bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Nuances to Reduce and Manage Cerebrospinal Fluid Leaks after Microvascular Decompression
Authors: Go Kyeong-O , Hwang Kihwan , Han Jung Ho
Published: April 2020

Background: No dural substitute has proven to be complication-free in a large clinical trial, even suggesting some benefit during watertight closure. However, primary dural closure is not always possible due to dural shrinkage from electrocautery for dural bleeding. Objective: This study is performed to analyze the clinical outcomes related to cerebrospinal fluid (CSF) leakage after microvascular decompression (MVD) using a simple surgical technique. Methods: Three hundred and sixty consecutive cases were treated with MVD and followed up for more than one month after surgery. Bleeding from the cut veins during dural incision was controlled by pulling stay sutures instead of electrocautery to avoid dural shrinkage. Additionally, a wet cottonoid was placed on the cerebellar side dural flap to prevent dural dehydration. During dural closure, primary dural closure was always attempted. If not possible, a “plugging muscle” method was used for watertight dural closure. Results: The mean age was 54.1 ± 10.8 years (range, 24–85 years), and 238 (66.1%) were female. Primary MVD was performed in 345 (95.8%) patients. The mean operation time (from skin incision to skin closure) was 96.7 ± 33.0 min (range, 38–301 min). Primary dural closure was possible in 344 (95.6%) patients. The “plugging muscle method” was performed more frequently in patients older than 60 years (8 of 99 cases, 8.08%) than in younger cases (8 of 261 cases, 3.07%) (p = 0.039; chi-squared test). After surgery, 5 (1.4%) patients were treated for middle ear effusion, and another 5 (1.4%) patients experienced transient CSF rhinorrhea, which was spontaneously resolved within 1 to 7 days. No patients required additional treatments for CSF leakage. Conclusion: A simple technique using pulling stay sutures to stop bleeding from the dural edges and placing a wet cottonoid on the exposed dura can make primary dural closure easier.
Long-Term Follow-Up of Patients with Catecholaminergic Polymorphic Ventricular Arrhythmia
Authors: Veith Michael , El-Battrawy Ibrahim , Roterberg Gretje , Raschwitz Laura , Lang Siegfried , Wolpert Christian , Schimpf Rainer , Zhou Xiaobo , Akin Ibrahim , Borggrefe Martin
Published: April 2020

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited disorder causing life-threatening arrhythmias. Long-term outcome studies of the channelopathy are limited. Objective: The aim of the present study was to summarize our knowledge on CPVT patients, including the clinical profile treatment approach and long-term outcome. Methods: In this single center study, we retrospectively and prospectively collected data from nine CPVT patients and analyzed them. Results: We reviewed nine patients with CPVT in seven families (22% male), with a median follow-up time of 8.6 years. Mean age at diagnosis was 26.4 ± 12 years. Symptoms at admission were syncope (four patients) and aborted cardiac arrest (four patients). Family history of sudden cardiac death was screened in five patients. In genetic analyses, we found five patients with ryanodine type 2 receptor (RYR2) mutations. Seven patients were treated with beta-blockers, and if symptoms persisted flecainide was added (four patients). Despite beta-blocker treatment, three patients suffered from seven adverse cardiac events. An implantable cardioverter defibrillator was implanted in seven patients (one primary, six secondary prevention). Over the follow-up period, three patients suffered from ventricular tachycardia (ten times) and five patients from ventricular fibrillation (nine times). No one died during follow-up. Conclusion: Our CPVT cohort showed a high risk of cardiac events. Family screening, optimal medical therapy and individualized treatment are necessary in affected patients in referral centers.
Importance of Footwear Outsole Rigidity in Improving Spatiotemporal Parameters in Patients with Diabetes and Previous Forefoot Ulcerations
Authors: López-Moral Mateo , Molines-Barroso Raúl Juan , Álvaro-Afonso Francisco Javier , Uccioli Luigi , Senneville Eric , Lázaro-Martínez José Luis
Published: April 2020

We aimed to identify if any differences existed in spatiotemporal parameters during gait among different densities of rocker soles in patients with a history of neuropathic ulcerations and the differences in comfort between shoe conditions. This study was a cross-sectional study of 24 patients with diabetes and a history of neuropathic diabetic foot ulcers (DFUs). Spatiotemporal parameters (duration of stance phase (ms), stride length (cm), and step velocity (m/s)) were analyzed in barefoot, semirigid outsole, and rigid outsole footwear conditions. A dynamic pressure measurement system (Footscan® system, RSscan International, Olen, Belgium) was used to assess shoe conditions. We also analyzed differences in comfort between the shoe conditions using a visual analog scale. A Wilcoxon test for paired samples was used to assess gait differences. Result showed that a rigid outsole causes changes in the subphases of the stance phase (p < 0.001; Cohen d = 0.6) compared to a semirigid outsole. Stride length (p < 0.001; Cohen d = 0.66) and step velocity were significantly longer (p < 0.001; Cohen d = 2.03) with the use of rigid outsole footwear. A rigid rocker sole reduces the time of the stance phase, in addition to increasing the stride length and velocity of step in patients with a previous history of DFUs.
The Development of the Ascending Aortic Wall in Tricuspid and Bicuspid Aortic Valve: A Process from Maturation to Degeneration
Authors: Grewal Nimrat , Gittenberger-de Groot Adriana C. , von der Thusen Jan , Wisse Lambertus J. , Bartelings Margot M. , DeRuiter Marco C. , Klautz Robert J.M. , Poelmann Robert E.
Published: April 2020

