bluuebunny/crossref_metadata_2025 huggingface dataset:
1α, 25-dihydroxyvitamin D3 inhibits transforming growth factor β1-induced epithelial-mesenchymal transition via β-catenin pathway
Authors: Xiong Xin-Rong , Tian Xin-Li , Huo Ru-Jie , Dong Yan-Ting , Liu Dai , Bai Jing-Cui , Qi Yun-Feng , Tian Xin-Rui
Published: May 2020

Background:

The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated.

Methods:

Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.

Results:

Both 1α, 25(OH)2D3and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001.

Conclusion:

1α, 25(OH)2D3synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.
Primary central nervous system lymphoma: status and advances in diagnosis, molecular pathogenesis, and treatment
Authors: Zhang Yan , Zhou Dao-Bin
Published: May 2020

Primary central nervous system lymphoma (PCNSL) is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes. This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients. The authors retrieved information from the PubMed database up to September 2019. The annual incidence of PCNSL increased over the last four decades. The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate, which is now the backbone of all first-line treatment polychemotherapy regimens. Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-κB, B cell antigen receptor, and Janus kinases/signal transducer and activator of transcription proteins signal pathways. Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy. In particular, lenalidomide and ibrutinib have demonstrated durable efficiency. Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups, but there is still room to improve outcome by optimizing current chemotherapy and novel agents.
Far from MCAR
Authors: Balzer Laura B. , Ayieko James , Kwarisiima Dalsone , Chamie Gabriel , Charlebois Edwin D. , Schwab Joshua , van der Laan Mark J. , Kamya Moses R. , Havlir Diane V. , Petersen Maya L.
Published: May 2020

Background:

Population-level estimates of disease prevalence and control are needed to assess prevention and treatment strategies. However, available data often suffer from differential missingness. For example, population-level HIV viral suppression is the proportion of all HIV-positive persons with suppressed viral replication. Individuals with measured HIV status, and among HIV-positive individuals those with measured viral suppression, likely differ from those without such measurements.

Methods:

We discuss three sets of assumptions to identify population-level suppression in the intervention arm of the SEARCH Study (NCT01864603), a community randomized trial in rural Kenya and Uganda (2013–2017). Using data on nearly 100,000 participants, we compare estimates from (1) an unadjusted approach assuming data are missing-completely-at-random (MCAR); (2) stratification on age group, sex, and community; and (3) targeted maximum likelihood estimation to adjust for a larger set of baseline and time-updated variables.

Results:

Despite high measurement coverage, estimates of population-level viral suppression varied by identification assumption. Unadjusted estimates were most optimistic: 50% (95% confidence interval [CI] = 46%, 54%) of HIV-positive persons suppressed at baseline, 80% (95% CI = 78%, 82%) at year 1, 85% (95% CI = 83%, 86%) at year 2, and 85% (95% CI = 83%, 87%) at year 3. Stratifying on baseline predictors yielded slightly lower estimates, and full adjustment reduced estimates meaningfully: 42% (95% CI = 37%, 46%) of HIV-positive persons suppressed at baseline, 71% (95% CI = 69%, 73%) at year 1, 76% (95% CI = 74%, 78%) at year 2, and 79% (95% CI = 77%, 81%) at year 3.

Conclusions:

Estimation of population-level disease burden and control requires appropriate adjustment for missing data. Even in large studies with limited missingness, estimates relying on the MCAR assumption or baseline stratification should be interpreted cautiously.
The Left-handed Plastic Surgery Trainee: Perspectives and Recommendations
Authors: Savetsky Ira L. , Cammarata Michael J. , Kantar Rami S. , Diaz-Siso J. Rodrigo , Avashia Yash J. , Rohrich Rod J. , Saadeh Pierre B.
Published: May 2020

Background:

Left-handed surgeons experience difficulty with tools designed for use in the right hand. The purpose of this study was to examine instrument laterality and to survey the experiences of left-handed plastic surgery trainees.

Methods:

Count sheets for plastic surgery trays (reconstructive, microsurgery, rhinoplasty, craniofacial) were acquired from Tisch Hospital, NYU Langone Health. Instruments with right-handed laterality were tallied. A survey was also distributed to plastic surgery residents and fellows to determine hand preference for surgical tasks, and those who identified as left-handed described how handedness impacted their training.

Results:

Right-handed laterality was seen in 15 (31.3%) of the 48 reconstructive instruments, 17 (22.7%) of the 75 rhinoplasty instruments, and 22 (31.0%) of the 71 craniofacial instruments. One-hundred percent of the 25 microsurgery instruments were ambidextrous. There were 97 survey responses. Trainees (17.5%) were identified as left-handed and were more likely than right-handed trainees to report operating with both hands equally or with the opposite hand (47.1% versus 1.3%; P < 0.001). Left-handed trainees were significantly more likely than right-handed trainees to use their nondominant hand with scissors (P < 0.001), electrocautery (P = 0.03), and needle drivers (P < 0.001) and when performing tissue dissection (P < 0.001) and microsurgery (P = 0.008). There was no difference in use of the nondominant hand between right and left-handed trainees for knot tying (P = 0.83) and in use of the scalpel (P = 0.41).

