Journal of Clinical Medicine

16 pages, 1933 KiB

Open AccessReview

by Willemien van Zwol, Antoine Rimbert and Jan Albert Kuivenhoven

J. Clin. Med. 2019, 8(7), 1085; https://doi.org/10.3390/jcm8071085 - 23 Jul 2019

Cited by 8 | Viewed by 8700

The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on [...] Read more.

The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on lipoprotein(a) (Lp(a)) or plasma triglycerides, two other risk factors for ASCVD. This review summarizes the evidence and the rationale to target Lp(a) and triglycerides and provides an overview of currently tested strategies to lower Lp(a), apolipoprotein C-III and angiopoietin-like protein 3. In addition, it summarizes new findings on the use of omega-3 fatty acids (OM3FA) to fight ASCVD. With the exception of OM3FA supplementation, the promise of the experimental drugs discussed here depends on the long-term safety and efficacy of monoclonal antibodies and/or antisense oligonucleotides Clinical outcome trials will ultimately prove whether these new therapeutic modalities will reduce ASCVD risk. Full article

(This article belongs to the Special Issue Developing Novel Therapies to Prevent Atherosclerosis)

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15 pages, 1647 KiB

Open AccessArticle

Silent Myocardial Perfusion Abnormalities Detected by Stress Cardiovascular Magnetic Resonance in Antiphospholipid Syndrome: A Case-Control Study

by Sophie I. Mavrogeni, George Markousis-Mavrogenis, Olga Karapanagiotou, Konstantinos Toutouzas, Panagiotis Argyriou, Stella Velitsista, George Kanoupakis, Dimitrios Apostolou, David Hautemann, Petros P. Sfikakis and Maria G. Tektonidou

J. Clin. Med. 2019, 8(7), 1084; https://doi.org/10.3390/jcm8071084 - 23 Jul 2019

Cited by 19 | Viewed by 3716

Abstract

Objective: To examine the prevalence of silent myocardial ischemia and fibrosis in antiphospholipid syndrome (APS), using stress cardiovascular magnetic resonance (CMR). Methods: Forty-four consecutive APS patients without prior cardiac disease (22 primary APS, 22 systemic lupus erythematosus (SLE)/APS, mean age 44 (12.9) years, [...] Read more.

Objective: To examine the prevalence of silent myocardial ischemia and fibrosis in antiphospholipid syndrome (APS), using stress cardiovascular magnetic resonance (CMR). Methods: Forty-four consecutive APS patients without prior cardiac disease (22 primary APS, 22 systemic lupus erythematosus (SLE)/APS, mean age 44 (12.9) years, 64% women) and 44 age/gender-matched controls were evaluated using CMR at 1.5 T. Steady-state free precession imaging for function assessment and adenosine stress-CMR for perfusion-fibrosis evaluation were employed. The myocardial perfusion reserve index (MPRI), and myocardial fibrosis expressed as late gadolinium enhancement (LGE), were evaluated. Coronary angiography was indicated in patients with LGE. Associations with APS characteristics, classic cardiovascular disease (CVD) risk factors, high-sensitivity CRP (hs-CRP) and high-sensitivity Troponin (hs-TnT) levels were tested. All patients were followed up for 12 months. Results: Median MPRI was significantly lower in APS patients versus controls [1.5 (0.9–1.9) vs. 2.7 (2.2–3.2), p < 0.001], independently of any LGE presence. LGE was detected in 16 (36.3%) patients versus none of controls (p < 0.001); 12/16 were subsequently examined with coronary angiography and only two of them had coronary artery lesions. In multivariable analysis, none of the APS-related and classic CVD risk factors, or hs-CRP and hs-TnT covariates, were significant predictors of abnormal MPRI or LGE. At the twelve month follow-up, three (6.8%) patients experienced coronary artery disease, notably those with the lowest MPRI values. Conclusions: Abnormal MPRI and LGE are common in asymptomatic APS patients, independently so of any APS-related and classic CVD risk factors, or coronary angiography findings in cases with LGE. Stress-CMR is a valuable tool to detect silent myocardial ischemia and fibrosis in APS. Full article

(This article belongs to the Special Issue The Role of Cardiac Imaging in the Evaluation of Cardiac Involvement in Systemic and Neuromuscular Diseases)

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10 pages, 828 KiB

Open AccessArticle

Atrial Fibrillation: A New Indicator for Advanced Colorectal Neoplasia in Screening Colonoscopy

by Peter C. Kahr, Sabrina Hammerl, Ursula Huber-Schönauer, Christian M Schmied, Laurent M. Haegeli, Slayman Obeid, Sarah Eder, Sebastian Bachmayer, Elmar Aigner, Christian Datz and David Niederseer

J. Clin. Med. 2019, 8(7), 1083; https://doi.org/10.3390/jcm8071083 - 23 Jul 2019

Cited by 3 | Viewed by 3404

Abstract

Background: Colorectal cancer (CRC) is a common and potentially preventable malignancy. Evidence has emerged that coronary artery disease patients are at increased risk for developing CRC by shared risk factors. Here we investigated an association between CRC and atrial fibrillation (AF), a surrogate [...] Read more.

Background: Colorectal cancer (CRC) is a common and potentially preventable malignancy. Evidence has emerged that coronary artery disease patients are at increased risk for developing CRC by shared risk factors. Here we investigated an association between CRC and atrial fibrillation (AF), a surrogate marker of cardiovascular risk, in the setting of routine screening colonoscopy. Methods: We investigated 1949 asymptomatic participants (median age 61 [54–67] years, 49% females) undergoing screening colonoscopy within the SAKKOPI registry (Salzburg Colon Cancer Prevention Initiative). Forty-six participants with AF (2.4%) were identified, and colonoscopy findings were compared to non-AF participants. Propensity Score Matching (PSM) was used to create 1:1 and 3:1 age- and gender-matched couples. Results: Abnormal findings on screening colonoscopy (any form of adenoma or carcinoma) were more common in AF participants with an odds ratios (OR) of 2.4 [1.3–4.3] in the unmatched analysis, and 2.6 [1.1–6.3] and 2.0 [1.1–4.0] in the 1:1 and 3:1 matched groups, respectively. Correspondingly, the odds of finding advanced adenomas or carcinomas was elevated about three-fold across the different matched and unmatched analyses (OR 3.3 [1.1–10.8] for 3:1 matched participants). At the same time, the prevalence and number of colonic lesions were significantly higher in AF participants (63.0% vs. 33.4% for 3:1 matched participants, p < 0.001). Non-CRC related findings on colonoscopy, like diverticulosis, were non-different between groups. Conclusion: Participants with AF had a higher burden of advanced premalignant adenomas and CRC in routine colonoscopy screening. Our data suggest that practitioners should monitor the CRC screening status, especially in AF patients. Full article

(This article belongs to the Special Issue New Approaches to the Atrial Fibrillation Management)

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17 pages, 1197 KiB

Open AccessArticle

A History of Trauma is Associated with Aggression, Depression, Non-Suicidal Self-Injury Behavior, and Suicide Ideation in First-Episode Psychosis

by Rebecca E. Grattan, Natalia Lara, Renata M. Botello, Valerie L. Tryon, Adrienne M. Maguire, Cameron S. Carter and Tara A. Niendam

J. Clin. Med. 2019, 8(7), 1082; https://doi.org/10.3390/jcm8071082 - 23 Jul 2019

Cited by 22 | Viewed by 7392

Abstract

The association between trauma and psychosis outcomes is well-established, and yet the impact of trauma on comorbid clinical symptoms—such as aggression, non-suicidal self-injury behavior (NSSIB), suicide ideation, and suicide behavior—for those with psychosis is unclear. To effectively treat those with first-episode psychosis (FEP) [...] Read more.

