bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of arsenic bioremediation by a cyanobacterium isolated from the Salado River in the Atacama Desert
Authors: Pérez-Portilla Pablo , Araya Juan , Gallardo Karem , Aránguiz-Acuña Adriana
Published: March 2021

Cyanobacteria and microalgae are recognized as excellent metal(loid)s-bioremediators of aquatic systems. We isolated a cyanobacterium from the Salado River in the Atacama Desert, northern Chile, which was identified as Cyanobium sp. Growth inhibition bioassays were conducted with arsenic and cadmium, and tolerance of Cyanobium to these metals was estimated. Removal of arsenic was assessed under different pH conditions and over time. We showed that the Cyanobium strain isolated from the Salado River has a greater tolerance to the arsenic and cadmium compounds than other species commonly used in metal(loid)s-bioremediation. Removal of up to 90% of arsenic was obtained in alkaline conditions, within the first 3 hours of exposure suggesting that Cyanobium sp. isolated from the Atacama Desert could be further studied with biotechnological purposes and to understand the evolutionary mechanisms of adaption to arid environments.
Gene expression evolution in pattern-triggered immunity withinArabidopsis thalianaand across Brassicaceae species
Authors: Winkelmüller Thomas M , Entila Frederickson , Anver Shajahan , Piasecka Anna , Song Baoxing , Dahms Eik , Sakakibara Hitoshi , Gan Xiangchao , Kułak Karolina , Sawikowska Aneta , Krajewski Paweł , Tsiantis Miltos , Garrido-Oter Ruben , Fukushima Kenji , Schulze-Lefert Paul , Laurent Stefan , Bednarek Paweł , Tsuda Kenichi
Published: March 2021

Plants recognize surrounding microbes by sensing microbe-associated molecular patterns (MAMPs) to activate pattern-triggered immunity (PTI). Despite their significance for microbial control, the evolution of PTI responses remains largely uncharacterized. Here, by employing comparative transcriptomics of six Arabidopsis thaliana accessions and three additional Brassicaceae species to investigate PTI responses, we identified a set of genes that commonly respond to the MAMP flg22 and genes that exhibit species-specific expression signatures. Variation in flg22-triggered transcriptome responses across Brassicaceae species was incongruent with their phylogeny, while expression changes were strongly conserved within A. thaliana. We found the enrichment of WRKY transcription factor binding sites in the 5′-regulatory regions of conserved and species-specific responsive genes, linking the emergence of WRKY-binding sites with the evolution of gene expression patterns during PTI. Our findings advance our understanding of the evolution of the transcriptome during biotic stress.
Mapping and engineering of auxin-induced plasma membrane dissociation in BRX family proteins
Authors: Koh Samuel W H , Marhava Petra , Rana Surbhi , Graf Alina , Moret Bernard , Bassukas Alkistis E L , Zourelidou Melina , Kolb Martina , Hammes Ulrich Z , Schwechheimer Claus , Hardtke Christian S
Published: March 2021

Angiosperms have evolved the phloem for the long-distance transport of metabolites. The complex process of phloem development involves genes that only occur in vascular plant lineages. For example, in Arabidopsis thaliana, the BREVIS RADIX (BRX) gene is required for continuous root protophloem differentiation, together with PROTEIN KINASE ASSOCIATED WITH BRX (PAX). BRX and its BRX-LIKE (BRXL) homologs are composed of four highly conserved domains including the signature tandem BRX domains that are separated by variable spacers. Nevertheless, BRX family proteins have functionally diverged. For instance, BRXL2 can only partially replace BRX in the root protophloem. This divergence is reflected in physiologically relevant differences in protein behavior, such as auxin-induced plasma membrane dissociation of BRX, which is not observed for BRXL2. Here we dissected the differential functions of BRX family proteins using a set of amino acid substitutions and domain swaps. Our data suggest that the plasma membrane-associated tandem BRX domains are both necessary and sufficient to convey the biological outputs of BRX function and therefore constitute an important regulatory entity. Moreover, PAX target phosphosites in the linker between the two BRX domains mediate the auxin-induced plasma membrane dissociation. Engineering these sites into BRXL2 renders this modified protein auxin-responsive and thereby increases its biological activity in the root protophloem context.
The association of smoking with immunoglobulin G4–related disease: a case–control study
Authors: Wallwork Rachel , Perugino Cory A , Fu Xiaoqing , Harkness Tyler , Zhang Yuqing , Choi Hyon K , Stone John H , Wallace Zachary S
Published: March 2021

Objective

To evaluate the association between cigarette smoking and the odds of IgG4-related disease (IgG4-RD).

Methods

We performed a case–control study of patients with IgG4-RD compared in a 1:5 ratio with age-, race- and sex-matched controls. We included cases evaluated at the Massachusetts General Hospital, a hospital within the Mass General Brigham (MGB) System. Controls were identified from the MGB Biobank. Smoking status at the date of IgG4-RD diagnosis or corresponding index date was determined. Conditional logistic regression was used to estimate the association between cigarette smoking and the odds of having IgG4-RD.