Background: Patients with a bicuspid aortic valve (BAV) have an increased risk for aortic dilation and dissection. In this study, we provide a histological stratification of the developing aorta in the tricuspid aortic valve (TAV) and the BAV populations as a reference for future studies on aortopathy and related syndromes. Methods: Non-dilated TAV and BAV ascending aortic wall samples were collected, including 60 TAV (embryonic–70 years) and 32 BAV specimens (fetal–72 years, categorized in eight age groups. Results: In TAV, intimal development starts in the neonatal phase. After birth, the thickness of the medial layer increases significantly by increase of elastic lamellae up to and including the “young child” phase stabilizing afterwards. The BAV shows already prenatal intimal thickening becoming significantly thinner after birth subsequently stabilizing. In BAV, increase in elastic lamellae is seen between the young child and the adolescent phases, stabilizing afterwards. Conclusions: Vascular development in TAV is described in three phases: maturation, stabilization, and degeneration. For BAV, the development can be described in two phases: maturation (already prenatally) and degeneration. After birth, the development of the aorta is characterized by degeneration, leading to weakening of the ascending aortic wall and increasing the risk of aortopathy.
Prevalence of Depression in Coronary Artery Bypass Surgery: A Systematic Review and Meta-Analysis
Authors: Correa-Rodríguez María , Abu Ejheisheh Moath , Suleiman-Martos Nora , Membrive-Jiménez María José , Velando-Soriano Almudena , Schmidt-RioValle Jacqueline , Gómez-Urquiza José Luis
Published: April 2020

Coronary artery bypass graft surgery (CABG) might adversely affect the health status of the patients, producing cognitive deterioration, with depression being the most common symptom. The aim of this study is to analyse the prevalence of depression in patients before and after coronary artery bypass surgery. A systematic review and meta-analysis was carried out, involving a study of the past 10 years of the following databases: CINAHL, LILACS, MEDLINE, PsycINFO, SciELO, Scopus, and Web of Science. The total sample comprised n = 16,501 patients. The total number of items was n = 65, with n = 29 included in the meta-analysis. Based on the different measurement tools used, the prevalence of depression pre-CABG ranges from 19–37%, and post-CABG from 15–33%. There is a considerable presence of depression in this type of patient, but this varies according to the measurement tool used and the quality of the study. Systematically detecting depression prior to cardiac surgery could identify patients at potential risk.
Impact of Glucose-Lowering Medications on Cardiovascular and Metabolic Risk in Type 2 Diabetes
Authors: Patti Angelo Maria , Rizvi Ali A , Giglio Rosaria Vincenza , Stoian Anca Pantea , Ligi Daniela , Mannello Ferdinando
Published: April 2020

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage polarization, and reduced synthesis of resident endothelial progenitor cells. As consequence, a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque is arguable, finally leading to significantly increased cardiovascular mortality. Main managements are focused on both prevention and early diagnosis, by targeted treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (e.g., Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, and DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial (dys)functions, inflammatory markers, biomarkers of both oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of the main trials focused on the cardiovascular safety of these drugs from the CV standpoint.
Deproteinization as a Rapid Method of Saliva Purification for the Determination of Carbamazepine and Carbamazepine-10,11 Epoxide
Authors: Dziurkowska Ewelina , Wesolowski Marek
Published: April 2020

Saliva is a valuable diagnostic material that, in some cases, may replace blood. However, because of its different composition, its use requires the development of new, or the modification of existing, extraction procedures. Therefore, the aim of the study was to develop a method of saliva purification that would enable the determination of carbamazepine and its metabolite, carbamazepine-10,11 epoxide. When comparing two methods of sample purification (Solid Phase Extration (SPE) and deproteinization), it was found that the second method yielded more favorable results. A 1% formic acid solution in acetonitrile was used for extraction. The samples were shaken and centrifuged, and the supernatant obtained was evaporated and dissolved in a mobile phase, then chromatographically analyzed. The developed method was validated by determining its linearity in the range of 10–5000 ng/mL for both analytes. Intra- and inter-day precision did not exceed 14%. In order to check the usefulness of the method, both analytes were determined in the saliva samples from 20 patients treated with carbamazepine. The content of both analytes was detected and determined in all of the tested samples of saliva. It was found that the method developed is rapid, sensitive, reliable, and can be used to monitor the concentration of carbamazepine and metabolite in patients’ saliva.
Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug–Drug Interactions
Authors: Brown Joshua D.
Published: April 2020

Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug–drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in certain racial groups (up to 35% in Caucasians) and increase the bioavailability of THC. THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection. General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy. Future work and research must establish sufficient data resources to capture medical marijuana use for such studies. Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy.
Can an Observational Gait Scale Produce a Result Consistent with Symmetry Indexes Obtained from 3-Dimensional Gait Analysis?: A Concurrent Validity Study
Authors: Guzik Agnieszka , Drużbicki Mariusz , Perenc Lidia , Podgórska-Bednarz Justyna
Published: April 2020

To investigate whether a simple observational tool may be a substitute to the time-consuming and costly 3-dimensional (3D) analysis, the study applied the Wisconsin Gait Scale (WGS), enabling assessment which is highly consistent with 3D gait parameters in patients after a stroke. The aim of this study was to determine whether, and to what extent, observational information obtained from WGS-based assessment can be applied to predict results of 3D gait analysis for selected symmetry indicators related to spatiotemporal and kinematic gait parameters. Fifty patients at a chronic stage of recovery post-stroke were enrolled in the study. The spatiotemporal and kinematic gait parameters were measured using a movement analysis system. The symmetry index (SI), was calculated for selected gait parameters. The patients’ gait was evaluated by means of the WGS. It was shown that stance % SI, as well as hip and knee flexion-extension range of motion SI can most effectively be substituted by WGS-based estimations (coefficient of determination exceeding 80%). It was shown that information acquired based on the WGS can be used to obtain results comparable to those achieved in 3D assessment for selected SIs of spatiotemporal and kinematic gait parameters. The study confirms that observation of gait using the WGS, which is an ordinal scale, is consistent with the selected aims of 3D assessment. Therefore, the scale can be used as a complementary tool in gait assessment.
Calprotectin and Receptor for Advanced Glycation End Products as a Potential Biomarker in Abdominal Aortic Aneurysm
Authors: Hauzer Willy , Witkiewicz Wojciech , Gnus Jan
Published: April 2020

Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the diameter of the abdominal aorta was found. The purpose of this study was to investigate whether calprotectin and the RAGE plasma level may be a biomarker of human AAA occurrence. We determined two groups of research participants: a group of 32 patients aged 53–88 undergoing primary endovascular aneurysm repair and a control group of 43 volunteers aged 59–82 without the AAA. All the patients from the study group had their blood samples drawn in order to determine the level of calprotectin and RAGE in plasma. The second follow-up examination was carried out after three months. The concentration of calprotectin and RAGE in plasma was determined with the use of the immunoenzymatic method (ELISA). The study showed that patients with the AAA had significantly higher mean calprotectin and RAGE plasma levels (p = 0.0001 and p = 0.0002, respectively) as compared to the control group. After the AAA repair operations, the level of concentration of the calprotectin decreased significantly (p = 0.0002). So far, no studies on the connection between the increase of the calprotectin and RAGE in the patient’s plasma with the AAA have been published. Calprotectin may be a promising biomarker related to the occurrence of AAA. Larger studies are needed to fully elucidate and confirm the role of calprotectin in the development and progression of the aneurysm.
Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study
Authors: García Rodríguez Luis A. , Lanas Angel , Soriano-Gabarró Montse , Vora Pareen , Cea Soriano Lucía
Published: April 2020

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049 new users of low-dose aspirin (75–300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case–control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54–0.88) for >1 month PPI use and 2.65 (1.62–4.3) for ≤1 month PPI use. Among the latter group, ORs (95% CIs) were 3.05 (1.75–5.33) for PPI initiation after start of aspirin therapy, and 1.66 (0.63–4.36) for PPI initiation on/before start of aspirin therapy. For LGIB (n = 1428), ORs (95% CIs) were 0.98 (0.81–1.17) for >1 month PPI use and 1.12 (0.73–1.71) for ≤1 month PPI use. Among low-dose aspirin users, maintaining PPI use (>1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk.
Patient Characteristics, Treatment and Outcome in Non-Ischemic vs. Ischemic Cardiogenic Shock
Authors: Schrage Benedikt , Weimann Jessica , Dabboura Salim , Yan Isabell , Hilal Rafel , Becher Peter Moritz , Seiffert Moritz , Bernhardt Alexander M. , Kluge Stefan , Reichenspurner Hermann , Blankenberg Stefan , Westermann Dirk
Published: April 2020

