bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression prevention via digital cognitive behavioral therapy for insomnia: a randomized controlled trial
Authors: Cheng Philip , Kalmbach David A , Tallent Gabriel , Joseph Christine Lm , Espie Colin A , Drake Christopher L
Published: September 2019

Study Objectives

Insomnia is a common precursor to depression; yet, the potential for insomnia treatment to prevent depression has not been demonstrated. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces concurrent symptoms of insomnia and depression and can be delivered digitally (dCBT-I); however, it remains unclear whether treating insomnia leads to sustained reduction and prevention of depression. This randomized controlled trial examined the efficacy of dCBT-I in reducing and preventing depression over a 1-year follow-up period.

Methods

Patients with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) insomnia disorder were randomly assigned to receive dCBT-I or an attentional control. The follow-up sample included 358 patients in the dCBT-I condition and 300 patients in the online sleep education condition. The primary outcome measure was relative rate ratios for depression at 1-year follow-up. Insomnia responses to treatment were also tested as predictors of incident depression at the 1-year follow-up.

Results

At 1-year follow-up, depression severity continued to be significantly lower in the dCBT-I condition relative to control. In addition, the number of individuals who reported no depression at 1-year follow-up was 51% higher in the dCBT-I condition relative to control. In those with minimal to no depression at baseline, the incident rate of moderate-to-severe depression at 1-year follow-up was reduced by half in the dCBT-I condition relative to the control condition.

Conclusion

dCBT-I showed robust effects as an intervention that prevents depression. Future research should examine dose–response requirements and further characterize mechanisms of action of dCBT-I for depression prevention.

Clinical Trial

Sleep to Prevent Evolving Affective Disorders; NCT02988375.
Cardiolipin depletion‐induced changes in the Trypanosoma brucei proteome
Authors: Schädeli David , Serricchio Mauro , Hamidane Hisham Ben , Loffreda Alessio , Hemphill Andrew , Beneke Tom , Gluenz Eva , Graumann Johannes , Bütikofer Peter
Published: September 2019

The mitochondrial signature glycerophospholipid, cardiolipin (CL), binds to transporters of the inner mitochondrial membrane and plays a central role in formation and stability of respiratory supercomplexes. Functional and structural requirement of CL for mitochondrial membrane proteins has been studied in vitro using purified reconstituted proteins or in CL synthesis knockout cells that are viable under specific growth conditions. However, no information is available on mitochondrial function, protein stability, or expression levels in cells during CL depletion. In contrast to yeast and mammalian cells, CL synthesis is essential in Trypanosoma brucei. By stable isotope labeling with amino acids in cell culture and mass spectrometry, we analyzed protein levels in T. brucei procyclic forms at different time points during depletion of CL using tightly controllable conditional CL synthase knockout mutants and identified a set of novel CL‐dependent proteins (CLDPs) with unknown functions. Depletion of individual CLDPs using knockout or knockdown technologies showed that although CL synthesis is essential, expression of a given CLDP is not. In addition, ablation of CL synthesis leads to respiratory supercomplex instability and altered mitochondrial ultrastructure and function. Our findings suggest that CL may bind to and affect many more proteins in eukaryotes than previously thought.—Schädeli, D., Serricchio, M., Ben Hamidane, H., Loffreda, A., Hemphill, A., Beneke, T., Gluenz, E., Graumann, J., Bütikofer, P. Cardiolipin depletion‐induced changes in the Trypanosoma brucei proteome. FASEB J. 33, 13161–13175 (2019). www.fasebj.org
Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth
Authors: Disser Nathaniel P. , Sugg Kristoffer B. , Talarek Jeffrey R. , Sarver Dylan C. , Rourke Brennan J. , Mendias Christopher L.
Published: September 2019

