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J. Clin. Med., Volume 7, Issue 2 (February 2018) – 26 articles

Cover Story (view full-size image): The cover image represents 'moonlighting' by WDR5, a highly conserved protein that was first characterized in the context of histone methylation, but is now known to also act as a reader of the epigenetic 'code', a component of multiple chromatin modifying complexes, a co-factor for transcriptional regulators, and in mitotic regulation. We review the known functions of WDR5, discuss how a small, conserved, protein can achieve such versatility, consider how the multi-faceted actions of WDR5 need to be carefully considered when interpreting experimental results, and describe prospects for WDR5 as a target for anti-cancer agents. View this paper
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6 pages, 530 KiB  
Article
Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment
by Iain Hargreaves, Nimesh Mody, John Land and Simon Heales
J. Clin. Med. 2018, 7(2), 36; https://doi.org/10.3390/jcm7020036 - 20 Feb 2018
Cited by 20 | Viewed by 3685
Abstract
Objectives: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the [...] Read more.
Objectives: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10−3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10−3). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10−3) was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β-interferon. Full article
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11 pages, 553 KiB  
Review
From Prenatal to Preimplantation Genetic Diagnosis of β-Thalassemia. Prevention Model in 8748 Cases: 40 Years of Single Center Experience
by Giovanni Monni, Cristina Peddes, Ambra Iuculano and Rosa Maria Ibba
J. Clin. Med. 2018, 7(2), 35; https://doi.org/10.3390/jcm7020035 - 20 Feb 2018
Cited by 28 | Viewed by 6455
Abstract
The incidence of β-thalassemia in Sardinia is high and β-39 is the most common mutation. The prevention campaign started in 1977 and was performed in a single center (Microcitemico Hospital, Cagliari, Sardinia, Italy). It was based on educational programs, population screening by hematological [...] Read more.
The incidence of β-thalassemia in Sardinia is high and β-39 is the most common mutation. The prevention campaign started in 1977 and was performed in a single center (Microcitemico Hospital, Cagliari, Sardinia, Italy). It was based on educational programs, population screening by hematological and molecular identification of the carriers. Prenatal and pre-implantation diagnosis was offered to couples at risk. 8564 fetal diagnosis procedures using different invasive approaches and analysis techniques were performed in the last 40 years. Trans-abdominal chorionic villous sampling was preferred due to lower complication risks and early diagnosis. Chorionic villous DNA was analyzed by PCR technique. 2138 fetuses affected by β-thalassemia were diagnosed. Women opted for termination of the pregnancy (TOP) in 98.2% of these cases. Pre-implantation genetic diagnosis (PGD) was proposed to couples at risk to avoid TOP. A total of 184 PGD were performed. Initially, the procedure was exclusively offered to infertile couples, according to the law in force. The success rate of pregnancies increased from 11.1% to 30.8% when, crucial law changes were enacted, and PGD was offered to fertile women as well. Forty years of β-thalassemia prevention programs in Sardinia have demonstrated the important decrease of this severe genetic disorder. Full article
(This article belongs to the Section Hematology)
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7 pages, 1035 KiB  
Article
Influence of Iron Deficiency on HbA1c Levels in Pregnant Women: Comparison with Non-Pregnant Women
by Kunihiko Hashimoto and Masafumi Koga
J. Clin. Med. 2018, 7(2), 34; https://doi.org/10.3390/jcm7020034 - 20 Feb 2018
Cited by 14 | Viewed by 4807
Abstract
Although HbA1c is widely used as a glycemic control indicator, HbA1c is known to show falsely high levels in patients in an iron deficient state (IDS). We compared the influence of IDS on HbA1c levels between pregnant women, due to mainly an increase [...] Read more.
Although HbA1c is widely used as a glycemic control indicator, HbA1c is known to show falsely high levels in patients in an iron deficient state (IDS). We compared the influence of IDS on HbA1c levels between pregnant women, due to mainly an increase in demand for iron without bleeding, and non-pregnant women, due to mainly bleeding (menstruation). We studied 42 non-diabetic pregnant women (pregnant group) and 42 age-matched non-pregnant women with normal glucose tolerance (non-pregnant group). We compared HbA1c and glycated albumin (GA) levels between IDS and normal iron state (NIS) in both groups. Furthermore, we analyzed the correlation between indicators of glycemic control and iron-related parameters [mean corpuscular hemoglobin, serum transferrin saturation (%Tf), and serum ferritin] in both groups. Compared with non-pregnant women, pregnant women had significantly lower %Tf and serum ferritin levels and significantly higher morbidity of IDS. HbA1c, but not GA, had significantly higher levels in pregnant women with IDS compared with NIS; however, HbA1c in non-pregnant women showed no significant difference for both IDS and NIS. In pregnant women, significant negative correlations were observed between HbA1c and iron-related parameters. In non-pregnant women, negative correlations were observed between HbA1c and these parameters, but they were not significant. No significant correlations were observed between GA and iron-related parameters in both groups. HbA1c levels in pregnant women were found to be largely affected by iron deficiency compared with non-pregnant women. For this reason, GA, which is not affected by iron deficiency, is desirable for use in the assessment of glycemic control during pregnancy. Full article
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10 pages, 1169 KiB  
Article
Long-Term Oncologic Outcomes, Opioid Use, and Complications after Esophageal Cancer Surgery
by Tak Kyu Oh, Kwhanmien Kim, Sang Hoon Jheon, Sang-Hwan Do, Jung-Won Hwang, Young-Tae Jeon, Kooknam Kim and In-Ae Song
J. Clin. Med. 2018, 7(2), 33; https://doi.org/10.3390/jcm7020033 - 19 Feb 2018
Cited by 12 | Viewed by 3249
Abstract
Effective and adequate opioid use and prevention of postoperative complications are important for enhanced recovery after surgery. We examined the effects of postoperative opioid use and postoperative complications on overall survival and recurrence-free survival after esophageal cancer surgery. This retrospective cohort study analyzed [...] Read more.
