bluuebunny/crossref_metadata_2025 huggingface dataset:
FC 123RENAL TRANSPLANTATION MITIGATES INCREASED BIOLOGICAL (EPIGENETIC) AGE IN CHRONIC KIDNEY DISEASE
Authors: Neytchev Ognian , Witasp Anna , Nordfors Louise , Qureshi Abdul Rashid Tony , Wennberg Lars , Erlandsson Helen , Ebert Thomas , Selman Colin , Shiels Paul , Stenvinkel Peter
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) shares important features of a dysregulated ageing process with other common “burden of lifestyle” diseases, which aggregates into the diseasome of ageing. Typically, this is hallmarked by an acceleration of epigenetic (DNA methylation-based) clocks. It remains to be determined if current therapeutic interventions, such as renal transplantation or dialysis, can slow this clock, and thus the rate of biological ageing, in CKD. We therefore assessed the rate of biological ageing in CKD patients and whether these therapies impact on it, by measuring epigenetic age before and 1 year after treatment.

Methods

Whole blood samples were taken from CKD 5 patients at baseline and 1 year after renal transplantation (n=12) or dialysis (n=11; peritoneal dialysis n=7, haemodialysis n=4) as well as from age and sex-matched population-based controls (n=24). DNA methylation was measured using the Illumina Infinium Human Methylation 450K BeadChip and epigenetic age was calculated using three independent DNA methylation clocks: the Horvath, Hannum, and PhenoAge clocks. Additionally, a novel composite clock incorporating these three clocks was evaluated. We then calculated the age acceleration (difference between epigenetic and chronological age) for each clock and compared average age acceleration between groups and across time points.

Results

Incident dialysis patients displayed accelerated ageing versus chronologically age-matched controls (p<0.001). We observed a PhenoAge age acceleration difference in both the transplant (8.5 years, p=0.001) and dialysis (9.7 years, p<0.001) groups at baseline compared to control. After 1 year, we also observed a decrease of the age acceleration in the transplant group (mean reduced by 4.4 years, p=0.016), but not in the dialysis group (mean reduced by 0.7 years, p=0.668).

Conclusion

CKD 5 patients display an increased biological (i.e. epigenetic) age. This age acceleration is mitigated one year after renal transplantation, but not in patients undergoing dialysis. Neither therapy reverses high biological age.
FC 127SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS (SGLT2I) SHORT-TERM OUTCOME IN DIABETIC KIDNEY TRANSPLANT RECIPIENTS
Authors: Yagan Jude , Mahmoud Tarek S H , Geith Osama
Published: May 2021

Background and Aims

The emergence of positive data on the use of sodium glucose co-transporter inhibitors (SGLT2i) in the last several years, begged the question of whether their positive outcomes can be seen in kidney transplant recipients, as they have the same and even more pronounced cardiovascular risk factors than the general population and in addition, we got better in improving graft and patients survival in the short term , but we lack the tools to improve long term patients and graft survival where so many patients die from cardiovascular disease with a functioning graft or lose their graft from chronic changes and chronic antibody mediated rejection with difficult to control blood pressure and proteinuria

For these reasons we need more powerful tools , like the SGLT2i bearing in mind the unique side effects that might be amplified in kidney transplant recipients receiving immunosuppression like urinary tract infection, and the dip in serum creatinine.

Method

We collected data retrospectively from transplant records of patients with type II diabetes mellitus (T2D) or post-transplant diabetes mellitus (PTDM) (n=79) who were receiving SGLT2i agents plus standard of care [SOC] management and compared them to (n=56) similar diabetic patients who were only on SOC management.

Results

The two groups were comparable regarding age, sex, type of donor, type of diabetes (T2D PTDM), post-transplant period, induction immunosuppression and use of CNI. Though improvement of HbA1c was not significantly different between the two groups, patients on SGLT2i showed better drop in HbA1c compared to the SOC group (0.7% versus 0.5% respectively). Reduction of BMI was equal between the two groups (-1.1%) and there was no significant difference in the number of blood pressure medications (average 2 drugs per patient). Kidney function was assessed by the eGFR using CKD-EPI equation and by urine albumin/creatinine ratio (ACR). The eGFR was calculated at start then at 1,3,6 and 12 months. In SGLT2i group, eGFR showed a dip at 3 months (from 66 to 63.35 ml/min) then started to improve gradually toward the end of the year and maintained at a level close to baseline (65.44 ml/min). The SOC group showed gradual drop in eGFR over the year from 65.76 to 63.19 ml/min. Urine ACR reduced in the SGLT2i group from 48.79 to 23.79 mg/mmol creatinine and increased from 42.84 to 63.16 mg/mmol creatinine in the SOC group. The incidences of graft rejection, urinary tract infection, genital infection, myocardial infarction, heart failure or cerebrovascular stroke were not different between the groups.

Conclusion

Use of SGLT2i in managing diabetic patients post kidney transplantation is safe and has better short-term outcomes on renal function with comparable safety compared to standard of care therapy.
FC 129CHANGES IN PERIPHERAL NK CELLS IN KIDNEY TRANSPLANT RECIPIENTS WITH AND WITHOUT HLA DSA
Authors: Llinas Laura , Redondo Pachon Dolores , Raïch Regué Dàlia , Perez-Saez Maria Jose , Sanz Sara , Arias-Cabrales Carlos , Buxeda Anna , Burballa Carla , López-Botet José Miguel , Pascual Santos Julio , Crespo Marta
Published: May 2021

Background and Aims

Antibody-mediated rejection (ABMR) is a frequent cause of renal allograft loss. There is increasing evidence of the role of Natural Killer (NK) cells in the establishment of ABMR damage. Our group described that patients with donor-specific antibodies (DSA) and ABMR present higher proportions of NKG2A+ NK cell subset in peripheral blood than those without HLA DSA or HLA antibodies.

