bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic and Hybrid Configurations for Extracorporeal Membrane Oxygenation: An Analysis of the Chinese Extracorporeal Life Support Registry
Authors: Li Chenglong , Xie Haixiu , Li Jun , Qin Bingyu , Lu Junyu , Zhang Jinsong , Lv Liwen , Li Binfei , Zhou Chengbin , Yin Yongjie , Qiu Haibo , Li Yimin , Liu Xiaojun , Hou Xiaotong
Published: August 2021

Dynamic or hybrid configurations for extracorporeal membrane oxygenation (ECMO) are needed when patient physiology or clinical conditions change. Dynamic configurations included configurations converting from veno-arterial (V-A) ECMO or veno-venous (V-V) ECMO to other forms. Hybrid configurations included venous-arteriovenous (V-AV) and venovenous-arterial (VV-A) ECMO. This study retrospectively analyzed a total of 3,814 ECMO cases (3,102 adult cases) reported to the Chinese Society of Extracorporeal Life Support from January 1, 2017 to December 31, 2019. Eight-three adult patients had dynamic or hybrid ECMO configurations, whose primary diagnoses included cardiogenic shock (33.7%), cardiac arrest (6.0%), acute respiratory failure (39.8%), septic shock (9.6%), multiple trauma (3.6%), pulmonary hypertension (3.6%), and others (3.6%). Configuration changes occurred in 37 patients with the initial configuration of VA (20 to VV, 13 to V-AV, and 4 to VV-A) and 27 with the initial configuration of VV (7 to VA, and 20 to V-AV). A total of 46 (55.4%) patients received hybrid configurations of V-AV and 10 (12.0%) received VV-A. Patients with the initial configuration of VV who converted to other configurations had higher in-hospital mortality (74.1%) than other initial configurations (VA 45.9%, V-AV 76.9%, VV-A 66.7%, P = 0.021). We concluded that dynamic or hybrid ECMO configurations were used in various underlying diseases, in which V-AV was most commonly used. Patients receiving VV ECMO for respiratory support initially, who then converted to other configurations for both respiratory and circulatory support, had significantly worst outcomes among the groups studied. The initial configuration should be selected carefully after thorough assessment of patient condition.
Sequestration of Dexmedetomidine in Ex Vivo Cardiopulmonary Bypass Circuits
Authors: Wilder Nicole S. , Andropoulos Dean B. , Paugh Theron , Kibler Kathleen K. , Nicolson Susan C. , Zuppa Athena F. , Moorthy Ganesh S.
Published: August 2021

Dexmedetomidine (DEX) is a sedative used in combination with other drugs in neonates and infants undergoing cardiac surgery using cardiopulmonary bypass (CPB). This study aimed to evaluate the disposition of DEX after administration to the ex vivo CPB circuits following different bolus doses and continuous infusion of DEX, including the effect of circuit coating, temperature, and modified ultrafiltration (MUF). Cardiopulmonary bypass circuits were setup ex vivo and primed with reconstituted blood. Dexmedetomidine was administered to the circuit (as a single bolus or single bolus along with continuous infusion). The circuit was allowed to equilibrate during the first 5 minutes, blood samples were collected at multiple time points (5–240 minutes). Blood samples were processed to collect plasma and analyzed for DEX with a validated assay. The majority of DEX sequestration in ex vivo CPB circuits occurred within the first 15 minutes. The percent of DEX remained in plasma pre-MUF (16–71%) and post-MUF (22–92%) varied depending on the dose and dosing scheme. Modified ultrafiltration significantly increased the plasma concentration of DEX in 19 of 23 circuits by an average of 12.1 ± 4.25% (p < 0.05). The percent sequestration of DEX was lower in CPB circuits at lower DEX doses compared to higher doses. A combination of DEX initial loading dose and continuous infusion resulted in steady concentrations of DEX over 4 hours. At therapeutically relevant concentrations of DEX (485–1,013 pg/ml), lower sequestration was observed in ex vivo CPB circuits compared to higher doses. The sequestration of DEX to circuits should be considered to achieve the optimal concentration of DEX during CPB surgery.
The Role of Serial Right Heart Catheterization Survey in Patients Awaiting Heart Transplant on Ventricular Assist Device
Authors: Ruan Diana T. , Farr Maryjane , Ning Yuming , Kurlansky Paul , Sayer Gabriel , Uriel Nir , Naka Yoshifumi , Takeda Koji
Published: August 2021

