bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision medicine in autoimmune diseases: fact or fiction
Authors: Toro-Domínguez Daniel , Alarcón-Riquelme Marta E
Published: May 2021

Much is said about precision medicine, but its real significance and potential are far from certain. Several studies in each of the autoimmune diseases have provided important insights into molecular pathways, but the use of molecular studies, particularly those looking into transcriptome pathways, has seldom approached the possibility of using the data for disease stratification and then for prediction, or for diagnosis. Only the type I IFN signature has been considered for therapeutic purposes, particularly in the case of SLE. This review provides an update on precision medicine, on what can be translated into clinical practice and on what single-cell molecular studies contribute to our knowledge of autoimmune diseases, focusing on a few examples. The main message is that we should try to move from precision medicine of established diseases to preventive medicine in order to predict the development of disease.
The Political Underrepresentation of People with Disabilities in the Japanese Diet
Authors: OKURA Sae
Published: May 2021

This paper examines the political underrepresentation of people with disabilities in the Japanese Diet and the conditions that allow their participation in the body. The paper addresses the following three research questions: (a) how are people with disabilities represented in contemporary Japan and the EU member states, and what are the differences between them?; (b) why have people with disabilities been underrepresented in Japan? and (c) how do candidates with disabilities but lacking typical political careers become members of the Diet? This paper further discusses the electoral system, political parties' attitudes toward people with disabilities, social and community participation of people with disabilities, and political culture as factors that affect minority groups' participation in the Japanese Diet. Key findings: (a) a comparison with EU member states shows that the underrepresentation of people with disabilities in parliamentary bodies is a common issue; (b) people with disabilities are less involved in traditional political communities and society in general, which hampers their participation in the parliament and (c) in the immediate postwar period disabled Diet members were mainly wounded people with typical political careers, but from the 1990s onwards disabled people without typical political careers became Diet members. Moreover, the proportional electoral system and political parties' stronger commitment to include candidates with disabilities facilitated the increase in disabled membership.
Revealing the salt tolerance mechanism of Tamarix hispida by large-scale identification of genes conferring salt tolerance
Authors: Wang Zhibo , He Zihang , Xu Xin , Shi Xinxin , Ji Xiaoyu , Wang Yucheng
Published: May 2021

The identification of genes conferring salt tolerance is important to reveal plant salt tolerance mechanisms. Here, we employed yeast expression system combined with high-throughput sequencing to identify genes conferring salt tolerance from Tamarix hispida Willd. A total of 1224 potential genes conferring salt tolerance were identified. Twenty-one genes were randomly selected for functional characterization using transient transformation in T. hispida and stable transformation in Arabidopsis thaliana (L.) Heynh. More than 90% of studied genes are found to confer tolerance to salt stress, indicating that the identified genes are reliable. More than 75% of the identified genes were highly expressed in roots rather than in leaves, suggesting roots play an important role in salt tolerance. The genes belonging to ‘response to stimulus’ were highly accumulated , and these accounted for 32% of the total identified genes. In addition, the processes of ‘protein translation’, ‘osmotic adjustment’, ‘scavenging of free radicals’, ‘photosynthesis, detoxification of cells’, ‘protection of cellular macromolecules’ and ‘maintenance of cellular pH’ play important roles in salt tolerance. This study provides useful information on the salt tolerance mechanism of T. hispida and offers a valuable resource for exploring genes used in salt tolerance breeding.
Review of condition monitoring and fault diagnosis for marine power systems
Authors: Xu Xiaojian , Yan Xinping , Yang Kun , Zhao Jiangbin , Sheng Chenxing , Yuan Chengqing
Published: May 2021

The use of condition monitoring and fault diagnosis (CMFD) in marine power systems significantly influences ship safety. This study divides the development of CMFD for marine power systems into three periods and reviews the content, state and limitations of CMFD research for each period. According to the research achievements and engineering experience of the authors’ team, typical application cases are introduced for CMFD in ships, including CMFD platforms on engineering ships, salvage ships, container ships and ro-ro ships powered by solar photovoltaic systems. Finally, prospective research directions are proposed for CMFD in marine power systems, considering the research status of CMFD and the trend toward intelligent and eco-friendly ships.
Challenges in Managing Charcot Arthropathy
Authors: Hearty Thomas
Published: May 2021

Charcot arthropathy is a disabling disease and difficult to manage. The diagnosis can often be unclear because of limited accuracy of testing and differentiating it from infection can be a challenge. Whether to operate, the timing of the operation and the type of operation are wide ranging variables and there is no real consistent treatment recommendation based on strong evidence. This article presents case scenarios that are commonly seen in the orthopedic foot and ankle clinic to demonstrate the challenges the clinician faces in dealing with this difficult diagnosis.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Impact of Duration of N-Acetylcysteine in Non-Acetaminophen–Induced Acute Liver Failure
Authors: Bass Stephanie N. , Lumpkin Mollie , Mireles-Cabodevila Eduardo , Lindenmeyer Christina C. , Dolan Bridget , Pickett Caleigh , Kapoor Aanchal
Published: May 2021

OBJECTIVES:

Studies of the use of IV N-acetylcysteine in the management of non-acetaminophen-induced acute liver failure have evaluated various dosing regimens. The only randomized trial studying this application described a 72-hour regimen. However, observational studies have reported extended duration until normalization of international normalized ratio. This study seeks to compare differences in patient outcomes based on IV N-acetylcysteine duration.

