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J. Clin. Med., Volume 10, Issue 5 (March-1 2021) – 256 articles

Cover Story (view full-size image): Immune thrombocytopenia (ITP) results from a peripheral platelet destruction and an inappropriate bone marrow production. Recent advances have highlighted the multiple pathways involved in ITP pathogenesis such as antibody-dependent cell phagocytosis, complement dependent cytotoxicity, CD8 T cell mediated cytotoxicity, platelet desialylation and insufficient production of thrombopoietin. New upcoming therapies which specifically target one or multiple mechanisms involved in ITP, such as Syk inhibitors, IgG Fc receptor (FcγR) inhibitors, complement inhibitors and neonatal Fc receptor (FcRn) blockers are about to deeply modify the management of ITP, currently based on corticosteroids, intravenous immunoglobulins, thrombopoietin receptor agonists, immunosuppressants and splenectomy. View this paper
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Open AccessReview
Genetic Cardiomyopathies: The Lesson Learned from hiPSCs
J. Clin. Med. 2021, 10(5), 1149; https://doi.org/10.3390/jcm10051149 - 09 Mar 2021
Viewed by 496
Abstract
Genetic cardiomyopathies represent a wide spectrum of inherited diseases and constitute an important cause of morbidity and mortality among young people, which can manifest with heart failure, arrhythmias, and/or sudden cardiac death. Multiple underlying genetic variants and molecular pathways have been discovered in [...] Read more.
Genetic cardiomyopathies represent a wide spectrum of inherited diseases and constitute an important cause of morbidity and mortality among young people, which can manifest with heart failure, arrhythmias, and/or sudden cardiac death. Multiple underlying genetic variants and molecular pathways have been discovered in recent years; however, assessing the pathogenicity of new variants often needs in-depth characterization in order to ascertain a causal role in the disease. The application of human induced pluripotent stem cells has greatly helped to advance our knowledge in this field and enabled to obtain numerous in vitro patient-specific cellular models useful to study the underlying molecular mechanisms and test new therapeutic strategies. A milestone in the research of genetically determined heart disease was the introduction of genomic technologies that provided unparalleled opportunities to explore the genetic architecture of cardiomyopathies, thanks to the generation of isogenic pairs. The aim of this review is to provide an overview of the main research that helped elucidate the pathophysiology of the most common genetic cardiomyopathies: hypertrophic, dilated, arrhythmogenic, and left ventricular noncompaction cardiomyopathies. A special focus is provided on the application of gene-editing techniques in understanding key disease characteristics and on the therapeutic approaches that have been tested. Full article
(This article belongs to the Special Issue Clinical and Research of Genetic Cardiomyopathies)
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Open AccessArticle
Association of Genetic Polymorphisms in Oxidative Stress and Inflammation Pathways with Glaucoma Risk and Phenotype
J. Clin. Med. 2021, 10(5), 1148; https://doi.org/10.3390/jcm10051148 - 09 Mar 2021
Viewed by 333
Abstract
Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. [...] Read more.
Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma. Full article
(This article belongs to the Special Issue Recent Clinical Research on Glaucoma)
Open AccessReview
The Biochemical Diagnosis of Acromegaly
J. Clin. Med. 2021, 10(5), 1147; https://doi.org/10.3390/jcm10051147 - 09 Mar 2021
Viewed by 349
Abstract
Background: The diagnosis of acromegaly still poses a clinical challenge, and prolonged diagnostic delay is common. The most important assays for the biochemical diagnosis and management of acromegaly are growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Objective: Discuss the role of IGF-1, [...] Read more.
Background: The diagnosis of acromegaly still poses a clinical challenge, and prolonged diagnostic delay is common. The most important assays for the biochemical diagnosis and management of acromegaly are growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Objective: Discuss the role of IGF-1, basal serum GH, and nadir GH after oral glucose tolerance test (OGTT) for the diagnosis, management, and treatment of patients with acromegaly. Methods: We performed a narrative review of the published data on the biochemical diagnosis and monitoring of acromegaly. An English-language search for relevant studies was conducted on PubMed from inception to 1 January 2021. The reference lists of relevant studies were also reviewed. Results: Serum IGF-1 levels, basal GH values, and nadir GH after OGTT play a major role in the diagnosis, management, and treatment of patients with acromegaly. Measurement of IGF-1 levels is the key factor in the diagnosis and monitoring of acromegaly, but basal and nadir GH following OGTT are also important. However, several factors may significantly influence the concentrations of these hormones, including assay methods, physiologic and pathologic factors. In some cases, discordant GH and IGF-1 levels may be challenging and usually requires additional data and monitoring. Conclusion: New GH and IGF-1 standards are much more precise and provide more accurate tools to diagnose and monitor patients with acromegaly. However, all these biochemical tools have their limitations, and these should be taken under consideration, along with the history, clinical features and imaging studies, when assessing patients for acromegaly. Full article
Open AccessReview
Ischemic Stroke and Heart Failure: Facts and Numbers. An Update
J. Clin. Med. 2021, 10(5), 1146; https://doi.org/10.3390/jcm10051146 - 09 Mar 2021
Viewed by 401
Abstract
Heart failure (HF) is a severe clinical syndrome accompanied by a number of comorbidities. Ischemic stroke occurs frequently in patients with HF as a complication of the disease. In the present review, we aimed to summarize the current state of research on the [...] Read more.