Results

There were 234 IgG4-RD cases and 1170 controls. The mean age (59 years), sex (62% male) and race (75% white) were well balanced. IgG4-RD cases were more likely to be current smokers compared with controls [25 (11%) vs 70 (6%); odds ratio (OR) 1.79 (95% CI 1.08, 2.95)]. This association was strongest among female cases [13 (14%) vs 19 (4%);, OR 3.79 (95% CI 1.71, 8.39)] and those with retroperitoneal fibrosis [RPF; 13 (28%) vs 13 (6%);, OR 6.93 (95% CI 2.78, 17.26)] or normal IgG4 concentrations [21 (21%) vs 21 (4%); OR 6.22 (95% CI 3.09, 12.49)]. When RPF cases were excluded, there was no longer an association between current smoking and the odds of having IgG4-RD [12 (6%) vs 57 (6%); OR 0.95 (95% CI 0.49, 1.86)].

Conclusion

Being a current smoker is associated with greater odds of having IgG4-RD, especially among women and those with RPF or normal IgG4 concentrations. Current smoking is the first recognized modifiable risk factor for IgG4-RD.
The Tn7-Based Genomic Integration Is Dependent on an attTn7 Box in the glms Gene and Is Site-Specific With Monocopy in Ralstonia solanacearum Species Complex
Authors: Zhang Yong , Cao Yuzhu , Zhang Lichun , Hikichi Yasufumi , Ohnishi Kouhei , Li Jing
Published: March 2021

The Tn7-based genomic integration system enables direct insertion of foreign gene elements into the chromosome downstream of glms in many bacteria species. The glms gene is greatly conserved in Ralstonia solanacearum species complex (RSSC), while its downstream regions are mostly different in the RSSC. Here, we provided genetic evidence to validate that this Tn7 integration is dependent on a conserved 30-bp motif in the glms, called an attTn7 box, and artificial attTn7 boxes elsewhere are competent for the Tn7 integration, which is further confirmed to be simultaneous downstream of both original and artificial attTn7 boxes, using PCR. With the whole-genome resequencing on 500 Tn7-colonies, the Tn7 integration was confirmed to be site- specific at 25 bp downstream of glms with monocopy as a chromosome of the RSSC. Characteristic of a monocopy in a chromosome enables the Tn7-based complementation to fully restore phenotypes of mutants to those of parent strains that are advantageous rather than those based on plasmids with low-copy numbers. The Tn7-based genomic integration system provides a generally applicable and versatile genetic tool for studies of complementation, pathogenesis, overexpression, and in-vivo promoter activity assays with monocopy in the RSSC.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Creation of a COVID-19 Based Educational Curriculum: A Blueprint for Redesigning Surgical Education During Times of National Crisis
Authors: Zhang Lindsey M. , Symalla Trever , Roggin Kevin K. , Matthews Jeffrey B. , Hussain Mustafa
Published: March 2021

Objective:

To create a COVID-19 based educational curriculum for surgical residents.

Background Data:

The COVID-19 pandemic has resulted in disruptions to operative volume and clinical education for surgery residents. This has placed a greater importance on didactic education. However, in the face of pandemic-related uncertainty, focusing on a traditional educational curriculum may be a challenge for surgical residents.

Methods:

A dedicated resident educational team was created. This team identified specific surgical resident needs, evaluated institutional resources, created a curriculum and timeline, determined a feasible implementation format, and assessed resident opinions on the impact of the curriculum via anonymous survey.

Results:

A 1-month long COVID-19 based curriculum was developed, which covered (1) advanced critical care and resuscitation techniques pertinent to patients with COVID-19, (2) institutional physician experience in the COVID-units, (3) ethical dilemmas in resource management, (4) triaging of operative cases during the pandemic, and (5) published and ongoing COVID-19-related surgical research. In the postimplementation survey, a majority of residents reported that the curriculum helped improve their ability to take care of patients during the pandemic, provided an opportunity for questions, alleviated anxieties and concerns, and that they preferred the COVID-19 curriculum over traditional surgical topics.

Conclusions:

In the midst of national crisis and significant clinical disruption, real-time adjustments to surgical education can and should occur to address resident needs. The results of our study may serve as a blueprint for implementing rapid change to resident education in the future.
Anterior Cruciate Ligament Tear Following Operative Treatment of Pediatric Tibial Eminence Fractures in a Multicenter Cohort
Authors: O’Donnell Ryan , Bokshan Steven , Brown Kelsey , Aoyama Julien T. , Ganley Theodore J. , Fabricant Peter D. , Patel Neeraj M. , Ellis Henry B. , Green Daniel W. , Kushare Indranil , Lee R. Jay , McKay Scott , Rhodes Jason , Sachleben Brant , Sargent Catherine , Schmale Gregory A. , Yen Yi-Meng , Mistovich R. Justin , Cruz Aristides I.
Published: March 2021

Background:

Postoperative ipsilateral anterior cruciate ligament (ACL) tears after tibial eminence fracture fixation has been previously noted in the literature. This study aims to describe the prevalence of and risk factors for postoperative ACL tears in a cohort of patients operatively treated for tibial eminence fracture.

