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Volume 10, April-1

J. Clin. Med., Volume 10, Issue 8 (April-2 2021) – 148 articles

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Open AccessReview
Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness
J. Clin. Med. 2021, 10(8), 1693; https://doi.org/10.3390/jcm10081693 (registering DOI) - 14 Apr 2021
Abstract
In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by [...] Read more.
In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules. It undergoes quantitative as well as qualitative changes which can be measured using the HDL inflammatory index (HII). Pro-inflammatory, or dysfunctional HDL (dysHDL) lacks the ability to perform these functions, and we have also found it to independently predict adverse outcomes and organ failure in sepsis. Another important class of lipids known as specialized pro-resolving mediators (SPMs) positively affect the escalation and resolution of inflammation in a temporal fashion. These undergo phenotypic changes in sepsis and differ significantly between survivors and non-survivors. Certain subsets of sepsis survivors go on to have perilous post-hospitalization courses where this inflammation continues in a low grade fashion. This is associated with immunosuppression in a syndrome of persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The continuous release of tissue damage-related patterns and viral reactivation secondary to immunosuppression feed this chronic cycle of inflammation. Animal data indicate that dysregulation of endogenous lipids and SPMs play important roles in this process. Lipids and their associated pathways have been the target of many clinical trials in recent years which have not shown mortality benefit. These results are limited by patient heterogeneity and poor animal models. Considerations of sepsis phenotypes and novel biomarkers in future trials are important factors to be considered in future research. Further characterization of lipid dysregulation and chronic inflammation during sepsis will aid mortality risk stratification, detection of sepsis, and inform individualized pharmacologic therapies. Full article
(This article belongs to the Section Intensive Care)
Open AccessArticle
Diversity of Pathological Conditions Affecting Pituitary Stalk
J. Clin. Med. 2021, 10(8), 1692; https://doi.org/10.3390/jcm10081692 (registering DOI) - 14 Apr 2021
Abstract
Pituitary stalk lesions (PSL) are a very rare pathology. The majority of conditions affecting the infundibulum do not present with clinically apparent symptoms, what makes the diagnosis difficult. The recognition might be also complicated by the non-specific and transient characteristics of hormonal insufficiencies. [...] Read more.
Pituitary stalk lesions (PSL) are a very rare pathology. The majority of conditions affecting the infundibulum do not present with clinically apparent symptoms, what makes the diagnosis difficult. The recognition might be also complicated by the non-specific and transient characteristics of hormonal insufficiencies. In our study, we retrospectively analysed demographic, biochemical, and clinical long-term data of 60 consecutive, unselected adult patients (34 women and 26 men) with PSL diagnosed in the Department of Endocrinology, Jagiellonian University in Krakow. The diagnosis of PSL were categorized as confirmed, probable, or undetermined in 26, 26 and 8 patients, accordingly. Given the possible aetiology congenital, inflammatory, and neoplastic stalk lesions were diagnosed in 17, 15 and 20 patients, accordingly. In eight cases the underlying pathology remained undetermined. The most common pituitary abnormality was gonadal insufficiency diagnosed in 50.8% of cases. Diabetes insipidus was detected in 23.3% of cases. In 5% of patients the pituitary function recovered partially over time. Stalk lesions were extensively discussed in the context of the current literature. Based on the published data and our own experience a diagnostic algorithm has been proposed to help physicians with the management of patients with this challenging condition. Full article
(This article belongs to the Section Endocrinology & Metabolism)
Open AccessArticle
A COVID-19 Rehabilitation Prospective Surveillance Model for Use by Physiotherapists
J. Clin. Med. 2021, 10(8), 1691; https://doi.org/10.3390/jcm10081691 (registering DOI) - 14 Apr 2021
Abstract
The long-term sequelae of coronavirus disease 2019 (COVID-19) are only now beginning to be defined, but it is already known that the disease can have direct and indirect impacts mainly on the cardiorespiratory and neuromuscular systems and may affect mental health. A role [...] Read more.
The long-term sequelae of coronavirus disease 2019 (COVID-19) are only now beginning to be defined, but it is already known that the disease can have direct and indirect impacts mainly on the cardiorespiratory and neuromuscular systems and may affect mental health. A role for rehabilitation professionals from all disciplines in addressing COVID-19 sequelae is recognised, but it is essential that patient assessment be systematic if health complications are to be identified and treated and, if possible, prevented. The aim is to present a COVID-19 prospective surveillance model based on sensitive and easily used assessment tools, which is urgently required. Following the Oxford Centre for Evidence-Based Medicine Level of Evidence Tool, an expert team in cardiorespiratory, neuromuscular and mental health worked via telemeetings to establish a model that provides guidelines to rehabilitation professionals working with patients who require rehabilitation after suffering from COVID-19. A COVID-19 prospective surveillance model is proposed for use by rehabilitation professionals and includes both face-to-face and telematic monitoring components. This model should facilitate the early identification and management of long-term COVID-19 sequelae, thus responding to an arising need. Full article
(This article belongs to the Special Issue Improved Rehabilitation for Patients with Chronic Pain)
Open AccessArticle
Urinary Peptides as Potential Non-Invasive Biomarkers for Lupus Nephritis: Results of the Peptidu-LUP Study
J. Clin. Med. 2021, 10(8), 1690; https://doi.org/10.3390/jcm10081690 (registering DOI) - 14 Apr 2021
Abstract
Background: Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design: Urinary samples were collected from [...] Read more.
Background: Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design: Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery (n = 42) and an independent validation (n = 51) cohort. Clinical characteristics were collected at inclusion and prospectively for 24 months. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. The value of previously validated prognostic (CKD273) and differential diagnostic (LN172) signatures was evaluated. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Tubulo-interstitial fibrosis was correlated to the CKD273. The LN172 score identified 92.5% of samples as LN. Few patients developed new-onset CKD. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated. Full article
Open AccessArticle
The Anatomical Conditions of the Alveolar Process of the Anterior Maxilla in Terms of Immediate Implantation—Radiological Retrospective Case Series Study
J. Clin. Med. 2021, 10(8), 1688; https://doi.org/10.3390/jcm10081688 (registering DOI) - 14 Apr 2021
Abstract
The feasibility and the level of difficulty of immediate flapless implantation depend largely on the residual alveolar bone. The purpose of the study was to determine how often immediate flapless implantation in the anterior maxilla is feasible and assess the difficulty level using [...] Read more.
