bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmet Medical Needs of Patients with Benign Prostate Enlargement
Authors: Lee Munjae , Park Sewon , Choi Mankyu , Lee Kyu-Sung
Published: April 2020

This study aimed to analyze the factors affecting the unmet medical needs of patients with benign prostate enlargement (BPE) based on Andersen’s behavioral model. The data were taken from the 2009–2016 Korea Health Panel Study and 3003 participants were used for analysis. “Unmet medical needs” was used as a dependent variable. Independent variables were predisposing variables: age, educational attainment, and marital status; enabling factors: income, job type, and insurance type; and need factors: lying in a sickbed, activity limitation, subjective health status, and having chronic diseases. Results showed that younger patients experienced a higher probability of unmet medical needs. Those with higher educational attainment had a lower chance of experiencing unmet medical needs. Patients with national health insurance were less likely to experience unmet medical needs. In addition, patients who experienced lying in a sickbed had a higher probability of experiencing unmet medical needs. Therefore, in order to reduce the unmet medical needs of patients with BPE, it is necessary to allow patients to be treated early and give them accurate information about the disease. In addition, access to medical care should be strengthened through continuous care focused on primary care.
Strategies to Prevent Cardiovascular Toxicity in Breast Cancer: Is It Ready for Primetime?
Authors: Kikuchi Robin , Shah Nishant P. , Dent Susan F.
Published: April 2020

Cardio-oncology is an emerging field tasked with identifying and treating cancer therapy related cardiac dysfunction (e.g., cytotoxic agents, immunotherapies, radiation, and hormone therapies) and optimizing the cardiovascular health of cancer patients exposed to these agents. Novel cancer therapies have led to significant improvements in clinical outcomes for breast cancer patients. In this article, we review the current literature on assessing cardiovascular risk of breast cancer therapies and discuss strategies (including pharmacological and lifestyle interventions) to prevent cardiovascular toxicity.
Acute Abdominal Pain: Missed Diagnoses, Extra-Abdominal Conditions, and Outcomes
Authors: Osterwalder Isabelle , Özkan Merve , Malinovska Alexandra , Nickel Christian , Bingisser Roland
Published: April 2020

Abdominal pain (AP) is a common reason for presentation to an emergency department (ED). With this prospective, observational all-comer study, we aimed to answer three questions: Which diagnoses are most often missed? What is the incidence of extra-abdominal causes? What is the prognosis of abdominal pain in a tertiary urban European ED? Participants were systematically interviewed for the presence of 35 predefined symptoms. For all patients with abdominal pain, the index visit diagnoses were recorded. Related representation was defined as any representation, investigation, or surgery related to the index visit (open time frame). If a diagnosis changed between index visit and representation, it was classified as missed diagnosis. Among 3960 screened presentations, 480 (12.1%) were due to AP. Among 63 (13.1%) related representations, the most prevalent causes were cholelithiasis, gastroenteritis, and urinary retention. A missed diagnosis was attributed to 27 (5.6%) presentations. Extra-abdominal causes were identified in 162 (43%) presentations. Thirty-day mortality was comparable to that of all other ED patients (2.2% vs. 2.1%). Patients with abdominal pain had a low risk of representation, and the majority of representations due to missed diagnoses were of benign origin. The high incidence of extra-abdominal causes is noteworthy, as this may induce change to differential diagnosis of abdominal pain.
Bedside Renal Doppler Ultrasonography and Acute Kidney Injury after TAVR
Authors: Peillex Marilou , Marchandot Benjamin , Bayer Sophie , Prinz Eric , Matsushita Kensuke , Carmona Adrien , Heger Joe , Trimaille Antonin , Petit-Eisenmann Hélène , Jesel Laurence , Ohlmann Patrick , Morel Olivier
Published: April 2020

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel Hôpital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKIsCr and AKIsCyC. The whole cohort showed higher baseline RRI values (0.76 ± 0.7) compared to normal known and accepted values. AKIsCyC had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 ± 0.1 vs. 0.77 ± 0.6, CI 95%, p = 0.005). AUC for AKIsCyC was 0.766 and a RRI cut-off value of ≥ 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline >0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3–32.9; p = 0.021) but not RRI at baseline were significant predictors of AKIsCyC. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.
Physiopathological Bases of the Disease Caused by HACE1 Mutations: Alterations in Autophagy, Mitophagy and Oxidative Stress Response
Authors: Ugarteburu Olatz , Sánchez-Vilés Marta , Ramos Julio , Barcos-Rodríguez Tamara , Garrabou Gloria , García-Villoria Judit , Ribes Antonia , Tort Frederic
Published: April 2020