Conclusions:

Left-handed plastic surgery trainees frequently encounter instruments designed for the nondominant hand, with which they adaptively perform several surgical tasks. Mentoring may help trainees overcome the laterality-related challenges of residency.
Perioperative Thromboprophylaxis in Digital Replantation: A Systematic Review
Authors: Reissis Dimitris , Geoghegan Luke , Sarsam Raghda , Young Sing Quillan , Nikkhah Dariush
Published: May 2020

Background:

There is no international consensus on the use of perioperative thromboprophylaxis in digital replantation. Suboptimal perioperative management may lead to replant failure, which compromises extremity function, worsens psychosocial outcomes for patients, and incurs significant cost. This systematic review evaluates and compares the efficacy and safety of perioperative antithrombotic protocols used in digital replantation.

Methods:

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)--compliant prospectively registered (PROSPERO, CRD42018108695) systematic review was conducted. Cochrane Central Register of Controlled Trials, Medline, EMBASE, and Scopus were searched up until December 2019. Articles were assessed for eligibility in duplicate by 2 independent reviewers. All comparative studies that examined the use of perioperative thromboprophylaxis in digital replantation were eligible for inclusion.

Results:

Collectively, 1,025 studies were identified of which 7 met full inclusion criteria reporting data from 635 patients (908 digital replants, 86% men, average age 37.3 years). Laceration was the most commonly reported mechanism of injury (68%), with 33% of replantation occurring in Tamai zone III. Fourteen distinct perioperative protocols were identified. One study reported significantly higher digital survival with continuous heparin infusion versus bolus heparin. Five studies demonstrated a significantly higher incidence of complications among patients treated with systemic heparin.

Conclusions:

The clinical efficacy and safety of perioperative antithrombotic therapy following digital replantation remains equivocal. The perceived benefits of improved digital survival must be tempered against the adverse systemic side effects of antithrombotic and anticoagulant therapies until further prospectively collected data sets become available.
Articulating the “So, What?” in Clinical Research: Insight from the M-CHOIR Group
Authors: Kim You J. , Mack Shale J. , Chung Kevin C.
Published: May 2020

With the academic culture of “publish or perish,” authors must ensure that they are delivering high-quality data with a meaningful impact on clinical practice. Even for physician–scientists at the top of their fields, establishing the relevance of a study to clinical practice is a challenge. Thus, it is essential that research proposals ask questions that are clinically important, use appropriate methodologies, and examine outcomes that are relevant to both the physicians and the patients. The question of “so, what?” or in other words, “who cares?” is one that can make or break a study’s impact on clinical practice. Researchers should use models such as PICOS (Population, Intervention, Comparison, Outcomes, and Study design) and FINER (Feasible, Interesting, Novel, Ethical, Relevant) and ask why readers will care about their study’s findings before the study is conducted. By doing so, researchers can ensure the successful execution of their study and a meaningful impact of their findings, in both academia and clinical practice. This Special Topic article aims to guide researchers in producing relevant, impactful conclusions of their studies by providing input and resources from the Michigan Center for Hand Outcomes and Innovation (M-CHOIR) group.
Providing Long-acting Reversible Contraception to Adolescents: A Review
Authors: BAHAR YASMIN Z. , GOLD MELANIE A.
Published: May 2020

Unintended teen pregnancy continues to be a problem in the United States which has the highest rate of adolescent pregnancy among developed nations. Long-acting reversible contraception (LARC) has much higher continuation rates compared with moderately effective reversible contraception; however, moderately effective reversible contraception is more commonly used by adolescents. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend LARC as first-line contraception for adolescents. Clinicians providing contraception to adolescents should be knowledgeable of LARC indications, side effects, initiation guidelines, management of adverse reactions, and adolescent specific issues regarding LARC counseling, initiation, and continuation.
TOPOGRAPHIC CHANGES IN CHOROIDAL THICKNESS IN AGE-RELATED MACULAR DEGENERATION DURING THE DEVELOPMENT OF ACTIVE CHOROIDAL NEOVASCULARIZATION
Authors: Park Jae Yong , Kang Min-Ji , Kim Bum Gi , Chung Kyu Ho , Sim Ha Eun , Lee Seong Woo , Kim Jae Suk , Lee Hyeon Seok , Hwang Je Hyung
Published: May 2020

Purpose:

To evaluate topographic changes in choroidal thickness during development of choroidal neovascularization (CNV) in treatment-naive age-related macular degeneration (AMD) and to test the value of such changes as a predictive tool of CNV development.

Methods:

This retrospective cohort included 86 eyes that developed CNV from intermediate AMD, 43 eyes with intermediate AMD, and 36 eyes without AMD. Patients with intermediate AMD underwent spectral domain optical coherence tomography using enhanced depth imaging mode every 6 months until CNV was detected. Choroidal neovascularization was localized to one of the subfields of Early Treatment of Diabetic Retinopathy Study grid on fluorescein angiography. Average choroidal thickness of each subfield was calculated.

