bluuebunny/crossref_metadata_2025 huggingface dataset:
Syndecan‐3 enhances anabolic bone formation through WNT signaling
Authors: Johnson de Sousa Brito Francesca Manuela , Butcher Andrew , Pisconti Addolorata , Poulet Blandine , Prior Amanda , Charlesworth Gemma , Sperinck Catherine , Scotto di Mase Michele , Liu Ke , Bou‐Gharios George , Jurgen van 't Hof Robert , Daroszewska Anna
Published: March 2021

Osteoporosis is the most common age‐related metabolic bone disorder, which is characterized by low bone mass and deterioration in bone architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts to form new bone and restore bone structure, however, anabolic therapeutics are few and their use is time restricted. Here, we report that Syndecan‐3 increases new bone formation through enhancement of WNT signaling in osteoblasts. Young adult Sdc3−/− mice have low bone volume, reduced bone formation, increased bone marrow adipose tissue, increased bone fragility, and a blunted anabolic bone formation response to mechanical loading. This premature osteoporosis‐like phenotype of Sdc3−/− mice is due to delayed osteoblast maturation and impaired osteoblast function, with contributing increased osteoclast‐mediated bone resorption. Indeed, overexpressing Sdc3 in osteoblasts using the Col1a1 promoter rescues the low bone volume phenotype of the Sdc3−/− mice, and also increases bone volume in WT mice. Mechanistically, SDC3 enhances canonical WNT signaling in osteoblasts through stabilization of Frizzled 1, making SDC3 an attractive target for novel bone anabolic drug development.
Identifying Core Components of EPA Implementation: A Path to Knowing if a Complex Intervention Is Being Implemented as Intended
Authors: Carraccio Carol , Martini Abigail , Van Melle Elaine , Schumacher Daniel J.
Published: March 2021

Purpose

Competency-based assessment, using entrustable professional activities (EPAs), is rapidly being implemented worldwide without sufficient agreement on the essential elements of EPA-based assessment. The rapidity of implementation has left little time to understand what works in what circumstances and why or why not. The result is the attempted execution of a complex service intervention without a shared mental model for features needed to remain true to implementing an EPA assessment framework as intended. The purpose of this study was to identify the essential core components necessary to maintain integrity in the implementation of this intended intervention.

Method

A formal consensus-building technique, the Delphi process, was used to identify core components for implementing an EPA-based assessment framework. Twelve EPA experts from the United States, Canada, and the Netherlands participated in this process in February and March 2020. In each Delphi round, participants rated possible core components on a scale from 1 to 6, with 1 reflecting the worst fit and 6 the best fit for EPA-based assessment implementation. Predetermined automatic inclusion and exclusion criteria for candidate core components were set at ≥ 80% of participants assigning a value of 5 or 6 and ≥ 80% assigning a value of 1 or 2, respectively.

Results

After 3 rounds, participants prioritized 10 of 19 candidate core components for inclusion: performance prediction, shared local mental model, workplace assessment, high-stakes entrustment decisions, outcomes based, value of the collective, informed clinical competency committee members, construct alignment, qualitative data, and entrustment decision consequences. The study closed after 3 rounds on the basis of the rankings and comments.

Conclusions

Using the core components identified in this study advances efforts to implement an EPA assessment framework intervention as intended, which mitigates the likelihood of making an incorrect judgment that the intervention demonstrates negative results.
Four-level Anterior Cervical Discectomy and Fusions
Authors: Jack Megan M. , Lundy Paige , Reeves Alan R. , Arnold Paul M.
Published: March 2021

Study Design:

A retrospective review of prospectively collected case series.

Objective:

This is a retrospective review of prospectively collected data regarding the clinical outcomes, complications, and fusion rates of patients who underwent a 4-level (C3–C7) anterior cervical discectomy and fusion (ACDF).

Summary of Background:

The use of multilevel ACDF for cervical spondylosis has been controversial. The literature regarding fusion rates and outcomes have been variable. This study intends to evaluate the outcomes following multilevel ACDF in a large cohort of patients.

Clinical Materials and Methods:

Between 1994 and 2011, 60 patients underwent a 4-level ACDF by a single surgeon. All patients were followed for a minimum of 12 months, and outcome measures included neurological findings, presence or absence of radiographic fusion, and complication rates. All patients had radiographic documentation of spinal cord stenosis at 4 consecutive cervical levels as well as myelopathy and/or radiculopathy symptoms.

Results:

Forty-eight patients underwent a single anterior procedure, only 5 patients underwent concurrent anterior and posterior fusion, and 7 patients required a second posterior surgery due to new-onset or residual symptoms or hardware complications after undergoing ACDF. Patients most commonly presented with paresthesias and were diagnosed with cervical stenosis. Overall, 18.3% reported early postoperative dysphagia; however, only 2 patients continued to have mild dysphagia symptoms on long-term follow-up. Other complications included hardware failure (11), residual neck pain (7), residual paresthesias (6), new-onset weakness (3), neck hematoma (1), cellulitis (1), and C5 radiculopathy (1). Overall, 88.3% of patients reported improvement in initial symptoms. Nurick scores were significantly lower following 4-level ACDF. The radiographic fusion rate for all levels was 95%. No patients required reoperation for pseudarthrosis.