Aim: Evidence on non-ischemic cardiogenic shock (CS) is scarce. The aim of this study was to investigate differences in patient characteristics, use of treatments and outcomes in patients with non-ischemic vs. ischemic CS. Methods: Patients with CS admitted between October 2009 and October 2017 were identified and stratified as non-ischemic/ischemic CS based on the absence/presence of acute myocardial infarction. Logistic/Cox regression models were fitted to investigate the association between non-ischemic CS and patient characteristics, use of treatments and 30-day in-hospital mortality. Results: A total of 978 patients were enrolled in this study; median age was 70 (interquartile range 58, 79) years and 70% were male. Of these, 505 patients (52%) had non-ischemic CS. Patients with non-ischemic CS were more likely to be younger and female; were less likely to be active smokers, to have diabetes or decreased renal function, but more likely to have a history of myocardial infarction; and they were more likely to present with unfavorable hemodynamics and with mechanical ventilation. Regarding treatments, patients with non-ischemic CS were more likely to be treated with catecholamines, but less likely to be treated with extracorporeal membrane oxygenation or percutaneous left-ventricular assist devices. After adjustment for multiple relevant confounders, non-ischemic CS was associated with a significant increase in the risk of 30-day in-hospital mortality (hazard ratio 1.14, 95% confidence interval 1.04–1.24, p < 0.01). Conclusion: In this large study, non-ischemic CS accounted for more than 50% of all CS cases. Non-ischemic CS was not only associated with relevant differences in patient characteristics and use of treatments, but also with a worse prognosis. These findings highlight the need for effective treatment strategies for patients with non-ischemic CS.
Active Helicobacter pylori Infection is Independently Associated with Nonalcoholic Steatohepatitis in Morbidly Obese Patients
Authors: Doulberis Michael , Srivastava Simone , Polyzos Stergios A , Kountouras Jannis , Papaefthymiou Apostolis , Klukowska-Rötzler Jolanta , Blank Annika , Exadaktylos Aristomenis K , Srivastava David S
Published: April 2020

Nonalcoholic fatty liver disease (NAFLD) emerges as an important global burden and Helicobacter pylori infection (Hp-I) has been suggested as a risk factor of NAFLD, although controversy exists. This retrospective study aimed to investigate a potential impact of active Hp-I on NAFLD severity in morbidly obese patients, subjected to bariatric surgery and gastric biopsy for documentation of Hp-I. Of 64 eligible participants, 15 (23.4%) were diagnosed with active Hp-I, showing higher rates of nonalcoholic steatohepatitis (NASH) than those without Hp-I (86.7% vs. 26.5%, respectively; p < 0.001). Concerning histological lesions, steatosis grade (p = 0.027), ballooning (p < 0.001), lobular inflammation (p = 0.003), and fibrosis stage (p < 0.001) were also more severe in Hp-I positive patients. Likewise, liver function tests, insulin resistance, dyslipidemia, and arterial hypertension were significantly higher in Hp-I positive patients. Hp-I was independently positively associated with NASH (beta = 3.27; p = 0.002), severe NASH (beta = 2.37; p = 0.018), and the presence of fibrosis (beta = 3.86; p = 0.001) in a binary regression model, after adjustment for potential confounders. In conclusion, active Hp-Ι was independently associated with NASH and fibrosis, findings offering potential clinical implication.
Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma
Authors: Kawaguchi Takumi , Yoshio Sachiyo , Sakamoto Yuzuru , Hashida Ryuki , Koya Shunji , Hirota Keisuke , Nakano Dan , Yamamura Sakura , Niizeki Takashi , Matsuse Hiroo , Torimura Takuji
Published: April 2020

The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC.
Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction
Authors: Kubánek Miloš , Schimerová Tereza , Piherová Lenka , Brodehl Andreas , Krebsová Alice , Ratnavadivel Sandra , Stanasiuk Caroline , Hansíková Hana , Zeman Jiří , Paleček Tomáš , Houštěk Josef , Drahota Zdeněk , Nůsková Hana , Mikešová Jana , Zámečník Josef , Macek Milan , Ridzoň Petr , Malusková Jana , Stránecký Viktor , Melenovský Vojtěch , Milting Hendrik , Kmoch Stanislav
Published: April 2020

Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. Results: Rare, conserved, and possibly pathogenic DES variants were identified in six (1.8%) probands. Two DES variants previously classified as variants of uncertain significance (p.(K43E), p.(S57L)), one novel DES variant (p.(A210D)), and two known pathogenic DES variants (p.(R406W), p.(R454W)) were associated with characteristic desmin-immunoreactive aggregates in myocardial and/or skeletal biopsy samples. The individual with the novel DES variant p.(Q364H) had a decreased myocardial expression of desmin with absent desmin aggregates in myocardial/skeletal muscle biopsy and presented with familial left ventricular non-compaction cardiomyopathy (LVNC), a relatively novel phenotype associated with desminopathy. An assessment of the mitochondrial function in four probands heterozygous for a disease-causing DES variant confirmed a decreased metabolic capacity of mitochondrial respiratory chain complexes in myocardial/skeletal muscle specimens, which was in case of myocardial succinate respiration more profound than in other cardiomyopathies. Conclusions: The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases.
A Simulation on Potential Secondary Spread of Novel Coronavirus in an Exported Country Using a Stochastic Epidemic SEIR Model
Authors: Iwata Kentaro , Miyakoshi Chisato
Published: April 2020