Results:

Choroidal thickness of the subfield where CNV developed at first clinical detection significantly increased compared with that 6 months before (P = 0.000 for central, P = 0.001 for superior parafoveal, P = 0.002 for temporal parafoveal, P = 0.002 for inferior parafoveal, and P = 0.001 for nasal parafoveal subfield). In eight patients who visited unexpectedly 3 months before CNV development in central subfield, choroidal thickness of central subfield increased significantly compared with that 6 months before CNV development (P = 0.001).

Conclusion:

Choroidal neovascularization development accompanied choroidal thickening of the corresponding subfield. Regular measurement of choroidal thickness may assist in prediction of CNV.
PERFLUOROCARBON LIQUID–ASSISTED INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS INTERNAL LIMITING MEMBRANE PEELING FOR HIGHLY MYOPIC MACULAR HOLE RETINAL DETACHMENT
Authors: Gu Xunyi , Hu Zizhong , Qian Huiming , Fransisca Silvia , Mugisha Aime , Wang Jingfan , Zhang Zhengyu , Zhang Weiwei , Ji Jiangdong , Liu Qinghuai , Xie Ping
Published: May 2020

Purpose:

To compare the efficacy of a modified perfluorocarbon liquid–assisted inverted internal limiting membrane (ILM) flap technique with the standard ILM peeling for the treatment of macular hole retinal detachment in highly myopic eyes.

Methods:

This was a retrospective, consecutive, nonrandomized comparative study. Forty-two macular hole retinal detachment eyes of 42 patients were included into either a perfluorocarbon liquid–assisted inverted ILM flap technique group (n = 22, inverted group) or standard ILM removal group (n = 20, peeling group). Outcomes measured were macular hole closure, retinal reattachment, and best-corrected visual acuity at least 6 months after surgery.

Results:

Macular hole closure was achieved in 20 eyes (90.9%) in the inverted group and in eight eyes (40%) in the peeling group (P < 0.01). Reattachment rates were 100% in the inverted group and 95% in the peeling group (P = 0.476). The mean best-corrected visual acuity improvement from baseline was 27.4 ± 19.9 Early Treatment Diabetic Retinopathy Study letters in the inverted group while the best-corrected visual acuity improvement was 13.6 ± 22.5 Early Treatment Diabetic Retinopathy Study letters in the peeling group (P = 0.044).

Conclusion:

The perfluorocarbon liquid–assisted inverted ILM flap technique was effective in sealing the macular hole, reattaching retina, and improving visual function postoperatively in highly myopic macular hole retinal detachment.
Descemet Membrane Endothelial Keratoplasty in Asian Eyes: Intraoperative and Postoperative Complications
Authors: Ang Marcus , Ting Darren S. J. , Kumar Ashish , May Khin Oo , Htoon Hla Myint , Mehta Jodhbir S.
Published: May 2020

Purpose:

To describe intraoperative and postoperative complications of Descemet membrane endothelial keratoplasty (DMEK) in Asian eyes.

Methods: A

prospective comparative study of consecutive cases of DMEK cases between January 2016 and January 2018. A subgroup of consecutive patients were optimized with preoperative topical eye drops and modification of donor insertion. Main outcome measures were intraoperative complications and total surgical time. Secondary outcome measures were postoperative complications and endothelial cell loss (ECL) at the 6-month follow-up.

Results:

We included 50 consecutive patients in this study; mean age of 66 ± 9 years old with 70% women. The indications for DMEK were Fuchs endothelial dystrophy (82%) and bullous keratopathy (18%). When compared with the standard group (n = 24 eyes), the optimized DMEK group (n = 26 eyes) was associated with a significantly reduced surgical time (33.9 ± 12.7 vs. 26.9 ± 7.6 minutes; P = 0.041), lower ECL at 6 months (27.2 ± 17.1% vs. 13.7 ± 9.7%; P = 0.012) and lower risk of high vitreous pressure causing iris prolapse (16.7% vs. 0%; P = 0.046). Multivariate analysis revealed a shorter surgical time (Odds Ratio [OR]: 0.924; 95% confidence interval: 0.858–0.995; P = 0.036) and reduced ECL (OR: 0.907; 95% confidence interval: 0.843–0.977; P = 0.01) in the optimized group.

Conclusions:

We observed intraoperative challenges such as difficulty with donor insertion with increased vitreous pressure in Asian eyes by performing DMEK surgery, which may be reduced with anticipated preoperative and postoperative measures.
The Keratoconus Outcome Research Questionnaire: A Cross-Cultural Validation Study of the Danish Version
Authors: Bak-Nielsen Sashia , Groenborg Therese K. , Ivarsen Anders , Hjortdal Jesper
Published: May 2020

Purpose:

To evaluate the psychometric properties of the Danish Keratoconus Outcome Research Questionnaire (KORQ).

Methods:

Phase 1: Rasch analysis assessed the original Danish KORQ. Phase 2: Reengineering of the Danish KORQ to optimize the psychometric properties and functioning of the KORQ.