Method

We selected 177 kidney transplant recipients (KT) with renal biopsies 2011-2017: 77 with ABMR (DSA+: 53, DSA-: 24) and 100 without ABMR (DSA+: 15, DSA-: 85). We assessed graft survival with a median time of follow-up since the renal biopsy of 53 months. In 138 KT we evaluated the peripheral blood NK cell immunophenotyping and its value as a prognostic biomarker.

Results

Graft survival was worse in ABMR-KT at the end of follow-up (p<0.001) independently of DSA detection (p=0.63). Regarding NK cell immunophenotyping, we observed a lower proportion and absolute NK cell count in ABMR+DSA+-KT and ABMR+DSA--KT compared with ABMR-DSA--KT (p=0.027, p=0.017). ABMR+DSA+-KT showed higher proportion of NKG2A+ NK cells compared with ABMR-DSA--KT (p=0.007). All ABMR+ patients, independently of DSA detection, presented lower absolute NKG2A- NK cell count in comparison with ABMR-DSA--KT (p=0.001, p=0.017). Finally, a proportion of NKG2A- <30% was associated with lower graft survival 36 months after graft biopsy with ABMR (p=0.067) (Figure).

Conclusion

Graft survival is worse in ABMR+ compared with ABMR- KT independently of DSA detection. Kidney transplant recipients with ABMR show reduced peripheral absolute numbers of NK cells and NKG2A- NK cells regardless of undetectable DSA. This NK cell phenotype associated with a worse medium-term graft survival in cases with ABMR.
FC 089EFFECTS OF CANAGLIFLOZIN ON MAJOR ADVERSE CARDIOVASCULAR EVENTS BY BASELINE ALBUMINURIA: INTEGRATED ANALYSES FROM THE CANVAS PROGRAM AND CREDENCE TRIAL
Authors: Wheeler David C , Weir Matthew , Gogate Jagadish , Perkovic Vlado , Mahaffey Kenneth W
Published: May 2021

Background and Aims

People with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular (CV) disease and major adverse CV events (MACE) that is more common as renal function declines. The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of MACE (CV death, nonfatal myocardial infarction [MI], and nonfatal stroke) in patients with T2DM and high CV risk or nephropathy in the CANVAS Program and CREDENCE trials, respectively.

Method

This post hoc analysis included integrated, pooled data from the CANVAS Program and the CREDENCE trial. The effects of canagliflozin compared with placebo on MACE were assessed in subgroups defined by baseline urinary albumin:creatinine ratio (UACR; <30, 30-300, and >300 mg/g). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using stratified (by study) Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity. Interaction P values were calculated by including the terms of treatment group, baseline UACR, and their interaction in the model.

Results

A total of 14,543 participants from the CANVAS Program (N = 10,142) and CREDENCE (N = 4,401) were included, with mean estimated glomerular filtration rate of 70.3 mL/min/1.73 m2 and median (interquartile range) UACR of 501.0 (8.4-523.6) mg/g. Among participants with baseline UACR measurements, 7038 (48.8%), 2762 (19.1%), and 4634 (32.1%) participants had baseline UACR <30, 30-300, and >300 mg/g, respectively. Rates of MACE and its components increased as UACR increased (Figure). Canagliflozin reduced the risk of MACE compared with placebo in the overall population (HR, 0.83; 95% CI, 0.75, 0.92), with consistent effects observed across UACR subgroups (interaction P value = 0.42). Canagliflozin also reduced the risk of the individual components of CV death (HR, 0.84; 95% CI, 0.72, 0.97), nonfatal MI (HR, 0.83; 95% CI, 0.70, 0.99), and nonfatal stroke (HR, 0.84; 95% CI, 0.69, 1.03), independent of baseline UACR (interaction P values = 0.40, 0.88, and 0.69, respectively). Canagliflozin was generally well tolerated in the CANVAS Program and the CREDENCE trial, with consistent results on safety outcomes across UACR subgroups.

Conclusion

Event rates of MACE and its components increased with higher UACR. Canagliflozin reduced the risk of MACE and its components in participants with T2DM and high CV risk or CKD in the CANVAS Program and CREDENCE trial, with consistent benefits observed regardless of baseline UACR.
FC 091URINARY CCL5 MRNA, A POTENTIAL BIOMARKER FOR PROGRESSION OF TYPE 2 DIABETIC NEPHROPATHY
Authors: Feng Songtao , Gao Yueming , Cao Jingyuan , Yin Di , Lv Linli , Liu Bicheng
Published: May 2021

Background and Aims

In recent years, it has been found that targeted mRNA detection of sediment cells in urine can be used as novel biomarkers for the diagnosis of diabetic nephropathy (DN). However, its value in predicting the progression of DN is not clear. The purpose of this study is to seek for urinary mRNA markers that evaluate the prognosis of DN through systems biological screening, clinical verification and prospective studies.