Conclusion:

In appropriate patients, 4-level ACDF is a safe, efficacious method for treating multilevel cervical spinal cord compression, with acceptable complication rates and the ability to achieve neurological improvement and high fusion rates.
Surgical Treatment for Cervical Spine Fracture in Patients With Ankylosing Spondylitis
Authors: Liu Bingchuan , Ji Hongquan , Zhang Zhishan , Guo Yan , Lv Yang , Yang Zhongwei , Hou Guojin , Zhou Fang , Tian Yun
Published: March 2021

Study Design:

A retrospective single-center study.

Objective:

We aimed to compare the clinical outcomes of cervical spine fracture accompanied with ankylosing spondylitis (ASCSF) treated by single posterior approach (PA) and combined anterior-posterior approach (CA) for patients who were followed up for >1 year,

Summary of Background Data:

For ASCSF patients, surgical treatment has been widely accepted as a recommendable therapeutic option. But the optimal surgical approach is still under controversy, and few studies have focused on the comparison between PA and CA.

Materials and Methods:

From February 2007 to March 2019, 53 patients were enrolled and divided into the PA group (34 cases) and CA group (19 cases). Their general characteristics and clinical materials were recorded. From the aspects of reduction distance, bone fusion, neurological functional restoration, and postoperative complications, patients’ surgical outcomes were evaluated qualitatively and quantitatively.

Results:

The reduction degree of dislocation (mean PA=2.05 mm, mean CA=2.36 mm, P=0.94) was close between the 2 groups. Besides, with a similar follow-up period (P=0.10), the rate of bone fusion (both 100%) and neurological functional restoration (PA=31.03%, CA=35.29%, P=0.77) were also without significant difference. The occurrence rate of postoperative complications tended to be higher in the CA group (31.58% vs. 23.53%) but with no significant difference (P=0.52). Nevertheless, the surgical duration time (mean=209.15 min) and blood loss (average=388.91 mL) of PA group were significantly less than CA group (mean duration time=285.34 min, mean blood loss=579.27 mL) (P<0.01).

Conclusions:

Compared with to the CA approach and with the equally significant outcome, surgery by single PA was feasible and should be positively recommended for ASCSF patients, especially for those accompanying with a severe chin-on-chest deformity or poor physical conditions which restrain patients from tolerating a long surgery or major surgical trauma.
Impact of Discharge to Rehabilitation on Postdischarge Morbidity Following Multilevel Posterior Lumbar Fusion
Authors: Song Junho , Katz Austen D. , Perfetti Dean , Job Alan , Morris Matthew , Goldstein Jeffrey , Virk Sohrab , Silber Jeff , Essig David
Published: March 2021

Study Design:

This was a retrospective cohort study.

Objective:

The objective of this study was to compare 30-day postdischarge morbidity for 3-or-more level (multilevel) posterior lumbar fusion in patients who were discharged to home versus rehabilitation.

Summary of Background Data:

Spine surgery has been increasingly performed in the elderly population, with many of these patients being discharged to rehabilitation and skilled nursing facilities. However, research evaluating the safety of nonhome discharge following spine surgery is limited.

Materials and Methods:

Patients who underwent multilevel posterior lumbar fusion from 2005 to 2018 were identified using the National Surgical Quality Improvement Program (NSQIP) database. Regression was utilized to compare primary outcomes between discharge disposition and to evaluate for predictors thereof.

Results:

We identified 5276 patients. Unadjusted analysis revealed that patients who were discharged to rehabilitation had greater postdischarge morbidity (5.6% vs. 2.6%). After adjusting for baseline differences, discharge to rehabilitation no longer predicted postdischarge morbidity [odds ratio (OR)=1.409, confidence interval: 0.918–2.161, P=0.117]. Multivariate analysis also revealed that age (P=0.026, OR=1.023), disseminated cancer (P=0.037, OR=6.699), and readmission (P<0.001, OR=28.889) independently predicted postdischarge morbidity.

Conclusions:

Thirty days morbidity was statistically similar between patients who were discharged to home and rehabilitation. With appropriate patient selection, discharge to rehabilitation can potentially minimize 30-day postdischarge morbidity for more medically frail patients undergoing multilevel posterior lumbar fusion. These results are particularly important given an aging population, with a great portion of elderly patients who may benefit from postacute care facility discharge following spine surgery.
Immunohistochemical Expression of Galectin-3 in Pemphigus Vulgaris
Authors: Aghighi Maryam , Pukhalskaya Tatsiana , Smoller Bruce R.
Published: March 2021

Pemphigus vulgaris (PV) is an autoimmune bullous disorder related to immunoglobulin-G autoantibodies against desmoglein-3. Galectin-3 is one of the main elements of the immunoglobulin-E group which is essential in the cell–cell or cell–matrix adhesion. Although the presence of immunoglobulin-E autoantibodies in PV has been observed, no studies have been performed to describe the role of galectin-3 in PV. We evaluated galectin-3 expression in PV as a first step in assessing its impact in the pathogenesis of this autoimmune blistering process. In a retrospective study, 56 specimens from 45 patients diagnosed with PV were stained with antibodies to galectin-3. The percentages of nuclear and cytoplasmic galectin-3 expression as well as staining intensity were evaluated around blisters and adjacent unaffected skin. We observed a significant decrease in galectin-3 cytoplasmic and nuclear expression as well as stain intensity around blisters compared with adjacent unaffected skin. Although autoantibodies against desmogleins trigger the blister formation in PV patients, loss of galectin-3 may play a role in the extension of blister formation by initiating cell–cell disassembly at the level of the intercellular keratinocyte desmosome. We demonstrated a lower expression of galectin-3 around the blisters in PV. The pathogenesis of the blister formation may be related to lower expression of galectin-3. Additional studies are necessary to clarify the result of this outcome and determine the accurate pathogenesis of blister formation in PV.
Radiation therapy for uveal melanoma: a review of treatment methods available in 2021
Authors: Reichstein David A. , Brock Anderson L.
Published: March 2021