Results:

The KORQ was self-administered by 195 patients. Phase 1 displayed trouble with local dependency and poor item fit. In phase 2, local dependency was addressed, and acceptable item fit was obtained for both subscales by collapsing item pairs into superitems (A6+A7, A9+A17, and S6+S9) and deleting 2 items (S4 and S2). After these corrections, the inter-item range was 0.28 to 0.72 for activity limitation scale (AL-S) and 0.14 to 0.54 for symptoms scale (S-S). Ordered thresholds were present, except in items A11, S5, and S10. No differential item functioning was present. Person separation reliability was 0.93 for AL-S and 0.81 for S-S. The person–item maps showed that the target was slightly above the study population. The maximal corneal curvature was the clinical measure of keratoconus with the highest correlation of 0.33 for AL-S and 0.24 for S-S. Evaluating individual questions showed that patients had the most trouble seeing at distance, driving at night, and wearing rigid gas-permeable lenses, whereas the least troublesome areas were walking up/downstairs, doing household tasks, avoiding objects on their path, and doing their job.

Conclusions:

The revised Danish KORQ largely fulfilled the assumptions of the Rasch model and displayed satisfactory psychometric properties. The need to revise the Danish KORQ highlights that cross-cultural validation is of key importance when working with patient-reported outcomes.
Spontaneous Descemet Membrane Detachment After Penetrating Keratoplasty—Clinical Presentation and Outcome of Air/Gas Descemetopexy
Authors: Nahum Yoav , Gal-Or Orly , Dadon Judith , Greenbaum Aharon , Israeli David , Melles Gerrit R. J. , Bahar Irit , Livny Eitan
Published: May 2020

Purpose:

To describe the clinical characteristics and treatment of spontaneous Descemet membrane (DM) detachment occurring decades after penetrating keratoplasty (PK).

Methods:

A multicenter interventional case series design was used. We reviewed the medical records of 4 patients with a history of PK presenting with spontaneous DM detachment at 3 university hospitals in Israel and an ocular surgery institute in The Netherlands in 2016 to 2019. Patient demographic and clinical data, postoperative best corrected visual acuity, findings on preoperative and postoperative anterior segment optical coherence tomography (AS-OCT), and graft survival were recorded.

Results:

Patients were aged 46 to 50 years. All had undergone PK for keratoconus 20 to 26 years previously. Patients presented within 18 to 180 days of onset of visual disturbance. Symptoms included sudden painless visual loss (2 patients), gradual visual loss and foreign body sensation (1 patients), and visual loss not otherwise specified (1 patient). Slit-lamp examination showed corneal edema, and AS-OCT showed DM detachment of variable extent. In 2 patients, the initial diagnosis was graft rejection and failure. Treatment consisted of anterior chamber injection of air (n = 3) or 20% SF6 (n = 1). In 3 patients, the DM reattached and the cornea regained its clarity. The fourth patient had persistent DM detachment that required repeated PK.

Conclusions:

Spontaneous DM detachment can mimic late graft failure in patients after PK. If diagnosed early, DM reattachment may be performed by air/gas injection, avoiding repeated keratoplasty. Eyes with presumed late penetrating graft rejection or failure should be examined by AS-OCT to exclude DM detachment.
Simultaneous Penetrating Keratoplasty and Implantation of a New Scleral-Fixated, Sutureless, Posterior Chamber Intraocular Lens (Soleko, Carlevale): A Novel Technique
Authors: Petrelli Myrsini , Schmutz Lydia , Gkaragkani Evangelia , Droutsas Konstantinos , Kymionis George D.
Published: May 2020

Purpose:

To describe a novel technique of combined penetrating keratoplasty (PKP) with implantation of a new scleral-fixated, sutureless, posterior chamber intraocular lens (PC-IOL) (Soleko, Carlevale).

Methods:

New surgical approach description.

Results:

We describe a novel technique for the management of PKP graft failure and posttraumatic aphakia with repeat-PKP and simultaneous implantation of a new scleral-fixated, sutureless PC-IOL. The postoperative course was uneventful, and the patient reported marked improvement in his vision. Up to 6 months postoperatively, the graft showed no signs of failure or rejection, the intraocular lens remained well-positioned, and no complications were observed.

Conclusions:

The favorable final outcome of our patient suggests that simultaneous PKP and implantation of this new scleral-fixated, sutureless PC-IOL may represent an efficient and effective method for the management of aphakia combined with corneal scarring.
Preoperative, intraoperative, and postoperative assessment of corneal biomechanics in refractive surgery
Authors: Dackowski Evan K. , Lopath Patrick D. , Chuck Roy S.
Published: May 2020

Purpose of review

To review current and emerging methods and utilities of preoperative, intraoperative, and postoperative measurements of corneal biomechanics and their effects on refractive surgery decision-making.

Recent findings

Several recent clinical and preclinical studies have demonstrated the utility of corneal biomechanical analysis in refractive surgery. These studies focus on both screening surgical candidates for keratoconic disease as well as intraoperative and postoperative monitoring. The measurement of spatially resolved biomechanics is beginning to be studied in humans.