Method

GEO database and “Nephroseq” platform were searched, and the transcriptome data of DN glomeruli and tubules and their clinical information were obtained. Weighted gene co-expression network analysis (WGCNA) combined with gene ontology (GO) annotation and KEGG pathway enrichment analysis were used to screen the hub genes negatively related to eGFR, and the hub genes were used as candidate markers for mRNA detection in urine sediment in DN patients. A total of 91 patients with DN diagnosed by renal biopsy were included, and 60 patients with type 2 diabetes and 61 healthy people were selected as the control groups. The mRNA expression of candidate molecules was detected by Taqman probe quantitative PCR, and the correlation between mRNA expression and eGFR and urinary protein levels were analyzed. Patients with DN were followed up for a median time of 21 months, and the primary end point was defied as end stage renal disease or eGFR decreasing by more than 50%. Multivariate Cox regression was used to evaluate the value of mRNA in predicting DN progression.

Results

GSE30528 and GSE30529 datasets were selected for analysis, including mRNA expression data of 9 cases of DN and 13 cases of normal glomeruli; and 10 cases of DN and 12 cases of normal tubules respectively. The clinical data of the patients in this study, including gender, race, age and eGFR, were searched on the Nephroseq platform. The gene modules negatively related to eGFR were screened by WGCNA. GO and KEGG analysis showed that the main function of the gene modules in both datasets were related to the activation of inflammatory cells and chemokines pathway. Through the screening of hub genes and the comparison of expression levels, CCL5, CXCL1, CXCL6 and CXCL12 were finally obtained as candidate genes. Quantitative PCR showed that the levels of CCL5 and CXCL1 was significantly increased in DN group, CCL5 was negatively correlated with eGFR and positively correlated with urinary protein level, while CXCL1 was negatively correlated with eGFR, but had no significant correlation with urinary protein level. Multivariate Cox regression showed that eGFR, urinary protein level, degree of renal fibrosis and urinary CCL5 were independent risk factors of primary end point.

Conclusion

The activation of chemokine signal pathway in renal tissue is involved in the progression of DN. Urinary CCL5 mRNA can independently predict the prognosis of DN and may be served as a novel biomarker for the progression of DN.
FC 092EFFECT OF GEMIGLIPTIN ON BIOMARKERS OF KIDNEY INJURY AND VASCULAR CALCIFICATION IN DIABETIC NEPHROPATHY: A RANDOMIZED CONTROLLED TRIAL
Authors: Trakarnvanich Thananda , Satirapoj Bancha , Suraamornkul Swangjit , Chiranantawat Thanit , Sanpatchayapong Anoma , Chaimon Torpong
Published: May 2021

Background and Aims

Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and contain pleiotropic actions on kidney injury, albuminuria and vascular inflammation especially in animal models. We plan to evaluate the efficacy of potent DPP4-inhibitors (gemigliptin) in response to these aspects in diabetic nephropathy patients.

Method

This is a multi-center, prospective, randomized, placebo-controlled trial. A total of 201 participants were enrolled and randomly assigned to gemigliptin 50 mg daily and standard care of diabetes mellitus for 6 months. The changes of coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (GFR), markers of vascular calcification and markers of tubular renal injury were evaluated at baseline and 6 months.

Results

Overall 182 patients completed the study. Significantly reductions in hemoglobinA1C level were seen at month 6 with gemigliptin group (-0.67%) vs. control group (-0.15%; P=0.048). Changes of CAC score, CAVI, estimated GFR and proteinuria did not significantly difference in the both groups during 6 months of study. However, biomarkers of vascular calcification including serum bone alkaline phosphatase and biomarkers of kidney injury including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr improved significantly after gemigliptin treatment when compared to the control group. No serious adverse event was found during study.

Conclusion

Our study shows that gemigliptin has significant benefits on biomarkers of renal tubular injury and vascular calcification in patients with diabetic nephropathy, but gemigliptin does not affect on renal function and coronary calcification compared with control. The larger and longer follow-up will be essential to determine these beneficial effects.
Lessons Learned From Implementation of SARS-CoV-2 Screening in K-12 Public Schools in Massachusetts
Authors: Ciaranello Andrea , Goehringer Cathryn , Nelson Sandra B , Ruark Liz J , Pollock Nira R
Published: June 2021

In-person learning provides substantial benefits for K-12 school students. Risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among educators, staff, students, and household members can be markedly reduced by mitigation measures including masking, ventilation, and hygiene. In addition to these measures, where community transmission is moderate to high, regular SARS-CoV-2 screening testing is recommended by recent Centers for Disease Control and Prevention (CDC) guidance for unvaccinated K-12 students and staff, and supported financially by CDC and Department of Health and Human Services initiatives. Screening can provides an added layer of risk reduction, as well as data and reassurance about in-school transmission. Financial and logistical constraints have challenged implementation of screening in public schools. We report lessons learned from a collaborative of public K-12 schools implementing and evaluating screening programs, including details of population screened, site of specimen collection, assay selection, pooled testing, and resources needed. This work supported the development of a state-wide screening program and led to dissemination of online technical resources that may support other public schools in implementing CDC guidance.
Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Infusions in High-Risk Outpatients
Authors: Piccicacco Nicholas , Zeitler Kristen , Montero Jose , Kumar Ambuj , Lakshmi Seetha , Kim Kami , Wein David , Vasey Tiffany , Vasey Matthew , Oxner Asa
Published: June 2021

Background

Coronavirus disease 2019 (COVID-19) continues to stress the health care system. Neutralizing monoclonal antibodies (mAbs) were effective in reducing COVID-19–related hospitalizations and emergency department (ED) visits in their respective clinical trials. However, these results have yet to be reproduced in a practical setting following implementation of current US Food and Drug Administration (FDA) guidance.