Tenocytes serve to synthesize and maintain collagen fibrils and other extracellular matrix proteins in tendon. Despite the high prevalence of tendon injury, the underlying biologic mechanisms of postnatal tendon growth and repair are not well understood. IGF1 plays an important role in the growth and remodeling of numerous tissues but less is known about IGF1 in tendon. We hypothesized that IGF1 signaling is required for proper tendon growth in response to mechanical loading through regulation of collagen synthesis and cell proliferation. To test this hypothesis, we conditionally deleted the IGF1 receptor (IGF1R) in scleraxis (Scx)‐expressing tenocytes using a tamoxifen‐inducible Cre‐recombinase system and caused tendon growth in adult mice via mechanical overload of the plantaris tendon. Compared with control Scx‐expressing IGF1R‐positive (Scx:IGF1R+) mice, in which IGF1R is present in tenocytes, mice that lacked IGF1R in their tenocytes [Scx‐expressing IGF1R‐negative (Scx:IGF1RΔ) mice] demonstrated reduced cell proliferation and smaller tendons in response to mechanical loading. Additionally, we identified that both the PI3K/protein kinase B and ERK pathways are activated downstream of IGF1 and interact in a coordinated manner to regulate cell proliferation and protein synthesis. These studies indicate that IGF1 signaling is required for proper postnatal tendon growth and support the potential use of IGF1 in the treatment of tendon disorders.—Disser, N. P., Sugg, K. B., Talarek, J. R., Sarver, D. C., Rourke, B. J., Mendias, C. L. Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth. FASEB J. 33, 12680–12695 (2019). www.fasebj.org
Assessment and treatment of dizziness and vertigo
Authors: Pfieffer Mary Lauren , Anthamatten Angelina , Glassford Melissa
Published: September 2019

Dizziness is a common patient complaint with multiple etiologies. Many causes are benign, but NPs should consider red flags for serious differential diagnoses. A systematic patient history and physical exam are crucial to accurately diagnosing conditions related to dizziness. This article reviews common etiologies of dizziness and vertigo, assessment techniques, and treatment options.
Pharmacogenetic testing in primary care
Authors: Parve Julie , Carlile Jennifer , Parve Josiah
Published: September 2019

The purpose of pharmacogenetic testing is to determine the risk of adverse reactions and/or likelihood of a medication's effectiveness. Pharmacogenetic testing can assist primary care providers in tailoring treatment according to a patient's genetic traits and his or her ability to metabolize certain medication. This article will discuss the benefits and limitations of pharmacogenetic testing and how to interpret results.
Recommendations for Measuring the Electrically Evoked Compound Action Potential in Children With Cochlear Nerve Deficiency
Authors: He Shuman , Chao Xiuhua , Wang Ruijie , Luo Jianfen , Xu Lei , Teagle Holly F. B. , Park Lisa R. , Brown Kevin D. , Shannon Michelle , Warner Cynthia , Pellittieri Angela , Riggs William J.
Published: September 2019

Objectives:

This study reports a method for measuring the electrically evoked compound action potential (eCAP) in children with cochlear nerve deficiency (CND).

Design:

This method was developed based on experience with 50 children with CND who were Cochlear Nucleus cochlear implant users.

Results:

This method includes three recommended steps conducted with recommended stimulating and recording parameters: initial screen, pulse phase duration optimization, and eCAP threshold determination (i.e., identifying the lowest stimulation level that can evoke an eCAP). Compared with the manufacturer-default parameters, the recommended parameters used in this method yielded a higher success rate for measuring the eCAP in children with CND.

Conclusions:

The eCAP can be measured successfully in children with CND using recommended parameters. This specific method is suitable for measuring the eCAP in children with CND in clinical settings. However, it is not suitable for intraoperative eCAP recordings due to the extensive testing time required.
A Practical Study of Diagnostic Accuracy
Authors: Chen Chao , Yu Ronghua , Xu Wei , Li Zhikun , Li Yifan , Hu Ruixi , Zhu Xiaodong
Published: September 2019

Study Design.

Cross-sectional.

Objective.

This study aimed to assess the accuracy of smartphone-aided diagnosis of scoliosis by a trained nurse compared with scoliometer-based diagnosis by a spine surgeon.

Summary of Background Data.

Many assessments have been developed to estimate the reliability of smartphone-aided measurements in diagnosing scoliosis. However, clinical studies assessing the accuracy of smartphone-aided diagnosis with radiographs or scoliometers are scarce.

Methods.

A total of 2702 grade 7 students (mean age 13.56 yrs, range 13–15) at 10 middle schools were first screened with a smartphone by a trained nurse from the orthopedics department. Approximately half a year later, most of the students underwent a chest x-ray examination as part of a compulsory medical examination. Students with suspicious findings in either the first screen or the chest x-ray were recommended to a scoliosis clinic for single-blind tests, such as a forward bending test (FBT) and an analysis of the angle of trunk rotation (ATR) with a scoliometer, performed by an experienced spine surgeon. Finally, the Cobb method was conducted with full-spine radiographs to serve as the gold standard.

Results.

The agreement between the first screening by the nurse and the second test by the spine surgeon was low in cases with a Cobb angle <10° (κ = 0.128 [0.04–0.22], P = 0.035) and fair in cases with a Cobb angle >10° (κ = 0.349 [0.19–0.50], P < 0.001). The results of receiver operating characteristic (ROC) curve analysis also suggested that these two tests were similar in their ability to diagnose scoliosis. However, when the Cobb angle cutoff was adjusted to 15°, the latter had markedly better diagnostic ability than the former. Overall, the sensitivity of the smartphone screening was not acceptable for recognizing scoliosis.