Recessive HACE1 mutations are associated with a severe neurodevelopmental disorder (OMIM: 616756). However, the physiopathologycal bases of the disease are yet to be completely clarified. Whole-exome sequencing identified homozygous HACE1 mutations (c.240C>A, p.Cys80Ter) in a patient with brain atrophy, psychomotor retardation and 3-methylglutaconic aciduria, a biomarker of mitochondrial dysfunction. To elucidate the pathomechanisms underlying HACE1 deficiency, a comprehensive molecular analysis was performed in patient fibroblasts. Western Blot demonstrated the deleterious effect of the mutation, as the complete absence of HACE1 protein was observed. Immunofluorescence studies showed an increased number of LC3 puncta together with the normal initiation of the autophagic cascade, indicating a reduction in the autophagic flux. Oxidative stress response was also impaired in HACE1 fibroblasts, as shown by the reduced NQO1 and Hmox1 mRNA levels observed in H2O2-treated cells. High levels of lipid peroxidation, consistent with accumulated oxidative damage, were also detected. Although the patient phenotype could resemble a mitochondrial defect, the analysis of the mitochondrial function showed no major abnormalities. However, an important increase in mitochondrial oxidative stress markers and a strong reduction in the mitophagic flux were observed, suggesting that the recycling of damaged mitochondria might be targeted in HACE1 cells. In summary, we demonstrate for the first time that the impairment of autophagy, mitophagy and oxidative damage response might be involved in the pathogenesis of HACE1 deficiency.
The Effect of Exercise Training on Brain Structure and Function in Older Adults: A Systematic Review Based on Evidence from Randomized Control Trials
Authors: Chen Feng-Tzu , Hopman Rachel J. , Huang Chung-Ju , Chu Chien-Heng , Hillman Charles H. , Hung Tsung-Min , Chang Yu-Kai
Published: April 2020

Accumulating evidence suggests that exercise training is associated with improvements in brain health in older adults, yet the extant literature is insufficient in detailing why exercise training facilitates brain structure and function. Specifically, few studies have employed the FITT-VP principle (i.e., Frequency, Intensity, Time, Type, Volume, and Progression) to characterize the exercise exposure, thus research is yet to specify which characteristics of exercise training benefit brain outcomes. To determine whether exercise training is consequential to cognitive and brain outcomes, we conducted a systematic review investigating the effects of exercise training on brain structure and function in older adults. PubMed and Scopus were searched from inception to February 2020, and study quality was assessed using the Cochrane risk-of-bias tool. A total of 24 randomized controlled trials were included. This systematic review indicates that older adults involved in exercise training may derive general benefits to brain health, as reflected by intervention-induced changes in brain structure and function. However, such benefits are dependent upon the dose of the exercise intervention. Importantly, current evidence remains limited for applied exercise prescriptions (e.g., volume, progression) and future research is needed to clarify the effects of exercise training on cognitive and brain outcomes in older adults.
Assessment of the Efficacy of Lowering LDL Cholesterol with Rosuvastatin 10 mg in Four Korean Statin Benefit Groups as per ACC/AHA Guidelines (NewStaR4G)
Authors: Kim Kyung-Jin , Yoon Junghan , Won Kyung Heon , Lim Sang-Wook , Chae In-Ho , Lee Sung Yun , Kim Sang-Wook , Kim Hyo-Soo
Published: April 2020

The American College of Cardiology and American Heart Association (ACC/AHA) guidelines identified four statin benefit groups on the basis of atherosclerotic cardiovascular disease risk reduction and proposed statin therapy by evidence-based intensity. Although these guidelines used randomized controlled trials with hard outcomes as exclusive evidence for its recommendations, a limited number of studies conducted in Asian countries makes its application of treatment strategy, intensity, and statin doses uncertain in these population. This prospective, multicenter study aimed to evaluate the efficacy of rosuvastatin 10 mg in the four statin benefit groups requiring high- or moderate-intensity statin therapy according to the ACC/AHA guidelines in the Korean population. The primary endpoint was percentage reduction in low-density lipoprotein (LDL) cholesterol. Secondary endpoints were percentage reduction in other lipids and achievement of ≥50% reduction in LDL cholesterol. Rosuvastatin 10 mg lowered LDL cholesterol by 61.4 mg/dL, a 44.9% decrease from baseline after eight weeks. Reduction of LDL cholesterol ≥50% was achieved in 46.3% of patients. Rosuvastatin 10 mg was generally well tolerated. In the Korean population, rosuvastatin 10 mg was favorable and tolerant in lowering LDL cholesterol in the four statin benefit groups requiring high- or moderate-intensity statin therapy according to the ACC/AHA guidelines.
The Vascular Side of Chronic Bed Rest: When a Therapeutic Approach Becomes Deleterious
Authors: Pedrinolla Anna , Colosio Alessandro L. , Magliozzi Roberta , Danese Elisa , Kirmizi Emine , Rossi Stefania , Pogliaghi Silvia , Calabrese Massimiliano , Gelati Matteo , Muti Ettore , Cè Emiliano , Longo Stefano , Esposito Fabio , Lippi Giuseppe , Schena Federico , Venturelli Massimo
Published: April 2020