Clinically available screening methods combining corneal biomechanics with topographic and tomographic data provide increased utility when screening for keratoconic disorder. Spatially resolved measurement of corneal biomechanics holds great potential for preoperative, intraoperative, and postoperative evaluation of refractive surgery candidates as well as for more individualized procedures in the future.
Severe Rifampicin-induced Vitamin K Deficiency Coagulopathy in a Child
Authors: Torres-Fernandez David , de Pazos Azpeitia Blanca , Gijon Mediavilla Manuel , Lopez-Roa Paula , Epalza Cristina , Grasa Lozano Carlos Daniel , Blazquez-Gamero Daniel
Published: May 2020

An 8-month-old child under tuberculosis treatment presented with multiple ecchymotic lesions. A severe coagulopathy was evidenced compatible with vitamin K deficiency [II (3%), VII (2%), IX (3%) and X (1%)]. It was reversed with vitamin K and plasma administration. Rifampicin-induced vitamin K deficiency is very rare, reported only once before, possibly related to an inhibition of vitamin K cycle.
Using Preventive Health Alerts in the Electronic Health Record Improves Hepatitis C Virus Testing Among Infants Perinatally Exposed to Hepatitis C
Authors: Hojat Leila S. , Greco Peter J. , Bhardwaj Amrita , Bar-Shain David , Abughali Nazha
Published: May 2020

Background:

Perinatal exposure to hepatitis C virus (HCV) is a major public health issue, and poor testing rates leave many children with infection unidentified. We sought to use the electronic health record (EHR) to promote guideline-directed HCV testing among infants born to mothers with HCV infection in an urban, safety-net hospital system.

Methods:

Our study population was identified using our EHR database, Epic. Children were included in the study if they had perinatal HCV exposure, were 18 months to 18 years of age and had at least 1 encounter in a primary or urgent care clinic during the study period. Our study included retrospective (October 2011 to February 2015) and prospective (February 2015 to May 2018) arms. Our EHR-based intervention was initiated in the prospective arm and recommended a one-time HCV antibody test at or after the age of 18 months using a health maintenance reminder. The health maintenance reminder activated a point-of-care alert and a linked HCV testing order set in all prespecified encounters during the intervention period.

Results:

Median time to appropriate HCV testing decreased from 96.2 months preintervention to 9.1 months postintervention (P < 0.0001), and rate of completed antibody testing increased from 14% to 61% (P < 0.0001).

Conclusions:

Among children with perinatal HCV exposure, using a point-of-care alert within the EHR significantly increased the HCV antibody testing rate in accordance with American Academy of Pediatrics (AAP) recommendations. More effective EHR-based interventions combined with increased provider awareness of appropriate HCV testing in perinatally exposed infants is imperative.
Applying the Developmental Systems Approach to Inclusive Community-Based Early Intervention Programs
Authors: Guralnick Michael J.
Published: May 2020

A developmentally oriented framework is presented designed to establish or enhance the quality of inclusive community-based early intervention systems. This conceptually and empirically integrated developmental approach supports a comprehensive family-centered model. Outlined is a process that coordinates children's goals with family priorities, identifies developmental pathways most likely to influence those goals, guides the selection of objectives and intervention activities, and provides an approach for evaluation and problem solving. Principles of relationships, comprehensiveness, and continuity are central to this framework and address the general problem of “what to implement” in inclusive community-based early childhood programs.
Early Hearing Detection and Intervention (EHDI) Within the Medical Home
Authors: Woodruff Torri Ann , Lutz Tara M.
Published: May 2020

The pediatric medical home is a model to provide quality health care to a child that is coordinated and overseen by a team of professionals who are grounded in family-centered practice (Cleveland Clinic, 2012
;
Munoz, Nelson, Bradham, Hoffman, & Houston, 2011). The medical home can be a centralized, consolidated, and comprehensive approach to address concerns for a child and can bolster the early intervention goals of Early Hearing Detection and Intervention ([EHDI]; Buchino et al., 2019
;
Munoz, Shisler, Moeller, & White, 2009
;
Munoz et al., 2011). With early access to screening information for children who are D/deaf or hard of hearing, the medical home plays a role in early diagnostic services and follow-up care that are critical to EHDI. This connection allows for discussion of how the medical home can exist and be supported within the context of existing service provision systems as a potential preemptive intervention to address the needs of children and families. By reviewing publicly accessible materials, the state of Connecticut can be used as a case study to look at various methods of medical home engagement with the outcome of supporting EHDI-based benchmarks (Connecticut Department of Public Health, 2014
,
2018). At the same time, a novel means of data collection through the medical home is proposed.
Estimands and missing data in clinical trials of chronic pain treatments: advances in design and analysis
Authors: Cai Xueya , Gewandter Jennifer S. , He Hua , Turk Dennis C. , Dworkin Robert H. , McDermott Michael P.
Published: May 2020