Effective and adequate opioid use and prevention of postoperative complications are important for enhanced recovery after surgery. We examined the effects of postoperative opioid use and postoperative complications on overall survival and recurrence-free survival after esophageal cancer surgery. This retrospective cohort study analyzed the records of patients diagnosed with esophageal cancer who underwent the Ivor Lewis operation between January 2005 and December 2011. We collected data on total opioid use for 8 days postoperatively, as well as information on postoperative complications (Clavien-Dindo classification). One hundred and twenty-one patients were included in the final analysis. Total opioid use was not significantly associated with overall survival (p = 0.520) and recurrence-free survival (p = 0.818). In contrast, the hazard ratio of postoperative overall survival was significantly higher with respect to Clavien-Dindo classification 1–2 (hazard ratio: 2.009, p = 0.046), 3a–3b (hazard ratio: 5.759, p < 0.001), and 4a–5 (hazard ratio: 3.982, p = 0.020) complications compared to no complications. Additionally, the hazard ratio of the recurrence-free survival was significantly higher in class 1–2 complications (hazard ratio: 2.336, p = 0.028) compared to none. Our study demonstrates that postoperative opioid use is not associated with survival and recurrence-free survival after esophageal cancer surgery, while postoperative complications may increase the hazard ratio for survival and recurrence-free survival. Full article
(This article belongs to the Special Issue Management of Postoperative Pain)
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8 pages, 657 KiB  
Review
Update on the Non-Pharmacological Management of Stroke Prevention in Patients with Atrial Fibrillation
by Aneesh Tolat and Neal Lippman
J. Clin. Med. 2018, 7(2), 32; https://doi.org/10.3390/jcm7020032 - 12 Feb 2018
Cited by 2 | Viewed by 4005
Abstract
Non-surgical left atrial appendage occlusion has emerged as an alternative to anticoagulant therapy in the management of stroke risk in patients with atrial fibrillation. This review reports on some of the more common devices that are currently being used to manage patients in [...] Read more.
Non-surgical left atrial appendage occlusion has emerged as an alternative to anticoagulant therapy in the management of stroke risk in patients with atrial fibrillation. This review reports on some of the more common devices that are currently being used to manage patients in this challenging group. Full article
(This article belongs to the Special Issue Advances in Interventional Cardiology and Vascular Medicine)
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7 pages, 510 KiB  
Article
Canaloplasty in Corticosteroid-Induced Glaucoma. Preliminary Results
by Paolo Brusini, Claudia Tosoni and Marco Zeppieri
J. Clin. Med. 2018, 7(2), 31; https://doi.org/10.3390/jcm7020031 - 11 Feb 2018
Cited by 8 | Viewed by 3618
Abstract
Purpose: to present the mid-term results of canaloplasty in a small cohort of corticosteroid glaucoma patients. Material and Methods: Nine eyes from seven patients with various types of corticosteroid glaucoma in maximum medical therapy underwent canaloplasty. Patients underwent complete ophthalmic examination every six [...] Read more.
Purpose: to present the mid-term results of canaloplasty in a small cohort of corticosteroid glaucoma patients. Material and Methods: Nine eyes from seven patients with various types of corticosteroid glaucoma in maximum medical therapy underwent canaloplasty. Patients underwent complete ophthalmic examination every six months. Success was defined as: post-operative intraocular pressure (IOP) ≤ 21 mmHg and ≤ 16 mmHg without (“complete success”), and with/without medical treatment (“qualified success”). The IOP reduction had to be ≥ 20. The number of medications before and after surgery was considered. The follow-up mean period was 32.7 ± 20.8 months (range 14–72 months). Results: The pre-operative mean IOP was 30.7 ± 7.2 mmHg (range: 24–45). The mean IOP at 6 and 12-month follow-up was 13.1 ± 2.6 mmHg, and 13.7 ± 1.9 mmHg, respectively. Qualified and complete success at 6 and 12 months was 100% for both of the two definitions. The number of medications used preoperatively and at the 12-month follow-up was 4.3 ± 0.7, and 0.2 ± 1.0, respectively. No serious complication was observed. Conclusions: The mid-term results of canaloplasty in patients with corticosteroid-induced glaucoma appear to be very promising. Canaloplasty should be considered as a possible alternative to filtering surgery in this form of glaucoma, when medical therapy is not sufficient to maintain the IOP within reasonable limits. Full article
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8 pages, 187 KiB  
Article
Experience of Nurses in Hemodialysis Care: A Phenomenological Study
by Hosien Shahdadi and Mozhgan Rahnama
J. Clin. Med. 2018, 7(2), 30; https://doi.org/10.3390/jcm7020030 - 11 Feb 2018
Cited by 22 | Viewed by 7380
Abstract
This study aimed to describe the experiences of nurses in hemodialysis care. In this phenomenological study, purposive sampling began and continued until data saturation. The research environment was the Hemodialysis unit. Data was collected through semi-structured interviews. Finally, two main classes and four [...] Read more.
