bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse Models Expressing Mutant CUL3 Provide Insight into the Mechanism of Familial Hyperkalemic Hypertension (FHHT) and Reveal Additional Functional Defects
Authors: McCormick James A. , Blatt Phillip J. , Sharma Avika , Ferdaus Mohammed Z.
Published: April 2020

The pathogenesis of essential hypertension is complex and multifactorial. Studying Mendelian forms of hypertension like Familial Hyperkalemic Hypertension (FHHt) is a powerful approach to identify and understand pathways that may contribute. Cullin‐3 (Cul3) mutations cause the most severe form of FHHt. Cullin 3 (CUL3) along with a substrate adaptor and RING ligase forms a complex that ubiquitinates proteins for proteasomal degradation. In FHHt, mutant CUL3 (CUL3‐D9) activity impairs With‐No‐lysine [K] kinase 4 (WNK4) degradation, leading to increased phosphorylation and thus activation of the Na+ Cl− cotransporter (NCC) along the renal distal convoluted tubule (DCT). We previously reported that CUL3‐D9 degrades the WNK4 adaptor KLHL3 in vitro, and a recent study suggests this occurs in vivo. This depletion of KLHL3 could prevent WNK4 degradation, providing a mechanism by which CUL3‐D9 leads to FHHt. To confirm that CUL3‐D9 degrades KLHL3 in vivo and determine whether it has any other activities, we studied inducible renal epithelial‐specific Cul3 knock‐out (CUL3‐KO) mice and CUL3‐KO mice expressing CUL3‐D9 (CUL3‐KO/D9). Western blotting and immunofluorescence showed that CUL3‐KO mice had higher KLHL3 abundance compared with controls, while CUL3‐KO/D9 had similar KLHL3 abundance to controls. CUL3‐KO and CUL3‐KO/D9 mice also had higher WNK4 abundance compared with controls. These data suggest that KLHL3 is a substrate of wild‐type CUL3, and that CUL3‐D9 is an active form of CUL3 since it can prevent KLHL3 accumulation in CUL3‐KO mice. However, CUL3‐D9 cannot promote WNK4 degradation and did not rescue the chronic kidney disease CUL3‐KO phenotype, suggesting a generalized loss‐of‐function of CUL3‐D9‐containing ubiquitin ligase complexes. A model of FHHt, inducible renal epithelia‐specific heterozygous Cul3 mice with CUL3‐D9 expression (CUL3‐Het/D9), further confirmed this observation with significantly lower KLHL3 abundance compared with control and heterozygous Cul3 mice. To investigate effects of CUL3‐D9 on other CUL3 targets, we investigated the abundance of another CUL3 adaptor protein, Kelch‐like ECH Associated Protein 1 (Keap1), the adaptor for Nuclear factor erythroid 2‐related factor 2 (NRF2). Both CUL3‐KO/D9 and CUL3‐Het/D9 had similar Keap 1 abundance compared with controls, but NAD(P)H Quinone Dehydrogenase 1 (NQO1), a surrogate for NRF2 activity, was significantly higher. These data suggest that in addition to effects on KLHL3/WNK4, CUL3‐D9 forms a dysfunctional complex with Keap1, leading to increased NRF2 activity. In conclusion, we confirm that CUL3‐D9 degrades its adaptor KLHL3 in vivo resulting in WNK4 accumulation, and also show that CUL3‐D9 cannot form normally‐functioning complexes with other substrate adaptors.

Support or Funding Information

NIH grants DK098141 and DK117903 to JAM, and AHA 17POST33670206 to MZF
EGFR signaling in breast cancer requires licensing from separate membrane nanodomains
Authors: Sugiyama Michael G. , Fairn Gregory D. , Antonescu Costin N.
Published: April 2020

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase with numerous roles in maintaining cell physiology; it is upregulated in many cancers, including breast cancer, where it contributes to tumor growth and metastasis. This feature of EGFR signaling in cancer has prompted the development of anti‐EGFR therapies. However, many cancers, while initially responsive to anti‐EGFR therapies, develop resistance to prolonged treatment, which imposes a significant challenge in applying anti‐EGFR therapies to the treatment of difficult to treat cancers such as triple negative breast cancer. Resistance to anti‐EGFR therapy is not a consequence of EGFR mutation, and instead it has been speculated that alterations in EGFR plasma membrane confinement within specialized membrane nanodomains contributes to aberrant signaling in cancer. We previously reported that EGFR activation of downstream Akt signaling requires clathrin nanodomains; the contribution of other nanodomains (flotillins, tetraspanins, caveolae, etc.) to EGFR signaling remains unknown. To probe EGFR signaling in membrane nanodomains we developed tools to track EGFR, EGF‐ligand, and various nanodomains at the single molecule level by dual‐colour, live‐cell TIRF microscopy coupled with MATLAB automated detection and particle analysis. Treatment of breast cancer cell lines with EGFR tyrosine kinase inhibitors (TKI) attenuated EGFR confinement within clathrin nanodomains and subsequent Akt signaling, but only in cell lines sensitive to the cytotoxic effects of the drugs. Interestingly, mobilization of EGFR to clathrin following stimulation with EGF‐ligand required PKC activation and confinement within non‐clathrin nanodomains, a feature that was altered in EGFR TKI‐resistant breast cancer cells. This two nanodomain model of EGFR activation resolves some longstanding, unexplained features of EGFR signaling, such the inability of the majority of EGFR to bind ligand and suggests that EGFR licensing by membrane nanodomains is a critical regulator of EGFR signaling that contributes to therapeutic resistance. Ongoing work will determine the mechanism that links EGFR licensing between membrane nanodomains, EGFR signaling, and drug resistance in breast cancer.