Methods:

A retrospective review of children undergoing treatment of a tibial eminence fracture at 10 tertiary care children’s hospitals was performed. The primary outcome of interest was subsequent ACL rupture. Incidence of ACL tear was recorded for the entire cohort. Patients who sustained a postoperative ACL tear were compared with those without ACL tear and analyzed for demographics and risk factors. A subgroup analysis was performed on patients with a minimum of 2-year follow-up data or those who had met the primary outcome (ACL tear) before 2 years.

Results:

A total of 385 pediatric patients were reviewed. 2.6% of the cohort experienced a subsequent ACL tear. The median follow-up time was 6.5 months (SD=6.4 mo). Subsequent ACL tears occurred at a median of 10.2 months (SD=19.5 mo) postoperatively. There was a statistically significant association with higher grade tibial spine fractures (Myers and McKeever type III and IV) and subsequent ACL tear (P=0.01). Patients with a subsequent ACL tear were older on average (13.5 vs. 12.2 y old), however, this difference was not statistically significant (P=0.08). Subgroup analysis of 46 patients who had a 2-year follow-up or sustained an ACL tear before 2 years showed a 21.7% incidence of a subsequent ACL tear. There was a statistically significant association with higher grade tibial spine fractures (Myers and McKeever type III and IV) and subsequent ACL rupture (P=0.006) in this subgroup. Postoperative ACL tears occurred in patients who were older at the time that they sustained their original tibial eminence fracture (13.4 vs. 11.3 y old,P=0.035).

Conclusions:

Ipsilateral ACL tears following operatively treated pediatric tibial eminence fractures in a large multicenter cohort occurred at a rate of 2.6%. However, in those with at least 2 years of follow-up, the incidence was 21.7%. Subsequent ACL tear was more likely in those with completely displaced (type III or IV) tibial eminence fractures and older patients.

Level of Evidence:

Level III—retrospective cohort study.
Novel Use of Pennig External Fixation for the Treatment of Pediatric Syndactyly
Authors: Li Jin , Wang Qin , Panayi Adriana C. , Wu Mengfan , Tang Xin , Hong Pan , Ze Renhao
Published: March 2021

Syndactyly is one of the most common congenital limb malformations, second only to polydactyly. Syndactyly is treated with surgical intervention. During separation, free skin grafting or skin flap transplantation is required to allow for adequate skin closure. We introduce a novel application method of the Pennig external fixation device for the management of pediatric syndactyly without skin grafting. The Pennig minifixator was used in syndactyly to expand the web space soft tissue in order to allow a Z-plasty to be performed in a second operation. All patients had developed sufficient skin tissue from the external fixation. No infection, cutaneous necrosis or nonunion was noted in any of the patients. All patients had a satisfactory outcome in terms of final appearance and digit function. On the basis of the principle of strain-stress, use of the Penning external minifixator allows development of sufficient tissue in the web space for a second phase of reconstruction in syndactyly. The need for skin grafting and risk of blood vessel damage were avoided in this study, and, the incidence of skin necrosis and scar formation was reduced. Both the patients’ families and our research members expressed high satisfaction with the postoperative function and appearance. Overall, application of the Pennig external fixation frame in our novel method is effective for the management of syndactyly and should be studied further.

Level of Evidence: Level IV, case series.
Prenatal Diagnosis of Dystrophinopathy and Cytogenetic Analysis in 303 Chinese Families
Authors: Li Mengmeng , Hao Na , Yao Fengxia , Zhang Weimin , Zhou Jing , Tan Li , Qiu Zhengqing , Liu Juntao
Published: March 2021

Objective:

This study was to supply information of the Duchenne muscular dystrophy (DMD) mutational spectrum in 303 Chinese families and further offer 5-year clinical experience of DMD/Becker muscular dystrophy genetic counseling and prenatal diagnosis.

Methods:

In this retrospective cohort study, three hundred and five pregnancies in 303 pregnant women who has a birth history of DMD/Becker muscular dystrophy patients underwent prenatal diagnosis using multiplex ligation-dependent probe amplification followed by Sanger sequencing between January 2014 and December 2018 at Peking Union Medical College Hospital. The mean age of pregnant women was (33.0 ± 4.1) years old. Karyotype analysis was performed to exclude fetal abnormal karyotype.

Results:

The detection rate of DMD gene mutation in 303 probands was (296/303) 97.7% with seven families having a negative genetic diagnosis. The mutational spectrum comprised of large arrangements in 288/303 (95.0%) and small mutations in 8/303 (2.6%). Carrier testing was performed among 204 pregnant women among whom, 108 mothers had the same mutation as family proband. Of the 305 pregnancies underwent prenatal diagnosis, 55 of 173 male fetuses were affected. We also performed karyotype analysis and found three abnormal karyotypes of trisomy 21. We even found a fetus with DMD gene mutation and trisomy 21 in a same fetus by further analysis. We also identified two times of germline mosaicism.

Conclusion:

This study demonstrated the distribution and mutation profile of 303 probands and 305 fetuses. Furthermore, considering the possbility of maternl germilne mosaicism, prenatal diagnosis should be suggested to mothers with a proband whether they carry the causative mutation in their blood or not.
Effects of inverted photoperiods on the blood pressure and carotid artery of spontaneously hypertensive rats and Wistar–Kyoto rats
Authors: Wang YunLei , Zhang Tong , Zhang YuGe , Yu Yan , Bai Fan , Zhang HaoJie , Chi YaFei
Published: March 2021

Objective:

The objective of this study was to investigate the effects of inverted photoperiods on the blood pressure and carotid arteries in spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) rats (homologous control group).