Conclusion.

This study revealed that smartphone-aided screening for scoliosis is risky.

Level of Evidence: 3
American Society of Anesthesiologists’ Status Association With Cost and Length of Stay in Lumbar Laminectomy and Fusion
Authors: Bronheim Rachel S. , Caridi John M. , Steinberger Jeremy , Hunter Samuel , Neifert Sean N. , Deutsch Brian C. , DeMaria Samuel , Hermann Luke , Gal Jonathan S.
Published: September 2019

Study Design.

Retrospective cohort study.

Objective.

The objective of this study was to characterize the costs associated with American Society of Anesthesiologists (ASA) class, and to determine the extent to which ASA status is a predictor of increased cost and LOS following lumbar laminectomy and fusion (LLF).

Summary of Background Data.

Spinal fusion accounts for the highest hospital costs of any surgical procedure performed in the United States, and ASA (American Society of Anesthesiologists) status is a known risk factor for cost and length of stay (LOS) in the orthopedic literature. There is a paucity of literature that directly addresses the influence of ASA status on cost and LOS following LLF.

Methods.

This is a retrospective cohort study of an institutional database of patients undergoing single-level LLF at an academic tertiary care facility from 2006 to 2016. Univariate comparisons were made using χ
2 tests for categorical variables and t tests for continuous variables. Multivariate linear regression was utilized to estimate regression coefficients, and to determine whether ASA status is an independent risk factor for cost and LOS.

Results.

A total of 1849 patients met inclusion criteria. For every one-point increase in ASA score, intensive care unit (ICU) LOS increased by 0.518 days (P < 0.001), and hospital length of stay increased by 1.93 days (P < 0.001). For every one-point increase in ASA score, direct cost increased by $7474.62 (P < 0.001).

Conclusion.

ASA status is a predictor of hospital LOS, ICU LOS, and direct cost. Consideration of the ways in which ASA status contributes to increased cost and prolonged LOS can allow for more accurate reimbursement adjustment and more precise targeting of efficiency and cost effectiveness initiatives.

Level of Evidence: 3
Impact of a Blood Pressure Practice Initiative on Attitude, Practice Behavior, and Knowledge Among Outpatient Rehabilitation Providers: An Observational Study
Authors: Arena Sara K. , Peterson Edward
Published: September 2019

Purpose:

The purpose of this study is to describe the impact of a blood pressure (BP) educational initiative on the attitude, practice behaviors, and knowledge of outpatient (OP) physical therapists.

Methods:

An observational pre-test and post-test study design was initiated using a sample of convenience at 12 OP rehabilitation clinics. A 4-phase protocol included (1) evaluation of BP equipment, (2) pre-test questionnaire, (3) attendance at a 1-hour lecture on BP practice recommendations, and (4) performing BP measures on patient evaluations for 1 week followed by the post-test questionnaire. Descriptive statistics reported demographics, whereas a paired t test compared means of the presurvey and postsurvey responses with statistical significance set at P < .05.

Results:

Of the 55 therapists included, 70.9% were female and 29.1% male, whereas 41.8% and 58.2% reported having ≤15 and >15 years of experience, respectively. A significant improvement in BP attitudes (P = .02), practice behaviors (P = .001), and knowledge (P = .002) was identified.

Conclusions:

An educational initiative that provided BP assessment tools, a 1-hour evidence-based BP lecture, a decision-making reference, and a directive to perform valid and reliable BP techniques and interventions resulted in positive changes to an OP therapists attitude, immediate practice behavior, and knowledge of BP.
Exploration of a Simulation-Based Learning Experience in Critical Care: The Use of Standardized Patients for Early Mobility Training
Authors: Cunningham Shala , Cunningham Cynthia
Published: September 2019

Purpose:

The purpose of this study was to examine the influence of a simulation experience, using standardized patients (SPs), on physical therapy students' perceptions of comfort with early mobilization of patients in a critical care environment.

Methods:

To explore the influence of the simulation experience on students' confidence in the assessment and treatment of critically ill patients, a survey investigating the skills associated with cardiovascular and pulmonary physical therapy was developed and administered before and after the experience. In addition, focus group interviews explored the students' perceptions of the simulation scenarios.