Methods

This retrospective cohort study included outpatients with confirmed COVID-19 infection, who had mild/moderate symptoms for 10 days or less, and who were deemed high-risk for severe COVID-19 under FDA’s Emergency Use Authorization for mAbs. Patients who received either bamlanivimab or casirivimab/imdevimab from 18 November 2020 through 5 January 2021 were included (n = 200). This was compared against a control cohort of randomly selected high-risk COVID-19 outpatients who declined or were not referred for mAb treatment during the same period (n = 200). The primary outcome was a composite of 29-day COVID-19–related hospitalizations and/or ED visits. Prespecified secondary outcomes included the individual components of the primary endpoint, 29-day all-cause mortality, and serious adverse drug events.

Results

Patients treated with mAbs were significantly less likely to be hospitalized or visit the ED compared with patients not treated with mAb (13.5% vs 40.5%; odds ratio, 0.23 [95% confidence interval, .14–.38]; P < .001). The mortality rate was 0% in the mAb group compared with 3.5% in the control group (P = .02). Only 2 patients receiving mAb experienced a serious adverse event requiring treatment.

Conclusions

Among high-risk COVID-19 outpatients with mild/moderate symptoms, early administration of mAbs can potentially reduce the strain on the health care system during the current pandemic.
The chloroplast ribosomal protein large subunit 1 interacts with viral polymerase and promotes virus infection
Authors: Cheng De-Jie , Xu Xiao-Jie , Yan Zhi-Yong , Tettey Carlos Kwesi , Fang Le , Yang Guang-Ling , Geng Chao , Tian Yan-Ping , Li Xiang-Dong
Published: May 2021

Chloroplasts play an indispensable role in the arms race between plant viruses and hosts. Chloroplast proteins are often recruited by plant viruses to support viral replication and movement. However, the mechanism by which chloroplast proteins regulate potyvirus infection remains largely unknown. In this study, we observed that Nicotiana benthamiana ribosomal protein large subunit 1 (NbRPL1), a chloroplast ribosomal protein, localized to the chloroplasts via its N-terminal 61 amino acids (transit peptide), and interacted with tobacco vein banding mosaic virus (TVBMV) nuclear inclusion protein b (NIb), an RNA-dependent RNA polymerase. Upon TVBMV infection, NbRPL1 was recruited into the 6K2-induced viral replication complexes in chloroplasts. Silencing of NbRPL1 expression reduced TVBMV replication. NbRPL1 competed with NbBeclin1 to bind NIb, and reduced the NbBeclin1-mediated degradation of NIb. Therefore, our results suggest that NbRPL1 interacts with NIb in the chloroplasts, reduces NbBeclin1-mediated NIb degradation, and enhances TVBMV infection.
Federalism, Defunding the Police, and Democratic Values: A Functional Accountability Framework for Analyzing Police Reform Proposals
Authors: Sinclair J Andrew , Love Maya , Gutiérrez-Vera María
Published: May 2021

This article examines recent proposals to “defund the police” using a perspective informed by literature on agency termination and political accountability. These concepts allow us to build a framework for categorizing such proposals based on the assignment of functions to organizations. These proposals operate in the context of a federal system which can shape the character of each category, make some choices more or less feasible, influence where functions may be assigned, and create political incentives out of the complex geography of conflict. We use examples from Minneapolis, New York, Los Angeles, and Seattle to illustrate our framework. We conclude by offering a preliminary analysis of why these cities tend towards adopting one of the alternatives we outline.
Interventricular systolic asynchrony predicts prognosis in patients with systemic sclerosis-associated pulmonary arterial hypertension
Authors: Lai Jinzhi , Guo Xiaoxiao , Zhao Jiuliang , Wang Hui , Tian Zhuang , Wang Qian , Li Mengtao , Fang Quan , Fang Ligang , Liu Yongtai , Zeng Xiaofeng
Published: May 2021

Objective

Pulmonary arterial hypertension (PAH) is a serious complication of SSc with high mortality. Interventricular systolic asynchrony (IVSA) is observed in PAH patients, but the effect of IVSA and its association with long-term mortality and clinical events in SSc-associated PAH are unclear. This study aimed to investigate the impact of IVSA on the prognosis of SSc-associated PAH.

Methods

Between March 2010 and July 2018, a total of 60 consecutive patients with SSc-associated PAH were enrolled. The end point was a composite of all-cause mortality and clinical worsening. Asynchrony was assessed by colour-coded tissue Doppler imaging (TDI) echocardiography. The myocardial sustained systole curves (Sm) of the basal portion of the right ventricular (RV) free wall and left ventricular (LV) lateral wall were obtained. IVSA was defined as the time difference from the onset of the QRS complex to the end of Sm between LV and RV.

Results

Patients with greater IVSA time differences presented with advanced pulmonary vascular resistance (PVR). The IVSA time difference was an independent predictive factor (Hazard Ratio (HR) = 1.018, 95% CI: 1.005, 1.031, P =0.005) for the composite end point and was significantly associated with PVR (r = 0.399, R2=0.092, P =0.002). Kaplan–Meier survival curves showed that patients with greater IVSA had worse prognoses (log-rank P =0.001).

