
Repeated Emergency Department Visits Among Children with Invasive Bacterial Infections
Authors: Gangoiti Iker , Gorostizaga Zaloa , Aranzamendi Maitane , Gomez Borja , Benito Javier , Mintegi Santiago
Published: January 2021

We carried out a retrospective cohort study of 271 previously healthy children younger than 14 years old diagnosed with invasive bacterial infection in an emergency department. Of them, 72 (26.6%) had previous visits to the emergency department. Not identifying children with an invasive bacterial infection and not administering antibiotics on the first visit was associated with a severe outcome.
Body Fat Distribution and Metabolic Changes in a Cohort of Adolescents Living With HIV Switched to an Antiretroviral Regimen Containing Dolutegravir
Authors: Giacomet Vania , Lazzarin Samuel , Manzo Andrea , Paradiso Laura , Maruca Katia , Barera Graziano , Zuccotti Gian Vincenzo , Mora Stefano
Published: January 2021

Use of antiretrovirals is associated to body fat accumulation. We measured body composition in adolescents living with HIV switched to a dolutegravir-containing regimen. Trunk fat and trunk/body fat ratio markedly increased after 12 months. Total and low density lipoprotein cholesterol decreased after 3 months. Increase in trunk fat may put at risk of future cardiovascular problems, despite improvement in the lipid profile.
Advances in acute pancreatitis
Authors: Sinonquel Pieter , Laleman Wim , Wilmer Alexander
Published: January 2021

Purpose of review

With a potentially life-threatening course, acute pancreatitis (AP) is one of the most common gastrointestinal diseases requiring hospitalization and often necessitating intensive care. Based on recent insights and recommendations, this review provides an overview on clinical management of AP patients with a focus on intensive care unit care.

Recent findings

Possible benefits of percutaneous paracentesis and/or drainage on outcome or inflammation have been further explored. Combined opioid and epidural analgesia for pain management might be a valuable alternative for pain management. Very recent international guidelines now agree on a step-up approach for the management of acute necrotizing pancreatitis favoring a minimally invasive approach with either endoscopic or percutaneous drainage first. Studies for the best timing of these interventions are ongoing. In spite of a better understanding of pathophysiological mechanisms mediating AP, specific treatments are still awaited.

New evidence and recent international consensus direct the current management of AP toward a tailored, multidisciplinary and less invasive therapy with complementary roles for hepatologists, intensivists, radiologists, and surgeons.
Open reduction and internal fixation (ORIF) versus ORIF and primary subtalar arthrodesis for complex displaced intraarticular calcaneus fractures
Authors: Eisenstein Emmanuel David , Kusnezov Nicholas A. , Waterman Brian R. , Orr Justin D. , Blair James A.
Published: January 2021

Objectives:

To determine the optimal patient-oriented treatment between open reduction and internal fixation (ORIF) with or without primary subtalar arthrodesis (PSTA) for patients with displaced intraarticular calcaneus fractures (DIACFs, OTA 82-C3 and C4).

Design:

Expected value decision analysis.

Setting:

Academic military treatment facility

Participants:

One hundred randomly selected volunteers.

Intervention:

Hypothetical clinical scenario involving ORIF versus ORIF with PSTA.

Main outcome measurements:

Decision analysis was used to elucidate the superior treatment option based on expected patient values, composed of: the product of the average outcome probabilities established by previously published studies and the average ascribed patient utility values for each outcome probability. One-way sensitivity analysis was performed to quantify the amount of change required for the inferior treatment to equal or surpass the superior option.

Results:

Expected values for ORIF and ORIF with PSTA were 8.96 and 18.06, respectively, favoring ORIF with PSTA. One-way sensitivity analysis was performed by artificially decreasing the rate of secondary fusion following isolated ORIF thus increasing its overall expected value. Adjusting the rate of secondary fusion to 0%, the expected value of ORIF with PSTA nearly doubled that of ORIF (18.06 vs 9.45). Similarly, when adjusting the moderate and severe complication rates following ORIF with PSTA to 100%, the expected value of ORIF with PSTA still exceeded that of ORIF (15.45 vs 8.96, and 13.52 vs 8.96, respectively).

Conclusion:

Expected value decision analysis favors ORIF with PSTA as the optimal treatment for complex DIACF.
A salvage strategy for heel pad degloving injury
Authors: Cantrell William A. , Lawrenz Joshua M. , Vallier Heather A.
Published: January 2021

Case:

A 50-year-old female experienced a crush injury to the foot resulting in open degloving of her heel pad. This study details a surgical strategy to achieve healing and limb salvage.