Results:

Similar to studies using high-fidelity human simulators, students reported increased comfort with the skills required for early rehabilitation of patients in critical care settings. In addition, students discussed the realism of scenarios, the practical application of previously acquired knowledge, and the need to adapt to the patient response during the scenarios.

Conclusions:

With the advancement of the simulation technology, SPs can be used to accurately portray patients in critical care units. The use of SPs allows for the unrestricted ability to mobilize the patient and, therefore, the ability to practice the skills associated with early rehabilitation in the intensive care setting.
Area Deprivation as a Risk Factor for Methicillin-resistant Staphylococcus aureus Infection in Pediatric Cystic Fibrosis
Authors: Oates Gabriela R. , Harris William T. , Rowe Steven M. , Solomon George M. , Dey Suranjana , Zhu Aowen , Hoover Wynton C. , Gutierrez Hector H.
Published: September 2019

Background:

In US cystic fibrosis (CF) patients, methicillin-resistant Staphylococcus aureus (MRSA) rates have tripled in the past 2 decades. Known clinical risk factors include exposure to a healthcare setting, Pseudomonas aeruginosa and CF-related diabetes. Area-level socio-environmental exposures have not been evaluated. We explored the association of area-level deprivation with MRSA prevalence in a pediatric CF Center in the Southeastern United States.

Methods:

Patients’ residential addresses were geocoded and linked to a composite Area Deprivation Index and Rural-Urban Commuting Area scores. The association of MRSA with Area Deprivation Index and Rural-Urban Commuting Area scores was evaluated using logistic regression with robust standard errors adjusted for sociodemographic covariates (age, sex, race, mother’s and father’s education and household income), clinical risk factors (P. aeruginosa, CF-related diabetes, hospitalizations and number of clinic visits) and clustering.

Results:

The study included all pediatric patients (N = 231; mean age 12) at a single CF Center. MRSA was present in 44% of subjects. Higher area-level deprivation was correlated with rural residence, lack of parental college education and lower household income (P < 0.001 for each). In a multiple regression model fully adjusted for patient-level sociodemographic covariates, clinical risk factors and clustering, neighborhood deprivation was associated with more than 2-fold increase in the odds of having MRSA [OR 2.26 (1.14–4.45), P < 0.05].

Conclusions:

Neighborhood deprivation is a risk factor for MRSA in pediatric CF, doubling the odds of infection. Community-level socioeconomic risk factors should be considered when developing prevention strategies and treatment plans for MRSA infection in pediatric patients with CF.
A Nonopioid, Nonbenzodiazepine Treatment Approach for Intractable Nausea and Vomiting in the Emergency Department
Authors: Valdovinos Erica M. , Frazee Bradley W. , Hailozian Christian , Haro Daniel A. , Herring Andrew A.
Published: September 2019

Goal:

We sought to assess the feasibility and efficacy of a treatment protocol for nausea and vomiting using the combination of chlorpromazine, a dopamine antagonist antiemetic, and ketamine, a nonopioid analgesic.

Background:

Increasing numbers of patients with cannabis use disorder are presenting to emergency departments with a poorly understood syndrome characterized by intractable nausea and vomiting.

Methods:

This is a prospective, observational study involving a convenience sample of patients with unexplained nausea and vomiting. Subjects were given ketamine 15 mg slow intravenous push and chlorpromazine 12.5 mg intravenous over 15 minutes. Outcomes were number of episodes of emesis after study drug administration; change in nausea severity; change in pain severity; adverse events; and patient satisfaction.

Results:

We enrolled 28 subjects on 30 emergency department visits. Twenty-three subjects (82%) reported at least weekly cannabis use with 19 reporting daily use. Initial symptoms were severe, with median pain and nausea scores both 10. After receiving study medication, the mean decrease in pain score over 120 minutes was 4.1 (95% confidence interval: 3.2, 5.0) and the mean decrease in nausea score was 4.9 (95% confidence interval: 4.0, 5.8). There were no adverse events. All 28 subjects who were asked reported they would want to receive these medications again.

Conclusion:

In this single-center study, the majority of patients presenting with intractable nausea and vomiting reported heavy cannabis use, and symptoms were severe. The combination of chlorpromazine plus ketamine resulted in rapid, definitive cessation of symptoms in most of these patients without the need for opioids or benzodiazepines.
Diagnosis and Management of Adrenal Insufficiency in Hospitalized Patients
Authors: Reddy Pramod
Published: September 2019

Background:

Plasma cortisol is commonly obtained in hospitalized hypotensive patients, and adrenocorticotropic hormone (ACTH) challenge is typically conducted to further workup hypocortisolemia. It is important to recognize that relative adrenal insufficiency (AI) is the most common cause of low cortisol levels and failed ACTH challenge in ill patients. Both cortisol and synthetic ACTH challenge assays are unreliable in critically ill patients. In clinical practice, corticosteroid therapy in septic shock patients results in immediate hemodynamic benefits with less vasopressor and ventilator dependence.