Methods and results:

This study used two inverted photoperiods [inverted light:dark (ILD)16 : 8 and ILD12 : 12] to create the model. A total of 27 male SHR and 27 male WKY rats were randomly divided into six groups (nine rats per group): SHR (LD12 : 12), SHR (ILD16 : 8), SHR (ILD12 : 12), WKY (LD12 : 12), WKY (ILD16 : 8) and WKY (ILD12 : 12). We recorded the trajectory of the activity rhythm of the rats and performed carotid vascular ultrasound examination, MRI (arterial spin labelling) analysis and carotid biopsy. The results showed that inverted photoperiods increased the blood pressure, carotid intima-media thickness, resistance index and blood flow velocity. In addition, inverted photoperiods led to the development of carotid arterial thrombosis, significantly reduced cerebral blood flow and increased the number of collagen fibres. Moreover, it increased the expression of angiotensin receptor and low-density lipoprotein receptor in the carotid arteries, leading to decreased expression of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase and nitric oxide synthase. Inverted photoperiods induced the formation of atherosclerotic plaque. Multiple results of SHR were worse than those of WKY rats.

Conclusion:

Taken together, inverted photoperiods can produce a series of adverse consequences on blood pressure and carotid arteries. Hypertension can aggravate the adverse effects of inverted photoperiods.
How Frequent Is Switching From an Initial Stimulant Family to the Alternative One in the Clinical Setting?
Authors: Biederman Joseph , DiSalvo Maura , Green Allison , Woodworth K. Yvonne , Law Cecilia , Gabrieli John D.E. , Faraone Stephen V.
Published: March 2021

Purpose/Background

This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants.

Methods/Procedures

Subjects were 49 unmedicated adults (18–45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function—Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale—Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics.

Findings/Results

Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment (“strugglers”) was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance.

Implications/Conclusions

Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.
Impact of ABO blood group on bleeding complications after surgery for acute type A aortic dissection
Authors: Guné Henrik , Larsson Mårten , Nozohoor Shahab , Herou Erik , Luts Cecilia , Ragnarsson Sigurdur , Samuelsson Maria , Sjögren Johan , Svensson Peter J. , Zindovic Igor
Published: March 2021

Excessive bleeding is a serious complication associated with impaired survival after surgery for acute type A aortic dissection (ATAAD). Different ABO blood groups are associated with variable levels of circulating von Willebrand factor and therefore potentially altered risks of surgical haemorrhage. The current study aimed to assess the impact of blood group on bleeding complications after ATAAD surgery. This was a retrospective cohort study including 336 patients surgically treated for ATAAD between January 2004 and January 2019. Patients with blood group O were compared with non-O patients. In total, 152 blood group O patients were compared with 184 non-O patients. There were no differences in rates of massive bleeding (27.0 vs. 25.5%, P = 0.767) or re-exploration for bleeding (16.4 vs. 13.0%, P = 0.379) in blood group O and non-O patients, respectively. Median chest tube output 12 h after surgery was 520 ml (350–815 ml) in blood group O and 490 ml (278–703 ml) in non-O patients (P = 0.229). Blood group O patients received more fibrinogen concentrate (6.1 ± 4.0 vs. 4.9 ± 3.3 g, P = 0.023) but administered units of packed red blood cells [5 (2–8) vs. 4 (2–9) U, P = 0.736], platelets [4 (2–4) vs. 3 (2–5) U, P = 0.521] or plasma [4 (1–7) vs. 4 (0–7) U, P = 0.562] were similar. This study could not demonstrate any association between blood group and bleeding after surgery for ATAAD. It cannot be ruled out that potential differences were levelled out by blood group O patients receiving significantly more fibrinogen concentrate.
Which tests can most effectively indicate the clinical phenotype of paediatric haemophilia patients with prophylaxis?
Authors: Ay Yilmaz , Toret Ersin , Gozmen Salih , Cubukcu Duygu , Karapinar Tugba Hilkay , Oymak Yesim , Vergin Raziye Canan
Published: March 2021

Patients with haemophilia A who have similar FVIII levels show clinical heterogeneity, and 10–15% of patients with severe haemophilia do not have a severe bleeding phenotype. The aim of this study was to assess whether global haemostasis tests, such as thrombin generation assay (TGA) and thromboelastography (TEG), can predict the bleeding pattern of severe haemophilia better than trough levels and pharmacokinetic profiles, particularly in the prophylactic setting. The study group consisted of 39 patients with haemophilia A and 75 healthy controls. The annual bleeding rate (ABR) and Hemophilia Joint Health Score 2.1 (HJHS) of the patients were determined. Basal factor FVIII, inhibitor levels, TEG and TGA of participants with prophylaxis were performed after a washout period. Then, a recombinant FVIII product was administered to patients. After factor replacement, the above tests were repeated at 30 min, 6 and 48 h. There was a significant difference in the ABR and HJHS between the groups according to the basal factor VIII activity of patients after wash-out. TEG and TGA parameters of patients with factor activity above 1% were significantly better than those of patients with factor activity below 1%. After factor concentrate administration, factor activities, TEG and TGA parameters at 30 min, 6 and 48 h were similar in the two groups. We showed that the 1% trough level but not for the 3% trough level is critical for both clinical phenotypes and thrombin generation for haemophilia patients in the prophylactic setting.
Leukocyte-platelet rich fibrin on the treatment of a large paradental cyst: a novel regenerative approach
Authors: Heggendorn Fabiano Luiz , Heggendorn Christiane , Vidal Fábio , Silva Gabriela Cristina de Carvalho , Gonçalves Lucio Souza , Lione Viviane de Oliveira Freitas
Published: March 2021