This study aimed to describe the experiences of nurses in hemodialysis care. In this phenomenological study, purposive sampling began and continued until data saturation. The research environment was the Hemodialysis unit. Data was collected through semi-structured interviews. Finally, two main classes and four sub-classes were identified, including factors effective on care (inhibitors and facilitators) and care outcomes (the negative effects of care on the nurse and the positive effects of care on the patient), and “challenging care” as the main theme. As the results show, nurses suffer from several physical and mental harm, and this harm even extends to their family environment, and their families are indirectly affected by the negative effects of this care. Therefore, strengthening management approaches to eliminate the inhibitor factors is essential in order to prevent nurses’ burnout or quitting while improving the quality of care provided by them. Full article
(This article belongs to the Section Epidemiology & Public Health)
15 pages, 218 KiB  
Review
A Practical Review of the Emerging Direct Anticoagulants, Laboratory Monitoring, and Reversal Agents
by Stephanie A. Joppa, Justin Salciccioli, Jill Adamski, Salma Patel, Waldemar Wysokinski, Robert McBane, Farah Al-Saffar, Heidi Esser and Fadi Shamoun
J. Clin. Med. 2018, 7(2), 29; https://doi.org/10.3390/jcm7020029 - 11 Feb 2018
Cited by 31 | Viewed by 8449
Abstract
Millions of patients in the United States use anticoagulation for a variety of indications, such as the prevention of stroke in those with atrial fibrillation (AF) and the treatment and prevention of venous thrombosis. For over six decades warfarin was the only available [...] Read more.
Millions of patients in the United States use anticoagulation for a variety of indications, such as the prevention of stroke in those with atrial fibrillation (AF) and the treatment and prevention of venous thrombosis. For over six decades warfarin was the only available oral anticoagulant, but now several DOACs are available and their use has become more prevalent in recent years. In spite of this increased use, many physicians remain reluctant to prescribe DOACs due to concerns about bleeding and reversibility. Full article
(This article belongs to the Special Issue Image Guided Interventions and Emerging Technologies)
2 pages, 145 KiB  
Editorial
Comment from the Editor to the Special Issue: “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis”
by Roberto Gasparri, Giulia Sedda and Lorenzo Spaggiari
J. Clin. Med. 2018, 7(2), 28; https://doi.org/10.3390/jcm7020028 - 09 Feb 2018
Cited by 2 | Viewed by 2979
Abstract
With this Editorial we want to present the Special Issue “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis” to the scientific community, which aims to gather experts on the early detection of lung cancer in order to implement common efforts [...] Read more.
With this Editorial we want to present the Special Issue “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis” to the scientific community, which aims to gather experts on the early detection of lung cancer in order to implement common efforts in the fight against cancer. Full article
(This article belongs to the Special Issue Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis)
12 pages, 2182 KiB  
Review
Impact of PSP Technique on Clinical Outcomes Following Bioresorbable Scaffolds Implantation
by Luis Ortega-Paz, Salvatore Brugaletta and Manel Sabaté
J. Clin. Med. 2018, 7(2), 27; https://doi.org/10.3390/jcm7020027 - 06 Feb 2018
Cited by 12 | Viewed by 3650
Abstract
Bioresorbable scaffolds (BRS) were introduced in clinical practice to overcome the long-term limitations of newer-generation drug-eluting stents. Despite some initial promising results of the Absorb BRS, safety concerns have led to the discontinuation of the commercialization of this device. Several retrospective studies have [...] Read more.
Bioresorbable scaffolds (BRS) were introduced in clinical practice to overcome the long-term limitations of newer-generation drug-eluting stents. Despite some initial promising results of the Absorb BRS, safety concerns have led to the discontinuation of the commercialization of this device. Several retrospective studies have assessed the impact of the so-called Pre-dilation, Sizing and Post-dilation (PSP) technique concluding that an optimal PSP technique can improve clinical outcomes following BRS implantation. In this article, the definition of the PSP technique, and the current evidence of its impact on clinical outcomes are put in perspective. Additionality, the relationship between the PSP technique and the dual-antiplatelet therapy to prevent scaffold thrombosis is addressed. Finally, the future perspectives of BRS technology in clinical practice are commented. Full article
(This article belongs to the Section Vascular Medicine)
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5 pages, 1482 KiB  
Review
Effect of MUC8 on Airway Inflammation: A Friend or a Foe?
by Hee-Jae Cha and Kyoung Seob Song
J. Clin. Med. 2018, 7(2), 26; https://doi.org/10.3390/jcm7020026 - 06 Feb 2018
Cited by 7 | Viewed by 2937
Abstract
In this review, we compile identifying molecular mechanisms of MUC8 gene expression and studies characterizing the physiological functions of MUC8 in the airway and analyzing how altered MUC8 gene expression in the lung is affected by negative regulators. Full article
(This article belongs to the Section Pulmonology)
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11 pages, 1087 KiB  
Article
Mental Health Effects of Stress over the Life Span of Refugees
by Michael Hollifield, Teddy D. Warner, Barry Krakow and Joseph Westermeyer
J. Clin. Med. 2018, 7(2), 25; https://doi.org/10.3390/jcm7020025 - 06 Feb 2018
Cited by 24 | Viewed by 7432
Abstract
Information about the relative impact of stressful events across the lifespan on the mental health of refugees is needed. Cross-sectional data from a community sample of 135 Kurdish and 117 Vietnamese refugees were fit to a path model about the effects of non-war [...] Read more.