Support or Funding Information

CIHR PJT‐156355 to GDF and CNA
Incidence and Influencing Factors of Medical Adhesive-Related Skin Injury in Critically Ill Patients
Authors: Zhang Yu , Wang Shuo , Zhang Xiaoxue , Zhang Wenting , Wang Xinran
Published: April 2020

OBJECTIVE

To determine the incidence and influencing factors of medical adhesive-related skin injury (MARSI) among ICU patients.

METHODS

Study authors enrolled patients admitted to two ICUs at a class 3, grade A hospital in Beijing between January and June 2018 in this prospective cohort study. A data collection sheet was designed, and the data were collected by querying the electronic medical record and via direct assessment. Univariate and multivariate logistic regression analyses were performed to identify factors that independently influenced MARSI incidence. The STROBE checklist was used.

RESULTS

In total, 39 of 356 patients (27 men and 12 women with an average age of 61.51 ± 17.49 years) developed MARSI, an incidence of 10.96%. The median time from admission to MARSI occurrence was 26 days. Multivariate logistic regression analysis revealed that the ICU length of stay, Braden Scale score, and mechanical ventilation all independently influenced incidence. The Braden Scale score (odds ratio [OR], 0.758; 95% confidence interval [CI], 0.636-0.904; P < .05) was a protective factor against MARSI, with higher scores indicating lower risk. The ICU length of stay (OR, 1.098; 95% CI, 1.061-1.136; P < .05) and mechanical ventilation (OR, 3.373; 95% CI, 0.889-12.795; P < .05) were independent risk factors for MARSI.

CONCLUSIONS

The incidence of MARSI in ICU patients was relatively high. Awareness of MARSI should be increased among medical staff, and proper skin care should be provided to prevent and treat MARSI effectively.
Teaching Professional Formation in Response to the COVID-19 Pandemic
Authors: McCullough Laurence B. , Coverdale John , Chervenak Frank A.
Published: April 2020

In response to the COVID-19 pandemic, the Association of American Medical Colleges has called for a temporary suspension of clinical teaching activities for medical students. Planning for the continued involvement of learners in patient care during this pandemic should include teaching learners professional formation. The authors provide an ethical framework to guide such teaching, based on the ethical principle of beneficence and the professional virtues of courage and self-sacrifice from professional ethics in medicine. The authors show that these concepts support the conclusion that learners are ethically obligated to accept reasonable, but not unreasonable, risk. Based on this ethical framework, the authors provide an account of the process of teaching professional formation that medical educators and academic leaders should implement. Medical educators and academic leaders should embrace the opportunity that the COVID-19 pandemic presents for teaching professional formation. Learners should acquire the conceptual vocabulary of professional formation. Learners should recognize that risk of infection from patients is unavoidable. Learners should become aware of established ethical standards for professional responsibility during epidemics from the history of medicine. Learners should master understandable fear. Medical educators and academic leaders should ensure that didactic teaching of professional formation continues when it becomes justified to end learners’ participation in the processes of patient care; topics should include the professionally responsible management of scarce medical resources. The COVID-19 pandemic will not be the last major infectious disease that puts learners at risk. Professional ethics in medicine provides powerful conceptual tools that can be used as an ethical framework to guide medical educators to teach learners, who will bear leadership responsibilities in responses to future pandemics, professional formation.
Managing a Specialty Service During the COVID-19 Crisis: Lessons From a New York City Health System
Authors: Ammar Adam , Stock Ariel D. , Holland Ryan , Gelfand Yaroslav , Altschul David
Published: April 2020

The COVID-19 pandemic has stretched health care resources to a point of crisis throughout the world. To answer the call for care, health care workers in a diverse range of specialties are being retasked to care for patients with COVID-19. Consequently, specialty services have had to adapt to decreased staff available for coverage coupled with a need to remain available for specialty-specific emergencies, which now require a dynamic definition. In this Invited Commentary, the authors describe their experiences and share lessons learned regarding triage of patients, staff safety, workforce management, and the psychological impact as they have adapted to a new reality in the Department of Neurosurgery at Montefiore Medical Center, a COVID-19 hot spot in New York City.
Stress Management Training Improves Overall Performance during Critical Simulated Situations
Authors: Sigwalt Florent , Petit Guillaume , Evain Jean-Noel , Claverie Damien , Bui Monique , Guinet-Lebreton Angélique , Trousselard Marion , Canini Frédéric , Chassard Dominique , Duclos Antoine , Lehot Jean-Jacques , Rimmelé Thomas , Lilot Marc
Published: April 2020

Background

High-fidelity simulation improves participant learning through immersive participation in a stressful situation. Stress management training might help participants to improve performance. The hypothesis of this work was that Tactics to Optimize the Potential, a stress management program, could improve resident performance during simulation.