Leukocyte-platelet rich fibrin (PRF) is an autologous biomaterial formed by platelets, cytokines, growth factors and cells imprisoned on a fibrin mesh, produced according to Choukroun's protocol. The aim of the present article was to report the use of PRF, associated with a bone substitute, on the regenerative treatment of a large bone defect resulting from the enucleation of a paradental cyst involving the posterior mandible. The treatment resulted in the maintenance of the bone volume, and radiographic evaluation showed new bone formation after 40 days, suggesting an osteogenic and osteoinductive effect. Also, the current literature was reviewed.
Management of immunosuppressants in the era of coronavirus disease-2019
Authors: Manansala Michael , Baughman Robert , Novak Richard , Judson Marc , Sweiss Nadera
Published: March 2021

Purpose of review

Patients on chronic immunosuppressive treatments at baseline are at increased risk of opportunistic infections. These patients are at especially increased risk of morbidity and mortality during the coronavirus-19 (COVID-19) pandemic. This review will focus on patients with diseases in which immunosuppression is a vital part of the treatment regimen, including those with solid organ transplants, rheumatologic disorders, sarcoidosis, and inflammatory bowel disease (IBD). We will summarize the current knowledge of immunosuppression in these diseases and the risk of contracting COVID-19. Furthermore, we will discuss if immunosuppression increases severity of COVID-19 presentation.

Recent findings

Since the start of the COVID-19 pandemic, a large number patients receiving chronic immunosuppression have been infected with SARS-CoV-2. Moreover, our understanding of the immunology of SARS-CoV-2 is advancing at a rapid pace. Currently, a number of clinical trials are underway to investigate the role of immunosuppressive treatments in the management of this disease.

Currently, there is no conclusive evidence to suggest that solid organ transplant recipients on chronic immunosuppression are at increased risk of contracting COVID-19. Solid organ transplant recipients may be at increased risk for worse COVID-19 outcomes but the data are not consistent. There is evidence to suggest that patients with rheumatologic disorders or IBDs are not at increased risk of contracting COVID-19 and do not necessarily experience worse clinical outcomes. Patients with sarcoidosis are not necessarily at increased risk of COVID-19, although there is limited data available to determine if immunosuppression worsens outcomes in this population.
The liver in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
Authors: Davidov-Derevynko Yana , Ben Yakov Gil , Wieder Anat , Segal Gad , Naveh Lior , Orlova Natalia , Gringauz Irina , Amit Sharon , Mor Orna , Klempfner Robert , Rahav Galia , Ben Ari Ziv
Published: March 2021

Background

The ongoing outbreak of COVID-19 is associated with higher levels of morbidity and mortality among patients with comorbidities, including the metabolic syndrome. Liver impairment has been reported in up to 54% of hospitalized patients with COVID-19. The impact of COVID-19 on a preexisting chronic liver disease is an actively studied area of research. The contribution of our study is towards determining the predictors of severity and the outcome of liver injury among hospitalized patients with COVID-19 infection, including patients with a preexisting liver disease and COVID-19.

Methods

This single center retrospective cohort study included all patients ≥18 years, admitted in Sheba Medical Center with confirmed COVID-19 infection. Demographic, clinical and laboratory data were obtained using the MDClone platform and rechecked after data decryption using electronic health records.

Results

Of 382 patients with COVID-19, 66.4% had increased liver biochemistry. Mild increase was observed in 76.7%. The higher level of fibrosis-4 (FIB-4) at admission was independently associated with higher mortality rate. Preexisting liver disease was detected in 15.4% patients. Most common etiology was nonalcoholic fatty liver disease (78.7%). The mortality of hospitalized patients with preexisting liver disease was 16.7% compared to 6.8% in patients without preexisting liver disease (RR = 2.792, P = 0.01). In multivariate analysis, liver disease adjusted to age and BMI was associated with mortality with high statistical significance.

Conclusions

Patients with preexisting chronic liver disease were at a higher risk of mortality. The FIB-4 level at admission was associated with worse prognosis. These findings should be reevaluated in a larger cohort of patients.
The utility of faecal and urine biomarkers for small bowel diseases
Authors: Ismail M.S. , Semenov Serhiy , McNamara Deirdre
Published: March 2021

Purpose of review

Small bowel diseases pose a unique diagnostic and management challenge and often requires tertiary specialist referral. The use of biomarkers may provide a cheap, noninvasive tool to assess the small bowel in terms of diagnosis, offering a better way to triage referrals and select patients for early management. This review looks at the most recent evidence behind the use of several faecal and urine biomarkers for small bowel diseases.