Current guidelines recommend serial right heart catheterization (RHC) to survey pulmonary hypertension in patients awaiting heart transplant. However, the role and impact of this surveillance is unclear in patients with a left ventricular assist device (LVAD). We reviewed our surveillance RHC protocol to determine whether useful data were obtained to justify the risks of serial invasive procedures (i.e., excessive bleeding). Between January 2015 and December 2018, 78 patients who received an LVAD as bridge-to-transplant (BTT) were included in this study. Routine RHC surveillance was performed every 6 months. Hemodynamic variables were retrospectively collected and reviewed. In 78 patients, 205 RHCs were analyzed. Median patient age was 54 years (IQR 46–61), and 64 (82%) were male. Thirty-six patients (46%) had pulmonary vascular resistance (PVR) ≤ 3 Wood units (WUs), and 42 patients (54%) had PVR > 3 WUs before LVAD. After LVAD implantation, mean PVR decreased by 36% from 3.8 ± 2.1 to 2.4 ± 1.1 WUs (p < 0.001) at 6 months and stabilized below 3 WUs at all post-LVAD time points. Four patients (11%) with pre-LVAD PVR ≤ 3 and 16 patients (38%) with a pre-LVAD PVR > 3 had PVR > 3 at least once during RHC survey. Of the 56 (76%) transplanted patients, six (40%) of 15 patients with a post-LVAD PVR >3 at least once developed moderate-to-severe right ventricular dysfunction. Although PVR significantly decreased after LVAD implant, PVR values fluctuated, particularly for those with pre-LVAD PVR > 3.0 WUs. Routine RHC appears valid for all BTT patients.
Cross-Circulation for Extracorporeal Liver Support in a Swine Model
Authors: Wu Wei Kelly , Tumen Andrew , Stokes John W. , Ukita Rei , Hozain Ahmed , Pinezich Meghan , O’Neill John D. , Lee Michael J. , Reimer Jonathan A. , Flynn Charles R. , Talackine Jennifer R. , Cardwell Nancy L. , Benson Clayne , Vunjak-Novakovic Gordana , Alexopoulos Sophoclis P. , Bacchetta Matthew
Published: August 2021

Although machine perfusion has gained momentum as an organ preservation technique in liver transplantation, persistent organ shortages and high waitlist mortality highlight unmet needs for improved organ salvage strategies. Beyond preservation, extracorporeal organ support platforms can also aid the development and evaluation of novel therapeutics. Here, we report the use of veno-arterial-venous (V-AV) cross-circulation (XC) with a swine host to provide normothermic support to extracorporeal livers. Functional, biochemical, and morphological analyses of the extracorporeal livers and swine hosts were performed over 12 hours of support. Extracorporeal livers maintained synthetic function through alkaline bile production and metabolic activity through lactate clearance and oxygen consumption. Beyond initial reperfusion, no biochemical evidence of hepatocellular injury was observed. Histopathologic injury scoring showed improvements in sinusoidal dilatation and composite acute injury scores after 12 hours. Swine hosts remained hemodynamically stable throughout XC support. Altogether, these outcomes demonstrate the feasibility of using a novel V-AV XC technique to provide support for extracorporeal livers in a swine model. V-AV XC has potential applications as a translational research platform and clinical biotechnology for donor organ salvage.
Intra-aortic Balloon Pump Use With Extra Corporeal Membrane Oxygenation—A Mock Circulation Loop Study
Authors: Farag James , Stephens Andrew F. , Juene Chong W. , Gregory Shaun D. , Marasco Silvana F.
Published: August 2021

Venoarterial extracorporeal membrane oxygenation (ECMO) is used in cardiogenic shock refractory to inotropic support and intra-aortic balloon pump (IABP) support. Peripheral ECMO can lead to ventricular distention, and IABP can be used to mitigate these effects. The aim of this study was to quantify the effects of IABP concomitant with ECMO, under different simulated hemodynamic conditions in a mock circulatory loop. Different simulated states of isolated left ventricular (LV) failure and biventricular failure with graded LV failure severities were supported with ECMO and ECMO with IABP. The impact on left ventricular end-diastolic pressure (LVEDP), volume (LVEDV), coronary flow rate, and cerebral flow rate were evaluated. Left ventricular volumes and pressures increased from the heart failure states with the addition of ECMO. The IABP provided between 3% and 7% reductions in LVEDP and between 1% and 10% reductions in LVEDV. The addition of IABP had minimal effect on cerebral blood flow (0% to 7%), but the variable impact on coronary blood flow with increased diastolic coronary flow of 23% to 50%, but the reduction in mean coronary flow by up to 30%. The efficacy of the IABP was strongly related to ventricular contractility. This study demonstrates the need for careful IABP selection concomitant with ECMO.
Janus Kinase inhibitors for the treatment of hospitalized patients with COVID-19
Authors: Florescu Diana F. , Kalil Andre C.
Published: August 2021

Purpose of review

Janus Kinase (JAK) inhibitors have been successfully utilized in the clinical treatment of several rheumatologic (e.g. rheumatoid arthritis) and inflammatory diseases (e.g. hemophagocytic lymphohistiocytosis). Based on the growing evidence that moderate and severe COVID-19 infections are associated with a dysregulated inflammatory state, this class of medications has been repurposed as a potential therapy for COVID-19, an infection caused by Severe Acute Respiratory Syndrome Coronavirus 2.

Recent findings

Three JAK inhibitors have been evaluated in human studies of COVID-19: Baricitinib, Tofacitinib, and Ruxolitinib. Most published studies are observational, but three randomized placebo-controlled double-blind trials have been completed: two large trials (N = 2,558 patients) with baricitinb demonstrated significant faster improvement in clinical status and reduction in the recovery time, as well as, significant reduction in the progression to invasive mechanical ventilation and mortality. One smaller randomized trial (N = 289) involving tofacitinib showed significant reduction in the progression to invasive ventilation or death. Notably, these three randomized placebo-controlled trials with close to 3,000 patients did not reveal any safety concerns associated with JAK inhibitors in terms of secondary infections or venous thromboembolism. Based on this high-quality evidence, both the Infectious Diseases Society of America and the National Institutes of Health guidelines recommend using baricitinib as part of the treatment approach for hospitalized patients with COVID-19.

