Journal of Clinical Medicine

14 pages, 2177 KiB

Open AccessArticle

A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network

by J. Curtis Nickel, Alisa J. Stephens-Shields, J. Richard Landis, Chris Mullins, Adrie van Bokhoven, M. Scott Lucia, Jeffrey P. Henderson, Bhaswati Sen, Jaroslaw E. Krol, Garth D. Ehrlich and The MAPP Research Network

J. Clin. Med. 2019, 8(3), 415; https://doi.org/10.3390/jcm8030415 - 26 Mar 2019

Cited by 41 | Viewed by 4993

Abstract

We surveyed urine microbiota of females diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) and matched control participants enrolled in the National Institutes of Health (NIH) Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network using the culture-independent methodology. Midstream urine [...] Read more.

We surveyed urine microbiota of females diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) and matched control participants enrolled in the National Institutes of Health (NIH) Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network using the culture-independent methodology. Midstream urine specimens were analyzed with the Plex-ID molecular diagnostic platform that utilizes polymerase chain reaction–electrospray ionization–time-of-flight–mass spectrometry (PCR-ESI-TOF MS) to provide a comprehensive identification of bacterial and select fungal species. IC/BPS and control participants were evaluated for differences (presence, diversity, and abundance) in species and genus. Urine specimens obtained from 181 female IC/BPS and 182 female control participants detected a total of 92 species (41 genera). Mean (SD) species count was 2.49 (1.48) and 2.30 (1.28) among IC/BPS and control participants, respectively. Overall species composition did not significantly differ between IC/BPS and control participants at any level (p = 0.726 species level, p = 0.222 genus level). IC/BPS participants urine trended to an overabundance of Lactobacillus gasseri (p = 0.09) detected but had a lower prevalence of Corynebacterium compared with control participants (p = 0.002). The relative abundance data analysis mirrored the prevalence data differences with no significant differences in most species or genus abundance other than Lactobacillus gasseri and Corynebacterium (p = 0.08 and p = 0.001, respectively). No cause and/or effect conclusion can be drawn from this observation, but it suggests that a more comprehensive evaluation (vaginal, bowel, catheterized bladder and/or tissue-based specimens) of the lower urinary tract microbiota in IC/BPS patients is warranted. Full article

(This article belongs to the Section Infectious Diseases)

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20 pages, 287 KiB

Open AccessReview

Are There New Biomarkers in Tissue and Liquid Biopsies for the Early Detection of Non-Small Cell Lung Cancer?

by Fiorella Calabrese, Francesca Lunardi, Federica Pezzuto, Francesco Fortarezza, Stefania Edith Vuljan, Charles Marquette and Paul Hofman

J. Clin. Med. 2019, 8(3), 414; https://doi.org/10.3390/jcm8030414 - 26 Mar 2019

Cited by 35 | Viewed by 5192

Abstract

Lung cancer is one of the most lethal malignancies worldwide, mainly due to its late diagnoses. The detection of molecular markers on samples provided from routine bronchoscopy including several liquid-based cytology tests (e.g., bronchoaspirate, bronchoalveolar lavage) and/or on easily obtained specimens such as [...] Read more.

Lung cancer is one of the most lethal malignancies worldwide, mainly due to its late diagnoses. The detection of molecular markers on samples provided from routine bronchoscopy including several liquid-based cytology tests (e.g., bronchoaspirate, bronchoalveolar lavage) and/or on easily obtained specimens such as sputum could represent a new approach to improve the sensitivity in lung cancer diagnoses. Recently growing interest has been reported for “noninvasive” liquid biopsy as a valuable source for molecular profiling. Unfortunately, a biomarker and/or composition of biomarkers capable of detecting early-stage lung cancer has yet to be discovered even if in the last few years there has been, through the use of revolutionary new technologies, an explosion of lung cancer biomarkers. Assay sensitivity and specificity need to be improved particularly when new approaches and/or tools are used. We have focused on the most important markers detected in tissue, and on several cytological specimens and liquid biopsies overall. Full article

(This article belongs to the Special Issue Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis)

15 pages, 765 KiB

Open AccessArticle

Mental Health and Proximal Stressors in Transgender Men and Women

by Noelia Fernández-Rouco, Rodrigo J. Carcedo, Félix López and M. Begoña Orgaz

J. Clin. Med. 2019, 8(3), 413; https://doi.org/10.3390/jcm8030413 - 25 Mar 2019

Cited by 16 | Viewed by 5172

Abstract

This paper explores the subjective perception of some personal and interpersonal aspects of the lives of transgender people and the relationship they have with their mental health. One hundred and twenty transgender people (60 men and 60 women) participated in semi-structured interviews. Following [...] Read more.

This paper explores the subjective perception of some personal and interpersonal aspects of the lives of transgender people and the relationship they have with their mental health. One hundred and twenty transgender people (60 men and 60 women) participated in semi-structured interviews. Following quantitative methodology, analysis highlighted that social loneliness is the main predictor of lower levels of mental health (anxiety and depression) for both genders and recognized romantic loneliness as the strongest factor among transgender men. In both cases, higher levels of loneliness were associated with lower levels of mental health. The results have guided us to improve institutional and social responses and have provided an opportunity to promote the mental health of transgender people. Full article

(This article belongs to the Special Issue Novel Research in Sexuality and Mental Health)

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18 pages, 3459 KiB

Open AccessArticle

Re-Evaluating the Protective Effect of Hemodialysis Catheter Locking Solutions in Hemodialysis Patients

by Chang-Hua Chen, Yu-Min Chen, Yu Yang, Yu-Jun Chang, Li-Jhen Lin and Hua-Cheng Yen

J. Clin. Med. 2019, 8(3), 412; https://doi.org/10.3390/jcm8030412 - 25 Mar 2019

Cited by 5 | Viewed by 4516

Abstract

Catheter-related bloodstream infections (CRBSIs) and exit-site infections (ESIs) are common complications associated with the use of central venous catheters for hemodialysis. The aim of this study was to analyze the impact of routine locking solutions on the incidence of CRBSI and ESI, in [...] Read more.

Catheter-related bloodstream infections (CRBSIs) and exit-site infections (ESIs) are common complications associated with the use of central venous catheters for hemodialysis. The aim of this study was to analyze the impact of routine locking solutions on the incidence of CRBSI and ESI, in preserving catheter function, and on the rate of all-cause mortality in patients undergoing hemodialysis. We selected publications (from inception until July 2018) with studies comparing locking solutions for hemodialysis catheters used in patients undergoing hemodialysis. A total of 21 eligible studies were included, with a total of 4832 patients and 318,769 days of catheter use. The incidence of CRBSI and ESI was significantly lower in the treated group (citrate-based regimen) than in the controls (heparin-based regimen). No significant difference in preserving catheter function and all-cause mortality was found between the two groups. Our findings demonstrated that routine locking solutions for hemodialysis catheters effectively reduce the incidence of CRBSIs and ESIs, but our findings failed to show a benefit for preserving catheter function and mortality rates. Therefore, further studies are urgently needed to conclusively evaluate the impact of routine locking solutions on preserving catheter function and improving the rates of all-cause mortality. Full article

(This article belongs to the Special Issue Clinical Medicine for Healthcare and Sustainability)

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19 pages, 15054 KiB

Open AccessArticle

Indocyanine Green—Mediated Photodynamic Therapy Reduces Methicillin-Resistant Staphylococcus aureus Drug Resistance

by Tak-Wah Wong, Shu-Zhen Liao, Wen-Chien Ko, Chi-Jung Wu, Shin Bei Wu, Yin-Ching Chuang and I-Hsiu Huang