DESIGN:

Retrospective cohort study.

SETTING:

Medical ICU at a large quaternary care academic medical institution and liver transplant center.

PATIENTS:

Adult patients admitted to the medical ICU who received IV N-acetylcysteine for the treatment of non-acetaminophen-induced acute liver failure.

INTERVENTIONS:

Patients were divided into cohorts based on duration; standard duration of IV N-acetylcysteine was considered 72 hours, whereas extended duration was defined as continuation beyond 72 hours.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was time to normalization of international normalized ratio to less than 1.3 or less than 1.5; secondary outcomes included all-cause mortality and transplant-free survival at 3 weeks. In total, 53 patients were included: 40 in the standard duration cohort and 13 in the extended duration. There were no major differences in baseline characteristics. There was no significant difference in time to international normalized ratio normalization between cohorts. Transplant-free survival was higher with extended duration (76.9% extended vs 41.4% standard; p = 0.03). All-cause mortality at 3 weeks was numerically lower in the extended duration group (0% extended vs 24.1% standard; p = 0.08).

CONCLUSIONS:

Patients with non-acetaminophen-induced acute liver failure who received extended duration N-acetylcysteine were found to have significantly higher transplant-free survival than patients who received standard duration, although there was no significant difference in time to normalization of international normalized ratio or overall survival. Prospective, randomized, multicenter study is warranted to identify subpopulations of patients with non-acetaminophen-induced acute liver failure who could benefit from extended treatment duration as a bridge to transplant or spontaneous recovery.
A Multicenter Evaluation of Survival After In-Hospital Cardiac Arrest in Coronavirus Disease 2019 Patients
Authors: Bhardwaj Abhishek , Alwakeel Mahmoud , Saleem Talha , Afzal Saira , Alqaisi Sura , Saand Aisha R. , Najjar Hanan Al. , Griffiths Lori , Han Xiaozhen , Wang Xiaofeng , Perez-Protto Silvia , Abella Benjamin S. , Gaieski David F. , Duggal Abhijit , Abi Fadel Francois
Published: May 2021

IMPORTANCE:

In-hospital cardiac arrest survival among coronavirus disease 2019 patients has been reported to range from 0% to 12%. These numbers are significantly lower than reported prepandemic in-hospital cardiac arrest survival rates of approximately 20–25% in the United States for non–coronavirus disease 2019 patients.

OBJECTIVE:

To assess the incidence of in-hospital cardiac arrest survival of coronavirus disease 2019 patients.

DESIGN:

A retrospective cohort study of adult patients with coronavirus disease 2019 subsequently found to have in-hospital cardiac arrest and underwent cardiopulmonary resuscitation (cardiopulmonary resuscitation).

SETTING:

Multiple hospitals of the Cleveland Clinic Health System.

PATIENTS:

All adult patients (age ≥ 18 yr) admitted to Cleveland Clinic Health System with a diagnosis of coronavirus disease 2019 who experienced in-hospital cardiac arrest requiring cardiopulmonary resuscitation.

MEASUREMENTS AND MAIN RESULTS:

From March 01, 2020 to October 15, 2020, 3,555 patients with coronavirus disease 2019 were hospitalized; 1,372 were admitted to the ICU; 58 patients had in-hospital cardiac arrest. Median age of this cohort was 66.5 years (interquartile range, 55.0–76.0 yr). Patients were predominantly male (62.5%), White (53.4%), with a median body mass index of 29.7 (interquartile range, 25.8–34.6). Most in-hospital cardiac arrests were in critical care environments (ICU), 51 of 58 (87.9%); seven of 58 (12.1%) were on ward locations. Thirty-four of 58 patients (58.6%) were on mechanical ventilation prior to in-hospital cardiac arrest with a median duration of mechanical ventilation of 9 days (interquartile range, 2–18 d). Twenty-four of 58 patients (44%) were on vasopressors prior to arrest. Initial arrest rhythm was pulseless electrical activity at (63.8%), asystole (29.3%), and pulseless ventricular tachycardia/fibrillation (6.9%). Of the 58 patients, 35 (60.3%) attained return of spontaneous circulation, and 13 of 58 (22.4%) were discharged alive.

CONCLUSIONS:

We report a 22% survival to discharge after in-hospital cardiac arrest in coronavirus disease 2019 patients, a survival rate similar to before the coronavirus disease 2019 pandemic.
Educational level and colorectal cancer risk: the mediating roles of lifestyle and dietary factors
Authors: Li Lei , Fang Yu-Jing , Abulimiti Alinuer , Huang Chu-Yi , Liu Kai-Yan , Chen Yu-Ming , Zhang Cai-Xia
Published: May 2021

Objective

The association between the educational level and colorectal cancer risk was controversial in developed countries and evidence was limited in Chinese population. This study aimed to investigate the association between the educational level and colorectal cancer risk in Guangdong Province, China.

Methods

From July 2010 to April 2019, 2502 newly diagnosed colorectal cancer patients and 2538 sex- and age-matched controls were recruited in this case–control study. Multivariable logistic regression models were used to examine the association between the educational level and colorectal cancer risk. Path analysis was used to investigate whether behavioral risk factors potentially mediated the association between the educational level and colorectal cancer risk.