The feasibility and the level of difficulty of immediate flapless implantation depend largely on the residual alveolar bone. The purpose of the study was to determine how often immediate flapless implantation in the anterior maxilla is feasible and assess the difficulty level using cone-beam computed tomography (CBCT) scans. A radiological retrospective case series study was conducted. In total, 1200 CBCT scans from 300 consecutive patients were analyzed with dedicated planning software. Immediate flapless implants were possible in 78.33% of cases. Drilling direction was either through the apex or the palatal slope. Bimodal was conducted in 9% of the cases; only through the apex in 13.08% of the cases and in 56.25% only in the slope. In 21.67%, immediate flapless implants were excluded. The feasibility and degree of difficulty differed statistically to the disadvantage of the lateral incisors compared to the central incisors. Drilling direction caused that BASE classification reflects the difficulty level of immediate implantation. CBCT is a helpful diagnostic tool for assessing the feasibility of immediate flapless implants due to the residual bone shape and volume. BASE classification helps to determine a challenge level that may also facilitate communication and result in comparison. The alveolar bone condition allows for immediate flapless implants in most cases in the aesthetic region of the maxilla, but they should be performed by an experienced specialist with regard to the bone and soft tissue quality. Full article
Open AccessArticle
Quality of Life, Postoperative Pain, and Lymph Node Dissection in a Robotic Approach Compared to VATS and OPEN for Early Stage Lung Cancer
J. Clin. Med. 2021, 10(8), 1687; https://doi.org/10.3390/jcm10081687 (registering DOI) - 14 Apr 2021
Abstract
We compare the perioperative course, postoperative pain, and quality-of-life (QOL) in patients undergoing anatomic resections of early-stage lung cancer by means of robotic surgery (RATS), video-assisted thoracic surgery (VATS), or muscle-sparing thoracotomy (OPEN); 169 consecutive patients with known/suspected lung cancer, candidates to anatomic [...] Read more.
We compare the perioperative course, postoperative pain, and quality-of-life (QOL) in patients undergoing anatomic resections of early-stage lung cancer by means of robotic surgery (RATS), video-assisted thoracic surgery (VATS), or muscle-sparing thoracotomy (OPEN); 169 consecutive patients with known/suspected lung cancer, candidates to anatomic resection, were enrolled in a single-center prospective study from April 2016 to December 2018. EORTC QLQ-C30 and QLQ-LC13 scores were obtained preoperatively and, at three time points, postoperatively. RATS and VATS groups were matched for ASA scores, while RATS and open surgery were matched for gender, ASA score, cancer stage, and tumor size; 58 patients underwent open surgery, 58 had VATS, and 53 had RATS. Hospital stay was shorter after RATS than OPEN (median 4.5 versus 5; p = 0.047). Comparing matched RATS and VATS groups, the number of hilar lymph nodes and nodal stations removed was significantly higher in the former approach (p = 0.01 vs. p < 0.0001); conversely, pain at 2 weeks was slightly lower after VATS (p = 0.004). No significant difference was observed in conversions, complications, duration of surgery, and postoperative hospitalization. The robotic approach was superior to OPEN in terms of QOL, pain, and length of postoperative stay and showed improved lymph node dissection compared to VATS. Full article
(This article belongs to the Special Issue Lung Cancer: Symptoms, Treatment, and Early Diagnosis)
Open AccessArticle
500 Meters Is a Result of 6-Minute Walk Test Which Differentiates Patients with High and Low Risk of Postoperative Complications after Lobectomy—A Validation Study
J. Clin. Med. 2021, 10(8), 1686; https://doi.org/10.3390/jcm10081686 (registering DOI) - 14 Apr 2021
Abstract
The 6-minute walk test (6MWT) is a simple method of identifying patients with a high risk of postoperative complications. In this study, we internally validated the previously obtained threshold value of 500 m in the 6MWT as differentiating populations with a high and [...] Read more.
The 6-minute walk test (6MWT) is a simple method of identifying patients with a high risk of postoperative complications. In this study, we internally validated the previously obtained threshold value of 500 m in the 6MWT as differentiating populations with a high and a low risk of postoperative complications after a lobectomy. Between November 2011 and November 2016, 624 patients who underwent a lobectomy and performed the 6MWT preoperatively entered this study. We compared the complication rates of two groups of patients—those who walked more than and those who walked less than 500 m. The patients who did not reach the distance of 500 m in the 6MWT were older (70 vs. 63 years p < 0.001), had worse pulmonary function tests (FEV1% 84 vs. 88 p = 0.041) and had a higher Charlson Comorbidity Index (p < 0.001). The patients who had a worse result in the 6MWT had a higher complication rate (52% vs. 42% p = 0.019; OR: 1.501 95% CI: 1.066–2.114) and a longer median postoperative hospital stay (7 vs. 6 days p = 0.010). In a multivariate analysis, the result of the 6MWT and pack-years proved to independently influence the risk of postoperative complications. This internal validation study confirms that 500 m is a result of the 6MWT which differentiates patients with a higher risk of postoperative complications and a prolonged hospital stay after a lobectomy. Full article
(This article belongs to the Special Issue Lung Cancer: Symptoms, Treatment, and Early Diagnosis)
Open AccessReview
Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives
J. Clin. Med. 2021, 10(8), 1685; https://doi.org/10.3390/jcm10081685 (registering DOI) - 14 Apr 2021
Abstract
Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is [...] Read more.
Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is a disease that by definition has micrometastatic disease at diagnosis and a dismal prognosis for patients with macrometastatic or recurrent disease. International collaborations have defined the current standard of care in prospective studies, delivering multiple cycles of systemic therapy combined with local treatment; both are associated with significant morbidity that may result in strong psychological and physical burden for survivors. Nevertheless, the combination of non-directed chemotherapeutics and ever-evolving local modalities nowadays achieve a realistic chance of cure for the majority of patients with Ewing sarcoma. In this review, we focus on the current standard of diagnosis and treatment while attempting to answer some of the most pressing questions in clinical practice. In addition, this review provides scientific answers to clinical phenomena and occasionally defines the resulting translational studies needed to overcome the hurdle of treatment-associated morbidities and, most importantly, non-survival. Full article
(This article belongs to the Special Issue The Current Treatment of Childhood Cancer)
Open AccessArticle
Venetoclax-Based Regimens for Relapsed/Refractory Acute Myeloid Leukemia in a Real-Life Setting: A Retrospective Single-Center Experience
J. Clin. Med. 2021, 10(8), 1684; https://doi.org/10.3390/jcm10081684 (registering DOI) - 14 Apr 2021
Abstract
Relapsed/refractory (R/R) acute myeloid leukemia (AML) is a largely unmet medical need, owing to the lack of standardized, effective treatment approaches, resulting in an overall dismal outcome. The only curative option for R/R AML patients is allogeneic hematopoietic stem cell transplantation (HSCT) which [...] Read more.
Relapsed/refractory (R/R) acute myeloid leukemia (AML) is a largely unmet medical need, owing to the lack of standardized, effective treatment approaches, resulting in an overall dismal outcome. The only curative option for R/R AML patients is allogeneic hematopoietic stem cell transplantation (HSCT) which is only applicable in a fraction of patients due to the scarce efficacy and high toxicity of salvage regimens. Recently, a number of targeted agents with relatively favorable toxicity profiles have been explored in clinical trials for R/R AML patients. The Bcl-2 inhibitor venetoclax, in combination with hypomethylating agents or low dose cytarabine, has produced impressive results for newly diagnosed AML, while its role in R/R disease is not well defined yet. We retrospectively analyzed the clinical outcomes of 47 R/R AML patients treated with venetoclax-based regimens between March 2018 and December 2020 at our institution. Overall, we report a composite complete response rate of 55% with an overall acceptable toxicity profile. Outcomes were particularly favorable for NPM1 mutated patients, unlike for FLT3-ITD positive patients irrespective of NPM1 status. For patients treated with intention to transplant, the procedure could be finally performed in 54%. These findings suggest a role for venetoclax-based regimens in R/R AML patients and support the design of prospective studies. Full article
(This article belongs to the Special Issue New Developments in the Field of Myeloid Neoplasms)
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Open AccessReview
Tumoral Phenocopies of Hypertrophic Cardiomyopathy: The Role of Cardiac Magnetic Resonance
J. Clin. Med. 2021, 10(8), 1683; https://doi.org/10.3390/jcm10081683 (registering DOI) - 14 Apr 2021
Abstract
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that presents with cardiac hypertrophy. HCM phenocopies are clinical conditions that are phenotypically undistinguishable from HCM, but with a different underlying etiology. Cardiac tumors are rare entities that can sometimes mimic HCM in their echocardiographic [...] Read more.
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that presents with cardiac hypertrophy. HCM phenocopies are clinical conditions that are phenotypically undistinguishable from HCM, but with a different underlying etiology. Cardiac tumors are rare entities that can sometimes mimic HCM in their echocardiographic appearance, thus representing an example of HCM phenocopy. At present, only case reports of tumoral HCM phenocopies can be found in literature. In this systematic review, we analyzed all the published cases in which a cardiac tumor mimicked HCM to the point of misleading the diagnosis, providing a structured overview of the currently available evidence on this topic. Full article
(This article belongs to the Special Issue Hypertrophic Cardiomyopathy: Phenotypes and Phenocopies)
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Open AccessReview
Founder Effects in Hereditary Hemorrhagic Telangiectasia
J. Clin. Med. 2021, 10(8), 1682; https://doi.org/10.3390/jcm10081682 (registering DOI) - 14 Apr 2021
Abstract
A founder effect can result from the establishment of a new population by individuals from a larger population or bottleneck events. Certain alleles may be found at much higher frequencies because of genetic drift immediately after the founder event. We provide a systematic [...] Read more.
A founder effect can result from the establishment of a new population by individuals from a larger population or bottleneck events. Certain alleles may be found at much higher frequencies because of genetic drift immediately after the founder event. We provide a systematic literature review of the sporadically reported founder effects in hereditary hemorrhagic telangiectasia (HHT). All publications from the ACVRL1, ENG and SMAD4 Mutation Databases and publications searched for terms “hereditary hemorrhagic telangiectasia” and “founder” in PubMed and Scopus, respectively, were extracted. Following duplicate removal, 141 publications were searched for the terms “founder” and “founding” and the etymon “ancest”. Finally, 67 publications between 1992 and 2020 were reviewed. Founder effects were graded upon shared area of ancestry/residence, shared core haplotypes, genealogy and prevalence. Twenty-six ACVRL1 and 12 ENG variants with a potential founder effect were identified. The bigger the cluster of families with a founder mutation, the more remarkable is its influence to the populational ACVRL1/ENG ratio, affecting HHT phenotype. Being aware of founder effects might simplify the diagnosis of HHT by establishing local genetic algorithms. Families sharing a common core haplotype might serve as a basis to study potential second-hits in the etiology of HHT. Full article
(This article belongs to the Special Issue Hereditary Hemorrhagic Telangiectasia: Diagnosis and Management)
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Open AccessArticle
Influence of Placental Abnormalities and Pregnancy-Induced Hypertension in Prematurity Associated with Various Assisted Reproductive Technology Techniques
J. Clin. Med. 2021, 10(8), 1681; https://doi.org/10.3390/jcm10081681 (registering DOI) - 14 Apr 2021
Abstract
Objective. Assisted reproductive technology (ART)-treated women exhibit increased risk of premature delivery compared to fertile women. We evaluated whether ART treatment modalities increase prematurity and whether placental abnormalities and pregnancy-induced hypertensive (PIH) disorders mediate these risks. Method(s): This retrospective study of ART-treated and [...] Read more.