Conclusion

In conclusion, IVSA analysed by colour-coded TDI echocardiography provided added value as a noninvasive, easy-to-use approach for assessing the prognosis of patients with SSc-associated PAH. A significant IVSA time difference identifies the subgroup of patients at high risk of a poor prognosis.
Severe Coronavirus Disease Pneumonia in Pediatric Patients in a Referral Hospital
Authors: Ozcan Serhan , Emeksiz Serhat , Perk Oktay , Uyar Emel , Kanik Yüksek Saliha
Published: May 2021

Objective

We aimed to evaluate the characteristics and outcomes of critically ill children managed in an intensive care unit because of coronavirus disease (COVID-19) pneumonia with respiratory support requirements.

Methods

We performed a single-center retrospective observational study in a pediatric intensive care unit (PICU) with 32 beds in Ankara City Hospital, Ankara, Turkey, from 13 March 2020 to 31 December 2020. Patients who needed positive-pressure ventilation (PPV) therapy for COVID-19 pneumonia were included in the study. Demographic, clinical and laboratory data were extracted from the patients’ electronic medical records. As outcomes, the hospitalization rate of all pediatric patients diagnosed as having with COVID-19 by Polymerase Chaın Reactıon(PCR), PICU admission rate for COVID-19 pneumonia among all hospitalized patients, PPV support rate, intensive care hospitalization duration (days), total hospitalization duration (days), survival rate and tracheotomy requirement were evaluated.

Results

During the study period, 7033 children tested positive for COVID-19 in PCR tests. Of these patients, 1219 were hospitalized for COVID-19. Seventeen patients needed PPV support because of COVID-19 pneumonia. High proportion (65%) of patients admitted to the PICU had comorbid diseases. Noninvasive ventilation was applied in 15 patients (88%). The hospitalization rate among the children with COVID-19 was 17%, of whom 1.6% were admitted to the PICU. Mortality rates were 0.056% of all the cases and 0.32% of the hospitalized patients in our hospital.

Conclusion

The presence of a comorbid disease could be a sign of severe disease in children with higher lethality. Very few children required PPV support because of severe COVID-19 pneumonia.
Evolution and Evaluation of a Quality and Patient Safety Fellowship for Practicing Health Professionals
Authors: Oshman Lauren , Solomonides Anthony E. , Masi Christopher , Liederbauer Victoria , Rao Goutham , Ewigman Bernard
Published: May 2021

Developing clinical quality champions is an important strategy for improving health care quality. The NorthShore Quality and Patient Safety Fellowship was a yearlong program for practicing physicians devoting 4 hours/wk to a didactic curriculum and quality practicum. Thirty-seven clinicians completed the Fellowship from 2011 to 2018. Sixty percent of graduates reported a significant impact on their quality-related career trajectory, with 44% of early graduates and 64% of recent graduates reporting a new quality role or responsibility as a result of the Fellowship. Fifty-four percent of practicum projects were adopted or adapted by the organization. The Fellowship has been an effective framework to identify and train future quality champions and has led to further quality leadership opportunities for many graduates. Evolution of the Fellowship aligned practicum projects with organizational quality priorities. This curricular framework may be useful for other organizations that seek to develop quality champions among practicing physicians.
Total Hip Arthroplasty for Acute Femoral Neck Fractures: Who Should Perform the Operation—Adult Reconstructive or Trauma Surgeons?
Authors: Thomas John C. , Haidukewych George J.
Published: May 2021

Objective:

To compare the results and complications of a large consecutive series of total hip arthroplasty (THA) performed for acute femoral neck (FN) fracture by adult reconstructive (AR) and trauma (T) surgeons to determine if there is a difference in outcomes.

Design:

Retrospective chart review.

Setting:

Level 1 trauma center.

Patients:

One hundred forty-nine consecutive patients who presented to our institution with displaced FN fractures treated by THA were included in this study.

Intervention:

All patients were treated with THA.

Main Outcome Measurements:

Implant survival, 90-day complications, 90-day readmission, 1-year complications.

Results:

For the group as a whole, the major surgical complication rate (defined as dislocation, deep infection, loosening, fracture) was significantly higher for T surgeons (20%) than for AR surgeons (7%) (P = 0.021). AR surgeons had significantly less radiographic component malpositioning 12% versus 3% (P = 0.024). Mortality and readmission rates were similar between the 2 cohorts at all time points. Implant survivorship was significantly higher at 1 year for AR surgeons (P = 0.05).

Conclusions:

THA for acute FN fracture performed by AR surgeons demonstrated higher rates of accurate radiographic component positioning, significantly lower major complication rates at 90 days and 1 year, and greater implant survival at 1 year.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Primary Versus Secondary Radiotherapy for Heterotopic Ossification Prevention About the Elbow
Authors: Geller Joseph S. , Allegra Paul R. , Seldon Crystal S. , Spieler Benjamin O. , Cohen Lara L. , Barnhill Spencer W. , Huntley Samuel R. , De La Zerda Alberto , Samuels Stuart , Wang Lora , Isrow Derek , Wolfson Aaron H. , Yechieli Raphael L.
Published: May 2021

Objectives:

To examine the efficacy and safety of radiotherapy for the prevention of heterotopic ossification (HO) about the elbow.

Design:

Retrospective chart review.

Setting:

Level 1 trauma center.

Patients/Participants:

Two hundred and twenty-nine patients who received prophylactic radiotherapy (XRT) over a 15-year period were identified. Patients were included if they received XRT to the elbow joint and had at least 12 weeks of follow-up after XRT. Fifty-four patients were ultimately included.

Intervention:

All patients were treated with a single dose of 7 Gy. Ninety-eight percentage of patients received XRT within 24 hours after surgery, and all patients received XRT within 72 hours after surgery.