Methods

Residents participating in high-fidelity simulation were randomized into two parallel arms (Tactics to Optimize the Potential or control) and actively participated in one scenario. Only residents from the Tactics to Optimize the Potential group received specific training a few weeks before simulation and a 5-min reactivation just before beginning the scenario. The primary endpoint was the overall performance during simulation measured as a composite score (from 0 to 100) combining a specific clinical score with two nontechnical scores (the Ottawa Global Rating Scale and the Team Emergency Assessment Measure scores) rated for each resident by four blinded independent investigators. Secondary endpoints included stress level, as assessed by the Visual Analogue Scale during simulation.

Results

Of the 134 residents randomized, 128 were included in the analysis. The overall performance (mean ± SD) was higher in the Tactics to Optimize the Potential group (59 ± 10) as compared with controls ([54 ± 10], difference, 5 [95% CI, 1 to 9]; P = 0.010; effect size, 0.50 [95% CI, 0.16 to 0.91]). After specific preparation, the median Visual Analogue Scale was 17% lower in the Tactics to Optimize the Potential group (52 [42 to 64]) than in the control group (63 [50 to 73]; difference, −10 [95% CI, −16 to −3]; P = 0.005; effect size, 0.44 [95% CI, 0.26 to 0.59].

Conclusions

Residents coping with simulated critical situations who have been trained with Tactics to Optimize the Potential showed better overall performance and a decrease in stress level during high-fidelity simulation. The benefits of this stress management training may be explored in actual clinical settings, where a 5-min Tactics to Optimize the Potential reactivation is feasible prior to delivering a specific intervention.

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Magnesium and Bladder Discomfort after Transurethral Resection of Bladder Tumor
Authors: Park Jun-Young , Hong Jun Hyuk , Kim Doo-Hwan , Yu Jihion , Hwang Jai-Hyun , Kim Young-Kug
Published: April 2020

Background

Catheter-related bladder discomfort occurs because of involuntary contractions of the bladder smooth muscle after urinary catheterization. Magnesium is associated with smooth muscle relaxation. This study hypothesized that among patients having transurethral resection of bladder tumor, magnesium will reduce the incidence of postoperative moderate-to-severe catheter-related bladder discomfort.

Methods

In this double-blind, randomized study, patients were randomly allocated to the magnesium group (n = 60) or the control group (n = 60). In magnesium group, a 50 mg/kg loading dose of intravenous magnesium sulfate was administered for 15 min, followed by an intravenous infusion of 15 mg · kg−1 · h−1 during the intraoperative period. Patients in the control group similarly received normal saline. The primary outcome was the incidence of catheter-related bladder discomfort above a moderate grade at 0 h postoperatively. None, mild, moderate, and severe catheter-related bladder discomfort at 1, 2, and 6 h postoperatively, patient satisfaction, and magnesium-related adverse effects were also assessed.

Results

The incidence of catheter-related bladder discomfort above a moderate grade at 0 h postoperatively was significantly lower in the magnesium group than in the control group (13 [22%] vs. 46 [77%]; P < 0.001; relative risk = 0.283; 95% CI, 0.171 to 0.467; absolute risk reduction = 0.55; number needed to treat = 2); similar results were observed for catheter-related bladder discomfort above a moderate grade at 1 and 2 h postoperatively (5 [8%] vs. 17 [28%]; P = 0.005; relative risk = 0.294; 95% CI, 0.116 to 0.746; and 1 [2%] vs. 14 [23%]; P < 0.001; relative risk = 0.071; 95% CI, 0.010 to 0.526, respectively). Patient satisfaction on a scale from 1 to 7 was significantly higher in the magnesium group than in the control group (5.1 ± 0.8 vs. 3.5 ± 1.0; P < 0.001; 95% CI, 1.281 to 1.919). Magnesium-related adverse effects were not significantly different between groups.

Conclusions

Magnesium reduced the incidence of catheter-related bladder discomfort above a moderate grade and increased patient satisfaction among patients having transurethral resection of bladder tumor.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Treatment of Osteochondral Lesions of the Talus: An Evidence-based Opinionated Review
Authors: Cong Guang-Ting , Chinnakkannu Karthikeyan , Krishnamoorthy Vignesh P. , Di Lenarda Luca , Mikhail Christopher M. , Vulcano Ettore
Published: April 2020

Osteochondral lesions of the talus (OLTs) are a much-discussed topic in foot and ankle surgery due to their refractive nature to therapy. OLTs include fractures of the talar osteochondral surface from acute trauma or chronic repetitive injury, and their chronic subset in young patients conventionally referred to as osteochondritis dessicans. OLTs do not tend to heal well, and their treatments remain only moderately successful without an obvious superior method. The purpose of this review is to summarize the treatment of OLTs using current available literature and provide an opinionated preferred treatment algorithm.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Treatment of Osteochondral Lesions of the Talus With Matrix-induced Autologous Chondrocyte Implantation (MACI)
Authors: Delman Connor , White Carter , Natsuhara Kyle , Kreulen Christopher , Giza Eric
Published: April 2020

An osteochondral lesion of the talus is a common injury often resulting from an ankle fracture or ankle sprain. The role of nonoperative management is limited given the diminished healing capacity of these lesions. Among the available surgical options are cell-based techniques, which aim to regenerate hyaline-like articular cartilage. Matrix-induced autologous chondrocyte implantation is one such promising technique that has been validated as an effective and durable treatment option. This article reviews the matrix-induced autologous chondrocyte implantation technique and the evidence supporting its use.
Transpatellar Approach: Intramedullary Nailing of the Tibia Through an Open Patella Fracture
Authors: Comadoll Shea M. , Jinnah Alexander H. , Miller Anna N. , Aneja Arun
Published: April 2020