The interplay between chronic constraint and advanced aging on blood flow, shear-rate, vascular function, nitric oxide (NO)-bioavailability, microcirculation, and vascular inflammation factors is still a matter of debate. Ninety-eight individuals (Young, n = 28, 23 ± 3 yrs; Old, n = 36, 85 ± 7 yrs; Bedridden, n = 34, 88 ± 6 yrs) were included in the study. The bedridden group included old individuals chronically confined to bed (3.8 ± 2.3 yrs). A blood sample was collected and analyzed for plasma nitrate, and vascular inflammatory markers. Hyperemic response (∆peak) during the single passive leg movement (sPLM) test was used to measure vascular function. Skeletal muscle total hemoglobin was measured at the vastus lateralis during the sPLM test, by means of near infrared spectroscopy (NIRS). Bedridden subjects revealed a depletion of plasma nitrates compared with Old (−23.8%) and Young (−31.1%). Blood flow was lower in the Bedridden in comparison to Old (−20.1%) and Young (−31.7%). Bedridden presented lower sPLM ∆peak compared Old (−72.5%) and the Young (−83.3%). ∆peak of NIRS total hemoglobin was lower in the Bedridden compared to that in the Young (−133%). All vascular inflammatory markers except IL-6 were significantly worse in the Bedridden compared to Old and Young. No differences were found between the Old and Young in inflammatory markers. Results of this study confirm that chronic physical constraint induces an exacerbation of vascular disfunction and differential regulation of vascular-related inflammatory markers. The mechanisms involved in these negative adaptations seems to be associated with endothelial dysfunction and consequent diminished NO-bioavailability likely caused by the reduced shear-rate consequential to long-term reduction of physical activity.
Effective Asthma Management: Is It Time to Let the AIR out of SABA?
Authors: Kaplan Alan , Mitchell Patrick D. , Cave Andrew J. , Gagnon Remi , Foran Vanessa , Ellis Anne K.
Published: April 2020

For years, standard asthma treatment has included short acting beta agonists (SABA), including as monotherapy in patients with mild asthma symptoms. In the Global Initiative for Asthma 2019 strategy for the management of asthma, the authors recommended a significant departure from the traditional treatments. Short acting beta agonists (SABAs) are no longer recommended as the preferred reliever for patients when they are symptomatic and should not be used at all as monotherapy because of significant safety concerns and poor outcomes. Instead, the more appropriate course is the use of a combined inhaled corticosteroid–fast acting beta agonist as a reliever. This paper discusses the issues associated with the use of SABA, the reasons that patients over-use SABA, difficulties that can be expected in overcoming SABA over-reliance in patients, and our evolving understanding of the use of “anti-inflammatory relievers” in our patients with asthma.
Circadian Patterns in Postvoid Residual and Voided Percentage among Older Women with Urinary Incontinence
Authors: Decalf Veerle , Monaghan Thomas F. , Denys Marie-Astrid , Petrovic Mirko , Pieters Ronny , Weiss Jeffrey P. , Everaert Karel
Published: April 2020

Background: Women with urinary incontinence incur an increased risk of elevated postvoid residual (PVR) volume and impaired voiding efficiency (i.e., voided percentage (Void%)), but the clinical significance of these parameters remains poorly described. Further characterization of PVR and voiding efficiency may thus be useful in refining the evaluation and management of urinary incontinence. This study aims to explore possible circadian variations in PVR and Void% in older women with stress (SUI), urge (UUI) and mixed urinary incontinence (MUI). Methods: A single center prospective study which enrolled a convenience sample of 90 older women who consulted a tertiary referral hospital for urinary incontinence. Participants underwent an extensive medical interview and were hospitalized to complete a 24-h frequency-volume chart (FVC) with PVR measurement after each void (FVCPVR). Results: FVCPVR analysis demonstrated no differences in mean PVR and Void% between patients with SUI, UUI and MUI. Likewise, no daytime or nighttime differences were observed in mean PVR or Void% within or between groups. Conclusions: No evidence of circadian variation in PVR or Void% was observed in older women with SUI, UUI or MUI.
Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress
Authors: Nath Shubhankar , Pigula Michael , Khan Amjad P. , Hanna William , Ruhi Mustafa Kemal , Dehkordy Farzaneh Mahmoodpoor , Pushpavanam Karthik , Rege Kaushal , Moore Kaitlin , Tsujita Yujiro , Conrad Christina , Inci Fatih , del Carmen Marcela G. , Franco Walfre , Celli Jonathan P. , Demirci Utkan , Hasan Tayyaba , Huang Huang-Chiao , Rizvi Imran
Published: April 2020

A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis. In addition to providing a cell and protein-rich environment for cancer growth and progression, ascitic fluid also confers physical stress on tumors. An understudied area in ovarian cancer research is the impact of fluid shear stress on treatment failure. Here, we investigate the effect of fluid shear stress on response to platinum-based chemotherapy and the modulation of molecular pathways associated with aggressive disease in a perfusion model for adherent 3D ovarian cancer nodules. Resistance to carboplatin is observed under flow with a concomitant increase in the expression and activation of the epidermal growth factor receptor (EGFR) as well as downstream signaling members mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and extracellular signal-regulated kinase (ERK). The uptake of platinum by the 3D ovarian cancer nodules was significantly higher in flow cultures compared to static cultures. A downregulation of phospho-focal adhesion kinase (p-FAK), vinculin, and phospho-paxillin was observed following carboplatin treatment in both flow and static cultures. Interestingly, low-dose anti-EGFR photoimmunotherapy (PIT), a targeted photochemical modality, was found to be equally effective in ovarian tumors grown under flow and static conditions. These findings highlight the need to further develop PIT-based combinations that target the EGFR, and sensitize ovarian cancers to chemotherapy in the context of flow-induced shear stress.
Angiogenesis and Immunity in Renal Carcinoma: Can We Turn an Unhappy Relationship into a Happy Marriage?
Authors: Mennitto Alessia , Huber Veronica , Ratta Raffaele , Sepe Pierangela , de Braud Filippo , Procopio Giuseppe , Guadalupi Valentina , Claps Mélanie , Stellato Marco , Daveri Elena , Rivoltini Licia , Verzoni Elena
Published: April 2020