The association between trauma and psychosis outcomes is well-established, and yet the impact of trauma on comorbid clinical symptoms—such as aggression, non-suicidal self-injury behavior (NSSIB), suicide ideation, and suicide behavior—for those with psychosis is unclear. To effectively treat those with first-episode psychosis (FEP) and a history of trauma, we need to understand the impact of trauma on their whole presentation. FEP participants were recruited from an Early Psychosis Program (N = 187, ages 12–35, 72.2% male). Clinicians gathered history of trauma, aggression, and suicide data, and rated current symptom severity and functioning. Data was coded using clinician rated measures, self-report measures, and retrospective clinical chart review. Regression analyses examined whether trauma was associated with a history of aggression, suicidal ideation, suicide behavior, NSSIB, symptoms, and functioning. Trauma was associated with aggression, aggression severity and type of aggression (aggression towards others). Trauma was also associated with depression severity, suicide ideation, most severe suicide ideation, and NSSIB. Trauma was not associated with suicide behavior, severity of suicide behavior or psychosocial functioning. Integrating trauma treatment into FEP care could reduce rates of depression, aggression, suicide ideation, and NSSIB for those with a history of trauma. To reduce suicide attempt occurrence and improve functioning, more research is needed. Full article

(This article belongs to the Special Issue Relationships between Trauma and Psychosis)

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13 pages, 910 KiB

Open AccessArticle

Early Parental Death and Risk of Psychosis in Offspring: A Six-Country Case-Control Study

by Supriya Misra, Bizu Gelaye, Karestan C. Koenen, David R. Williams, Christina P.C. Borba, Diego Quattrone, Marta Di Forti, Caterina La Cascia, Daniele La Barbera, Ilaria Tarricone, Domenico Berardi, Andrei Szöke, Celso Arango, Andrea Tortelli, Lieuwe de Haan, Eva Velthorst, Julio Bobes, Miguel Bernardo, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Jean-Paul Selten, Peter B. Jones, James B. Kirkbride, EU-GEI WP2 Group, Bart P.F. Rutten, Jim van Os, Robin M. Murray, Charlotte Gayer-Anderson and Craig Morgan Show full author list Hide full author list

J. Clin. Med. 2019, 8(7), 1081; https://doi.org/10.3390/jcm8071081 - 23 Jul 2019

Cited by 10 | Viewed by 5388

Abstract

Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We analyzed data from a six-country, case-control study to examine the associations of early parental death, type of death (maternal, paternal, both), and child’s age at death with [...] Read more.

Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We analyzed data from a six-country, case-control study to examine the associations of early parental death, type of death (maternal, paternal, both), and child’s age at death with psychosis, both overall and by ethnic group. In fully adjusted multivariable mixed-effects logistic regression models, experiencing early parental death was associated with 1.54-fold greater odds of psychosis (95% confidence interval (CI): 1.23, 1.92). Experiencing maternal death had 2.27-fold greater odds (95% CI: 1.18, 4.37), paternal death had 1.14-fold greater odds (95% CI: 0.79, 1.64), and both deaths had 4.42-fold greater odds (95% CI: 2.57, 7.60) of psychosis compared with no early parental death. Experiencing parental death between 11 and 16 years of age had 2.03-fold greater odds of psychosis than experiencing it before five years of age (95% CI: 1.02, 4.04). In stratified analyses, experiencing the death of both parents had 9.22-fold greater odds of psychosis among minority ethnic groups (95% CI: 2.02–28.02) and no elevated odds among the ethnic majority (odds ratio (OR): 0.96; 95% CI: 0.10–8.97), which could be due in part to the higher prevalence of early parental death among minority ethnic groups but should be interpreted cautiously given the wide confidence intervals. Full article

(This article belongs to the Special Issue Relationships between Trauma and Psychosis)

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15 pages, 1050 KiB

Open AccessArticle

Incidence of Cardiovascular Disease in Patients with Familial Hypercholesterolemia Phenotype: Analysis of 5 Years Follow-Up of Real-World Data from More than 1.5 Million Patients

by Luís Masana, Alberto Zamora, Núria Plana, Marc Comas-Cufí, Maria Garcia-Gil, Ruth Martí-Lluch, Anna Ponjoan, Lia Alves-Cabratosa, Roberto Elosua, Jaume Marrugat, Irene R. Dégano and Rafel Ramos

J. Clin. Med. 2019, 8(7), 1080; https://doi.org/10.3390/jcm8071080 - 23 Jul 2019

Cited by 39 | Viewed by 5426

Abstract

In the statin era, the incidence of atherosclerotic cardiovascular diseases (ASCVD) in patients with familial hypercholesterolemia (FH) has not been updated. We aimed to determine the incidence of ASCVD in patients with FH-phenotype (FH-P) and to compare it with that of normal low-density [...] Read more.

In the statin era, the incidence of atherosclerotic cardiovascular diseases (ASCVD) in patients with familial hypercholesterolemia (FH) has not been updated. We aimed to determine the incidence of ASCVD in patients with FH-phenotype (FH-P) and to compare it with that of normal low-density lipoprotein cholesterol (LDL-C) patients. We performed a retrospective cohort study using the Database of the Catalan primary care system, including ≥18-year-old patients with an LDL-C measurement. From 1,589,264 patients available before 2009, 12,823 fulfilled FH-P criteria and 514,176 patients were normolipidemic (LDL-C < 115 mg/dL). In primary prevention, patients with FH-P had incidences of ASCVD and coronary heart disease (CHD) of 14.9/1000 and 5.8/1000 person-years, respectively, compared to 7.1/1000 and 2.1/1000 person-years in the normolipidemic group. FH-P showed hazard ratio (HR) of 7.1 and 16.7 for ASCVD and CHD, respectively, in patients younger than 35 years. In secondary prevention, patients with FH-P had incidences of ASCVD and CHD of 89.7/1000 and 34.5/1000 person-years, respectively, compared to 90.9/1000 and 28.2/1000 person-years in the normolipidemic group (HR in patients younger than 35 years: 2.4 and 6.0). In the statin era, FH-P remains associated with high cardiovascular risk, compared with the normolipidemic population. This excess of risk is markedly high in young individuals. Full article

(This article belongs to the Special Issue Genetics of Hereditary Heart Diseases)

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12 pages, 1222 KiB

Open AccessReview

Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response

by Jan Oscarsson, Rolf Claesson, Mark Lindholm, Carola Höglund Åberg and Anders Johansson

J. Clin. Med. 2019, 8(7), 1079; https://doi.org/10.3390/jcm8071079 - 22 Jul 2019

Cited by 38 | Viewed by 7841

Abstract

Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. [...] Read more.

Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. Aggregatibacter actinomycetemcomitans is a facultative anaerobic Gram-negative bacterium associated with such cellular and molecular mechanisms associated with the pathogenesis of periodontitis. In the present review, we outline virulence mechanisms that help the bacterium to escape the host response. These properties include invasiveness, secretion of exotoxins, serum resistance, and release of outer membrane vesicles. Virulence properties of A. actinomycetemcomitans that can contribute to treatment resistance in the infected individuals and upon translocation to the circulation, also induce pathogenic mechanisms associated with several systemic diseases. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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11 pages, 217 KiB

Open AccessArticle

Relationships between Hearing Loss and the Prevalences of Cataract, Glaucoma, Diabetic Retinopathy, and Age-Related Macular Degeneration in Korea

by Joon Mo Kim, Se Young Kim, Hee Seung Chin, Hyun Ji Kim, Na Rae Kim and on behalf of the Epidemiologic Survey Committee of the Korean Ophthalmological Society

J. Clin. Med. 2019, 8(7), 1078; https://doi.org/10.3390/jcm8071078 - 22 Jul 2019

Cited by 16 | Viewed by 3767

Abstract

This study was conducted using the database of the Korea National Health and Nutrition Examination Survey to determine whether age-related eye diseases such as cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are related to hearing loss. 12,899 participants ≥ 40 [...] Read more.