Conclusion:

Heel pad injuries with degloving are difficult to salvage and have a poor prognosis. Amputation is often the only therapeutic option, unless part of the blood supply to the heel pad is intact, rendering limb salvage a possibility.
Atrophic nonunion stromal cells form bone and recreate the bone marrow environment in vivo
Authors: Vallim Frederico C. , Guimarães João Antonio Matheus , Dias Rhayra B. , Sartore Rafaela C. , Cavalcanti Amanda dos S. , Leal Ana C. , Duarte Maria Eugenia L. , Bonfim Danielle C.
Published: January 2021

Introduction:

Nonunion is a challenging condition in orthopaedics as its etiology is not fully understood. Clinical interventions currently aim to stimulate both the biological and mechanical aspects of the bone healing process by using bone autografts and surgical fixation. However, recent observations showed that atrophic nonunion tissues contain putative osteoprogenitors, raising the hypothesis that its reactivation could be explored to achieve bone repair.

Methods:

Here we characterized atrophic nonunion stromal cells (NUSC) in vitro, using bone marrow stromal cells (BMSC) and osteoblasts as controls cells of the osteoblastic lineage, and evaluated its ability to form bone in vivo.

Results:

NUSC had proliferative and senescence rates comparable to BMSC and osteoblasts, and homogeneously expressed the osteolineage markers CD90 and CD73. Regarding CD105 and CD146 expression, NUSC were closely related to osteoblasts, both with an inferior percentage of CD105+/CD146+cells as compared to BMSC. Despite this, NUSC differentiated along the osteogenic and adipogenic lineages in vitro; and when transplanted subcutaneously into immunocompromised mice, new bone formation and hematopoietic marrow were established.

Conclusions:

This study demonstrates that NUSC are osteogenically competent, supporting the hypothesis that their endogenous reactivation could be a strategy to stimulate the bone formation while reducing the amount of bone autograft requirements.
Adaptive optics enhanced all-optical photoacoustic tomography
Authors: Czuchnowski Jakub , Prevedel Robert
Published: January 2021

All-optical ultrasound detection bears a number of unique advantages for photoacoustic tomography, including the ability for high resolution sampling of the acoustic field and its compatibility with a wide variety of other optical modalities. However, optical schemes based on miniaturized cavities are sensitive to optical aberrations as well as manufacturing-induced cavity imperfections which degrade sensor sensitivity and deteriorate photoacoustic image quality. Here we present an experimental method based on adaptive optics that is capable of enhancing the overall sensitivity of Fabry-Pérot based photoacoustic sensors. We experimentally observe clear improvements in photoacoustic signal detection as well as overall image quality after photoacoustic tomography reconstructions when applied to mammalian tissuesin vivo.
Lower neural value signaling in the prefrontal cortex is related to childhood family income and depressive symptomatology during adolescence
Authors: Palacios-Barrios Esther E. , Hanson Jamie L. , Barry Kelly R. , Albert Dustin , White Stuart F. , Skinner Ann T. , Dodge Kenneth A. , Lansford Jennifer E.
Published: January 2021

Lower family income during childhood is related to increased rates of adolescent depression, though the specific mechanisms are poorly understood. Evidence suggests that individuals with depression demonstrate hypoactivation in brain regions involved in reward learning and decision-making processes (e.g., portions of the prefrontal cortex). Separately, lower family income has been associated with neural alterations in similar regions. We examined associations between family income, depression, and brain activity during a reward learning and decision-making fMRI task in a sample of adolescents (full n=94; usable n=78; mean age=15.4 years). We identified neural regions representing 1) expected value (EV), the learned subjective value of an object, and 2) prediction error, the difference between EV and the actual outcome received. Regions of interest related to reward learning were examined in connection to childhood family income and parent-reported adolescent depressive symptoms. As hypothesized, lower activity in the subgenual anterior cingulate (sACC) for EV in response to approach stimuli was associated with lower childhood family income, as well as greater symptoms of depression measured one-year after the neuroimaging session. These results are consistent with the hypothesis that lower early family income leads to disruptions in reward and decision-making brain circuitry, which leads to adolescent depression.
Friction is preferred over grasp configuration in precision grip grasping
Authors: Klein Lina K. , Maiello Guido , Fleming Roland W. , Voudouris Dimitris
Published: January 2021

How humans visually select where to grasp an object depends on many factors, including grasp stability and preferred grasp configuration. We examined how endpoints are selected when these two factors are brought into conflict: Do people favor stable grasps or do they prefer their natural grasp configurations? Participants reached to grasp one of three cuboids oriented so that its two corners were either aligned with, or rotated away from, each individual’s natural grasp axis (NGA). All objects were made of brass (mass: 420 g) but the surfaces of their sides were manipulated to alter friction: 1) all-brass, 2) two opposing sides covered with wood, while the other two remained of brass, or 3) two opposing sides covered with sandpaper, and the two remaining brass sides smeared with vaseline. Grasps were evaluated as either clockwise (thumb to the left of finger in frontal plane) or counterclockwise of the NGA. Grasp endpoints depended on both object orientation and surface material. For the all-brass object, grasps were bimodally distributed in the NGA-aligned condition but predominantly clockwise in the NGA-unaligned condition. These data reflected participants’ natural grasp configuration independently of surface material. When grasping objects with different surface materials, endpoint selection changed: Participants sacrificed their usual grasp configuration to choose the more stable object sides. A model in which surface material shifts participants’ preferred grip angle proportionally to the perceived friction of the surfaces accounts for our results. Our findings demonstrate that a stable grasp is more important than a biomechanically comfortable grasp configuration.