The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells’ (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC.
The Effects of SJP-001 on Alcohol Hangover Severity: A Pilot Study
Authors: Verster Joris C , Dahl Thomas A , Scholey Andrew , Iversen Jacqueline M
Published: April 2020

Background. Despite a clear market need and many hangover products available, currently there is no hangover treatment that is supported by substantial scientific evidence demonstrating its efficacy and safety. A pilot study was conducted to investigate the effects of a potential new hangover treatment, SJP-001, and its constituents (220 mg naproxen and 60 mg fexofenadine) on hangover severity. Methods. N = 13 healthy social drinkers (36.3 ± 8.9 years old) participated in a double-blind, factorial design, cross-over study. On each test day, they consumed their own choice of alcohol up to a self-reported level sufficient to elicit a next-day hangover. Treatments were administered prior to onset of drinking. Next morning, hangover severity was assessed with the Acute Hangover Scale (AHS). Subjects were included in the efficacy analysis only if they reported a hangover after placebo. Results. N = 5 subjects (60% male, 35.2 ± 9.0 years old) were included in the analysis. They consumed a mean (SD) of 4.6 ± 1.1 units of alcohol and had an average peak breath alcohol concentration (BrAC) of 0.065% across conditions. Compared to placebo, SJP-001 significantly improved the AHS overall hangover severity score (0.8 ± 0.3 versus 1.5 ± 0.9, p = 0.042). Compared to placebo, SJP-001 also reduced scores on the individual item ‘hangover’, although the observed improvement (−1.6) did not reach statistical significance (p = 0.102). The differences from placebo after naproxen alone and fexofenadine alone were not statistically significant. SJP-001 also improved scores for the individual hangover symptoms tired, thirsty, headache, dizziness, nausea, and loss of appetite, but these effects did not reach statistical significance. Discussion. Compared to placebo, SJP-001 significantly reduced overall hangover severity. The effects of SJP-001 should be further examined in a double-blind, placebo-controlled trial with a larger sample size and controlled administration of sufficient amounts of alcohol to provoke a more substantial alcohol hangover.
Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis
Authors: Borges do Nascimento Israel Júnior , Cacic Nensi , Abdulazeem Hebatullah Mohamed , von Groote Thilo Caspar , Jayarajah Umesh , Weerasekara Ishanka , Esfahani Meisam Abdar , Civile Vinicius Tassoni , Marusic Ana , Jeroncic Ana , Carvas Junior Nelson , Pericic Tina Poklepovic , Zakarija-Grkovic Irena , Meirelles Guimarães Silvana Mangeon , Luigi Bragazzi Nicola , Bjorklund Maria , Sofi-Mahmudi Ahmad , Altujjar Mohammad , Tian Maoyi , Arcani Diana Maria Cespedes , O’Mathúna Dónal P. , Marcolino Milena Soriano
Published: April 2020

A growing body of literature on the 2019 novel coronavirus (SARS-CoV-2) is becoming available, but a synthesis of available data has not been conducted. We performed a scoping review of currently available clinical, epidemiological, laboratory, and chest imaging data related to the SARS-CoV-2 infection. We searched MEDLINE, Cochrane CENTRAL, EMBASE, Scopus and LILACS from 01 January 2019 to 24 February 2020. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. Qualitative synthesis and meta-analysis were conducted using the clinical and laboratory data, and random-effects models were applied to estimate pooled results. A total of 61 studies were included (59,254 patients). The most common disease-related symptoms were fever (82%, 95% confidence interval (CI) 56%–99%; n = 4410), cough (61%, 95% CI 39%–81%; n = 3985), muscle aches and/or fatigue (36%, 95% CI 18%–55%; n = 3778), dyspnea (26%, 95% CI 12%–41%; n = 3700), headache in 12% (95% CI 4%–23%, n = 3598 patients), sore throat in 10% (95% CI 5%–17%, n = 1387) and gastrointestinal symptoms in 9% (95% CI 3%–17%, n = 1744). Laboratory findings were described in a lower number of patients and revealed lymphopenia (0.93 × 109/L, 95% CI 0.83–1.03 × 109/L, n = 464) and abnormal C-reactive protein (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL; n = 1637). Radiological findings varied, but mostly described ground-glass opacities and consolidation. Data on treatment options were limited. All-cause mortality was 0.3% (95% CI 0.0%–1.0%; n = 53,631). Epidemiological studies showed that mortality was higher in males and elderly patients. The majority of reported clinical symptoms and laboratory findings related to SARS-CoV-2 infection are non-specific. Clinical suspicion, accompanied by a relevant epidemiological history, should be followed by early imaging and virological assay.
Concomitant Intra-Articular Glenohumeral Lesions in Fractures of the Scapula Body
Authors: Zyskowski Michael , Pesch Sebastian , Greve Frederik , Wurm Markus , von Matthey Francesca , Pfeiffer Daniela , Felix Sophie , Buchholz Arne , Kirchhoff Chlodwig
Published: April 2020

