bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial Fibrosis as a Pathway of Prediction of Ventricular Arrhythmias and Sudden Cardiac Death in Patients With Nonischemic Dilated Cardiomyopathy
Authors: Centurión Osmar Antonio , Alderete José Fernando , Torales Judith María , García Laura Beatriz , Scavenius Karina Elizabeth , Miño Luis Marcelo
Published: May 2019

The mechanism of sudden cardiac death (SCD) in patients with nonischemic dilated cardiomyopathy (NIDCM) is mostly due to sustained ventricular tachycardia and ventricular fibrillation. The clinical guidelines for the therapeutic management of this set of patients are mostly based on left ventricular ejection fraction value which has a low specificity to differentiate the risk of SCD from the risk of mortality associated with heart failure or other comorbidities. Moreover, since SCD can occur in patients with normal or mildly depressed ejection fraction, it is necessary to identify new markers to improve the prognostic stratification of SCD. Several studies that analyzed the ventricular arrhythmia substrate found that myocardial fibrosis plays an important role in the genesis of ventricular arrhythmias in patients with NIDCM. The surrounding zone of the area of fibrosis is a heterogeneous medium, where tissue with different levels of fibrosis coexists, resulting in both viable and nonviable myocardium. This myocardial fibrosis may constitute a substrate for ventricular arrhythmias, where slow and heterogeneous conduction may favor the genesis of reentry mechanism increasing the chance to develop sustained ventricular tachycardia or ventricular fibrillation. Therefore, the evaluation of ventricular fibrosis by late gadolinium enhancement (LGE) cardiac magnetic resonance imaging has been suggested as an indicator for SCD risk stratification. Indeed, LGE in patients with NIDCM is associated with increased risk of all-cause mortality, heart failure hospitalization, and SCD. Detection of myocardial fibrosis as LGE by cardiac magnetic resonance imaging can be considered as a useful pathway of prediction of malignant ventricular arrhythmias since it has excellent prognostic characteristics and may help guide risk stratification and management in patients with NIDCM.
Andexanet Alfa (Andexxa) Formulary Review
Authors: Beik Nahal , Reddy Prabashni , Sylvester Katelyn W. , Connell Nathan T. , Giugliano Robert P. , Piazza Gregory , Connors Jean M.
Published: May 2019

Andexanet alfa, a recombinant modified human “decoy” factor Xa (FXa) protein, is the first and only available antidote approved by the Food and Drug Administration to manage life-threatening or uncontrolled bleeding associated with the anti-Xa agents. It binds to direct and indirect anti-Xa oral anticoagulants with high specificity to reverse their inhibitory effects and restore the activity of FXa. Andexanet alfa is administered via two different dosing regimens, standard and high dose, based on the specific FXa inhibitor, dose, and time since the patient’s last dose of FXa inhibitor. The approval for andexanet alfa is supported by data from two phase 3 studies (ANNEXA-A, ANNEXA-R) and preliminary data from the phase 3b/4 ANNEXA-4 trial. The first study found that andexanet alfa rapidly reduced anti-Xa activity by 92%–94% in healthy volunteers taking apixaban or rivaroxaban. The ANNEXA-4 study found that the median anti-Xa activity decreased by 89%–93% in patients with major bleeding taking apixaban or rivaroxaban. However, thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up in ANNEXA-4. Additionally, only 40% of patients had restarted anticoagulation and, in this group, the rate of thrombotic events was 12%. Four patients had a thrombotic event within 3 days after andexanet alfa treatment. The wholesale acquisition cost of the standard dose regimen is $24,750, and the high-dose regimen is $49,500. The estimated annual drug budget of treating 10–100 patients ranges from $248K to $495M. Effective October 1, 2018, Medicare will provide an add-on payment for andexanet alfa of up to $14,063 per qualifying case to Inpatient Prospective Payment System-participating acute care hospitals. In this formulary review for a health system’s pharmacy and therapeutics committee, andexanet alfa clinical trials and medication package insert were summarized and, after consulting with clinical experts from our institutions, practical recommendations for use were generated to ensure appropriate and safe use of this agent.
Dynamic Scheimpflug Ocular Biomechanical Parameters in Healthy and Medically Controlled Glaucoma Eyes
Authors: Miki Atsuya , Yasukura Yuichi , Weinreb Robert N. , Yamada Tomomi , Koh Shizuka , Asai Tomoko , Ikuno Yasushi , Maeda Naoyuki , Nishida Kohji
Published: May 2019

Purpose:

To evaluate the relationship between biomechanical parameters measured with a dynamic Scheimpflug analyzer and glaucoma.

Patients and Methods:

Cross-sectional observational data of 47 eyes of 47 consecutive subjects with medically controlled primary open-angle glaucoma and 75 eyes of 75 healthy subjects examined with a dynamic Scheimpflug analyzer (Corvis ST) were retrospectively investigated. Eight biomechanical parameters were compared between eyes with and without glaucoma using multivariable models adjusting for intraocular pressure (IOP), central corneal thickness, age, and axial length.

Results:

In multivariable models, glaucoma was negatively correlated with A1 time (P<0.001, coefficient=−0.5535), A2 time (P=0.008, coefficient=−0.1509), radius (P=0.011, coefficient=−0.4034), and whole eye movement (P<0.001, coefficient=−0.0622). Negative correlation between glaucoma and 3 parameters (A1 time, A2 time, and radius) consistently indicate larger deformability of the cornea and negative correlation between glaucoma and whole eye movement indicate smaller eye movement, in glaucoma eyes. There were significant correlations of many biomechanical parameters with other baseline factors (8 parameters with IOP, 2 with central corneal thickness, 4 with age, and 7 with axial length).