Information about the relative impact of stressful events across the lifespan on the mental health of refugees is needed. Cross-sectional data from a community sample of 135 Kurdish and 117 Vietnamese refugees were fit to a path model about the effects of non-war stress, war-related stress, and post-migration stress on mental health. Kurdish and Vietnamese data were generally consistent with the model. However, war-related stress produced no direct but a large indirect effect through post-migration stress on mental health in Kurds. Vietnamese data indicated a modest direct war-related stress effect but no indirect influence through post-migration stress. Different types of stressful events lead to adverse mental health of displaced refugees in a somewhat group-dependent manner. Implications for prevention and treatment are discussed. Full article
(This article belongs to the Section Mental Health)
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20 pages, 1854 KiB  
Review
Alternative Erythropoietin Receptors in the Nervous System
by Daniela Ostrowski and Ralf Heinrich
J. Clin. Med. 2018, 7(2), 24; https://doi.org/10.3390/jcm7020024 - 02 Feb 2018
Cited by 60 | Viewed by 6692
Abstract
In addition to its regulatory function in the formation of red blood cells (erythropoiesis) in vertebrates, Erythropoietin (Epo) contributes to beneficial functions in a variety of non-hematopoietic tissues including the nervous system. Epo protects cells from apoptosis, reduces inflammatory responses and supports re-establishment [...] Read more.
In addition to its regulatory function in the formation of red blood cells (erythropoiesis) in vertebrates, Erythropoietin (Epo) contributes to beneficial functions in a variety of non-hematopoietic tissues including the nervous system. Epo protects cells from apoptosis, reduces inflammatory responses and supports re-establishment of compromised functions by stimulating proliferation, migration and differentiation to compensate for lost or injured cells. Similar neuroprotective and regenerative functions of Epo have been described in the nervous systems of both vertebrates and invertebrates, indicating that tissue-protective Epo-like signaling has evolved prior to its erythropoietic function in the vertebrate lineage. Epo mediates its erythropoietic function through a homodimeric Epo receptor (EpoR) that is also widely expressed in the nervous system. However, identification of neuroprotective but non-erythropoietic Epo splice variants and Epo derivatives indicated the existence of other types of Epo receptors. In this review, we summarize evidence for potential Epo receptors that might mediate Epo’s tissue-protective function in non-hematopoietic tissue, with focus on the nervous system. In particular, besides EpoR, we discuss three other potential neuroprotective Epo receptors: (1) a heteroreceptor consisting of EpoR and common beta receptor (βcR), (2) the Ephrin (Eph) B4 receptor and (3) the human orphan cytokine receptor-like factor 3 (CRLF3). Full article
(This article belongs to the Special Issue Injury and Repair in the Nervous System)
15 pages, 3984 KiB  
Review
Robotic-Assisted Percutaneous Coronary Intervention: Rationale, Implementation, Case Selection and Limitations of Current Technology
by Michael Ragosta and Kanwar P. Singh
J. Clin. Med. 2018, 7(2), 23; https://doi.org/10.3390/jcm7020023 - 30 Jan 2018
Cited by 13 | Viewed by 4850
Abstract
Interventional cardiologists have witnessed an explosive growth in the field. A wide array of percutaneous procedures allow us to treat numerous cardiac conditions less invasively. However, the way we work has changed very little over the past decades. We continue to stand at [...] Read more.
Interventional cardiologists have witnessed an explosive growth in the field. A wide array of percutaneous procedures allow us to treat numerous cardiac conditions less invasively. However, the way we work has changed very little over the past decades. We continue to stand at the tableside for prolonged periods of time, exposing ourselves to the very real risks of radiation exposure as well as to the associated orthopedic injuries from radiation protection. The precision of our procedures is limited by the distance from the fluoroscopic images and, furthermore, patients are potentially at risk from operator fatigue caused by a physician standing at the table for prolonged periods while wearing cumbersome radiation protection gear. Robotic-assisted coronary intervention removes the operator from the radiation field and has been shown to markedly reduce operator exposure as well as allow for more precise positioning of balloons and stents. This technology holds great promise for making interventional procedures safer and more comfortable for the operators as well as reducing fatigue, potentially improving patient outcomes. Currently, we are in an ‘early adopter’ phase of this technology and this paper reviews the rationale, methodology, optimal case selection, and limitations of robotic-assisted coronary intervention. Full article
(This article belongs to the Special Issue Advances in Interventional Cardiology and Vascular Medicine)
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12 pages, 1843 KiB  
Article
Evaluation of Colorectal Cancer Incidence Trends in the United States (2000–2014)
by Benjamin E. Ansa, Steven S. Coughlin, Ernest Alema-Mensah and Selina A. Smith
J. Clin. Med. 2018, 7(2), 22; https://doi.org/10.3390/jcm7020022 - 30 Jan 2018
Cited by 95 | Viewed by 7902
Abstract
Colorectal cancer (CRC) incidence rates have declined in recent years for people of all races/ethnicities; however, the extent to which the decrease varies annually by demographic and disease-related characteristics is largely unknown. This study examines trends and annual percent change (APC) in the [...] Read more.