Background: Scapula body fractures are rare injuries with an incidence of 1% of all fractures accounting for 3% to 5% of all upper extremity fractures. Fractures of the scapula commonly result from high-energetic trauma and fall from great height. While several studies focused on concomitant injuries of chest and head as well as the cervical spine, up to now in the common literature, no study exists analyzing the prevalence of concomitant intra-articular glenohumeral injury following extra-articular scapular fracture. Objectives: The aim of this study was to analyze the prevalence of concomitant intra-articular glenohumeral injuries in acute fractures of the scapula by performing magnetic resonance imaging (MRI) of the shoulder joint. Study Design and Methods: This prospective cohort study was performed at our academic Level I trauma center from November 2014 to October 2016. According to our clinical algorithm, all patients suffering from an acute scapula body fracture primarily underwent computed tomography (CT) for assigning the fracture according to the Orthopedic Trauma Association (OTA)-classification and therapy planning. In addition, 3 T MRI-scans of all patients were performed within seven days after trauma. Results: Twenty-one (16 male/5 female, mean age 53 years (25–83 y) patients with scapula body fractures (OTA 14.A3.2 80.1%, OTA 14.A3.1 4.8%, OTA14.B3.1 4.8%, OTA14.C3 9.5%) were enrolled. MRI revealed 11 acute intra-articular injuries in 8 of 21 patients (38%). In all 21 patients, hematoma of the rotator cuff and periarticular muscles was present. Three patients (14.3%) presented a partial bursa sided tear of the supraspinatus tendon, whereas in 5 (23.8%), a partial articular sided supraspinatus tendon tear and in 2 (9.5%) patients, a subtotal tear was observed. One patient (4.8%) showed a complete transmural supraspinatus tendon tear. Conclusions: Traumatic concomitant glenohumeral injuries in scapula body fractures seem to be more frequent than generally expected. Subsequent surgical treatment of these formerly missed but therapy-relevant injuries may increase functional outcome and reduce the postoperative complication rate following scapula body fractures.
GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists
Authors: Górriz José Luis , Soler María José , Navarro-González Juan F. , García-Carro Clara , Puchades María Jesús , D’Marco Luis , Martínez Castelao Alberto , Fernández-Fernández Beatriz , Ortiz Alberto , Górriz-Zambrano Carmen , Navarro-Pérez Jorge , Gorgojo-Martinez Juan José
Published: April 2020

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.
Acute Kidney Injury Patterns Following Transplantation of Steatotic Liver Allografts
Authors: Jadlowiec Caroline , Smith Maxwell , Neville Matthew , Mao Shennen , Abdelwahab Dina , Reddy Kunam , Moss Adyr , Aqel Bashar , Taner Timucin
Published: April 2020

Background: Steatotic grafts are increasingly being used for liver transplant (LT); however, the impact of graft steatosis on renal function has not been well described. Methods: A total of 511 allografts from Mayo Clinic Arizona and Minnesota were assessed. We evaluated post-LT acute kidney injury (AKI) patterns, perioperative variables and one-year outcomes for patients receiving moderately steatotic allografts (>30% macrovesicular steatosis, n = 40) and compared them to non-steatotic graft recipients. Results: Post-LT AKI occurred in 52.5% of steatotic graft recipients versus 16.7% in non-steatotic recipients (p < 0.001). Ten percent of steatotic graft recipients required new dialysis post-LT (p = 0.003). At five years, there were no differences for AKI vs. no AKI patient survival (HR 0.95, 95% CI 0.08–10.6, p = 0.95) or allograft survival (HR 1.73, 95% CI 0.23–13.23, p = 0.59) for those using steatotic grafts. Lipopeliosis on biopsy was common in those who developed AKI (61.0% vs. 31.6%, p = 0.04), particularly when the Model for End-Stage Liver Disease (MELD) was ≥20 (88.9%; p = 0.04). Lipopeliosis was a predictor of post-LT AKI (OR 6.0, 95% CI 1.1–34.6, p = 0.04). Conclusion: One-year outcomes for moderately steatotic grafts are satisfactory; however, a higher percentage of post-LT AKI and initiation of dialysis can be expected. Presence of lipopeliosis on biopsy appears to be predictive of post-LT AKI.
Clinical and Neurophysiological Correlates of Emotion and Food Craving Regulation in Patients with Anorexia Nervosa
Authors: Mallorquí-Bagué Nuria , Lozano-Madrid María , Testa Giulia , Vintró-Alcaraz Cristina , Sánchez Isabel , Riesco Nadine , César Perales José , Francisco Navas Juan , Martínez-Zalacaín Ignacio , Megías Alberto , Granero Roser , Veciana De Las Heras Misericordia , Chami Rayane , Jiménez-Murcia Susana , Fernández-Formoso José Antonio , Treasure Janet , Fernández-Aranda Fernando
Published: April 2020