Objective. Assisted reproductive technology (ART)-treated women exhibit increased risk of premature delivery compared to fertile women. We evaluated whether ART treatment modalities increase prematurity and whether placental abnormalities and pregnancy-induced hypertensive (PIH) disorders mediate these risks. Method(s): This retrospective study of ART-treated and fertile deliveries (2004–2017) used an ART-cycle database linked to Massachusetts birth certificates and hospital discharges. Outcomes of late preterm birth (LPTB: 34–36 weeks gestation) and early preterm birth (EPTB: <34 weeks gestation) were compared with term deliveries (≥37 weeks gestation) in ART-treated (linked to the ART database) and fertile (no indicators of infertility or ART) deliveries. ART treatments with autologous oocyte, donor oocyte, fresh or frozen embryo transfer (FET), intracytoplasmic sperm injection (ICSI) and no-ICSI were separately compared to the fertile group. Adjusted odds ratios (AOR) were calculated with multivariable logistic regression: placental abnormalities or PIH were quantified in the pathway as mediators. Results: There were 218,320 deliveries: 204,438 fertile and 13,882 ART-treated. All treatment types increased prematurity (AOR 1.31–1.58, LPTB; AOR 1.34–1.48, EPTB). Placental abnormalities mediated in approximately 22% and 38% of the association with LPTB and EPTB, respectively. PIH mediated 25% and 33% of the association with LPTB and EPTB in FET and donor oocyte cycles, more than other treatments (<10% LPTB and <13% EPTB). Conclusions: ART-treatment and all ART modalities increased LPTB and EPTB when compared with fertile deliveries. Placental abnormalities modestly mediated associations approximately equally, while PIH was a stronger mediator in FET and donor oocyte cycles. Reasons for differences require exploration. Full article
(This article belongs to the Special Issue Assisted Reproductive Technology and Pregnancy Outcomes)
Open AccessArticle
Fast-Track Programs in Total Hip and Knee Replacement at Swedish Hospitals—Influence on 2-Year Risk of Revision and Mortality
J. Clin. Med. 2021, 10(8), 1680; https://doi.org/10.3390/jcm10081680 (registering DOI) - 14 Apr 2021
Abstract
Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the [...] Read more.
Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan–Meier survival analysis and Cox regression analysis with adjustments. Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03–1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79–1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74–0.97) for TKR and 0.96 (CI: 0.85–1.09) for THR in fast-track hospitals compared to non-fast-track. Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track. Full article
(This article belongs to the Special Issue Surgical Treatment of Joint Replacement)
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Open AccessArticle
Perioperative ABO Blood Group Isoagglutinin Titer and the Risk of Acute Kidney Injury after ABO-Incompatible Living Donor Liver Transplantation
J. Clin. Med. 2021, 10(8), 1679; https://doi.org/10.3390/jcm10081679 (registering DOI) - 14 Apr 2021
Abstract
For ABO-incompatible liver transplantation (ABO-i LT), therapeutic plasma exchange (TPE) is performed preoperatively to reduce the isoagglutinin titer of anti-ABO blood type antibodies. We evaluated whether perioperative high isoagglutinin titer is associated with postoperative risk of acute kidney injury (AKI). In 130 cases [...] Read more.
For ABO-incompatible liver transplantation (ABO-i LT), therapeutic plasma exchange (TPE) is performed preoperatively to reduce the isoagglutinin titer of anti-ABO blood type antibodies. We evaluated whether perioperative high isoagglutinin titer is associated with postoperative risk of acute kidney injury (AKI). In 130 cases of ABO-i LT, we collected immunoglobulin (Ig) G and Ig M isoagglutinin titers of baseline, pre-LT, and postoperative peak values. These values were compared between the patients with and without postoperative AKI. Multivariable logistic regression analysis was used to evaluate the association between perioperative isoagglutinin titers and postoperative AKI. Clinical and graft-related outcomes were compared between high and low baseline and postoperative peak isoagglutinin groups. The incidence of AKI was 42.3%. Preoperative baseline and postoperative peak isoagglutinin titers of both Ig M and Ig G were significantly higher in the patients with AKI than those without AKI. Multivariable logistic regression analysis showed that preoperative baseline and postoperative peak Ig M isoagglutinin titers were significantly associated with the risk of AKI (baseline: odds ratio 1.06, 95% confidence interval 1.02 to 1.09; postoperative peak: odds ratio 1.08, 95% confidence interval 1.04 to 1.13). Cubic spline function curves show a positive relationship between the baseline and postoperative peak isoagglutinin titers and the risk of AKI. Clinical outcomes other than AKI were not significantly different according to the baseline and postoperative peak isoagglutinin titers. Preoperative high initial and postoperative peak Ig M isoagglutinin titers were significantly associated with the development of AKI. As the causal relationship between high isoagglutinin titers and risk of AKI is unclear, the high baseline and postoperative isoagglutinin titers could be used simply as a warning sign for the risk of AKI after liver transplantation. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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Open AccessArticle
Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study
J. Clin. Med. 2021, 10(8), 1678; https://doi.org/10.3390/jcm10081678 - 14 Apr 2021
Abstract
The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the [...] Read more.
The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at −20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size. Full article
(This article belongs to the Special Issue Bone Regeneration in Dentistry, Oral and Maxillofacial Surgery)
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Open AccessArticle
New Perspective for Soft Tissue Closure in Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Barbed Sutures
J. Clin. Med. 2021, 10(8), 1677; https://doi.org/10.3390/jcm10081677 - 14 Apr 2021
Abstract
The aim of this study was to compare the effectiveness of barbed versus smooth sutures for soft tissue closure of exposed jawbone sites in medication-related osteonecrosis of the jaw (MRONJ) patients. Exposed necrotic jawbone sites surgically managed by intraoral soft tissue closure were [...] Read more.