Colorectal cancer (CRC) incidence rates have declined in recent years for people of all races/ethnicities; however, the extent to which the decrease varies annually by demographic and disease-related characteristics is largely unknown. This study examines trends and annual percent change (APC) in the incidence among persons diagnosed with CRC in the United States of America from 2000–2014. The data obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program were analyzed, and all persons (N = 577,708) with malignant CRC recorded in the SEER 18 database from 2000 to 2014 were characterized according to sex, race, age at diagnosis, disease site and stage. Incidence rates and APC were calculated for the entire study period. Overall, the incidence rate of CRC decreased from 54.5 in 2000 to 38.6 per 100,000 in 2014, with APC = −2.66 (p < 0.0001). Decline in rates was most profound between 2008 and 2011 from 46.0 to 40.7 per 100,000 (APC = −4.04; p < 0.0001). Rates were higher for males (vs. females; rate ratio (RR) = 1.33) and for blacks (vs. whites; RR = 1.23). Proximal colon cancers at the localized stage were the predominant cancers. An increase in rate was observed among people younger than 50 years (6.6 per 100,000, APC= 1.5). The annual rate of CRC has decreased over time. However, the development and implementation of interventions that further reduce the disparities among demographic and disease-related subgroups are warranted. Full article
(This article belongs to the Section Oncology)
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17 pages, 12269 KiB  
Review
Moonlighting with WDR5: A Cellular Multitasker
by Alissa DuPuy Guarnaccia and William Patrick Tansey
J. Clin. Med. 2018, 7(2), 21; https://doi.org/10.3390/jcm7020021 - 30 Jan 2018
Cited by 88 | Viewed by 9916
Abstract
WDR5 is a highly conserved WD40 repeat-containing protein that is essential for proper regulation of multiple cellular processes. WDR5 is best characterized as a core scaffolding component of histone methyltransferase complexes, but emerging evidence demonstrates that it does much more, ranging from expanded [...] Read more.
WDR5 is a highly conserved WD40 repeat-containing protein that is essential for proper regulation of multiple cellular processes. WDR5 is best characterized as a core scaffolding component of histone methyltransferase complexes, but emerging evidence demonstrates that it does much more, ranging from expanded functions in the nucleus through to controlling the integrity of cell division. The purpose of this review is to describe the current molecular understandings of WDR5, discuss how it participates in diverse cellular processes, and highlight drug discovery efforts around WDR5 that may form the basis of new anti-cancer therapies. Full article
(This article belongs to the Special Issue Trends in Precision Oncology from Data Science)
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18 pages, 244 KiB  
Review
Benzodiazepines II: Waking Up on Sedatives: Providing Optimal Care When Inheriting Benzodiazepine Prescriptions in Transfer Patients
by Jeffrey Guina and Brian Merrill
J. Clin. Med. 2018, 7(2), 20; https://doi.org/10.3390/jcm7020020 - 30 Jan 2018
Cited by 29 | Viewed by 9331
Abstract
This review discusses risks, benefits, and alternatives in patients already taking benzodiazepines when care transfers to a new clinician. Prescribers have the decision—sometimes mutually agreed-upon and sometimes unilateral—to continue, discontinue, or change treatment. This decision should be made based on evidence-based indications (conditions [...] Read more.
This review discusses risks, benefits, and alternatives in patients already taking benzodiazepines when care transfers to a new clinician. Prescribers have the decision—sometimes mutually agreed-upon and sometimes unilateral—to continue, discontinue, or change treatment. This decision should be made based on evidence-based indications (conditions and timeframes), comorbidities, potential drug-drug interactions, and evidence of adverse effects, misuse, abuse, dependence, or diversion. We discuss management tools involved in continuation (e.g., monitoring symptoms, laboratory testing, prescribing contracts, state prescription databases, stages of change) and discontinuation (e.g., tapering, psychotherapeutic interventions, education, handouts, reassurance, medications to assist with discontinuation, and alternative treatments). Full article
(This article belongs to the Section Pharmacology)
11 pages, 1123 KiB  
Article
Red Blood Cell Transfusion Need for Elective Primary Posterior Lumbar Fusion in A High-Volume Center for Spine Surgery
by Giuseppe Ristagno, Simonetta Beluffi, Dario Tanzi, Federica Belloli, Paola Carmagnini, Massimo Croci, Giuseppe D’Aviri, Guido Menasce, Juan C. Pastore, Armando Pellanda, Alberto Pollini and Giorgio Savoia
J. Clin. Med. 2018, 7(2), 19; https://doi.org/10.3390/jcm7020019 - 30 Jan 2018
Cited by 17 | Viewed by 3845
Abstract
(1) Background: This study evaluated the perioperative red blood cell (RBC) transfusion need and determined predictors for transfusion in patients undergoing elective primary lumbar posterior spine fusion in a high-volume center for spine surgery. (2) Methods: Data from all patients undergoing spine surgery [...] Read more.