Background: Difficulties in emotion regulation and craving regulation have been linked to eating symptomatology in patients with anorexia nervosa (AN), contributing to the maintenance of their eating disorder. Methods: To investigate clinical and electrophysiological correlates of these processes, 20 patients with AN and 20 healthy controls (HC) completed a computerized task during EEG recording, where they were instructed to down-regulate negative emotions or food craving. Participants also completed self-report measures of emotional regulation and food addiction. The P300 and Late Positive Potential (LPP) ERPs were analysed. Results: LPP amplitudes were significantly smaller during down-regulation of food craving among both groups. Independent of task condition, individuals with AN showed smaller P300 amplitudes compared to HC. Among HC, the self-reported use of re-appraisal strategies positively correlated with LPP amplitudes during emotional regulation task, while suppressive strategies negatively correlated with LPP amplitudes. The AN group, in comparison to the HC group, exhibited greater food addiction, greater use of maladaptive strategies, and emotional dysregulation. Conclusions: Despite the enhanced self-reported psychopathology among AN, both groups indicated neurophysiological evidence of food craving regulation as evidenced by blunted LPP amplitudes in the relevant task condition. Further research is required to delineate the mechanisms associated with reduced overall P300 amplitudes among individuals with AN.
Three-Dimensional Morphological Changes of the True Cleft under Passive Presurgical Orthopaedics in Unilateral Cleft Lip and Palate: A Retrospective Cohort Study
Authors: Nalabothu Prasad , Benitez Benito K. , Dalstra Michel , Verna Carlalberta , Mueller Andreas A.
Published: April 2020

The aim of this cohort study was to quantify the morphological changes in the palatal cleft and true cleft areas with passive plate therapy using a new analysis method based on three-dimensional standardized reproducible landmarks. Forty-five casts of 15 consecutive patients with complete unilateral cleft lip and palate were laser scanned and investigated retrospectively. The landmarks and the coordinate system were defined, and the interrater and intrarater measurement errors were within 1.0 mm. The morphological changes of the cleft palate area after a period of 8 months of passive plate therapy without prior lip surgery are presented graphically. The median decrease in cleft width was 38.0% for the palatal cleft, whereas it was 44.5% for the true cleft. The width of the true and palatal cleft decreased significantly over a period of 8 months. The true cleft area decreased by 34.7% from a median of 185.4 mm2 (interquartile range, IQR = 151.5–220.1) to 121.1 mm2 (IQR = 100.2–144.6). The palatal cleft area decreased by 31.5% from a median of 334 mm2 (IQR = 294.9–349.8) to 228.8 mm2. The most important clinical considerations are the reproducibility and reliability of the anatomical points, as well as the associated morphological changes. We propose using the vomer edge to establish a validated measuring method for the width, area, and height of the true cleft.
Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder
Authors: Yoon Sang , Choi Joonhyuk , Lee Won , Do Jeong
Published: April 2020

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by difficulties in social interaction, language development delays, repeated body movements, and markedly deteriorated activities and interests. Environmental factors, such as viral infection, parental age, and zinc deficiency, can be plausible contributors to ASD susceptibility. As ASD is highly heritable, genetic risk factors involved in neurodevelopment, neural communication, and social interaction provide important clues in explaining the etiology of ASD. Accumulated evidence also shows an important role of epigenetic factors, such as DNA methylation, histone modification, and noncoding RNA, in ASD etiology. In this review, we compiled the research published to date and described the genetic and epigenetic epidemiology together with environmental risk factors underlying the etiology of the different phenotypes of ASD.
A Systematic Review of COVID-19 Epidemiology Based on Current Evidence
Authors: Park Minah , Cook Alex R. , Lim Jue Tao , Sun Yinxiaohe , Dickens Borame L.
Published: April 2020

As the novel coronavirus (SARS-CoV-2) continues to spread rapidly across the globe, we aimed to identify and summarize the existing evidence on epidemiological characteristics of SARS-CoV-2 and the effectiveness of control measures to inform policymakers and leaders in formulating management guidelines, and to provide directions for future research. We conducted a systematic review of the published literature and preprints on the coronavirus disease (COVID-19) outbreak following predefined eligibility criteria. Of 317 research articles generated from our initial search on PubMed and preprint archives on 21 February 2020, 41 met our inclusion criteria and were included in the review. Current evidence suggests that it takes about 3-7 days for the epidemic to double in size. Of 21 estimates for the basic reproduction number ranging from 1.9 to 6.5, 13 were between 2.0 and 3.0. The incubation period was estimated to be 4-6 days, whereas the serial interval was estimated to be 4-8 days. Though the true case fatality risk is yet unknown, current model-based estimates ranged from 0.3% to 1.4% for outside China. There is an urgent need for rigorous research focusing on the mitigation efforts to minimize the impact on society.
Serum GlycA Level Is Elevated in Active Systemic Lupus Erythematosus and Correlates to Disease Activity and Lupus Nephritis Severity
Authors: Dierckx Tim , Chiche Laurent , Daniel Laurent , Lauwerys Bernard , Van Weyenbergh Johan , Jourde-Chiche Noémie
Published: April 2020