JAK inhibitors are novel treatment agents in the field of infectious diseases. One JAK inhibitor, baricitinib has demonstrated significant clinical and survival benefits in hospitalized patients with COVID-19 in phase III randomized placebo-controlled trials. Baricitinib is already recommended for clinical practice by multiple guidelines.
Case Report: Bilateral Ciliary Body Detachment in a Patient Taking Oral Diet Pills
Authors: Li Yanzhen , Tao Yuan , Gao Xiaofang , Yu Fanglei
Published: August 2021

SIGNIFICANCE

The use of antiobesity drugs is becoming more widespread, and the resulting adverse effects are also increasing. Visual impairments caused by weight-loss pills need a timely and accurate diagnosis and treatment. Prompt diagnosis and treatment can achieve a satisfactory prognosis.

PURPOSE

This report describes a case of a significant decline in bilateral visual acuity caused by taking diet pills and explores the possible pathogenesis.

CASE REPORT

A 32-year-old Chinese woman showed shallow anterior chambers, and intraocular pressure (IOP) was 38 mmHg bilaterally after taking Korean prescription diet pills for 6 days. The best-corrected visual acuity of both eyes was 0.03. The ultrasound biomicroscopy showed complete ciliary body detachment accompanied with angle closure. The central anterior chamber depths were 1.70 mm in the right eye and 1.61 mm in the left eye. The patient was diagnosed with ciliary body detachment with secondary elevated IOP. The patient was treated with pilocarpine, carteolol hydrochloride, brinzolamide, mannitol, and dexamethasone sodium phosphate. The patient had rewarding prognosis after treatment with discontinuation of diet pills, control of IOP, and glucocorticoids.

CONCLUSIONS

Extensive publicity and education are needed to ensure that consumers do not abuse diet pills; meanwhile, a timely diagnosis and withdrawal are crucial for a desirable prognosis. Clinicians need to consider the possibility of drug-secondary ocular diseases.
Challenges in Reading Arabic among Children with Dyslexia
Authors: Alabdulkader Balsam , Alshubaili Hayfa , Alhashmi Areej
Published: August 2021

SIGNIFICANCE

There are limited studies assessing reading performance and children's difficulties with dyslexia especially when reading Arabic, a language that has a substantially different script from English and other Latin-based languages.

PURPOSE

This study aimed to (1) measure reading performance in children with dyslexia by acuity level and (2) conduct an indirect comparison between the effects of dyslexia on Arabic versus English readers.

METHODS

Twenty children aged 9 to 12 years with dyslexia and 30 controls aged 9 to 11 years were included in the study. Reading performance was evaluated using maximum reading speed, reading acuity, and critical print size (CPS). Two Arabic charts, the Balsam Alabdulkader–Leat chart and the International Reading Speed Texts chart, were used to evaluate reading performance. The number of errors was calculated and plotted against print size.

RESULTS

ANOVA revealed a significant difference between the two groups in all reading performance measures (P < .05). Reading speed for children with dyslexia was significantly lower than that for the control group (33 vs. 90 standard-length words per minute). Critical print sizes were 0.25 and 0.10 logMAR for children with dyslexia and the control group, respectively. Reading acuity was worse for children with dyslexia in comparison with the control group. Error number above the CPS was significantly higher in children with dyslexia than in the control group.

CONCLUSIONS

Reading speed measures were lower for children with dyslexia compared with controls. Children with dyslexia required larger CPS to read at their maximum speed, indicating that larger print sizes may improve reading with greater speed. The difference in reading performance measures between controls and children with dyslexia is higher when reading Arabic than when reading English. This suggests that the intricate Arabic script and crowding may more strongly affect children with dyslexia reading Arabic.
Image Size and the Range of Clear and Single Binocular Vision in 3D Displays
Authors: McCormack Glen L. , Kulowski Kathryn A.
Published: August 2021

SIGNIFICANCE

The range of clear and single binocular vision differs between 3D displays and clinical prism vergences, but this difference is unexplained. This difference prevents clinicians from predicting the range of clear and single binocular vision in 3D-viewing patients. In this study, we tested a hypothesis for this difference.

PURPOSE

The purpose of this study was to determine whether changing fixation target size in 3D viewing significantly affects the vergence ranges and, if so, then to determine whether the target size effect is driven by fusional vergence gain changes, threshold of blur changes, or both.

METHODS

Twenty-one visually normal adults aged 18 to 28 years viewed 3D images at 40 cm in an electronic stereoscopic. The fixation target, a Maltese cross, moved in depth at 2∆/s by way of changing crossed or uncrossed disparity until blur and diplopia ensued. We used four target sizes: (1) small (width × height, 0.21° × 0.63°), (2) medium (1.43° × 4.3°), (3) large (3.6° × 10.8°), and (4) 3D (size changing congruently with disparity). The effect of target size on responses was tested by mixed ANOVAs.

RESULT

Mean convergence blurs and breaks increased with target size by 40% (P < .001) and 71% (P < .001), respectively, and in divergence by 33% (P = .03) and 30% (P = .04), respectively. The increases in break magnitude with target size implicate fusional vergence gain change in the size effect. Increasing target size raised the threshold of blur from 1.06 to 1.82 D in convergence and from 0.97 to 1.48 D in divergence (P = .008).