Areas of Uncertainty:

There is no consensus about the diagnostic criteria of relative AI, appropriate cortisol level, and the dose used for synthetic ACTH challenge in patients with septic shock. There is controversy about the mortality benefits of supplemental steroid therapy and about the use of adjunctive fludrocortisone.

Data Sources:

PubMed search of randomized control trials and meta-analyses.

Therapeutic Opinion:

Despite all the controversies, hospital physicians frequently use steroids in patients with septic shock with hypocortisolemia. Hydrocortisone should be the choice of steroid for most relative AI patients, and fludrocortisone can be added on a case-by-case basis in refractory shock. Most of the adverse effects induced by a short course of steroids are easily managed in the inpatient setting.
Is Insulin Therapy Safe?
Authors: Home Philip , Itzhak Baruch
Published: September 2019

Background:

After 98 years of insulin therapy, issues of safety remain of concern.

Areas of Uncertainty:

Uncertainty has been expressed variously in regard of arterial cell wall proliferation, promotion of proliferative retinopathy, promotion of tumor growth, and for pregnancy. Immunological issues have been little studied since the advent of highly purified insulins in the 1970s. A specific topic is whether hypoglycemia, severe or otherwise, might promote cardiac thrombotic or dysrhythmic events.

Data Sources:

A literature review in these areas is difficult because nearly all clinical trials with insulin refer to adverse events. However, the specific topics aforementioned allow for some informed literature searching supplemented by finger-searching of published articles, notably in connection with the insulin analogues.

Therapeutic Understandings:

Safety data for pregnancy are weak because of power problems, but there are no signals for added maternal or fetal risk. Clinical-outcome trials that assess insulin against other glucose-lowering therapies or with significantly different insulin preparations in different arms are few and are sometimes conducted at modest dosage but fail to suggest promotion of arterial disease. Concern over growth-promoting activity of insulin glargine turned out to be ill-founded when the circulating moiety after injection was noted to have a lower IGF-1:insulin activity than human insulin, and a direct study of retinopathy progression or meta-analysis of malignancy incidence failed to show signals of concern. It does seem that severe hypoglycemia can cause death in some people with type 1 diabetes, although the tissue mechanism is unknown, but reducing severe hypoglycemia in type 2 diabetes does not protect against arterial events. Both symptomatic and severe hypoglycemia can however be reduced by use of more recently marketed insulin analogues, and this improves tolerability if not safety.

Conclusions:

In conclusion, although insulin therapy clearly gives health benefits, the evidence for long-term harm is absent or weak.
The controversial role of red cell transfusions for sickle cell pain
Authors: Karafin Matthew S. , Field Joshua J.
Published: September 2019

Purpose of review

Red cell transfusions are one of the most common and important therapies used for patients with sickle cell disease (SCD). For prevention of strokes, there is abundant evidence that transfusions are efficacious, whereas for other indications, such as prevention of pain, there are less data. Nonetheless, with few therapeutic options, the use of transfusion for prevention of acute pain has increased in children and adults with SCD without a clear understanding of its benefits.

Recent findings

Although it makes conceptual sense that red cell transfusions would prevent pain that arises from vaso-occlusion, we now know that the mechanism of pain is more complex than vaso-occlusion alone. Recent taxonomies recognize a chronic pain syndrome that is both common in adults with SCD and affects the presentation of acute pain. It is not known if acute pain on the background of chronic pain responds differently to sickle cell therapies, such as hydroxyurea and blood transfusion.

In this review, we will examine the studies that have investigated whether red cell transfusions are efficacious for preventing pain. In the absence of high-quality data that specifically addresses this question, we will outline our approach, which might soon change with new drugs and curative therapies on the horizon.
Single-Room Ward Design and Its Impact on Service and Patient Outcomes
Authors: Davis Melissa , Elliott Rosalind , Hills Rosemary , Fry Margaret
Published: September 2019

BACKGROUND:

Evidence suggests that single-room inpatient wards are associated with better patient outcomes than open-room wards but little is known about the impact on adverse events, patient satisfaction, and clinician experiences.

METHODS/PURPOSE:

We evaluated the impact of a new inpatient single-room orthopaedic ward on patient and clinician outcomes using a medical record audit; patient, nurse, and medical doctor surveys; and nonparticipant observations in a tertiary hospital in Sydney, Australia.