Purpose of review

Radiation therapy has become the standard of care for the treatment of uveal melanoma. We intend to outline the current radiation therapy methods that are employed to treat uveal melanoma. We will outline their relative benefits over one another. We will also provide some background about radiation therapy in general to accustom the ophthalmologists likely reading this review.

Recent findings

Four main options exist for radiation therapy of uveal melanoma. Because the eye is a small space, and because melanomas are relatively radioresistant, oncologists treating uveal melanoma must deliver highly focused doses in high amounts to a small space. Therapies incorporating external beams include proton beam therapy and stereotactic radiosurgery. Stereotactic radiosurgery comes in two forms, gamma knife therapy and cyberknife therapy. Radiation may also be placed directly on the eye surgically via plaque brachytherapy. All methods have been used effectively to treat uveal melanoma.

Each particular radiotherapy technique employed to treat uveal melanoma has its own set of benefits and drawbacks. The ocular oncologist can choose amongst these therapies based upon his or her clinical judgment of the relative risks and benefits. Availability of the therapy and cost to the patient remain significant factors in the ocular oncologist's choice.
New treatment algorithm for keratoconus and cataract: small-aperture IOL insertion with sequential topography-guided photorefractive keratectomy and simultaneous accelerated corneal crosslinking
Authors: Northey Luke C. , Holland Simon P. , Lin David T.C. , Moloney Gregory
Published: March 2021

Purpose:

To describe a new treatment algorithm aimed at optimizing refractive outcomes for patients with keratoconus and cataract.

Setting:

Private practice in Sydney, Australia.

Design:

Retrospective case series.

Methods:

This procedural approach involves cataract extraction with small-aperture intraocular lens (IOL) insertion, IC-8 IOL (AcuFocus, Inc.), followed by topography-guided photorefractive keratectomy (T-PRK) with simultaneous corneal crosslinking (CXL). Cataract surgery was performed with an initial 2.4 mm clear corneal incision enlarged to 3.5 mm to accommodate IC-8 IOL insertion. Once eyes demonstrated stable corneal tomography and refraction, T-PRK was performed using Schwind excimer laser (500 Hz) with the Vancouver custom topographical neutralization technique, aiming to achieve low myopia. CXL was performed immediately after T-PRK using Optolink hypotonic riboflavin with LIGHTLink-CXL (Lightmed) with 5.4 J total energy delivered at an 18 mw/cm2 irradiance.

Results:

Outcomes of 4 eyes are reported with all achieving rigid gas-permeable (RGP) contact lens independence, improved corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA), and regularization of corneal curvature with cone reduction. The mean CDVA improved from 0.43 preoperatively to 0.07 postoperatively (P = .00), and the mean UDVA improved from 0.81 preoperatively to 0.29 postoperatively (P = .04). Postoperative UNVA ranged from N.8 to N.12.

Conclusions:

This treatment algorithm demonstrates unique combination of existing corneal and cataract surgical procedures to achieve satisfactory refractive outcomes and RGP contact lens independence in patients with keratoconus and cataract.
Experimental study of occlusion break surge volume in 3 different phacoemulsification systems
Authors: Miller Kevin M. , Dyk David W. , Yalamanchili Satish
Published: March 2021

Purpose:

To evaluate surge volume after occlusion breaks in 3 different phacoemulsification systems.

Setting:

Alcon Research LLC, Lake Forest, California.

Design:

Experimental study.

Methods:

A mechanical spring eye model was used to test the Centurion with Active Sentry, WhiteStar Signature Pro, and Stellaris PC. Raw oscilloscope data were converted to volumetric and pressure measurements. Fitted average surge traces were generated for each test condition and used to develop an interpolation algorithm to predict transient occlusion break surge events. Two-dimensional heat maps were generated.

Results:

During occlusion break surge, the Centurion with Active Sentry had smaller aqueous volume losses than the WhiteStar or Stellaris PC. Maximum surge volumes within the mechanical spring eye model displacement limit were 74.7 μL, 157.5 μL, and 151.7 μL using Centurion with Active Sentry, WhiteStar, and Stellaris PC, respectively. In the aphakic state, heat maps showed that Centurion with Active Sentry had less than 20% aqueous volume loss across all vacuum limits and target intraocular pressure; WhiteStar and Stellaris PC systems had up to 35% and 50% aqueous volume losses, respectively, at the higher vacuum limits. In the phakic state, Centurion with Active Sentry had up to 30% aqueous volume loss and WhiteStar and Stellaris PC systems had up to 50% aqueous volume losses. In addition, predicted transient traces demonstrated that Centurion with Active Sentry had the lowest percentage simulated aqueous volume loss compared with WhiteStar or Stellaris PC.