Recent findings

Faecal calprotectin shows the most promise, with evidence to support its role in predicting relapse postsurgery and monitoring treatment response in patients with Crohn's disease. A faecal calprotectin less than 50 μg/g may also be used as a cut-off to triage further investigation. Faecal lactoferrin also appears promising as a marker of small bowel inflammation. A positive faecal immunohistochemistry test precapsule may help to prioritize referrals for obscure bleeding.

The use of biomarkers in the diagnosis and management of small bowel disease is still controversial and remains unclear. More studies are required to further develop their potential and before societal guidelines can be developed to direct their appropriate use in clinical practice.
Pediatric Severe Sepsis and Shock in Three Asian Countries: A Retrospective Study of Outcomes in Nine PICUs
Authors: Samransamruajkit Rujipat , Wong Judith Ju-Ming , Smathakane Chutima , Anantasit Nattachai , Sunkonkit Kanokkarn , Ong Jacqueline , Lee Olive Pei Ee , Lee Pei-Chuen , Phumeetham Suwannee , Sultana Rehena , Lapwanich Usa , Lee Jan Hau , Kongkiattikul Lalida
Published: March 2021

OBJECTIVES:

Pediatric sepsis remains a major health problem and is a leading cause of death and long-term disability worldwide. This study aims to characterize epidemiologic, therapeutic, and outcome features of pediatric severe sepsis and septic shock in three Asian countries.

DESIGN:

A multicenter retrospective study with longitudinal clinical data over 1, 6, 24, 48, and 72 hours of PICU admission. The primary outcome was PICU mortality. Multivariable logistic regression analysis was used to identify factors at PICU admission that were associated with mortality

SETTING:

Nine multidisciplinary PICUs in three Asian countries.

PATIENTS:

Children with severe sepsis or septic shock admitted to the PICU from January to December 2017.

INTERVENTION:

None.

MEASUREMENT AND MAIN RESULTS:

A total of 271 children were included in this study. Median (interquartile range) age was 4.2 years (1.3–10.8 yr). Pneumonia (77/271 [28.4%]) was the most common source of infection. Majority of patients (243/271 [90%]) were resuscitated within the first hour, with fluid bolus (199/271 [73.4%]) or vasopressors (162/271 [59.8%]). Fluid resuscitation commonly took the form of normal saline (147/199 [74.2%]) (20 mL/kg [10–20 mL/kg] over 20 min [15–30 min]). The most common inotrope used was norepinephrine 81 of 162 (50.0%). Overall PICU mortality was 52 of 271 (19.2%). Improved hemodynamic variables (e.g., heart rate, blood pressure, and arterial lactate) were seen in survivors within 6 hours of admission as compared to nonsurvivors. In the multivariable model, admission severity score was associated with PICU mortality.

CONCLUSIONS:

Mortality from pediatric severe sepsis and septic shock remains high in Asia. Consistent with current guidelines, most of the children admitted to these PICUs received fluid therapy and inotropic support as recommended.
Use of Negative Pressure Ventilation in Pediatric Critical Care: Experience in 56 PICUs in the Virtual Pediatric Systems Database (2009–2019)
Authors: Moffitt Cynthia A. , Deakins Kathleen , Cheifetz Ira , Clayton Jason A. , Slain Katherine N. , Shein Steven L.
Published: March 2021

OBJECTIVES:

Negative pressure ventilation may be more physiologic than positive pressure ventilation, but data describing negative pressure ventilation use in the PICU are limited. We aimed to describe the epidemiology and outcomes of PICU patients receiving negative pressure ventilation.

DESIGN:

Descriptive analysis of a large, quality-controlled multicenter database.

SETTING:

Fifty-six PICUs in the Virtual Pediatric Systems database who reported use of negative pressure ventilation.

PATIENTS:

Children admitted to a participating PICU between 2009 and 2019 who received negative pressure ventilation.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Among 788 subjects, 71% were less than 2 years old, and 45% had underlying health conditions. Two concurrent aspiration events were the only adverse events reported. After excluding one over-represented center, the 3 years with the most negative pressure ventilation usage were 2017–2019 (all > 25 cases/yr and ≥ 13 centers reporting usage). Among those 187 children, the most common primary diagnoses were bronchiolitis and cardiac disease (both 15.5%), 24.1% required endotracheal intubation after negative pressure ventilation, and 9.1% died.

CONCLUSIONS:

Negative pressure ventilation is being used in many PICUs, most commonly for pulmonary infections or cardiac disease, in children with high rates of subsequent intubation and mortality and with few documented adverse events. Use at individual centers is rare but increasing, suggesting need for prospective collaboration to better evaluate the role of negative pressure ventilation in the PICU.
Diagnosis of Posterior Urethral Valves in an Infant Using Point-of-Care Ultrasound
Authors: Gillon Jason T. , Cohen Stephanie G.
Published: March 2021