(1) Background: This study evaluated the perioperative red blood cell (RBC) transfusion need and determined predictors for transfusion in patients undergoing elective primary lumbar posterior spine fusion in a high-volume center for spine surgery. (2) Methods: Data from all patients undergoing spine surgery between 1 January 2014 and 31 December 2016 were reviewed. Patients’ demographics and comorbidities, perioperative laboratory results, and operative time were analyzed in relation to RBC transfusion. Multivariate logistic regression analysis was performed to identify the predictors of transfusion. (3) Results: A total of 874 elective surgeries for primary spine fusion were performed over the three years. Only 54 cases (6%) required RBC transfusion. Compared to the non-transfused patients, transfused patients were mainly female (p = 0.0008), significantly older, with a higher ASA grade (p = 0.0002), and with lower pre-surgery hemoglobin (HB) level and hematocrit (p < 0.0001). In the multivariate logistic regression, a lower pre-surgery HB (OR (95% CI) 2.84 (2.11–3.82)), a higher ASA class (1.77 (1.03–3.05)) and a longer operative time (1.02 (1.01–1.02)) were independently associated with RBC transfusion. (4) Conclusions: In the instance of elective surgery for primary posterior lumbar fusion in a high-volume center for spine surgery, the need for RBC transfusion is low. Factors anticipating transfusion should be taken into consideration in the patient’s pre-surgery preparation. Full article
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9 pages, 210 KiB  
Review
In-Hospital Palliative Care: Should We Need to Reconsider What Role Hospitals Should Have in Patients with End-Stage Disease or Advanced Cancer?
by Paolo Cotogni, Andrea Saini and Anna De Luca
J. Clin. Med. 2018, 7(2), 18; https://doi.org/10.3390/jcm7020018 - 30 Jan 2018
Cited by 26 | Viewed by 7621
Abstract
Traditionally, palliative care (PC) systems focused on the needs of advanced cancer patients, but most patients needing PC have end-stage organ diseases. Similarly, PC models focus on the needs of patients in hospices or at home; however, in most cases PC is provided [...] Read more.
Traditionally, palliative care (PC) systems focused on the needs of advanced cancer patients, but most patients needing PC have end-stage organ diseases. Similarly, PC models focus on the needs of patients in hospices or at home; however, in most cases PC is provided in acute hospitals. Indeed, the symptom burden that these patients experience in the last year of life frequently forces them to seek care in emergency departments. The majority of them are admitted to the hospital and many die. This issue poses important concerns. Despite the efforts of attending healthcare professionals, in-hospital patients do not receive optimal care near the end-of-life. Also, evidence is emerging that delay in identifying patients needing PC have a detrimental impact on their quality of life (QoL). Therefore, there is an urgent need to identify, early and properly, these patients among those hospitalized. Several trials reported the efficacy of PC in improving the QoL in these patients. Each hospital should ensure that a multidisciplinary PC team is available to support attending physicians to achieve the best QoL for both PC patients and their families. This review discusses the role and the impact of in-hospital PC in patients with end-stage disease or advanced cancer. Full article
(This article belongs to the Section Epidemiology & Public Health)
22 pages, 279 KiB  
Review
Benzodiazepines I: Upping the Care on Downers: The Evidence of Risks, Benefits and Alternatives
by Jeffrey Guina and Brian Merrill
J. Clin. Med. 2018, 7(2), 17; https://doi.org/10.3390/jcm7020017 - 30 Jan 2018
Cited by 145 | Viewed by 26858
Abstract
Benzodiazepines are some of the most commonly prescribed medications in the world. These sedative-hypnotics can provide rapid relief for symptoms like anxiety and insomnia, but are also linked to a variety of adverse effects (whether used long-term, short-term, or as needed). Many patients [...] Read more.
Benzodiazepines are some of the most commonly prescribed medications in the world. These sedative-hypnotics can provide rapid relief for symptoms like anxiety and insomnia, but are also linked to a variety of adverse effects (whether used long-term, short-term, or as needed). Many patients take benzodiazepines long-term without ever receiving evidence-based first-line treatments (e.g., psychotherapy, relaxation techniques, sleep hygiene education, serotonergic agents). This review discusses the risks and benefits of, and alternatives to benzodiazepines. We discuss evidence-based indications and contraindications, and the theoretical biopsychosocial bases for effectiveness, ineffectiveness and harm. Potential adverse effects and drug-drug interactions are summarized. Finally, both fast-acting/acute and delayed-action/chronic alternative treatments for anxiety and/or insomnia are discussed. Response to treatment—whether benzodiazepines, other pharmacological agents, or psychotherapy—should be determined based on functional recovery and not merely sedation. Full article
(This article belongs to the Section Pharmacology)
9 pages, 211 KiB  
Review
Biomarkers for Detecting Mitochondrial Disorders
by Josef Finsterer and Sinda Zarrouk-Mahjoub
J. Clin. Med. 2018, 7(2), 16; https://doi.org/10.3390/jcm7020016 - 30 Jan 2018
Cited by 29 | Viewed by 6505
Abstract
(1) Objectives: Mitochondrial disorders (MIDs) are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and [...] Read more.