The aim of this study was to compare the effectiveness of barbed versus smooth sutures for soft tissue closure of exposed jawbone sites in medication-related osteonecrosis of the jaw (MRONJ) patients. Exposed necrotic jawbone sites surgically managed by intraoral soft tissue closure were evaluated. Either barbed sutures (Stratafix™ or V-Loc™) together with Prolene® or Vicryl® sutures were used. We estimated the effect of barbed sutures (BS) with Prolene® compared to smooth sutures (Vicryl®) on the hazard rate of intraoral soft tissue dehiscence using a multivariate Cox regression model within a target trial framework, adjusting for relevant confounders. In total, 306 operations were performed in 188 sites. In the primary analysis 182 sites without prior surgery were included. Of these, 113 sites developed a dehiscence during follow-up. 84 sites were operated using BS and Prolene®. A total of 222 sites were operated with Vicryl® (control group). In the BS group, the median time to event (i.e., dehiscence) was 148 days (interquartile range (IQR), 42–449 days) compared to 15 days (IQR, 12–52 days) in the control group. The hazard rate of developing intraoral dehiscence was 0.03 times (95%-confidence interval (CI): 0.01; 0.14, p < 0.001) lower for BS patients compared to the control group. Within the limits of a retrospective study, BS showed a high success rate and are therefore recommended for soft tissue closure of exposed jawbone sites in MRONJ patients. Additional studies are warranted to further evaluate this novel application of BS. Full article
(This article belongs to the Special Issue New Perspectives in Maxillo-Facial Surgery)
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Open AccessArticle
Forensic Analysis of Umbilical and Newborn Blood Gas Values for Infants at Risk of Cerebral Palsy
J. Clin. Med. 2021, 10(8), 1676; https://doi.org/10.3390/jcm10081676 - 14 Apr 2021
Abstract
Cerebral palsy litigation cases account for the highest claims involving obstetricians/gynecologists, a specialty that ranks among the highest liability medical professions. Although epidemiologic studies indicate that only a small proportion of cerebral palsy (10–20%) is due to birth asphyxia, negligent obstetrical care is [...] Read more.
Cerebral palsy litigation cases account for the highest claims involving obstetricians/gynecologists, a specialty that ranks among the highest liability medical professions. Although epidemiologic studies indicate that only a small proportion of cerebral palsy (10–20%) is due to birth asphyxia, negligent obstetrical care is often alleged to be the etiologic factor, resulting in contentious medical-legal conflicts. Defense and plaintiff expert opinions regarding the etiology and timing of injury are often polarized, as there is a lack of established methodology for analysis. The objective results provided by umbilical cord and newborn acid/base and blood gas values and the established association with the incidence of cerebral palsy provide a basis for the forensic assessment of both the mechanism and timing of fetal neurologic injury. Using established physiologic and biochemical principles, a series of case examples demonstrates how an unbiased expert assessment can aid in both conflict resolution and opportunities for clinical education. Full article
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Open AccessReview
Management of Implantable Cardioverter-Defibrillators during Pregnancy—A Systematic Review
J. Clin. Med. 2021, 10(8), 1675; https://doi.org/10.3390/jcm10081675 - 14 Apr 2021
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Abstract
Background: With the advent of implantable cardioverter-defibrillator (ICD) technology in recent decades, patients with inherited or congenital cardiomyopathy have a greater chance of survival into adulthood. Women with ICDs in this group are now more likely to reach reproductive age. However, pregnancy represents [...] Read more.
Background: With the advent of implantable cardioverter-defibrillator (ICD) technology in recent decades, patients with inherited or congenital cardiomyopathy have a greater chance of survival into adulthood. Women with ICDs in this group are now more likely to reach reproductive age. However, pregnancy represents a challenge for clinicians, as no guidelines for the treatment of pregnant women with an ICD are currently available. Methods: To analyze this issue, we performed a systematic screening of the literature using the keywords: pregnancy with ICD, lead fracture in pregnancy, lead thrombi in pregnancy, ventricular tachycardia in pregnancy, inappropriate shocks in pregnancy, ICD discharge in pregnancy and ICD shock in pregnancy. Of 1101 publications found, 27 publications were eligible for further analysis (four retrospective trials and 23 case reports). Results: According to physiological changes in pregnancy, resulting in an increase in heart rate and cardiac output, a vulnerability for malignant arrhythmias and device-related complications in ICD carriers might be suspected. While the literature is limited on this issue, maternal complications including arrhythmia burden with following ICD therapies, thromboembolic events and lead complications as well as inappropriate shock therapy have been reported. According to the limited available studies, associated risk seems not to be more frequent than in the general population and depends on the underlying cardiac pathology. Furthermore, worsening of heart failure and related cardiovascular disease have been reported with associated risk of preterm delivery. These observations are exaggerated by restricted applications of diagnostics and treatment due to the risk of fetal harm in this population. Conclusions: Due to limited data on management of ICDs during pregnancy, further scientific investigations are required. Consequently, careful risk assessment with individual risk evaluation and close follow ups with interdisciplinary treatment are recommended in pregnant ICD carriers. Full article
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Open AccessReview
Understanding Why Post-Stroke Depression May Be the Norm Rather Than the Exception: The Anatomical and Neuroinflammatory Correlates of Post-Stroke Depression
J. Clin. Med. 2021, 10(8), 1674; https://doi.org/10.3390/jcm10081674 - 14 Apr 2021
Viewed by 133
Abstract
Ischemic Stroke precedes depression. Post-stroke depression (PSD) is a major driver for poor recovery, negative quality of life, poor rehabilitation outcomes and poor functional ability. In this systematic review, we analysed the inflammatory basis of post-stroke depression, which involves bioenergetic failure, deranged iron [...] Read more.