In clinical trials of treatments for chronic pain, the percentage of participants who withdraw early can be as high as 50%. Major reasons for early withdrawal in these studies include perceived lack of efficacy and adverse events. Commonly used strategies for accommodating missing data include last observation carried forward, baseline observation carried forward, and more principled methods such as mixed-model repeated-measures and multiple imputation. All these methods require strong and untestable assumptions concerning the conditional distribution of outcomes after dropout, given the observed data. We review recent developments in statistical methods for handling missing data in clinical trials, including implications of the increased emphasis being placed on precise formulation of the study objectives and the estimand (treatment effect to be estimated) of interest. A flexible method that seems to be well suited for the analysis of chronic pain clinical trials is control-based imputation, which allows a variety of assumptions to be made concerning the conditional distribution of postdropout outcomes that can be tailored to the estimand of interest. These assumptions can depend, for example, on the stated reasons for dropout. We illustrate these methods using data from 4 clinical trials of pregabalin for the treatment of painful diabetic peripheral neuropathy and postherpetic neuralgia. When planning chronic pain clinical trials, careful consideration of the trial objectives should determine the definition of the trial estimand, which in turn should inform methods used to accommodate missing data in the statistical analysis.
Optical coherence tomography–based diabetic macula edema screening with artificial intelligence
Authors: Hwang De-Kuang , Chou Yu-Bai , Lin Tai-Chi , Yang Hsin-Yu , Kao Zih-Kai , Kao Chung-Lan , Yang Yi-Ping , Chen Shih-Jen , Hsu Chih-Chien , Jheng Ying-Chun
Published: May 2020

Background:

Optical coherence tomography (OCT) is considered as a sensitive and noninvasive tool to evaluate the macular lesions. In patients with diabetes mellitus (DM), the existence of diabetic macular edema (DME) can cause significant vision impairment and further intravitreal injection (IVI) of anti–vascular endothelial growth factor (VEGF) is needed. However, the increasing number of DM patients makes it a big burden for clinicians to manually determine whether DME exists in the OCT images. The artificial intelligence (AI) now enormously applied to many medical territories may help reduce the burden on clinicians.

Methods:

We selected DME patients receiving IVI of anti-VEGF or corticosteroid at Taipei Veterans General Hospital in 2017. All macular cross-sectional scan OCT images were collected retrospectively from the eyes of these patients from January 2008 to July 2018. We further established AI models based on convolutional neural network architecture to determine whether the DM patients have DME by OCT images.

Results:

Based on the convolutional neural networks, InceptionV3 and VGG16, our AI system achieved a high DME diagnostic accuracy of 93.09% and 92.82%, respectively. The sensitivity of the VGG16 and InceptionV3 models was 96.48% and 95.15%., respectively. The specificity was corresponding to 86.67% and 89.63% for VGG16 and InceptionV3, respectively. We further developed an OCT-driven platform based on these AI models.

Conclusion:

We successfully set up AI models to provide an accurate diagnosis of DME by OCT images. These models may assist clinicians in screening DME in DM patients in the future.
Atherogenic Diet Accelerates Ectopic Mineralization in a Mouse Model of Pseudoxanthoma Elasticum
Authors: Zhao Jing-Yi , Kingman Joshua , Jacobs Ida Joely , Uitto Jouni , Cao Yi , Li Qiao-Li
Published: May 2020

Objective:

Pseudoxanthoma elasticum (PXE) is a multisystem heritable disorder caused by mutations in the Abcc6 gene. The disease is characterized by ectopic mineralization of the skin, eyes, and arterial blood vessels. Previous studies have suggested that cardiovascular complications in patients with PXE are caused in part by premature atherosclerosis. The aim of this study is to determine the effect of an atherogenic diet on ectopic mineralization.

Methods:

We used Abcc6

tm1JfK
mice (Abcc6

−/−
mice) as an established preclinical model of PXE. The offspring at age of 4 weeks were divided into two groups and fed the standard control laboratory diet (control group) and the atherogenic diet. Serum lipid profiles and bile acids were measured, and steatosis and tissue mineralization were evaluated by histopathologic analysis and chemical calcium quantification assay, respectively.

Results:

After 50–58 weeks of feeding an atherogenic diet, the concentrations of total cholesterol, low-density lipoprotein/very-low-density lipoprotein cholesterol, and bile acids were significantly higher in the Abcc6

−/−
mice on the atherogenic diet (180.9 ± 14.8 g/L, 145.9 ± 12.9 g/L, and 9.7 ± 1.4 μmol/L, respectively) than in Abcc6

−/−
mice on a control diet (85.2 ± 4.8 g/L, 25.1 ± 5.5 g/L, and 3.3 ± 0.5 μmol/L, respectively) (P < 0.001). Hypercholesterolemia was accompanied by extensive lipid accumulation in the liver and aorta, a characteristic feature of steatosis. The direct calcium assay demonstrated significantly increased mineralization of the muzzle skin containing the dermal sheath of vibrissae (57.2 ± 4.4 μmol Ca/gram tissue on the atherogenic diet and 43.9 ± 2.2 μmol Ca/gram tissue on control diet; P < 0.01), a reproducible biomarker of the ectopic mineralization process in these mice. An increased frequency of mineralization was also observed in the kidneys and eyes of mice on the atherogenic diet (P < 0.01).

Conclusion:

These observations suggest that the atherogenic diet caused hypercholesterolemia and accelerated ectopic mineralization in the Abcc6

−/−
mice. Our findings have clinical implications for patients with PXE, a currently intractable disorder with considerable morbidity and occasional mortality.
Epidemiology of Genital Chlamydial Infection in China in 2019
Authors: Yue Xiao-Li , Gong Xiang-Dong , Li Jing , Zhang Jia-Hui , Gu Heng
Published: May 2020

Objective:

Genital chlamydial infection is a globally common sexually transmitted infection caused by Chlamydia trachomatis. This study aimed to describe the epidemiological characteristics of the disease reported in China in 2019.