CONCLUSIONS

Growing fixation target size in 3D viewing increases fusional vergence gain and blur thresholds, which together increase the limits of clear and single binocular vision. Therefore, the clarity of a 3D image depends not only on its disparity but also on the size of the viewed image.
Case Report: Subconjunctival Bevacizumab for the Treatment of Refractory Pseudophakic Cystoid Macular Edema
Authors: Yeter Volkan , Koçak Nurullah , Eraydin Bilge
Published: August 2021

SIGNIFICANCE

In this report, the authors present a case of a 63-year-old man with recurrent pseudophakic cystoid macular edema. Macular edema was refractory to the treatments with periocular corticosteroid injection and topical anti-inflammatory medications. It was treated with subconjunctival bevacizumab (2.5 mg) injections.

PURPOSE

The purpose of this report was to demonstrate the efficacy and safety of repeated injections of subconjunctival bevacizumab in pseudophakic cystoid macular edema.

CASE REPORT

A 63-year-old White man presented with ongoing blurred vision in his left eye 4 months after a complicated cataract surgery. Despite the administration of sub-Tenon triamcinolone in the first-month visit because of cystoid macular edema and the use of topical steroid and nonsteroidal anti-inflammatory medications during the 4 months, there was no change in his vision. The first subconjunctival bevacizumab injection was performed 16 weeks after cataract surgery. The best-corrected visual acuity was significantly improved, and central retinal thickness dramatically decreased after the first injection. Macular edema reoccurred 26 and 46 weeks after cataract surgery. At these relapses, repeated subconjunctival injections of bevacizumab were influential in resolving macular edema and restoration of vision, even in the chronic phase. After 6 months, visual acuity (20/20) and central retinal thickness (274 μm) were stable after four total injections. No drug-related adverse events were observed during the follow-up period.

CONCLUSIONS

The repeated subconjunctival injections of bevacizumab were effective and well tolerated in pseudophakic cystoid macular edema. Subconjunctival bevacizumab may be a safe alternative to intravitreal applications in patients with pseudophakic cystoid macular edema.
Reducing Supply Cost by Standardization of Surgical Equipment in Laparoscopic Appendectomy
Authors: Kim Soo-Hong , Kim Hyun-Yul , Lee Si-Hak , Yang Kwangho , Park Byung-Soo , Choi Byung-Hyun , Jung Hyuk Jae
Published: August 2021

Background and Objectives:

Compensation for increased medical services from reimbursement systems are sometimes insufficient. Generally, appendectomies are performed by individual surgeons with their preferred instrument. Surgical equipment standardization is known to reduce medical cost without compromising patient safety. Hence, we investigated the effectiveness of surgical equipment standardization to reduce the required operative cost for laparoscopic appendectomy at our tertiary hospital.

Methods:

Nine surgeons at our tertiary hospital agreed to use standardized equipment for laparoscopic appendectomy. We compared outcomes among patients who underwent laparoscopic appendectomy between December 2012 and June 2013 before standardization (control group) and between August 2015 and February 2016 after standardization. Participating provider and staff convenience was also surveyed using a questionnaire.

Results:

The implementation of standardized equipment for laparoscopic appendectomy decreased intraoperative supply cost from US $552.92 to $450.17. Operative times also decreased from 73.8 to 53.3 minutes. However, hospital days and complication rates remained unchanged. Participants responded that surgical equipment standardization improved efficiency in the operating room and reduced the cost.

Conclusion:

Surgical equipment standardization in laparoscopic appendectomy is effective in reducing intraoperative supply cost without compromising patient safety.
Using Accountable Care Teams to Improve Timely Discharge: A Pilot Study
Authors: Orewa Gregory N. , Feldman Sue S. , Hearld Kristine Ria , Kennedy Kierstin Cates , Hall Allyson G.
Published: August 2021

Background and Objective:

Hospitals worldwide are faced with the problem of discharging patients on time. Delayed discharge creates domino effects with significant implications for hospitals. The accountable care team (ACT) is a multidisciplinary, unit-based approach to identifying opportunities to improve patient care and address inefficiencies in care delivery and throughput, including assuring timely discharges. In response to concerns about emergency department boarding times and delays in timely discharge, the ACT recommended a set of strategies to improve communication across team members and to reduce wait times for transportation within and outside the hospital. Collectively these strategies were thought to increase the proportion of patients discharged on time. In this article, we describe and assess changes in timely discharge resulting from the implementation of strategies recommended by the ACT.

Methods:

This study uses a retrospective, quasi-experimental design to compare the percentage of discharges by 1 pm of hospital units implementing the ACT intervention to those units not implementing the intervention. Median discharge time was compared pre- and post-implementation using the Wilcoxon rank sum test. Difference-in-differences modeling was employed to assess whether changes in the percentage of discharges by 1 pm differed between units implementing the intervention and units not implementing the intervention.

Results:

One month post-implementation, the percentage discharged by 1 pm was statistically significantly higher for units implementing the intervention (53.6%) compared with comparison units (22.5%, t = −4.48, P < .01). Statistically significant differences in the percentage discharged by 1 pm were also seen at 3 and 6 months post-implementation. The median discharge time showed a statistically significant decrease by 77 minutes from the baseline to intervention period (P < .01).