Main Outcomes Measurements:

The primary study measures evaluated were the presence or absence of clinically symptomatic HO and the presence of radiographic HO after XRT to the elbow joint.

Results:

Eighteen patients were treated with XRT after a traumatic injury requiring surgery (primary prophylaxis), and 36 were treated with XRT after excision surgery to remove HO which had already formed (secondary prophylaxis). In the primary cohort, 16.7% developed symptomatic HO after XRT and 11.1% required surgery to resect the heterotopic bone. In the secondary cohort, 11.1% developed symptomatic HO after surgery and XRT and 5.5% required resection surgery. No secondary malignancies were identified.

Conclusions:

Our findings suggest that XRT for elbow HO may be safe and effective for both primary and secondary HO. XRT for HO was not shown to be associated with radiation-induced sarcoma in this series, at least in the short term. Further study in a large patient population with extended follow-up is required to better characterize populations at high risk for development of HO and secondary malignancy.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Agricultural Trauma Causing Open Fractures: Is Antibiotic Coverage Against Anaerobic Organisms Indicated?
Authors: Wynn Malynda , Kesler Kyle , Morellato John , Higginbotham Robert , Robertson Michael , Marsh John Lawrence , Hogue Matthew
Published: May 2021

Objective:

To compare deep infection rate and causative organisms in open fractures of the lower extremity from agricultural trauma with similar injuries in nonagricultural trauma.

Design:

Retrospective.

Setting:

Two tertiary care institutions.

Methods:

Open lower extremity fractures sustained between 2003 and 2018 caused by agriculture-related trauma in adult patients were reviewed. A nonagriculture open fracture control group (NAG) was identified for comparison. Patient demographics and injury characteristics were assessed. Outcomes included occurrence of deep infection and causative organisms.

Results:

One hundred seventy-eight patients were identified in the agriculture (AG) (n = 89) and control (NAG) (n = 89) groups. Among patients with agricultural injury, farm machinery was the most common mechanism in 69 (77.5%) of them. Open injuries of the foot (38.2%) and tibial shaft injuries (25.8%) were the most common in the AG and NAG groups, respectively. Deep infection was seen in 21% of patients in the AG group compared with 10% in the NAG group (P < 0.05). In the AG group, anaerobic infection occurred in 44% of patients with deep infection compared with 9.1% in the NAG group (P < 0.05). The most common anaerobic organisms included enterococci, Pseudomonas aeruginosa, and Clostridium perfringens.

Conclusions:

This study supports that open fractures due to agricultural trauma have a high infection rate, with anaerobic infection occurring at higher rates than in injuries due to nonagricultural trauma. Prophylactic treatment with antibiotics directed against anaerobes is indicated in these injuries.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Incidence and Risk Factors for Postoperative Urinary Retention Following Lumbar Spine Fusion
Authors: Bowman John J. , Edwards Charles C. , Dean Clayton , Park Justin , Edwards Charles C.
Published: May 2021

Study Design:

This was a prospective cohort study (observational—retrospective chart review).

Objective:

The objective of this study was to determine clinical rates and correlations of postoperative urinary retention (POUR) in elective spine decompression and fusion procedures.

Summary of Background Data:

POUR is a common postoperative complication that often has a major adverse impact on a patient’s recovery from elective lumbar spine surgery. The etiology of POUR in most cases is unknown. Patients undergoing lumbar spine surgery are considered to be at increased risk for POUR due to prone positioning during surgery and intraoperative cauda equina nerve root manipulation. Current studies reporting on POUR after elective spine surgery provide limited insight regarding risk factors and effective prevention strategies for this at-risk population. The purpose of this study is to identify risk factors for POUR after elective lumbar spine surgery and strategies for reducing its incidence.

Materials and Methods:

Two hundred consecutive patients aged 50 years or older undergoing combined lumbar decompression and fusion procedures over a 5-month period at a single institution were prospectively observed. Demographic and clinical data were prospectively recorded, including: medical history, surgical data, medications administered, complications, and postoperative hospital course. Factors correlating with POUR through a univariate analysis with P≤0.20 were considered for multivariate analysis.

Results:

POUR occurred in 19 of 200 patients. Those with POUR were more likely to be male (20% vs. 4%, odds ratio=6.2). Administration of scopolamine (P=0.02), neostigmine (P=0.01), and the total number of levels operated on (P=0.02) were found to be independent risk factors for the development of POUR. Length of surgery, surgical level, the performance of an interbody fusion did not have a bearing on the development of POUR (P>0.05).

Discussion:

We describe a single institution’s experience of POUR incidence in 200 consecutive patients aged 50 years or older undergoing single or multilevel lumbar spine fusion procedures by 1 of 4 surgeons. Specific demographic and clinical risk factors were identified and a codified classification for POUR in a surgical population is presented.

The results of this study will help clinicians appropriately counsel patients undergoing elective lumbar fusion about the potential development of POUR. The perioperative administration of scopolamine and neostigmine should be cautiously considered in men over 50 years of age due to the increased POUR risk.

Conclusions:

Perioperative scopolamine and neostigmine administration in men over 50 should be avoided when possible to minimize the risk of POUR.

Level of Evidence:

Level III.
Impact of Obesity Severity on Achieving a Minimum Clinically Important Difference Following Minimally Invasive Transforaminal Lumbar Interbody Fusion
Authors: Cha Elliot D.K. , Lynch Conor P. , Mohan Shruthi , Geoghegan Cara E. , Jadczak Caroline N. , Singh Kern
Published: May 2021

Study Design:

This was a retrospective cohort study.