J. Clin. Med. 2019, 8(3), 411; https://doi.org/10.3390/jcm8030411 - 25 Mar 2019

Cited by 38 | Viewed by 6064

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) skin-wound infections are associated with considerable morbidity and mortality. Indocyanine green (ICG), a safe and inexpensive dye used in clinical imaging, can be activated by near-infrared in photodynamic therapy (PDT) and photothermal therapy (PTT) to effectively kill MRSA. However, [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) skin-wound infections are associated with considerable morbidity and mortality. Indocyanine green (ICG), a safe and inexpensive dye used in clinical imaging, can be activated by near-infrared in photodynamic therapy (PDT) and photothermal therapy (PTT) to effectively kill MRSA. However, how this treatment affects MRSA drug sensitivity remains unknown. The drug-sensitivity phenotypes, bacterial growth rate, and cell-wall thickness of three MRSA strains were analyzed after ICG-PDT. Drug-resistant gene expressions were determined by polymerase chain reaction (PCR) and quantitative reverse transcription (qRT)-PCR. Related protein expressions were examined with immunoblotting. Drug sensitivity was further evaluated in animal models. MRSA that survived the treatment grew faster, and the cell wall became thinner compared to parental cells. These cells became more sensitive to oxacillin, which was partly related to mecA complex gene deletion. Skin necrosis caused by ICG-PDT-treated MRSA infection was smaller and healed faster than that infected with parental cells. With oxacillin therapy, no bacteria could be isolated from mouse lung tissue infected with ICG-PDT-treated MRSA. ICG-PDT drives MRSA toward an oxacillin-sensitive phenotype. It has the potential to develop into an alternative or adjuvant clinical treatment against MRSA wound infections. Full article

(This article belongs to the Special Issue Advances in Antibacterial Drug Discovery and Therapy)

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12 pages, 210 KiB

Open AccessEditorial

Evolution of Guidelines for Testosterone Replacement Therapy

by Hyun Jun Park, Sun Tae Ahn and Du Geon Moon

J. Clin. Med. 2019, 8(3), 410; https://doi.org/10.3390/jcm8030410 - 25 Mar 2019

Cited by 29 | Viewed by 9630

Abstract

Testosterone is an essential hormone required for the developmental growth and maintenance of the male phenotype during the whole life. With the increasing male life expectancy worldwide and development of adequate testosterone preparations, the prescription of testosterone has increased tremendously. Testosterone replacement should [...] Read more.

Testosterone is an essential hormone required for the developmental growth and maintenance of the male phenotype during the whole life. With the increasing male life expectancy worldwide and development of adequate testosterone preparations, the prescription of testosterone has increased tremendously. Testosterone replacement should be based on low serum testosterone and related clinical symptoms. In the last two decades, with the accumulation of data, official recommendations have evolved in terms of definition, diagnosis, treatment, and follow-up. In practice, it is better for physicians to follow the Institutional Official Recommendations or Clinical Practice Guideline for an adequate diagnosis and treatment of testosterone deficiency. Currently, four official recommendations are available for diagnosis and treatment of patients with testosterone deficiency. The inconsistencies in the guidelines merely create confusion among the physicians instead of providing clear information. Furthermore, there is no definite method to assess serum testosterone and clinical symptoms. In the era of active testosterone replacement therapy (TRT), physicians’ practice patterns should be consistent with the clinical practice guidelines to avoid the misuse of testosterone. In this review, the author introduces the evolution of clinical guidelines to provide a comprehensive understanding of the differences and controversies with respect to TRT. Full article

(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)

14 pages, 1236 KiB

Open AccessArticle

High-Intensity Interval Training is Associated with Improved Long-Term Survival in Heart Failure Patients

by Chih-Chin Hsu, Tieh-Cheng Fu, Shin-Sheng Yuan, Chao-Hung Wang, Min-Hui Liu, Yu-Chiau Shyu, Wen-Jin Cherng and Jong-Shyan Wang

J. Clin. Med. 2019, 8(3), 409; https://doi.org/10.3390/jcm8030409 - 25 Mar 2019

Cited by 16 | Viewed by 5876

Abstract

This matched-control cohort study explored the effects of high-intensity interval training (HIIT) on left ventricle (LV) dimensions and survival in heart failure (HF) patients between 2009 and 2016. HF patients who underwent the multidisciplinary disease management program (MDP) were enrolled. Non-exercising participants, aged [...] Read more.

This matched-control cohort study explored the effects of high-intensity interval training (HIIT) on left ventricle (LV) dimensions and survival in heart failure (HF) patients between 2009 and 2016. HF patients who underwent the multidisciplinary disease management program (MDP) were enrolled. Non-exercising participants, aged (mean (95% confidence interval)) 62.8 (60.1–65.5) years, were categorized as the MDP group (n = 101). Participants aged 61.5 (58.7–64.2) years who had completed 36 sessions of HIIT were treated as the HIIT group (n = 101). Peak oxygen consumption (VO_2peak) and LV geometry were assessed during the 8-year follow-up period. The 5-year all-cause mortality risk factors and overall survival rates were determined in the longitudinal observation. An increased VO_2peak of 14–20% was observed in the HIIT group after exercise training. Each 1-mL/kg/min increase in VO_2peak conferred a 58% improvement in 5-year mortality. Increased LV end-systolic diameter (LVESD) was significantly (p = 0.0198) associated with increased mortality. The 8-month survival rate was significantly improved (p = 0.044) in HIIT participants compared to non-exercise participants. HF patients with VO_2peak ≥14.0 mL/kg/min and LVESD <44 mm had a significantly better 5-year survival rate (98.2%) than those (57.3%) with lower VO_2peak and greater LVESD. Both HIIT-induced increased VO_2peak and decreased LVESD are associated with improved survival in HF patients. Full article

(This article belongs to the Special Issue Cardiac Rehabilitation)

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16 pages, 3199 KiB

Open AccessArticle

Epigenetic Changes at the Birc5 Promoter Induced by YM155 in Synovial Sarcoma

by Aleksander Mika, Sarah E. Luelling, Adriene Pavek, Christopher Nartker, Alexandra L. Heyneman, Kevin B. Jones and Jared J. Barrott

J. Clin. Med. 2019, 8(3), 408; https://doi.org/10.3390/jcm8030408 - 24 Mar 2019

Cited by 5 | Viewed by 4927

Abstract

YM155 is an anti-cancer therapy that has advanced into 11 different human clinical trials to treat various cancers. This apoptosis-inducing therapy indirectly affects the protein levels of survivin (gene: Birc5), but the molecular underpinnings of the mechanism remain largely unknown. Synovial sarcoma [...] Read more.

YM155 is an anti-cancer therapy that has advanced into 11 different human clinical trials to treat various cancers. This apoptosis-inducing therapy indirectly affects the protein levels of survivin (gene: Birc5), but the molecular underpinnings of the mechanism remain largely unknown. Synovial sarcoma is a rare soft-tissue malignancy with high protein expression of survivin. We investigated whether YM155 would be a viable therapeutic option to treat synovial sarcoma. YM155 therapy was applied to human synovial sarcoma cell lines and to a genetically engineered mouse model of synovial sarcoma. We discovered that YM155 exhibited nanomolar potency against human synovial sarcoma cell lines and the treated mice with synovial sarcoma demonstrated a 50% reduction in tumor volume compared to control treated mice. We further investigated the mechanism of action of YM155 by looking at the change of lysine modifications of the histone tails that were within 250 base pairs of the Birc5 promoter. Using chromatin immunoprecipitation (ChIP)-qPCR, we discovered that the histone epigenetic marks of H3K27 for the Birc5 promoter changed upon YM155 treatment. H3K27me3 and H3K27ac increased, but the net result was decreased Birc5/survivin expression. Furthermore, the combination of molecular events resulted in caspase 3/7/8 upregulation and death of the sarcoma cells. Full article

(This article belongs to the Section Oncology)

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Graphical abstract

20 pages, 900 KiB

Open AccessReview

The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys—The Future Is Now?

by Vedran Stefanovic

J. Clin. Med. 2019, 8(3), 407; https://doi.org/10.3390/jcm8030407 - 24 Mar 2019

Cited by 28 | Viewed by 7154

Abstract

Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence [...] Read more.

Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Eculizumab, the humanized monoclonal IgG2/4-antibody targeting C5 was approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of two rare diseases: PNH in 2007 and aHUS in 2011. There is an increasing number of publications of successful use of eculizumab for off-label indications, e.g., in pregnant women with antiphospholipid syndrome, sickle-cell anemia, and HELLP syndrome. These severe diseases are associated with both high maternal and fetal morbidity and mortality rate and substantial prematurity. Eculizumab has considerably improved overall outcome of patients with PNH and aHUS, enabling safe pregnancy for many women. Prolongation of pregnancy and the use of eculizumab, even for only a few weeks, may protect not only maternal renal function, but also alleviate acute and long-term renal consequences of prematurity in offspring. Full article

(This article belongs to the Special Issue Kidney Diseases and Kidney Involvement in Pregnancy: the Crossroad of Obstetrics, Nephrology, Urology and Internal Medicine)

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16 pages, 1458 KiB

Open AccessArticle

Smoking Dependent Alterations in Bone Formation and Inflammation Represent Major Risk Factors for Complications Following Total Joint Arthroplasty

by Sabrina Ehnert, Romina H. Aspera-Werz, Christoph Ihle, Markus Trost, Barbara Zirn, Ingo Flesch, Steffen Schröter, Borna Relja and Andreas K. Nussler

J. Clin. Med. 2019, 8(3), 406; https://doi.org/10.3390/jcm8030406 - 24 Mar 2019

Cited by 32 | Viewed by 5097

Abstract

Numerous studies have described a correlation between smoking and reduced bone mass. This not only increases fracture risk but also impedes reconstruction/fixation of bone. An increased frequency of complications following surgery is common. Here, we investigate the effect of smoking on the clinical [...] Read more.

Numerous studies have described a correlation between smoking and reduced bone mass. This not only increases fracture risk but also impedes reconstruction/fixation of bone. An increased frequency of complications following surgery is common. Here, we investigate the effect of smoking on the clinical outcome following total joint arthroplasty (TJA). 817 patients receiving primary or revision (including clinical transfers) TJA at our level-one trauma center have been randomly interviewed twice (pre- and six months post-surgery). We found that 159 patients developed complications (infections, disturbed healing, revisions, thrombosis, and/or death). Considering nutritional status, alcohol and cigarette consumption as possible risk factors, OR was highest for smoking. Notably, mean age was significantly lower in smokers (59.2 ± 1.0a) than non-smokers (64.6 ± 0.8; p < 0.001). However, the number of comorbidities was comparable between both groups. Compared to non-smokers (17.8 ± 1.9%), the complication rate increases with increasing cigarette consumption (1–20 pack-years (PY): 19.2 ± 2.4% and >20 PY: 30.4 ± 3.6%; p = 0.002). Consequently, mean hospital stay was longer in heavy smokers (18.4 ± 1.0 day) than non-smokers (15.3 ± 0.5 day; p = 0.009) or moderate smokers (15.9 ± 0.6 day). In line with delayed healing, bone formation markers (BAP and CICP) were significantly lower in smokers than non-smokers 2 days following TJA. Although, smoking increased serum levels of MCP-1, OPG, sRANKL, and Osteopontin as well as bone resorption markers (TRAP5b and CTX-I) were unaffected. In line with an increased infection rate, smoking reduced 25OH vitamin D3 (immune-modulatory), IL-1β, IL-6, TNF-α, and IFN-γ serum levels. Our data clearly show that smoking not only affects bone formation after TJA but also suppresses the inflammatory response in these patients. Thus, it is feasible that therapies favoring bone formation and immune responses help improve the clinical outcome in smokers following TJA. Full article

(This article belongs to the Special Issue Complications in Total Joint Arthroplasties)

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11 pages, 503 KiB

Open AccessArticle

Carcinoid Heart Disease and Decreased Overall Survival among Patients with Neuroendocrine Tumors: A Retrospective Multicenter Latin American Cohort Study

by Deise Uema, Carolina Alves, Marcella Mesquita, Jose Eduardo Nuñez, Timo Siepmann, Martin Angel, Juliana F. M. Rego, Rui Weschenfelder, Duilio R. Rocha Filho, Frederico P. Costa, Milton Barros, Juan M. O’Connor, Ben M. Illigens and Rachel P. Riechelmann

J. Clin. Med. 2019, 8(3), 405; https://doi.org/10.3390/jcm8030405 - 23 Mar 2019

Cited by 13 | Viewed by 4322

Abstract

The background to this study was that factors associated with carcinoid heart disease (CHD) and its impacts on overall survival (OS) are scantly investigated in patients (pts) with neuroendocrine tumors (NETs). In terms of materials and methods, a retrospective multicenter cohort study was [...] Read more.

The background to this study was that factors associated with carcinoid heart disease (CHD) and its impacts on overall survival (OS) are scantly investigated in patients (pts) with neuroendocrine tumors (NETs). In terms of materials and methods, a retrospective multicenter cohort study was conducted of factors associated with CHD in advanced NET pts with carcinoid syndrome (CS) and/or elevated urinary 5-hidroxyindole acetic acid (u5HIAA). CHD was defined as at least moderate right valve alterations. The results were the following: Among the 139 subjects included, the majority had a midgut NET (54.2%), 81.3% had CS, and 93% received somatostatin analogues. In a median follow-up of 39 months, 48 (34.5%) pts developed CHD, with a higher frequency in pts treated in public (77.2%) versus private settings (22.9%). In a multivariate logistic regression, unknown primary or colorectal NETs (Odds Ratio (OR) 4.35; p = 0.002), at least 50% liver involvement (OR 3.45; p = 0.005), and being treated in public settings (OR 4.76; p = 0.001) were associated with CHD. In a Cox multivariate regression, bone metastases (Hazard Ratio {HR} 2.8; p = 0.031), CHD (HR 2.63; p = 0.038), and a resection of the primary tumor (HR 0.33; p = 0.026) influenced the risk of death. The conclusions were the following: The incidence of CHD was higher in pts with a high hepatic tumor burden and in those treated in a public system. Delayed diagnosis and limited access to effective therapies negatively affected the lives of NET patients. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Therapy of Neuroendocrine Neoplasms)

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10 pages, 268 KiB

Open AccessReview

Daylight Saving Time and Acute Myocardial Infarction: A Meta-Analysis

by Roberto Manfredini, Fabio Fabbian, Rosaria Cappadona, Alfredo De Giorgi, Francesca Bravi, Tiziano Carradori, Maria Elena Flacco and Lamberto Manzoli

J. Clin. Med. 2019, 8(3), 404; https://doi.org/10.3390/jcm8030404 - 23 Mar 2019

Cited by 45 | Viewed by 35707

Abstract

Background: The available evidence on the effects of daylight saving time (DST) transitions on major cardiovascular diseases is limited and conflicting. We carried out the first meta-analysis aimed at evaluating the risk of acute myocardial infarction (AMI) following DST transitions. Methods: We searched [...] Read more.