Heart failure (HF) is a severe clinical syndrome accompanied by a number of comorbidities. Ischemic stroke occurs frequently in patients with HF as a complication of the disease. In the present review, we aimed to summarize the current state of research on the role of cardio–cerebral interactions in the prevalence, etiology, and prognosis of both diseases. The main pathophysiological mechanisms underlying the development of stroke in HF and vice versa are discussed. In addition, we reviewed the results of recent clinical trials investigating the prevalence and prevention of stroke in patients with HF. Full article
(This article belongs to the Special Issue Intracerebral Hemorrhage: Clinical and Neuroimaging Characteristics)
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Open AccessArticle
Cancer Patients’ Prehospital Emergency Care: Post Hoc Analysis from the French Prospective Multicenter Study EPICANCER
J. Clin. Med. 2021, 10(5), 1145; https://doi.org/10.3390/jcm10051145 - 09 Mar 2021
Viewed by 589
Abstract
Background: Very little data are available concerning the prehospital emergency care of cancer patients. The objective of this study is to report the trajectories and outcomes of cancer patients attended by prehospital emergency services. Methods: This was an ancillary study from a three-day [...] Read more.
Background: Very little data are available concerning the prehospital emergency care of cancer patients. The objective of this study is to report the trajectories and outcomes of cancer patients attended by prehospital emergency services. Methods: This was an ancillary study from a three-day cross-sectional prospective multicenter study in France. Adult patients with cancer were included if they called the emergency medical dispatch center Service d’Aide Médicale Urgente (SAMU). The study was registered on ClinicalTrials.gov (NCT03393260, accessed on 8th January 2018). Results: During the study period, 1081 cancer patients called the SAMU. The three most frequent reasons were dyspnea (20.2%), neurological disorder (15.4%), and fatigue (13.1%). Among those patients, 949 (87.8%) were directed to the hospital, among which 802 (90.8%) were directed to an emergency department (ED) and 44 (5%) were transported directly to an intensive care unit (ICU). A mobile intensive care unit (MICU) was dispatched 213 (31.6%) times. The decision to dispatch an MICU seemed generally based on the patient’s reason for seeking emergency care and the presence of severity signs rather than on the malignancy or the patient general health status. Among the patients who were directed to the ED, 98 (16.1%) were deceased on day 30. Mortality was 15.4% for those patients directed to the ED but who were not admitted to the ICU in the next 7 days, 28.2% for those who were admitted to ICU in the next 7 days, and 56.1% for those patients transported by the MICU directly to the ICU. Conclusion: Cancer patients attending prehospital emergency care were most often directed to EDs. Patients who were directly transported to the ICU had a high mortality rate, raising the question of improving triage policies. Full article
(This article belongs to the Section Emergency Medicine)
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Open AccessArticle
Sleeve Gastrectomy Is Associated with a Greater Reduction in Plasma Liver Enzymes Than Bypass Surgeries—A Registry-Based Two-Year Follow-Up Analysis
J. Clin. Med. 2021, 10(5), 1144; https://doi.org/10.3390/jcm10051144 - 09 Mar 2021
Viewed by 498
Abstract
Bariatric surgeries may lead to an improvement in metabolic fatty liver disease, and a reduction in the levels of the hepatic enzyme Alanine Aminotransferase (ALT). We compared the effects of Sleeve Gastrectomy (SG), Roux en Y Gastric Bypass (RYGB) and One Anastomosis Gastric [...] Read more.
Bariatric surgeries may lead to an improvement in metabolic fatty liver disease, and a reduction in the levels of the hepatic enzyme Alanine Aminotransferase (ALT). We compared the effects of Sleeve Gastrectomy (SG), Roux en Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) on the levels of ALT by analysis of two-year follow-up data from 4980 patients in the Israeli Bariatric Registry that included laboratory tests and demographic information. Pre-operative characteristics of patients, and particularly levels of liver enzymes, were similar across surgery types. Regression modeling and retrospective matching showed that SG was superior to RYGB and OAGB in reducing ALT levels, and in reducing the fraction of patients with abnormally high ALT levels. Two-year post-surgery, an increase in ALT levels from normal to abnormal levels was observed in 5% of SG patients, and in 18% and 23% of RYGB and OAGB patients. In conclusion, SG leads to a greater reduction in ALT levels compared with bypass surgeries and a lower incidence of post-surgical elevation of ALT levels. Further studies are required to identify the cause for the rise in liver enzymes, and to determine whether ALT levels correlate with liver pathology especially following bariatric surgery. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessArticle
Acute Management Should Be Optimized in Patients with Less Specific Stroke Symptoms: Findings from a Retrospective Observational Study
J. Clin. Med. 2021, 10(5), 1143; https://doi.org/10.3390/jcm10051143 - 09 Mar 2021
Viewed by 273
Abstract
Anterior circulation stroke (ACS) is associated with typical symptoms, while posterior circulation stroke (PCS) may cause a wide spectrum of less specific symptoms. We aim to assess the correlation between the initial presentation of acute ischemic stroke (AIS) symptoms and the treatment timeline. [...] Read more.