(1) Objectives: Mitochondrial disorders (MIDs) are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2) Methods: Literature review. (3) Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), MR-spectroscopy (MRS), positron emission tomography (PET), or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF) for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4) Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available) and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs. Full article
14 pages, 6306 KiB  
Article
CERA Attenuates Kidney Fibrogenesis in the db/db Mouse by Influencing the Renal Myofibroblast Generation
by Christin Fischer, Natalie Deininger, Gunter Wolf and Ivonne Loeffler
J. Clin. Med. 2018, 7(2), 15; https://doi.org/10.3390/jcm7020015 - 30 Jan 2018
Cited by 13 | Viewed by 4224
Abstract
Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing [...] Read more.
Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing myofibroblasts can originate from different sources and different mechanisms are involved in the activation process of the myofibroblasts in the fibrotic kidney. In this study, 16-week-old db/db mice, a model for type 2 DN, were treated for two weeks with continuous erythropoietin receptor activator (CERA), a synthetic erythropoietin variant with possible non-hematopoietic, tissue-protective effects. Non-diabetic and diabetic mice treated with placebo were used as controls. The effects of CERA on tubulointerstitial fibrosis (TIF) as well as on the generation of the matrix-producing myofibroblasts were evaluated by morphological, immunohistochemical, and molecular biological methods. The placebo-treated diabetic mice showed significant signs of beginning renal TIF (shown by picrosirius red staining; increased connective tissue growth factor (CTGF), fibronectin and collagen I deposition; upregulated KIM1 expression) together with an increased number of interstitial myofibroblasts (shown by different mesenchymal markers), while kidneys from diabetic mice treated with CERA revealed less TIF and fewer myofibroblasts. The mechanisms, in which CERA acts as an anti-fibrotic agent/drug, seem to be multifaceted: first, CERA inhibits the generation of matrix-producing myofibroblasts and second, CERA increases the ability for tissue repair. Many of these CERA effects can be explained by the finding that CERA inhibits the renal expression of the cytokine TGF-β1. Full article
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10 pages, 371 KiB  
Article
Prevalence of Vitamin D Deficiency Varies Widely by Season in Canadian Children and Adolescents with Sickle Cell Disease
by Kaitlyn L. I. Samson, Heather McCartney, Suzanne M. Vercauteren, John K. Wu and Crystal D. Karakochuk
J. Clin. Med. 2018, 7(2), 14; https://doi.org/10.3390/jcm7020014 - 30 Jan 2018
Cited by 7 | Viewed by 4191
Abstract
Sickle cell disease (SCD) is an inherited disorder caused by a variant (rs334) in the β-globin gene encoding hemoglobin. Individuals with SCD are thought to be at risk of vitamin D deficiency. Our aim was to assess serum 25-hydroxyvitamin D (25OHD) [...] Read more.
Sickle cell disease (SCD) is an inherited disorder caused by a variant (rs334) in the β-globin gene encoding hemoglobin. Individuals with SCD are thought to be at risk of vitamin D deficiency. Our aim was to assess serum 25-hydroxyvitamin D (25OHD) concentrations, estimate deficiency prevalence, and investigate factors associated with 25OHD concentrations in children and adolescents with SCD attending BC Children’s Hospital in Vancouver, Canada. We conducted a retrospective chart review of SCD patients (2–19 y) from 2012 to 2017. Data were available for n = 45 patients with n = 142 25OHD measurements assessed using a EUROIMMUN analyzer (EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany). Additional data were recorded, including age, sex, and season of blood collection. Linear regression was used to measure associations between 25OHD concentration and predictor variables. Overall, mean ± SD 25OHD concentration was 79 ± 36 nmol/L; prevalence of low 25OHD concentrations (<30, <40, and <75 nmol/L) was 5%, 17% and 50%, respectively. Mean 25OHD concentrations measured during Jul–Sep were higher (28 (95% confidence interval CI: 16–40) nmol/L higher, P < 0.001) compared to Jan–Mar. Vitamin D deficiency rates varied widely by season: Based on 25OHD <30 nmol/L, prevalence was 0% in Oct–Dec and 6% in Jan–Mar; based on <40 nmol/L, prevalence was 0% in Oct–Dec and 26% in Jan–Mar. Full article
(This article belongs to the Section Hematology)
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8 pages, 1188 KiB  
Case Report
Intraneural Platelet-Rich Plasma Injections for the Treatment of Radial Nerve Section: A Case Report
by Unai García de Cortázar, Sabino Padilla, Enrique Lobato, Diego Delgado and Mikel Sánchez
J. Clin. Med. 2018, 7(2), 13; https://doi.org/10.3390/jcm7020013 - 29 Jan 2018
Cited by 11 | Viewed by 5934
Abstract
The radial nerve is the most frequently injured nerve in the upper extremity. Numerous options in treatment have been described for radial nerve injury, such as neurolysis, nerve grafts, or tendon transfers. Currently, new treatment options are arising, such as platelet-rich plasma (PRP), [...] Read more.