Tibial shaft fractures are most commonly treated via reamed intramedullary nail (IMN). Surgical approaches for tibial IMN insertion include the parapatellar (medial or lateral), transpatellar (ie, tendon splitting), or suprapatellar approach. Irrespective of the approach, the ideal start point is generally medial to the lateral tibial spine. Because of the traumatic nature of high energy tibial shaft fractures, they occasionally present with ipsilateral open knee and patellar injuries. These ipsilateral injuries are usually associated with extensive soft tissue damage and nonviable skin flaps. When an additional incision is created for tibial IMN placement this can be particularly problematic with small skin bridges. Accordingly, the authors introduce a method that minimizes further insult to the soft tissue while concomitantly providing easy access for the tibial IMN starting point through an injured patella.
Salidroside suppresses nonsmall cell lung cancer cells proliferation and migration via microRNA-103-3p/Mzb1
Authors: Zhu Xiaohong , Liu Duo , Wang Yanbo , Dong Mei
Published: April 2020

Lung cancer is the leading cause of cancer death in both men and women in the worldwide. Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Salidroside, a glycoside of tyrosol, is isolated from Rhodiola rosea and shows anticancer functions in several cancers. Recently, studies have reported that salidroside could inhibit the proliferation and metastasis of lung cancer; however, we need to explore further mechanism to provide evidence for clinical treatment. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and a key role in carcinogenesis through regulation of their target genes. Consistent with previous reports, we found that salidroside could inhibit the proliferation of nonsmall cell lung cancer (NSCLC) cells, and elevated the level of miR-103-3p. Furthermore, we showed that the level of miR-103-3p was significantly downregulated in NSCLC tissues and NSCLC cell lines A549 and H460 and was significantly correlated with NSCLC proliferation and metastasis. Further studies indicated that an endoplasmic reticulum calcium regulator Mzb1 (marginal zone B and B-1 cell-specific protein) was a direct target gene of miR-103-3p, evidenced by the direct binding of miR-103-3p with the 3′ untranslated region of Mzb1. We have also shown that overexpressing Mzb1 was able to inhibit the suppression effect of miR-103-3p on A549 migration and metastasis. These results demonstrate that salidroside suppresses NSCLC proliferation and metastasis by regulating miR-103-3p/Mzb1.
Procedures Performed by Advanced Practice Providers Compared With Medical Residents in the ICU: A Prospective Observational Study
Authors: Kreeftenberg Herman G. , Aarts Jeroen T. , Bindels Alexander J. G. H. , van der Meer Nardo J. M. , van der Voort Peter H. J.
Published: April 2020

Objective:

To assess the frequency and safety of procedures performed by advanced practice providers and medical residents in a mixed-bed ICU.

Design:

A prospective observational study where consecutive invasive procedures were studied over a period of 1 year and 8 months. The interventions were registered anonymously in an online database. Endpoints were success rate at first attempt, number of attempts, complications, level of supervision, and teamwork.

Setting:

A 33-bedded mixed ICU.

Subjects:

Advanced practice providers and medical residents.

Interventions:

Registration of the performance of tracheal intubation, central venous and arterial access, tube thoracostomies, interhospital transportation, and electrical cardioversion.

Measurement and Main Results:

A full-time advanced practice provider performed an average of 168 procedures and a medical resident an average of 68. The advanced practice provider inserted significant more radial, brachial, and femoral artery catheters (66% vs 74%, p = 0.17; 15% vs 12%, p = 0.14; 18% vs 14%, p = 0.14, respectively). The median number of attempts needed to successfully insert an arterial catheter was lower, and the success rate at first attempt was higher in the group treated by advanced practice providers (1.30 [interquartile range, 1–1.82] vs 1.53 [interquartile range, 1–2.27], p < 0.0001; and 71% vs 54%, p < 0.0001). The advanced practice providers inserted more central venous catheters (247 vs 177) with a lower median number of attempts (1.20 [interquartile range, 1–1.71] vs 1.33 [interquartile range, 1–1.86]) and a higher success rate at first attempt (81% vs 70%; p < 0.005). The number of intubations by advanced practice providers was 143 and by medical residents was 115 with more supervision by the advanced practice provider (10% vs 0%; p = 0.01). Team performance, as reported by nursing staff, was higher during advanced practice provider procedures compared with medical resident procedures (median, 4.85 [interquartile range, 4.85–5] vs 4.73 [interquartile range, 4.22–5]). Other procedures were also more often performed by advanced practice providers. The complication rate in the advanced practice provider–treated patient group was lower than that in the medical resident group.

Conclusions:

Advanced practice providers in critical care performed procedures safe and effectively when compared with medical residents. Advanced practice providers appear to be a valuable addition to the professional staff in critical care when it comes to invasive procedures.
Assessing the Course of Organ Dysfunction Using Joint Longitudinal and Time-to-Event Modeling in the Vasopressin and Septic Shock Trial
Authors: Harhay Michael O. , Gasparini Alessandro , Walkey Allan J. , Weissman Gary E. , Crowther Michael J. , Ratcliffe Sarah J. , Russell James A.
Published: April 2020

Objectives:

Non-mortality septic shock outcomes (e.g., Sequential Organ Failure Assessment score) are important clinical endpoints in pivotal sepsis trials. However, comparisons of observed longitudinal non-mortality outcomes between study groups can be biased if death is unequal between study groups or is associated with an intervention (i.e., informative censoring). We compared the effects of vasopressin versus norepinephrine on the Sequential Organ Failure Assessment score in the Vasopressin and Septic Shock Trial to illustrate the use of joint modeling to help minimize potential bias from informative censoring.