Anterior circulation stroke (ACS) is associated with typical symptoms, while posterior circulation stroke (PCS) may cause a wide spectrum of less specific symptoms. We aim to assess the correlation between the initial presentation of acute ischemic stroke (AIS) symptoms and the treatment timeline. Using a retrospective, observational, single-center study, the set consists of 809 AIS patients treated with intravenous thrombolysis (IVT) and/or endovascular treatment (EVT). We investigate the impact of baseline clinical AIS symptoms and the affected vascular territory on recanalization times in patients treated with IVT only and EVT (±IVT). Regarding the IVT-only group, increasing the National Institutes of Health Stroke Scale (NIHSS) score on admission and speech difficulties are associated with shorter (by 1.59 ± 0.76 min per every one-point increase; p = 0.036, and by 24.56 ± 8.42 min; p = 0.004, respectively) and nausea/vomiting with longer (by 43.72 ± 13.13 min; p = 0.001) onset-to-needle times, and vertigo with longer (by 8.58 ± 3.84 min; p = 0.026) door-to-needle times (DNT). Regarding the EVT (±IVT) group, coma is associated with longer (by 22.68 ± 6.05 min; p = 0.0002) DNT, anterior circulation stroke with shorter (by 47.32 ± 16.89 min; p = 0.005) onset-to-groin time, and drooping of the mouth corner with shorter (by 20.79 ± 6.02 min; p = 0.0006) door-to-groin time. Our results demonstrate that treatment is initiated later in strokes with less specific symptoms than in strokes with typical symptoms. Full article
(This article belongs to the Special Issue Thrombolysis and Thrombectomy in Acute Ischemic Stroke)
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Open AccessArticle
Partial Lipodystrophy and LMNA p.R545H Variant
J. Clin. Med. 2021, 10(5), 1142; https://doi.org/10.3390/jcm10051142 - 09 Mar 2021
Viewed by 325
Abstract
Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. We herein examine the [...] Read more.
Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. We herein examine the case of a patient carrying a heterozygous LMNA c.1634G>A (p.R545H) variant with a mild, transient myopathy, who was referred to our center for the suspicion of lipodystrophy. At physical examination, an abnormal distribution of subcutaneous fat was noticed, with fat accumulation in the anterior regions of the neck, resembling the fat distribution pattern of familial partial lipodystrophy type 2 (FPLD2). The R545H missense variant has been found at very low allelic frequency in public databases, and in silico analysis showed that this amino acid substitution is predicted to have a damaging role. Other patients carrying the heterozygous LMNA p.R545H allele have shown a marked clinical heterogeneity in terms of phenotypic body fat distribution and severity of organ system involvement. These findings indicate that the LMNA p.R545H heterozygous variant exhibits incomplete penetrance and highly variable expressivity. We hypothesized that additional genetic factors, epigenetic mechanisms, or environmental triggers might explain the variable expressivity of phenotypes among various patients. Full article
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Open AccessReview
Efficacy of Surgery for the Treatment of Gastric Cancer Liver Metastases: A Systematic Review of the Literature and Meta-Analysis of Prognostic Factors
J. Clin. Med. 2021, 10(5), 1141; https://doi.org/10.3390/jcm10051141 - 09 Mar 2021
Viewed by 267
Abstract
Background: In the last 10 years, the management of patients with gastric cancer liver metastases (GCLM) has changed from chemotherapy alone, towards a multidisciplinary treatment with liver surgery playing a leading role. The aim of this systematic review and meta-analysis is to assess [...] Read more.
Background: In the last 10 years, the management of patients with gastric cancer liver metastases (GCLM) has changed from chemotherapy alone, towards a multidisciplinary treatment with liver surgery playing a leading role. The aim of this systematic review and meta-analysis is to assess the efficacy of hepatectomy for GCLM and to analyze the impact of related prognostic factors on long-term outcomes. Methods: The databases PubMed (Medline), EMBASE, and Google Scholar were searched for relevant articles from January 2010 to September 2020. We included prospective and retrospective studies that reported the outcomes after hepatectomy for GCLM. A systematic review of the literature and meta-analysis of prognostic factors was performed. Results: We included 40 studies, including 1573 participants who underwent hepatic resection for GCLM. Post-operative morbidity and 30-day mortality rates were 24.7% and 1.6%, respectively. One-year, 3-years, and 5-years overall survival (OS) were 72%, 37%, and 26%, respectively. The 1-year, 3-years, and 5-years disease-free survival (DFS) were 44%, 24%, and 22%, respectively. Well-moderately differentiated tumors, pT1–2 and pN0–1 adenocarcinoma, R0 resection, the presence of solitary metastasis, unilobar metastases, metachronous metastasis, and chemotherapy were all strongly positively associated to better OS and DFS. Conclusion: In the present study, we demonstrated that hepatectomy for GCLM is feasible and provides benefits in terms of long-term survival. Identification of patient subgroups that could benefit from surgical treatment is mandatory in a multidisciplinary setting. Full article
(This article belongs to the Special Issue Multimodality Treatments in Metastatic Gastric Cancer)
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Open AccessReview
Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making
J. Clin. Med. 2021, 10(5), 1140; https://doi.org/10.3390/jcm10051140 - 09 Mar 2021
Viewed by 482
Abstract
Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and [...] Read more.
Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight. Full article
(This article belongs to the Special Issue Osteoporosis Treatment: Recent Developments and Ongoing Challenges)
Open AccessReview
Analysis of the Clinical and Epidemiological Meaning of Screening Test for SARS-CoV-2: Considerations in the Chronic Kidney Disease Patients during the COVID-19 Pandemic
J. Clin. Med. 2021, 10(5), 1139; https://doi.org/10.3390/jcm10051139 - 09 Mar 2021
Viewed by 516
Abstract
The COronaVIrus Disease 19 (COVID-19) pandemic is an emerging reality in nephrology. In a continuously changing scenario, we need to assess our patients’ additional risk in terms of attending hemodialysis treatments, follow-up peritoneal dialysis, and kidney transplant visits. The prevalence of severe acute [...] Read more.