The radial nerve is the most frequently injured nerve in the upper extremity. Numerous options in treatment have been described for radial nerve injury, such as neurolysis, nerve grafts, or tendon transfers. Currently, new treatment options are arising, such as platelet-rich plasma (PRP), an autologous product with proved therapeutic effect for various musculoskeletal disorders. We hypothesized that this treatment is a promising alternative for this type of nerve pathology. The patient was a healthy 27-year-old man who suffered a deep and long cut in the distal anterolateral region of the right arm. Forty-eight hours after injury, an end-to-end suture was performed without a microscope. Three months after the surgery, an electromyogram (EMG) showed right radial nerve neurotmesis with no tendency to reinnervation. Four months after the trauma, serial intraneural infiltrations of PRP were conducted using ultrasound guidance. The therapeutic effect was assessed by manual muscle testing and by EMG. Fourteen months after the injury and 11 months after the first PRP injection, functional recovery was achieved. The EMG showed a complete reinnervation of the musculature of the radial nerve dependent. The patient remains satisfied with the result and he is able to practice his profession. Conclusions: PRP infiltrations have the potential to enhance the healing process of radial nerve palsy. This case report demonstrates the therapeutic potential of this technology for traumatic peripheral nerve palsy, as well as the apt utility of US-guided PRP injections. Full article
(This article belongs to the Special Issue Injury and Repair in the Nervous System)
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13 pages, 775 KiB  
Article
Evaluation of Two-Diabetes Related microRNAs Suitability as Earlier Blood Biomarkers for Detecting Prediabetes and type 2 Diabetes Mellitus
by Haifa Abdullah Al-Muhtaresh and Ghada Al-Kafaji
J. Clin. Med. 2018, 7(2), 12; https://doi.org/10.3390/jcm7020012 - 26 Jan 2018
Cited by 44 | Viewed by 5605
Abstract
Increased the incidence of prediabetes and type 2 diabetes (T2D) worldwide raises an urgent need to develop effective tools for early disease detection to facilitate future preventive interventions and improve patient’s care. We evaluated the suitability of diabetes-related miR-375 and miR-9 as earlier [...] Read more.
Increased the incidence of prediabetes and type 2 diabetes (T2D) worldwide raises an urgent need to develop effective tools for early disease detection to facilitate future preventive interventions and improve patient’s care. We evaluated the suitability of diabetes-related miR-375 and miR-9 as earlier biomarkers for detecting prediabetes and T2D.TaqMan-based RT-qPCR was used to quantify the expression of miRNAs in peripheral blood of 30 prediabetes patients, 30 T2D patients and 30 non-diabetic healthy controls. Compared to controls, miR-375 and miR-9 were expressed at higher levels in prediabetes patients and progressively more enriched in T2D patients. Both miRNAs were directly associated with the presence of prediabetes and T2D independently of known risk factors to T2D and miR-375 was independently associated with the development of T2D. Both miRNAs were positively correlated with the glycemic status and other T2D risk factors. The ROC analysis indicated good diagnostic abilities for miR-375 to distinguish overall patients from control and prediabetes from T2D patients. Whereas, miR-9 showed lower values and borderline significance in discriminating the subject groups. The combination of miRNAs enhanced the predictability to discriminate patients from control. These results suggest that miR-375 and miR-9 are associated with the susceptibility to developing T2D and miR-375 alone or in combination with miR-9 could serve as biomarkers for early detection of prediabetes and T2D. Full article
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13 pages, 756 KiB  
Review
Controversies and Advances in Gestational Diabetes—An Update in the Era of Continuous Glucose Monitoring
by Marina P. Carreiro, Anelise I. Nogueira and Antonio Ribeiro-Oliveira
J. Clin. Med. 2018, 7(2), 11; https://doi.org/10.3390/jcm7020011 - 25 Jan 2018
Cited by 28 | Viewed by 7032
Abstract
Diabetes in pregnancy, both preexisting type 1 or type 2 and gestational diabetes, is a highly prevalent condition, which has a great impact on maternal and fetal health, with short and long-term implications. Gestational Diabetes Mellitus (GDM) is a condition triggered by metabolic [...] Read more.
Diabetes in pregnancy, both preexisting type 1 or type 2 and gestational diabetes, is a highly prevalent condition, which has a great impact on maternal and fetal health, with short and long-term implications. Gestational Diabetes Mellitus (GDM) is a condition triggered by metabolic adaptation, which occurs during the second half of pregnancy. There is still a lot of controversy about GDM, from classification and diagnosis to treatment. Recently, there have been some advances in the field as well as recommendations from international societies, such as how to distinguish previous diabetes, even if first recognized during pregnancy, and newer diagnostic criteria, based on pregnancy outcomes, instead of maternal risk of future diabetes. These new recommendations will lead to a higher prevalence of GDM, and important issues are yet to be resolved, such as the cost-utility of this increase in diagnoses as well as the determinants for poor outcomes. The aim of this review is to discuss the advances in diagnosis and classification of GDM, as well as their implications in the field, the issue of hyperglycemia in early pregnancy and the role of hemoglobin A1c (HbA1c) during pregnancy. We have looked into the determinants of the poor outcomes predicted by the diagnosis by way of oral glucose tolerance tests, highlighting the relevance of continuous glucose monitoring tools, as well as other possible pathogenetic factors related to poor pregnancy outcomes. Full article
(This article belongs to the Special Issue Therapeutic Strategies for Diabetes in Pregnancy)
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