Objective: Reliable non-invasive biomarkers are needed to assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). Glycoprotein acetylation (GlycA), a novel biomarker for chronic inflammation, has been reported to be increased in several inflammatory diseases. We investigated the relevance of serum GlycA in SLE patients exhibiting various levels of activity and severity, especially with regards to renal involvement. Methods: Serum GlycA was measured by nuclear magnetic resonance spectroscopy in samples from well characterized SLE patients and from both healthy controls and patients with other kidney diseases (KD). Disease activity was evaluated using the Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K). Renal severity was assessed by kidney biopsy. Results: Serum GlycA was elevated in active (n = 105) compared to quiescent SLE patients (n = 39, p < 10−6), healthy controls (n = 20, p = 0.009) and KD controls (n = 21, p = 0.04), despite a more severely altered renal function in the latter. GlycA level was correlated to disease activity (SLEDAI-2K, ρ = 0.37, p < 10−4), C-reactive protein, neutrophil count, triglyceride levels, proteinuria and inversely to serum albumin. In patients with biopsy-proven lupus nephritis (LN), GlycA levels were higher in proliferative (n = 26) than non-proliferative LN (n = 10) in univariate analysis (p = 0.04), and was shown to predict proliferative LN independently of renal parameters, immunological activity, neutrophil count and daily corticosteroid dosage by multivariate analysis (p < 5 × 10−3 for all models). In LN patients with repeated longitudinal GlycA measurement (n = 11), GlycA varied over time and seemed to peak at the time of the flare. Conclusions: GlycA, as a summary measure for different inflammatory processes, could be a valuable biomarker of disease activity in patients with SLE, and a non-invasive biomarker of pathological severity in the context of LN.
Subclinical Arteriosclerosis is Associated with Common Vascular Risk Factors in Long-Term Survivors of Testicular Cancer
Authors: Espíldora-Hernández Javier , Díaz-Antonio Tania , Baena-Espinar Javier , Alonso-Calderón Inmaculada , Rioja José , Alba-Conejo Emilio , Valdivielso Pedro , Sánchez-Chaparro Miguel-Ángel
Published: April 2020

Cardiovascular disease risk is increased in survivors of testicular cancer because of exposure to treatment (chemotherapy and radiotherapy), as well as modification in lifestyle. Our aim was to assess the presence of subclinical arteriosclerosis in survivors of testicular cancer in comparison with a control group. This was a cross-sectional, observational, case–control study including 50 survivors of Germ Cell Tumor (GCT) (14 years of follow-up) and 53 age-matched controls with no cancer. We registered clinical data, cardiovascular risk factors, physical and Mediterranean questionnaires, intima-media thickness and plaque at carotid and femoral arteries by ultrasound, calcium score at the abdominal aorta, and liver steatosis by computed tomography, and applied analytical tests to quantify metabolic risk factors and inflammation markers. Patients showed a trend toward greater intima-media thickness (IMT) and plaques than controls, as well as a higher calcium score in the abdominal aorta. Remarkably, patients had higher waist circumference, insulin resistance (HOMA-IR), and liver steatosis, but lower physical activity and high-density lipoprotein (HDL) cholesterol than controls (all p < 0.05). In multivariate analyses, only common vascular risk factors were associated with subclinical arteriosclerosis. As a conclusion, in our study, a higher rate of subclinical arteriosclerosis in testicular cancer survivors was associated with classical metabolic risk factors and lifestyle, but not with exposure to chemotherapy.
Arthroscopy-Assisted Corrective Osteotomy, Reduction, Internal Fixation and Strut Allograft Augmentation for Tibial Plateau Malunion or Nonunion
Authors: Wang Jr-Yi , Cheng Chun-Ying , Chen Alvin Chao-Yu , Chan Yi-Sheng
Published: April 2020

Purpose: The purpose of this study was to present the results of arthroscopy-assisted corrective osteotomy (AACO), reduction, internal fixation, and strut allograft augmentation for tibial plateau malunion or nonunion. Methods: Fifty-eight patients, mean age 49 ± 11.9 years old, with tibial plateau malunion (n = 44) or nonunion (n = 14), were included in this study. There were 19 Schatzker type II fractures (32.7%), 2 type III fractures (3.4%), 7 type IV fractures (12%), 20 type V fractures (34.5%), and 10 type VI fractures (17.2%). The mean follow-up period was 46.2 ± 17.6 months. Clinical and radiologic outcomes were scored by the Rasmussen system. Articular depression was measured from computed tomography. Secondary osteoarthritis was diagnosed when radiographs showed a narrowed joint space in the injured knee at follow-up. Results: Mean clinical score improved from 15.4 ± 3.9 (pre-revision) to 23.2 ± 4.5 (post-revision). Mean radiologic score improved from 7.7 ± 2.5 (pre-revision) to 12.0 ± 3.9 (post-revision). Fifty-six fractures achieved successful union. The average union time was 19.6 ± 7.5 weeks. Post-revision, 81% had good or excellent clinical results and 62% had good or excellent radiological results. Secondary osteoarthritis (OA) was noted in 91% of all injured knees, where 25.8% were mild OA, 25.8 % were moderate OA, and 38% were severe OA. There were 6 cases of deep infection (10.3%) and 1 case of wound edge necrosis (1.7%). Five cases were converted to total knee replacement after the index surgery with an average period of 13.5 months (range 8–24 months). Conclusions: Arthroscopy-assisted corrective osteotomy, reduction, internal fixation, and strut allograft augmentation can restore tibial plateau malunion/nonunion with well-documented radiographic healing and good clinical outcomes.
Fully Digital Workflow for Planning Static Guided Implant Surgery: A Prospective Accuracy Study
Authors: Lin Chia-Cheng , Wu Ching-Zong , Huang Mao-Suan , Huang Chiung-Fang , Cheng Hsin-Chung , Wang Dayen Peter
Published: April 2020