Ongoing outbreak of pneumonia caused by novel coronavirus (2019-nCoV) began in December 2019 in Wuhan, China, and the number of new patients continues to increase. Even though it began to spread to many other parts of the world, such as other Asian countries, the Americas, Europe, and the Middle East, the impact of secondary outbreaks caused by exported cases outside China remains unclear. We conducted simulations to estimate the impact of potential secondary outbreaks in a community outside China. Simulations using stochastic SEIR model were conducted, assuming one patient was imported to a community. Among 45 possible scenarios we prepared, the worst scenario resulted in the total number of persons recovered or removed to be 997 (95% CrI 990–1000) at day 100 and a maximum number of symptomatic infectious patients per day of 335 (95% CrI 232–478). Calculated mean basic reproductive number (R0) was 6.5 (Interquartile range, IQR 5.6–7.2). However, better case scenarios with different parameters led to no secondary cases. Altering parameters, especially time to hospital visit. could change the impact of a secondary outbreak. With these multiple scenarios with different parameters, healthcare professionals might be able to better prepare for this viral infection.
Validation of the mTICCS Score as a Useful Tool for the Early Prediction of a Massive Transfusion in Patients with a Traumatic Hemorrhage
Authors: Horst Klemens , Lentzen Rachel , Tonglet Martin , Mert Ümit , Lichte Philipp , Weber Christian D. , Kobbe Philipp , Heussen Nicole , Hildebrand Frank
Published: April 2020

The modified Trauma-Induced Coagulopathy Clinical Score (mTICCS) presents a new scoring system for the early detection of the need for a massive transfusion (MT). While validated in a large trauma cohort, the comparison of mTICCS to established scoring systems is missing. This study therefore validated the ability of six scoring systems to stratify patients at risk for an MT at an early stage after trauma. A dataset of severely injured patients (ISS ≥ 16) derived from the database of a level I trauma center (2010–2015) was used. Scoring systems assessed were Trauma-Associated Severe Hemorrhage (TASH) score, Prince of Wales Hospital (PWH) score, Larson score, Assessment of Blood Consumption (ABC) score, Emergency Transfusion Score (ETS), and mTICCS. Demographics, diagnostic data, mechanism of injury, injury pattern (graded by AIS), and outcome (length of stay, mortality) were analyzed. Scores were calculated, and the area under the receiver operating characteristic curves (AUCs) were evaluated. From the AUCs, the cut-off point with the best relationship of sensitivity-to-specificity was used to recalculate sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). A total of 479 patients were included; of those, blunt trauma occurred in 92.3% of patients. The mean age of patients was 49 ± 22 years with a mean ISS of 25 ± 29. The overall MT rate was 8.4% (n = 40). The TASH score had the highest overall accuracy as reflected by an AUC of 0.782 followed by the mTICCS (0.776). The ETS was the most sensitive (80%), whereas the TASH score had the highest specificity (82%) and the PWH score had the lowest (51.83%). At a cut-off > 5 points, the mTICCS score showed a sensitivity of 77.5% and a specificity of 74.03%. Compared to sophisticated systems, using a higher number of weighted variables, the newly developed mTICCS presents a useful tool to predict the need for an MT in a prehospital situation. This might accelerate the diagnosis of an MT in emergency situations. However, prospective validations are needed to improve the development process and use of scoring systems in the future.
Clinical Presentations and Outcome Studies of Cranial Nerve Involvement in Herpes Zoster Infection: A Retrospective Single-Center Analysis
Authors: Tsau Po-Wei , Liao Ming-Feng , Hsu Jung-Lung , Hsu Hui-Ching , Peng Chi-Hao , Lin Yu-Ching , Kuo Hung-Chou , Ro Long-Sun
Published: April 2020

Varicella-zoster virus (VZV) infection can cause chickenpox and herpes zoster. It sometimes involves cranial nerves, and rarely, it can involve multiple cranial nerves. We aimed to study clinical presentations of cranial nerve involvement in herpes zoster infection. We included patients who had the diagnosis of herpes zoster infection and cranial nerve involvement. The diagnosis was confirmed by typical vesicles and a rash. We excluded patients who had cranial neuralgias or neuropathies but without typical skin lesions (zoster sine herpete or post-herpetic neuralgia). We included 330 patients (mean age, 55.0 ± 17.0 years) who had herpes zoster with cranial nerve involvement, including 155 men and 175 women. Most frequently involved cranial nerves were the trigeminal nerve (57.9%), facial nerve (52.1%), and vestibulocochlear nerve (20.0%). Other involved cranial nerves included the glossopharyngeal nerve (0.9%), vagus nerve (0.9%), oculomotor nerve, trochlear nerve, and abducens nerve (each 0.3%, respectively). One hundred and seventy patients (51.5%) had only sensory symptoms/signs; in contrast, 160 patients (48.5%) had both sensory and motor symptoms/signs. Of those 160 patients, sensory preceded motor symptoms/signs in 64 patients (40.0%), sensory and motor symptoms/signs occurred simultaneously in 38 patients (23.8%), and motor preceded sensory symptoms/signs in 20 patients (12.5%). At one month after herpes zoster infection, vesicles and rash disappeared in 92.6% of patients; meanwhile facial palsy showed a significant improvement in 81.4% of patients (p < 0.05). Cranial motor neuropathies are not infrequent in herpes zoster infections. Multiple cranial nerve involvement frequently occurred in Ramsay Hunt syndrome. We found a significantly increased seasonal occurrence of cranial nerve zoster in spring rather than summer. Cranial motor nerves were affected while the hosts sometimes had a compromised immune system.
Prevalence and Causes of Anemia in Hospitalized Patients: Impact on Diseases Outcome
Authors: Randi Maria Luigia , Bertozzi Irene , Santarossa Claudia , Cosi Elisabetta , Lucente Fabrizio , Bogoni Giulia , Biagetti Giacomo , Fabris Fabrizio
Published: April 2020