Conclusions:

Eyes with medically controlled glaucoma were more deformable than healthy eyes, which may increase the risk of optic nerve damage through an underestimation of IOP and biomechanical vulnerability of the globe. Many parameters showed a significant correlation with baseline factors, suggesting the importance of adjustment for these confounding factors when evaluating the correlation between biomechanical parameters and ocular diseases. These results suggest the relevance of measuring biomechanical properties of glaucoma eyes for accurate IOP measurement and risk assessment.
Longitudinal translocator protein-18 kDa–positron emission tomography imaging of peripheral and central myeloid cells in a mouse model of complex regional pain syndrome
Authors: Cropper Haley C. , Johnson Emily M. , Haight Elena S. , Cordonnier Stephanie A. , Chaney Aisling M. , Forman Thomas E. , Biswal Anjali , Stevens Marc Y. , James Michelle L. , Tawfik Vivianne L.
Published: May 2019

Complex regional pain syndrome (CRPS) is a severely disabling disease characterized by pain, temperature changes, motor dysfunction, and edema that most often occurs as an atypical response to a minor surgery or fracture. Inflammation involving activation and recruitment of innate immune cells, including both peripheral and central myeloid cells (ie, macrophages and microglia, respectively), is a key feature of CRPS. However, the exact role and time course of these cellular processes relative to the known acute and chronic phases of the disease are not fully understood. Positron emission tomography (PET) of translocator protein-18 kDa (TSPO) is a method for noninvasively tracking these activated innate immune cells. Here, we reveal the temporal dynamics of peripheral and central inflammatory responses over 20 weeks in a tibial fracture/casting mouse model of CRPS through longitudinal TSPO-PET using [18F]GE-180. Positron emission tomography tracer uptake quantification in the tibia revealed increased peripheral inflammation as early as 2 days after fracture and lasting 7 weeks. Centralized inflammation was detected in the spinal cord and brain of fractured mice at 7 and 21 days after injury. Spinal cord tissue immunofluorescent staining revealed TSPO expression in microglia (CD11b+) at 7 days but was restricted mainly to endothelial cells (PECAM1+) at baseline and 7 weeks. Our data suggest early and persistent peripheral myeloid cell activation and transient central microglial activation are limited to the acute phase of CRPS. Moreover, we show that TSPO-PET can be used to noninvasively monitor the spatiotemporal dynamics of myeloid cell activation in CRPS progression with potential to inform disease phase–specific therapeutics.
Current perspectives on the opioid crisis in the US healthcare system
Authors: Stoicea Nicoleta , Costa Andrew , Periel Luis , Uribe Alberto , Weaver Tristan , Bergese Sergio D.
Published: May 2019

Introduction:

The administration of opioids has been used for centuries as a viable option for pain management. When administered at appropriate doses, opioids prove effective not only at eliminating pain but further preventing its recurrence in long-term recovery scenarios. Physicians have complied with the appropriate management of acute and chronic pain; however, this short or long-term opioid exposure provides opportunities for long-term opioid misuse and abuse, leading to addiction of patients who receive an opioid prescription and/or diversion of this pain medication to other people without prescription. Several reviews attempted to summarize the epidemiology and management of opioid misuse, this integrative review seeks to summarize the current literature related with responsible parties of this opioid abuse crisis and discuss potential associations between demographics (ethnicity, culture, gender, religion) and opioid accessibility, abuse and overdose.

Methods:

We performed an extensive literature search in Google Scholar and Pub Med databases that were published between December 7, 1999 and January 9, 2018 in accordance with the Preferred Reporting Items for Systematic Reviews and meta-Analysis (PRISMA) guidelines. Searches were referenced using medical subject headings (MeSH) that included “opioids”, “over-prescription”, “opioid consumption”, or “opioid epidemic”. The final review of all data bases was conducted on July 24, 2018.

Results:

A total of 7160 articles were originally identified. After 3340 duplicate articles were removed, 3820 manuscripts were removed after title and abstract screening. Following this, 120 manuscripts underwent eligibility selection with only 70 publications being selected as reliable full-texts addressing related factors surrounding the opioid crisis.

Conclusion:

With approximately 100 million people suffering from both chronic and acute pain in the United States (US) in 2016, opiates will continue to remain a prominent class of medication in healthcare facilities and homes across the US. Over 66% of total overdose episodes in 2016 were opioid-related, a figure that attests to the severity and wide-spread nature of this issue. A three-point approach accentuating the prevention, treatment, and rehabilitation of both those currently affected and at-risk in the future may be the comprehensive solution.
Interpregnancy weight change and perinatal outcomes
Authors: Martínez-Hortelano Jose Alberto , Berlanga-Macías Carlos , Pozuelo-Carrascosa Diana Patricia , Sanabria-Martínez Gema , Poyatos-León Raquel , Martínez-Vizcaíno Vicente
Published: May 2019

Background:

Growing evidence suggests that interpregnancy weight change (IPWC) is a risk factor for perinatal outcomes, since it may increase the probability of gestational complications including gestational diabetes or cesarean delivery. Additionally, IPWC may affect neonatal outcomes increasing the prevalence of newborns small for gestational age or preterm birth. However, the association between IPWC and perinatal outcomes has not systematically synthesized thus far. This study protocol aims to provide a clear, transparent and standardized procedure for systematically reviewing the association between IPWC and perinatal outcomes.