Objective:

The objective of this study was to determine the impact of obesity on postoperative outcomes and minimum clinically important difference (MCID) achievement following minimally invasive transforaminal lumbar interbody fusion (MIS TLIF).

Summary of Background Data:

Obesity is a proven risk factor for poorer outcomes in MIS TLIF patients. However, few studies have investigated the impact of body mass index (BMI) on achievement of a MCID for Patient-Reported Outcome Measurement Information System Physical Function (PROMIS PF).

Methods:

A prospective surgical database was retrospectively reviewed for primary, elective, single level MIS TLIF patients. Patients were categorized into BMI groups: nonobese (<30 kg/m2); obese I (≥30 and <35 kg/m2); severe (≥35 and <40 kg/m2); and morbid (≥40 kg/m2). Demographic, perioperative information, and complication rates were compared between groups. Visual Analog Scale (VAS) back and leg, Oswestry Disability Index (ODI), 12-Item Short Form-12 Physical Composite Score (SF-12 PCS), and PROMIS PF were collected preoperatively and up to 2-year postoperatively. Impact of BMI on outcome measures and MCID achievement at all timepoints was evaluated.

Results:

A total of 162 patients were included with 88 patients categorized as normal weight, 37 obese I, 25 severe, and 12 morbid. SF-12 PCS, and PROMIS PF significantly differed by BMI at all timepoints, but only at 6- and 12-week for VAS back, preoperatively and 12 weeks for VAS leg, and preoperatively to 1-year for ODI. MCID achievement only differed for PROMIS PF and VAS back at 2 years, but did not for overall MCID achievement.

Conclusions:

BMI is a significant predictor of ODI, SF-12 PCS, and PROMIS PF preoperatively to 1-year postoperatively, but only through 12-week for VAS scores. MCID achievement varied for PROMIS PF and VAS back, suggesting that though BMI may affect postoperative outcome values, obesity may impact a patient’s perception of meaningful improvements in pain and physical function.
A Primer on the Use of Artificial Intelligence in Spine Surgery
Authors: Katsuura Yoshihiro , Colón Luis F. , Perez Alberto A. , Albert Todd J. , Qureshi Sheeraz A.
Published: May 2021

Design:

This was a narrative review.

Purpose:

Summarize artificial intelligence (AI) fundamentals as well as current and potential future uses in spine surgery.

Summary of Background Data:

Although considered futuristic, the field of AI has already had a profound impact on many industries, including health care. Its ability to recognize patterns and self-correct to improve over time mimics human cognitive function, but on a much larger scale.

Methods:

Review of literature on AI fundamentals and uses in spine pathology.

Results:

Machine learning (ML), a subset of AI, increases in hierarchy of complexity from classic ML to unsupervised ML to deep leaning, where Language Processing and Computer Vision are possible. AI-based tools have been developed to segment spinal structures, acquire basic spinal measurements, and even identify pathology such as tumor or degeneration. AI algorithms could have use in guiding clinical management through treatment selection, patient-specific prognostication, and even has the potential to power neuroprosthetic devices after spinal cord injury.

Conclusion:

While the use of AI has pitfalls and should be adopted with caution, future use is promising in the field of spine surgery and medicine as a whole.

Level of Evidence:

Level IV.
Exploring Nursing Students' Perspectives on Telenursing Using Q-methodology
Authors: Kim Ick-Jee , Kim Mi Sook , Jeon Min Kyung
Published: May 2021

With the rapid development of information and communications technologies, the medical care paradigm has been transformed, making telenursing a reality. Along with the introduction of telenursing, new changes are anticipated in the following central nursing domains: “human,” “environment,” “nursing,” and “health.” Current nursing students living in a hyperconnected world are expected to expand telenursing and foster changes in nursing. Therefore, it is important to understand nursing students' perceptions about telenursing to prepare innovatively for this changing field. This study explored nursing students' subjective perceptions about telenursing in South Korea using Q-methodology. Forty Q-statements, which reflected the nursing metaparadigm, were extracted from 175 generated statements; then, 40 nursing students—recruited purposively through snowball sampling—ranked the set of Q-statements. The data were analyzed using the PQMethod program. Five perceptions concerning telenursing were identified: “concerns and suggestions for telenursing,” “complete support for telenursing,” “inevitable acceptance of telenursing,” “distrust and criticism regarding telenursing,” and “optional acceptance of telenursing.” This study provides strategies for introducing and implementing telenursing services in countries with commercial 5G coverage and informs policies related to nursing education.
Effects of chemotherapy on operant responding for palatable food in male and female mice
Authors: Meade Julie A. , Fowlkes Alison N. , Wood Mackinsey J. , Kurtz Mary Claire , May Madeline M. , Toma Wisam B. , Warncke Urszula O. , Mann Jared , Mustafa Mohammed , Lichtman Aron H. , Damaj M. Imad
Published: May 2021