Conclusion:

The result from the study suggests that ACTs can be used to develop approaches aimed at improving patient care in general, and discharge efficiencies in particular. Health care organizations are encouraged to utilize and then evaluate the specific activities of multidisciplinary teams aimed at developing recommendations for practice improvement.
Presentation, Treatment, and Prognosis of Esophageal Carcinoma in a Nationwide Comparison of Sweden and the Netherlands
Authors: Kalff Marianne C. , Gottlieb-Vedi Eivind , Verhoeven Rob H. A. , van Laarhoven Hanneke W. M. , Lagergren Jesper , Gisbertz Suzanne S. , Markar Sheraz R. , van Berge Henegouwen Mark I.
Published: August 2021

Objective:

This population-based study aimed to compare presentation, treatment allocation and survival of potentially curable esophageal cancer patients between Sweden and the Netherlands.

Summary of Background data:

Identification of inter-country differences in treatment allocation and survival may be used for targeted esophageal cancer care improvement.

Methods:

Nationwide datasets were acquired from a Swedish cohort study and the Netherlands Cancer Registry. Patients with potentially curable (cT1-T4a/Tx, cN0/+, cM0/x) esophageal adenocarcinoma or squamous cell carcinoma (SCC) diagnosed in 2011–2015 were included. Multivariable logistic regression provided odds ratios (OR) for treatment allocation, and multivariable Cox model provided hazard ratios (HR) for overall survival, all with 95% confidence intervals (CI), adjusted for age, sex, year, tumor sub-location and stage.

Results:

Among 1980 Swedish and 7829 Dutch esophageal cancer patients, Swedish patients were older (71 vs 69 years, P <0.001) and had higher cT-stage (cT3: 49% vs 46%, P <0.001). After adjustment for confounders, Swedish patients were less frequently allocated to curative treatment (adenocarcinoma: OR=0.31, 95%CI 0.26–0.36; SCC: OR=0.28, 95%CI 0.22–0.36). Overall survival was lower in Swedish patients (adenocarcinoma: HR=1.36, 95%CI 1.27–1.46; SCC: HR=1.38, 95%CI 1.24–1.53), also when allocated to curative treatment (adenocarcinoma: HR=1.12, 95%CI 1.01–1.24; SCC: HR=1.34, 95%CI 1.14–1.59).

Conclusion:

Swedish patients with potentially curable esophageal cancer were less frequently allocated to curative treatment, and showed lower survival compared to Dutch patients. The less pronounced inter-country survival difference after curative treatment suggests that the overall survival difference could at least partly be due to relative undertreatment of Swedish patients. Shared curative treatment thresholds across Europe may help improve survival of esophageal cancer patients.
Incisional Surgical Site Infections After Mass and Layered Closure of Upper Abdominal Transverse Incisions
Authors: Grąt Michał , Morawski Marcin , Krasnodębski Maciej , Borkowski Jan , Krawczyk Piotr , Grąt Karolina , Stypułkowski Jan , Maczkowski Bartosz , Figiel Wojciech , Lewandowski Zbigniew , Kobryń Konrad , Patkowski Waldemar , Krawczyk Marek , Wróblewski Tadeusz , Otto Włodzimierz , Paluszkiewicz Rafał , Zieniewicz Krzysztof
Published: August 2021

Objective:

To compare the early results of mass and layered closure of upper abdominal transverse incisions.

Summary of Background Data:

Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking.

Methods:

This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727).

Results:

A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13–0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12–0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively.

Conclusions:

Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.
Effect of multiple freeze–thaw cycles on the detection of anti-SARS-CoV-2 IgG antibodies
Authors: Shurrab Farah M. , Al-Sadeq Duaa W. , Amanullah Fathima , Younes Salma N. , Al-Jighefee Hadeel , Younes Nadin , Dargham Soha R. , Yassine Hadi M. , Abu Raddad Laith J. , Nasrallah Gheyath K.
Published: August 2021

Several studies have investigated the effect of repeated freeze–thaw (F/T) cycles on RNA detection for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, no data are available regarding the effect of repeated F/T cycles on SARS-CoV-2 antibody detection in serum. We investigated the effect of multiple F/T cycles on anti-SARS-CoV-2 IgG detection using an ELISA test targeting the nucleocapsid antibodies. Ten positive and 1 negative SARS-CoV-2 IgG sera from 11 participants, in replicates of 5, were subjected to a total of 16 F/T cycles and stored at 4 °C until tested by ELISA. Statistical analysis was performed to test for F/T cycle effect. None of the 10 positive sera became negative after 16 F/T cycles. There was no significant difference in the OD average reading between the first and last F/T cycles, except for one serum with a minimal decline in the OD. The random effect linear regression of log (OD) on the number of cycles showed no significant trend, with a slope consistent with zero (B=−0.0001; 95 % CI −0.0008; 0.0006; P-value=0.781). These results suggest that multiple F/T cycles had no effect on the ability of the ELISA assay to detect SARS-CoV-2 IgG antibodies.
CuNA: Cumulant-based Network Analysis of genotype-phenotype associations in Parkinson’s Disease
Authors: Bose Aritra , Platt Daniel E. , Haiminen Niina , Parida Laxmi
Published: August 2021