Methods and analysis:

This systematic review and meta-analyses protocol is based on the preferred reporting items for systematic review and meta-analysis protocols and the Cochrane Collaboration Handbook. MEDLINE, EMBASE, the Cochrane Library, and Web of Science will be systematically searched from their inception. No limits will be defined by study design, as such different tools to assess risk of bias will be used:

Odd ratios and their corresponding 95% confidence intervals will be reported to evaluate associations between IPWC and perinatal outcomes.

Results:

The results of this study will be published in a peer-reviewed journal.

Conclusion:

This systematic review and meta-analysis will systematically synthesize the evidence regarding the association between IPWC and perinatal outcomes. Data will be extracted from published articles and findings will be published in peer-reviewed journals. Ethical approval and informed consent will not be required due to the nature of the study.

Systematic review registration:

PROSPERO CRD42018100449.
Primary hepatic gastrointestinal stromal tumor with right adrenal gland invasion
Authors: Xu Liangliang , Zhang Ming , Xu Mingqing
Published: May 2019

Introduction:

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors that mainly occur in the gastrointestinal tract. The GISTs that are sporadically reported in extra-gastrointestinal regions are named as extra-gastrointestinal stromal tumors (EGISTs). However, the primary EGISTs that originate from the liver are rare.

Patient Concerns:

A 64-year-old female presenting with right upper abdominal pain and thirsty for more than 20 days.

Diagnosis:

A diagnosis of a 15 × 14 × 7 cm liver mass located in the posterior right lobe of liver and spread to the right adrenal gland was confirmed. Pathological results showed that the tumor was mainly composed of epithelial cells and tested positive for CD117 and SDHB (succinate dehydrogenase complex iron sulfur subunit B). The gene mutational analyses for c-Kit and platelet-derived growth factor receptor alpha exons revealed negative results. Fluorescence in situ hybridization of murine double minute 2 produced negative fluorescence results which distinguished it from dedifferentiated liposarcomas. The postoperative gastroduodenal and colorectal endoscopy did not find any neoplastic lesions. To this end, the diagnosis of primary hepatic EGIST of wild type nature was confirmed.

Interventions:

The patient received right hepatectomy and adrenalectomy, no postoperative chemotherapy was administered.

Outcomes:

The patient died 11 months after surgery due to tumor metastasis.

Conclusion:

Primary hepatic EGIST is a rare and complicated disease of liver, a multidisciplinary team is necessary in diagnosis and treatment of primary hepatic EGIST.
Uterine rupture in patients with a history of laparoscopy or hysteroscopy procedures
Authors: Zhao Baojing , Wang Yanling , Zhang Ying
Published: May 2019

Rationale:

Uterine rupture is a rare incidence but can lead to catastrophic maternal and fetal consequences. We still need to place a high premium on these cases.

Patient concerns:

The patients all showed hemodynamic shock with complaints of serious pain in the abdomen. They all had a history of laparoscopy or hysteroscopy procedures.

Diagnoses:

Case 1 and 2 were diagnosed during surgery. Case 3 was diagnosed by an urgent abdominal ultrasonogram before surgery.

Interventions:

We performed emergency surgeries for the 3 cases.

Outcomes:

Three patients all recovered well. But only the child in case 2 survived.

Lessons:

It must be emphasized that pregnant women with a history of such surgeries should be aware of uterine rupture during pregnancy.
A novel heterozygous mutation c.680A>G (p. N227S) in SLC34A1 gene leading to autosomal dominant hypophosphatemia
Authors: Chen Xiang , Xie Ying , Wan Shan , Xu Jin , Cai Bei , Zhang Yi , Yu Xijie
Published: May 2019

Rationale:

Currently, the relationship between heterozygous mutations in SLC34A1 and hypophosphatemia is controversial. Here we report an autosomal dominant hypophosphatemia pedigree carrying a novel heterozygous mutation in SLC34A1.

Patient concerns:

The proband is a 32-year old young man, presented with progressive pain and weakness in his lower extremities for more than 5 years. The proband showed persistent hypophosphatemia and low TmPO4/GFR values, indicating renal phosphate leak. His grandfather, father, and one of his uncles showed the similar symptoms.

Diagnoses:

Autosomal dominant hypophosphatemia.

Interventions and outcomes:

Phosphorus supplement was prescribed to the proband and his affected uncle. Both their serum phosphorus levels recovered to normal and their symptoms such as back pain and lower extremity weakness were completely relieved. Whole exome sequencing was performed to identify disease-causing mutations in proband.

Lessons:

A novel heterozygous missense mutation c.680A>G (p. N227S) in exon 7 of SLC34A1 was found in proband by whole exome sequencing, which was also found in other 4 family members of this pedigree. Our report of an autosomal dominant hypophosphatemia pedigree with 5 mutant carriers enriches the clinical phenotype caused by the SLC34A1 mutations and further affirms the heterozygous mutations are causative for hypophosphatemia.
Proposal of a new nodal classification for operable non-small cell lung cancer based on the number of negative lymph nodes and the anatomical location of metastatic lymph nodes
Authors: Liu Hongfeng , Yan Tao , Zhang Tiehong , Chen Xiaowei , Wang Yadong , Du Jiajun
Published: May 2019

Lymph node metastasis is one of the most important prognostic indicators in patients with radically resected non-small cell lung cancer (NSCLC). This retrospective study aimed to compare the predictive value of metastatic lymph nodes (MNs), lymph node ratio (LNR), resected lymph nodes (RNs), and negative lymph nodes (NNs) with the currently used pathologic nodal (pN) staging category.

We conducted a retrospective analysis of 1019 consecutive NSCLC patients treated with complete resection in a single institution. Prognostic values of various lymph node factors were evaluated by analysis of univariate and multivariate Cox proportional hazards model, and the results were compared with those using the location-based pN stage classification.