Patients treated with cancer chemotherapeutics frequently report chemotherapy-induced peripheral neuropathy (CIPN), changes in mood (depression and anxiety) and functional impairments. Rodent models of CIPN elicit limited alterations in functional behaviors, which pose challenges in developing preclinical models of chemotherapy-induced behavioral depression. The study examined the consequences of chemotherapy-induced mechanical hypersensitivity (paclitaxel: 32 or 64 mg/kg, cumulative; oxaliplatin: 30 mg/kg, cumulative) on behavioral depression, as measured with operant responding for palatable food during periods of food restriction and ad libitum chow, consumption of noncontingently available palatable food in the presence of ad libitum chow, and voluntary wheel running. The study employed two inbred mouse strains (C57BL/6J and Balb/cJ) and examined potential sex differences. All chemotherapeutic regimens caused profound mechanical hypersensitivity for the duration of the observation periods (up to 7 months), but no treatments changed voluntary wheel running or consumption of noncontingent palatable food. The high dose of paclitaxel temporarily reduced operant responding for palatable food in male C57BL/6J mice undergoing food restriction or maintained on ad libitum chow. However, paclitaxel failed to decrease operant responding for palatable food in free-feeding female C57BL/6J mice or Balb/cJ mice of either sex. Moreover, oxaliplatin did not significantly alter operant responding for palatable food in male or female C57BL/6J mice maintained on ad libitum chow. These findings demonstrate a dissociation between chemotherapy-induced mechanical hypersensitivity and behavioral depression. The transient effects of paclitaxel on operant responding in male C57BL/6J mice may represent a fleeting behavioral correlate of chemotherapy-associated pain-like behaviors.
Knockdown of circ_0004104 Alleviates Oxidized Low-Density Lipoprotein-Induced Vascular Endothelial Cell Injury by Regulating miR-100/TNFAIP8 Axis
Authors: Ji Pan , Song Xuyang , Lv Zhiping
Published: May 2021

Coronary artery disease (CAD) is a common cardiovascular disease, mainly due to vascular endothelial cell (VEC) injury caused by atherosclerosis. Circular RNA has been shown to be involved in the regulation of various diseases. However, the role and mechanism of circ_0004104 in CAD are still unclear. Oxidized low-density lipoprotein (ox-LDL) was used to construct the VEC injury model in vitro. The expression levels of circ_0004104 and miR-100 were measured by quantitative real-time polymerase chain reaction. The proliferation of VECs was determined using 3-(45)-dimethylthiahiazo (-z-y1)-35-di-phenytetrazoliumromide assay and 5-ethynyl-2′-deoxyuridine staining assay. VEC apoptosis rate was assessed using flow cytometry, and caspase-3 activity was measured using a Caspase-3 Assay Kit. The protein expression levels of Ki-67, cleaved-caspase3, and tumor necrosis factor-α-induced protein 8 (TNFAIP8) were detected by western blot analysis. Furthermore, enzyme-linked immunosorbent assay was performed to assess the concentrations of inflammatory cytokines. In addition, the relationship between miR-100 and circ_0004104 or TNFAIP8 was confirmed by dual-luciferase reporter assay and biotin-labeled RNA pull-down assay. Our results revealed that circ_0004104 was upregulated and miR-100 was downregulated in patients with CAD and ox-LDL–induced VECs. Ox-LDL could inhibit the proliferation and promote the apoptosis and inflammation of VECs to induce VEC injury. However, silenced circ_0004104 could alleviate VEC injury induced by ox-LDL. Moreover, we found that circ_0004104 could sponge miR-100 and a miR-100 inhibitor could reverse the inhibition effect of circ_0004104 knockdown on ox-LDL–induced VEC injury. In addition, TNFAIP8 was a target of miR-100, and miR-100 alleviated ox-LDL–induced VEC injury by targeting TNFAIP8. Our data suggested that circ_0004104 promoted ox-LDL–induced VEC injury by the miR-100/TNFAIP8 axis, indicating that circ_0004104 might be a potential biomarker for CAD treatment.
Carbon Monoxide Releasing Molecule A1 Reduces Myocardial Damage After Acute Myocardial Infarction in a Porcine Model
Authors: Iqbal Javaid , Chamberlain Janet , Alfaidi Mabruka , Hughes Matthew , Alizadeh Tooba , Casbolt Helen , Evans Paul , Mann Brian , Motterlini Roberto , Francis Sheila , Gunn Julian
Published: May 2021

Infarct size is a major determinant of outcomes after acute myocardial infarction (AMI). Carbon monoxide–releasing molecules (CORMs), which deliver nanomolar concentrations of carbon monoxide to tissues, have been shown to reduce infarct size in rodents. We evaluated efficacy and safety of CORM-A1 to reduce infarct size in a clinically relevant porcine model of AMI. We induced AMI in Yorkshire White pigs by inflating a coronary angioplasty balloon to completely occlude the left anterior descending artery for 60 minutes, followed by deflation of the balloon to mimic reperfusion. Fifteen minutes after balloon occlusion, animals were given an infusion of 4.27 mM CORM-A1 (n = 7) or sodium borate control (n = 6) over 60 minutes. Infarct size, cardiac biomarkers, ejection fraction, and hepatic and renal function were compared amongst the groups. Immunohistochemical analyses were performed to compare inflammation, cell proliferation, and apoptosis between the groups. CORM-A1–treated animals had significant reduction in absolute infarct area (158 ± 16 vs. 510 ± 91 mm2, P < 0.001) and infarct area corrected for area at risk (24.8% ± 2.6% vs. 45.2% ± 4.0%, P < 0.0001). Biochemical markers of myocardial injury also tended to be lower and left ventricular function tended to recover better in the CORM-A1 treated group. There was no evidence of hepatic or renal toxicity with the doses used. The cardioprotective effects of CORM-A1 were associated with a significant reduction in cell proliferation and inflammation. CORM-A1 reduces infarct size and improves left ventricular remodeling and function in a porcine model of reperfused MI by a reduction in inflammation. These potential cardioprotective effects of CORMs warrant further translational investigations.