This study was conducted using the database of the Korea National Health and Nutrition Examination Survey to determine whether age-related eye diseases such as cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are related to hearing loss. 12,899 participants ≥ 40 years of age were included. The weighted prevalence of diabetic retinopathy was not significantly different between the normal hearing group and hearing-impaired group, but the weighted prevalences of cataract, glaucoma, early AMD, and late AMD were significantly different in the two groups. The odds ratio for cataract in the hearing-impaired group was 1.373 (1.118–1.687). The odds ratios of glaucoma, DR, early AMD, and late AMD were not significantly different in the hearing-impaired group. Age was significantly associated with the presence of concurrent cataract and hearing impairment by 6.574-fold per decade. Significant factors that increased the risk of concurrent glaucoma and hearing impairment were age, male gender, and triglyceride. Age, ex-smoker, systolic BP elevation, BMI decline, and fasting blood sugar significantly predicted the presence of concurrent DR and hearing loss. In early AMD, age and triglyceride, and in late AMD, age and systolic BP elevations increased the risk of concurrent AMD and hearing impairment. Full article

(This article belongs to the Section Ophthalmology)

16 pages, 2188 KiB

Open AccessArticle

Compensatory Neural Recruitment for Error-Related Cerebral Activity in Patients with Moderate-To-Severe Obstructive Sleep Apnea

by Ping-Song Chou, Sharon Chia-Ju Chen, Chung-Yao Hsu, Li-Min Liou, Meng-Ni Wu, Ching-Kuan Liu and Chiou-Lian Lai

J. Clin. Med. 2019, 8(7), 1077; https://doi.org/10.3390/jcm8071077 - 22 Jul 2019

Cited by 3 | Viewed by 2508

Abstract

(1) Background: Although it is known that obstructive sleep apnea (OSA) impairs action-monitoring function, there is only limited information regarding the associated cerebral substrate underlying this phenomenon. (2) Methods: The modified Flanker task, error-related event-related potentials (ERPs), namely, error-related negativity (ERN) and error [...] Read more.

(1) Background: Although it is known that obstructive sleep apnea (OSA) impairs action-monitoring function, there is only limited information regarding the associated cerebral substrate underlying this phenomenon. (2) Methods: The modified Flanker task, error-related event-related potentials (ERPs), namely, error-related negativity (ERN) and error positivity (Pe), and functional magnetic resonance imaging (fMRI) were used to evaluate neural activities and the functional connectivity underlying action-monitoring dysfunction in patients with different severities of OSA. (3) Results: A total of 14 control (Cont) subjects, 17 patients with moderate OSA (mOSA), and 10 patients with severe OSA (sOSA) were enrolled. A significant decline in posterror correction rate was observed in the modified Flanker task when patients with mOSA were compared with Cont subjects. Comparison between patients with mOSA and sOSA did not reveal any significant difference. In the analysis of ERPs, ERN and Pe exhibited declined amplitudes in patients with mOSA compared with Cont subjects, which were found to increase in patients with sOSA. Results of fMRI revealed a decreased correlation in multiple anterior cingulate cortex functional-connected areas in patients with mOSA compared with Cont subjects. However, these areas appeared to be reconnected in patients with sOSA. (4) Conclusions: The behavioral, neurophysiological, and functional image findings obtained in this study suggest that mOSA leads to action-monitoring dysfunction; however, compensatory neural recruitment might have contributed to the maintenance of the action-monitoring function in patients with sOSA. Full article

(This article belongs to the Section Clinical Neurology)

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11 pages, 387 KiB

Open AccessArticle

Dry Eye Symptoms and Ocular Pain in Veterans with Glaucoma

by Aubrey R Tirpack, Elizabeth Vanner, James M Parrish, Anat Galor, Hong-Uyen Hua and Sarah R Wellik

J. Clin. Med. 2019, 8(7), 1076; https://doi.org/10.3390/jcm8071076 - 22 Jul 2019

Cited by 18 | Viewed by 3770

Abstract

Dry eye and glaucoma are two frequently encountered ocular conditions, which can lead to substantial morbidity and decreased quality of life. Patients on topical glaucoma medications are known to be at greater risk for ocular surface symptoms. Veterans seen in the eye clinics [...] Read more.

Dry eye and glaucoma are two frequently encountered ocular conditions, which can lead to substantial morbidity and decreased quality of life. Patients on topical glaucoma medications are known to be at greater risk for ocular surface symptoms. Veterans seen in the eye clinics at the Miami Veterans Affairs Hospital from January to July 2016 completed surveys assessing dry eye and ocular pain symptoms, including the five item Dry Eye Questionnaire (DEQ5). A total of 62 patients with glaucoma completed the survey. Of those, 52 were on glaucoma medications at the time of the survey, with the majority requiring more than one medication to control intraocular pressure. The frequency of mild or greater dry eye symptoms (defined as DEQ5 >6) tended to increase with increasing medication burden, and patients on brimonidine were more likely to report a DEQ5 >6. Patients on three or more glaucoma medications were more likely to report symptoms of shooting pain, dryness, and itchiness. Patients using timolol were more likely to report throbbing and pain by light, while those on latanoprost reported stinging. Our data support an association between increasing number of glaucoma medications and worsening of dry eye symptoms. Patient and medication-associated symptoms can be used to tailor individual medication regimens. Full article

(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)

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16 pages, 1639 KiB

Open AccessArticle

Could Neutrophil-to-Lymphocyte Ratio (NLR) Serve as a Potential Marker for Delirium Prediction in Patients with Acute Ischemic Stroke? A Prospective Observational Study

by Katarzyna Kotfis, Marta Bott-Olejnik, Aleksandra Szylińska and Iwona Rotter

J. Clin. Med. 2019, 8(7), 1075; https://doi.org/10.3390/jcm8071075 - 22 Jul 2019

Cited by 43 | Viewed by 4505

Abstract

Delirium is an acute brain disorder that commonly occurs in patients with acute ischemic stroke (AIS). Pathomechanism of delirium is related to the neuroinflammatory process and oxidative stress. Search for readily available diagnostic marker that will aid clinicians in early identification of delirium [...] Read more.

Delirium is an acute brain disorder that commonly occurs in patients with acute ischemic stroke (AIS). Pathomechanism of delirium is related to the neuroinflammatory process and oxidative stress. Search for readily available diagnostic marker that will aid clinicians in early identification of delirium is ongoing. The aim of this study was to investigate whether neutrophil-to-lymphocyte ratio (NLR) could serve as a potential marker for delirium prediction in patients with AIS and to find an easy diagnostic tool using laboratory and clinical parameters to predict delirium. Prospective observational study (NCT03944694) included patients with AIS admitted to the neurology department of a district general hospital. All patients were screened for delirium using CAM-ICU (Confusion Assessment Method for Intensive Care Unit). Demographic and medical history data and admission lab results, including differential white blood cell analysis, were collected from all patients. We included 1001 patients in the final analysis. The mean age of the sample was 71 years, and 52% of patients were males. The incidence of early-onset delirium was 17.2%. The NLR was elevated in delirious patients (6.39 ± 8.60 vs. 4.61 ± 5.61, p < 0.001). The best cut-off value of NLR to predict delirium using the receiver operating characteristics (ROC) was determined at 4.86. Multivariable logistic regression analysis showed that the odds ratio (OR) for developing delirium with NLR > 4.86 (adjusted for age, sex, body mass index (BMI), comorbidities, and baseline neurology) was 1.875 (95% CI 1.314–2.675, p = 0.001). As a result of different combinations of markers and clinical parameters based on logistic regression, a formula—DELirium in Acute Ischemic Stroke (DELIAS score)—was obtained with the area under the ROC curve of 0.801 (p < 0.001). After regression of the cut-off points of the obtained curve, a significant correlation of the DELIAS score was observed with the occurrence of early-onset delirium (OR = 8.976, p < 0.001) and with delirium until the fifth day after AIS (OR = 7.744, p < 0.001). In conclusion, NLR can be regarded as a potential marker for prediction of early-onset delirium after AIS. On the basis of combined laboratory and clinical parameters, the DELIAS score was calculated, which gave the highest predictive value for delirium in the analyzed group of patients after ischemic stroke. However, further studies are needed to validate these findings. Full article

(This article belongs to the Section Clinical Neurology)

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18 pages, 2784 KiB

Open AccessArticle

Phenotypic Characterization of Diffuse Large B-Cell Lymphoma Cells and Prognostic Impact

by Julie Devin, Alboukadel Kassambara, Angélique Bruyer, Jérôme Moreaux and Caroline Bret

J. Clin. Med. 2019, 8(7), 1074; https://doi.org/10.3390/jcm8071074 - 22 Jul 2019

Cited by 7 | Viewed by 7042

Abstract

Multiparameter flow cytometry (MFC) is a fast and cost-effective technique to evaluate the expression of many lymphoid markers in mature B-cell neoplasms, including diffuse large B cell lymphoma (DLBCL), which is the most frequent non-Hodgkin lymphoma. In this study, we first characterized by [...] Read more.