Design:

Secondary analysis of the Vasopressin and Septic Shock Trial data.

Setting:

Twenty-seven ICUs in Canada, Australia, and United States.

Subjects:

Seven hundred sixty-three participants with septic shock who received blinded vasopressin (n = 389) or norepinephrine infusions (n = 374).

Measurements and Main Results:

Sequential Organ Failure Assessment scores were calculated daily until discharge, death, or day 28 after randomization. Mortality was numerically higher in the norepinephrine arm (28 d mortality of 39% vs 35%; p = 0.25), and there was a positive association between higher Sequential Organ Failure Assessment scores and patient mortality, characteristics that suggest a potential for bias from informative censoring of Sequential Organ Failure Assessment scores by death. The best-fitting joint longitudinal (i.e., linear mixed-effects model) and survival (i.e., Cox proportional hazards model for the time-to-death) model showed that norepinephrine was associated with a more rapid improvement in the total Sequential Organ Failure Assessment score through day 4, and then the daily Sequential Organ Failure Assessment scores converged and overlapped for the remainder of the study period.

Conclusions:

Short-term reversal of organ dysfunction occurred more rapidly with norepinephrine compared with vasopressin, although differences between study arms did not persist after day 4. Joint models are an accessible methodology that could be used in critical care trials to assess the effects of interventions on the longitudinal progression of key outcomes (e.g., organ dysfunction, biomarkers, or quality of life) that may be informatively truncated by death or other censoring events.
Siderotic cataract after intraocular foreign body removal
Authors: Watane Arjun , Quan Ann , Koo Eubee , Patel Nish , Dubovy Sander , Sridhar Jayanth
Published: April 2020

A 39-year-old man developed ocular siderosis months after an intraocular foreign body (IOFB) entered the eye during trauma from hammering metal. He presented to the emergency department with progressive blurry vision in the right eye 4 months after initial trauma, and examination disclosed an IOFB in the vitreous. Electroretinogram demonstrated an increased a-wave and decreased b-wave, consistent with ocular siderosis. He underwent vitrectomy and IOFB removal, with resolution of symptoms. Five months later, the patient developed a siderotic cataract in the same eye, and slitlamp examination showed rust-colored metal deposits on the anterior capsule and posterior subcapsular cataract of the right eye. The patient underwent a successful cataract surgery, and his vision returned to baseline. This case highlights an uncommon complication of IOFBs, the variable timeline and manifestations of siderosis, and the possibility of an underlying chemical process determining the visual pattern of the siderotic cataract.
Surface profiles of new-generation IOLs with improved intermediate vision
Authors: Tognetto Daniele , Cecchini Paolo , Giglio Rosa , Turco Gianluca
Published: April 2020

Purpose:

To evaluate the surface profile of different new-generation intraocular lenses (IOLs) designed to improve intermediate vision.

Setting:

Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

Design:

Prospective experimental laboratory study.

Methods:

One higher-order aspheric monofocal IOL (Tecnis Eyhance ICB00) and 2 extended depth-of-focus (EDOF) IOLs (Tecnis Symfony ZXR00, Mini Well Ready) were examined and compared with monofocal IOLs with the same platform (Sensar AAB00, Tecnis ZCB00, Mini 4 Ready) using contact profilometry. Raw profiles were obtained and compared. The best-fit circle was then subtracted from each raw profile to highlight differences.

Results:

The new higher-order aspheric IOL presented a peculiar profile, which appeared similar to the conventional monofocal IOL based on the same platform, with just minimal differences in the central design. One of the EDOF IOLs showed a diffractive design. The EDOF IOL based on spherical aberration presented a central steepening surrounded by a symmetric lateral change in depths.

Conclusions:

Improved intermediate vision can be achieved by means of different optic designs. Unlike the traditional EDOF and multifocal IOLs based on a diffractive design, the profiles of new-generation IOLs are characterized by smooth and progressive changes of the superficial geometry.
Scholarly Productivity Among Doctor of Physical Therapy Faculty in the United States
Authors: Myers Bradley J. , Tudini Frank T. , Sawyer Scot M.
Published: April 2020

Introduction.

Doctor of Physical Therapy (DPT) faculty members are expected to participate in scholarly endeavors that contribute to the knowledge of our profession. There is currently limited evidence describing the level of productivity among DPT faculty throughout the country or how it is influenced by various factors. The purpose of this project is to describe the scholarly productivity of DPT faculty members within the United States and how it is influenced by the highest earned degree, academic rank, and institutional Carnegie classification.

Methods.

The authors extracted the faculty information from the web sites of all accredited DPT programs in the United States. A systematic search query was performed, using Google Scholar, on each identified faculty member. Bibliometric values related to scholarly productivity were collected including the number of papers and citations along with the h-index, g-index, and e-index for each author. Data were analyzed through nonparametric methods to identify how highest earned degree, academic rank, and institutional classification affected scholarly productivity.

Results.