This case describes a 7-week-old male infant presenting with vomiting and decreased urine output. Initial point-of-care ultrasound (POCUS) demonstrated a normal pylorus; however, assessment of bladder volume revealed the problem. The bladder was distended with a thickened, trabeculated wall and there was bilateral hydroureter, consistent with bladder outlet obstruction. Renal POCUS revealed bilateral hydronephrosis and perinephric fluid collections consistent with calyceal rupture. A voiding cystourethrogram confirmed the diagnosis of posterior urethral valves which were eventually ablated by urology. To our knowledge, this is the first case report of POCUS leading to a diagnosis of posterior urethral valves in an infant. This case highlights how POCUS can expedite evaluation of decreased urine output.
Mental Health in Early Childhood and Changes in Cardiometabolic Dysregulation by Preadolescence
Authors: Qureshi Farah , Derks Ivonne P.M. , Jaddoe Vincent W.V. , Williams Michelle A. , Koenen Karestan C. , Tiemeier Henning , Kubzansky Laura D.
Published: March 2021

Objective

Poor mental health in childhood is associated with a greater risk of cardiometabolic disease in adulthood, but less is known about when these associations begin to emerge. This study tests whether poor mental health (indexed by emotional and behavioral problems) in early childhood predicts increases in cardiometabolic dysregulation over 4 years of follow-up.

Methods

Data are from 4327 participants in the Generation R Study. Problem behaviors were reported by mothers using the Child Behavior Checklist at age 6 years. Repeated measurements of six cardiometabolic parameters were collected at ages 6 and 10 years: high-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, systolic and diastolic blood pressures, C-reactive protein, and body mass index. Standardized measures were used to create continuous cardiometabolic dysregulation scores at ages 6 and 10 years. Change in dysregulation was defined as the difference in dysregulation scores over time. Cross-sectional and prospective associations were tested using linear regression, sequentially adjusting for relevant confounders. Additional analyses examined whether prospective relationships were robust to adjustment for baseline levels of dysregulation.

Results

There was no association between child problem behaviors and cardiometabolic dysregulation at age 6 years. However, higher levels of problem behaviors predicted increases in cardiometabolic dysregulation (β = 0.12, 95% confidence interval = 0.00–0.23) from ages 6 to 10 years.

Conclusions

Worse child mental health may be associated with increases in cardiometabolic dysregulation by preadolescence. To our knowledge, this is the first study to demonstrate that adverse physiologic effects of psychological distress identified in adult populations may be observed as early as childhood.
Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1
Authors: Ackerman Peter , Thompson Melanie , Molina Jean-Michel , Aberg Judith , Cassetti Isabel , Kozal Michael , Castagna Antonella , Martins Marcelo , Ramgopal Moti , Sprinz Eduardo , Treviño-Pérez Sandra , Streinu-Cercel Adrian , Latiff Gulam H. , Pialoux Gilles , Kumar Princy N. , Wang Marcia , Chabria Shiven , Pierce Amy , Llamoso Cyril , Lataillade Max
Published: March 2021

Objectives:

The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens.

Design:

BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes).

Methods:

Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc).

Results:

In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups.

Conclusion:

Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options.
Early Fat Grafting for Augmentation in Craniofacial Microsomia
Authors: Sakamoto Yoshiaki , Arnaud Eric
Published: March 2021

Patients with craniofacial microsomia often require multiple surgical interventions to address both hard and soft tissue defects. For improvement of soft tissue defects, microvascular free tissue transfers have been widely performed after puberty. To camouflage facial asymmetry, early fat grafting was performed on five six-month-old patients, and acceptable outcomes were obtained without overcorrection. This result suggests that early fat grafting in craniofacial microsomia is useful to camouflage asymmetrical facial contours.
The Use of Three-Dimensional Printed Technology for Mandibular Reconstruction in a Rare Case of Giant Odontogenic Myxofibroma
Authors: Yilmaz Yetkin Zeki , Elkhatroushi Taha , Erdur Zülküf Burak , Karaaltin Mehmet Veli , Çomunoğlu Nil , Batioğlu-Karaaltin Ayşegül
Published: March 2021

Odontogenic myxofibroma is a benign odontogenic tumor of mesenchymal tissue that generally originates from the mandible. It is an extremely rare tumor accounting for approximately 2% of all odontogenic tumors. In this report, the authors presented a giant right mandibular mass that extends to the angle of the mandible and displacing the tongue laterally caused significant malocclusion, pain, and impaired oral intake. The tumoral involvement of the mandibula required a partial mandibulectomy with the resection of right mandibular ramus, body, and bilateral parasymphysis. Right mandibular condyle was preserved. The mandibular defect was reconstructed with a fibula free flap. Three-dimensional printed maxillofacial bone model of the patient was used as contour modeling and guide. Histopathologic examination confirmed the diagnosis as odontogenic myxofibroma.

The purpose of the report is to present a very rare case of odontogenic myxofibroma and its general characteristics, radiological features, differential diagnosis, surgical management, and the use of three-dimensional printing technology in the field of mandibular reconstruction.
Unilateral Zygomatic Complex Fracture – A Comparison Between Nonsurgical Treatment and Surgical Treatment
Authors: Ling Xiao Feng , Yew Ching Ching , Mohd Nazri Syakiroh bt , Tew Mei Mei
Published: March 2021

Background:

Medical advances have enabled zygomatic complex (ZMC) fractures to be treated by various approaches. This study aims to analyze the demographics and treatment outcomes of unilateral ZMC fractures, treated nonsurgically or surgically.