Multiparameter flow cytometry (MFC) is a fast and cost-effective technique to evaluate the expression of many lymphoid markers in mature B-cell neoplasms, including diffuse large B cell lymphoma (DLBCL), which is the most frequent non-Hodgkin lymphoma. In this study, we first characterized by MFC the expression of 27 lymphoid markers in 16 DLBCL-derived cell lines to establish a robust algorithm for their authentication. Then, using the expression profile in DLBCL samples of the genes encoding B lymphoid markers that are routinely investigated by MFC, we built a gene expression-based risk score, based on the expression level of BCL2, BCL6, CD11c, and LAIR1, to predict the outcome of patients with DLBCL. This risk score allowed splitting patients in four risk groups, and was an independent predictor factor of overall survival when compared with the previously published prognostic factors. Lastly, to investigate the potential correlation between BCL2, BCL6, CD11c, and LAIR1 protein level and resistance to treatment, we investigated the response of the 16 DLBCL cell lines to cyclophosphamide, etoposide, doxorubicin, and gemcitabine. We found a correlation between BCL6 overexpression and resistance to etoposide. These results show the interest of MFC for the routine characterization of DLBCL cells and tumors samples for research and diagnostic/prognostic purposes. Full article

(This article belongs to the Section Hematology)

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15 pages, 5329 KiB

Open AccessArticle

Invasive Validation of Antares, a New Algorithm to Calculate Central Blood Pressure from Oscillometric Upper Arm Pulse Waves

by Marcus Dörr, Stefan Richter, Siegfried Eckert, Marc-Alexander Ohlow, Fabian Hammer, Astrid Hummel, Vivien Dornberger, Elisabeth Genzel and Johannes Baulmann

J. Clin. Med. 2019, 8(7), 1073; https://doi.org/10.3390/jcm8071073 - 22 Jul 2019

Cited by 13 | Viewed by 4558

Abstract

Background: Antares is an algorithm for pulse wave analysis (PWA) by oscillometric blood pressure (BP) monitors in order to estimate central (aortic) blood pressure (cBP). Antares aims to enable brachial cuff-based BP monitors to be type II-devices, determining absolute cBP values independently of [...] Read more.

Background: Antares is an algorithm for pulse wave analysis (PWA) by oscillometric blood pressure (BP) monitors in order to estimate central (aortic) blood pressure (cBP). Antares aims to enable brachial cuff-based BP monitors to be type II-devices, determining absolute cBP values independently of potential peripheral BP inaccuracies. The present study is an invasive validation of the Antares algorithm in the custo screen 400. Methods: We followed entirely the 2017 ARTERY protocol for validation of non-invasive cBP devices, the 2013 American National Standards Institute, Inc./Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2 and 2018 AAMI/European Society of Hypertension (ESH)/ISO validation standard protocols. In total, 191 patients undergoing cardiac catheterization were included, of which 145 patients entered analysis. Invasive cBP recordings were compared to simultaneous non-invasive cBP estimations using the Antares algorithm, integrated into an oscillometric BP monitor. Results: Mean difference between invasive and non-invasively estimated systolic cBP was 0.71 mmHg with standard deviation of 5.95 mmHg, fulfilling highest validation criteria. Conclusion: Antares is the first algorithm for estimation of cBP that entirely fulfills the 2017 ARTERY and AAMI/ESH/ISO validation protocols. The Antares algorithm turns the custo screen 400 BP monitor into a type II-device. Integration of Antares into commercially available BP monitors could make it possible to measure PWA parameters in virtually every practice in future. Full article

(This article belongs to the Section Vascular Medicine)

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10 pages, 684 KiB

Open AccessArticle

Caregiver Burden and Sleep Quality in Dependent People’s Family Caregivers

by Miguel A. Simón, Ana M. Bueno, Patricia Otero, Vanessa Blanco and Fernando L. Vázquez

J. Clin. Med. 2019, 8(7), 1072; https://doi.org/10.3390/jcm8071072 - 22 Jul 2019

Cited by 29 | Viewed by 4030

Abstract

This study examined the relationship between caregiver burden and sleep quality in dependent people’s family caregivers. A cross-sectional study was carried out with 201 dependent people’s family caregivers and 92 non-caregivers controls. Participants completed the Pittsburgh Sleep Quality Index (PSQI), the Caregiver Burden [...] Read more.

This study examined the relationship between caregiver burden and sleep quality in dependent people’s family caregivers. A cross-sectional study was carried out with 201 dependent people’s family caregivers and 92 non-caregivers controls. Participants completed the Pittsburgh Sleep Quality Index (PSQI), the Caregiver Burden Inventory (CBI), and an ad-hoc questionnaire to collect sociodemographic data. Based on CBI scores, subjects were categorized into three groups: family caregivers with high levels of perceived burden, family caregivers with low and medium levels of perceived burden and non-caregiver controls. There were significant differences among the groups in the PSQI total (F = 40.39; p < 0.001), subjective sleep quality (F = 25.55; p < 0.001), sleep latency (F = 16.99; p < 0.001), sleep disturbances (F = 14.90; p < 0.001), use of sleep medications (F = 6.94; p < 0.01) and daytime dysfunction (F = 20.12; p < 0.001). These differences were found only between the caregivers with high levels of perceived burden and the other two groups (p < 0.05). There were also significant differences between the groups in sleep duration (F = 18.34; p < 0.001) and habitual sleep efficiency (F = 24.24; p < 0.001). In these dependent measures, the differences were found in all the pairs examined (p < 0.05). These results suggest that caregiver burden is related to sleep quality, so that caregivers with greater perceived burden have a worse sleep quality. Full article

(This article belongs to the Section Epidemiology & Public Health)

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13 pages, 585 KiB

Open AccessArticle

Antibiotic Resistance and Genotypes of Helicobacter pylori Strains in Patients with Gastroduodenal Disease in Southeast Poland

by Izabela Korona-Glowniak, Halina Cichoz-Lach, Radoslaw Siwiec, Sylwia Andrzejczuk, Andrzej Glowniak, Przemyslaw Matras and Anna Malm

J. Clin. Med. 2019, 8(7), 1071; https://doi.org/10.3390/jcm8071071 - 21 Jul 2019

Cited by 22 | Viewed by 4488

Abstract

The aim of this study was to investigate genetic diversity of Helicobacter pylori virulence markers to predict clinical outcome as well as to determine an antibiotic susceptibility of H. pylori strains in Poland. Gastric biopsies from 132 patients with gastrointestinal disorders were tested [...] Read more.