Parkinson’s Disease (PD) is a progressive neurodegenerative movement disorder characterized by loss of striatal dopaminergic neurons. Progression of PD is usually captured by a host of clinical features represented in different rating scales. PD diagnosis is associated with a broad spectrum of non-motor symptoms such as depression, sleep disorder as well as motor symptoms such as movement impairment, etc. The variability within the clinical phenotype of PD makes detection of the genes associated with early onset PD a difficult task. To address this issue, we developed CuNA, a cumulant-based network analysis algorithm that creates a network from higher-order relationships between eQTLs and phenotypes as captured by cumulants. We also designed a multi-omics simulator, CuNAsim to test CuNA’s qualitative accuracy. CuNA accurately detects communities of clinical phenotypes and finds genes associated with them. When applied on PD data, we find previously unreported genes INPP5J, SAMD1 and OR4K13 associated with symptoms of PD affecting the kidney, muscles and olfaction. CuNA provides a framework to integrate and analyze RNA-seq, genotype and clinical phenotype data from complex diseases for more targeted diagnostic and therapeutic solutions in personalized medicine. CuNA and CuNAsim binaries are available upon request.
Combining SNP-to-gene linking strategies to pinpoint disease genes and assess disease omnigenicity
Authors: Gazal Steven , Weissbrod Omer , Hormozdiari Farhad , Dey Kushal , Nasser Joseph , Jagadeesh Karthik , Weiner Daniel , Shi Huwenbo , Fulco Charles , O’Connor Luke , Pasaniuc Bogdan , Engreitz Jesse M. , Price Alkes L.
Published: August 2021

Although genome-wide association studies (GWAS) have identified thousands of disease-associated common SNPs, these SNPs generally do not implicate the underlying target genes, as most disease SNPs are regulatory. Many SNP-to-gene (S2G) linking strategies have been developed to link regulatory SNPs to the genes that they regulate in cis, but it is unclear how these strategies should be applied in the context of interpreting common disease risk variants. We developed a framework for evaluating and combining different S2G strategies to optimize their informativeness for common disease risk, leveraging polygenic analyses of disease heritability to define and estimate their precision and recall. We applied our framework to GWAS summary statistics for 63 diseases and complex traits (average N=314K), evaluating 50 S2G strategies. Our optimal combined S2G strategy (cS2G) included 7 constituent S2G strategies (Exon, Promoter, 2 fine-mapped cis-eQTL strategies, EpiMap enhancer-gene linking, Activity-By-Contact (ABC), and Cicero), and achieved a precision of 0.75 and a recall of 0.33, more than doubling the precision and/or recall of any individual strategy; this implies that 33% of SNP-heritability can be linked to causal genes with 75% confidence. We applied cS2G to fine-mapping results for 49 UK Biobank diseases/traits to predict 7,111 causal SNP-gene-disease triplets (with S2G-derived functional interpretation) with high confidence. Finally, we applied cS2G to genome-wide fine-mapping results for these traits (not restricted to GWAS loci) to rank genes by the heritability linked to each gene, providing an empirical assessment of disease omnigenicity; averaging across traits, we determined that the top 200 (1%) of ranked genes explained roughly half of the heritability linked to all genes. Our results highlight the benefits of our cS2G strategy in providing functional interpretation of GWAS findings; we anticipate that precision and recall will increase further under our framework as improved functional assays lead to improved S2G strategies.
Pre-diagnostic plasma metabolomics and the risk of exfoliation glaucoma
Authors: Kang Jae H. , Zeleznik Oana , Frueh Lisa , Lasky-Su Jessica , Eliassen A. Heather , Clish Clary , Rosner Bernard A. , Pasquale Louis R. , Wiggs Janey L.
Published: August 2021

Objective

To identify pre-diagnostic plasma metabolomic biomarkers associated with risk of exfoliation glaucoma (XFG).

Methods

We conducted a metabolomic study using a 1:1 matched nested case-control study design within the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Participants provided blood samples in 1989-’90 (NHS) and 1993-’95 (HPFS); we identified 205 participants who newly developed XFG during follow-up to 2018 (average time to diagnosis from blood draw =11.8 years); XFG was confirmed with medical record review. We profiled plasma metabolites using liquid chromatography- mass spectrometry and identified 379 known metabolites that passed quality control checks. Metabolites were transformed using probit scores for normality. We used multivariable-adjusted logistic regression adjusting for matching factors (such as age, residential latitude, season and time of blood draw), glaucoma family history and other covariates. Metabolite Set Enrichment Analysis was used to identify metabolite classes associated with risk of XFG. Number of effective tests (NEF) and False Discovery Rate (FDR) were used to adjust for multiple comparisons.

Results

Mean age of cases (n=205) at diagnosis was 71 years; 84% were women and >99% were Caucasian; matched controls (n=205) all reported eye exams as of the matched cases’ index date. A total of 33 metabolites were nominally significantly associated with XFG risk (p<0.05) and 4 metabolite classes were significantly associated (FDR<0.05). Overall, adverse associations were observed for the classes of lysophosphatidylcholines (FDR=0.02) and phosphatidylethanolamine plasmalogens (FDR=0.004). Inverse associations were observed for triglycerides (FDR<0.001) and steroid and steroid derivatives (FDR=0.03); in particular, the multivariable-adjusted odds ratio for XFG risk associated with each 1 standard deviation increase in plasma cortisone levels was 0.49 (95% CI=0.32-0.74; NEF=0.05). Results did not differ materially by time between blood draw and diagnosis, latitude of residence (< or ≥41°N latitude), age (< or ≥60 years), sex or glaucoma family history.