Results

Educational level was inversely associated with the colorectal cancer risk. People who graduated from the college or above had a lower risk of colorectal cancer than those from the primary school or below, with an adjusted odds ratio of 0.42 [95% confidence intervals (CI), 0.34–0.52]. The total, direct and indirect effects of the educational level for the colorectal cancer risk were statistically significant in the path diagram. Path analysis showed that lower red and processed meat intake and higher tea and coffee drinking among high educational participants contributed to the inverse association between the educational level and colorectal cancer risk.

Conclusion

The findings suggested that the educational level was inversely associated with the colorectal cancer risk. The association might be mediated by red and processed meat intake, household and leisure-time activities, and tea and coffee drinking.
Two factors affecting the success rate of the second non-invasive prenatal screening after initial no-call result: experience from a single tertiary center in China
Authors: Lin Ying , Liang Dong , Li Hang , Luo Chun-Yu , Hu Ping , Xu Zheng-Feng
Published: May 2021

Background:

One inevitable shortcoming of non-invasive prenatal screening (NIPS)/cell-free DNA (cfDNA) sequencing is the uninterpretable (“no-call”) result, which is mainly caused by an insufficient fetal fraction. This study was performed to investigate the factors associated with a successful second NIPS in these cases and determine the optimal management for women with initial no-call results.

Methods:

We retrospectively analyzed the data of women who underwent NIPS with initial no-call results due to an insufficient fetal fraction from 2017 to 2019 in our center. We compared these women's maternal and pregnancy information with the data of women who had attained a successful second NIPS result and women who had received no-call results for a second time.

Results:

Among the 33,684 women who underwent NIPS, 137 with a no-call result underwent a retest. Comparison between the 87 (63.50%) women with a successful retest and the other 50 (36.50%) women showed a significant difference in both the initial fetal fraction and maternal body mass index (BMI), whereas the other factors showed no significant differences. In addition, with an initial fetal fraction of < 2.00%, the retest success rate was very limited.

Conclusions:

We identified two major factors associated with a successful NIPS retest: the initial fetal fraction and the maternal BMI. These findings suggest the need for specialized management for this subset of women and would be instructional for the counseling for these women.
Expression of p40 in Primary Cutaneous Mucinous Carcinoma Versus Primary Mucinous Carcinomas of the Breast and Colon
Authors: Chung Jina , Rico-Castillo Jesus , Sebastiano Christopher , Lee Jason B.
Published: May 2021

Background:

The transcription factor p63 is a homolog of p53, expressed in basal layers of epithelia and myoepithelial cells. Some studies have suggested that p63 may provide utility in differentiating primary versus metastatic mucinous carcinoma of the skin, given its preferential expression in primary adnexal neoplasms. There have been few studies investigating the expression patterns of p40, an isoform of p63, in primary cutaneous mucinous carcinomas.

Methods:

An immunohistochemical panel including p40, CK7, CK20, estrogen receptor, and progesterone receptor was applied to primary mucinous carcinomas of the skin, breast, and colon.

Results:

Only a small subset (25%) of primary cutaneous mucinous carcinomas displayed focal positive staining with p40, similar to what has been reported in the literature for p63. All primary mucinous carcinomas of skin and breast labeled positively with CK7, estrogen receptor, and progesterone receptor. Primary colon mucinous carcinomas were only positive for CK20.

Conclusions:

Based on these results, p40 seems to be an insufficient marker for distinguishing primary versus metastatic mucinous carcinoma due to its low rate of positivity in primary cutaneous mucinous carcinomas.
Cutaneous Langerhans Cell Histiocytosis as Presenting Sign of Systemic B-Cell Lymphoma
Authors: Beatty Colleen , Okal Ryan , Lynch Michael C.
Published: May 2021

Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder most commonly involving the bone and skin; however, it can arise in many other locations. It is predominantly a pediatric disease, but adult cases occur. Here, we present a case of adult-onset cutaneous LCH with systemic symptoms, believed to represent disseminated LCH. Further evaluation, however, revealed concomitant bone marrow involvement by a small B-cell lymphoma. An association between B-cell lymphoma and cutaneous LCH has only rarely been previously reported. This report adds to the growing body of literature, however, on associations of cutaneous LCH with hematologic malignancies, and it illustrates the need for a complete systemic evaluation including a bone marrow biopsy in suspected cases of disseminated LCH.
Unusual Case of a Caruncular Oncocytoma
Authors: Vaidya Parth R. , Simpson Sarah E. , Phillips Mariana A. , Ramey Nicholas A. , Grider Douglas J.
Published: May 2021