The accuracy of static guided implant surgery (sGIS) using conventional planning workflow has been extensively examined; however, more information is required to justify the application of fully digital planning protocol. The purpose of this study was to investigate the clinical accuracy of sGIS with a fully digital planning workflow. Twenty-one partially edentulous patients were enrolled in this prospective study. Cone-beam computed tomography (CBCT) and intraoral scans were taken and superimposed by matching the dental surface images directly (surface registration protocol) or by matching fiducial markers on a stereolithographic (SLA) radiographic template fabricated from the digital data of the intraoral scan (fiducial marker registration protocol). Virtual implant treatment plans were then determined, and tooth-supported SLA surgical guides were fabricated according to the plans. Twenty-six implant surgeries were performed via the surgical guide by one surgeon. Pre- and post-operative CBCT images were superimposed, and the positional and angular deviations between placed and planned implants were measured with metrology software. A total of 43 fully guided implants were placed, in which 25 implants were planned with the surface registration protocol. Implants planned based on the surface registration protocol had a larger mean angular deviation than the fiducial marker registration protocol. No significant differences were found for any deviations of the examined variables. Within the limits of this study, we concluded that the clinical accuracy of the sGIS planned with a fully digital workflow was consistent with the conventional workflow for partially edentulous patients.
Combined DNase and Proteinase Treatment Interferes with Composition and Structural Integrity of Multispecies Oral Biofilms
Authors: Karygianni Lamprini , Attin Thomas , Thurnheer Thomas
Published: April 2020

Modification of oral biofilms adhering to dental hard tissues could lead to new treatment approaches in cariology and periodontology. In this study the impact of DNase I and/or proteinase K on the formation of a simulated supragingival biofilm was investigated in vitro. Six-species biofilms were grown anaerobically in the presence of DNase I and proteinase K. After 64 h biofilms were either harvested and quantified by culture analysis or proceeded to staining followed by confocal laser scanning microscopy. Microbial cells were stained using DNA-dyes or fluorescent in situ hybridization. Exopolysaccharides, eDNA and exoproteins were stained with Calcofluor, anti-DNA-antibody, and SyproTM Ruby, respectively. Overall, results showed that neither DNase I nor proteinase K had an impact on total colony-forming units (CFUs) compared to the control without enzymes. However, DNase I significantly suppressed the growth of Actinomyces oris, Fusobacterium nucleatum, Streptococcus mutans, Streptococcus oralis and Candida albicans. Proteinase K treatment induced significant increase in S. mutans and S. oralis CFUs (p < 0.001), whereas C. albicans and V. dispar showed lower CFUs compared to the control. Interestingly, confocal images visualized the biofilm degradation caused by DNase I and proteinase K. Thus, enzymatic treatment should be combined with conventional antimicrobial agents aiming at both bactericidal effectiveness and biofilm dispersal.
Wound Lavage in Studies on Vital Pulp Therapy of Permanent Teeth with Carious Exposures: A Qualitative Systematic Review
Authors: Munir Amina , Zehnder Matthias , Rechenberg Dan-Krister
Published: April 2020

The aim of this study was to systematically review pulp wound lavage in vital pulp therapy (VPT). A search was conducted in six life science databases to identify clinical trials carried out on permanent teeth with a carious pulp exposure and a recall interval of at least six months. Twenty-seven trials of low to moderate risk of bias (RoB-2 and ROBINS-I) were included. Data was extracted and analyzed regarding study characteristics and methods used for pulp wound lavage. The agent used for pulp wound lavage was specified in all included trials. Most of the identified trials (23/27) randomized the pulp capping material. Many (14/27) reported the use of sodium hypochlorite (NaOCl); ten used only saline or water. One trial was identified that compared pulp wound lavage with 2.5% (NaOCl) to saline, another compared 5% glutaraldehyde to water, both in immature molar pulpotomies. Both studies were underpowered. Neither showed a significant difference between treatments. The use of NaOCl was positively correlated to recent year of publication and use of hydraulic calcium silicate cements for pulp capping (p < 0.05). In conclusion, despite a lack of well-designed trials on pulp wound lavage in VPT, a trend towards using NaOCl for this purpose was observed.