The COronaVIrus Disease 19 (COVID-19) pandemic is an emerging reality in nephrology. In a continuously changing scenario, we need to assess our patients’ additional risk in terms of attending hemodialysis treatments, follow-up peritoneal dialysis, and kidney transplant visits. The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-20 infection in the general population plays a pivotal role in estimating the additional COVID-19 risk in chronic kidney disease (CKD) patients. Unfortunately, local prevalence is often obscure, and when we have an estimation, we neglect the number of asymptomatic subjects in the same area and, consequently, the risk of infection in CKD patients. Furthermore, we still have the problem of managing COVID-19 diagnosis and the test’s accuracy. Currently, the gold standard for SARS-CoV-2 detection is a real-time reverse transcription-polymerase chain reaction (rRT-PCR) on respiratory tract samples. rRT-PCR presents some vulnerability related to pre-analytic and analytic problems and could impact strongly on its diagnostic accuracy. Specifically, the operative proceedings to obtain the samples and the different types of diagnostic assay could affect the results of the test. In this scenario, knowing the local prevalence and the local screening test accuracy helps the clinician to perform preventive measures to limit the diffusion of COVID-19 in the CKD population. Full article
(This article belongs to the Special Issue Impact of COVID-19 Pandemic on Global Diseases and Human Well-Being)
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Open AccessArticle
Pilot Study to Evaluate the Efficacy of Polynucleotide Sodium Compared to Sodium Hyaluronate and Crosslinked Sodium Hyaluronate in Patients with Knee Osteoarthritis
J. Clin. Med. 2021, 10(5), 1138; https://doi.org/10.3390/jcm10051138 - 09 Mar 2021
Viewed by 405
Abstract
Degenerative arthritis of the knee joint has become a major social problem worldwide due to population aging. There are several treatment options for knee osteoarthritis, and the intraarticular injection of sodium hyaluronate is commonly selected by many clinicians as a nonsurgical treatment. However, [...] Read more.
Degenerative arthritis of the knee joint has become a major social problem worldwide due to population aging. There are several treatment options for knee osteoarthritis, and the intraarticular injection of sodium hyaluronate is commonly selected by many clinicians as a nonsurgical treatment. However, the efficacy of the treatment is controversial. In this pilot study, we aimed to compare polynucleotide sodium (Conjuran®) with sodium hyaluronate (Hyruan Plus®) and 1,4-butanediol diglycidyl ether-crosslinked sodium hyaluronate (Synovian®) in terms of analgesic efficacy after intraarticular injection in patients with knee osteoarthritis. One of the three intraarticular agents was selected according to what agents were available for outpatients when each patient was enrolled in the study. The 15 enrolled patients were subdivided into 3 groups of 5 patients each. Three injections were performed under ultrasound guidance at a 1-week intervals over a total of 3 weeks. The visual analog scale (VAS) score, the Korean version of the Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), the EuroQol five-dimension scale (EQ-5D) score, and the Korean version of the painDETECT Questionnaire (K-PDQ) score were evaluated before injection and at 1, 2, and 6 weeks after the start of the treatment protocol. The primary endpoint was the change in weight-bearing pain at 4 weeks after the last injection. Secondary endpoints included pain at rest and during walking and the K-WOMAC, EQ-5D, and K-PDQ scores. Weight-bearing pain decreased significantly more from pretreatment to 6 weeks after the start of the treatment protocol in the polynucleotide sodium-treated patients than in the patients who were treated with other agents (p = 0.006, one-way ANOVA). There were no significant between-group differences in the other secondary endpoints. No adverse events occurred. In conclusion, polynucleotide sodium could effectively reduce weight-bearing pain in the patients with knee osteoarthritis compared to standard hyaluronic acid viscosupplementation. Full article
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Open AccessArticle
MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation
J. Clin. Med. 2021, 10(5), 1137; https://doi.org/10.3390/jcm10051137 - 09 Mar 2021
Viewed by 305
Abstract
Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent [...] Read more.
Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.59 ± 2.39 years), assessing CRP, galectin-3, monocyte chemoattractant protein-1 (MCP-1), N-terminal fragment of brain natriuretic peptide (NT-proBNP) and troponin-I plasma levels. The primary outcome was the combination of cardiovascular events (acute coronary syndrome, stroke or transient ischemic event, heart failure or death). Patients with persistent inflammation (n = 343) showed higher NT-proBNP and MCP-1 plasma levels compared to patients with CRP < 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP < 2 mg/L. However, NT-proBNP and MCP-1 plasma levels were associated with increased risk of the primary outcome in patients with persistent inflammation. When patients were divided by type of event, MCP-1 was associated with an increased risk of acute ischemic events. A significant interaction between MCP-1 and persistent inflammation was found (synergy index: 6.17 (4.39–7.95)). In conclusion, MCP-1 plasma concentration is associated with recurrent cardiovascular events in patients with persistent inflammation. Full article
(This article belongs to the Section Cardiovascular Medicine)
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Open AccessArticle
Prognostic Markers for Chorioamnionitis: IL-6, TNF-α, and MMP-8 in Vaginally Obtained Amniotic Fluid
J. Clin. Med. 2021, 10(5), 1136; https://doi.org/10.3390/jcm10051136 - 08 Mar 2021
Viewed by 337
Abstract
Background. Earlier chorioamnionitis diagnosis is crucial to improve maternal and neonatal health outcomes. This study was conducted to evaluate the inlerleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and matrix metalloproteinase 8 (MMP-8) levels in vaginally obtained amniotic fluid to investigate their prognostic value [...] Read more.
