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J. Clin. Med., Volume 11, Issue 20 (October-2 2022) – 250 articles

Cover Story (view full-size image): Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), affecting up to 90% of patients and representing the onset symptom in 60–80% of cases. SLE arthritis can be classified into three different subtypes, with different prevalences and biomarkers. The most frequent clinical phenotype is represented by nondeforming nonerosive polyarthritis; more rarely, radiologically nonerosive but deforming arthropathy (Jaccoud’s arthropathy) and rheumatoid-like erosive arthritis (rhupus) can be observed. Identifying the pathogenetic mechanisms underlying the development of musculoskeletal manifestations is crucial for developing therapeutic strategies with which to suppress synovial inflammation, prevent erosions as well as deformities, and improve SLE patients’ quality of life. View this paper
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10 pages, 938 KiB  
Case Report
Case Report with Systematic Literature Review on Vascular Complications of BCG Intravesical Therapy for Bladder Cancer
by Brianna King, Dhanveer Singh, Animesh Rathore, Ronald Flenner and Mark Flemmer
J. Clin. Med. 2022, 11(20), 6226; https://doi.org/10.3390/jcm11206226 - 21 Oct 2022
Cited by 3 | Viewed by 2047
Abstract
(1) Background: Intravesical instillation of therapeutic Bacillus Calmette-Guerin (BCG) is the standard of treatment for non-muscular invasive bladder cancer. Although the exact immunomodulatory effects of BCG therapy in non-muscular invasive bladder cancer (NMIBC) are still unclear, it has been considered a safe and [...] Read more.
(1) Background: Intravesical instillation of therapeutic Bacillus Calmette-Guerin (BCG) is the standard of treatment for non-muscular invasive bladder cancer. Although the exact immunomodulatory effects of BCG therapy in non-muscular invasive bladder cancer (NMIBC) are still unclear, it has been considered a safe and effective treatment with the largest to-date report of complications citing minimal side effects, none of which included arterial involvement; (2) Methods: A systematic literature review was performed using PubMed, Cochrane, Medline, and Google Scholar from database inception to March 2021. Only eligible studies reporting aneurysm formation in adult patients with a history of BCG immunotherapy and no previous vascular pathology were included; (3) Results: A systematic literature review was conducted, highlighting 17 reports suggestive of BCG-induced mycotic aneurysm development. We added a case of a 78-year-old male, 30 months after last BCG-instillation, with a mycotic abdominal aneurysm yielding Mycobacterium tuberculosis with pyrazinamide resistance culture.; (4) Conclusions: Concluding results suggest a higher incidence of vascular complications from BCG intravesical therapy in the treatment of non-muscular invasive bladder cancer than previously reported. Recommendations are made to emphasize further research of this immunotherapy complication to facilitate the creation of guidelines for diagnosis and management of these patients. Full article
(This article belongs to the Section Nephrology & Urology)
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15 pages, 657 KiB  
Review
The Role of Selected Serpins in Gastrointestinal (GI) Malignancies
by Sara Pączek and Barbara Mroczko
J. Clin. Med. 2022, 11(20), 6225; https://doi.org/10.3390/jcm11206225 - 21 Oct 2022
Cited by 2 | Viewed by 2070
Abstract
Gastrointestinal (GI) cancers, which are a diverse group of malignant diseases, represent a major healthcare problem around the world. Due to the lack of specific symptoms in the early stages as well as insufficient diagnostic possibilities, these malignancies occupy the leading position in [...] Read more.
Gastrointestinal (GI) cancers, which are a diverse group of malignant diseases, represent a major healthcare problem around the world. Due to the lack of specific symptoms in the early stages as well as insufficient diagnostic possibilities, these malignancies occupy the leading position in the causes of death worldwide. The currently available tests have too many limitations to be part of routine diagnostics. Therefore, new potential biomarkers that could be used as diagnostic and prognostic factors for these cancers are still being sought. Among the proteins that might fit this role are serpins, which are serine protease inhibitors. Although the serpins themselves have been known for many years, they have recently become the centre of attention for many authors, especially due to the fact that a number of proteins in this family are involved in many stages of neoplasia formation, from angiogenesis through tumour growth to progression. Therefore, the aim of this review is to present the current knowledge about the significance of serpins in GI malignancies, especially their involvement in the development and progression of oesophageal, gastric, pancreatic and colorectal cancers. This review summarises and confirms the important roles of selected serpins in the pathogenesis of various GI cancers and also points to their promising roles as therapeutic targets. However, due to the relatively nonspecific nature of serpins, future research should be carried out to elucidate the mechanisms involved in tumour pathogenesis in more detail. Full article
(This article belongs to the Special Issue Colorectal Disorders: Diagnosis and Treatments)
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33 pages, 8371 KiB  
Review
A Systematic Review of Treatments of Post-Concussion Symptoms
by Camille Heslot, Philippe Azouvi, Valérie Perdrieau, Aurélie Granger, Clémence Lefèvre-Dognin and Mélanie Cogné
J. Clin. Med. 2022, 11(20), 6224; https://doi.org/10.3390/jcm11206224 - 21 Oct 2022
Cited by 19 | Viewed by 7190
Abstract
Approximately 10–20% of patients who have sustained a mild Traumatic Brain Injury (mTBI) show persistent post-concussion symptoms (PCS). This review aims to summarize the level of evidence concerning interventions for PCS. Following the PRISMA guidelines, we conducted a systematic review regarding interventions for [...] Read more.