The median follow-up duration was 47 months. During this period, 353 cases of cancer recurrence and 337 deaths were reported. Multivariate cox analysis indicated that both pN and NN categories were independent predictors of patient survival. The patients were divided into six groups on the basis of pN and NN categories. The survival rates of the groups were as follows: pN0, NN≥8, 81.4%; pN0, NN<8, 73.8%; pN1, NN≥8, 61.4%; pN1, NN<8, 54.2%; pN2, NN≥8, 48.4%; and pN2>1, NN<8, 35.0%. Comparison of the predictive values of the lymph node factors showed that the new N category was a more valuable prognostic factor in operable NSCLC.

The combination of anatomically based pN stage classification and the number of MNs is an accurate prognostic determinant in patients with operable NSCLC which can be equal to 8th N category.
Erector spinae plane block for multimodal analgesia after wide midline laparotomy
Authors: Bang Seunguk , Chung Jihyun , Kwon Woojin , Yoo Subin , Soh Hyojung , Lee Sang Mook
Published: May 2019

Rationale:

The most commonly used regional techniques for analgesia following laparotomy thoracic epidural analgesia and paravertebral blocks are technically difficult to perform and carry a risk of severe complications. Recently, the erector spinae plane block (ESPB) has been reported to effectively treat neuropathic pain. The ultrasound-guided ESPB is an easily performed fascial plane block that can provide sensory blockade from T2–4 to T12–L1. Moreover, the ESPB reportedly blocks both the ventral rami of spinal nerves and the rami communicants, which contain sympathetic nerve fibres, through spread into the thoracic paravertebral space.

Patient concerns:

We report the case of a 35-year-old female patient who underwent excision of a larger ovarian mass via laparotomy with a wide, midline incision from the xiphoid process to the pubic tubercle.

Diagnoses:

They were diagnosed with mucinous cystadenoma originated from the right ovary and fallopian tube, and a right oophorectomy and salpingectomy were performed.

Interventions:

The ESPB was performed for postoperative pain control at the level of the T8 transverse process. Postoperative multimodal analgesia was provided according to the acute pain service protocol of our hospital. The patient was prescribed oral acetaminophen 175 mg every 6 hours and intravenous patient-controlled analgesia (PCA) with fentanyl 7 μg/mL. A 1:1 mixture of 0.75% ropivacaine (20 mL) and saline (20 mL) with epinephrine (1: 200,000) was manually injected through the indwelling catheter every 8 hours (20 mL per side).

Outcomes:

The first demand dose of fentanyl was administered at 9 hours and 39 minutes after the surgery. There were no reported resting pain scores >4, nor were any rescue analgesics needed during the first 5 postoperative days.

Lessons:

The ESPB provided highly effective analgesia as a part of multimodal analgesia after laparotomy with a wide midline incision.
Novel mutations in patients with X-linked Alport syndrome
Authors: Oh Songhee , Kim Jieun , Kim Hyoungnae , Jeon Jin Seok , Noh Hyunjin , Han Dong Cheol , Jin So-Young , Kwon Soon Hyo
Published: May 2019

Rationale:

A genotype-phenotype correlation is known to be associated with Alport syndrome (AS). Identifying novel mutations can expand the knowledge about the natural course of AS.

Patient concerns:

The first patient was a-15-year-old boy detected with proteinuria during the school health check-up. The second case was a-29-year-old woman, who visited the outpatient clinic for edema.

Diagnosis:

We performed targeted next-generation sequencing to identify the mutations associated with AS. Results were confirmed by Sanger sequencing and multiplex ligation-dependent probe amplification. Missense mutation (c.2332G>C, p.Gly778Arg) was identified in the first case and an exon 16 deletion was also identified in the second case.

Intervention:

We treated both cases with angiotensin receptor blocker (ARB).

Outcomes:

The amount of proteinuria in the first case did not change after ARB therapy, during the follow-up period (1 year). Proteinuria in the woman decreased to half of the baseline level, 1 year after treatment. Glomerular filtration rate was also maintained during the follow-up.

Conclusion:

We identified novel mutations in Koreans with an X-linked AS mutation in the COL4A5 gene and an individual phenotype. This is the first report of AS patients with a novel missense mutation and copy number variation.
Efficacy of traditional Chinese medicine for chronic gastritis
Authors: Yan Zi-xing , Dai Yun-kai , Ma Teng , Lin Xiao-ying , Chen Wen-hui , Liu You-mei , Zu Ruo-zhen , Zhang Xiao-bin , Jiang Peng , Yang Jian-hua , Li Sheng , Zheng Li-sheng , Lin Zhen-wen
Published: May 2019

Background:

To systematically evaluate efficacy of traditional Chinese medicine (TCM) in treating chronic gastritis (CG).

Methods:

Data sources from PubMed, Embase, Springer Link, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Biomedicine Database, and Wan-fang database were searched up to July 5, 2018. Review Manager software version 5.3, the Cochrane Collaboration's risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation profiler software were conducted for this meta-analysis.

Results:

Sixteen studies involving 1673 participants (906 vs 767) were included in this study. Pooled data showed significant statistical differences between TCM groups and current routine pharmacotherapy (RP) groups in overall clinical efficacy (odds ratio [OR] 4.65; 95% confidence interval [CI] 3.29, 6.56; P < .00001), efficacy under endoscopy (OR 2.46; 95% CI 1.12, 5.43; P = .03), stomach distension (mean difference [MD] −0.37; 95% CI −0.56, −0.19; P < .0001), stomachache (standardized MD [SMD] −0.80; 95% CI −1.45, −0.14; P = .02), and belching (SMD −2.00; 95% CI −3.80, −0.20; P = .03). However, acid regurgitation (SMD −0.71; 95% CI −1.69, 0.28; P = .16) and anorexia (SMD −0.75; 95% CI −2.30, 0.80; P = .35) showed no significant statistical differences between 2 groups. In addition, incidence of adverse reactions of TCM groups was lower than that of RP groups.