Methods:

Genital chlamydial infection cases were identified in 105 national sexually transmitted disease surveillance sites from the National Notifiable Infectious Disease Reporting System, which covers 31 provinces, autonomous regions, and municipalities in Chinese mainland. Data were collected and used to calculate the overall incidence, and the incidences per surveillance site, province, sex, and age group.

Results:

In 2019, there were 50,874 new cases of genital chlamydial infection reported in China, corresponding to an incidence of 55.32 cases per 100,000 population, and comprising a 9.98% increase from 2018 (50.30 cases per 100,000 population). The highest incidences of genital chlamydial infection occurred in Zhejiang, Guangdong province, Guangxi autonomous region, and Hainan province (average 137.49–233.37 cases per 100,000 population). The incidence of genital chlamydial infection was much higher in females than males, with a female-to-male ratio of 3.09 (84.55 per 100,000 population vs 27.35 per 100,000 population). The highest incidence of genital chlamydial infection was reported in the 20–24-year age group (184.70 cases per 100,000 population), followed by the 25–29-year age group (180.79 cases per 100,000) and 30–34-year age group (151.53 cases per 100,000 population). The highest proportion (68.30%) of genital chlamydial infection was reported from general hospitals, followed by maternal and child health hospitals (25.59%).

Conclusion:

The incidence rate of genital chlamydial infection in 2019 has an increase trend from 2018 and be a common sexually transmitted infection in China. The incidence is much higher in females than in males. Sexually active young adults are the highest risk population. There is substantial geographic diversity in incidence, with the highest incidence occurring in the southeast coastal areas with a developed economy. Epidemic of genital chlamydial infection in China should be concerned, and its surveillance needs to be improved.
Screening, brief intervention, and referral to treatment training for family nurse practitioner students
Authors: Arends Robin , Anderson Elverson Cynthia , Pike Keefner Tamara , Mylant MaryLou
Published: May 2020

Alcohol and substance-related disorders affect individuals throughout the global community. It is important that nurse practitioners understand the use of screening, brief intervention, and referral to treatment (SBIRT) in recognizing these disorders before development of chronic disease conditions. The SBIRT curriculum was adapted and integrated in a family nurse practitioner program. After completion of the curriculum in the didactic setting, students used what they learned in a clinical setting. Following the experience, students reflected on the encounters leading to increased awareness of personal feelings. Students were able to use their training in patient encounters and identified a variety of thoughts and feelings about working with patients who screened positive for overuse of alcohol or substances. The SBIRT is an important component of the education of nurse practitioners. It is through timely screening and intervention that conditions can be addressed early in substance use disorder. It is important for students to be aware of personal thoughts and feelings when working with this population.
Parent and child perceptions of the child's health at 2, 4, 6, and 13 months after sibling intensive care or emergency department death
Authors: Roche Rosa , Youngblut JoAnne M. , Brooten Dorothy A.
Published: May 2020

Background:

Approximately 50,000 US infants and children die annually, leaving surviving children and families with long-lasting effects. In most studies, children's health is rated by parents, but not the children.

Purpose:

To compare the surviving children’s self-rated health with parents’ ratings at 2, 4, 6, and 13 months after sibling neonatal intensive care unit/pediatric intensive care unit/emergency department death death and identify the related factors.

Methods:

Children and their parents rated the child’s health “now,” “now compared with others your age,” and “now versus before” the sibling’s death.

Sample:

One hundred thirty-two children (58% girls, 72% school-aged, and 50% Black non-Hispanic), 70 mothers, and 26 fathers from 71 bereaved families.

Conclusions:

Children self-rated their health: “now” as lower than their mothers at 4, 6, and 13 months and their fathers at 2, 4, and 13 months; “now compared with others your age” as lower than their mothers at each time point and fathers at 4, 6, and 13 months; and “now versus before” their sibling’s death as higher than their mothers at 4, 6, and 13 months and fathers at 6 months. Ratings did not differ by age, gender, or race/ethnicity. At 6 months, children self-rated their health “now” as higher than their fathers in families with one to two surviving children but lower than their fathers in families with three to eight surviving children.

Implications for practice:

Parents often perceive their children as healthier than children perceive themselves after sibling death, especially in larger families. Talking with children separately can identify the children at risk for emotional and physical illnesses earlier, providing more timely and appropriate interventions and referrals.
Elevated troponin levels in patients with atrial tachyarrhythmias
Authors: Rozenbaum Zach , Sapir Orly , Taieb Philippe , Ziv-Baran Tomer , Konigstein Maayan , Hochstadt Aviram , Rosso Raphael , Banai Shmuel , Chorin Ehud
Published: May 2020

Objective

Data regarding the significance of elevated troponin in the setting of atrial tachyarrhythmia remain inconclusive. In the present study, we aimed to explore the discriminative ability of troponin for obstructive coronary artery disease (CAD) among patients with atrial tachyarrhythmias.

Methods

We retrospectively identified patients with atrial tachyarrhythmias and elevated serum troponin levels, who underwent invasive coronary angiography during the same admission. The prevalence of obstructive CAD among these patients was compared to that of historically matched patients who underwent coronary angiography due to suspected non-ST elevation myocardial infarction and had no arrhythmias.