RESULTS:

The audit (1,569 patients; 819 open-room ward and 750 new single-room ward) revealed unchanged adverse event rates and fewer emergency calls after the move to a single-room ward. Survey responses from nurses, medical doctors, and patients were positive. Observations suggested that clinicians devised solutions to potential threats to patient safety.

CONCLUSION:

The single-room ward design did not negatively impact on patient and clinician outcomes and was preferred by them. Clinicians organized their work to ensure patient safety.
Assessment of the Independent and Synergistic Effects of Fluid Overload and Acute Kidney Injury on Outcomes of Critically Ill Children*
Authors: Gist Katja M. , Selewski David T. , Brinton John , Menon Shina , Goldstein Stuart L. , Basu Rajit K.
Published: September 2019

Objectives:

Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients.

Design:

Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study.

Setting:

Single-center quaternary level PICU.

Patients:

One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days.

Interventions:

None.

Measurements and Main Results:

Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload+ patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload– patients, regardless of acute kidney injury status. Fluid overload+/acute kidney injury– patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload+/acute kidney injury+ patients compared with patients without both classifications (17.4; 95% CI, 11.0–23.7 vs 8.8; 95% CI, 7.3–10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality.

Conclusions:

The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.
Fluid Overload in Pediatric Severe Traumatic Brain Injury*
Authors: Stulce Casey , Reisner Andrew , Kane Jason M. , Shin H. Stella , McCracken Courtney , Williamson Julie , Walson Karen , Paden Matthew
Published: September 2019

Objective:

Pediatric traumatic brain injury is a major public health problem in the United States. Hypertonic saline therapy is a well-established treatment in patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) who have intracranial hypertension. In children, fluid overload is associated with increased mortality, ventilator duration, and length of PICU stay, even when controlling for severity of illness. This study reports prevalence of fluid overload in pediatric patients with severe traumatic brain injury treated with 3% hypertonic saline and effect on clinical outcomes.

Design:

Single-center retrospective chart review.

Setting:

PICUs at two tertiary children’s hospitals.

Patients:

One hundred thirty-eight patients with traumatic brain injury with postresuscitation Glasgow Coma Scale less than or equal to 8 who received hypertonic saline from September 1, 2010, to February 28, 2016, and intracranial pressure monitoring and survived at least 24 hours from admission.

Interventions:

None.

Measurements and Main Results:

We used fluid balance percentage greater than or equal to 10% as our definition of fluid overload. Ninety-one percent of patients less than 1 year old had fluid overload on day 10 of admission compared with 47% of patients greater than 1 year. Fluid overloaded patients did not have increased mortality, acute kidney injury, PICU length of stay, or ventilator days. Hypertonic saline was not the cause of fluid overload in these patients.

Conclusions:

Patients with severe traumatic brain injury do have high rates of fluid overload. However, fluid overload did not contribute to mortality, longer days on the ventilator, increased risk of acute kidney injury, or increased PICU length of stay.
Less Pain and Reduced Risk of Early Postoperative Ileus After Clipless Versus Conventional Laparoscopic Appendectomy
Authors: Park Jesung , Suh Suk-Won , Kim Min Kyoon , Park Byung Kwan , Lee Seung Eun , Kim Jong Won , Park Joong-Min , Choi Yoo Shin , Kim Beom Gyu , Park Yong Gum
Published: September 2019

Laparoscopic appendectomy (LA) is perceived as a procedure requiring a short hospital stay; however, some patients require prolonged hospitalization because of postoperative ileus and pain; therefore, we introduced clipless LA, using only an ultrasonic energy device only for coagulation. A total of 1013 patients (clipless LA; n=290 and conventional LA; n=723) who underwent LA at our hospital between January 2015 and February 2018 were analyzed. The mean operative time was shorter (P<0.001), and postoperative pain score at 24 hours was lower (P<0.001) for clipless than for conventional LA. There were no significant differences in postoperative complications, except with regard to early postoperative ileus (clipless LA; 18.1% vs. conventional LA; 31.6%, P=0.025), and the operative method had significantly influenced early postoperative ileus (relative risk, 0.505; 95% confidence interval, 0.257-0.994; P=0.048). Clipless LA is comparable to conventional LA with regard to operative safety but results in significantly less pain and postoperative ileus.
Urine Injury Biomarkers Are Not Associated With Kidney Transplant Failure
Authors: Koyawala Neel , Reese Peter P. , Hall Isaac E. , Jia Yaqi , Thiessen-Philbrook Heather R. , Mansour Sherry G. , Doshi Mona D. , Akalin Enver , Bromberg Jonathan S. , Harhay Meera N. , Mohan Sumit , Muthukumar Thangamani , Schröppel Bernd , Singh Pooja , Weng Francis L. , Parikh Chirag R.
Published: September 2019

Background.

Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes.

Methods.

In the 2010–2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m2.

Results.

Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF.

Conclusions.

AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.
A Multicenter Japanese Survey Assessing the Long-term Outcomes of Liver Retransplantation Using Living Donor Grafts
Authors: Kuramitsu Kaori , Fukumoto Takumi , Egawa Hiroto , Ohdan Hideki , Umeshita Koji , Uemoto Shinji , Hibi Taizo , Kasahara Mureo , Yoshizumi Tomoharu , Mizuta Koichi , Shimamura Tsuyoshi , Furukawa Hiroyuki
Published: September 2019

Background.

Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation.

Methods.

Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015.

Results.

Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients.

Conclusions.

In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor.
Antithymocyte Globulin Versus Interleukin-2 Receptor Antagonist in Kidney Transplant Recipients With Hepatitis C Virus
Authors: Bae Sunjae , Durand Christine M. , Garonzik-Wang Jacqueline M. , Chow Eric K.H. , Kucirka Lauren M. , McAdams-DeMarco Mara A. , Massie Allan B. , Al Ammary Fawaz , Coresh Josef , Segev Dorry L.
Published: September 2019

Background.

Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that antithymocyte globulin (ATG) might increase HCV-related complications.

Methods.

Using Scientific Registry of Transplant Recipients and Medicare claims data, we studied 6780 HCV+ and 139 681 HCV− KT recipients in 1999–2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (versus IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (versus IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression.

Results.

HCV+ recipients were less likely to receive ATG than HCV− recipients (living donor, adjusted odds ratio [aOR] =0.640.770.91; deceased donor, aOR =0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-y crude incidence = 11.6% versus 12.6%; aOR =0.680.820.99). There was no significant difference in the risks of graft failure (adjusted hazard ratio [aHR] =0.861.001.17), death (aHR =0.850.951.07), liver transplant registration (aHR =0.580.971.61), and cirrhosis (aHR =0.730.921.16).

Conclusions.

Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.
Late Graft Loss After Kidney Transplantation: Is “Death With Function” Really Death With a Functioning Allograft?
Authors: Gaston Robert S. , Fieberg Ann , Helgeson Erika S. , Eversull Jason , Hunsicker Lawrence , Kasiske Bertram L. , Leduc Robert , Rush David , Matas Arthur J. ,   for the DeKAF Investigators*
Published: September 2019

Background.

About half of late kidney allograft losses are attributed to death with function (DWF), a poorly characterized outcome. An ongoing question is whether DWF is a consequence of chronic allograft dysfunction. Using the prospective Long-term Deterioration of Kidney Allograft Function study database, we sought to better define the impact, phenotype, and clinical course of DWF in the current era.

Methods.

Three thousand five hundred eighty-seven kidney recipients with functional grafts at 90 days post-transplant were followed prospectively for a median of 5.2 years.

Results.

Characteristics at transplantation in those with DWF (N = 350, 9.8%) differed from those who otherwise lost their grafts (death-censored graft failure [DC-GF], N = 295, 8.2%) or maintained function (N = 2942, 82.0%); DWF patients were older, sicker, and had been on dialysis longer, with more preexisting cardiovascular disease, whereas DC-GF patients experienced more early rejection, more acute rejection after 90 days, and a clinically significant decrease in kidney function before graft failure. In contrast, the clinical course after transplantation in DWF patients did not differ before death from those who maintained function throughout.

Conclusions.

DWF and DC-GF in kidney transplant recipients represent differing clinical phenotypes occurring in distinct patient populations. Reducing the impact of DWF requires better definition of causes and clinical course and then trials of therapies to improve outcomes. Composite endpoints in clinical trials that group DWF and DC-GF together may obscure important clinical findings.
Racial and Ethnic Disparities in Kidney Transplant Access Within a Theoretical Context of Medical Eligibility
Authors: Ku Elaine , Lee Brian K. , McCulloch Charles E. , Roll Garrett R. , Grimes Barbara , Adey Deborah , Johansen Kirsten L.
Published: September 2019

Background.

Non-Hispanic black (NHB) and Hispanic patients have lower access to kidney transplantation compared to non-Hispanic whites (NHWs). We examined whether differences in the prevalence of comorbidities that affect eligibility for transplant contribute to disparities in receipt of transplantation.

Methods.