A total of 2,961 faculty members were identified, although only 2,468 (83.4%) were used for the analysis. Median bibliometric values included publications = 7, citations = 42, h-index = 2, g-index = 5, and e-index = 5.4. Overall scholarly productivity varied with the highest earned degree and academic rank with moderate effect size, and institutional classification with low to moderate effect size.

Discussion and Conclusion.

This is the first national study of DPT educators describing the bibliometrics of the DPT professoriate. Individual and institutional factors appear to influence scholarly productivity of individual faculty members. The data yielded by this study can aide faculty members along with internal and external stakeholders in developing meaningful targets for scholarly productivity.
Contributory Role of Positron Emission Tomography in a Left Ventricular Assist Device Recipient at the Time of COVID-19 Pandemic
Authors: Loforte Antonio , Gliozzi Gregorio , Martin Suarez Sofia , Pacini Davide
Published: April 2020

In this study, We report on the use of fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) scan examinations for detecting potential COVID-19 respiratory syndrome in asymptomatic left ventricular assist device (LVAD) recipients. Thus, extreme caution and thoughtful approaches should be taken for a timely detection in delicate LVAD populations, especially if patients are living in a high-density COVID-19-infected area, and the potential intention for LVAD treatment is bridge to transplantation.
COVID-19 Respiratory Failure: Targeting Inflammation on VV-ECMO Support
Authors: Hartman Matthew E. , Hernandez Roland A. , Patel Krish , Wagner Teresa E. , Trinh Tony , Lipke Anne B. , Yim Eric T. , Pulido Juan N. , Pagel John M. , Youssef Samuel J. , Mignone John L.
Published: April 2020

The outbreak of novel coronavirus (SARS-CoV-2) that causes the respiratory illness COVID-19 has led to unprecedented efforts at containment due to its rapid community spread, associated mortality, and lack of immunization and treatment. We herein detail a case of a young patient who suffered life-threatening disease and multiorgan failure. His clinical course involved rapid and profound respiratory decompensation such that he required support with venovenous extracorporeal membrane oxygenation (VV-ECMO). He also demonstrated hyperinflammation (C-reactive protein peak 444.6 mg/L) with severe cytokine elevation (Interleukin-6 peak > 3000 pg/ml). Through treatment targeting hyperinflammation, he recovered from critical COVID-19 respiratory failure and required only 160 hours of VV-ECMO support. He was extubated 4 days after decannulation, had progressive renal recovery, and was discharged to home on hospital day 24. Of note, repeat SARS-CoV-2 test was negative 21 days after his first positive test. We present one of the first successful cases of VV-ECMO support to recovery of COVID-19 respiratory failure in North America.
Regional perfusion monitoring in shock
Authors: Noitz Matthias , Szasz Johannes , Dünser Martin W.
Published: April 2020

Purpose of review

Despite restoration of adequate systemic blood flow in patients with shock, single organs may remain hypoperfused. In this review, we summarize the results of a literature research on methods to monitor single organ perfusion in shock. We focused on methods to measure heart, brain, kidney, and/or visceral organ perfusion. Furthermore, only methods that can be used in real-time and at the bedside were included.

Recent findings

We identified studies on physical examination techniques, electrocardiography, echocardiography, contrast-enhanced ultrasound, near-infrared spectroscopy, and Doppler sonography to assess single organ perfusion.

Physical examination techniques have a reasonable negative predictive value to exclude single organ hypoperfusion but are nonspecific to detect it. Technical methods to indirectly measure myocardial perfusion include ECG and echocardiography. Contrast-enhanced ultrasound can quantify myocardial perfusion but has so far only been used to detect regional myocardial hypoperfusion. Near-infrared spectroscopy and transcranial Doppler sonography can be used to assess cerebral perfusion and determine autoregulation thresholds of the brain. Both Doppler and contrast-enhanced ultrasound techniques are novel methods to evaluate renal and visceral organ perfusion. A key limitation of most techniques is the inability to determine adequacy of organ blood flow to meet the organs’ metabolic demands.
Optimal ventilator settings after return of spontaneous circulation
Authors: Eastwood Glenn M. , Nichol Alistair
Published: April 2020

Purpose of review

To describe current practice, recent advances in knowledge and future directions for research related to the post return of spontaneous circulation (ROSC) ventilatory management of cardiac arrest patients.

Recent findings

Out-of-hospital cardiac arrest (OHCA) is a major public health problem with an estimated incidence of approximately one per 1000 persons per year. A priority of intensive care management of resuscitated OHCA patients is to reduce secondary reperfusion injury. Most OHCA patients are mechanically ventilated. Most of these require mechanical ventilation as they are unconscious and for oxygen (O2) management and carbon dioxide (CO2) control. Low levels of O2 and CO2 following OHCA is associated with poor outcome. Recently, very high fraction of inspired oxygen has been associated with poor outcomes and elevated CO2 levels have been associated with improved neurological outcomes. Moreover, it is increasingly being appreciated that the ventilator may be a tool to adjust physiological parameters to enhance the chances of favourable outcomes. Finally, ventilator settings themselves and the adoption of protective ventilation strategies may affect lung–brain interactions and are being explored as other avenues for therapeutic benefit.