Approximately 10–20% of patients who have sustained a mild Traumatic Brain Injury (mTBI) show persistent post-concussion symptoms (PCS). This review aims to summarize the level of evidence concerning interventions for PCS. Following the PRISMA guidelines, we conducted a systematic review regarding interventions for PCS post-mTBI until August 2021 using the Medline, Cochrane, and Embase databases. Inclusion criteria were the following: (1) intervention focusing on PCS after mTBI, (2) presence of a control group, and (3) adult patients (≥18 y.o). Quality assessment was determined using the Incog recommendation level, and the risk of bias was assessed using the revised Cochrane risk-of-bias tool. We first selected 104 full-text articles. Finally, 55 studies were retained, including 35 that obtained the highest level of evidence. The risk of bias was high in 22 out of 55 studies. Cognitive training, psycho-education, cognitive behavioral therapy, and graded return to physical activity demonstrated some effectiveness on persistent PCS. However, there is limited evidence of the beneficial effect of Methylphenidate. Oculomotor rehabilitation, light therapy, and headache management using repetitive transcranial magnetic stimulation seem effective regarding somatic complaints and sleep disorders. The preventive effect of early (<3 months) interventions remains up for debate. Despite its limitations, the results of the present review should encourage clinicians to propose a tailored treatment to patients according to the type and severity of PCS and could encourage further research with larger groups. Full article
(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Recent Trends and Future Perspectives)
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13 pages, 1470 KiB  
Article
Prospective Evaluation of Different Methods for Volumetric Analysis on [18F]FDG PET/CT in Pediatric Hodgkin Lymphoma
by Egesta Lopci, Caterina Elia, Barbara Catalfamo, Roberta Burnelli, Valli De Re, Lara Mussolin, Arnoldo Piccardo, Angelina Cistaro, Eugenio Borsatti, Pietro Zucchetta, Maurizio Bianchi, Salvatore Buffardi, Piero Farruggia, Alberto Garaventa, Alessandra Sala, Luciana Vinti, Christine Mauz-Koerholz and Maurizio Mascarin
J. Clin. Med. 2022, 11(20), 6223; https://doi.org/10.3390/jcm11206223 - 21 Oct 2022
Cited by 8 | Viewed by 2127
Abstract
Rationale: Therapy response evaluation by 18F-fluorodeoxyglucose PET/CT (FDG PET) has become a powerful tool for the discrimination of responders from non-responders in pediatric Hodgkin lymphoma (HL). Recently, volumetric analyses have been regarded as a valuable tool for disease prognostication and biological characterization [...] Read more.
Rationale: Therapy response evaluation by 18F-fluorodeoxyglucose PET/CT (FDG PET) has become a powerful tool for the discrimination of responders from non-responders in pediatric Hodgkin lymphoma (HL). Recently, volumetric analyses have been regarded as a valuable tool for disease prognostication and biological characterization in cancer. Given the multitude of methods available for volumetric analysis in HL, the AIEOP Hodgkin Lymphoma Study Group has designed a prospective analysis of the Italian cohort enrolled in the EuroNet-PHL-C2 trial. Methods: Primarily, the study aimed to compare the different segmentation techniques used for volumetric assessment in HL patients at baseline (PET1) and during therapy: early (PET2) and late assessment (PET3). Overall, 50 patients and 150 scans were investigated for the current analysis. A dedicated software was used to semi-automatically delineate contours of the lesions by using different threshold methods. More specifically, four methods were applied: (1) fixed 41% threshold of the maximum standardized uptake value (SUVmax) within the respective lymphoma site (V41%), (2) fixed absolute SUV threshold of 2.5 (V2.5); (3) SUVmax(lesion)/SUVmean liver >1.5 (Vliver); (4) adaptive method (AM). All parameters obtained from the different methods were analyzed with respect to response. Results: Among the different methods investigated, the strongest correlation was observed between AM and Vliver (rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at all scan timing), along with V2.5 and AM or Vliver (rho 0.98, p < 0.001 for TLG at baseline; rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at PET2 and PET3, respectively). To determine the best segmentation method, we applied logistic regression and correlated different results with Deauville scores at late evaluation. Logistic regression demonstrated that MTV (metabolic tumor volume) and TLG (total lesion glycolysis) computation according to V2.5 and Vliver significantly correlated to response to treatment (p = 0.01 and 0.04 for MTV and 0.03 and 0.04 for TLG, respectively). SUVmean also resulted in significant correlation as absolute value or variation. Conclusions: The best correlation for volumetric analysis was documented for AM and Vliver, followed by V2.5. The volumetric analyses obtained from V2.5 and Vliver significantly correlated to response to therapy, proving to be preferred thresholds in our pediatric HL cohort. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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15 pages, 712 KiB  
Article
Factors Influencing the Survival Rate of Teeth and Implants in Patients after Tumor Therapy to the Head and Neck Region—Part 1: Tooth Survival
by Ramona Schweyen, Waldemar Reich, Dirk Vordermark, Thomas Kuhnt, Andreas Wienke and Jeremias Hey
J. Clin. Med. 2022, 11(20), 6222; https://doi.org/10.3390/jcm11206222 - 21 Oct 2022
Cited by 1 | Viewed by 1608
Abstract
We aimed to evaluate possible factors influencing the long-term survival of teeth after tumor therapy (TT) to the head and neck region with and without radiation. Between January 2019 and January 2020, patients who underwent TT for head and neck cancer and received [...] Read more.