Ischemic Stroke precedes depression. Post-stroke depression (PSD) is a major driver for poor recovery, negative quality of life, poor rehabilitation outcomes and poor functional ability. In this systematic review, we analysed the inflammatory basis of post-stroke depression, which involves bioenergetic failure, deranged iron homeostasis (calcium influx, Na influx, potassium efflux etc), excitotoxicity, acidotoxicity, disruption of the blood brain barrier, cytokine-mediated cytotoxicity, reactive oxygen mediated toxicity, activation of cyclooxygenase pathway and generation of toxic products. This process subsequently results in cell death, maladapted, persistent neuro-inflammation and deranged neuronal networks in mood-related brain regions. Furthermore, an in-depth review likewise reveals that anatomic structures related to post-stroke depression may be localized to complex circuitries involving the cortical and subcortical regions. Full article
(This article belongs to the Special Issue Novel Approaches for the Treatment of Cerebrovascular Disorders)
Open AccessArticle
Neurogenic Bowel in Acute Rehabilitation Following Spinal Cord Injury: Impact of Laxatives and Opioids
J. Clin. Med. 2021, 10(8), 1673; https://doi.org/10.3390/jcm10081673 - 14 Apr 2021
Viewed by 153
Abstract
Objective: To explore the association between bowel dysfunction and use of laxatives and opioids in an acute rehabilitation setting following spinal cord injury (SCI). Methods: Data was collected regarding individuals with acute traumatic/non-traumatic SCI over a two-year period (2012–2013) during both the week [...] Read more.
Objective: To explore the association between bowel dysfunction and use of laxatives and opioids in an acute rehabilitation setting following spinal cord injury (SCI). Methods: Data was collected regarding individuals with acute traumatic/non-traumatic SCI over a two-year period (2012–2013) during both the week of admission and discharge of their inpatient stay. Results: An increase in frequency of bowel movement (BM) (p = 0.003) and a decrease in frequency of fecal incontinence (FI) per week (p < 0.001) between admission and discharge was found across all participants. There was a reduction in the number of individuals using laxatives (p = 0.004) as well as the number of unique laxatives taken (p < 0.001) between admission and discharge in our cohort. The number of individuals using opioids and the average dose of opioids in morphine milligram equivalents (MME) from admission to discharge were significantly reduced (p = 0.001 and p = 0.02, respectively). There was a positive correlation between the number of laxatives and frequency of FI at discharge (r = 0.194, p = 0.014), suggesting that an increase in laxative use results in an increased frequency of FI. Finally, there was a significant negative correlation between average dose of opioids (MME) and frequency of BM at discharge, confirming the constipating effect of opioids (r = −0.20, p = 0.009). Full article
(This article belongs to the Special Issue Neurogenic Bowel Dysfunction)
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Open AccessArticle
Complex Liver Resections for Intrahepatic Cholangiocarcinoma
J. Clin. Med. 2021, 10(8), 1672; https://doi.org/10.3390/jcm10081672 - 13 Apr 2021
Viewed by 214
Abstract
The only curative treatment option for intrahepatic cholangiocarcinoma (iCCA) is liver resection. Due to central tumor localization and vascular invasion, complex liver resections play an important role in curative treatment. However, the long-term outcomes after complex liver resection are not known. Methods: A [...] Read more.
The only curative treatment option for intrahepatic cholangiocarcinoma (iCCA) is liver resection. Due to central tumor localization and vascular invasion, complex liver resections play an important role in curative treatment. However, the long-term outcomes after complex liver resection are not known. Methods: A retrospective cohort study was conducted for all patients undergoing liver surgery for iCCA. Complex liver resections included ante situm resections, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and major liver resection with vascular reconstructions. Results: Forty-nine patients (34%) received complex liver resection, 66 patients (46%) received conventional liver resection and 28 patients (20%) were not resectable during exploration. Preoperative characteristics were not different between the groups, except for Union for International Cancer Control (UICC) stages. The postoperative course for complex liver resections was associated with more complications and perioperative mortality. However, long-term survival was not different between complex and conventional resections. Independent risk factors for survival were R0 resections and UICC stage. Four patients underwent ante situm resection without any mortality. Conclusions: Complex liver resections are justified in selected patients and survival is comparable with conventional liver resections. Survival in iCCA is affected by UICC stage or resections margins and not by the complexity of the case. Full article
(This article belongs to the Special Issue Management of Intrahepatic Cholangiocarcinoma)
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Open AccessArticle
Carotid Plaque Assessment Reclassifies Patients with Inflammatory Bowel Disease into Very-High Cardiovascular Risk
J. Clin. Med. 2021, 10(8), 1671; https://doi.org/10.3390/jcm10081671 - 13 Apr 2021
Viewed by 203
Abstract
The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease [...] Read more.
The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease (IBD) into the very high-CV-risk category and whether this may be related to disease features. In this cross-sectional study encompassing 186 IBD patients and 175 controls, Systematic Coronary Risk Evaluation (SCORE), disease activity measurements, and the presence of carotid plaques by ultrasonography were assessed. Reclassification was compared between patients and controls. A multivariable regression analysis was performed to evaluate if the risk of reclassification could be explained by disease-related features and to assess the influence of traditional CV risk factors on this reclassification. After evaluation of carotid ultrasound, a significantly higher frequency of reclassification was found in patients with IBD compared to controls (35% vs. 24%, p = 0.030). When this analysis was performed only on subjects included in the SCORE low-CV-risk category, 21% IBD patients compared to 11% controls (p = 0.034) were reclassified into the very high-CV-risk category. Disease-related data, including disease activity, were not associated with reclassification after fully multivariable regression analysis. Traditional CV risk factors showed a similar influence over reclassification in patients and controls. However, LDL-cholesterol disclosed a higher effect in controls compared to patients (beta coef. 1.03 (95%CI 1.02–1.04) vs. 1.01 (95%CI 1.00–1.02), interaction p = 0.035) after adjustment for confounders. In conclusion, carotid plaque assessment is useful to identify high-CV risk IBD patients. Full article
(This article belongs to the Special Issue Gastrointestinal Tract Disorders)
Open AccessArticle
Individual Lymphocyte Sensitivity to Steroids as a Reliable Biomarker for Clinical Outcome after Steroid Withdrawal in Japanese Renal Transplantation
J. Clin. Med. 2021, 10(8), 1670; https://doi.org/10.3390/jcm10081670 - 13 Apr 2021
Viewed by 198
Abstract
Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to [...] Read more.
Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC50) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC50 values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual’s lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation. Full article
(This article belongs to the Special Issue Selected Papers from the JSOPB 2020—Cell and Organ Biology)
Open AccessReview
Neurogenic Bowel Dysfunction in Children and Adolescents
J. Clin. Med. 2021, 10(8), 1669; https://doi.org/10.3390/jcm10081669 - 13 Apr 2021
Viewed by 194
Abstract
Neurogenic/neuropathic bowel dysfunction (NBD) is common in children who are affected by congenital and acquired neurological disease, and negatively impacts quality of life. In the past, NBD received less attention than neurogenic bladder, generally being considered only in spina bifida (the most common [...] Read more.
Neurogenic/neuropathic bowel dysfunction (NBD) is common in children who are affected by congenital and acquired neurological disease, and negatively impacts quality of life. In the past, NBD received less attention than neurogenic bladder, generally being considered only in spina bifida (the most common cause of pediatric NBD). Many methods of conservative and medical management of NBD are reported, including relatively recently Transanal Irrigation (TAI). Based on the literature and personal experience, an expert group (pediatric urologists/surgeons/gastroenterologists with specific experience in NBD) focused on NBD in children and adolescents. A statement document was created using a modified Delphi method. The range of causes of pediatric NBD are discussed in this paper. The various therapeutic approaches are presented to improve clinical management. The population of children and adolescents with NBD is increasing, due both to the higher survival rate and better diagnosis. While NBD is relatively predictable in producing either constipation or fecal incontinence, or both, its various effects on each patient will depend on a wide range of underlying causes and accompanying comorbidities. For this reason, management of NBD should be tailored individually with a combined multidisciplinary therapy appropriate for the status of the affected child and caregivers. Full article
(This article belongs to the Special Issue Neurogenic Bowel Dysfunction)
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Open AccessReview
Cardiovascular Calcification as a Marker of Increased Cardiovascular Risk and a Surrogate for Subclinical Atherosclerosis: Role of Echocardiography
J. Clin. Med. 2021, 10(8), 1668; https://doi.org/10.3390/jcm10081668 - 13 Apr 2021
Viewed by 80
Abstract
The risk prediction of future cardiovascular events is mainly based on conventional risk factor assessment by validated algorithms, such as the Framingham Risk Score, the Pooled Cohort Equations and the European SCORE Risk Charts. The identification of subclinical atherosclerosis has emerged as a [...] Read more.
The risk prediction of future cardiovascular events is mainly based on conventional risk factor assessment by validated algorithms, such as the Framingham Risk Score, the Pooled Cohort Equations and the European SCORE Risk Charts. The identification of subclinical atherosclerosis has emerged as a promising tool to refine the individual cardiovascular risk identified by these models, to prognostic stratify asymptomatic individuals and to implement preventive strategies. Several imaging modalities have been proposed for the identification of subclinical organ damage, the main ones being coronary artery calcification scanning by cardiac computed tomography and the two-dimensional ultrasound evaluation of carotid arteries. In this context, echocardiography offers an assessment of cardiac calcifications at different sites, such as the mitral apparatus (including annulus, leaflets and papillary muscles), aortic valve and ascending aorta, findings that are associated with the clinical manifestation of atherosclerotic disease and are predictive of future cardiovascular events. The aim of this paper is to summarize the available evidence on clinical implications of cardiac calcification, review studies that propose semiquantitative ultrasound assessments of cardiac calcifications and evaluate the potential of ultrasound calcium scores for risk stratification and prevention of clinical events. Full article
(This article belongs to the Special Issue CT Coronary Angiography in Early Detection of Atherosclerosis)
Open AccessArticle
Prognostic Value of Bioactive Adrenomedullin in Critically Ill Patients with COVID-19 in Germany: An Observational Cohort Study
J. Clin. Med. 2021, 10(8), 1667; https://doi.org/10.3390/jcm10081667 - 13 Apr 2021
Viewed by 148
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has placed a significant burden on hospitals worldwide. Objective biomarkers for early risk stratification and clinical management are still lacking. The aim of this work was to determine whether bioactive adrenomedullin can assist in the risk stratification [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has placed a significant burden on hospitals worldwide. Objective biomarkers for early risk stratification and clinical management are still lacking. The aim of this work was to determine whether bioactive adrenomedullin can assist in the risk stratification and clinical management of critically ill COVID-19 patients. Fifty-three patients with confirmed COVID-19 were included in this prospective observational cohort study between March and April 2020. Bioactive adrenomedullin (bio-ADM) plasma concentration was measured daily for seven days after admission. The prognostic value and clinical significance of bio-ADM plasma levels were evaluated for the severity of respiratory failure, the need for extracorporeal organ support and outcome (28-day mortality). Bio-ADM levels increased with the severity of acute respiratory distress syndrome (ARDS; p < 0.001) and were significantly elevated in invasively ventilated patients (p = 0.006) and patients in need of extracorporeal membrane oxygenation (p = 0.040) or renal replacement therapy (RRT; p < 0.001) compared to patients without these conditions. Non-survivors showed significantly higher bio-ADM levels than survivors (p = 0.010). Bio-ADM levels predicted 28-day mortality (C-index 0.72, 95% confidence interval 0.56–0.87, p < 0.001). Bio-ADM plasma levels correlate with disease severity, the need for extracorporeal organ assistance, and outcome, and highlight the promising value of bio-ADM in the early risk stratification and management of patients with COVID-19. Full article
(This article belongs to the Section Intensive Care)
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Open AccessArticle
Comorbidities and Susceptibility to COVID-19: A Generalized Gene Set Data Mining Approach
J. Clin. Med. 2021, 10(8), 1666; https://doi.org/10.3390/jcm10081666 - 13 Apr 2021
Viewed by 130
Abstract
The COVID-19 pandemic has led to over 2.26 million deaths for almost 104 million confirmed cases worldwide, as of 4 February 2021 (WHO). Risk factors include pre-existing conditions such as cancer, cardiovascular disease, diabetes, and obesity. Although several vaccines have been deployed, there [...] Read more.