Current evidence supports the targeting of normal arterial O2 and CO2 tensions during mechanical ventilation following ROSC after cardiac arrest. Use of protective lung strategies during mechanical ventilation in resuscitated cardiac arrest patients is advocated. The potential therapeutic benefits of conservative O2 therapy, mild hypercapnia and the optimal ventilator settings to use post-ROSC period will be confirmed or refuted in clinical trials.
Hydrocephalus in Guillain barre syndrome
Authors: Abdulaziz Ammar Taha Abdullah , Zhou Dong , Li Jin Mei
Published: April 2020

Rationale:

Guillian-Barré syndrome (GBS) is a devastating autoimmune disorder characterized by progressive ascending weakness, areflexia with or without autonomic and sensory disturbances. Hydrocephalus is a rare but well-documented complication in patients with GBS. However, due to the rarity of this condition, no treatment guideline for GBS with hydrocephalus is currently available.

Patient concerns:

We describe a 23-year old woman with a history of bilateral limbs pain followed by dysarthria, dysphagia, severe quadriplegia 0/5, areflexia, loss of consciousness and dysautonomia. Neuroimaging studies revealed enlarged lateral ventricles; while Electromyography demonstrated demyelination and nerve injury. Lumbar puncture results showed elevated protein level 2.6 g/L; normal glucose and cell count.

Diagnosis:

GBS with hydrocephalus.

Interventions:

The patient was started on intravenous immunoglobulin for 5 consecutive days followed by endotracheal intubation and supportive therapy including osmotherapy and CSF drainage.

Outcomes:

At 2 months after admission, the patient stopped choking and had a significant improvement in muscles’ strength (grade 4) and pain; then was discharged. On 1 year post-discharge follow-up, CT has revealed a significant improvement of hydrocephalus, and the patient has completely returned to the normal baseline.

Lessons:

Respiratory failure is the strongest predictor of concurrent hydrocephalus in patients with GBS. The prognosis of hydrocephalus in patients with GBS is usually good, and it can be medically treated; thereby shunt surgery is rarely required.
Prognostic impact of red blood cell distribution width in pulmonary hypertension patients
Authors: Liu Jie , Yang Jiao , Xu Shuanglan , Zhu Yun , Xu Shuangyan , Wei Li , Qian Panpan , Lv Yuanyuan , Zhang Chunfang , Xing Xiqian , Deng Yishu
Published: April 2020

Elevated red blood cell distribution width (RDW) may correlate with a worse prognosis in pulmonary hypertension (PH), though results to date are inconsistent. The goal of this study is to detect the impact of RDW on the prognosis of PH.

PubMed and EMBASE databases were searched from their inception to July 22, 2019 for relevant publications reporting the relationship between RDW and the prognosis of PH. A meta-analysis was performed, and the heterogeneity across the included studies was evaluated using I
2 and Q statistics. We conducted sensitivity and subgroup analyses to detect sources of heterogeneity. In addition, potential publication bias was evaluated by Begg's and Egger's tests.

In total, 1236 publications were retrieved, and 7 eligible publications with 666 PH patients were included in our meta-analysis. The results suggested that increased RDW can predict worse prognosis in PH (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.11–1.45). According to subgroup analysis, study design, region, various endpoints, time of follow-up, and patient age were not sources of heterogeneity. In addition, RDW showed prognostic value in retrospective studies (HR = 1.32, 95%CI 1.15–1.51) but not in prospective studies (HR = 1.14, 95%CI 0.78–1.67). Additionally, RDW may serve as a predictive biomarker of PH in Europe (HR = 1.33, 95%CI 1.18–1.49) but not in Asia (HR = 1.20, 95%CI 0.90–1.58). Further analysis indicated that the prognostic value of RDW was influenced by patient age (>44 years: HR = 1.34, 95%CI 1.17–1.55; ≤44 years: HR = 1.20, 95%CI 0.90–1.58) and follow-up (<3 years, HR = 1.36, 95%CI 0.53–3.47; ≥3 years, HR = 1.29, 95%CI 1.14–1.45).

RDW provides important prognostic information for PH patients, and this measure may be used to optimize patient management and guide clinical treatment.

PROSPERO registration number: CRD42019122636.
Association between personality traits and suicidality by age groups in a nationally representative Korean sample
Authors: Na Kyoung-Sae , Cho Seo-Eun , Hong Jin Pyo , Lee Jun-Young , Chang Sung Man , Jeon Hong Jin , Cho Seong-Jin
Published: April 2020

Suicide is a leading health issue, which substantially contributes to the causes of death worldwide. Personality traits are some of the major risk factors for suicidality. We sought to identify the relationships between personality traits and suicidality by age group.

The Big-Five Inventory-10 traits were measured in community-dwelling individuals in a nationally representative sample in the Republic of Korea. Because personality traits are long-standing patterns throughout one's lifetime, suicidality was measured based on lifetime history, rather than in a recent period. To comprehensively examine independent influences of personality traits on suicidality, psychiatric comorbidity and sociodemographic data were adjusted for.

A total of 6022 subjects (3714 females and 2308 males) were included. Agreeableness (odds ratio (OR) [95% confidential intervals (CI)] = 0.79 [0.64–0.98]) was negatively associated with suicidal ideation, whereas neuroticism (1.27 [1.05–1.54]) and openness (1.36 [1.11–1.67]) were positively associated with suicidal ideation among young adults. Openness (1.25 [1.10–1.43]) had a positive association, and conscientiousness (0.86 [0.75–0.98]) had a negative association with suicidal ideation among the middle-aged group. Neuroticism is the only influencing factor for suicidal attempts among the young adult (1.88 [1.24–2.86]) and older (1.65 [1.24–2.20]) groups.