We aimed to evaluate possible factors influencing the long-term survival of teeth after tumor therapy (TT) to the head and neck region with and without radiation. Between January 2019 and January 2020, patients who underwent TT for head and neck cancer and received dental treatment before and after TT at the Department of Prosthetic Dentistry of the Martin Luther University Halle-Wittenberg were enrolled in the study. Clinical examination with assessment of dental status and stimulated salivary flow rate (SFR) was performed and information about disease progression and therapy was retrieved from medical records. Of 118 patients (male: 70.3%; mean age: 63.2 ± 12.4 years), 95 received radiotherapy (RT), and 47 were administered radio-chemotherapy (RCT). The teeth of irradiated patients exhibited a lower 5-year survival probability (74.2%) than those of non-irradiated patients (89.4%). The risk of loss (RL) after RT increased with nicotine use, presence of intraoral defects, reduced SFR, RCT and regarding mandibular teeth, and decreased with crowning following TT. Lower SFR increased the RL even without RT. Consideration of patient’s treatment history, individual risk profile, and clinical findings during the prosthetic planning phase could enable earlier, more targeted dental treatment after TT (e.g., timely crowning). Full article
(This article belongs to the Special Issue Clinical Advances in Osseointegrated Oral Implants)
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10 pages, 655 KiB  
Article
Multimodal Treatment with Cognitive Behavioral Therapeutic Intervention Plus Bladder Treatment Is More Effective than Monotherapy for Patients with Interstitial Cystitis/Bladder Pain Syndrome—A Randomized Clinical Trial
by Wan-Ru Yu, Jia-Fong Jhang, Bai-Yueh Chen, Syuan-Ru Ou, Hao-Ming Li and Hann-Chorng Kuo
J. Clin. Med. 2022, 11(20), 6221; https://doi.org/10.3390/jcm11206221 - 21 Oct 2022
Cited by 5 | Viewed by 2001
Abstract
(1) Background: Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) not only induces physiological damage but also greatly affects psychological stress. Multidisciplinary therapy has been recommended for IC/BPS treatment, but clinical trial data of combined bladder therapy and cognitive behavioral therapy (CBT) are lacking. This [...] Read more.
(1) Background: Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) not only induces physiological damage but also greatly affects psychological stress. Multidisciplinary therapy has been recommended for IC/BPS treatment, but clinical trial data of combined bladder therapy and cognitive behavioral therapy (CBT) are lacking. This study evaluated CBT efficacy in patients with IC/BPS. (2) Methods: Patients with IC/BPS were randomized to the bladder monotherapy (BT) or combined CBT (CBT) group. The primary endpoint was the self-reported outcome by global response assessment (GRA). Secondary endpoints included IC symptoms and problem index, bladder pain score, Beck’s anxiety inventory (BAI), and depression inventory, and objective parameters were also compared. (3) Result: A total of 30 patients receiving BT and 30 receiving CBT therapy were enrolled. Significant improvement of the BAI at 8 (p = 0.045) and 12 weeks (p = 0.02) post-treatment was observed in the CBT group, with significantly greater GRA scores at 12 weeks (p < 0.001). Repeated measures analysis of variance showed a significant effect within the CBT group on IC/BPS patients’ self-reported treatment outcomes (p = 0.001) and anxiety severity BAI scores (p = 0.033). (4) Conclusion: A multimodal treatment of CBT combined with suitable bladder treatment more effectively improves anxiety severity and treatment outcomes in patients with IC/BPS. Full article
(This article belongs to the Topic Clinical, Translational, Basic Researches, and Application of Bacterial Toxins on Bladder Diseases and Lower Urinary Tract Dysfunctions)
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17 pages, 3712 KiB  
Article
Cardiac-Gated Neuromodulation Increased Baroreflex Sensitivity and Reduced Pain Sensitivity in Female Fibromyalgia Patients
by Kati Thieme, Kathrin Jung, Marc G. Mathys, Richard H. Gracely and Dennis C. Turk
J. Clin. Med. 2022, 11(20), 6220; https://doi.org/10.3390/jcm11206220 - 21 Oct 2022
Cited by 3 | Viewed by 1555
Abstract
The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned [...] Read more.
The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. A total of 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 min-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with two control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed. Reduced BRS in FM at baseline increased by 41% during two, ≈8 min-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps < 0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (p < 0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic responses. Full article
(This article belongs to the Section Anesthesiology)
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13 pages, 1352 KiB  
Article
Diagnosing Hemophagocytic Lymphohistiocytosis with Machine Learning: A Proof of Concept
by Thomas El Jammal, Arthur Guerber, Martin Prodel, Maxime Fauter, Pascal Sève and Yvan Jamilloux
J. Clin. Med. 2022, 11(20), 6219; https://doi.org/10.3390/jcm11206219 - 21 Oct 2022
Cited by 2 | Viewed by 1787
Abstract
Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by uncontrolled activation of immune cells and mediators. Two diagnostic tools are widely used in clinical practice: the HLH-2004 criteria and the Hscore. Despite their good diagnostic performance, these scores were constructed after a selection of [...] Read more.
Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by uncontrolled activation of immune cells and mediators. Two diagnostic tools are widely used in clinical practice: the HLH-2004 criteria and the Hscore. Despite their good diagnostic performance, these scores were constructed after a selection of variables based on expert consensus. We propose here a machine learning approach to build a classification model for HLH in a cohort of patients selected by glycosylated ferritin dosage in our tertiary center in Lyon, France. On a dataset of 207 adult patients with 26 variables, our model showed good overall diagnostic performances with a sensitivity of 71.4% and high specificity, and positive and negative predictive values which were 100%, 100%, and 96.9%, respectively. Although generalization is difficult on a selected population, this is the first study to date to provide a machine-learning model for HLH detection. Further studies will be required to improve the machine learning model performances with a large number of HLH cases and with appropriate controls. Full article
(This article belongs to the Section Immunology)
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15 pages, 8305 KiB  
Article
Chondral/Desmal Osteogenesis in 3D Spheroids Sensitized by Psychostimulants
by Nele Wagener, Wolfgang Lehmann, Kai O. Böker, Eric Röhner and Pietro Di Fazio
J. Clin. Med. 2022, 11(20), 6218; https://doi.org/10.3390/jcm11206218 - 21 Oct 2022
Cited by 1 | Viewed by 1785
Abstract
Attention deficit hyperactivity disorder (ADHD) affects 6.4 million children in the United States of America. Children and adolescents, the main consumers of ADHD medication, are in the bone growth phase, which extends over a period of up to two decades. Thus, impaired proliferation [...] Read more.