The COVID-19 pandemic has led to over 2.26 million deaths for almost 104 million confirmed cases worldwide, as of 4 February 2021 (WHO). Risk factors include pre-existing conditions such as cancer, cardiovascular disease, diabetes, and obesity. Although several vaccines have been deployed, there are few alternative anti-viral treatments available in the case of reduced or non-existent vaccine protection. Adopting a long-term holistic approach to cope with the COVID-19 pandemic appears critical with the emergence of novel and more infectious SARS-CoV-2 variants. Our objective was to identify comorbidity-associated single nucleotide polymorphisms (SNPs), potentially conferring increased susceptibility to SARS-CoV-2 infection using a computational meta-analysis approach. SNP datasets were downloaded from a publicly available genome-wide association studies (GWAS) catalog for 141 of 258 candidate COVID-19 comorbidities. Gene-level SNP analysis was performed to identify significant pathways by using the program MAGMA. An SNP annotation program was used to analyze MAGMA-identified genes. Differential gene expression was determined for significant genes across 30 general tissue types using the Functional and Annotation Mapping of GWAS online tool GENE2FUNC. COVID-19 comorbidities (n = 22) from six disease categories were found to have significant associated pathways, validated by Q–Q plots (p < 0.05). Protein–protein interactions of significant (p < 0.05) differentially expressed genes were visualized with the STRING program. Gene interaction networks were found to be relevant to SARS and influenza pathogenesis. In conclusion, we were able to identify the pathways potentially affected by or affecting SARS-CoV-2 infection in underlying medical conditions likely to confer susceptibility and/or the severity of COVID-19. Our findings have implications in future COVID-19 experimental research and treatment development. Full article
Open AccessReview
Pancreatic Cancer Exposome Profile to Aid Early Detection and Inform Prevention Strategies
J. Clin. Med. 2021, 10(8), 1665; https://doi.org/10.3390/jcm10081665 - 13 Apr 2021
Viewed by 186
Abstract
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence [...] Read more.
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals’ risk for PCa. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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Open AccessReview
Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-up
J. Clin. Med. 2021, 10(8), 1664; https://doi.org/10.3390/jcm10081664 - 13 Apr 2021
Viewed by 193
Abstract
Fabry disease (FD) is a lysosomal storage disorder caused by deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene, resulting in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes different pathogenic mechanisms in [...] Read more.
Fabry disease (FD) is a lysosomal storage disorder caused by deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene, resulting in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes different pathogenic mechanisms in which several mediators could be implicated, inducing multiorgan lesions, mainly in the kidney, heart and nervous system, resulting in clinical manifestations of the disease. Enzyme replacement therapy was shown to delay disease progression, mainly if initiated early. However, a diagnosis in the early stages represents a clinical challenge, especially in patients with a non-classic phenotype, which prompts the search for biomarkers that help detect and predict the evolution of the disease. We have reviewed the mediators involved in different pathogenic mechanisms that were studied as potential biomarkers and can be easily incorporated into clinical practice. Some accumulation biomarkers seem to be useful to detect non-classic forms of the disease and could even improve diagnosis of female patients. The combination of such biomarkers with some response biomarkers, may be useful for early detection of organ injury. The incorporation of some biomarkers into clinical practice may increase the capacity of detection compared to that currently obtained with the established diagnostic markers and provide more information on the progression and prognosis of the disease. Full article
(This article belongs to the Special Issue Biomarkers in Genetic Metabolic Disorders)
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Open AccessArticle
Epidemiology of Primary Epithelial Salivary Gland Tumors in Southern Poland—A 26-Year, Clinicopathologic, Retrospective Analysis
J. Clin. Med. 2021, 10(8), 1663; https://doi.org/10.3390/jcm10081663 - 13 Apr 2021
Viewed by 154
Abstract
(1) Background: Epidemiological studies of epithelial salivary gland neoplasms are difficult to conduct effectively due to tumor rarity, histological heterogeneity, tumor location diversity, and a lack of national registries collecting data. This study presents 26 years of epidemiological data from a single institution [...] Read more.
(1) Background: Epidemiological studies of epithelial salivary gland neoplasms are difficult to conduct effectively due to tumor rarity, histological heterogeneity, tumor location diversity, and a lack of national registries collecting data. This study presents 26 years of epidemiological data from a single institution in southern Poland that estimates incidence rates of primary epithelial salivary gland tumors. (2) Methods: The charts of 805 patients with epithelial salivary gland tumors were retrospectively reviewed. (3) Results: Pleomorphic adenomas occurred less frequently in elderly patients; however, Warthin tumors were more common (p < 0.001). Pediatric patients mainly suffered from mucoepidermoid carcinoma. The estimated crude and European age-standardized incidence rates of all primary epithelial salivary gland tumors were 6.7 and 6.02 per 100,000 population, respectively. The incidence rates of salivary gland tumors increased in recent years; however, this is attributed to an increase in benign tumors (p < 0.001). (4) Conclusions: The incidence of primary epithelial salivary gland tumors in southern Poland has increased over the past 26 years. This increase is attributed to a rise in the number of patients with benign tumors, particularly Warthin tumors in elderly patients. Moreover, the incidence of malignant salivary gland tumors appears to be higher in pediatric patients. Full article
(This article belongs to the Section Otolaryngology)
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