Background: The available evidence on the effects of daylight saving time (DST) transitions on major cardiovascular diseases is limited and conflicting. We carried out the first meta-analysis aimed at evaluating the risk of acute myocardial infarction (AMI) following DST transitions. Methods: We searched cohort or case-control studies evaluating the incidence of AMI, among adults (≥18 y), during the weeks following spring and/or autumn DST shifts, versus control periods. The search was made in MedLine and Scopus, up to 31 December 2018, with no language restriction. A summary odds ratio of AMI was computed after: (1) spring, (2) autumn or (3) both transitions considered together. Meta-analyses were also stratified by gender and age. Data were combined using a generic inverse-variance approach. Results: Seven studies (>115,000 subjects) were included in the analyses. A significantly higher risk of AMI (Odds Ratio: 1.03; 95% CI: 1.01–1.06) was observed during the two weeks following spring or autumn DST transitions. However, although AMI risk increased significantly after the spring shift (OR: 1.05; 1.02–1.07), the incidence of AMI during the week after winter DST transition was comparable with control periods (OR 1.01; 0.98–1.04). No substantial differences were observed when the analyses were stratified by age or gender. Conclusion: The risk of AMI increases modestly but significantly after DST transitions, supporting the proposal of DST shifts discontinuation. Additional studies that fully adjust for potential confounders are required to confirm the present findings. Full article

(This article belongs to the Special Issue Therapies for Myocardial Injury and Infarction)

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13 pages, 1200 KiB

Open AccessArticle

Treatment of Liver Metastases from Midgut Neuroendocrine Tumours: A Systematic Review and Meta-Analysis

by Enes Kaçmaz, Charlotte M. Heidsma, Marc G. H. Besselink, Koen M. A. Dreijerink, Heinz-Josef Klümpen, Elisabeth J. M. Nieveen van Dijkum and Anton F. Engelsman

J. Clin. Med. 2019, 8(3), 403; https://doi.org/10.3390/jcm8030403 - 22 Mar 2019

Cited by 25 | Viewed by 4120

Abstract

Strong evidence comparing different treatment options for liver metastases (LM) arising from gastroenteropancreatic neuroendocrine tumours (GEP-NET) is lacking. The aim of this study was to determine which intervention for LMs from GEP-NETs shows the longest overall survival (OS). A systematic search was performed [...] Read more.

Strong evidence comparing different treatment options for liver metastases (LM) arising from gastroenteropancreatic neuroendocrine tumours (GEP-NET) is lacking. The aim of this study was to determine which intervention for LMs from GEP-NETs shows the longest overall survival (OS). A systematic search was performed in MEDLINE, Embase and the Cochrane Library in February 2018. Studies reporting on patients with LMs of any grade of sporadic GEP-NET comparing two intervention groups were included for analysis. Meta-analyses were performed where possible. Eleven studies, with a total of 1108, patients were included; 662 patients had LM from pancreatic NETs (pNET), 164 patients from small-bowel NETs (SB-NET) and 282 patients of unknown origin. Improved 5-year OS was observed for surgery vs. chemotherapy (OR 0.05 95% CI [0.01, 0.21] p < 0.0001), for surgery vs. embolization (OR 0.18 95% CI [0.05, 0.61] p = 0.006) and for LM resection vs. no LM resection (OR 0.15 95% CI [0.05, 0.42] p = 0.0003). This is the largest meta-analysis performed comparing different interventions for LMs from GEP-NETs. Despite the high risk of bias and heterogeneity of data, surgical resection for all tumour grades results in the longest overall survival. Chemotherapy and embolization should be considered as an alternative in case surgery is not feasible. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Therapy of Neuroendocrine Neoplasms)

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10 pages, 996 KiB

Open AccessArticle

Quantitative Assessment of the Learning Curve for Robotic Thyroid Surgery

by HyunGoo Kim, Hyungju Kwon, Woosung Lim, Byung-In Moon and Nam Sun Paik

J. Clin. Med. 2019, 8(3), 402; https://doi.org/10.3390/jcm8030402 - 22 Mar 2019

Cited by 20 | Viewed by 3466

Abstract

With the increased utilization of robot thyroidectomy in recent years, surgical proficiency is the paramount consideration. However, there is no single perfect or ideal method for measuring surgical proficiency. In this study, we evaluated the learning curve of robotic thyroidectomy using various parameters. [...] Read more.

With the increased utilization of robot thyroidectomy in recent years, surgical proficiency is the paramount consideration. However, there is no single perfect or ideal method for measuring surgical proficiency. In this study, we evaluated the learning curve of robotic thyroidectomy using various parameters. A total of 172 robotic total thyroidectomies were performed by a single surgeon between March 2014 and February 2018. Cumulative summation analysis revealed that it took 50 cases for the surgeon to significantly improve the operation time. Mean operation time was significantly shorter in the group that included the 51st to the 172nd case, than in the group that included only the first 50 cases (132.8 ± 27.7 min vs. 166.9 ± 29.5 min; p < 0.001). On the other hand, the surgeon was competent after the 75th case when postoperative transient hypoparathyroidism was used as the outcome measure. The incidence of hypoparathyroidism gradually decreased from 52.0%, for the first 75 cases, to 40.2% after the 76th case. These results indicated that the criteria used to assess proficiency greatly influenced the interpretation of the learning curve. Incorporation of the operation time, complications, and oncologic outcomes should be considered in learning curve assessment. Full article

(This article belongs to the Special Issue Robotic Surgery)

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11 pages, 211 KiB

Open AccessReview

Uncovering Female Child Sexual Offenders—Needs and Challenges for Practice and Research

by Safiye Tozdan, Peer Briken and Arne Dekker

J. Clin. Med. 2019, 8(3), 401; https://doi.org/10.3390/jcm8030401 - 22 Mar 2019

Cited by 27 | Viewed by 25446

Abstract

This article provides a short literature overview on female child sexual offenders (FCSO) focusing on the discrepancy between prevalence rates from different sources, characteristics of FCSO and their victims, as well as the societal “culture of denial” surrounding these women. FCSO are a [...] Read more.

This article provides a short literature overview on female child sexual offenders (FCSO) focusing on the discrepancy between prevalence rates from different sources, characteristics of FCSO and their victims, as well as the societal “culture of denial” surrounding these women. FCSO are a powerful social taboo. Even professionals in the healthcare or justice system were shown to respond inappropriately in cases of child sexual abuse committed by women. As a result, offences of FCSO may be underreported and therefore difficult to research. The lack of scientific data on FSCO lowers the quality of child protection and treatment services. We therefore deem it particularly necessary for professionals in health care to break the social taboo that is FCSO and to further stimulate research on the topic of FCSO. We provide some general implications for professionals in health care systems as well as specific recommendations for researchers. We end with an overall conclusion. Full article

(This article belongs to the Special Issue Novel Research in Sexuality and Mental Health)

8 pages, 623 KiB

Open AccessArticle

Efficacy and Safety of Intravenous Thrombolysis in Patients with Acute Ischemic Stroke and Pre–Existing Disability

by Giovanni Merlino, Elisa Corazza, Simone Lorenzut, Gian Luigi Gigli, Daniela Cargnelutti and Mariarosaria Valente

J. Clin. Med. 2019, 8(3), 400; https://doi.org/10.3390/jcm8030400 - 22 Mar 2019

Cited by 18 | Viewed by 3236

Abstract

Little is known about intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with pre-existing disability. Disabled patients are often excluded from IVT treatment. Previous studies investigated the role of pre-existing disability on outcomes in AIS patients after IVT. However, no studies have [...] Read more.