Conclusions

Four broad classes of metabolites (including steroids such as cortisone and 3 lipid classes) in pre-diagnostic plasma collected almost a decade before diagnosis were associated with XFG risk; these results should be confirmed in future studies.
Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome
Authors: Toescu Sebastian M. , Bruckert Lisa , Jabarkheel Rashad , Yecies Derek , Zhang Michael , Clark Christopher A. , Mankad Kshitij , Aquilina Kristian , Grant Gerald A. , Feldman Heidi M. , Travis Katherine E. , Yeom Kristen W.
Published: August 2021

Cerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome.

In this retrospective case-control study, twenty-eight children with medulloblastoma (mean age 8.8 ± 3.8 years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy at 30 nodes along each tract.

Thirteen patients developed cerebellar mutism syndrome. Fractional anisotropy was significantly lower in the distal segments of the superior cerebellar peduncle pre-operatively in all patients (p=0.01). Pre-operative changes in fractional anisotropy did not predict cerebellar mutism syndrome. However, post-operative reductions in fractional anisotropy were highly specific to the distal left superior cerebellar peduncle, and were most pronounced at follow-up timepoints (p=0.042,0.038), in those that developed cerebellar mutism syndrome compared to patients that did not.

High spatial resolution cerebellar profilometry identifies a site-specific alteration of the distal segment of the superior cerebellar peduncle unique to cerebellar mutism syndrome with important surgical implications in the treatment of these devastating tumours of childhood.
Development and performance evaluation of a low-cost in-house rRT-PCR assay in Ecuador for the detection of SARS-CoV-2
Authors: Salinas Marco A. , Aguirre Diana F. , De la Torre David I. , Pérez-Galarza Jorge , Pibaque Ronny J. , Beltran Paul A. , Veloz Tatiana J. , Baldeón Lucy Y.
Published: August 2021

Antecedents

Ecuador has had the greatest fatality rate from Coronavirus (COVID-19) in South America during the SARS-CoV-2 pandemic. To control the pandemic, it is necessary to test as much population as possible to prevent the spread of the SARS-CoV-2 infection. For the Ecuadorian population, accessing a PCR test is challenging, since commercial screening kits tend to be expensive. Objective: the objective of this study was to develop an in-house duplex rRT-PCR protocol for the detection of SARS-CoV-2 that contributes to the screening while keeping quality and low testing costs. Results: An in-house duplex rRT-PCR protocol based on the viral envelope (E) gene target of SARS-CoV-2 and a human ribonuclease P gene (RP) as an internal control is reported. The protocol was optimized to obtain primers E with an efficiency of up to 94.45% and detection of 100% of SARS-CoV-2 up to 15 copies per uL. The clinical performance was determined by a sensibility of 93.8% and specificity of 98.3%. Conclusion: we developed, standardized, and validated a low-cost, sensitive in-house duplex rRT-PCR assay that may be utilized in low-income countries.
Returning Actionable Genomic Results in a Research Biobank: Analytic Validity, Clinical Implementation and Resource Utilization
Authors: Blout Zawatsky Carrie L. , Shah Nidhi , Machini Kalotina , Perez Emma , Christensen Kurt D. , Zouk Hana , Steeves Marcie , Koch Christopher , Uveges Melissa , Shea Janelle , Gold Nina , Krier Joel , Boutin Natalie , Mahanta Lisa , Rehm Heidi L. , Weiss Scott T. , Karlson Elizabeth W. , Smoller Jordan W. , Lebo Matthew S. , Green Robert C.
Published: August 2021

Over 100 million research participants around the world have had research array-based genotyping (GT) or sequencing (GS), but only a small fraction of these have been offered return of actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to patient recontact revealed that GT falsely identified PLPVs in 44.9% of samples, and GT failed to identify 72.0% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1% and 2.5% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5% actively or passively declined further disclosure. 76.3% of those carrying PLPVs were unaware that they were carrying the variant and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately $129,000 USD per year in laboratory testing and research staff support, representing $14 per participant whose DNA was analyzed or $3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.
Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort
Authors: Israel Ariel , Merzon Eugene , Schäffer Alejandro A. , Shenhar Yotam , Green Ilan , Golan-Cohen Avivit , Ruppin Eytan , Magen Eli , Vinker Shlomo
Published: August 2021

Importance

Israel was among the first countries to launch a large-scale COVID-19 vaccination campaign, and quickly vaccinated its population, achieving early control over the spread of the virus. However, the number of COVID-19 cases is now rapidly increasing, which may indicate that vaccine protection decreases over time.

Objective

To determine whether time elapsed since the second BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) injection is significantly associated with the risk of post-vaccination COVID-19 infection.

Design

This is a retrospective cohort study performed in a large state-mandated health care organization in Israel.

Participants

All fully vaccinated adults who have received a RT-PCR test between May 15, 2021 and July 26, 2021, at least two weeks after their second vaccine injection were included. Patients with a history of past COVID-19 infection were excluded.

Main Outcome and Measure

Positive result for the RT-PCR test.