Conclusions:

Centurion with Active Sentry had lower aqueous volume losses after occlusion break than WhiteStar and Stellaris PC systems at all surgical settings.
Visual outcomes after optic exchange of a modular intraocular lens
Authors: Ang Robert Edward T. , Yoo Paul , Liu Jingbo
Published: March 2021

Purpose:

To evaluate the effectiveness of the Harmoni Modular IOL (HMIOL).

Setting:

3 study sites.

Design:

Prospective, multicenter clinical study.

Methods:

HMIOL is a foldable, posterior chamber lens with separate base and exchangeable optic components. Eligible adults undergoing cataract surgery received HMIOL in the study eye (monovision target −1.50 diopters [D]) and standard monofocal IOL in contralateral eye (control). After 3 months, subjects could undergo optic exchange based on visual outcomes. End points included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refractive spherical equivalent (MRSE). Follow-up was 12 months or greater postoperatively.

Results:

114 subjects had successful HMIOL implantation in study eye and control IOL in contralateral eye. At 3 months, subjects could undergo optic exchange if unsatisfied with monovision; 65 eyes had optic exchange (exchange cohort), and 49 eyes had no exchange (no exchange cohort). In exchange cohort, the proportion of eyes with UDVA of 20/40 or greater and of 20/20 or greater increased 3 months after optic exchange vs preexchange levels by 23% (97% vs 74%) and 40% (49% vs 9%), respectively. In all cohorts, 95% of subjects or greater achieved UDVA of 20/40 or greater after 12 months or greater. Control and no exchange cohorts achieved CDVA of 20/40 or greater by 3 months; 97% of eyes or greater had CDVA of 20/40 or greater at 12 months after optic exchange. In exchange cohort, the proportion of eyes with MRSE within ±0.50 D and ±1.00 D of target changed by 57% and 36%, respectively, from preexchange (20% and 59%, respectively) to 12 months postexchange (77% and 95%, respectively), reaching levels similar to control subjects (72% and 97%, respectively).

Conclusions:

HMIOL provided visual outcomes comparable with standard monofocal IOLs.
Encoding of cutaneous stimuli by lamina I projection neurons
Authors: Chisholm Kim I. , Lo Re Laure , Polgár Erika , Gutierrez-Mecinas Maria , Todd Andrew J. , McMahon Stephen B.
Published: March 2021

Lamina I of the dorsal horn, together with its main output pathway, lamina I projection neurons, has long been implicated in the processing of nociceptive stimuli, as well as the development of chronic pain conditions. However, the study of lamina I projection neurons is hampered by technical challenges, including the low throughput and selection biases of traditional electrophysiological techniques. Here we report on a technique that uses anatomical labelling strategies and in vivo imaging to simultaneously study a network of lamina I projection neurons in response to electrical and natural stimuli. Although we were able to confirm the nociceptive involvement of this group of cells, we also describe an unexpected preference for innocuous cooling stimuli. We were able to characterize the thermal responsiveness of these cells in detail and found cooling responses decline when exposed to stable cold temperatures maintained for more than a few seconds, as well as to encode the intensity of the end temperature, while heating responses showed an unexpected reliance on adaptation temperatures.
Transthoracic echocardiography monitoring during atrial septal defect and ventricular septal defect device closures using a three-dimensional printed transducer holder
Authors: Jian Wen-Yen , Lin Su-Man , Tsai Shen-Kou , Hwang Betau
Published: March 2021

Transthoracic echocardiography (TTE) is noninvasive but can only be performed intermittently during fluoroscopy. In a prior study, we created a transducer holder device to allow for hemodynamic monitoring in the intensive care unit. The current study is the first instance of the use of a three-dimensional (3D)-printed TTE transducer holder, which is easily customized and personalized to a previous transducer holder at relatively low cost and short production time, to enable continuous TTE monitoring during device closure of an atrial septal defect (ASD) and ventricular septal defect (VSD). There were 14 ASD patients and 9 VSD patients scheduled to undergo device closure. The study’s real-time TTE monitoring was performed by using a 3D-printed transducer holder over the course of the entire implantation procedure. There were 23 patients who successfully underwent septal closures using the 3D-printed holder that enabled real-time images over the entire procedure. The median duration for real-time TTE guidance was 15 minutes for the ASD and 36 minutes for the VSD and the median fluoroscopy time was 11 minutes for the ASD and 30 minutes for the VSD. One migrating VSD occluder and one case of aortic regurgitation after occluder deployment were noted by real-time TTE monitoring during the procedure. Our novel 3D-printed transducer holder can provide transesophageal echocardiography-like real-time imaging during device closure of an ASD and a VSD and may become a new alternative method in ASD and VSD closures. It can also prevent radiation exposure for the intervention team who would otherwise need to perform TTE during live fluoroscopy.
Invasive Treatments for Low Back Disorders
Authors: Hegmann Kurt T. , Travis Russell , Andersson Gunnar B.J. , Belcourt Roger M. , Carragee Eugene J. , Eskay-Auerbach Marjorie , Galper Jill , Goertz Michael , Haldeman Scott , Hooper Paul D. , Lessenger James E. , Mayer Tom , Mueller Kathryn L. , Murphy Donald R. , Tellin William G. , Thiese Matthew S. , Weiss Michael S. , Harris Jeffrey S.
Published: March 2021

Objective:

This abbreviated version of the American College of Occupational and Environmental Medicine's Low Back Disorders guideline reviews the evidence and recommendations developed for invasive treatments used to manage low back disorders.