Attention deficit hyperactivity disorder (ADHD) affects 6.4 million children in the United States of America. Children and adolescents, the main consumers of ADHD medication, are in the bone growth phase, which extends over a period of up to two decades. Thus, impaired proliferation and maturation of chondrocytes and osteoblasts can result in impaired bone formation. The aim of this study is to investigate, for the first time, the effects of the ADHD-medication modafinil, atomoxetine and guanfacine on bone growth and repair in vitro. Using two-dimensional and three-dimensional cell models, we investigated the chondrogenic/osteogenic differentiation, proliferation and viability of human mesenchymal progenitor cells. Real-time cell proliferation was measured by xCELLigence. Live/dead staining and size measurement of hMSC- and MG63 monolayer and spheroids were performed after administration of therapeutic plasma concentrations of modafinil, atomoxetine and guanfacine. Chondrogenic differentiation was quantified by RTqPCR. The chondrogenic and osteogenic differentiation was evaluated by histological cryo-sections. Modafinil, atomoxetine and guanfacine reduced chondrogenic and osteogenic differentiation terms of transcript expression and at the histological level. Cell viability of the MG63- and hMSC monolayer was not impeded by ADHD-medication. Our in vitro results indicate that modafinil, atomoxetine and guanfacine may impair chondrogenic and osteogenic differentiation in a 3D model reflecting the in vivo physiologic condition. Full article
(This article belongs to the Special Issue Recent Research in Skeletal Diseases)
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15 pages, 1409 KiB  
Article
Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients
by Natalia Estrada, Lurdes Zamora, Francisca Ferrer-Marín, Laura Palomo, Olga García, Patricia Vélez, Iris De la Fuente, Miguel Sagüés, Marta Cabezón, Montserrat Cortés, Rolando Omar Vallansot, María Alicia Senín-Magán, Concepción Boqué and Blanca Xicoy
J. Clin. Med. 2022, 11(20), 6217; https://doi.org/10.3390/jcm11206217 - 21 Oct 2022
Cited by 1 | Viewed by 1952
Abstract
Imatinib is the most common first-line tyrosine kinase inhibitor (TKI) used to treat chronic-phase chronic myeloid leukemia (CP-CML). However, only a proportion of patients achieve major molecular response (MMR), so there is a need to find biological factors that aid the selection of [...] Read more.
Imatinib is the most common first-line tyrosine kinase inhibitor (TKI) used to treat chronic-phase chronic myeloid leukemia (CP-CML). However, only a proportion of patients achieve major molecular response (MMR), so there is a need to find biological factors that aid the selection of the optimal therapeutic strategy (imatinib vs. more potent second-generation TKIs). The aim of this retrospective study was to understand the contribution of germline single-nucleotide variants (gSNVs) in the achievement of MMR with imatinib. In particular, a discovery cohort including 45 CP-CML patients was analyzed through the DMET array, which interrogates 1936 variants in 231 genes related to the absorption, distribution, metabolism and excretion (ADME) process. Variants statistically significant in the discovery cohort were then tested in an extended and independent cohort of 137 CP-CML patients. Finally, a total of 7 gSNVs (ABCG1-rs492338, ABCB11-rs496550, ABCB11-rs497692, CYP2D6-rs1135840, CYP11B1-rs7003319, MAT1A-rs4934027 and SLC22A1-rs628031) and one haplotype in the ABCB11 gene were significantly associated with the achievement of MMR with first-line imatinibtreatment. In conclusion, we identified a genetic signature of response to imatinib in CP-CML patients that could be useful in selecting those patients that may benefit from starting imatinib as first-line therapy, therefore avoiding the toxicity related to second-generation TKIs. Full article
(This article belongs to the Special Issue Chronic Myeloid Leukemia: Clinical Diagnosis and Treatment)
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9 pages, 555 KiB  
Article
Approach to Knee Arthropathy through 180-Degree Immersive VR Movement Visualization in Adult Patients with Severe Hemophilia: A Pilot Study
by Roberto Ucero-Lozano, Raúl Pérez-Llanes, José Antonio López-Pina and Rubén Cuesta-Barriuso
J. Clin. Med. 2022, 11(20), 6216; https://doi.org/10.3390/jcm11206216 - 21 Oct 2022
Cited by 2 | Viewed by 1515
Abstract
(1) Background: Hemarthrosis is a typical clinical manifestation in patients with hemophilia. Its recurrence causes hemophilic arthropathy, characterized by chronic joint pain. Watching movement recorded from a first-person perspective and immersively can be effective in the management of chronic pain. The objective of [...] Read more.