Anemia is extremely common in hospitalized patients who are old and often with multiple diseases. We evaluated 435 consecutive patients admitted in the internal medicine department of a hub hospital and 191 (43.9%) of them were anemic. Demographic, historic and clinical data, laboratory tests, duration of hospitalization, re-admission at 30 days and death were recorded. Patients were stratified by age (<65, 65–80, >80 years), anemia severity, and etiology of anemia. The causes of anemia were: iron deficiency in 28 patients, vitamin B12 and folic acid deficiencies in 6, chronic inflammatory diseases in 80, chronic kidney disease in 15, and multifactorial in 62. The severity of the clinical picture at admission was significantly worse (p < 0.001), length of hospitalization was longer (p < 0.001) and inversely correlated to the Hb concentration, re-admissions and deaths were more frequent (p 0.017) in anemic compared to non-anemic patients. A specific treatment for anemia was used in 99 patients (36.6%) (transfusions, erythropoietin, iron, vitamin B12 and/or folic acid). Anemia (and/or its treatment) was red in the discharge letter only 54 patients. Even if anemia is common, in internal medicine departments scarce attention is paid to it, as it is generally considered a “minor” problem, particularly in older patients often affected by multiple pathologies. Our data indicate the need of renewed medical attention to anemia, as it may positively affect the outcome of several concurrent medical conditions and the multidimensional loss of function in older hospitalized patients.
Changes in Respiratory Muscle Strength Following Cardiac Rehabilitation for Prognosis in Patients with Heart Failure
Authors: Hamazaki Nobuaki , Kamiya Kentaro , Yamamoto Shohei , Nozaki Kohei , Ichikawa Takafumi , Matsuzawa Ryota , Tanaka Shinya , Nakamura Takeshi , Yamashita Masashi , Maekawa Emi , Meguro Kentaro , Noda Chiharu , Yamaoka-Tojo Minako , Matsunaga Atsuhiko , Ako Junya
Published: April 2020

Respiratory muscle weakness, frequently observed in patients with heart failure (HF), is reported as a predictor for poor prognosis. Although increased respiratory muscle strength ameliorates exercise tolerance and quality of life in HF patients, the relationship between changes in respiratory muscle strength and patient prognosis remains unclear. A total of 456 patients with HF who continued a 5-month cardiac rehabilitation (CR) were studied. We measured maximal inspiratory pressure (PImax) at hospital discharge as the baseline and five months thereafter to assess the respiratory muscle strength. Changes in PImax during the 5-month observation period (⊿PImax) were examined. We investigated the composite multiple incidence of all-cause death or unplanned readmission after 5-month CR. The relationship between ⊿PImax and the incidence of clinical events was analyzed. Over a median follow-up of 1.8 years, 221 deaths or readmissions occurred, and their rate of incidence was 4.3/100 person-years. The higher ⊿PImax was significantly associated with lower incidence of clinical event. In multivariate Poisson regression model after adjustment for clinical confounding factors, ⊿PImax remained a significant and independent predictor for all-cause death/readmission (adjusted incident rate ratio for ⊿PImax increase of 10 cmH2O: 0.77, 95% confidence interval: 0.70–0.86). In conclusion, the changes in respiratory muscle strength independently predict the incidence of clinical events in patients with HF.
Elevated Lactate Levels in Acute Pulmonary Embolism Are Associated with Prothrombotic Fibrin Clot Properties: Contribution of NETs Formation
Authors: Ząbczyk Michał , Natorska Joanna , Janion-Sadowska Agnieszka , Malinowski Krzysztof P. , Janion Marianna , Undas Anetta
Published: April 2020