Methods:

This 5-year nonrandomized prospective study had included 65 cases of unilateral ZMC fractures from October 2014 until December 2019. Patients were treated and divided into nonsurgical and surgically treated group. Treatment outcomes in terms of step deformities, malar depression, diplopia, infraorbital hypoaesthesia, and mouth opening were evaluated up to six months post-trauma/intervention.

Results:

Road traffic accident (96.9%) was the main cause, with predominant male involvement (80%) and median age of 28 years. Significant improvements (P < 0.05) were observed for step deformities and malar depression among the surgically treated group at postoperative day 1 and week 1. Throughout the six months review, infraorbital hypoesthesia and diplopia showed no significant differences between both groups, (P > 0.05). Besides, all patients showed significant mouth opening improvement (P < 0.05) over six months period.

Conclusion:

The authors found that infraorbital hypoaesthesia and limited of mouth opening should not be the absolute indications for surgical treatment of ZMC fractures. Nonsurgical treatment that included early jaw exercise and symptomatic treatment had potential value for satisfactory functional gain.
Graft-derived Cell-free DNA as a Noninvasive Biomarker of Cardiac Allograft Rejection: A Cohort Study on Clinical Validity and Confounding Factors
Authors: Knüttgen Franziska , Beck Julia , Dittrich Marcus , Oellerich Michael , Zittermann Armin , Schulz Uwe , Fuchs Uwe , Knabbe Cornelius , Schütz Ekkehard , Gummert Jan , Birschmann Ingvild
Published: March 2021

Background.

Circulating graft-derived cell-free DNA (dd-cfDNA) is a new marker of cardiac allograft damage that is used for noninvasive rejection diagnostics. We performed dd-cfDNA (%) in heart transplant recipients during the first posttransplant year.

Methods.

In 87 patients, serial dd-cfDNA determination at predefined time-points was performed in 770 single samples. dd-cfDNA fraction (%) was measured using an established universal droplet digital polymerase chain reaction method, providing same-day turn-around. Rejection was diagnosed according to clinical parameters and biopsies.

Results.

Median dd-cfDNA (%) was high (5.36%) immediately after reperfusion and decreased to a median (interquartile range) of 0.10% (0.05%–0.24%) in clinically stable patients by postoperative day 10. Compared to dd-cfDNA (%) samples in clinically stable patients, values were higher (P < 0.001) in biopsy-proven rejection ISHLT 1R (0.42% [0.15%–0.53%]) and 2R rejection (0.84% [0.39%–0.97%]). Moreover, dd-cfDNA (%) was already significantly increased 9–30 days before biopsy-proven rejection (0.36% [0.20%–0.61%]). An as yet unknown finding was a slightly, but significantly (P < 0.0001) higher dd-cfDNA (%) value in samples of stable patients with pericardial effusions (PEs) (n = 94; 0.18% [0.07%–0.30%]) compared to samples of non-PE patients (n = 132; 0.07% [0.04%–0.17%]). Using a cutoff of 0.35%, sensitivity and specificity of dd-cfDNA for cardiac rejection were 0.76 and 0.83 (area under the curve [AUC] ROC-curve: 0.81 [95% confidence interval, 0.73-0.89]). Omitting PE samples from the control group yielded an AUC of 0.86 [95% confidence interval, 0.76-0.95]. Samples drawn <12 hours after endomyocardial biopsy showed high (0.40% [0.15%–1.21%]) dd-cfDNA values, also in ISHLT0R (0.36% [0.10%–0.60%]).

Conclusions.

dd-cfDNA plasma values were significantly associated with cardiac rejection. However, PE or improper sampling (eg, shortly after biopsy) should be considered as confounders for rejection diagnoses using dd-cfDNA.
Investigating the neural correlates of phonological encoding using a cluster-based analysis approach
Authors: Sasisekaran Jayanthi , Chow Ricky , Burton Philip , Alain Claude
Published: March 2021

Phonological encoding, a subprocess in speech production, proceeds incrementally from word onset to offset. However, the incremental nature of encoding for multisyllabic words is unclear, and limited research has examined neural activity underlying the seriality of the process. In the present study, we investigated the timing of encoding between and within syllables of bisyllabic words using a data-driven cluster-based analysis of electroencephalography (EEG) data. In a phoneme-monitoring task, young adults covertly named pictures of bisyllabic words with a prespecified target phoneme present or absent. Target phonemes in target-present trials were distributed among four serial positions of the word concept: first syllable (S1) onset or offset and second syllable (S2) onset or offset. Upon covert naming, participants responded to target presence via button press or withheld responses for target absence. Neuroelectric activity during task performance was recorded using EEG and analyzed using cluster-based permutation testing. Faster response times and differences in neural activity were observed for monitoring targets at S1 onset than S2 onset, and for monitoring targets at S1 onset than S1 offset. No differences were found between monitoring targets at S2 onset and S2 offset. Our study supports the incremental nature of phonological encoding in bisyllabic words. Furthermore, the neural findings confirm that the serial time course of encoding in bisyllabic words extends to phonemes within the first, but not the subsequent syllable. Findings may have implications for current models of speech production.