(1) Background: Hemarthrosis is a typical clinical manifestation in patients with hemophilia. Its recurrence causes hemophilic arthropathy, characterized by chronic joint pain. Watching movement recorded from a first-person perspective and immersively can be effective in the management of chronic pain. The objective of this study was to evaluate the effectiveness of an immersive virtual reality intervention in improving the pain intensity, joint condition, muscle strength and range of motion in patients with hemophilic knee arthropathy. (2) Methods: Thirteen patients with hemophilic knee arthropathy were recruited. The patients wore virtual reality glasses and watched a flexion–extension movement of the knee on an immersive 180° video, recorded from a first-person perspective over a 28-day period. The primary variable was the pain intensity (visual analog scale). The secondary variables were the joint status (Hemophilia Joint Health Score), quadriceps and hamstring strength (dynamometry), and range of motion (goniometry). (3) Results: After the intervention period, statistically significant differences were observed in the intensity of the joint pain (Standard error [SE] = 19.31; 95% interval confidence [95%CI] = −1.05; −0.26), joint condition (SE = 18.68; 95%CI = −1.16; −0.52) and quadriceps strength (SE = 35.00; 95%CI = 2.53; 17.47). We found that 38.46% and 23.07% of the patients exhibited an improvement in their quadriceps muscle strength and joint condition above the minimum detectable change for both variables (8.21% and 1.79%, respectively). (4) Conclusions: One hundred and eighty degree immersive VR motion visualization can improve the intensity of joint pain in patients with hemophilic knee arthropathy. An intervention using immersive virtual reality can be an effective complementary approach to improve the joint condition and quadriceps strength in these patients. Full article
(This article belongs to the Special Issue Health, Quality of Life and Sport Rehabilitation)
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8 pages, 2911 KiB  
Article
Characteristics of Synovial Fistula of the Ankle Joint: A Case Series
by Chul-Hyun Park, Jeong Jin Park, In Ha Woo, Hongfei Yan and Woo-Chun Lee
J. Clin. Med. 2022, 11(20), 6215; https://doi.org/10.3390/jcm11206215 - 21 Oct 2022
Cited by 1 | Viewed by 3471
Abstract
(1) Background: Little is known about the etiology, clinical features, diagnosis methods, treatments, and the prognosis of synovial fistula of the ankle joint. The purpose of this study is to investigate the clinical features of synovial fistula of the ankle joint. (2) Methods: [...] Read more.
(1) Background: Little is known about the etiology, clinical features, diagnosis methods, treatments, and the prognosis of synovial fistula of the ankle joint. The purpose of this study is to investigate the clinical features of synovial fistula of the ankle joint. (2) Methods: Between March 2003 and December 2018, 40 cysts associated with synovial fistula of the ankle joint were treated consecutively by two surgeons. Case histories, clinical manifestations, intraoperative findings, surgical treatment methods, and treatment outcomes were evaluated to characterize fistula-associated cysts. The clinical results were assessed using the visual analog scale (VAS) and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot functional scores, preoperatively and at the last follow-up. (3) Results: The main complaints were ankle instability and pain (15 patients), pain only (15 patients), instability (seven patients), and cosmetic problems (three patients). Eleven patients had a cyst with an open skin wound, and eight of these patients had undergone surgery under a misdiagnosis of bursitis. Cysts were located anterior to the lateral malleolus in 22 cases, next to the lateral malleolus in 13 cases, posterior to the lateral malleolus in three cases, and across the entire lateral malleolus in two cases. Mean VAS and AOFAS scores improved from 5.2 (range, from 1 to 7) and 72.3 (range, from 65 to 87) preoperatively to 1.1 (range, from 0 to 3) and 93.6 (range, from 85 to 100), respectively, at final follow-up visits. (4) Conclusions: Cyst occurrence due to a synovial fistula should be considered when treating a cyst around the lateral malleolus. Fistula repair and reinforcement with fibular periosteum provides a good treatment option for cysts attributed to synovial fistula of the ankle that fail to respond to conservative treatment. Full article
(This article belongs to the Section Orthopedics)
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13 pages, 552 KiB  
Article
The Interactive Effects of Post-Traumatic Stress Symptoms and Breathlessness on Fatigue Severity in Post-COVID-19 Syndrome
by Sari Harenwall, Suzanne Heywood-Everett, Rebecca Henderson, Joanne Smith, Rachel McEnery and Amy R. Bland
J. Clin. Med. 2022, 11(20), 6214; https://doi.org/10.3390/jcm11206214 - 21 Oct 2022
Cited by 8 | Viewed by 3032
Abstract
Background: Post-traumatic stress symptoms (PTSS) and breathlessness have been well documented in the acute phase of COVID-19 as well as in Post-COVID-19 Syndrome (PCS), commonly known as Long-COVID. The present study aimed to explore whether PTSS and breathlessness interact to exacerbate fatigue among [...] Read more.
Background: Post-traumatic stress symptoms (PTSS) and breathlessness have been well documented in the acute phase of COVID-19 as well as in Post-COVID-19 Syndrome (PCS), commonly known as Long-COVID. The present study aimed to explore whether PTSS and breathlessness interact to exacerbate fatigue among individuals recovering from PCS, similar to the effects evidenced in other health conditions that feature respiratory distress.. Methods: Outcome measures were collected from 154 participants reporting persistent fatigue following acute COVID-19 infection who were enrolled in a 7-week rehabilitation course provided by the Primary Care Wellbeing Service (PCWBS) in Bradford District Care NHS Foundation Trust (BDCFT). Results: Hierarchical multiple linear regression revealed that fatigue severity was associated with a significant interaction between PTSS and breathlessness, even when controlling for pre-COVID health related quality of life (HRQoL), age, symptom duration and hospital admittance during the acute phase. Furthermore, improvements in fatigue following rehabilitation were significantly associated with improvements in PTSS. Conclusions: PTSS may be an important therapeutic target in multidisciplinary rehabilitation for reducing fatigue in the recovery from PCS. It is therefore important that treatment for PCS takes a biopsychosocial approach to recovery, putting emphasis on direct and indirect psychological factors which may facilitate or disrupt physical recovery. This highlights the need for all PCS clinics to screen for PTSD and if present, target as a priority in treatment to maximise the potential for successful rehabilitation. Full article
(This article belongs to the Section Epidemiology & Public Health)
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9 pages, 3975 KiB  
Article
Two-Year Healing Success Rates after Endodontic Treatment Using 3D Cleaning Technique: A Prospective Multicenter Clinical Study
by Giuseppe Pantaleo, Alessandra Amato, Alfredo Iandolo, Dina Abdellatif, Federica Di Spirito, Mario Caggiano, Massimo Pisano, Andrea Blasi, Roberto Fornara and Massimo Amato
J. Clin. Med. 2022, 11(20), 6213; https://doi.org/10.3390/jcm11206213 - 21 Oct 2022
Cited by 13 | Viewed by 2081
Abstract
Background: Various irrigation techniques for cleansing the endodontic space have been proposed, and internal heating combined with ultrasonic activation (3D cleaning technique) is considered an effective technique. This prospective multicenter clinical study aims to evaluate healing rates for teeth after root canal treatment [...] Read more.