Conclusion:

Evidence from this meta-analysis suggests that TCM could be more efficacious than current RP in treating CG. But further standardized research of rigorous design should be needed to further validate its efficacy.
Pregnancy outcomes in patients with primary antiphospholipid syndrome
Authors: Liu Liping , Sun Dan
Published: May 2019

Background:

Antiphospholipid syndrome (APS) is a rare heterogenous autoimmune disorder with severe life-threatening complications shown during pregnancy. In this analysis, we aimed to systematically compare the pregnancy outcomes (both maternal and fetal) in patients with APS.

Methods:

Web of Science, Google Scholar, Medicus, Cochrane Central, Embase, and Medline were searched for relevant English publications. The main inclusion criteria were based on studies that compared pregnancy outcomes in patients with APS vs a control group. Statistical analysis was carried out by the RevMan software version 5.3. This analysis involved dichotomous data, and risk ratios (RR) with 95% confidence intervals (CIs) were used to represent the analysis.

Results:

Eight studies consisting of a total number of 212,954 participants were included. Seven hundred seventy participants were pregnant women with APS and 212,184 participants were assigned to the control group. Pregnancy-induced hypertension was significantly higher in women with APS (RR: 1.81, 95% CI: 1.33 – 2.45; P = .0002). The risks of fetal loss (RR: 1.33, 95% CI: 1.00–1.76; P = .05), abortion (RR: 2.42, 95% CI: 1.46–4.01; P = .0006), thrombosis (RR: 2.83, 95% CI: 1.47–5.44; P = .002), and preterm delivery (RR: 1.89, 95% CI: 1.52–2.35; P = .00001) were also significantly higher in women with APS. However, placental abruption (RR: 1.35, 95% CI: 0.78–2.34; P = .29) and pulmonary embolism were not significantly different (RR: 1.47, 95% CI: 0.11–19.20; P = .77). The risk of neonatal mortality (RR: 3.95, 95% CI: 1.98–7.86; P = .0001), infants small for gestational age (RR: 1.38, 95% CI: 1.04–1.82; P = .02), premature infants (RR: 1.86, 95% CI: 1.52–2.28; P = .0001), and infants who were admitted to neonatal intensive care unit (RR: 3.35, 95% CI: 2.29–4.89; P = .00001) were also significantly higher in women with APS.

Conclusion:

This analysis showed APS to be associated with significantly worse pregnancy outcomes when compared to the control group. A significantly higher risk of maternal and fetal complications was observed in this category of patients. Therefore, intense care should be given to pregnant women with APS to monitor unwanted outcomes and allow a successful pregnancy.
Addressing Rural Geographic Disparities Through Health IT
Authors: Krakow Melinda , Hesse Bradford W. , Oh April , Patel Vaishali , Vanderpool Robin C. , Jacobsen Paul B.
Published: May 2019

Background:

Rural communities experience disparate rates of chronic diseases and face distinct challenges in gaining access to health care. Increasing the reach of the US health information and communication technology infrastructure can support rural health by overcoming geographic and temporal health care barriers.

Objectives:

The goal of the study is to establish statistically valid point estimates for the use of health information technology within rural versus urban populations, and to understand the degree to which structural factors may account for the overall variance in the use of these technologies.

Methods:

Data from the National Cancer Institute’s 2017 Health Information National Trends Survey were used to estimate prevalence of Health IT engagement across rural and urban populations and model factors influencing use of online medical records.

Results:

Rural residents reported similar rates of providers maintaining electronic health records and offering access to online medical records. However, rural residents with provider-maintained records were less likely to receive a provider recommendation to use online medical records and were subsequently less likely to actually access records. Observed differences in online medical record use were accounted for by variance in Internet access, access to a regular health care provider, and whether providers encouraged patients to use online records.

Conclusions:

Findings shed light on structural opportunities for overcoming geographic and temporal barriers to Health IT and extending the benefits of digital health information technologies to underserved populations.
Measuring Exposure to Incarceration Using the Electronic Health Record
Authors: Wang Emily A. , Long Jessica B. , McGinnis Kathleen A. , Wang Karen H. , Wildeman Christopher J. , Kim Clara , Bucklen Kristofer B. , Fiellin David A. , Bates Jonathan , Brandt Cynthia , Justice Amy C.
Published: May 2019

Background:

Electronic health records (EHRs) are a rich source of health information; however social determinants of health, including incarceration, and how they impact health and health care disparities can be hard to extract.

Objective:

The main objective of this study was to compare sensitivity and specificity of patient self-report with various methods of identifying incarceration exposure using the EHR.

Research Design:

Validation study using multiple data sources and types.

Subjects:

Participants of the Veterans Aging Cohort Study (VACS), a national observational cohort based on data from the Veterans Health Administration (VHA) EHR that includes all human immunodeficiency virus–infected patients in care (47,805) and uninfected patients (99,060) matched on region, age, race/ethnicity, and sex.

Measures and Data Sources:

Self-reported incarceration history compared with: (1) linked VHA EHR data to administrative data from a state Department of Correction (DOC), (2) linked VHA EHR data to administrative data on incarceration from Centers for Medicare and Medicaid Services (CMS), (3) VHA EHR-specific identifier codes indicative of receipt of VHA incarceration reentry services, and (4) natural language processing (NLP) in unstructured text in VHA EHR.