Oncocytomas are benign neoplasms that are most often found in the salivary glands and kidneys. Ocular oncocytoma typically present as an asymptomatic dark blue papule on the lacrimal caruncle. Histologically, the tumor is composed of oncocytes, cells notable for eosinophilic cytoplasmic granules representing large quantities of dysfunctional mitochondria. The neoplastic proliferation may be partially or totally encapsulated and may be surrounded by myoepithelial cells. Discussed is the pathophysiology and histopathology of an ocular oncocytoma from the right lacrimal caruncle of a 68-year-old man. The patient complained of a foreign body sensation and tearing associated with a purpuric 1 × 1-mm papule of the right caruncle that had been present for 6 months. An excisional biopsy showed an oxyntic neoplasm with small cystic glandular spaces associated with goblet cells and mucin, confirmed by mucicarmine stain. Given the rarity of ocular oncocytomas and presence of mucin, exclusion of an endocrine mucin-producing sweat gland carcinoma was necessary. Peripheral myoepithelial cells noted on p63 immunostaining are seen in both endocrine mucin-producing sweat gland carcinoma and oncocytomas. However, endocrine mucin-producing sweat gland carcinoma is excluded by the presence of goblet cells, the uniform oxyphilic cytoplasm of the epithelial cells, and the negative immunohistochemical staining for neuron-specific enolase, chromogranin, synaptophysin, estrogen receptor, and progesterone receptor. Complete surgical excision is the treatment of choice for oncocytomas. This case highlights the clinical and histopathological presentation of ocular oncocytomas and raises awareness of this rare entity for both the practicing dermatologist and dermatopathologist.
Validated Outcome Measures and Postsurgical Scar Assessment Instruments in Eyelid Surgery: A Systematic Review
Authors: Ramanathan Diya , Chu Sherman , Prendes Mark , Carroll Bryan T.
Published: May 2021

BACKGROUND

Determining which postsurgical scar assessment instruments, if any, cover important eyelid outcome measures can either attest to the strength of one or more instruments or reveal the need for a more comprehensive scale.

OBJECTIVE

To systematically review validated outcome measures after eyelid surgery and postsurgical scar assessment tools to see whether any individual or combination of 2 assessment tools encompass all relevant, validated eyelid outcome measures.

METHODS

Systematic reviews of validated eyelid outcome measures and postsurgical scar assessment tools were conducted using PubMed/MEDLINE and Ovid. Outcome measure papers that met inclusion criteria were sorted into 8 categories: Patient Subjective, Visual Function, Mechanical Function, Daily Activities, Adverse Effects, Aesthetic Quantitative: Clinical Measurements, Aesthetic Qualitative: Global, and Aesthetic Qualitative: Specific. Outcome measure papers were categorized into tiers of evidence support, and assessment tools were evaluated based on which outcome measures each covered.

RESULTS

No one or combination of 2 assessment tools covered all selected eyelid outcome measures. Although measures related to the subjective patient experience were included in several of the assessment scales, none covered measures of visual function or eyelid-specific clinical measurements.

CONCLUSION

There is currently no existing postsurgical scar assessment instrument that covers all important eyelid-specific outcome measures.
AUTOLOGOUS NEUROSENSORY RETINAL TRANSPLANTATION
Authors: Patel Saagar N. , Mahmoud Tamer H. , Kazahaya Masayuki , Todorich Bozho
Published: May 2021

Purpose:

To review the autologous retinal transplantation surgical technique, indications, rationale, and current outcomes of data published to date.

Methods:

Review of surgical technique, preoperative and postoperative best-corrected visual acuity, and macular hole (MH) closure rate in studies with at least five eyes.

Results:

The weighted average macular hole closure rate is 88%, with a MH closure rate ranging from 66.7% to 100%. The weighted average best-corrected visual acuity improved from mean logarithm of the minimum angle of resolution 1.35 (Snellen equivalent of 20/450) preoperatively to mean logarithm of the minimum angle of resolution 1.02 (Snellen equivalent of 20/210) postoperatively. From the largest autologous retinal transplantation case series, 37% of patients gained 3 or more lines of visual acuity after autologous retinal transplantation for primary or refractory MHs and 74% gained 3 or more lines of visual acuity after autologous retinal transplantation for MH–retinal detachments. Functional improvement including negative Watzke–Allen sign and conversion from positive to negative scotoma was reported in large case series.

Conclusion:

Autologous retinal transplantation is a promising technique for closure of large and refractory MHs otherwise difficult to repair with conventional techniques. This technique may allow for replacement of neural tissue in the macula through cell rehabilitation and regeneration through presumed ectopic synaptogenesis, retinal progenitor cell differentiation and integration, and/or retinal progenitor cell material transfer to host neurons.
Neurotrophic keratopathy and refractive surgery
Authors: Kristan Joseph , Kang Joann J.
Published: May 2021

Purpose of review

Corneal nerve function is an important consideration for the refractive surgeon. In patients without a history of neuropathy, refractive surgery can lead to destruction of corneal nerves and may predispose to keratopathy. The purpose of this review is to provide an update on the effect of refractive surgery on corneal nerve function and the potential for an increased risk of neurotrophic keratopathy development.

Recent findings

Recent studies have reinforced that refractive surgery can cause anatomical and functional changes in corneal nerve function. Among the most commonly performed refractive surgery procedures are Laser Assisted In-situ Keratomileusis, Photorefractive Keratectomy, and Small Incision Lenticule Extraction. Due to differences in technique, these procedures can have varying effects on corneal nerve structure. Using in vivo confocal microscopy, postrefractive patients were found to have decreased total nerve density when compared with controls in the immediate postoperative period. In some studies, patients have been shown to undergo re-innervation and regain significant amounts of nerve function. The majority of studies have found that despite decreased nerve cell density, long-term outcomes of refractive surgery patients are generally favorable. However, loss of corneal nerve function can lead to a variety of serious effects ranging from dry eye disease, corneal hypoesthesia/anesthesia, neuropathic pain, to neurotrophic keratopathy and ulceration in the rare cases.