Background: Various irrigation techniques for cleansing the endodontic space have been proposed, and internal heating combined with ultrasonic activation (3D cleaning technique) is considered an effective technique. This prospective multicenter clinical study aims to evaluate healing rates for teeth after root canal treatment utilizing the 3D cleaning technique and to report predictive values for success. Material and Methods: Ninety patients referred for a root canal treatment were included. All enrolled patients were treated with the 3D cleaning protocol. Four endodontists performed the clinical procedures and follow-up evaluations. Preoperative, postoperative and follow-up data were gathered from the consented patients. Each patient was assessed for any clinical signs or symptoms. Afterwards, two trained, blinded, and independent evaluators scored the subject’s periapical radiographs. This score was made by checking for the presence or absence of apical periodontitis using the periapical index (PAI). Then, the teeth were classified as healing or healed and were considered a success based on a cumulative success rate of healing. Statistical analysis was performed using the Fisher’s exact test, Pearson correlation, and logistic regression analyses of the preoperative prognostic factors at a 0.05 significance level. Results: 90 patients were evaluated at two years with a follow-up rate of 97.7%. The cumulative success rate of healing was 95.4%. Eight predicting aspects were identified by employing bivariate analyses. Then, using logistic analyses, the two prognostic significant variables directly correlated to healing were the preoperative presence of periapical index (p value = 0.016). Conclusions: In this two-year clinical study, the cumulative success rate of healing was 95.4% when patients were treated with the 3D cleaning protocol. Full article
(This article belongs to the Special Issue The State of the Art in Endodontics—Part II)
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9 pages, 255 KiB  
Article
Predictive Factors for Failure of Intraarticular Injection in Management of Adhesive Capsulitis of the Shoulder
by Stefan J. Hanish, Mathew L. Resnick, Hyunmin M. Kim and Matthew J. Smith
J. Clin. Med. 2022, 11(20), 6212; https://doi.org/10.3390/jcm11206212 - 21 Oct 2022
Cited by 3 | Viewed by 1905
Abstract
Intraarticular (IA) corticosteroid injections have been demonstrated to be an effective management for adhesive capsulitis in both the short- and mid-term. Yet, certain patients fail to improve both subjectively and clinically. This study aims to identify predictive factors for treatment failure of IA [...] Read more.
Intraarticular (IA) corticosteroid injections have been demonstrated to be an effective management for adhesive capsulitis in both the short- and mid-term. Yet, certain patients fail to improve both subjectively and clinically. This study aims to identify predictive factors for treatment failure of IA injections in management of adhesive capsulitis. A retrospective review found 533 patients undergoing IA corticosteroid or IA NSAID injection for adhesive capsulitis between June 2015 and May 2020 at a single healthcare institution. Patient demographics characteristics, comorbidities, pain scores, and range of motion were compared. Treatment failure was defined as need for subsequent IA injection within 6 months or progression to surgical management within 12 months. 152 patients (28.52%) experienced treatment failure of IA corticosteroid injection. Pre-injection pain scores were greater for those who experienced treatment failure (5.40 vs. 4.21, p < 0.05). Post-injection pain scores were greater for those who experienced treatment failure (3.77 vs. 2.17, p < 0.01). Reduced post-injection external rotation in abduction also predicted treatment failure (56.88° vs. 70.22°, p < 0.01). IA corticosteroid injections are associated with increased rates of failure and progression to surgical management when patients present with increased pain levels as well as with less improvement in pain levels and ROM following injection. Full article
(This article belongs to the Special Issue Clinical Challenges and Advances in Shoulder and Elbow Surgery)
14 pages, 646 KiB  
Review
The Quality of Life of Patients with Surgically Treated Colorectal Cancer: A Narrative Review
by Filip Świątkowski, Tomasz Górnicki, Kacper Bułdyś and Mariusz Chabowski
J. Clin. Med. 2022, 11(20), 6211; https://doi.org/10.3390/jcm11206211 - 21 Oct 2022
Cited by 7 | Viewed by 2729
Abstract
Introduction. Quality of life is a topic increasingly being addressed by researchers. Due to the increasing incidence of colorectal cancer, this issue is particularly relevant. Despite the increasing number of publications on this topic each year, it still requires further research. The aim [...] Read more.