Background. Earlier chorioamnionitis diagnosis is crucial to improve maternal and neonatal health outcomes. This study was conducted to evaluate the inlerleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and matrix metalloproteinase 8 (MMP-8) levels in vaginally obtained amniotic fluid to investigate their prognostic value and to determine the most appropriate cut-off values for the prediction of chorioamnionitis. Methods. This case control study included women who were diagnosed with preterm premature rupture of the membranes before 34 weeks of gestation and were admitted to Vilnius University Hospital Santaros Klinikos. Free-leaking amniotic fluid was obtained vaginally with a sterile speculum less than 48h before delivery. Amniotic fluid IL-6, TNF-α, and MMP-8 levels were determined by the Enzyme Linked Immunosorbent Assay. Diagnosis of chorioamnionitis was confirmed by histological examination of the placenta and membranes after delivery. Results. The study included 156 women, 65 patients in the histological chorioamnionitis group (Group I) and 91 in a group without diagnosed histological chorioamnionitis (Group II). The median concentrations of IL-6, MMP-8, and TNF-α in amniotic fluid were statistically significantly higher in Group I than in Group II (p-value < 0.001). The area under the curve of TNF-α and MMP-8 were higher than the area under the curve of IL-6 (0.91, 0.89, and 0.81, respectively). No statistically significant difference was found when comparing the receiver operating characteristic (ROC) curves of TNF-α and MMP-8. The optimum cut-off values for the prediction of chorioamnionitis were found to be 1389.82 pg/mL for IL-6, 21.17 pg/mL for TNF-α, and 172.53 ng/mL for MMP-8. The sensitivity, specificity, positive prognostic value (PPV), and negative prognostic value (NPV) of the IL-6 cut-off for chorioamnionitis were 88%, 70%, 67%, and 89%, respectively. The sensitivity, specificity, PPV, and NPV of the TNF-α cut-off were 88%, 84%, 79%, and 90%, respectively. The sensitivity, specificity, PPV, and NPV of the MMP-8 cut-off were 80%, 87%, 81%, and 86%, respectively. Conclusions. The vaginally obtained amniotic fluid IL-6, MMP-8, and TNF-α seem to be good predictors for chorioamnionitis of patients with preterm premature rupture of membranes before 34 weeks of gestation. The noninvasive technique of sampling amniotic fluid could be alternative method to invasive amniocentesis. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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Open AccessArticle
The Addition of Transdermal Delivery of Neostigmine and Glycopyrrolate by Iontophoresis to Thrice Weekly Bowel Care in Persons with Spinal Cord Injury: A Pilot Study
J. Clin. Med. 2021, 10(5), 1135; https://doi.org/10.3390/jcm10051135 - 08 Mar 2021
Viewed by 380
Abstract
Persons with spinal cord injury (SCI) have neurogenic bowel disorders characterized by difficulty with evacuation (DWE), fecal incontinence, and discoordination of defecation. Six medically stable in-patients with SCI with a mean age of 57 ± 10 years (range: 39–66 years) and time since [...] Read more.
Persons with spinal cord injury (SCI) have neurogenic bowel disorders characterized by difficulty with evacuation (DWE), fecal incontinence, and discoordination of defecation. Six medically stable in-patients with SCI with a mean age of 57 ± 10 years (range: 39–66 years) and time since injury of 18 ± 17 years (range: 3–47 years) were investigated. Standard of care (SOC) for bowel care was followed by two weeks of SOC plus neostigmine (0.07 mg/kg) and glycopyrrolate (0.014 mg/kg) administered transcutaneously by iontophoresis thrice weekly for two weeks while patients continued to receive SOC. The primary endpoint was time to bowel evacuation. Body weights and abdominal radiographs were obtained. Ten questions related to bowel function and the Treatment Satisfaction Questionnaire for Medication were acquired after each arm. Bowel evacuation time decreased after the dual drug intervention arm (106.9 ± 68.4 vs. 40.8 ± 19.6 min; p < 0.0001). Body weight decreased (2.78 ± 0.98 kg; p < 0.0001), a finding confirmed on abdominal radiograph. Both questionnaires demonstrated improvement after the dual drug intervention arm. No major adverse events occurred. The addition of neostigmine and glycopyrrolate by transcutaneous administration to SOC for bowel care in persons with SCI and DWE resulted in the safe, effective, and predictable bowel evacuation with subjective improvement in bowel care. Full article
(This article belongs to the Special Issue Neurogenic Bowel Dysfunction)
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Open AccessArticle
Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy
J. Clin. Med. 2021, 10(5), 1134; https://doi.org/10.3390/jcm10051134 - 08 Mar 2021
Viewed by 351
Abstract
To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing [...] Read more.
To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (PD). Study population: 94 patients with recurrence of MPM after multimodality treatment underwent macroscopic complete resection (52.1% with EPP and 47.9% with PD) between July 1994 and February 2020. Distant spread was the most frequent pattern of recurrence (71.3%), mostly in the EPP group, while the PD group showed a higher local-only failure rate. Post-recurrence treatment was administered in 86.2%, whereas best supportive care was administered in 13.8%. Median post-recurrence survival (PRS) was 12 months (EPP 14 vs. PD 8 months, p = 0.4338). At multivariate analysis, predictors of best PRS were epithelial histology (p = 0.026, HR 0.491, IC95% 0.263–0.916), local failure (p = 0.027, HR 0.707, IC95% 0.521–0.961), DFS ≥ 12 months (p = 0.006, HR 0.298, IC95% 0.137–0.812) and post-recurrence medical treatment (p = 0.046, HR 0.101, IC95% 0.897–0.936). The type of surgical intervention seems not to influence the PRS if patients are fit enough to face post-recurrence treatments. In patients with a prolonged disease-free interval, in the case of recurrence the most appropriate treatment seems to be the systemic medical therapy, even in the case of local-only relapse. Full article
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Open AccessReview
An Update on the Role of Ubiquitination in Melanoma Development and Therapies
J. Clin. Med. 2021, 10(5), 1133; https://doi.org/10.3390/jcm10051133 - 08 Mar 2021
Viewed by 324
Abstract
The ubiquitination system plays a critical role in regulation of large array of biological processes and its alteration has been involved in the pathogenesis of cancers, among them cutaneous melanoma, which is responsible for the most deaths from skin cancers. Over the last [...] Read more.