Results

The cohort included 33,993 fully vaccinated adults, 49% women, with a mean age of 47 years (SD, 17 years), who received an RT-PCR test for SARS-CoV-2 during the study period. The median time between the second dose of the vaccine and the RT-PCR test was 146 days, interquartile range [121-167] days. 608 (1.8%) patients had positive test results. There was a significantly higher rate of positive results among patients who received their second vaccine dose at least 146 days before the RT-PCR test compared to patients who have received their vaccine less than 146 days before: odds ratio for infection was 3.00 for patients aged over 60 (95% CI 1.86-5.11); 2.29 for patients aged between 40 and 59 (95% CI 1.67-3.17); and 1.74 for patients aged between 18 and 39 (95% CI 1.27-2.37); P<0.001 in each age group.

Conclusions and Relevance

In this large population study of patients tested for SARS-CoV-2 by RT-PCR following two doses of mRNA BNT162b2 vaccine, we observe a significant increase of the risk of infection in individuals who received their last vaccine dose since at least 146 days ago, particularly among patients older than 60.
Cytogenetic & Molecular analysis in Premature Ovarian Failure
Authors: sahni Chetan , dada Rima
Published: August 2021

Introduction

Premature Ovarian Failure (POF) being a heterogeneous genetic disease involves the interaction of multiple genetic defects and environmental factors and has been associated with several chromosomal abnormalities, single gene mutations, and genetic polymorphisms. BMP15 is a member of the transforming growth factor β (TGF-β) family. BMP15 gene product (protein) have 3 domians, mature domain (c-terminal region) of BMP15 binds to receptors located on granulosa cell surface to participate in key steps regarding ovarian function, such as granulosa cell proliferation and follicle maturation, ovulation rate modulation, oocyte competence determination and regulating granulosa cell sensitivity to FSH. Single nucleotide polymorphisms (SNPs) of the BMP-15 gene are associated with POF.

Materials & Methods

30 POF patients and 30 healthy age matched controls were recruited for cytogenetic and molecular analysis. 10 ml whole blood was collected for karyotyping and PCR and PCR was performed for known SNPs of BMP-15 gene (−9C>G, 538G>A, 788insTCT and 852C>T) respectively. Amplified PCR products were sequenced commercially.

Observation/Result

Thirty cases (mean age 30 years) and thirty healthy controls (mean age 23 years) were recruited for the study. On cytogenetic analysis 2 cases had a 45, XO chromosomal complement. One case was heterozygous for the SNP (−9C>G) and one control was homozygous for the same SNP.

Discussion

The prevalence of this SNP was about 10.7% in cases & 3.3% in healthy controls. This polymorphism in promoter region may cause altered expression of the gene and results in POF.
Identification and in silico comparison of transposable elements of Solanum tuberosum subsp. andigena from two localities of Peru
Authors: Carmen Sifuentes Sheyla , Cornejo Villanueva Victor
Published: August 2021

The potato is one of the main crops in Peru, being one of the pillars in the country’s economy. It also has a cultural importance, being a basic element of Peruvian gastronomy and an emblematic crop of the Peruvian highlands, where small farmers over time have been able to conserve and cultivate 6048 native varieties. In Peru, around 300,000 hectares of potatoes are planted annually, and in 2019 Peru remained the main potato producer in Latin America, registering an annual production of 5.3 million tons. Therefore, it is necessary to study and characterize the genome of this very important tuber for the country. Although there are many potato genomic studies in the world and in Peru; these have been based on the search for genes of importance, genetic diversity, etc. and little has been deeply studied about the transposable elements (ETs) that are part of its genome. It is known that in many eukaryotes, transposable elements are powerful drivers of genome evolution, and they occupy a considerable part in plant genomes, so with these studies, more could be understood about how these ETs have intervened in the evolution of the potato in Peru; thus, how these mechanisms would help in the future to the survival of the species in scenarios of climate change, among others. This study proposes the identification and comparison of the transposable elements of the only 2 complete genomes of potatoes grown in Peru, found in the NCBI database, one from the department of Puno and the other from Cusco. There are various approaches to search for ETs in genomes, but for a complete and reliable annotation, it has been shown that the best strategy is the adoption of combined approaches, in this study, we will use 2 approaches, one based on homology, with the program RepeatMasker, and the other de novo, with the RepeatModeler2 program.
Quantifying RNA Synthesis at Rate-Limiting Steps of Transcription Using Nascent RNA-Sequencing Data
Authors: Rabenius Adelina , Chandrakumaran Sajitha , Sistonen Lea , Vihervaara Anniina
Published: August 2021

Nascent RNA-sequencing tracks transcription at nucleotide resolution. The genomic distribution of engaged transcription complexes, in turn, uncovers functional genomic regions. Here, we provide data-analytical steps to 1) identify transcribed regulatory elements de novo genome-wide, 2) quantify engaged transcription complexes at enhancers, promoter-proximal regions, divergent transcripts, gene bodies and termination windows, and 3) measure distribution of transcription machineries and regulatory proteins across functional genomic regions. This protocol follows RNA synthesis and genome-regulation in mammals, as demonstrated in human K562 erythroleukemia cells.

For complete details on the use and execution of this protocol, please refer to Vihervaara, et al., 2021.

Graphical Abstract