Methods:

Comprehensive systematic literature reviews were accomplished with article abstraction, critiquing, grading, evidence table compilation, and guideline finalization by a multidisciplinary expert panel and extensive peer-review to develop evidence-based guidance. Consensus recommendations were formulated when evidence was lacking and often relied on analogy to other disorders for which evidence exists. A total of 47 high-quality and 321 moderate-quality trials were identified for invasive management of low back disorders.

Results:

Guidance has been developed for the invasive management of acute, subacute, and chronic low back disorders and rehabilitation. This includes 49 specific recommendations.

Conclusion:

Quality evidence should guide invasive treatment for all phases of managing low back disorders.
Job Absenteeism Costs of Obesity in the United States
Authors: Cawley John , Biener Adam , Meyerhoefer Chad , Ding Yuchen , Zvenyach Tracy , Smolarz B. Gabriel , Ramasamy Abhilasha
Published: March 2021

Objective:

To estimate the causal effect of obesity on job absenteeism and the associated lost productivity in the United States, both nationwide and by state.

Methods:

We conducted a retrospective pooled cross-sectional analysis using the 2001 to 2016 Medical Expenditure Panel Survey and estimated two-part models of instrumental variables.

Results:

Obesity, relative to normal weight, raises job absenteeism due to injury or illness by 3.0 days per year (128%). Annual productivity loss due to obesity ranges from $271 to $542 (lower/upper bound) per employee with obesity, with national productivity losses ranging from $13.4 to $26.8 billion in 2016. Trends in state-level estimates mirror those at the national level, varying across states.

Conclusions:

Obesity significantly raises job absenteeism. Reductions in job absenteeism should be included when calculating the cost-effectiveness of interventions to prevent or reduce obesity among employed adults.
Impact of Covid-19 in Global Health and Psychosocial Risks at Work
Authors: Gaspar Tania , Paiva Teresa , Matos Margarida Gaspar
Published: March 2021

Objective:

The main objective is to understand and characterize the impact of Covid-19 pandemic on mental health and psychosocial risks at work in professionally active adults.

Methods:

This specific work includes 4708 professionally active participants from all over the country, of which 3354 are women (71.2%), aged between 19 and 86 years, with an average age of 45.8 years (SD = 12.56).

Results:

The global impact of Covid-19 is explained by socio-demographic factors (sex, age, and education), by work-related and volume of work and health that is reflected in most symptoms. We found sex, age, education level, and professional area differences related to global impact of Covid-19.

Conclusion:

The Covid-19 pandemic accounts for the challenge to identify the important factors to promote resilience of citizens, professionals, and organizations.
Investigation of Apnea Testing During Brain Death Determination in China
Authors: Chen Zhongyun , Su Yingying , Liu Gang , Fan Linlin , Zhang Yan , Chen Weibi , Ye Hong , Huang Huijing
Published: March 2021

Apnea testing (AT) is one of the key steps for brain death (BD) diagnosis and confirmation. However, the completion rate of AT is not well in China. The aim of this study was to investigate the completion rates of the AT during BD determination in China and analyze the determinant factors. We reviewed and analyzed potential BD patients registered in our database from 2013 to 2019. The patients were divided into those with completed and aborted AT. Preconditions and organ function status were compared between the two groups. A total of 1,531 (1,301 adults and 230 pediatrics) cases of potential BD were extracted, and BD determination was performed 2,185 and 377 times in adults and pediatrics respectively. The nonperformance and aborted rates of AT were 12.2% and 34.5% in adults, and 11.7% and 44.4% in pediatrics respectively. Compared with the completed group, the aborted group had a lower PaO2, systolic blood pressure, PaO2/FiO2 ratios, and higher alveolar-arterial (A-a) gradient both in adults and pediatrics, and higher PaCO2 and higher heart rates in adults. PaO2 and A-a gradient had higher predictive efficacy for AT completion in both adults and pediatrics. The implementation and completion rates of AT are not ideal in China. PaO2 and A-a gradient are important factors for the successful completion of AT and should be optimized before AT.
Apolipoprotein L1 and mechanisms of kidney disease susceptibility
Authors: Bruggeman Leslie A. , Sedor John R. , O’Toole John F.
Published: March 2021

Purpose of review

Allelic variants in the gene for apolipoprotein L1 (APOL1), found only in individuals of African ancestry, explain a majority of the excess risk of kidney disease in African Americans. However, a clear understanding how the disease-associated APOL1 variants cause kidney injury and the identity of environmental stressors that trigger the injury process have not been determined.

Recent findings

Basic mechanistic studies of APOL1 biochemistry and cell biology, bolstered by new antibody reagents and inducible pluripotent stem cell-derived cell systems, have focused on the cytotoxic effect of the risk variants when APOL1 gene expression is induced. Since the APOL1 variants evolved to alter a key protein–protein interaction with the trypanosome serum resistance-associated protein, additional studies have begun to address differences in APOL1 interactions with other proteins expressed in podocytes, including new observations that APOL1 variants may alter podocyte cytoskeleton dynamics.