Results

Overall 318 patients with suspected non-ST elevation myocardial infarction were analyzed (n = 159 with atrial tachyarrhythmias and n = 159 without arrhythmias). Obstructive CAD was detected in 39% of patients with an arrhythmia compared to 85.5% in the control group (P < 0.001). A multivariable analysis demonstrated that parameters associated with obstructive CAD among patient with atrial tachyarrhythmias and elevated troponin were diabetes mellitus [odds ratio (OR) 2.7, 95% confidence interval (CI) 1.23–5.91, P = 0.013], prior ischemic heart disease (OR 4.48, 95% CI 1.93–10.4, P < 0.001) and troponin level (OR 3.18 for every 1000 ng/L increment, 95% CI 1.85–5.48, P < 0.001).

Conclusions

Elevated troponin is not a reliable indicator for the presence of underlying obstructive CAD among patients who present with atrial tachyarrhythmias. Risk stratification of these patients should rely on the degree of troponin elevation, and the presence of diabetes mellitus and prior ischemic heart disease.
Noncoeliac wheat sensitivity and diet
Authors: Mańkowska-Wierzbicka Dorota , Stelmach-Mardas Marta
Published: May 2020

Purpose of review

Noncoeliac gluten sensitivity (NCGS) can be suspected after exclusion of coeliac disease and wheat allergy. However, poorly understood pathogenesis of the NCGS, lack of gold standard for diagnosis and agreement in the definition for the NCGS condition, open the space for future investigation. This review aims to give an overview on the diagnosis and effective diet composition in the treatment of NCGS symptoms.

Recent findings

It appears that a diet low in fermentable oligo, di, and monosaccharides and polyols (FODMAPs) and gluten-free diet play a prominent role in the strategy of NCGS management. Considering available evidence with respect to diagnostic tools, it is challenging to prepare a standard guideline for NCGS diagnosis and treatment with clear cut-offs for symptom reduction/improvement that could directly be translated into test results. Nutritional support, including the use of pre/probiotics, has to be tailored to the individual situation of NCGS patients.

The exclusion of such components of wheat as amylase/trypsin inhibitors, wheat-germ agglutinins, or free of FODMAPs diet can reduce clinical symptoms of NCGS. The further investigation on microbiota changes may strengthen the knowledge in this area, where the major challenge is to develop biomarkers for NCGS investigation.
The role of taxane-based chemotherapy in the treatment of prostate cancer
Authors: Huebner Nicolai A. , Shariat Shahrokh F. , Resch Irene , Gust Kilian , Kramer Gero
Published: May 2020

Purpose of review

Indications for chemotherapy have increased in prostate cancer (PCA), many of which are shared with new hormonal agents (NHA). With no head to head comparison available, defining the optimal sequence and identifying biomarkers to predict response, has been a focus of intense research in PCA. We aim to summarize the best currently available evidence in all stages of disease to help guide therapy.

Recent findings

In metastatic castration-resistant prostate cancer, Cabazitaxel has shown improved radiographic progression-free survival over another NHA after Docetaxel and one NHA. For hormone sensitive PCA (mHSPC) multiple meta-analyses have shown combination therapy with Docetaxel or an NHA to be superior to androgen deprivation therapy alone, yet no clear benefit over each other. For peri-interventional chemotherapy with local therapy, there is currently only one positive prospective trial, for very high-risk disease.

Cabazitaxel is underutilized and should be used earlier. NHAs should not be used in succession as there is significant cross resistance. Combination therapy should be used in mHSPC, yet there is no clear benefit for any combination. Peri-interventional chemotherapy might have a benefit for a small group of patients with very high-risk disease, yet this must be carefully evaluated, and side effects must be taken into account.
Pediatric Crohn Disease and Multisystem Inflammatory Syndrome in Children (MIS‐C) and COVID‐19 Treated With Infliximab
Authors: Dolinger Michael T. , Person Hannibal , Smith Rachel , Jarchin Lauren , Pittman Nanci , Dubinsky Marla C. , Lai Joanne
Published: May 2020

Coronavirus disease 2019 (COVID‐19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID‐19 infection in a recently diagnosed pediatric Crohn disease patient successfully treated with tumor necrosis factor‐alpha (TNF‐α) blockade. The patient presented with 5 days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS‐CoV‐2 polymerase chain reaction was positive. Despite inpatient treatment for COVID‐19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid‐refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)‐6, IL‐8, and TNF‐α, higher than those described in either inflammatory bowel disease or severe COVID‐19 alone. The patient was treated with infliximab for TNF‐α blockade to address both moderately to severely active Crohn disease and multisystem inflammatory syndrome in children temporally related to COVID‐19. Within hours of infliximab treatment, fever, tachycardia, and hypotension resolved. Cytokine profile improved with normalization of TNF‐α, a decrease in IL‐6, and IL‐8 concentrations. This case supports a role for blockade of TNF‐α in the treatment of COVID‐19 inflammatory cascade. The role of anti‐TNF agents in patients with multisystem inflammatory syndrome in children temporally related to COVID‐19 requires further investigation.