The aim of this study was to investigate genetic diversity of Helicobacter pylori virulence markers to predict clinical outcome as well as to determine an antibiotic susceptibility of H. pylori strains in Poland. Gastric biopsies from 132 patients with gastrointestinal disorders were tested for presence of H. pylori with the use of rapid urease test, microbial culture, and polymerase chain reaction (PCR) detection. The genetic diversity of 62 H. pylori positive samples was evaluated by detection of cagA and PCR-typing of vacA and iceA virulence-associated genes. Most common H. pylori genotypes were cagA(+)vacAs1m2 (27.4%) and cagA(−)vacAs2m2 (24.2%). In logistic regression analysis, we recognized the subsequent significant associations: gastritis with ureC, i.e., H. pylori infection (p = 0.006), BMI index (p = 0.032); and negatively with iceA1 (p = 0.049) and peptic ulcer with cagA (p = 0.018). Thirty-five H. pylori strains were cultured and tested by E-test method showing that 49% of strains were resistant to at least one of the tested antibiotics. This is the first study that reports the high incidence and diversity of allelic combination of virulence genes in gastroduodenitis patients in Poland. Genotyping of H. pylori strains confirmed the involvement of cagA gene and vacAs1m1 genotype in development and severity of gastric disorder. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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13 pages, 3823 KiB

Open AccessArticle

ATP Synthase Subunit Epsilon Overexpression Promotes Metastasis by Modulating AMPK Signaling to Induce Epithelial-to-Mesenchymal Transition and Is a Poor Prognostic Marker in Colorectal Cancer Patients

by Yan-Jiun Huang, Yi-Hua Jan, Yu-Chan Chang, Hsing-Fang Tsai, Alexander TH Wu, Chi-Long Chen and Michael Hsiao

J. Clin. Med. 2019, 8(7), 1070; https://doi.org/10.3390/jcm8071070 - 21 Jul 2019

Cited by 17 | Viewed by 4684

Abstract

Metastasis remains the major cause of death from colon cancer. We intend to identify differentially expressed genes that are associated with the metastatic process and prognosis in colon cancer. ATP synthase epsilon subunit (ATP5E) gene was found to encode the mitochondrial [...] Read more.

Metastasis remains the major cause of death from colon cancer. We intend to identify differentially expressed genes that are associated with the metastatic process and prognosis in colon cancer. ATP synthase epsilon subunit (ATP5E) gene was found to encode the mitochondrial F₀F₁ ATP synthase subunit epsilon that was overexpressed in tumor cells compared to their normal counterparts, while other genes encoding the ATP synthase subunit were repressed in public microarray datasets. CRC cells in which ATP5E was silenced showed markedly reduced invasive and migratory abilities. ATP5E inhibition significantly reduced the incidence of distant metastasis in a mouse xenograft model. Mechanistically, increased ATP5E expression resulted in a prominent reduction in E-cadherin and an increase in Snail expression. Our data also showed that an elevated ATP5E level in metastatic colon cancer samples was significantly associated with the AMPK-AKT-hypoxia-inducible factor-1α (HIF1α) signaling axis; silencing ATP5E led to the degradation of HIF1α under hypoxia through AMPK-AKT signaling. Our findings suggest that elevated ATP5E expression could serve as a marker of distant metastasis and a poor prognosis in colon cancer, and ATP5E functions via modulating AMPK-AKT-HIF1α signaling. Full article

(This article belongs to the Special Issue Epithelial-Mesenchymal Plasticity in Cancer Metastasis: Molecular Reprogramming, Cellular Adaptation, and Clinical Implications)

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9 pages, 740 KiB

Open AccessArticle

Severity of Coronary Atherosclerosis and Risk of Diabetes Mellitus

by Iginio Colaiori, Raffaele Izzo, Emanuele Barbato, Danilo Franco, Giuseppe Di Gioia, Antonio Rapacciuolo, Jozef Bartunek, Costantino Mancusi, Maria Angela Losi, Teresa Strisciuglio, Maria Virginia Manzi, Giovanni de Simone, Bruno Trimarco and Carmine Morisco

J. Clin. Med. 2019, 8(7), 1069; https://doi.org/10.3390/jcm8071069 - 21 Jul 2019

Cited by 11 | Viewed by 3707

Abstract

Background: Cardio-vascular target organ damage predicts the onset of type 2 diabetes mellitus (DM) in hypertensive patients. Whether an increased incidence of DM is also in relation to the severity of coronary atherosclerosis is unknown. Objective: We evaluated the onset of DM in [...] Read more.

Background: Cardio-vascular target organ damage predicts the onset of type 2 diabetes mellitus (DM) in hypertensive patients. Whether an increased incidence of DM is also in relation to the severity of coronary atherosclerosis is unknown. Objective: We evaluated the onset of DM in relation to the extent and severity of coronary atherosclerosis, using the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS), in patients with stable angina or acute coronary syndromes, referred for coronary angiography (CA). Methods: Non-diabetic patients that underwent CA for the first time were included, and the SS was computed. Predictors of DM onset in low, medium, and high SSs were investigated. Results: Five hundred and seventy patients were included, and the mean SS was 6.3 ± 7.6. During a median follow-up of 79 months (interquartile range (IQR): 67–94), 74 patients (13%) developed DM. The risk of DM onset was significantly higher in the patients with a medium or high SS (hazard ratio (HR)—95% confidence interval (CI): 16 (4–61), p < 0.0001; and 30 (9–105), p < 0.0001, vs low SS, respectively), even after adjustment for obesity, history of hypertension, impaired fasting glucose, and cardiovascular therapy. Conclusions: The severity and extent of the coronary atherosclerosis, evaluated by the SS, is a strong and independent predictor of the development of DM in patients, referred to CA. Full article

(This article belongs to the Special Issue Cardiovascular Disease: From Molecular Mechanisms to Clinical Therapies)

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20 pages, 732 KiB

Open AccessArticle

Cost–Utility of Mindfulness-Based Stress Reduction for Fibromyalgia versus a Multicomponent Intervention and Usual Care: A 12-Month Randomized Controlled Trial (EUDAIMON Study)

by Adrián Pérez-Aranda, Francesco D’Amico, Albert Feliu-Soler, Lance M. McCracken, María T. Peñarrubia-María, Laura Andrés-Rodríguez, Natalia Angarita-Osorio, Martin Knapp, Javier García-Campayo and Juan V. Luciano

J. Clin. Med. 2019, 8(7), 1068; https://doi.org/10.3390/jcm8071068 - 20 Jul 2019

Cited by 21 | Viewed by 6804

Abstract

Fibromyalgia (FM) is a prevalent, chronic, disabling, pain syndrome that implies high healthcare costs. Economic evaluations of potentially effective treatments for FM are needed. The aim of this study was to analyze the cost–utility of Mindfulness-Based Stress Reduction (MBSR) as an add-on to [...] Read more.

Fibromyalgia (FM) is a prevalent, chronic, disabling, pain syndrome that implies high healthcare costs. Economic evaluations of potentially effective treatments for FM are needed. The aim of this study was to analyze the cost–utility of Mindfulness-Based Stress Reduction (MBSR) as an add-on to treatment-as-usual (TAU) for patients with FM compared to an adjuvant multicomponent intervention (“FibroQoL”) and to TAU. We performed an economic evaluation alongside a 12 month, randomized, controlled trial; data from 204 (68 per study arm) of the 225 patients (90.1%) were included in the cost–utility analyses, which were conducted both under the government and the public healthcare system perspectives. The main outcome measures were the EuroQol (EQ-5D-5L) for assessing Quality-Adjusted Life Years (QALYs) and improvements in health-related quality of life, and the Client Service Receipt Inventory (CSRI) for estimating direct and indirect costs. Incremental cost-effectiveness ratios (ICERs) were also calculated. Two sensitivity analyses (intention-to-treat, ITT, and per protocol, PPA) were conducted. The results indicated that MBSR achieved a significant reduction in costs compared to the other study arms (p < 0.05 in the completers sample), especially in terms of indirect costs and primary healthcare services. It also produced a significant incremental effect compared to TAU in the ITT sample (ΔQALYs = 0.053, p < 0.05, where QALYs represents quality-adjusted life years). Overall, our findings support the efficiency of MBSR over FibroQoL and TAU specifically within a Spanish public healthcare context. Full article

(This article belongs to the Special Issue Rehabilitation for Persistent Pain Across the Lifespan)

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13 pages, 568 KiB

Open AccessArticle

The Role of a “Treat-to-Target” Approach in the Long-Term Renal Outcomes of Patients with Gout

by Woo-Joong Kim, Jung Soo Song and Sang Tae Choi

J. Clin. Med. 2019, 8(7), 1067; https://doi.org/10.3390/jcm8071067 - 20 Jul 2019

Cited by 2 | Viewed by 3087

Abstract

Background: Although gout is accompanied by the substantial burden of kidney disease, there are limited data to assess renal function as a therapeutic target. This study evaluated the importance of implementing a “treat-to-target” approach in relation to renal outcomes. Methods: Patients [...] Read more.