Neurotrophic keratopathy is a rare occurrence after keratorefractive surgery and is largely due to damage to corneal nerves. Proper patient selection and counseling are essential to decrease the risk of development of this devastating complication.
Left Ventricular Decompression by Transaortic Catheter Venting in Extracorporeal Membrane Oxygenation
Authors: Jung Jae Jun , Kang Dong Hoon , Moon Seong Ho , Yang Jun Ho , Kim Sung Hwan , Kim Jong Woo , Byun Joung Hun
Published: May 2021

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely applied to patients with cardiogenic shock. Left ventricle (LV) decompression is important when LV distension develops with pulmonary edema. The purpose of this study was to present the results of transaortic catheter venting (TACV) performed during VA-ECMO. We retrospectively reviewed the medical records of 18 patients who underwent both VA-ECMO and TACV between January 2017 and December 2019. Venoarterial extracorporeal membrane oxygenation was applied uneventfully. Lactate level and norepinephrine requirement for patients of weaning success were lower than those of patients of weaning failure after the application of TACV (p = 0.032 and p = 0.015, respectively). The successful weaning rate of ECMO was 77.8% (15/18) and survival rate was 50% (9/18). Transaortic catheter venting may be an easy, safe, and effective technique for LV decompression in patients with VA-ECMO for cardiogenic shock. Also, this technique may be helpful as an alternative or bridge method.
Hemodynamic Predictors of Renal Function After Pediatric Left Ventricular Assist Device Implantation
Authors: Chen Chiu-Yu , Montez-Rath Maria E. , May Lindsay J. , Maeda Katsuhide , Hollander Seth A. , Rosenthal David N. , Krawczeski Catherine D. , Sutherland Scott M.
Published: May 2021

Although renal function often improves after pediatric left ventricular assist device (LVAD) implantation, recovery is inconsistent. We aimed to identify hemodynamic parameters associated with improved renal function after pediatric LVAD placement. A single-center retrospective cohort study was conducted in patients less than 21 years who underwent LVAD placement between June 2004 and December 2015. The relationship between hemodynamic parameters and estimated glomerular filtration rate (eGFR) was assessed using univariate and multivariate modeling. Among 54 patients, higher preoperative central venous pressure (CVP) was associated with eGFR improvement after implantation (p = 0.012). However, 48 hours postimplantation, an increase in CVP from baseline was associated with eGFR decline over time (p = 0.01). In subgroup analysis, these associations were significant only for those with normal pre-ventricular assist device renal function (p = 0.026). In patients with preexisting renal dysfunction, higher absolute CVP values 48 and 72 hours after implantation predicted better renal outcome (p = 0.005). Our results illustrate a complex relationship between ventricular function, volume status, and renal function. Additionally, they highlight the challenge of using CVP to guide management of renal dysfunction in pediatric heart failure. Better methods for evaluating right heart function and volume status are needed to improve our understanding of how hemodynamics impact renal function in this population.
Cyclohexanone Exposure in Children on Extracorporeal Membrane Oxygenation Support
Authors: Bembea Melania M. , Ng Derek K. , Carroll Megan , Roem Jennifer L. , Groopman John , Caprarola Sherrill D. , McElrath Schwartz Jamie , Felling Ryan J. , Salorio Cynthia F. , Ellis Greg , Graham David , Everett Allen D.
Published: May 2021

The aim of this study was to determine if plasma cyclohexanone and metabolites are associated with clinical outcomes of children on extracorporeal membrane oxygenation (ECMO) support. We performed a secondary analysis of a prospective observational study of children on ECMO support at two academic centers between July 2010 and June 2015. We measured plasma cyclohexanone and metabolites on the first and last days of ECMO support. Unfavorable outcome was defined as in-hospital death or discharge Pediatric Cerebral Performance Category score > 2 or decline ≥ 1 from baseline. Among 90 children included, 49 (54%) had unfavorable outcome at discharge. Cyclohexanediol, a cyclohexanone metabolite, was detected in all samples and at both time points; concentrations on the first ECMO day were significantly higher in those with unfavorable versus favorable outcome at hospital discharge (median, 5.7 ng/µl; interquartile range [IQR], 3.3–10.6 ng/µl vs. median, 4.2 ng/µl; IQR, 1.7–7.3 ng/µl; p = 0.04). Twofold higher cyclohexanediol concentrations on the first ECMO day were associated with increased risk of unfavorable outcome at hospital discharge (multivariable-adjusted hazard ratio [HR], 1.24 [95% CI, 1.05–1.48]). Higher cyclohexanediol concentrations on the first ECMO day were not significantly associated with new abnormal neuroimaging or 1-year Vineland Adaptive Behavior Scales-II score < 85 or death among survivors.
First Report of Proton Beam Therapy in a Patient With a Left Ventricular Assist Device
Authors: Schumer Erin M. , Schettle Sarah , Stulak John M. , Rosenbaum Andrew N.
Published: May 2021