A unified mechanism of pathogenesis for the various APOL1 nephropathies still remains unclear and controversial. As ongoing studies have consistently implicated the pathogenic gain-of-function effects of the variant proteins, novel therapeutic development inhibiting the synthesis or function of APOL1 proteins is moving toward clinical trials.
Primary Fallopian Tube Mullerian Adenosarcoma With Sarcomatous Overgrowth and a Previously Unreported MEIS1-NCOA2 Gene Fusion
Authors: Ribeiro e Ribeiro Renan , Lewin Eleanor R. , Hart Jesse L. , Quddus Mohammad Ruhul , Hansen Katrine
Published: March 2021

Extrauterine Mullerian adenosarcomas (MA) are rare and often associated with endometriosis. We report a 55-yr-old patient seen in consultation for abdominal pain and bloating. Imaging was suggestive of a left adnexal mass and “peritoneal carcinomatosis”. Pathological examination of the specimen revealed a MA arising in the left fallopian tube, with sarcomatous overgrowth, diffuse peritoneal involvement and omental “caking”. Next-generation sequencing identified a MEIS1-NCOA2 gene fusion, previously unreported in MA.
Survival Following Self-Inflicted Gunshot Injuries to the Face Using the National Trauma Data Bank
Authors: Wasicek Philip J. , Kantar Rami S. , Yoon Joshua , Elegbede Adekunle , Nam Arthur J.
Published: March 2021

Introduction:

Self-inflicted gunshot wounds to the face frequently result in devastating injuries; however, there is a paucity of large experiences describing determinants of mortality and outcomes.

Methods:

Using the National Trauma Databank from 2007 to 2015, patients suffering self-inflicted firearm facial injuries were included.

Results:

Over 9 years 7869 patients were included: 87.7% were male, 46.4% suffered traumatic brain injury (TBI) and overall in-hospital mortality was 44.7%. The majority (67.8%) of in-hospital mortality occurred within the first 24 hours. Using multiple regression, advanced age (>65 years), presence of TBI, admission hypotension, and decreased Glasgow coma score were each independently associated with increased odds of mortality (all P < 0.001). Mandible or combined mandible/midface fracture injury patterns were most likely to survive (P < 0.001). Of those surviving to hospital discharge, the median [interquartile range] length of stay was 13 [6, 23] days, 86.6% required an intensive care unit stay with 67% requiring intubation and 42.5% tracheostomy. Among survivors, the combined mandible and midface fracture pattern resulted in the highest rates of tracheostomy (70.5%), gastrostomy tube placement (50.5%), and facial operations (87.0%) with a median [interquartile range] of 5 [3, 7] operative trips (all P < 0.001).

Conclusions:

Self-inflicted facial firearm injuries are highly morbid injuries with the majority of in-hospital deaths occurring the first hospital day. Differences including concomitant TBI, facial injury pattern, neurologic status, and presence of hypotension on admission were independently associated with survival/death. More extensive facial injuries (combined mandible and midface fracture patterns) were more likely to survive and required more intensive interventions.
Posterior Cranial Vault Distraction Osteogenesis Utilizing a Posterior—Superior Distraction Vector in the Treatment of Mercedes Benz Pattern Craniosynostosis
Authors: Marji Fady P. , Block Lisa M. , Anstadt Erin E. , Dvoracek Lucas A. , Bruce Madeleine K. , Williams Abraham A. , Hall Jennifer A. , Losee Joseph E. , Goldstein Jesse A.
Published: March 2021

Bilateral lambdoid and sagittal synostosis, or Mercedes Benz Syndrome, is a rare complex craniosynostosis resulting in frontal bossing, a tapered posterior fossa, and an anteriorly displaced cranial vertex. Its ideal surgical correction must result in posterior expansion, skull elongation, and caudal repositioning of the vertex. We present a craniometric analysis of skull changes with posterior-superior distraction and introduce a novel craniometric measure: vertex position. In this study, a retrospective review was performed to analyze outcomes of posterior cranial vault distraction osteogenesis (PVDO) using a posterior–superior distraction vector from 2016 to 2019. Cranial vertex position was measured as a fraction of the occipitofrontal diameter from rostral to caudal (0–1.0). Four patients underwent PVDO at mean age 10.61 ± 3.16 months utilizing a posterior–superior distraction vector. Linear distraction distance averaged 30.30 ± 0.90 mm with a mean consolidation period of 3.98 ± 0.72 months. Mean corrected change in intra-cranial volume was 236.30 ± 3.71 mL, at an average rate of 7.81 ± 2.00 mL/mm of distraction. Increases in anterior cranial height (7.83 ± 2.51 mm), middle cranial height (8.43 ± 4.21 mm), posterior cranial height (13.15 ± 7.45 mm), and posterior cranial fossa height (21.99 ± 8.55 mm) were observed. Cranial vertex demonstrated a mean posterior movement of 0.18 ± 0.13. PVDO utilizing a posterior-superior distraction vector for management of nonsyndromic bilateral lambdoid and sagittal synostosis effectively increases intracranial volume and height and provides an esthetic outcome with posterior movement of the cranial vertex.
Central nervous system infections and antimicrobial resistance: an evolving challenge
Authors: Nau Roland , Sörgel Fritz , Eiffert Helmut
Published: March 2021

Purpose of review

Antimicrobial resistance is an increasing threat to patients also in nosocomial central nervous system (CNS) infections. The present review focusses on optimizing intravenous treatment in order to achieve sufficient concentrations of antibiotics in the different compartments of the CNS when the causative pathogens have reduced sensitivity to antibiotics or/and the impairment of the blood–cerebrospinal fluid (CSF) and blood–brain barrier is mild.