Background: Although gout is accompanied by the substantial burden of kidney disease, there are limited data to assess renal function as a therapeutic target. This study evaluated the importance of implementing a “treat-to-target” approach in relation to renal outcomes. Methods: Patients with gout who underwent continuous urate-lowering therapy (ULT) for at least 12 months were included. The effect of ULT on renal function was investigated by means of a sequential comparison of the estimated glomerular filtration rate (eGFR). Results: Improvement in renal function was only demonstrated in subjects in whom the serum urate target of <6 mg/dL was achieved (76.40 ± 18.81 mL/min/1.73 m² vs. 80.30 ± 20.41 mL/min/1.73 m², p < 0.001). A significant difference in the mean change in eGFR with respect to serum urate target achievement was shown in individuals with chronic kidney disease stage 3 (−0.35 ± 3.87 mL/min/1.73 m² vs. 5.33 ± 11.64 mL/min/1.73 m², p = 0.019). Multivariable analysis predicted that patients ≥65 years old had a decreased likelihood of improvement (OR 0.31, 95% CI 0.13–0.75, p = 0.009). Conclusions: The “treat-to-target” approach in the long-term management of gout is associated with better renal outcomes, with a greater impact on those with impaired renal function. Full article

(This article belongs to the Section Immunology)

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9 pages, 641 KiB

Open AccessArticle

Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in “Real Life”

by Domenico Russo, Rocco Tripepi, Fabio Malberti, Biagio Di Iorio, Bernadette Scognamiglio, Luca Di Lullo, Immacolata Gaia Paduano, Giovanni Luigi Tripepi and Vincenzo Antonio Panuccio

J. Clin. Med. 2019, 8(7), 1066; https://doi.org/10.3390/jcm8071066 - 20 Jul 2019

Cited by 17 | Viewed by 5246 | Correction

Abstract

Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in “real world” setting that is different from randomized [...] Read more.

Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in “real world” setting that is different from randomized controlled trials (RCTs) to (1) evaluate the effectiveness of etelcalcetide in SHPT, (2) to assess calcium, phosphorus, alkaline phosphatase changes, (3) to register gastrointestinal side effects. Data were collected from twenty-three dialysis units with n = 1190 patients on the charge. From this cohort, n = 168 (14%) patients were on treatment with etelcalcetide, and they were evaluated for statistics. A median weekly dose of etelcalcetide was 15 mg (7.5–45 mg). Patients were either naïve (33%) or switched from cinacalcet to obtain better control of SHPT with reduced side effects or pills burden. Serum parathyroid hormone (PTH) declined over time from a median value of 636 pg/mL to 357 pg/mL. The median time for responders (intact PTH (iPTH) range: two to nine times the upper normal limit) was 53 days; the percentage of responders increased (from baseline 27% to 63%) being similar in switched-patients and naïve-patients. Few patients had symptomatic hypocalcemia requiring etelcalcetide withdrawal (four cases (3%) at 30-day control, two cases (2%) at 60-day, one case (1%) at 90-day control). Side effects with etelcalcetide were lower (3–4%) than that registered during cinacalcet treatment (53%). Etelcalcetide is a new therapeutic option for SHPT with low side effects and pills burden. Etelcalcetide may improve adherence to therapy, avoiding unremitting SHP. It remains to be assessed whether etelcalcetide may reduce parathyroidectomy, vascular calcification, or mortality. Being etelcalcetide very potent in suppressing PTH levels, even in severe SHPT, future studies should evaluate the potential risk of more adynamic bone disease during long-term therapy. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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19 pages, 537 KiB

Open AccessReview

Nutritional Risk Screening and Assessment

by Emilie Reber, Filomena Gomes, Maria F. Vasiloglou, Philipp Schuetz and Zeno Stanga

J. Clin. Med. 2019, 8(7), 1065; https://doi.org/10.3390/jcm8071065 - 20 Jul 2019

Cited by 249 | Viewed by 35572

Abstract

Malnutrition is an independent risk factor that negatively influences patients’ clinical outcomes, quality of life, body function, and autonomy. Early identification of patients at risk of malnutrition or who are malnourished is crucial in order to start a timely and adequate nutritional support. [...] Read more.

Malnutrition is an independent risk factor that negatively influences patients’ clinical outcomes, quality of life, body function, and autonomy. Early identification of patients at risk of malnutrition or who are malnourished is crucial in order to start a timely and adequate nutritional support. Nutritional risk screening, a simple and rapid first-line tool to detect patients at risk of malnutrition, should be performed systematically in patients at hospital admission. Patients with nutritional risk should subsequently undergo a more detailed nutritional assessment to identify and quantify specific nutritional problems. Such an assessment includes subjective and objective parameters such as medical history, current and past dietary intake (including energy and protein balance), physical examination and anthropometric measurements, functional and mental assessment, quality of life, medications, and laboratory values. Nutritional care plans should be developed in a multidisciplinary approach, and implemented to maintain and improve patients’ nutritional condition. Standardized nutritional management including systematic risk screening and assessment may also contribute to reduced healthcare costs. Adequate and timely implementation of nutritional support has been linked with favorable outcomes such as a decrease in length of hospital stay, reduced mortality, and reductions in the rate of severe complications, as well as improvements in quality of life and functional status. The aim of this review article is to provide a comprehensive overview of nutritional screening and assessment methods that can contribute to an effective and well-structured nutritional management (process cascade) of hospitalized patients. Full article

(This article belongs to the Special Issue Nutritional Management and Outcomes in Malnourished Medical Inpatients)

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10 pages, 404 KiB

Open AccessArticle

Clinical Trajectories and Causes of Death in Septic Patients with a Low APACHE II Score

by Chun-Ta Huang, Sheng-Yuan Ruan, Yi-Ju Tsai, Shih-Chi Ku and Chong-Jen Yu

J. Clin. Med. 2019, 8(7), 1064; https://doi.org/10.3390/jcm8071064 - 20 Jul 2019

Cited by 15 | Viewed by 3679

Abstract

Clinical course and mortality in septic patients with low disease severity remain poorly understood and is worth further investigation. We enrolled septic patients admitted to intensive care units (ICUs) between 2010 and 2014 with Acute Physiology and Chronic Health Evaluation II (APACHE II) [...] Read more.

Clinical course and mortality in septic patients with low disease severity remain poorly understood and is worth further investigation. We enrolled septic patients admitted to intensive care units (ICUs) between 2010 and 2014 with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≤15. We sought to determine their clinical trajectories and causes of death, and to analyze risk factors associated with in-hospital mortality. A total of 352 patients were included, of whom 89 (25%) did not survive to hospital discharge, at a rate higher than predicted (<21%) by the APACHE II score. Approximately one third (31/89) of non-survivors succumbed to index sepsis; however, more patients (34/89) died of subsequent sepsis. New-onset ICU sepsis developed in 99 (28%) patients and was an independent risk factor for mortality. In addition, septic patients with comorbid malignancy or index infection acquired in the hospital settings were more likely to have in-hospital mortality than those without. In conclusion, septic patients with low APACHE II scores were at a higher mortality risk than expected, and subsequent sepsis rather than index sepsis was the primary cause of death. This study provides insight into unexpected clinical trajectories and outcomes of septic patients with low disease severity at ICU admission and highlights the need for more research and clinical attention in this patient population. Full article

(This article belongs to the Section Vascular Medicine)

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24 pages, 482 KiB

Open AccessArticle

Best Evidence Rehabilitation for Chronic Pain Part 3: Low Back Pain

by Anneleen Malfliet, Kelly Ickmans, Eva Huysmans, Iris Coppieters, Ward Willaert, Wouter Van Bogaert, Emma Rheel, Thomas Bilterys, Paul Van Wilgen and Jo Nijs

J. Clin. Med. 2019, 8(7), 1063; https://doi.org/10.3390/jcm8071063 - 19 Jul 2019

Cited by 76 | Viewed by 25864

Abstract

Chronic Low Back Pain (CLBP) is a major and highly prevalent health problem. Given the high number of papers available, clinicians might be overwhelmed by the evidence on CLBP management. Taking into account the scale and costs of CLBP, it is imperative that [...] Read more.