A 77 year old man previously implanted with a HeartMate II left ventricular assist device (LVAD) as destination therapy and an implantable cardioverter defibrillator presented with a left upper lobe squamous cell lung cancer. Oncology determined that proton beam therapy was indicated for treatment, and a multidisciplinary team of radiation physicists, radiation oncologists, and LVAD providers developed a protocol to proceed safely. He was successfully treated with combined proton beam radiation therapy and reduced dose chemotherapy. This case demonstrates feasibility and considerations of proton beam therapy for malignancy relevant to patients with implantable cardiac devices including LVADs.
The HeartMate 6 and CardioMEMS for Fixed Pulmonary Hypertension
Authors: Angleitner Philipp , Schlöglhofer Thomas , Wiedemann Dominik , Riebandt Julia , Strassl Andreas , Mascherbauer Julia , Kainz Matthias , Laufer Günther , Zuckermann Andreas , Zimpfer Daniel
Published: May 2021

Fixed pulmonary hypertension (FPH) is a contraindication for heart transplantation (HTX). However, this condition might be reversed by continuous left-ventricular unloading with a left-ventricular assist device. We present a case of apical hypertrophic cardiomyopathy with extensive left-ventricular endocardial calcification and severe FPH (systolic pulmonary artery pressure, 102 mm Hg). To bridge the patient to candidacy for HTX, two Abbott HeartMate 3 ventricular assist devices were implanted in a total artificial heart (TAH) configuration (“HeartMate 6”). Before TAH implantation, an Abbott CardioMEMS pressure sensor was implanted to assess reversal of FPH before listing for HTX.
Acute kidney injury in COVID-19: are kidneys the target or just collateral damage? A comprehensive assessment of viral RNA and AKI rate in patients with COVID-19
Authors: Enikeev Dmitry , Taratkin Mark , Efetov Sergey , Shlomina Alexandra , Boldyreva Margarita , Galkina Irina , Spivak Leonid , Gitel Evgeniy , Kuchieva Agunda , Mikhailov Vasiliy , Teoh Jeremy Yuen-Chun , Herrmann Thomas R.W. , Kikic Željko , Fomin Viktor , Shariat Shahrokh F. , Glybochko Petr
Published: May 2021

Purpose of review

To investigate the possible effects of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) on kidney function and assess the rate of viral ribonucleic acid (RNA) shedding/detection in urine.

Recent findings

Most of the research on the topic suggests that for the moment our ability to estimate whether SARS-CoV-2 is a direct causative agent in acute kidney injury (AKI) or whether it has a cytokine storm effect is limited. During our prospective assessment of 333 patients with COronaVIrus Disease 2019 (COVID-19) it was found that frequency of AKI of 9.6% (32 cases). Despite previous data suggestive of the ability to detect SARS-CoV-2 in urine, we were unable to identify any traces of messenger ribonucleic acid (mRNA) in our group. Both COVID-19 severity (odds ratio, OR = 23.09, confidence interval, CI 7.89–67.57, P < 0.001) and chronic kidney disease (CKD) history (OR = 7.17, CI 2.09–24.47, P = 0.002) were associated with the AKI rate.

AKI is a relatively frequent condition for patients with COVID-19 and is normally correlated with the severity of the disease and the patient's history of CKD. The available data fail to address whether SARS-CoV-2 mRNA is present in urine, whereas our prospective trial data suggest that mRNA is undetectable in urine irrespective of the severity of the disease.
Nurse Listening as Perceived by Patients
Authors: Loos Nancy Mestler
Published: May 2021

OBJECTIVE

The purpose of this qualitative research study was to ascertain which nurse behaviors a subsection of adults 50 years and older who had had a recent inpatient admission believed conveyed nurse listening.

BACKGROUND

Listening by nurses has been identified as one of the factors with the greatest impact on patients' overall rating of their hospital experience. The behaviors of nurses that lead to patients' perceptions that listening has occurred have been unexamined, thus hampering attempts at improvement.

METHODS

Because of lack of literature support, a qualitative study using interpretative phenomenological analysis was undertaken to elicit a rich description of patients' lived experiences related to nurse listening behaviors.

RESULTS

Study participants provided specific behaviors, both verbal and nonverbal, which led them to believe the nurse was either listening or not. These perceptions affected their sense of safety and ability to trust.

CONCLUSIONS

Embracing these described behaviors could significantly impact patients' safety and recovery.
Characterizing Health Literacy Among Spanish Language-Preferring Latinos Ages 50–75
Authors: Christy Shannon M. , Cousin Lakeshia A. , Sutton Steven K. , Chavarria Enmanuel A. , Abdulla Rania , Gutierrez Liliana , Sanchez Julian , Lopez Diana , Gwede Clement K. , Meade Cathy D.
Published: May 2021

Background

Cultural background, language, and literacy are factors that may affect access, healthcare utilization, and cancer screening behaviors.

Objective

This study aimed to characterize health literacy among Spanish-preferring Hispanic/Latino individuals ages 50–75 and examine associations between sociodemographic characteristics, health beliefs, and health literacy.

Methods

Participants self-identified as Hispanic/Latino, preferring health information in Spanish, were ages 50–75 years old, at average risk for colorectal cancer (CRC), not up to date with CRC screening, and enrolled in a CRC screening education intervention trial. Sociodemographic characteristics, health beliefs, and health literacy (i.e., difficulty understanding written health information and confidence completing health forms) were assessed at baseline. Descriptive and logistic regression analyses were performed.

Results

Fifty-three percent of participants reported either sometimes having difficulty or always having difficulty with written health information, and 25% reported always asking for help or being not so confident in completing health forms. Univariate predictors of adequate health literacy for written health information were lower cancer worry and lower religious beliefs. Higher educational attainment predicted confidence in completing health forms.