Given the differential associations between personality traits and suicidality by age groups, future studies are needed to comprehensively identify possible roles of personality in suicide by age.
Diagnostic and prognostic predictive values of circulating KL-6 for interstitial lung disease
Authors: Zhang Hongying , Chen Lizhou , Wu Luling , Huang Jinbao , Li Hongyan , Wang Xinhang , Weng Heng
Published: April 2020

Background:

Past investigations showed inconsistent results for diagnostic and prognostic predictive values of Krebs von den Lungen-6 (KL-6) for interstitial lung disease (ILD).

Methods:

Web of Science and PubMed were systematically searched on for articles exploring the association of KL-6 and ILDs published between September 1993 and March 2019. For comparisons between-groups, the standard mean difference and 95% confidence intervals (CIs) were computed as the effect sizes. For diagnostic studies, a summary of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratio, which indicated the accuracy of KL-6 in the differentiation of ILDs and no ILDs, were calculated from the true positive, true negative, false positive, and false negative of each study. In addition, the summary receive-operating characteristics curve was constructed to summarize the TP and FP rates. For follow-up study, we computed hazard ratios (HRs) and 95% CIs for mortality. ILD patients showed elevated concentrations of KL-6, compared to healthy controls and patients without ILD.

Results:

The meta-analysis showed a sensitivity (0.85 [95% CI: 0.77–0.91]) and specificity (0.97 [95% CI: 0.90–0.99]) of KL-6 for ILDs. In addition, it showed elevated baseline circulating levels of KL-6 in subsequent active ILD, compared to subsequent inactive ILD. Moreover, there was a significant association between baseline levels of circulating KL-6 and mortality of ILD (HR 2.95, 95% CI 2.45–3.55, I
2 = 65.9%, P = .032).

Conclusion:

In conclusion, the study suggested that circulating KL-6 showed diagnostic and prognostic predictive values for ILDs.
Impact of healthy diet and physical activity on metabolic health in men and women
Authors: Bergens Oscar , Veen Jort , Montiel-Rojas Diego , Edholm Peter , Kadi Fawzi , Nilsson Andreas
Published: April 2020

Introduction:

Healthy dietary patterns and physical activity (PA) represent important lifestyle behaviors with considerable potential to influence on age-related metabolic health. Yet, data on the combined effects of these lifestyle behaviors on metabolic health including low-grade systemic inflammation in aging populations remain scarce. Therefore, this protocol describes a randomized controlled trial aiming to examine the impacts of healthy dietary patterns alone or combined with PA on metabolic health in middle-aged and older men and women.

Material and Methods:

The ORUDIET study is a 3-arm randomized controlled 16-week trial: Healthy Diet (HD), Healthy diet plus PA (HD-PA), and control (CON). The trial is open label, randomized with allocation concealment, parallel groups with passive controls. Participants without overt disease aged between 55 and 70 years, with BMI below 35, a current intake of a maximum of 1 serving of fruit and vegetable per day, and noncompliance to PA guidelines are eligible for inclusion. Participants in HD are instructed to increase fruit and vegetable intake to 5 servings per day (equivalent to 500 g). Participants in HD-PA receive the same dietary intervention as the HD and are additionally instructed to engage in moderate-to-vigorous physical activities for at least 150 minutes per week. The primary study outcomes are changes in metabolic and inflammatory health biomarkers. Secondary outcomes are changes in body composition and perceived health.

Ethics and dissemination:

The study protocol has been approved by the ethical review board in Uppsala, Sweden. The results will be published in peer-reviewed journals and disseminated in national and international conferences.

Trial registration number:

NCT04062682 Pre-results
Prognostic significance of red blood cell distribution width in gastrointestinal cancers
Authors: Zhou Yongping , Li Xiding , Lu Zhihua , Zhang Lei , Dai Tu
Published: April 2020

Background:

Many publications showed red blood cell distribution width (RDW) might associate with the prognosis of gastrointestinal (GI) cancers, however, the agreement has not been reached because of controversial results. This meta-analysis aimed to explore the prognostic value of RDW in GI cancers.

Methods:

Four common databases were comprehensively searched to look for relevant studies. The meta-analyses for overall survival (OS) and disease-free survival were performed using hazard ratio (HR) and 95% confidence interval (CI), and the meta-analyses for clinical parameters were conducted using odd ratio and 95% CI.

Results:

A total of 13 studies involving with 3,509 patients with GI cancers were included into this study. The results showed, compared to patients with low RDW, patients with high RDW tended to have shorter OS (HR = 1.75, 95%CI = 1.57–1.94, P < .01) and disease-free survival (HR = 1.67, 95%CI = 1.39–2.00, P < .01). High RDW was associated with larger tumor size (P < .01), worse differentiation (P = .02), deeper invasion (P < .01), earlier lymph node metastasis (P < .01), more advanced clinical stage (P < .01) and higher carcinoembryonic antigen level (P < .01) when compared to low RDW.

Conclusion:

High RDW was significantly associated with worse prognosis of GI cancers, which could be regarded as a prognostic biomarker for GI cancers. More prospective studies with large sample size and long follow-up period should be carried out to determine the prognostic significance of RDW in GI cancers in future.