Chronic Low Back Pain (CLBP) is a major and highly prevalent health problem. Given the high number of papers available, clinicians might be overwhelmed by the evidence on CLBP management. Taking into account the scale and costs of CLBP, it is imperative that healthcare professionals have access to up-to-date, evidence-based information to assist them in treatment decision-making. Therefore, this paper provides a state-of-the-art overview of the best evidence non-invasive rehabilitation for CLBP. Taking together up-to-date evidence from systematic reviews, meta-analysis and available treatment guidelines, most physically inactive therapies should not be considered for CLBP management, except for pain neuroscience education and spinal manipulative therapy if combined with exercise therapy, with or without psychological therapy. Regarding active therapy, back schools, sensory discrimination training, proprioceptive exercises, and sling exercises should not be considered due to low-quality and/or conflicting evidence. Exercise interventions on the other hand are recommended, but while all exercise modalities appear effective compared to minimal/passive/conservative/no intervention, there is no evidence that some specific types of exercises are superior to others. Therefore, we recommend choosing exercises in line with the patient’s preferences and abilities. When exercise interventions are combined with a psychological component, effects are better and maintain longer over time. Full article

(This article belongs to the Special Issue Rehabilitation for Persistent Pain Across the Lifespan)

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13 pages, 1042 KiB

Open AccessReview

How to Diagnose and Treat Local Allergic Rhinitis: A Challenge for Clinicians

by Ibon Eguiluz-Gracia, Natalia Pérez-Sánchez, Gádor Bogas, Paloma Campo and Carmen Rondón

J. Clin. Med. 2019, 8(7), 1062; https://doi.org/10.3390/jcm8071062 - 19 Jul 2019

Cited by 53 | Viewed by 11303

Abstract

Chronic rhinitis is a very common disease that can be divided in various phenotypes. Historically, the condition has been classified into the allergic rhinitis (AR) and non-allergic non-infectious rhinitis (NAR) forms, based on the results of the classical biomarkers of atopy: skin prick [...] Read more.

Chronic rhinitis is a very common disease that can be divided in various phenotypes. Historically, the condition has been classified into the allergic rhinitis (AR) and non-allergic non-infectious rhinitis (NAR) forms, based on the results of the classical biomarkers of atopy: skin prick test and serum allergen-specific IgE However, this classification does not reflect the complexity of the rhinitis syndrome, as illustrated by the existence of non-atopic rhinitis patients who display a nasal reactivity to environmental allergens. This new phenotype has been termed local allergic rhinitis (LAR) and can be only recognized if an additional test such as the nasal allergen challenge (NAC) is integrated in the diagnostic algorithm for chronic rhinitis. Recent data shows that the NAC is a very safe and reliable technique ready for the clinical practice. LAR is a differentiated rhinitis phenotype which often commences during childhood and quickly progresses towards a clinical worsening and the association of comorbidities in other mucosal organs. Recent evidence supports the existence of a bronchial counterpart of LAR (local allergic asthma), which highlights the pathophysiological links between the upper and lower airways and reinforces the united airways concept. Importantly, several controlled studies have demonstrated the ability of allergen immunotherapy to control LAR symptoms while the therapy is being administered. This review emphasizes the need to implement the NAC in the clinical practice in order to facilitate the recognition of LAR patients, allowing for an early prescription of specific therapies with disease-modifying potential. Full article

(This article belongs to the Special Issue Current Controversies and Challenges in Allergic Rhinitis Management)

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9 pages, 244 KiB

Open AccessReview

Vasopressin in the Amelioration of Social Functioning in Autism Spectrum Disorder

by Mohamed A. Hendaus, Fatima A. Jomha and Ahmed H. Alhammadi

J. Clin. Med. 2019, 8(7), 1061; https://doi.org/10.3390/jcm8071061 - 19 Jul 2019

Cited by 13 | Viewed by 4962

Abstract

Autism spectrum disorder (ASD) is a developmental disability described by diagnostic criteria that comprise deficits in social communication and the existence of repetitive, restricted patterns of behavior, interests, or activities that can last throughout life. Many preclinical studies show the importance of arginine [...] Read more.

Autism spectrum disorder (ASD) is a developmental disability described by diagnostic criteria that comprise deficits in social communication and the existence of repetitive, restricted patterns of behavior, interests, or activities that can last throughout life. Many preclinical studies show the importance of arginine vasopressin (AVP) physiology in social functioning in several mammalian species. Currently, there is a trend to investigate more specific pharmacological agents to improve social functioning in patients with ASD. Neurobiological systems that are crucial for social functioning are the most encouraging conceivable signaling pathways for ASD therapeutic discovery. The AVP signaling pathway is one of the most promising. The purpose of this commentary is to detail the evidence on the use of AVP as an agent that can improve social functioning. The pharmacologic aspects of the drug as well as its potential to ameliorate social functioning characteristics in human and animal studies are described in this manuscript. AVP, especially in its inhaled form, seems to be safe and beneficial in improving social functioning including in children with autism. Larger randomized studies are required to implement a long awaited safe and feasible treatment in people with a deficiency in social functioning. Full article

(This article belongs to the Special Issue The Hypothalamic Neuropeptides' Role in Metabolic Diseases and Immunoregulation)

19 pages, 6535 KiB

Open AccessReview

Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers—Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT

by Rudolf A. Werner, James T. Thackeray, Martin G. Pomper, Frank M. Bengel, Michael A. Gorin, Thorsten Derlin and Steven P. Rowe

J. Clin. Med. 2019, 8(7), 1060; https://doi.org/10.3390/jcm8071060 - 19 Jul 2019

Cited by 19 | Viewed by 8155

Abstract

The theranostic concept represents a paradigmatic example of personalized treatment. It is based on the use of radiolabeled compounds which can be applied for both diagnostic molecular imaging and subsequent treatment, using different radionuclides for labelling. Clinically relevant examples include somatostatin receptor (SSTR)-targeted [...] Read more.

The theranostic concept represents a paradigmatic example of personalized treatment. It is based on the use of radiolabeled compounds which can be applied for both diagnostic molecular imaging and subsequent treatment, using different radionuclides for labelling. Clinically relevant examples include somatostatin receptor (SSTR)-targeted imaging and therapy for the treatment of neuroendocrine tumors (NET), as well as prostate-specific membrane antigen (PSMA)-targeted imaging and therapy for the treatment of prostate cancer (PC). As such, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy using positron emission tomography (PET). While interpreting PSMA- or SSTR-targeted PET/computed tomography scans, the reader has to navigate certain pitfalls, including (I.) varying normal biodistribution between different PSMA- and SSTR-targeting PET radiotracers, (II.) varying radiotracer uptake in numerous kinds of both benign and malignant lesions, and (III.) resulting false-positive and false-negative findings. Thus, two novel reporting and data system (RADS) classifications for PSMA- and SSTR-targeted PET imaging (PSMA- and SSTR-RADS) have been recently introduced under the umbrella term molecular imaging reporting and data systems (MI-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied. Learning objectives of the present case-based review are as follows: (I.) the theranostic concept for the treatment of NET and PC will be briefly introduced, (II.) the most common pitfalls on PSMA- and SSTR-targeted PET/CT will be identified, (III.) the novel framework system for theranostic radiotracers (MI-RADS) will be explained, applied to complex clinical cases and recent studies in the field will be highlighted. Finally, current treatment strategies based on MI-RADS will be proposed, which will demonstrate how such a generalizable framework system truly paves the way for clinically meaningful molecular imaging-guided treatment of either PC or NET. Thus, beyond an introduction of MI-RADS, the present review aims to provide an update of recently published studies which have further validated the concept of structured reporting systems in the field of theranostics. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine Imaging and Therapy)

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12 pages, 1968 KiB

Open AccessReview

Intravesical Chemotherapy after Radical Nephroureterectomy for Primary Upper Tract Urothelial Carcinoma: A Systematic Review and Network Meta-Analysis

by Sang Hyun Yoo, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Min Soo Choo and Ja Hyeon Ku

J. Clin. Med. 2019, 8(7), 1059; https://doi.org/10.3390/jcm8071059 - 19 Jul 2019

Cited by 13 | Viewed by 3961

Abstract

The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention of bladder recurrence, after nephroureterectomy, for upper tract urothelial carcinoma by systematic review and network meta-analysis. A [...] Read more.