Conclusions

Findings highlight the need for interventions that address health beliefs and health literacy among Hispanic/Latino patients who have low confidence in completing written forms and difficulty understanding written information and reinforce the use of plain language and salient design features when developing patient education materials.
Accidental Deaths Involving Trees
Authors: Weyrauch Deland , Gill James R.
Published: May 2021

We examined all deaths in Connecticut involving tree mishaps (struck by a tree/tree limb, injuries associated with tree removal operations). Records of the Connecticut Office of the Chief Medical Examiner including autopsy, toxicology, and investigators' reports of deaths from 2004 to 2019 were reviewed. All underwent autopsy examination.

There were 64 fatalities, with ages ranging from 4 to 90 years (mean, 50 years). The causes of death involved the following: 56 blunt injury (primary site: 25 head, 13 multiple locations, 11 torso, and 7 neck), 5 traumatic asphyxia, 2 electrocution, and 1 chainsaw injury. Deaths were classified into 3 groups: 21 nonprofessional woodcutters, 19 professional woodcutters, and 24 tree failures. Among all woodcutters (100% men), impact by a falling tree/limb (78%) was the most common fatal event, and the most common lethal injury site was the head (45%). For tree failures, 58% involved storm/high-wind events, whereas 42% were spontaneous. Of the tree failure events, 58% involved motor vehicles, with most (86%) occurring while driving. Ethanol was detected in 6 decedents with blood concentrations ranging from 0.02 to 0.19 gm%, of which 4 were nonprofessional and 2 were professional woodcutters. There were some seasonal differences among the 3 groups.

Overall, fatalities of nonprofessional woodcutters, compared with professionals, were more likely to involve an older man (58 vs 40 years), working alone (67% vs 11%), and under the influence of ethanol (19% vs 11%) in late summer-autumn who dies of blunt head trauma from a falling tree or tree limb. Aggressive tree control management along highways has been used to attempt to decrease storm-related fatalities.
Fragile X-associated tremor/ataxia syndrome: pathophysiology and management
Authors: Hagerman Randi , Hagerman Paul
Published: May 2021

Purpose of review

The purpose of this paper is to review the prevalence, pathophysiology, and management of fragile X-associated tremor/ataxia syndrome (FXTAS).

Recent findings

The pathophysiology of FXTAS involves ribonucleic acid (RNA) toxicity due to elevated levels of the premutation-expanded CGG (eoxycytidylate-deoxyguanylate-deoxyguanylate)-repeat FMR1 mRNA, which can sequester a variety of proteins important for neuronal function. A recent analysis of the inclusions in FXTAS demonstrates elevated levels of several proteins, including small ubiquitin-related modifiers 1/2 (SUMO1/2), that target molecules for the proteasome, suggesting that some aspect(s) of proteasomal function may be altered in FXTAS. Recent neuropathological studies show that Parkinson disease and Alzheimer disease can sometimes co-occur with FXTAS. Lewy bodies can be found in 10% of the brains of patients with FXTAS. Microbleeds and iron deposition are also common in the neuropathology, in addition to white matter disease (WMD) and atrophy.

The premutation occurs in 1:200 females and 1:400 males. Penetrance for FXTAS increases with age, though lower in females (16%) compared to over 60% of males by age 70. To diagnose FXTAS, an MRI is essential to document the presence of WMD, a primary component of the diagnostic criteria. Pain can be a significant feature of FXTAS and is seen in approximately 50% of patients.
Evaluation of the ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe by trans-cerebellar section
Authors: xu pingping , zhang dirong , shi yu , kong fengbei , yao chunxiao , she ying , wu guoru
Published: May 2021

Objective On the basis of a prospective study of evaluating the development of frontal lobe in mid-to-late trimester by trans-cerebellar section, it had been found that the transverse frontal diameter had a higher correlation with gestational age than the anteroposterior frontal diameter. In order to provide more valuable information for the prenatal diagnosis of suspected fetal microcephaly, the reference value range of the ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe by trans-cerebellar section was further prospectively established.
Methods A prospective cross-sectional study was conducted on 870 normal fetuses at 21 to 36 weeks of gestation from January 2019 to June 2020. The transverse diameter of cerebellum and the transverse diameter of frontal lobe were measured by trans-cerebellar section, and the ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe was calculated, and the correlation was analyzed statistically.
Results The ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe increased positively with gestational age which correlation coefficient was 0.413 (P < 0.001). Taking gestational age as the independent variable and the ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe as the dependent variable, it showed that there was a linear relationship between the gestational age and the ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe. We got a correlation formula that the ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe =0.004X (gestational age-21)+0.530.
Conclusion This study has preliminarily established the normal reference range of the ratio of the transverse diameter of cerebellum to the transverse diameter of frontal lobe by trans-cerebellar section in normal mid-to-late pregnancy fetuses, which can provide valuable information for the prenatal diagnosis of suspected fetal microcephaly.
Key words
Fetus; prenatal ultrasound; transverse diameter of cerebellum; transverse diameter of frontal lobe; microcephaly
Hospitals That Report Severe Sepsis and Septic Shock Bundle (SEP-1) Compliance Have More Structured Sepsis Performance Improvement
Authors: Bolte Ty B. , Swanson Morgan B. , Kaldjian Anna , Mohr Nicholas M. , McDanel Jennifer , Ahmed Azeemuddin
Published: May 2021

Objective

Sepsis is a common cause of death in hospitalized patients. The Centers for Medicare & Medicaid Service (CMS) Severe Sepsis and Septic Shock Bundle (SEP-1) is an evidence-based early management bundle focused on improving sepsis outcomes. It is unknown which quality improvement (QI) practices are associated with SEP-1 compliance and if those practices reduce sepsis mortality. The objectives of this study were to compare sepsis QI practices in SEP-1 reporting and non-reporting hospitals and to measure the association between specific elements of sepsis QI processes and SEP-1 performance and hospital-specific risk-adjusted sepsis mortality.