Recent findings

Experience has been gathered with treatment protocols for several established antibiotics using increased doses or continuous instead of intermittent intravenous therapy. Continuous infusion in general does not increase the average CSF concentrations (or the area under the concentration–time curve in CSF) compared to equal daily doses administered by short-term infusion. In some cases, it is postulated that it can reduce toxicity caused by high peak plasma concentrations. In case reports, new β-lactam/β-lactamase inhibitor combinations were shown to be effective treatments of CNS infections.

Several antibiotics with a low to moderate toxicity (in particular, β-lactam antibiotics, fosfomycin, trimethoprim-sulfamethoxazole, rifampicin, vancomycin) can be administered at increased doses compared to traditional dosing with low or tolerable adverse effects. Intrathecal administration of antibiotics is only indicated, when multiresistant pathogens cannot be eliminated by systemic therapy. Intravenous should always accompany intrathecal treatment.
Acute bacterial meningitis
Authors: Wall Emma C. , Chan Jia Mun , Gil Eliza , Heyderman Robert S.
Published: March 2021

Purpose of review

Community-acquired bacterial meningitis is a continually changing disease. This review summarises both dynamic epidemiology and emerging data on pathogenesis. Updated clinical guidelines are discussed, new agents undergoing clinical trials intended to reduce secondary brain damage are presented.

Recent findings

Conjugate vaccines are effective against serotype/serogroup-specific meningitis but vaccine escape variants are rising in prevalence. Meningitis occurs when bacteria evade mucosal and circulating immune responses and invade the brain: directly, or across the blood–brain barrier. Tissue damage is caused when host genetic susceptibility is exploited by bacterial virulence. The classical clinical triad of fever, neck stiffness and headache has poor diagnostic sensitivity, all guidelines reflect the necessity for a low index of suspicion and early Lumbar puncture. Unnecessary cranial imaging causes diagnostic delays. cerebrospinal fluid (CSF) culture and PCR are diagnostic, direct next-generation sequencing of CSF may revolutionise diagnostics. Administration of early antibiotics is essential to improve survival. Dexamethasone partially mitigates central nervous system inflammation in high-income settings. New agents in clinical trials include C5 inhibitors and daptomycin, data are expected in 2025.

Clinicians must remain vigilant for bacterial meningitis. Constantly changing epidemiology and emerging pathogenesis data are increasing the understanding of meningitis. Prospects for better treatments are forthcoming.
Mismatch in Supply and Demand for Neuro-Ophthalmic Care
Authors: DeBusk Adam , Subramanian Prem S. , Scannell Bryan Molly , Moster Mark L. , Calvert Preston C. , Frohman Larry P.
Published: March 2021

Background:

Previous research suggests the number of neuro-ophthalmologists in the United States may be below a level that provides sufficient access to neuro-ophthalmic care in much of the United States. However, national estimates of the amount of clinical time spent on neuro-ophthalmology are lacking.

Methods:

The North American Neuro-Ophthalmology Society administered a survey on professional time allocation to its active members. Survey response was 95%. The survey characterized the hours each week each respondent allocated to overall work, clinical work, clinical work in ophthalmology/neurology, and clinical work in neuro-ophthalmology specifically. The survey additionally collected information regarding demographics, current wait times to be seen for new patients, and the difference in clinical time spent in neuro-ophthalmology spent between the current day compared with that shortly after completing clinical training. Linear regression was used to identify potential relationships between the above and average wait time.

Results:

On average, responding physicians spent 70% of their clinical time on neuro-ophthalmology. In 6 states, there were no reported practicing neuro-ophthalmologists, and in only 8 states was the clinical full-time equivalent to population ratio below the suggested threshold of 1 for every 1.2 million. The median wait time for a new patient was 6 weeks. This wait time was associated with the fraction of clinical time spent in neuro-ophthalmology (0.2 weeks longer wait for a 10 percentage point increase in the fraction of time spent in neuro-ophthalmology; P = 0.02), and suggestively associated with training (training in ophthalmology was associated with 1.0 week shorter wait time; P = 0.06).

Conclusion:

The survey suggests that neuro-ophthalmologists are unable to see patients in a timely manner and a decreasing number of clinicians are entering the field. Future interventions should be considered to incentivize neuro-ophthalmology training in ophthalmology and neurology residents such that the United States population is able to appropriately access neuro-ophthalmic care.
A rapid assessment of wastewater for genomic surveillance of SARS-CoV-2 variants at sewershed scale in Louisville, KY
Authors: Fuqua J. L. , Rouchka E.C. , Waigel S. , Sokoloski K. , Chung D. , Zacharias W. , Zhang M. , Chariker J. , Talley D. , Santisteban I. , Varsani A. , Moyer S. , Holm R. H. , Yeager R. A. , Smith T. , Bhatnagar A.
Published: March 2021