Introduction. Quality of life is a topic increasingly being addressed by researchers. Due to the increasing incidence of colorectal cancer, this issue is particularly relevant. Despite the increasing number of publications on this topic each year, it still requires further research. The aim of this study was to analyze the available literature from the past 10 years, addressing the topic of QoL in patients with colorectal cancer which has been treated surgically. Material and methods. This review is based on 93 articles published between 2012 and 2022. It analyzes the impact of socioeconomic factors, the location and stage of the tumor, stoma and the method of surgical treatment on patients’ QoL and sexual functioning. Results. CRC has a negative impact on patients’ financial status, social functioning, pain and physical functioning. Patients with stage II or III cancer have an overall lower QoL than patients with stage I. The more proximally the lesion is located to the sphincters, the greater the negative impact on the QoL. There was a significant difference in favor of laparoscopic surgery compared with open surgery. In patients with a stoma, the QoL is lower compared with patients with preserved gastrointestinal tract continuity. The more time has passed since surgery, the more the presence of a stoma has a negative impact on QoL. Surgery for CRC negatively affects patients’ sex lives, especially in younger people and among men. Conclusions. This study may contribute to the identification of the factors that affect the QoL of patients with surgically treated colorectal cancer. This will allow even more effective and complete treatment, facilitating patients’ return to normal physical, mental and social functioning. Full article
(This article belongs to the Section Oncology)
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10 pages, 658 KiB  
Article
The Effectiveness and Tolerability of Glycopyrronium for Patients with Chronic Obstructive Pulmonary Disease in a Clinical Setting: GLARE-Taiwan
by Wei-Chang Huang, Sheng-Hao Lin, Liang-Wen Hang, Ching-Hsiung Lin and Jeng-Yuan Hsu
J. Clin. Med. 2022, 11(20), 6210; https://doi.org/10.3390/jcm11206210 - 21 Oct 2022
Viewed by 1463
Abstract
Glycopyrronium (GLY) is a pharmacological maintenance treatment for chronic obstructive pulmonary disease (COPD). However, its effectiveness and tolerability for COPD patients in routine clinical practice have not been well-investigated. This study aimed to assess the effectiveness of GLY on health-related quality of life [...] Read more.
Glycopyrronium (GLY) is a pharmacological maintenance treatment for chronic obstructive pulmonary disease (COPD). However, its effectiveness and tolerability for COPD patients in routine clinical practice have not been well-investigated. This study aimed to assess the effectiveness of GLY on health-related quality of life and its safety in patients with COPD in a routine clinical care setting. This multi-center, prospective, six-month observational study recruited patients diagnosed with COPD and treated with GLY at three medical centers in central Taiwan. The full analysis set (n = 102) had a significant improvement in the Clinical COPD Questionnaire total (mean ± SD = −0.39 ± 0.90, p = 0.002), symptoms (mean ± SD = −0.61 ± 0.90, p < 0.001) and mental state scores (mean ± SD = −0.54 ± 1.72, p = 0.021) but not the functional state score (mean ± SD = −0.10 ± 1.15, p = 0.529). During the observational period, 58 patients (52.73%) experienced adverse events; only one adverse event (dizziness) was suspected to be related to the study drug. Three patients (2.73%) discontinued the study and GLY treatment because of an adverse event. One patient (0.91%) died during the study period because of a cerebral infarction, which was judged to be not associated with GLY treatment. In conclusion, GLY could be effective in improving the health status and is safe for patients with COPD in a real-life setting. Full article
(This article belongs to the Section Pulmonology)
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15 pages, 789 KiB  
Article
Efficacy of Dupilumab on Different Phenotypes of Adult with Moderate-to-Severe Atopic Dermatitis in Taiwan: A Real-World Study
by Chin-Yi Yang, Po-Ju Lai, Chun-Bing Chen, Tom C. Chan, Rosaline Chung-Yee Hui, Yu-Huei Huang, Han-Chi Tseng, Shang-Hung Lin, Chun-Wei Lu, Hua-En Lee, Jing-Yi Lin, Min-Hui Chi, Ming-Feng Tsai, Yih-Shiou Hwang, Chuang-Wei Wang, Chia-Yu Chu and Wen-Hung Chung
J. Clin. Med. 2022, 11(20), 6209; https://doi.org/10.3390/jcm11206209 - 21 Oct 2022
Cited by 3 | Viewed by 3883
Abstract
To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18–87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to [...] Read more.
To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18–87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator’s Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response. Full article
(This article belongs to the Section Dermatology)
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14 pages, 1329 KiB  
Systematic Review
Concomitant Endoscopic Surgery for Bladder Tumors and Prostatic Obstruction: Are We Safely Hitting Two Birds with One Stone? A Systematic Review and Meta-Analysis
by Eliophotos Savvides, Nikolaos Pyrgidis, Georgios Langas, Evangelos N. Symeonidis, Georgios Dimitriadis and Petros Sountoulides
J. Clin. Med. 2022, 11(20), 6208; https://doi.org/10.3390/jcm11206208 - 21 Oct 2022
Cited by 1 | Viewed by 1735
Abstract
Background: Lower urinary tract symptoms (LUTS) caused by benign prostatic obstruction (BPO) and bladder tumors may co-exist, especially among elderly patients. Transurethral resection of bladder tumors (TURBT) and endoscopic surgery for benign prostatic obstruction in the same setting are avoided by many surgeons [...] Read more.