Design, Setting, and Patients

This mixed methods study linked telephone survey data on QI practices from Iowa hospitals to SEP-1 performance data and risk-adjusted mortality from statewide all-payer administrative claims database. The survey assessed sepsis QI practices in eight categories. Characteristics of hospitals and sepsis QI practices were compared by SEP-1 reporting status. Univariable and multivariable logistic and linear regression estimated the association of QI practices with hospital SEP-1 performance and observed-to-expected sepsis mortality ratios.

Interventions

None

Measurements and Main Results

All 118 Iowa hospitals completed the survey (100% response rate). SEP-1 reporting hospitals were more likely to have sepsis QI practices, including reporting sepsis quality to providers (64% vs. 38%, p = 0.026) and using the case review process to develop sepsis care plans (87% vs. 64%, p = 0.013). Sepsis QI practices were not associated with increased SEP-1 scores. Two were associated with reduced mortality: having a sepsis committee β= -0.11, p = 0.036) and using case review results for sepsis care plans (β= -0.10, p = 0.049).

Conclusions

Hospitals reporting SEP-1 compliance to CMS conduct more sepsis QI practices. Most QI practices are not associated with increased SEP-1 performance or decreased sepsis mortality. Future work could explore how to implement these performance improvement practices in hospitals not reporting SEP-1 compliance.
Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homogeneous and heterogenous neutralising antibody responses
Authors: Roth Nicole , Schön Jacob , Hoffmann Donata , Thran Moritz , Thess Andreas , Mueller Stefan O. , Petsch Benjamin , Rauch Susanne
Published: May 2021

More than two years after the emergence of SARS-CoV-2, 33 COVID-19 vaccines, based on different platforms, have been approved in 197 countries. Novel variants that are less efficiently neutralised by antibodies raised against ancestral SARS-CoV-2 are circulating, highlighting the need to adapt vaccination strategies. Here, we compare the immunogenicity of a first-generation mRNA vaccine candidate, CVnCoV, with a second-generation mRNA vaccine candidate, CV2CoV, in rats. Higher levels of spike (S) protein expression were observed in cell culture with CV2CoV mRNA than with CVnCoV mRNA. Vaccination with CV2CoV also induced higher titres of virus neutralising antibodies with accelerated kinetics in rats compared with CVnCoV. Significant cross-neutralization of the SARS-CoV-2 variants, Alpha (B.1.1.7), Beta (B.1.351), and the ‘mink’ variant (B1.1.298) that were circulating at the time in early 2021 was also demonstrated. In addition, CV2CoV induced higher levels of antibodies at lower doses than CVnCoV, suggesting that dose-sparing could be possible with the next generation SARS-CoV-2 vaccine which could improve worldwide vaccine supply.
Common Mechanism of SARS-CoV and SARS-CoV-2 Pathogenesis across Species
Authors: Schafer Alexandra , Gralinski Lisa E. , Leist Sarah R. , Winkler Emma S. , Hampton Brea K. , Mooney Michael A. , Jensen Kara L. , Graham Rachel L. , Agnihothram Sudhakar , Jeng Sophia , Chamberlin Steven , Bell Timothy A. , Scobey D. Trevor , VanBlargan Laura A. , Thackray Larissa B. , Hock Pablo , Miller Darla R. , Shaw Ginger D. , Pardo Manuel de Villena Fernando , McWeeney Shannon K. , Montgomery Stephanie A. , Diamond Michael S. , Heise Mark T. , Menachery Vineet D. , Ferris Martin T. , Baric Ralph S.
Published: May 2021

Sarbecovirus (CoV) infections, including Severe Acute Respiratory CoV (SARS-CoV) and SARS-CoV-2, are considerable human threats. Human GWAS studies have recently identified loci associated with variation in SARS-CoV-2 susceptibility. However, genetically tractable models that reproduce human CoV disease outcomes are needed to mechanistically evaluate genetic determinants of CoV susceptibility. We used the Collaborative Cross (CC) and human GWAS datasets to elucidate host susceptibility loci that regulate CoV infections and to identify host quantitative trait loci that modulate severe CoV and pan-CoV disease outcomes including a major disease regulating loci including CCR9. CCR9 ablation resulted in enhanced titer, weight loss, respiratory dysfunction, mortality, and inflammation, providing mechanistic support in mitigating protection from severe SARS-CoV-2 pathogenesis across species. This study represents a comprehensive analysis of susceptibility loci for an entire genus of human pathogens conducted, identifies a large collection of susceptibility loci and candidate genes that regulate multiple aspects type-specific and cross-CoV pathogenesis, and also validates the paradigm of using the CC platform to identify common cross-species susceptibility loci and genes for newly emerging and pre-epidemic viruses.