The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention of bladder recurrence, after nephroureterectomy, for upper tract urothelial carcinoma by systematic review and network meta-analysis. A comprehensive literature search was conducted to search for studies published before 22 December 2016 using PubMed, Embase, and Scopus. All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The primary outcome was intravesical recurrence-free survival rate. In addition, we conducted indirect comparisons among regimens using network meta-analysis, as well as three randomized controlled trials (RCTs) on multicenter setting, and one large retrospective study with a total of 532 patients were analyzed. The pooled hazard ratio (HR) of bladder recurrence was 0.54 (95% CI: 0.38–0.76) in intravesical instillation patients. On network meta-analysis, pirarubicin was ranked the most effective regimen, while maintenance therapy of mitomycin C (MMC) with Ara-C and induction therapy of MMC were ranked as the second and third most effective regimens, respectively. Our study demonstrates that intravesical chemotherapy can prevent bladder recurrence in patients with upper tract urothelial carcinoma after nephroureterectomy. It also suggests that a single instillation of pirarubicin is the most efficacious intravesical regimen. Full article

(This article belongs to the Special Issue Novel Researches on Upper Tract Urothelial Carcinoma)

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14 pages, 403 KiB

Open AccessReview

The Potential of Cannabidiol as a Treatment for Psychosis and Addiction: Who Benefits Most? A Systematic Review

by Albert Batalla, Hella Janssen, Shiral S. Gangadin and Matthijs G. Bossong

J. Clin. Med. 2019, 8(7), 1058; https://doi.org/10.3390/jcm8071058 - 19 Jul 2019

Cited by 63 | Viewed by 17468

Abstract

The endogenous cannabinoid (eCB) system plays an important role in the pathophysiology of both psychotic disorders and substance use disorders (SUDs). The non-psychoactive cannabinoid compound, cannabidiol (CBD) is a highly promising tool in the treatment of both disorders. Here we review human clinical [...] Read more.

The endogenous cannabinoid (eCB) system plays an important role in the pathophysiology of both psychotic disorders and substance use disorders (SUDs). The non-psychoactive cannabinoid compound, cannabidiol (CBD) is a highly promising tool in the treatment of both disorders. Here we review human clinical studies that investigated the efficacy of CBD treatment for schizophrenia, substance use disorders, and their comorbidity. In particular, we examined possible profiles of patients who may benefit the most from CBD treatment. CBD, either as monotherapy or added to regular antipsychotic medication, improved symptoms in patients with schizophrenia, with particularly promising effects in the early stages of illness. A potential biomarker is the level of anandamide in blood. CBD and THC mixtures showed positive effects in reducing short-term withdrawal and craving in cannabis use disorders. Studies on schizophrenia and comorbid substance use are lacking. Future studies should focus on the effects of CBD on psychotic disorders in different stages of illness, together with the effects on comorbid substance use. These studies should use standardized measures to assess cannabis use. In addition, future efforts should be taken to study the relationship between the eCB system, GABA/glutamate, and the immune system to reveal the underlying neurobiology of the effects of CBD. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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13 pages, 420 KiB

Open AccessArticle

Serum Vitamin E Levels of Adults with Nonalcoholic Fatty Liver Disease: An Inverse Relationship with All-Cause Mortality in Non-Diabetic but Not in Pre-Diabetic or Diabetic Subjects

by Peiling Tsou and Chang-Jiun Wu

J. Clin. Med. 2019, 8(7), 1057; https://doi.org/10.3390/jcm8071057 - 19 Jul 2019

Cited by 10 | Viewed by 3633

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a growing health threat worldwide. Vitamin E supplementation is recommended for nonalcoholic steatohepatitis (NASH) patients, but only for non-diabetic subjects. We aimed to investigate whether serum vitamin E levels differently impact long-term prognosis in diabetic versus non-diabetic [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is a growing health threat worldwide. Vitamin E supplementation is recommended for nonalcoholic steatohepatitis (NASH) patients, but only for non-diabetic subjects. We aimed to investigate whether serum vitamin E levels differently impact long-term prognosis in diabetic versus non-diabetic NAFLD individuals. A total of 2404 ultrasonographically defined NAFLD individuals from National Health and Nutrition Examination Survey (NHANES) III were stratified by their glycemic statuses into diabetic (N = 662), pre-diabetic (N = 836) and non-diabetic (N = 906), and the relationship between serum vitamin E levels and all-cause mortality was analyzed. The serum vitamin E concentrations were 31.1 ± 14.1, 26.7 ± 9.6, and 24.7 ± 9.8 µmol/L and vitamin E: total cholesterol ratios were 5.16 ± 1.70, 4.81 ± 1.46, and 4.80 ± 1.34 µmol/mmol in in diabetic, pre-diabetic, and non-diabetic groups, respectively. Of 2404 NAFLD subjects, 2403 have mortality information and 152 non-diabetic, 244 pre-diabetic, and 342 diabetic participants died over a median follow-up period of 18.8 years. Both serum vitamin E levels and vitamin E: total cholesterol ratios were negatively associated with all-cause mortality after adjusting for possible confounders in non-diabetic subjects (HR = 0.483, and 0.451, respectively, p < 0.005), but not in either diabetic or pre-diabetic subjects. In NAFLD individuals, both serum vitamin E and lipid-corrected vitamin E were (1) higher in the diabetic group; and (2) negatively associated with all-cause mortality only in the non-diabetic group. Further investigations are warranted to elucidate the underlying mechanism of this inverse association of serum vitamin E concentration with all-cause mortality in non-diabetic but not pre-diabetic or diabetic subjects. Full article

(This article belongs to the Special Issue Non-Alcoholic Steatohepatitis (NASH))

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Open AccessArticle

Platelet Function Disturbance During Veno-Venous ECMO in ARDS Patients Assessed by Multiple Electrode Aggregometry—A Prospective, Observational Cohort Study

by Saskia Wand, Jan Felix Huber-Petersen, Joern Schaeper, Claudia Binder and Onnen Moerer

J. Clin. Med. 2019, 8(7), 1056; https://doi.org/10.3390/jcm8071056 - 19 Jul 2019

Cited by 12 | Viewed by 3047

Abstract

Extracorporeal (veno-venous) membrane oxygenation (vvECMO) has been shown to have negative effects on platelet number and function. This study aimed to gain more information about the impact of vvECMO on platelet function assessed by multiple electrode aggregometry (MEA). Twenty patients with the indication [...] Read more.

Extracorporeal (veno-venous) membrane oxygenation (vvECMO) has been shown to have negative effects on platelet number and function. This study aimed to gain more information about the impact of vvECMO on platelet function assessed by multiple electrode aggregometry (MEA). Twenty patients with the indication for vvECMO were included. Platelet function was analyzed using MEA (Multiplate^®) before (T-1), 6 h (T0), one (T1), two (T2), three (T3), and seven (T4) days after the beginning of vvECMO. Median aggregational measurements were already below the normal reference range before vvECMO initiation. Platelet aggregation was significantly reduced 6 h after vvECMO initiation compared to T-1 and spontaneously recovered with a significant increase at T2. Platelet count dropped significantly between T-1 and T0 and continuously decreased between T0 and T4. At T4, ADP-induced platelet aggregation showed an inverse correlation with the paO2 in the oxygenator. Platelet function should be assessed by MEA before the initiation of extracorporeal circulation. Although ECMO therapy led to a further decrease in platelet aggregation after 6 h, all measurements had recovered to baseline on day two. This implies that MEA as a whole blood method might not adequately reflect the changes in platelet function in the later stages of extracorporeal circulation. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS): Pathophysiological Insights and Lung Imaging)

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J. Clin. Med., Volume 8, Issue 7 (July 2019) – 175 articles

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