We performed a retrospective study of 986 019 adults who started dialysis between 2005 and 2014, according to the United States Renal Data System. We compared prevalence of comorbidities that could influence transplant eligibility by race/ethnicity. We examined time to first transplant by race/ethnicity in this overall cohort and in a very healthy sub-cohort without conditions that could be contraindications to transplantation.

Results.

During 2.3 years of mean follow-up, 64 892 transplants occurred. NHBs and Hispanics had a lower prevalence of medical barriers to transplantation at the time of dialysis initiation than NHWs, including age >70 years (26% in NHB versus 47% in NHW) and malignancy (4% in Hispanics versus 10% in NHWs). Access to transplant was 65% lower (95% CI, 0.33–0.37) in NHBs and 43% lower (95% CI, 0.54–0.62) in Hispanics (versus NHWs) in the first year after end-stage renal disease, but by Year 4, access to transplantation was not statistically significantly different between Hispanics or NHBs (versus NHWs). In our very healthy cohort, racial and ethnic disparities in access to transplantation persisted up to Year 5 in NHBs and Year 4 in Hispanics after end-stage renal disease onset.

Conclusions.

Differences in medical eligibility do not appear to explain racial/ethnic disparities in receipt of kidney transplantation and may mask the actual magnitude of the inequities that are present.
The Evolution of Monoclonal Gammopathy of Undetermined Significance in Kidney Transplant Recipients
Authors: Gagnon Marie-France , Cardinal Héloïse , Emond Jean-Pierre , Latour Mathieu , Lemieux Bernard
Published: September 2019

Background.

It is unclear if immunosuppression increases the likelihood of malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and whether adverse renal outcomes in kidney transplant recipients with MGUS are more frequent.

Methods.

We performed a retrospective cohort study of kidney transplant recipients at the Centre Hospitalier de l’Université de Montréal between 2000 and 2016.

Results.

Among 755 study participants, 13 (1.7%) were found to have MGUS before transplant. Two evolved to smoldering multiple myeloma and 2 presented paraprotein-induced allograft injury from light chain deposition disease. Forty-six patients developed posttransplant MGUS (2.5% 5-y cumulative incidence) of which 1 progressed to multiple myeloma and 1 experienced kidney allograft loss from light chain deposition disease. None of the patients with a malignant transformation or paraprotein-induced renal disease after transplantation had had a systematic workup before transplantation to exclude hematologic malignancies and paraprotein-related kidney injury. Nine posttransplant MGUS (21%) were transient. Multivariable analysis revealed that age at transplant (hazard ratio 1.05 per 1-y increase, 95% confidence intervals, 1.02-1.08) and prior cytomegalovirus infection (hazard ratio 2.22, 95% confidence intervals, 1.07-4.58) were associated with the development of MGUS after transplantation. Of 7 posttransplant lymphoproliferative disorders, none were preceded by MGUS.

Conclusions.

Our results suggest that the identification of MGUS in a transplant candidate should lead to further investigations to exclude a plasma cell neoplasm and monoclonal gammopathy of renal significance before transplantation. MGUS arising after transplantation appears to carry a favorable evolution.
Blood Pressure and Living Kidney Donors: A Clinical Perspective
Authors: Rastogi Anjay , Yuan Stanley , Arman Farid , Simon Lewis , Shaffer Kelly , Kamgar Mohammad , Nobakht Niloofar , Bromberg Jonathan S. , Weir Matthew R.
Published: September 2019

Elevated blood pressure (BP), or “hypertension,” has been one of the main exclusion criteria for living kidney donation, as it is a risk factor for renal and cardiovascular disease. The effect of elevated BP in living kidney donors is not well studied or understood. The most current living kidney donation guidelines state that donors with a BP >140/90 mm Hg with 1–2 antihypertensive medications or evidence of end-organ damage should be excluded from living kidney donation. Yet, the definitions of “hypertension” have changed with the release of the American Heart Association (AHA)/American College of Cardiology (ACC) clinical practice guidelines suggesting that 120–129 mm Hg is elevated BP and Stage 1 hypertension is 130 mm Hg. However, the kidney function (in terms of estimated GFR) of “hypertensive” living kidney donors does not fare significantly worse postdonation compared with that of “normotensive” donors. In addition, even though living kidney donation itself is not considered to be a risk factor for developing hypertension, there exist certain risk factors (African American or Hispanic descent, obesity, age) that may increase the risk of living kidney donors developing elevated BP postdonation. The choice of BP targets and medications needs to be carefully individualized. In general, a BP <130/80 mm Hg is needed, along with lifestyle modifications.