The ubiquitination system plays a critical role in regulation of large array of biological processes and its alteration has been involved in the pathogenesis of cancers, among them cutaneous melanoma, which is responsible for the most deaths from skin cancers. Over the last decades, targeted therapies and immunotherapies became the standard therapeutic strategies for advanced melanomas. However, despite these breakthroughs, the prognosis of metastatic melanoma patients remains unoptimistic, mainly due to intrinsic or acquired resistances. Many avenues of research have been investigated to find new therapeutic targets for improving patient outcomes. Because of the pleiotropic functions of ubiquitination, and because each step of ubiquitination is amenable to pharmacological targeting, much attention has been paid to the role of this process in melanoma development and resistance to therapies. In this review, we summarize the latest data on ubiquitination and discuss the possible impacts on melanoma treatments. Full article
(This article belongs to the Special Issue New Advances in Melanoma)
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Open AccessArticle
The Association of Oxidative Stress in the Uvular Mucosa with Obstructive Sleep Apnea Syndrome: A Clinical Study
J. Clin. Med. 2021, 10(5), 1132; https://doi.org/10.3390/jcm10051132 - 08 Mar 2021
Viewed by 304
Abstract
The hypothesis that individuals with obstructive sleep apnea syndrome (OSAS) demonstrate oxidative stress in the uvular mucosa that correlates with OSAS occurrence was investigated. A total of 128 participants (mean age 45.8, mean body mass index 30.7, female–male ratio 1:20) were divided into [...] Read more.
The hypothesis that individuals with obstructive sleep apnea syndrome (OSAS) demonstrate oxidative stress in the uvular mucosa that correlates with OSAS occurrence was investigated. A total of 128 participants (mean age 45.8, mean body mass index 30.7, female–male ratio 1:20) were divided into the non-OSAS group (apnea–hypopnea index—AHI < 5) and OSAS-group (AHI ≥ 5), in which mild (5 ≤ AHI < 15), moderate (15 ≤ AHI < 30), and severe (AHI ≥ 30) sub-groups were distinguished. Laryngological examination, Epworth Sleep Scale questionnaire, and home sleep study were performed to obtain AHI, mean oxygen saturation, and lowest oxygen saturation. Total oxidative status (TOS) and total antioxidative status (TAS) were assayed in the uvular mucosa taken during palatoplasty or palatopharyngoplasty. The severity of oxidative stress was expressed as oxidative stress index (OSI). Oxidative/reductive imbalance was noted in the mucosa of the uvula of OSAS individuals, and TAS of the uvular mucosa negatively correlated with the severity of this syndrome. TOS and OSI in the mild, moderate, and severe OSAS were higher than in the non-OSAS group, whereas TAS of the uvular mucosa in the OSAS group was lower compared to the non-OSAS group. In conclusion, oxidative stress in the uvular mucosa is associated with the occurrence of OSAS. Full article
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Open AccessReview
Haptoglobin and Its Related Protein, Zonulin—What Is Their Role in Spondyloarthropathy?
J. Clin. Med. 2021, 10(5), 1131; https://doi.org/10.3390/jcm10051131 - 08 Mar 2021
Viewed by 350
Abstract
Haptoglobin (Hp) is an acute phase protein which supports the immune response and protects tissues from free radicals. Its concentration correlates with disease activity in spondyloarthropathies (SpAs). The Hp polymorphism determines the functional differences between Hp1 and Hp2 protein products. The role of [...] Read more.
Haptoglobin (Hp) is an acute phase protein which supports the immune response and protects tissues from free radicals. Its concentration correlates with disease activity in spondyloarthropathies (SpAs). The Hp polymorphism determines the functional differences between Hp1 and Hp2 protein products. The role of the Hp polymorphism has been demonstrated in many diseases. In particular, the Hp 2-2 phenotype has been associated with the unfavorable course of some inflammatory and autoimmune disorders. Its potential role in modulating the immune system in SpA is still unknown. This article contains pathophysiological considerations on the potential relationship between Hp, its polymorphism and SpA. Full article
(This article belongs to the Special Issue Spondyloarthritis: From Pathophysiology to Treatment)
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Open AccessArticle
Association between Sudden Sensorineural Hearing Loss and Lyme Disease
J. Clin. Med. 2021, 10(5), 1130; https://doi.org/10.3390/jcm10051130 - 08 Mar 2021
Viewed by 314
Abstract
Objectives: Sudden sensorineural hearing loss (SSNHL) is defined as sensorineural hearing loss of 30 dB or more over at least three adjacent audiometric frequencies occurring within a 72-h period of time. One of the causes of SSNHL could be the progressive inflammatory state [...] Read more.