Results:

Linking the EHR to DOC data: sensitivity 2.5%, specificity 100%; linking the EHR to CMS data: sensitivity 7.9%, specificity 99.3%; VHA EHR-specific identifier for receipt of reentry services: sensitivity 7.3%, specificity 98.9%; and NLP, sensitivity 63.5%, specificity 95.9%.

Conclusions:

NLP tools hold promise as a feasible and valid method to identify individuals with exposure to incarceration in EHR. Future work should expand this approach using a larger body of documents and refinement of the methods, which may further improve operating characteristics of this method.
Isavuconazole Treatment of Cerebral and Pulmonary Aspergillosis in a Pediatric Patient With Acute Lymphoblastic Leukemia: Case Report and Review of Literature
Authors: De Leonardis Francesco , Novielli Chiara , Giannico Benedetta , Mariggiò Maria Addolorata , Castagnola Elio , Santoro Nicola
Published: May 2019

Invasive aspergillosis in hematologic pediatric patients is an opportunistic infection that is difficult to treat, with a high mortality rate when localized in the central nervous system. We are describing a 3-year-old girl who was affected by acute lymphoblastic leukemia who developed cerebral and pulmonary aspergillosis during induction chemotherapy. The patient failed first-line voriconazole treatment because of being a CYP2C19 ultrarapid metabolizer and received effective isavuconazole therapy with no notable side effects.
Plasma Cell Myeloma Type Posttransplant Lymphoproliferative Disorder in an 18-Month-Old Heart Transplant Recipient: Case Report and Review of the Literature
Authors: Xue Lijun , Zuppan Craig , Wang Tiannan , Kheradpour Albert , Rowsell Edward H. , Wang Jun
Published: May 2019

Plasma cell myeloma type posttransplant lymphoproliferative disorder (PTLD) is a rare subtype of monomorphic B-cell/plasmacytic-type PTLD. Only 10 cases of monomorphic plasmacytic-type PTLD have been previously reported in pediatric transplant recipients (kidney, liver, small bowel-liver, and heart). We present a case of Epstein-Barr virus positive monomorphic plasma cell myeloma type PTLD that developed 10 months after cardiac transplant in an 18-month-old boy. The bone marrow showed replacement by about 20% to 40% lambda-restricted plasmacytoid lymphocytes and plasma cells (by immunohistochemistry and flow cytometry, respectively). His serum free lambda to kappa light chain ratio was >300, comparable to that seen in myeloma in nontransplant patients. The neoplastic cells were Epstein-Barr virus small RNA positive by in situ hybridization. He was treated with rituximab in combination with ganciclovir, intravenous immune globulin, and discontinuation of immunosuppressants. However, he succumbed to septic shock and multiorgan failure 1 month after diagnosis.
A Novel Dual Immunostain to Characterize Sloughed Cells in Testicular Biopsies for Infertility
Authors: Dhakal Hari P. , Coleman Jennifer , Przybycin Christopher G.
Published: May 2019

Evaluation of testicular biopsies from azoospermic men requires recognition of phases of germ cell maturation as organized architecturally within the seminiferous tubule, as well as distinguishing the inability to generate mature spermatozoa (germ cell aplasia or maturation arrest) from normal spermatogenesis, which may be associated with a reversible obstruction. While traditional fixatives (eg, Bouin solution) provide exquisite nuclear detail and preserve the architectural integrity of the seminiferous tubule, formalin fixation yields biopsies with relatively poor nuclear detail and frequent luminal sloughing of cells, making it difficult to assess sperm maturation. One clone of the anti-DOG1 antibody was recently found to be expressed in late (postspermatogonial) germ cells. We developed a dual stain including DOG1 and SF-1 to mark late germ cells and Sertoli cells, respectively, in both sloughed and intact cells. Consecutive testicular biopsies (N=28) from men with azoospermia were classified by hematoxylin and eosin morphology and stained with a dual SF-1 (Perseus)/DOG1 (Cell Marque) immunohistochemical stain. Histologic patterns included normal spermatogenesis (5 cases), hypospermatogenesis (5 cases), late maturation arrest (2 cases), Sertoli cell only pattern (15 cases), and extensive tubular hyalinization (1 case). Architectural disruption of seminiferous tubules with sloughing of cells into the lumens was noted in all biopsies, at least focally. SF-1 (nuclear) was expressed in sloughed Sertoli cells; DOG1 (cytoplasmic) in sloughed postspermatogonial germ cells (spermatocytes and spermatids). This resulted in two distinct immunophenotypes: SF-1(+)/DOG1(−) sloughed cells in cases with the Sertoli cell only pattern and SF-1(+)/DOG1(+) sloughed cells in all other histologic patterns (normal spermatogenesis, hypospermatogenesis, and maturation arrest). Because the rate of sperm retrieval is lower in men with the Sertoli cell only pattern, this immunohistochemical stain may assist pathologists in the proper interpretation of testicular biopsies, allowing better-informed decision making by patients and clinicians regarding the subsequent use of assisted reproductive technologies.
State of the Unit: Physician Gender Diversity in Pediatric Critical Care Medicine Leadership
Authors: Maxwell Andrea R. , Riley Carley L. , Stalets Erika L. , Wheeler Derek S. , Dewan Maya
Published: May 2019