Background: Elevated plasma lactate levels correlate with high mortality rate in acute pulmonary embolism (PE) patients. We hypothesized that elevated lactate levels correlate with prothrombotic fibrin clot properties and enhanced neutrophil extracellular trap (NET) formation in acute PE. Methods: As many as 126 normotensive acute PE patients (aged 58 ± 14 years) were enrolled. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), citrullinated histone H3 (citH3), and plasminogen activator inhibitor-1 antigen (PAI-1), together with plasma L-lactate levels were evaluated on admission. Results: Lactate levels ≥2 mM were found in 70 (55.6%) patients in whom we observed 29% higher neutrophil count and 45% elevated plasma citH3 levels. Elevated lactate levels were associated with more prothrombotic fibrin properties as reflected by 11% reduced Ks, 13% longer CLT, along with 11% increased ETP. Lactate levels were positively associated with plasma citH3 concentrations, ETP, CLT, and PAI-1 (p < 0.05). An increase of lactate levels by 1 mM leading to the prolongation of CLT by 8.82 min was shown in the linear regression. Conclusions: Our findings suggest a new mechanism contributing to a negative impact of elevated lactate levels on prognosis in acute PE patients, in particular hypofibrinolysis, associated with enhanced NET formation.
Confusion and Anxiety Following Breast Density Notification: Fact or Fiction?
Authors: Dench Evenda K. , Darcey Ellie C. , Keogh Louise , McLean Kirsty , Pirikahu Sarah , Saunders Christobel , Thompson Sandra , Woulfe Catherine , Wylie Elizabeth , Stone Jennifer
Published: April 2020

In the absence of evidence-based screening recommendations for women with dense breasts, it is important to know if breast density notification increases women’s anxiety. This study describes psychological reactions and future screening intentions of women attending a public mammographic screening program in Western Australia. Two-thirds of notified women indicated that knowing their breast density made them feel informed, 21% described feeling anxious, and 23% confused. Of the notified women who reported anxiety, 96% intended to re-screen when due (compared to 91% of all notified women and 93% of controls; p = 0.007 and p < 0.001, respectively). In summary, reported anxiety (following breast density notification) appears to increase women’s intentions for future screening, not the reverse.
IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma
Authors: Kuei Chia-Hao , Lin Hui-Yu , Lee Hsun-Hua , Lin Che-Hsuan , Zheng Jing-Quan , Chen Kuan-Chou , Lin Yuan-Feng
Published: April 2020

Although mTOR inhibitors have been approved as first-line therapy for treating metastatic clear cell renal cell carcinoma (ccRCC), the lack of useful markers reduces their therapeutic effectiveness. The objective of this study was to estimate if inositol monophosphatase 2 (IMPA2) downregulation refers to a favorable outcome in metastatic ccRCC receiving mTOR inhibitor treatment. Gene set enrichment analysis predicted a significant activation of mTORC1 in the metastatic ccRCC with IMPA2 downregulation. Transcriptional profiling of IMPA2 and mTORC1-related gene set revealed significantly inverse correlation in ccRCC tissues. Whereas the enforced expression of exogenous IMPA2 inhibited the phosphorylation of Akt/mTORC1, artificially silencing IMPA2 led to increased phosphorylation of Akt/mTORC1 in ccRCC cells. The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. In contrast, blocking autophagosome formation with 3-methyladenine rescued the mitigated metastatic potential in vitro and in vivo in IMPA2-overexpressing ccRCC cells. Our findings indicated that IMPA2 downregulation negatively activates mTORC1 activity and could be a biomarker for guiding the use of mTOR inhibitors or autophagy inducers to combat metastatic ccRCC in the clinic.
The Clinical Impact of Hexanic Extract of Serenoa repens in Men with Prostatic Inflammation: A Post Hoc Analysis of a Randomized Biopsy Study
Authors: Samarinas Michael , Karatzas Anastasios , Tzortzis Vasileios , Gravas Stavros
Published: April 2020

A randomized biopsy study showed that hexanic Serenoa repens (HESr) treatment resulted in prostatic inflammation reduction. This post-hoc analysis evaluated the clinical impact of HESr and investigated correlations between baseline parameters and treatment response. Patients were randomized to receive HESr 320mg/day for six months or no therapy. Assessment included International Prostate Symptoms Score (IPSS), prostate volume (PV), and maximum flow rate (Qmax). Baseline characteristics were recorded, including body mass index (BMI) and metabolic syndrome (MetS) components. In patients under α1-adrenoceptor antagonists (α1-blockers), the addition of HESr resulted in statistically significant IPSS improvement after 6 months (p = 0.006). IPSS remained stable in patients under a1-blockers only (p = 0.346). Patients treated only with HESr reported a significant IPSS amelioration (p = 0.001). In the control group of naïve patients, no significant IPSS change was detected (p = 0.298). Baseline PV showed fair correlation (r = −0.20) with inflammation reduction in the HESr patients. BMI (r = 0.40), diabetes mellitus (r = 0.40), and PV (r = 0.23) showed fair correlation with Qmax increase but without reaching statistical significance. MetS (p = 0.06) was an influent biomarker for Qmax improvement. Treatment with HESr (as monotherapy or add-on therapy to a-blockers) may improve urinary symptoms in terms of IPSS in patients with prostatic inflammation.
Mastitis in Autoimmune Diseases: Review of the Literature, Diagnostic Pathway, and Pathophysiological Key Players
Authors: Goulabchand Radjiv , Hafidi Assia , Van de Perre Philippe , Millet Ingrid , Maria Alexandre Thibault Jacques , Morel Jacques , Le Quellec Alain , Perrochia Hélène , Guilpain Philippe
Published: April 2020