Little is known about intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with pre-existing disability. Disabled patients are often excluded from IVT treatment. Previous studies investigated the role of pre-existing disability on outcomes in AIS patients after IVT. However, no studies have been conducted to date to determine whether IVT may improve clinical outcomes in AIS patients with pre-existing disability. The aim of our study was to evaluate efficacy and safety of IVT in patients with pre-existing moderate and moderately severe disability (pre-stroke modified Rankin Scale score = 3 or 4) affected by AIS. This study was based on a retrospective analysis of a prospectively collected database of consecutive patients admitted to the Udine University Hospital with AIS from January 2015 to May 2018. The efficacy endpoints were the rate of favorable outcome and rate of major neurological improvement. The safety endpoints were the rate of mortality at three months, presence of intracranial hemorrhage (ICH), and presence of symptomatic intracranial hemorrhage (sICH). The study population included 110 AIS patients with pre-existing moderate and moderately severe disability, 36 of which received (IVT+) and 74 did not receive IVT (IVT−). AIS disabled patients treated with IVT had higher rates of favorable outcome (66.7% vs. 36.5%, p = 0.003) and major neurological improvement (39.4% vs. 17.4%, p = 0.01) compared to non-treated ones. Two in three disabled patients returned to their pre-stroke functional status when treated with IVT. Prevalence of three-month mortality, ICH, and sICH did not differ in the two groups. Disabled patients affected by AIS significantly improved after IVT. Moderate and moderately severe disability alone should not be considered, per se, as a contraindication to IVT treatment. Full article

(This article belongs to the Section Clinical Neurology)

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12 pages, 1821 KiB

Open AccessArticle

High-Resolution Computed Tomography (HRCT) Reflects Disease Progression in Patients with Idiopathic Pulmonary Fibrosis (IPF): Relationship with Lung Pathology

by Elisabetta Cocconcelli, Elisabetta Balestro, Davide Biondini, Giulio Barbiero, Roberta Polverosi, Fiorella Calabrese, Federica Pezzuto, Donato Lacedonia, Federico Rea, Marco Schiavon, Erica Bazzan, Maria Pia Foschino Barbaro, Graziella Turato, Paolo Spagnolo, Manuel G. Cosio and Marina Saetta

J. Clin. Med. 2019, 8(3), 399; https://doi.org/10.3390/jcm8030399 - 22 Mar 2019

Cited by 18 | Viewed by 5045

Abstract

High-Resolution Computed Tomography (HRCT) plays a central role in diagnosing Idiopathic Pulmonary Fibrosis (IPF) while its role in monitoring disease progression is not clearly defined. Given the variable clinical course of the disease, we evaluated whether HRCT abnormalities predict disease behavior and correlate [...] Read more.

High-Resolution Computed Tomography (HRCT) plays a central role in diagnosing Idiopathic Pulmonary Fibrosis (IPF) while its role in monitoring disease progression is not clearly defined. Given the variable clinical course of the disease, we evaluated whether HRCT abnormalities predict disease behavior and correlate with functional decline in untreated IPF patients. Forty-nine patients (with HRCT₁) were functionally categorized as rapid or slow progressors. Twenty-one had a second HRCT₂. Thirteen patients underwent lung transplantation and pathology was quantified. HRCT Alveolar (AS) and Interstitial Scores (IS) were assessed and correlated with Forced Vital Capacity (FVC) decline between HRCT₁ and HRCT₂. At baseline, AS was greater in rapids than in slows, while IS was similar in the two groups. In the 21 subjects with HRCT₂, IS increased over time in both slows and rapids, while AS increased only in rapids. The IS change from HRCT₁ to HRCT₂ normalized per month correlated with FVC decline/month in the whole population, but the change in AS did not. In the 13 patients with pathology, the number of total lymphocytes was higher in rapids than in slows and correlated with AS. Quantitative estimation of HRCTs AS and IS reflects the distinct clinical and pathological behavior of slow and rapid decliners. Furthermore, AS, which reflects the immune/inflammatory infiltrate in lung tissue, could be a useful tool to differentiate rapid from slow progressors at presentation. Full article

(This article belongs to the Special Issue The New Frontier in Pulmonary Fibrosis)

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10 pages, 2837 KiB

Open AccessCase Report

Efficacy and Metabolic Effect on Serum Lipids of Apremilast in Psoriatic Arthritis: A Case Report

by Roberta Gualtierotti and Orazio De Lucia

J. Clin. Med. 2019, 8(3), 398; https://doi.org/10.3390/jcm8030398 - 22 Mar 2019

Cited by 8 | Viewed by 5668

Abstract

Psoriatic arthritis (PsA) is a chronic immune-mediated disease manifesting as joint inflammation with functional impairment associated with psoriasis. Recently, PsA has emerged as a systemic disease with several comorbidities, such as cardiovascular diseases and metabolic disorders. Apremilast is a targeted synthetic disease-modifying anti-rheumatic [...] Read more.

Psoriatic arthritis (PsA) is a chronic immune-mediated disease manifesting as joint inflammation with functional impairment associated with psoriasis. Recently, PsA has emerged as a systemic disease with several comorbidities, such as cardiovascular diseases and metabolic disorders. Apremilast is a targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) directed against phosphodiesterase 4 (PDE4) with demonstrated efficacy and safety in PsA and psoriasis. We report the case of a patient with PsA manifesting as arthritis, dactylitis, mild psoriasis and a significantly reduced health-related quality of life (HRQoL). Treatment with apremilast in association with methotrexate led to a quick improvement of joint and skin involvement with a stable amelioration of HRQoL. Furthermore, we observed a persistent favorable shift of serum lipid profile. Our observations suggest that apremilast is effective in controlling mild skin and joint involvement, including dactylitis, and suggest a potentially advantageous metabolic effect in patients with PsA. Full article

(This article belongs to the Section Immunology)

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18 pages, 4813 KiB

Open AccessArticle

The New Synthetic Serum-Free Medium OptiPASS Promotes High Proliferation and Drug Efficacy Prediction on Spheroids from MDA-MB-231 and SUM1315 Triple-Negative Breast Cancer Cell Lines

by Clémence Dubois, Pierre Daumar, Corinne Aubel, Jean Gauthier, Bernard Vidalinc, Emmanuelle Mounetou, Frédérique Penault-Llorca and Mahchid Bamdad

J. Clin. Med. 2019, 8(3), 397; https://doi.org/10.3390/jcm8030397 - 21 Mar 2019

Cited by 8 | Viewed by 4496

Abstract

Triple-negative breast cancers are particularly aggressive. In vitro cultures are one of the major pathways for developing anticancer strategies. The effectiveness and reproducibility of the drug screenings depend largely on the homogeneity of culture media. In order to optimize the predictive responses of [...] Read more.

Triple-negative breast cancers are particularly aggressive. In vitro cultures are one of the major pathways for developing anticancer strategies. The effectiveness and reproducibility of the drug screenings depend largely on the homogeneity of culture media. In order to optimize the predictive responses of triple-negative breast cancer 3D cell culture models, these works were focused on the development of SUM1315 and MDA-MB-231 cell lines in OptiPASS medium, a new serum-free formulation (BIOPASS). In monolayer cell culture, OptiPASS medium was more suitable for MDA-MB-231 than SUM1315 cell line but maintained cell phenotype and allowed sufficient proliferation. For spheroids produced in OptiPASS, the size monitoring showed a 1.3 and 1.5-fold increase for MDA-MB-231 and SUM1315 cell lines, respectively and viability/mortality profiles were maintained. Spheroids drug sensitivity thresholds were also improved allowing quicker high throughput drug screenings. These results showed the suitability of OptiPASS for 2D and 3D cell cultures of these two triple-negative breast cancer cell lines, with reproducibility of spheroid formation superior to 98%. This opens the way to the common use of this synthetic medium in future preclinical breast cancer research studies. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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9 pages, 604 KiB

Open AccessArticle

Impact of Anesthetics on Cardioprotection Induced by Pharmacological Preconditioning

by Sebastian Bunte, Tobias Lill, Maximilian Falk, Martin Stroethoff, Annika Raupach, Alexander Mathes, André Heinen, Markus W. Hollmann and Ragnar Huhn

J. Clin. Med. 2019, 8(3), 396; https://doi.org/10.3390/jcm8030396 - 21 Mar 2019

Cited by 12 | Viewed by 3273

Abstract

Anesthetics, especially propofol, are discussed to influence ischemic preconditioning. We investigated whether cardioprotection by milrinone or levosimendan is influenced by the clinically used anesthetics propofol, sevoflurane or dexmedetomidine. Hearts of male Wistar rats were randomised, placed on a Langendorff system and perfused with [...] Read more.