Gender disparities in leadership are receiving increased attention throughout medicine and medical subspecialties. Little is known about the disparities in Pediatric Critical Care Medicine. In this piece, we explore gender disparities in Pediatric Critical Care Medicine physician leadership. We examine physician leadership in the Accreditation Council for Graduate Medical Education fellowship programs, as well as a limited sample of major Pediatric Critical Care Medicine textbooks and societies. Overall, the gender composition of division directors is not significantly different from that of workforce composition, although regional differences exist. More women than men lead fellowship programs, at a higher ratio compared with workforce composition. However, greater gender disparities are present in editorial leadership in this limited analysis. We conclude by recommending potential paths forward for further study and intervention, such as tracking gender diversity and being cognizant of the unique challenges that women currently experience in professional advancement.
Parent Medical Traumatic Stress and Associated Family Outcomes After Pediatric Critical Illness: A Systematic Review*
Authors: Yagiela Lauren M. , Carlton Erin F. , Meert Kathleen L. , Odetola Fola O. , Cousino Melissa K.
Published: May 2019

Objectives:

To critically review, analyze, and synthesize the literature on parent medical traumatic stress from a child’s critical illness requiring PICU admission and its association with outcomes of parent mental and physical health, and family functioning.

Data Sources:

Systematic literature search of Pubmed, Embase, CINAHL, and PsychInfo.

Study Selection:

Two reviewers identified peer-reviewed published articles with the following criteria: 1) published between January 1, 1980, and August 1, 2018; 2) published in English; 3) study population of parents of children with a PICU admission; and 4) quantitative studies examining factors associated with outcomes of parent mental health, parent physical health, or family functioning.

Data Extraction:

Literature search yielded 2,476 articles, of which 23 studies met inclusion criteria. Study data extracted included study characteristics, descriptive statistics of parent outcomes after critical illness, and variables associated with parent and family outcomes.

Data Synthesis:

Studies examined numerous variables associated with parent and family outcomes and used multiple survey measures. These variables were categorized according to their phase in the Integrative Trajectory Model of Pediatric Medical Traumatic Stress, which included peri-trauma, acute medical care, and ongoing care or discharge from care. The majority of objective elements of a child’s illness, such as severity of illness and length of hospitalization, did not have a clear relationship with parent and family outcomes. However, familial preexisting factors, a parent’s subjective experience in the PICU, and family life stressors after discharge were often associated with parent and family outcomes.

Conclusions:

This systematic literature review suggests that parent and family outcomes after pediatric critical illness are impacted by familial preexisting factors, a parent’s subjective experience in the PICU, and family life stressors after discharge. Developing parent interventions focused on modifying the parent’s subjective experience in the PICU could be an effective approach to improve parent outcomes.
Noninvasive Determination of Blood Pressure by Heart Sound Analysis Compared With Intra-Arterial Monitoring in Critically Ill Children—A Pilot Study of a Novel Approach
Authors: Kapur Gaurav , Chen Lingguang , Xu Yong , Cashen Katherine , Clark Jeff , Feng Xiaoce , Wu Sean F.
Published: May 2019

Objectives:

To develop a novel device to predict systolic and diastolic blood pressure based on measured heart sound signals and evaluate its accuracy in comparison to intra-arterial blood pressure readings.

Study Design:

Prospective, observational pilot study.

Setting:

PICU.

Patients:

Critically ill children (0–18 yr) undergoing continuous blood pressure monitoring via radial artery intra-arterial catheters were enrolled in the study after informed consent. The study included medical, cardiac, and surgical PICU patients.

Interventions:

Along with intra-arterial blood pressure, patient’s heart sounds were recorded simultaneously by a highly sensitive sensor taped to the chest. Additional hardware included a data acquisition unit and laptop computer. Subsequently, advanced signal processing technologies were used to minimize random interfering signals and extract and separate S1 and S2 signals. A computerized model was then developed using artificial neural network systems to estimate blood pressure from the extracted heart sound analysis.

Measurements and Main Outcomes:

We found a statistically significant correlation for systolic (r = 0.964; R
2 = 0.928) and diastolic (r = 0.935; R
2 = 0.868) blood pressure readings (n = 491) estimated by the novel heart-sound signal–based method and those recorded by intra-arterial catheters. The mean difference of the individually paired determinations of the blood pressure between the heart-sound–based method and intra-arterial catheters was 0.6 ± 7 mm Hg for systolic blood pressure and –0.06 ± 5 mm Hg for diastolic blood pressure, which was within the recommended range of 5 ± 8 mm Hg for any new blood pressure devices.

Conclusions:

Our findings provide proof of concept that the heart-sound signal-based method can provide accurate, noninvasive blood pressure monitoring.
Utilizing Electronic Laboratory Reporting Data to Assess the Burden of Hepatitis C in Arizona
Authors: Tsang Clarisse A. , Khan Mohammed A. , Brady Shane M. , Erhart Laura M. , Komatsu Kenneth K.
Published: May 2019

Context:

Hepatitis C virus (HCV) infections must be reported to public health departments in Arizona; however, Arizona Department of Health Services has not had the resources to conduct comprehensive HCV surveillance since 2008 and thus monitoring HCV is difficult. Cases were traditionally reported via mail, fax, or telephone; however, beginning in 2009, clinical laboratories could report HCV results through electronic laboratory reporting (ELR).

Objective:

To assess completeness of ELR in capturing HCV case reports and its utility for HCV surveillance and describing the current burden of HCV.

Design:

Two components of study: (1) HCV reporting from all sources for 2 months in 2015 was de-duplicated at the patient level and cross-matched with the 1998-2008 database and 2009-2015 ELR data to identify cases newly reported during the 2-month period and calculate the proportion reported through ELR. (2) HCV ELR results during 2009-2015 were similarly de-duplicated and compared with the 1998-2008 database to identify newly reported cases.