NEW & NOTEWORTHY

When grasping an object, humans can place their fingers at several positions on its surface. The selection of these endpoints depends on many factors, with two of the most important being grasp stability and grasp configuration. We put these two factors in conflict and examine which is considered more important. Our results highlight that humans are not reluctant to adopt unusual grasp configurations in order to satisfy grasp stability.
Microglia perform local protein synthesis at perisynaptic and phagocytic structures
Authors: Vasek Michael J. , Deajon-Jackson Jelani D. , Liu Yating , Crosby Haley W. , Yi Jiwon , Dougherty Joseph D.
Published: January 2021

Recent studies have illuminated the importance of several key signaling pathways in regulating the dynamic surveillance and phagocytic activity of microglia. Yet little is known about how these signals result in the assembly of phagolysosomal machinery near targets of phagocytosis, especially in processes distal from the microglial soma. Neurons, astrocytes, and oligodendrocytes locally regulate protein translation within distal processes. Therefore, we tested whether there is regulated local translation within peripheral microglia processes (PeMPs). We show that PeMPs contain ribosomes which engage inde novoprotein synthesis, and these associate with a subpool of transcripts involved in pathogen defense, motility, and phagocytosis. Using a live slice preparation, we further show that acute translation blockade impairs the formation of PeMP phagocytic cups, the localization of lysosomal proteins within them, and phagocytosis. Collectively, these data argue for a regulated local translation in PeMPs and indicate a need for new translation to support dynamic microglial function.
New Gene Embedding Learned from Biomedical Literature and Its Application in Identifying Cancer Drivers
Authors: Liang Lifan , Lu Xinghua , Lu Songjian
Published: January 2021

To investigate molecular mechanism of diseases, we need to understand how genes are functionally associated. Computational researchers have tried to capture functional relationships among genes by constructing an embedding space of genes from multiple sources of high-throughput data. However, correlations in high-throughput data does not necessarily imply functional relations. In this study, we generated gene embedding from literature by constructing semantic representation for each gene. This approach enabled us to cover genes less mentioned in literature and revealed novel functional relationships among genes. Evaluation showed that the learned gene embedding was consistent with pathway knowledge and enhanced the search for cancer driver genes. We further applied our gene embedding to identify protein complexes and functional modules from gene networks. Performance in both scenarios was significantly improved with gene embedding.
CRISPR/Cas-9 mediated knock-in by homology dependent repair in the West Nile Virus vectorCulex quinquefasciatusSay
Authors: Purusothaman Deepak-Kumar , Shackleford Lewis , Anderson Michelle A. E. , Harvey-Samuel Tim , Alphey Luke
Published: January 2021

Culex quinquefasciatusSay is a brown, medium sized mosquito distributed widely in both tropical and subtropical regions of the world. It is a night-active, opportunistic blood-feeder and is responsible for vectoring many animal and human diseases, including West Nile Virus and avian malaria. Current vector control methods (e.g. physical / chemical) are increasingly ineffective; use of insecticides also imposes some hazards to both human and ecosystem health. Recent advances in genome editing have allowed the development of genetic methods of insect control, which is species-specific and, theoretically, highly effective. CRISPR/Cas9 is a bacteria-derived programmable gene editing tool that has been shown to be functional in a range of species. We demonstrate here, the first successful germline gene knock-in by homology dependent repair inC. quinquefasciatus. Using CRISPR/Cas9, we integrated exogenous sequence comprising a sgRNA expression cassette and marker gene encoding a fluorescent protein fluorophore (Hr5/IE1-DsRed, Cq7SK-sgRNA) into the kynurenine 3-monooxygenase (kmo) gene. We achieved a minimum transformation rate of 2.8% similar to rates achieved in other mosquito species. Precise knock-in at the intended locus was confirmed by sequencing. Insertion homozygotes displayed a white eye phenotype in early-mid stage larvae and a recessive lethal phenotype by pupation. This work shows an alternative and efficient method for genetic engineering ofC. quinquefasciatus, providing a new tool for researchers interested in developing genetic control tools for this vector.