Mastitis frequently affects women of childbearing age. Of all the pathological breast conditions requiring specific management, autoimmune mastitis is in the third position after infection and breast cancer. The aim of this literature review was to make a comprehensive description of autoimmune diseases targeting the mammary gland. Four main histological patterns of autoimmune mastitis are described: (i) lymphocytic infiltrates; (ii) ductal ectasia; (iii) granulomatous mastitis; and (iv) vasculitis. Our literature search found that all types of autoimmune disease may target the mammary gland: organ-specific diseases (diabetes, thyroiditis); connective tissue diseases (such as systemic erythematosus lupus or Sjögren’s syndrome); vasculitides (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, giant cell arteritis, polyarteritis nodosa, Behçet’s disease); granulomatous diseases (sarcoidosis, Crohn’s disease); and IgG4-related disease. Cases of breast-specific autoimmune diseases have also been reported, including idiopathic granulomatous mastitis. These breast-limited inflammatory diseases are sometimes the first symptom of a systemic autoimmune disease. Although autoimmune mastitis is rare, it is probably underdiagnosed or misdiagnosed. Early diagnosis may allow us to detect systemic diseases at an earlier stage, which could help to initiate a prompt, appropriate therapeutic strategy. In case of suspected autoimmune mastitis, we hereby propose a diagnostic pathway and discuss the potential pathophysiological pathways leading to autoimmune breast damage.
The Glucocorticoid Receptor NR3C1 in Testicular Peritubular Cells is Developmentally Regulated and Linked to the Smooth Muscle-Like Cellular Phenotype
Authors: Welter Harald , Herrmann Carola , Dellweg Nils , Missel Annika , Thanisch Christiane , Urbanski Henryk F. , Köhn Frank-Michael , Schwarzer J. Ullrich , Müller-Taubenberger Annette , Mayerhofer Artur
Published: April 2020

Whether glucocorticoids (GC) can directly affect human testicular functions is not well understood. A predominant site of GC receptor (GR; NR3C1) expression in the adult testis are peritubular smooth muscle-like cells, which express smooth muscle actin (ACTA2), contract and thereby are involved in sperm transport. In contrast to the adult, neither GR nor ACTA2, or elastin (ELN) were detected in the peritubular compartment before puberty in non-human primate testes. In isolated human testicular peritubular cells (HTPCs), activation of GR by dexamethasone (Dex) caused the translocation of GR to the nucleus and stimulated expression of ACTA2 and ELN, without affecting the expression of collagens. Cytoskeletal ACTA2-rearrangements were observed and were associated with an increased ability to contract. Our results indicate post-pubertal testicular roles of GC in the maintenance of the contractile, smooth muscle-like phenotype of peritubular cells.
A Prospective Pilot Trial to Assess the Efficacy of Argatroban (Argatra®) in Critically Ill Patients with Heparin Resistance †
Authors: Bachler Mirjam , Hell Tobias , Bösch Johannes , Treml Benedikt , Schenk Bettina , Treichl Benjamin , Friesenecker Barbara , Lorenz Ingo , Stengg Daniel , Hruby Stefan , Wallner Bernd , Oswald Elgar , Ströhle Mathias , Niederwanger Christian , Irsara Christian , Fries Dietmar
Published: April 2020

The current study aims to evaluate whether prophylactic anticoagulation using argatroban or an increased dose of unfractionated heparin (UFH) is effective in achieving the targeted activated partial thromboplastin time (aPTT) of more than 45 s in critically ill heparin-resistant (HR) patients. Patients were randomized either to continue receiving an increased dose of UFH, or to be treated with argatroban. The endpoints were defined as achieving an aPTT target of more than 45 s at 7 h and 24 h. This clinical trial was registered on clinicaltrials.gov (NCT01734252) and on EudraCT (2012-000487-23). A total of 42 patients, 20 patients in the heparin and 22 in the argatroban group, were included. Of the patients with continued heparin treatment 55% achieved the target aPTT at 7 h, while only 40% of this group maintained the target aPTT after 24 h. Of the argatroban group 59% reached the target aPTT at 7 h, while at 24 h 86% of these patients maintained the targeted aPTT. Treatment success at 7 h did not differ between the groups (p = 0.1000), whereas at 24 h argatroban showed significantly greater efficacy (p = 0.0021) than did heparin. Argatroban also worked better in maintaining adequate anticoagulation in the further course of the study. There was no significant difference in the occurrence of bleeding or thromboembolic complications between the treatment groups. In the case of heparin-resistant critically ill patients, argatroban showed greater efficacy than did an increased dose of heparin in achieving adequate anticoagulation at 24 h and in maintaining the targeted aPTT goal throughout the treatment phase.