Setting:

Hepatitis C virus patients reported to Arizona Department of Health Services.

Participants:

Hepatitis C virus case patients reported during 1998-2008 and through ELR during 2009-2015. Hepatitis C virus patients through paper reports for January and June 2015.

Main Outcome Measures:

(1) Using 2 months of all HCV reporting in 2015 to examine the proportion of cases captured by ELR and the differences in the type of reports captured by ELR and non-ELR sources only. (2) Compared sex, birth year, viral load, and genotype from ELR-only data to other surveillance data.

Results:

Electronic laboratory reporting accounted for 1260 (64%) HCV cases newly reported during the 2 months, with 698 (36%) newly identified from non-ELR sources only. Based on these findings, an estimated 11 534 HCV cases were newly reported in 2015 (172 cases per 100 000 population). During 2009-2015, a substantial amount (23%) of newly reported cases were among persons born after 1978.

Conclusions:

Utilizing ELR data alone can provide meaningful HCV surveillance and offers a less resource-intensive means to describe HCV burden and identify trends in newly reported cases. An assessment like this one can provide a tool for HCV monitoring in other jurisdictions that lack resources for HCV surveillance as more laboratories transition to ELR.
Brief Report: Cofactors of Mortality Among Hospitalized HIV-Infected Children Initiating Antiretroviral Therapy in Kenya
Authors: Njuguna Irene N. , Cranmer Lisa M. , Wagner Anjuli D. , LaCourse Sylvia M. , Mugo Cyrus , Benki-Nugent Sarah , Richardson Barbra A. , Stern Joshua , Maleche-Obimbo Elizabeth , Wamalwa Dalton C. , John-Stewart Grace
Published: May 2019

Objectives:

Identifying factors associated with mortality among acutely ill HIV-infected children presenting with advanced HIV disease may help clinicians optimize care for those at highest risk of death.

Design:

Using data from a randomized controlled trial (NCT02063880), we determined baseline sociodemographic, clinical, and laboratory cofactors of mortality among HIV-infected children in Kenya.

Methods:

We enrolled hospitalized, HIV-infected, antiretroviral therapy–naive children (0–12 years), initiated antiretroviral therapy, and followed up them for 6 months. We used Cox proportional hazards regression to estimate hazard ratios (HRs) for death and 95% confidence intervals (CIs).

Results:

Of 181 enrolled children, 39 (22%) died. Common diagnoses at death were pneumonia or suspected pulmonary tuberculosis [23 (59%)] and gastroenteritis [7 (18%)]. Factors associated with mortality in univariate analysis included age <2 years [HR 3.08 (95% CI: 1.50 to 6.33)], orphaned or vulnerable child (OVC) [HR 2.05 (95% CI: 1.09 to 3.84)], weight-for-age Z score <−2 [HR 2.29 (95% CI: 1.05 to 5.00)], diagnosis of pneumonia with hypoxia [HR 5.25 (95% CI: 2.00 to 13.84)], oral thrush [HR 2.17 (95% CI: 1.15 to 4.09)], persistent diarrhea [HR 3.81 (95% CI: 1.89 to 7.69)], and higher log10 HIV-1 viral load [HR 2.16 (95% CI: 1.35 to 3.46)] (all P < 0.05). In multivariable analysis, age <2 years and OVC status remained significantly associated with mortality.

Conclusions:

Young age and OVC status independently predicted mortality. Hypoxic pneumonia, oral thrush, and persistent diarrhea are important clinical features that predict mortality. Strategies to enhance early diagnosis in children and improve hospital management of critically ill HIV-infected children are needed.
Olfactory Impairment and Hippocampal Volume in a Chinese MCI Clinical Sample
Authors: Yu Hong-li , Chen Zhi-juan , Zhao Ji-wei , Duan Shu-rong , Zhao Jing-kun
Published: May 2019

Purpose:

The aim of this study was to evaluate the relationship between olfactory function and hippocampal volume in patients with mild cognitive impairment (MCI).

Methods:

We enrolled a total of 31 MCI patients and 9 normal control subjects. All participants underwent 3.0 T-magnetic resonance imaging scanning. The scan results were processed using GE ADW4.6 processing software and V0xar 3D workstation to acquire the hippocampal volume. The University of Pennsylvania Smell Identification Test (UPSIT) was used to evaluate the olfactory function of MCI patients. The correlations of UPSIT score with hippocampal volume and hippocampal head volume were evaluated by Pearson correlation coefficient analysis.

Results:

MCI patients had significantly smaller left (2.78±0.50 vs. 3.19±0.31 cm3) and right (2.97±0.42 vs. 3.31±0.25 cm3) hippocampal volumes compared with normal controls (P<0.05). In addition, patients with olfactory dysfunction had smaller volumes of the hippocampus (left hippocampal volume, 2.57±0.39 vs. 3.23±0.40 cm3; right hippocampal volume, 2.86±0.43 vs. 3.22±0.30 cm3) and hippocampal head (left hippocampal head volume, 1.18±0.16 vs. 1.53±0.25 cm3; right hippocampal head volume, 1.25±0.22 vs. 1.54±0.22 cm3) compared with those with normal olfactory function (P<0.05). No significant difference in the hippocampal body volume and hippocampal tail volume was found between MCI patients with olfactory loss and those with normal olfactory function. The UPSIT score was significantly positively correlated with left hippocampal volume (r=0.55, P<0.05), right hippocampal volume (r=0.42, P<0.05), left hippocampal head volume (r=0.53, P<0.05), and right hippocampal head volume (r=0.45, P<0.05).

Conclusions:

Olfactory function correlates well with hippocampal volume among patients with MCI.