Anesthetics, especially propofol, are discussed to influence ischemic preconditioning. We investigated whether cardioprotection by milrinone or levosimendan is influenced by the clinically used anesthetics propofol, sevoflurane or dexmedetomidine. Hearts of male Wistar rats were randomised, placed on a Langendorff system and perfused with Krebs–Henseleit buffer (KHB) at a constant pressure of 80 mmHg. All hearts underwent 33 min of global ischemia and 60 min of reperfusion. Three different anesthetic regimens were conducted throughout the experiments: propofol (11 μM), sevoflurane (2.5 Vol%) and dexmedetomidine (1.5 nM). Under each anesthetic regimen, pharmacological preconditioning was induced by administration of milrinone (1 μM) or levosimendan (0.3 μM) 10 min before ischemia. Infarct size was determined by TTC staining. Infarct sizes in control groups were comparable (KHB-Con: 53 ± 9%, Prop-Con: 56 ± 9%, Sevo-Con: 56 ± 8%, Dex-Con: 53 ± 9%; ns). Propofol completely abolished preconditioning by milrinone and levosimendan (Prop-Mil: 52 ± 8%, Prop-Lev: 52 ± 8%; ns versus Prop-Con), while sevoflurane did not (Sevo-Mil: 31 ± 9%, Sevo-Lev: 33 ± 7%; p < 0.05 versus Sevo-Con). Under dexmedetomidine, results were inconsistent; levosimendan induced infarct size reduction (Dex-Lev: 36 ± 6%; p < 0.05 versus Dex-Con) but not milrinone (Dex-Mil: 51 ± 8%; ns versus Dex-Con). The choice of the anesthetic regimen has an impact on infarct size reduction by pharmacological preconditioning. Full article

(This article belongs to the Section Anesthesiology)

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12 pages, 1034 KiB

Open AccessArticle

by Wubshet H. Tesfaye, Gregory M. Peterson, Ronald L. Castelino, Charlotte McKercher, Matthew Jose, Syed Tabish R. Zaidi and Barbara C. Wimmer

J. Clin. Med. 2019, 8(3), 395; https://doi.org/10.3390/jcm8030395 - 21 Mar 2019

Cited by 8 | Viewed by 5197

Abstract

This study aimed to examine the association between medication-related factors and risk of hospital readmission in older patients with chronic kidney disease (CKD). A retrospective analysis was conducted targeting older CKD (n = 204) patients admitted to an Australian hospital. Medication appropriateness [...] Read more.

This study aimed to examine the association between medication-related factors and risk of hospital readmission in older patients with chronic kidney disease (CKD). A retrospective analysis was conducted targeting older CKD (n = 204) patients admitted to an Australian hospital. Medication appropriateness (Medication Appropriateness Index; MAI), medication regimen complexity (number of medications and Medication Regimen Complexity Index; MRCI) and use of selected medication classes were exposure variables. Outcomes were occurrence of readmission within 30 and 90 days, and time to readmission within 90 days. Logistic and Cox hazards regression were used to identify factors associated with readmission. Overall, 50 patients (24%) were readmitted within 30 days, while 81 (40%) were readmitted within 90 days. Mean time to readmission within 90 days was 66 (SD 34) days. Medication appropriateness and regimen complexity were not independently associated with 30- or 90-day hospital readmissions in older adults with CKD, whereas use of renin-angiotensin blockers was associated with reduced occurrence of 30-day (adjusted OR 0.39; 95% CI 0.19–0.79) and 90-day readmissions (adjusted OR 0.45; 95% CI 0.24–0.84) and longer time to readmission within 90 days (adjusted HR 0.52; 95% CI 0.33–0.83). This finding highlights the importance of considering the potential benefits of individual medications during medication review in older CKD patients. Full article

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

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9 pages, 1637 KiB

Open AccessArticle

Long-Term Effects of Initiating Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM) in People with Type 1 Diabetes and Unsatisfactory Diabetes Control

by Jon-Duri Senn, Stefan Fischli, Lea Slahor, Susanne Schelbert and Christoph Henzen

J. Clin. Med. 2019, 8(3), 394; https://doi.org/10.3390/jcm8030394 - 21 Mar 2019

Cited by 15 | Viewed by 4355

Abstract

Background: We aimed to assess the long-term effects of the introduction of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in people with type 1 diabetes (T1D). Methods: A prospective single-centre cohort study including participants with T1D and HbA1c > 7.5%. [...] Read more.

Background: We aimed to assess the long-term effects of the introduction of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in people with type 1 diabetes (T1D). Methods: A prospective single-centre cohort study including participants with T1D and HbA1c > 7.5%. After completing a course in flexible intensified insulin treatment (FIT), participants were offered treatment change to CSII/CGM. FIT participants with HbA1c ≤ 7.5% who remained on multiple daily injections (MDI) and without CGM were monitored as a separate cohort to compare the cumulative incidence of diabetic complications. Results: The study cohort included 41 participants with T1D (21 male/20 female). The mean age (±SD) at inclusion was 24.2 ± 10.9 years, the mean follow-up was 8.9 ± 2.8 years, and the mean diabetes duration at the end of the study was 15.9 ± 10.1 years. The mean HbA1c level before the introduction of CSII was 8.8 ± 1.3% (73 ± 8 mmol/mol), and decreased significantly thereafter to 8.0 ± 1.1% (63 ± 7 mmol/mol) (p = 0.0001), and further to 7.6 ± 1.1% (59 ± 11 mmol/mol) after the initiation of CGM (p = 0.051). In the MDI group the HbA1c levels did not change significantly during a mean follow-up of 6.8 ± 3.2 years. The frequency of severe hypoglycaemia after the introduction of CSII/CGM declined significantly (from 9.7 to 2.2 per 100 patient-years, p = 0.03), and the cumulative incidence of newly diagnosed diabetic microvascular complications were comparable between the study group and the observational cohort. Conclusion: In people with T1D and unsatisfactory diabetes control the introduction of CSII and CGM results in a substantial and long-term improvement. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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28 pages, 1114 KiB

Open AccessReview

Current Progress in Pharmacogenetics of Second-Line Antidiabetic Medications: Towards Precision Medicine for Type 2 Diabetes

by Chan Uk Heo and Chang-Ik Choi

J. Clin. Med. 2019, 8(3), 393; https://doi.org/10.3390/jcm8030393 - 21 Mar 2019

Cited by 24 | Viewed by 8576

Abstract

Precision medicine is a scientific and medical practice for personalized therapy based on patients’ individual genetic, environmental, and lifestyle characteristics. Pharmacogenetics and pharmacogenomics are also rapidly developing and expanding as a key element of precision medicine, in which the association between individual genetic [...] Read more.