In this communication, we report on the genomic surveillance of SARS-CoV-2 using wastewater samples in Jefferson County, KY. In February 2021, we analyzed seven wastewater samples for SARS-CoV-2 genomic surveillance. Variants observed in smaller catchment areas, such as neighborhood manhole locations, were not necessarily consistent when compared to associated variant results in downstream treatment plants, suggesting catchment size or population could impact the ability to detect diversity.
Identification and Analysis of Novel Synovial Tissue-based Biomarkers and Interacting Pathways for Rheumatoid Arthritis
Authors: Latawa Paridhi
Published: March 2021

Rheumatoid arthritis (RA) is an inflammatory disorder with autoimmune pathogenesis characterized by the immune system attacking the synovium. It is a clinically heterogeneous disease that affects approximately 1.2 million Americans and 20 million people worldwide. It is advantageous to diagnose RA before extensive erosion as treatments are more effective at early stages. RA treatments have made notable progress, yet a significant number of patients still fail to respond to current medication and most of these come with harmful side effects. While the mechanistic reason for such failure rates remains unknown, the cellular and molecular signatures in the synovial tissues of patients with RA are likely to play a role in the variable treatment response and heterogeneous clinical evolution. While blood-based criteria are currently employed for diagnostics and treatments. such serologic parameters do not necessarily reflect biological actions in the target tissue of the patient and are relatively nonspecific to RA. Synovial tissue-based biomarkers are especially attractive as they can provide a confirmed diagnosis for RA. The shortage of accurate synovial tissue-based identifiers for RA diagnosis encouraged this research. This study analyzed data from several gene expression studies for differentially expressed genes in donor synovial tissue. Bioinformatics tools were used to construct and analyse protein interaction networks. Analysis deduced that regulating hematopoietic stem cell migration could serve as a potential RA diagnostic. VAV1, CD3G, LCK, PTPN6, ITGB2, CXCL13, CD4, and IL7R are found to be previously unclassified, potential biomarkers.
The General Psychopathology Factor from Early to Middle Childhood: Longitudinal Genetic and Risk Analyses
Authors: Avinun Reut , Knafo-Noam Ariel , Israel Salomon
Published: March 2021

Accumulating research suggests the structure of psychopathology is best represented by continuous higher-order dimensions, including a general dimension, p-factor, and more specific dimensions, e.g., residualized externalizing and internalizing factors. Here, we aimed to 1) replicate p in early childhood; 2) externally validate the factors with key constructs of psychological functioning; 3) examine stability and change of genetic and environmental influences on the psychopathology factors from early-to mid-childhood; 4) examine the factors’ predictive utility; and 5) test whether the factors can be predicted by early life measures (e.g., neonatal complications). The Longitudinal Israeli Study of Twins from age 3 to 9 was used for the analyses. Mothers reported on developmental problems, pregnancy and neonatal conditions, and filled in questionnaires on each twin’s externalizing and internalizing symptoms. Cognitive ability was assessed in the lab at age 6.5 and personality traits, self-esteem, and life satisfaction were self-reported by the twins at ages 11-13. A bifactor model that included p and externalizing and internalizing factors fit the data best and associations between p, cognitive ability, and personality were replicated. Longitudinal twin analyses indicated that p is highly heritable (64-73%) with a substantial proportion of the genetic influences stable from age 3. The residualized internalizing and externalizing factors were also highly heritable. Higher p predicted developmental problems at age 8-9 and lower self-esteem at age 11. Early life measures were not strongly associated with psychopathology. Our results show that p is discernible in early childhood, highly heritable, and prospectively associated with negative outcomes.

General Scientific Summary

The general psychopathology factor is discernible in early childhood, highly heritable, with genetic influences contributing to both stability and change, and prospectively associated with developmental problems and lower self-esteem. Early life measures, such as birth complications or hospitalizations during the first year of life, were not strong predictors of the general psychopathology factor or the residualized externalizing and internalizing factors.
SARS-CoV-2 Acquisition and Immune Pathogenesis Among School-Aged Learners in Four Diverse Schools
Authors: Cooper Dan M. , Zulu Michael Z. , Jankeel Allen , Ibraim Izabela Coimbra , Ardo Jessica , Kasper Kirsten , Stephens Diana , Meyer Andria , Stehli Annamarie , Condon Curt , Londoño Mary E. , Schreiber Casey M. , Lopez Nanette V. , Camplain Ricky L. , Weiss Michael , Golden Charles , Aizik Shlomit , Boden-Albala Bernadette , Chau Clayton , Messaoudi Ilhem , Ulloa Erlinda R.
Published: March 2021

Background

Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely.

Methods

We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1(sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners; and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured.

Results

We found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p<0.01) and IgG positivity rates (13/66, 19.7%). School D (93% on-site learners) had the lowest infection and IgG positivity rates (1/63, 1.6%). Mitigation compliance [physical distancing (mean 87.4%) and face covering (91.3%)] was remarkably high at all schools. Documented SARS-CoV-2-infected learners had neutralizing antibodies (94.7%), robust IFN-γ+ T cell responses, and reduced monocytes.

Conclusion

Schools can implement successful mitigation strategies across a wide range of student diversity. Despite asymptomatic to mild SARS-CoV-2 infection, children generate robust humoral and cellular immune responses.

Key Points

Successful COVID-19 mitigation was implemented across a diverse range of schools.

School-associated SARS-CoV-2 infections reflect regional rates rather than remote or on-site learning.

Seropositive school-aged children with asymptomatic to mild SARS-CoV-2 infections generate robust humoral and cellular immunity.