Objectives: Sudden sensorineural hearing loss (SSNHL) is defined as sensorineural hearing loss of 30 dB or more over at least three adjacent audiometric frequencies occurring within a 72-h period of time. One of the causes of SSNHL could be the progressive inflammatory state caused by an infection. The aim of this study was to assess the prevalence of SSNHL caused by various factors, most importantly those potentially related to Lyme disease. Material and Methods: The study includes a group of 86 patients between the ages of 20 and 70 who were hospitalized due to SSNHL between 2017 and 2018. All of these patients underwent a detailed medical interview and an otolaryngological examination, including audiological and diagnostic tests. Additionally, ELISA and Western blot tests were performed to confirm the diagnosis of Lyme disease. Results: In this group of 86 patients, nine patients presented with positive antibodies toward Borrelia burgdorferi sensu lato. This group was treated with antibiotics and experienced partial or complete regression of their deafness. This may suggest a relationship between SSNHL and Lyme disease. Conclusion: Infections caused by Borrelia burgdorferi may contribute to the development of inflammatory and angiopathic lesions, which are a possible cause of SSNHL. The longer the duration of the infection, the greater the likelihood of permanent and irreversible changes in the vessels of the cochlea or auditory nerve. Therefore, serological tests for Borrelia burgdorferi should be performed during the diagnosis of SSNHL as a possible cause of this illness. Full article
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Open AccessArticle
Integrating Muscle Health in Predicting the Risk of Asymptomatic Vertebral Fracture in Older Adults
J. Clin. Med. 2021, 10(5), 1129; https://doi.org/10.3390/jcm10051129 - 08 Mar 2021
Viewed by 262
Abstract
Background: The utility of muscle health for predicting asymptomatic vertebral fracture (VF) is uncertain. We aimed to determine the effects of muscle health on bone quantity and quality in the older adults and to integrate these factors into a predictive model for VF. [...] Read more.
Background: The utility of muscle health for predicting asymptomatic vertebral fracture (VF) is uncertain. We aimed to determine the effects of muscle health on bone quantity and quality in the older adults and to integrate these factors into a predictive model for VF. Methods: We prospectively recruited participants with a body mass index <37 kg/m2. The total lean mass (TLM), appendicular skeletal muscle index, presence of sarcopenia, and bone mineral density were determined by dual-energy X-ray absorptiometry, and bone quality by the trabecular bone score (TBS). VF was diagnosed based on spine radiography. Results: A total of 414 females and 186 males were included; 257 participants had VF. Lower TLM was significantly associated with poorer bone quantity and quality in both males and females. A low TBS (OR: 11.302, p = 0.028) and sarcopenia (Odds ratio (OR): 2.820, p = 0.002) were significant predictors of VF in males, but not bone quantity. Moreover, integrating TBS and sarcopenia into the predictive model improved its performance. Conclusions: Although TLM was associated with bone quantity and quality in both sexes, sarcopenia and a low TBS were significant predictors of asymptomatic VF only in male participants. Full article
(This article belongs to the Section Orthopedics)
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Open AccessReview
Review of International Clinical Guidelines Related to Prenatal Screening during Monochorionic Pregnancies
J. Clin. Med. 2021, 10(5), 1128; https://doi.org/10.3390/jcm10051128 - 08 Mar 2021
Viewed by 713
Abstract
We conducted a search for international clinical guidelines related to prenatal screening during monochorionic pregnancies. We found 25 resources from 13 countries/regions and extracted information related to general screening as well as screening related to specific monochorionic complications, including twin-twin transfusion syndrome (TTTS), [...] Read more.
We conducted a search for international clinical guidelines related to prenatal screening during monochorionic pregnancies. We found 25 resources from 13 countries/regions and extracted information related to general screening as well as screening related to specific monochorionic complications, including twin-twin transfusion syndrome (TTTS), selective fetal growth restriction (SFGR), and twin anemia-polycythemia sequence (TAPS). Findings reveal universal recommendation for the early establishment of chorionicity. Near-universal recommendation was found for bi-weekly ultrasounds beginning around gestational week 16; routine TTTS and SFGR surveillance comprised of regularly assessing fetal growth, amniotic fluids, and bladder visibility; and fetal anatomical scanning between gestational weeks 18–22. Conflicting recommendation was found for nuchal translucency screening; second-trimester scanning for cervical length; routine TAPS screening; and routine umbilical artery, umbilical vein, and ductus venosus assessment. We conclude that across international agencies and organizations, clinical guidelines related to monochorionic prenatal screening vary considerably. This discord raises concerns related to equitable access to evidence-based monochorionic prenatal care; the ability to create reliable international datasets to help improve the quality of monochorionic research; and the promotion of patient safety and best monochorionic outcomes. Patients globally may benefit from the coming together of international bodies to develop inclusive universal monochorionic prenatal screening standards. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
Open AccessArticle
Prospective Study on Incidence, Risk Factors and Outcome of Recurrent Clostridioides difficile Infections
J. Clin. Med. 2021, 10(5), 1127; https://doi.org/10.3390/jcm10051127 - 08 Mar 2021
Viewed by 341
Abstract
Background: Limited and wide-ranging data are available on the recurrent Clostridioides difficile infection (rCDI) incidence rate. Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in [...] Read more.