Precision medicine is a scientific and medical practice for personalized therapy based on patients’ individual genetic, environmental, and lifestyle characteristics. Pharmacogenetics and pharmacogenomics are also rapidly developing and expanding as a key element of precision medicine, in which the association between individual genetic variabilities and drug disposition and therapeutic responses are investigated. Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia mainly associated with insulin resistance, with the risk of clinically important cardiovascular, neurological, and renal complications. The latest consensus report from the American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) on the management of T2D recommends preferential use of glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and some dipeptidyl peptidase-4 (DPP-4) inhibitors after initial metformin monotherapy for diabetic patients with established atherosclerotic cardiovascular or chronic kidney disease, and with risk of hypoglycemia or body weight-related problems. In this review article, we summarized current progress on pharmacogenetics of newer second-line antidiabetic medications in clinical practices and discussed their therapeutic implications for precision medicine in T2D management. Several biomarkers associated with drug responses have been identified from extensive clinical pharmacogenetic studies, and functional variations in these genes have been shown to significantly affect drug-related glycemic control, adverse reactions, and risk of diabetic complications. More comprehensive pharmacogenetic research in various clinical settings will clarify the therapeutic implications of these genes, which may be useful tools for precision medicine in the treatment and prevention of T2D and its complications. Full article

(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)

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15 pages, 3146 KiB

Open AccessArticle

Autologous Matrix-Induced Chondrogenesis (AMIC) and AMIC Enhanced by Autologous Concentrated Bone Marrow Aspirate (BMAC) Allow for Stable Clinical and Functional Improvements at up to 9 Years Follow-Up: Results from a Randomized Controlled Study

by Laura de Girolamo, Herbert Schönhuber, Marco Viganò, Corrado Bait, Alessandro Quaglia, Gabriele Thiebat and Piero Volpi

J. Clin. Med. 2019, 8(3), 392; https://doi.org/10.3390/jcm8030392 - 21 Mar 2019

Cited by 51 | Viewed by 5193

Abstract

The aims of the study were to evaluate long-term outcomes after autologous matrix-induced chondrogenesis (AMIC) in the treatment of focal chondral lesions and to assess the possible improvements given by the combination of this technique with bone marrow aspirate concentrate (BMAC). Twenty-four patients [...] Read more.

The aims of the study were to evaluate long-term outcomes after autologous matrix-induced chondrogenesis (AMIC) in the treatment of focal chondral lesions and to assess the possible improvements given by the combination of this technique with bone marrow aspirate concentrate (BMAC). Twenty-four patients (age range 18–55 years) affected by focal knee chondral lesions were treated with standard AMIC or AMIC enhanced by BMAC (AMIC+). Pain (Visual Analogue Scale (VAS)) and functional scores (Lysholm, International Knee Documentation Committee (IKDC), Tegner, Knee injury and Osteoarthritis Outcome Score (KOOS)) were collected pre-operatively and then at 6, 12, 24, 60, and 100 months after treatment. Magnetic resonance imaging (MRI) evaluation was performed pre-operatively and at 6, 12, and 24 months follow-ups. Patients treated with AMIC+ showed higher Lysholm scores (p = 0.015) and lower VAS (p = 0.011) in comparison with patients in the standard AMIC group at the 12 months follow-up. Both treatments allowed for functional and pain improvements with respect to pre-operative levels lasting up to 100 months. MRI revealed consistent cartilage repair at 24 months in both groups. This study shows that AMIC and AMIC+ are effective treatments for focal chondral lesions with beneficial effect lasting up to 9 years. AMIC+ allows for faster recovery from injury, and is thus more indicated for patients requiring a prompt return to activity. Level of evidence: II, randomized controlled trial in an explorative cohort. Full article

(This article belongs to the Special Issue Cartilage Repair and Restorative Procedures)

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12 pages, 401 KiB

Open AccessArticle

Efficacy of Three Different Prophylactic Treatments for Postoperative Nausea and Vomiting after Vitrectomy: A Randomized Clinical Trial

by Michele Reibaldi, Matteo Fallico, Antonio Longo, Teresio Avitabile, Marinella Astuto, Paolo Murabito, Carmelo Minardi, Vincenza Bonfiglio, Francesco Boscia, Claudio Furino, Robert Rejdak, Katarzyna Nowomiejska, Mario Toro, Gilda Cennamo, Salvatore Cillino, Michele Rinaldi, Tito Fiore, Carlo Cagini and Andrea Russo

J. Clin. Med. 2019, 8(3), 391; https://doi.org/10.3390/jcm8030391 - 21 Mar 2019

Cited by 12 | Viewed by 4313

Abstract

Postoperative nausea and vomiting (PONV) after vitreoretinal surgery may potentially be associated with severe complications, such as suprachoroidal hemorrhage. The purpose of the present multicenter clinical trial (NCT02386059) was to assess the efficacy of three different prophylactic treatments for PONV after vitrectomy under [...] Read more.

Postoperative nausea and vomiting (PONV) after vitreoretinal surgery may potentially be associated with severe complications, such as suprachoroidal hemorrhage. The purpose of the present multicenter clinical trial (NCT02386059) was to assess the efficacy of three different prophylactic treatments for PONV after vitrectomy under local anesthesia. Patients undergoing primary vitrectomy were randomized to the control arm or to one of the treatment arms (4 mg ondansetron, 4 mg dexamethasone, combination of the two drugs). The primary outcome measure was the proportion of complete response (no nausea, no vomiting, no retching, and no use of antiemetic rescue medication) during 24 h after vitrectomy. Secondary outcomes included the severity standardized score of PONV, postoperative pain standardized score, and rate of ocular and non-ocular adverse events. Baseline demographics of the 1287 patients were comparable between the four arms. The combined therapy group showed a statistically significant lower incidence of PONV compared to the placebo and monotherapy (p < 0.001). PONV severity was also reduced in the combination group compared to the others (p < 0.001). Postoperative pain scores and adverse events were comparable among the four groups. Combined therapy with dexamethasone and ondansetron was the most effective treatment for reducing the incidence and severity of PONV in patients undergoing vitrectomy under local anesthesia. Full article

(This article belongs to the Section Ophthalmology)

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10 pages, 217 KiB

Open AccessArticle

Clinical Characteristics and Predictors of Poor Hospital Discharge Outcome for Young Children with Abusive Head Trauma

by Chih-Chi Chen, Po-Chuan Hsieh, Carl P. C. Chen, Yu-Wei Hsieh, Chia-Ying Chung, Kuang-Lin Lin and Prevention, Protection Against Child Abuse, Neglect (PCHAN) Study Group

J. Clin. Med. 2019, 8(3), 390; https://doi.org/10.3390/jcm8030390 - 20 Mar 2019

Cited by 14 | Viewed by 3798

Abstract

Children with abusive head trauma tend to have worse outcomes than children with accidental head trauma. However, current predictors of poor outcomes for children with abusive head trauma are still limited. We aim to use clinical data to identify early predictors of poor [...] Read more.

Children with abusive head trauma tend to have worse outcomes than children with accidental head trauma. However, current predictors of poor outcomes for children with abusive head trauma are still limited. We aim to use clinical data to identify early predictors of poor outcome at discharge in children with abusive head trauma. In the 10-year observational retrospective cohort study, children aged between zero and four years with abusive or accidental head trauma were recruited. Multivariate logistic regression models were applied to evaluate factors associated with poor prognosis in children with abusive head trauma. The primary outcome was mortality or a Glasgow Coma Scale (GCS) motor component score of less than 6 at discharge. A total of 292 head trauma children were included. Among them, 59 children had abusive head trauma. In comparison to children with accidental head trauma, children with abusive head trauma were younger, had more severe head injuries, and experienced a higher frequency of post-traumatic seizures. Their radiologic findings showed common presence of subdural hemorrhage, cerebral edema, and less epidural hemorrhage. They were more in need of neurosurgical intervention. In the multivariate analysis for predictors of poor outcome in children with abusive head trauma, initial GCS ≤ 5 (versus GCS > 5 with the adjusted odds ratio (OR) = 25.7, 95% confidence interval (CI) = 1.5–432.8, p = 0.024) and older age (per year with the adjusted OR = 3.3, 95% CI = 1.2–9.5, p = 0.024) were independently associated with poor outcome. These findings demonstrate the characteristic clinical differences between children with abusive and accidental head trauma. Initial GCS ≤ 5 and older age are predictive of poor outcome at discharge in children with abusive head trauma. Full article

(This article belongs to the Special Issue Cardiovascular and Neurological Emergency)

2 pages, 537 KiB

Open AccessCorrection

Correction: Kim, Young-Gun; Jeon, Ja Young; Kim, Hae Jin; Kim, Dae Jung; Lee, Kwan-Woo; Moon, So Young; Han, Seung Jin. Risk of Dementia in Older Patients with Type 2 Diabetes on Dipeptidyl-Peptidase IV Inhibitors versus Sulfonylureas: A Real-World Population-Based Cohort Study. Journal of Clinical Medicine 2019, 8, 28

by Young-Gun Kim, Ja Young Jeon, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee, So Young Moon and Seung Jin Han

J. Clin. Med. 2019, 8(3), 389; https://doi.org/10.3390/jcm8030389 - 20 Mar 2019

Viewed by 2754

Abstract

The authors wish to make the following corrections to this paper [...] Full article

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15 pages, 2254 KiB

Open AccessArticle

Differential Responses of Colorectal Cancer Cell Lines to Enterococcus faecalis’ Strains Isolated from Healthy Donors and Colorectal Cancer Patients

by Carolina Vieira De Almeida, Matteo Lulli, Vincenzo di Pilato, Nicola Schiavone, Edda Russo, Giulia Nannini, Simone Baldi, Rossella Borrelli, Gianluca Bartolucci, Marta Menicatti, Antonio Taddei, Maria Novella Ringressi, Elena Niccolai, Domenico Prisco, Gian Maria Rossolini and Amedeo Amedei

J. Clin. Med. 2019, 8(3), 388; https://doi.org/10.3390/jcm8030388 - 20 Mar 2019

Cited by 28 | Viewed by 6442

Abstract

The metabolites produced by the host’s gut microbiota have an important role in the maintenance of intestinal homeostasis, but can also act as toxins and induce DNA damage in colorectal epithelial cells increasing the colorectal cancer (CRC) chance. In this scenario, the impact [...] Read more.

The metabolites produced by the host’s gut microbiota have an important role in the maintenance of intestinal homeostasis, but can also act as toxins and induce DNA damage in colorectal epithelial cells increasing the colorectal cancer (CRC) chance. In this scenario, the impact of some of the components of the natural human gastrointestinal microbiota, such as Enterococcus faecalis (E. faecalis), at the onset of CRC progression remains controversial. Since under dysbiotic conditions it could turn into a pathogen, the aim of this study was to compare the effect of E. faecalis’ strains (isolated from CRC patients and healthy subjects’ stools) on the proliferation of different colorectal cells lines. First, we isolated and genotyping characterized the Enterococcus faecalis’ strains. Then, we analyzed the proliferation index (by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) of three tumor and one normal intestinal cell lines, previously exposed to E. faecalis strains pre-cultured medium. Stool samples of CRC patients demonstrated a reduced frequency of E. faecalis compared to healthy subjects. In addition, the secreted metabolites of E. faecalis’ strains, isolated from healthy donors, decreased the human ileocecal adenocarcinoma cell line HCT-8 and human colon carcinoma cell line HCT-116 cell proliferation without effects on human colorectal adenocarcinoma cell line SW620 and on normal human diploid cell line CLR-1790. Notably, the metabolites of the strains isolated from CRC patients did not influence the cell growth of CRC cell lines. Our results demonstrated a new point of view in the investigation of E. faecalis’ role in CRC development, which raises awareness of the importance of not only associating the presence/absence of a unique microorganism, but also in defining the specific characteristics of the different investigated strains. Full article

(This article belongs to the Section Oncology)

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7 pages, 207 KiB

Open AccessReview

Golimumab for Rheumatoid Arthritis

by Eleftherios Pelechas, Paraskevi V. Voulgari and Alexandros A. Drosos

J. Clin. Med. 2019, 8(3), 387; https://doi.org/10.3390/jcm8030387 - 20 Mar 2019

Cited by 34 | Viewed by 6173

Abstract

Since the advent of infliximab for the treatment of rheumatoid arthritis (RA), new genetically-engineered molecules have appeared. This review aims to present the current data and body of evidence for golimumab (GLM). Safety, efficacy, tolerability and immunogenicity are all being investigated, not only [...] Read more.

Since the advent of infliximab for the treatment of rheumatoid arthritis (RA), new genetically-engineered molecules have appeared. This review aims to present the current data and body of evidence for golimumab (GLM). Safety, efficacy, tolerability and immunogenicity are all being investigated, not only through phase III trials (GO-BEFORE, GO-FORWARD, GO-AFTER, GO-MORE, GO-FURTHER, GO-NICE), but also through studies of real-world data. It seems that GLM in the subcutaneous form is an efficacious molecule with a good safety profile at the standard dosage scheme, but a 100 mg subcutaneous dose is associated with a higher risk of opportunistic infections, lymphoma and demyelination. Furthermore, when compared to other tumor necrosis factor-α molecules, it is non-inferior, and, at some points, such as when it comes to immunogenicity and persistence of the drug, it has a better profile. In summary, GLM is an effective, well-tolerated option for the treatment of RA, for both the clinician and patients who are seeking a convenient dosage scheme. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis Therapy Reappraisal: Strategies, Opportunities and Challenges)

14 pages, 627 KiB

Open AccessArticle

Couple Relationship and Parent-Child Relationship Quality: Factors Relevant to Parent-Child Communication on Sexuality in Romania

by Meda Veronica Pop and Alina Simona Rusu

J. Clin. Med. 2019, 8(3), 386; https://doi.org/10.3390/jcm8030386 - 19 Mar 2019

Cited by 8 | Viewed by 3880

Abstract

This study of parents in Romania explores how perceptions of their couple relationship quality and of factors associated with it (such as sexual communication anxiety and sexual perfectionism) were related to their perception of aspects describing parenting dimensions relevant to the sexual education [...] Read more.

This study of parents in Romania explores how perceptions of their couple relationship quality and of factors associated with it (such as sexual communication anxiety and sexual perfectionism) were related to their perception of aspects describing parenting dimensions relevant to the sexual education and sexual health of their children. The hypotheses tested in this study were supported by the data collected from 106 participants (aged 25 to 51 years), parents of 1 to 3 children: (1) sexual communication anxiety with one’s partner (but not sexual perfectionism) is a significant predictor for parents’ self-efficacy, outcome expectancy and communication and parenting behavior related to sexuality education; (2) parents’ self-efficacy and outcome expectancy about parent-child communication on sexual topics (including involvement in risky sexual behaviors) predict the level of parenting behavior in this respect; (3) parents’ sexual communication anxiety (but not their sexual perfectionism) together with their self-efficacy and outcome expectancy regarding parent-child communication about sexuality predict the level of parental sexuality-communication-and-education behavior. Full article

(This article belongs to the Special Issue Novel Research in Sexuality and Mental Health)

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