Background: Limited and wide-ranging data are available on the recurrent Clostridioides difficile infection (rCDI) incidence rate. Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case–control study was performed to identify risk factors associated with 30-day onset rCDI. Results: Three hundred nine patients with a first CDI were included in the study; 32% of the CDI episodes (99/309) were severe/complicated; complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up; rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7; 95% CI: 1.1–2.7, p = 0.03). Conclusion: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence. Full article
(This article belongs to the Special Issue Clostridium difficile Infection: Unmet Needs and Unsolved Questions)
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Open AccessArticle
Polymorphisms in the Gene Encoding Caspase 8 May Predict the Response to First-Line Platinum-Based Chemotherapy in Locally Advanced or Advanced Non-Small-Cell Lung Cancer
J. Clin. Med. 2021, 10(5), 1126; https://doi.org/10.3390/jcm10051126 - 08 Mar 2021
Viewed by 273
Abstract
Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in [...] Read more.
Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS). Full article
(This article belongs to the Section Oncology)
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Open AccessReview
Hodgkin Lymphoma—Review on Pathogenesis, Diagnosis, Current and Future Treatment Approaches for Adult Patients
J. Clin. Med. 2021, 10(5), 1125; https://doi.org/10.3390/jcm10051125 - 08 Mar 2021
Viewed by 311
Abstract
Hodgkin lymphoma (HL) is a rare malignancy accounting for roughly 15% of all lymphomas and mostly affecting young patients. A second peak is seen in patients above 60 years of age. The history of HL treatment represents a remarkable success story in which [...] Read more.
Hodgkin lymphoma (HL) is a rare malignancy accounting for roughly 15% of all lymphomas and mostly affecting young patients. A second peak is seen in patients above 60 years of age. The history of HL treatment represents a remarkable success story in which HL has turned from an incurable disease to a neoplasm with an excellent prognosis. First-line treatment with stage-adapted treatment consisting of chemotherapy and/or radiotherapy results in cure rates of approximately 80%. Second-line treatment mostly consists of intensive salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Novel approaches such as antibody drug conjugates and immunomodulatory drugs have shown impressive results in clinical trials in refractory and relapsed HL and are now increasingly implemented in earlier treatment lines. This review gives a comprehensive overview on HL addressing epidemiology, pathophysiology and current treatment options as well as recent developments and perspectives. Full article
(This article belongs to the Special Issue Lymphoma:New Diagnosis and Current Treatment Strategies)
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Open AccessEditorial
Age-Related Macular Degeneration (AMD): A View to the Future
J. Clin. Med. 2021, 10(5), 1124; https://doi.org/10.3390/jcm10051124 - 08 Mar 2021
Viewed by 303
Abstract
Age-related macular degeneration (AMD) is the leading cause of blindness in people over age 50 worldwide, and the third leading cause of blindness overall [...] Full article
Open AccessArticle
High Cortico-Trabecular Transitional Zone Porosity and Reduced Trabecular Density in Men and Women with Stress Fractures
J. Clin. Med. 2021, 10(5), 1123; https://doi.org/10.3390/jcm10051123 - 08 Mar 2021
Viewed by 286
Abstract
To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± [...] Read more.
To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure. Full article
(This article belongs to the Special Issue Osteoporosis and Related Bone Metabolic Disease)
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Open AccessReview
The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases
J. Clin. Med. 2021, 10(5), 1122; https://doi.org/10.3390/jcm10051122 - 08 Mar 2021
Viewed by 262
Abstract
The remodeling of extracellular matrix (ECM) within the intestine tissues, which simultaneously involves an increased degradation of ECM components and excessive intestinal fibrosis, is a defining trait of the progression of inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease [...] Read more.
The remodeling of extracellular matrix (ECM) within the intestine tissues, which simultaneously involves an increased degradation of ECM components and excessive intestinal fibrosis, is a defining trait of the progression of inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD). The increased activity of proteases, especially matrix metalloproteinases (MMPs), leads to excessive degradation of the extracellular matrix and the release of protein and glycoprotein fragments, previously joined with the extracellular matrix, into the circulation. MMPs participate in regulating the functions of the epithelial barrier, the immunological response, and the process of wound healing or intestinal fibrosis. At a later stage of fibrosis during IBD, excessive formation and deposition of the matrix is observed. To assess changes in the extracellular matrix, quantitative measurement of the concentration in the blood of markers dependent on the activity of proteases, involved in the breakdown of extracellular matrix proteins as well as markers indicating the formation of a new ECM, has recently been proposed. This paper describes attempts to use the quantification of ECM components as markers to predict intestinal fibrosis and evaluate the healing process of the gut. The markers which reflect increased ECM degradation, together with the ones which show the process of creating a new matrix during IBD, allow the attainment of important information regarding the changes in the intestinal tissue, epithelial integrity and extracellular matrix remodeling. This paper contains evidence confirming that ECM remodeling is an integral part of directional cell signaling in the progression of IBD, and not only a basis for the ongoing processes. Full article
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Open AccessEditorial
Is It Time for Machine Learning Algorithms to Predict the Risk of Kidney Failure in Patients with Chronic Kidney Disease?
J. Clin. Med. 2021, 10(5), 1121; https://doi.org/10.3390/jcm10051121 - 08 Mar 2021
Viewed by 222
Abstract
Chronic kidney disease (CKD) is a common clinical problem affecting more than 800 million people with different kidney diseases [...] Full article
(This article belongs to the Section Nephrology & Urology)
Open AccessEditorial
Delivering into the Mounting Evidence of a Probable Link between Maternal Hypothyroidism and Breech Presentation at Term: What Do We Know until Now?
J. Clin. Med. 2021, 10(5), 1120; https://doi.org/10.3390/jcm10051120 - 08 Mar 2021
Viewed by 276
Abstract
Approximately 3–5% of all women at term have a breech baby [...] Full article
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