Background: Lower urinary tract symptoms (LUTS) caused by benign prostatic obstruction (BPO) and bladder tumors may co-exist, especially among elderly patients. Transurethral resection of bladder tumors (TURBT) and endoscopic surgery for benign prostatic obstruction in the same setting are avoided by many surgeons due to concerns for tumor cell seeding and recurrences in the prostatic urethra. Aim: The aim of this study was assess the effect of concomitant TURBT and endoscopic BPO surgery on oncological safety and patient quality of life via systematic review and meta-analysis. Methods: We searched the PubMed, Cochrane Library, EMBASE, Scopus, and Clinicaltrials.gov databases and sources of grey literature published before June 2021 for relevant studies. We performed a random-effects meta-analysis of odds ratios (ORs) or weighted mean differences (WMD) to compare concomitant TURBT and BPO surgery versus TURBT alone in terms of recurrence and progression rates. Accordingly, we undertook multiple subgroups and sensitivity analyses (PROSPERO: CRD42020173363). Results: Three randomized and twelve retrospective observational studies with 2421 participants were included. Across studies with good methodological quality, no statistically significant differences were demonstrated regarding overall bladder tumors recurrence rates between concomitant endoscopic BPO surgery and TURBT versus TURBT alone (OR: 0.81, 95% CI: 0.60–1.09, I2 = 42%). Similarly, no significant differences were observed in recurrences located at the bladder neck and/or prostatic urethra (OR: 1.06, 95% CI: 0.76–1.47, I2 = 0%), time to first recurrence (WMD: −0.2 months, 95% Cl: −2.2–1.8, I2 = 48%), and progression rate (OR: 1.05, 95% CI: 0.67–1.64, I2 = 0%). Subgroup analyses based on tumor grade, number of tumors, and utilization of single-instillation chemotherapy post-TURBT did not detect any significant differences in overall bladder tumor recurrence. The level of evidence was estimated as low for all outcomes. Concomitant surgery improved lower urinary tract symptoms. Conclusion: Concomitant endoscopic BPO surgery and TURBT are oncologically safe and improve LUTS-related quality of life. Full article
(This article belongs to the Special Issue Current and Emerging Therapies for Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia)
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6 pages, 5930 KiB  
Article
Endoscopic Ultrasound-Guided Botox Injection for Refractory Anal Fissure
by Navkiran Randhawa, Ahamed Khalyfa, Rida Aslam, M. Christopher Roebuck, Mahnoor Inam and Kamran Ayub
J. Clin. Med. 2022, 11(20), 6207; https://doi.org/10.3390/jcm11206207 - 21 Oct 2022
Cited by 2 | Viewed by 2912
Abstract
Background: Anal fissures cause severe pain and can be difficult to treat. Medical therapy is initially used, followed by sigmoidoscopy-guided botox injections if the medical therapy is not successful. With this technique, however, it is not clear whether botox is injected into the [...] Read more.
Background: Anal fissures cause severe pain and can be difficult to treat. Medical therapy is initially used, followed by sigmoidoscopy-guided botox injections if the medical therapy is not successful. With this technique, however, it is not clear whether botox is injected into the muscle layer or submucosa. Aim: To evaluate the efficacy of EUS-guided botox injection directly into the internal sphincter. Methods: Consecutive patients with chronic anal fissure refractory to conventional endoscopic botulinum toxin type A injection were enrolled in the study. EUS was performed using a linear array echoendoscope, and a 25 G needle was used to inject botox. All patients were followed up at one- and two-month intervals. Results: Eight patients with chronic anal fissures were included in the study. Six patients had an excellent response to botox at the two-month interval using a visual analog pain scale, while one patient had a moderate response with a pain score reduction of 40%. One patient had no response. No complications were noted. An improvement in visual analog scale (pre-score > post-score) was statistically significant at the p < 0.01 level. Conclusion: EUS-guided botox injection into the internal sphincter appears to be a promising technique for patients with refractory anal fissure with pain. Full article
(This article belongs to the Special Issue Endoscopic Ultrasound-Guided Diagnosis and Treatment of Gastrointestinal Diseases)
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10 pages, 960 KiB  
Article
A Retrospective Taiwanese-Population-Based Clinical Study on Determining the Efficacy and Safety of Disposable Circumcision Anastomat
by An-Chi Chou, Chun-Yo Laih and Fang-Yu Ku
J. Clin. Med. 2022, 11(20), 6206; https://doi.org/10.3390/jcm11206206 - 21 Oct 2022
Cited by 3 | Viewed by 6559
Abstract
Traditional approaches for male circumcision are tedious and could lead to complications such as peri-/postoperative pain, bleeding, and infection. Thus, for the first time, we investigated the surgical outcomes of recently the discovered Disposable Circumcision Anastomat Type A (Dongguan ZSR Biomedical Technology Company [...] Read more.
Traditional approaches for male circumcision are tedious and could lead to complications such as peri-/postoperative pain, bleeding, and infection. Thus, for the first time, we investigated the surgical outcomes of recently the discovered Disposable Circumcision Anastomat Type A (Dongguan ZSR Biomedical Technology Company Ltd., China), a disposable circumcision suture device (DCSD), in terms of the operation time, surgical complexity, safety, satisfaction, and aesthetic outcomes and most importantly the prognostic factors for postoperative infection. A total of 394 individuals were circumcised, with a mean age, body mass index (BMI), stretched penile length (SPL), and penile circumference of 30.1 ± 7.05 years, 25.47 ± 4.73, 10.12 ± 1.61, and 7 ± 0.73 cm, respectively. Associated comorbidities included diabetes mellitus (6.09%), hypertension (2.03%), gout (1.02%), end-stage renal disease (ESRD, 0.25%), and HIV (0.25%). The mean operation time, average postoperative bleeding, and wound infection rate was 31.4 ± 9.96 min, 2.54%, and 9.39%, respectively. The mean VAS postoperative pain scores at D0 and D1 were 4.4 ± 2.4 and 1.9 ± 1.6, respectively. Moreover, 1.27% of subjects required reoperation, and a 2.03% rate of instrument malfunction was noted. The significant factors associated with the post-operative infection group were age (p = 0.0313), BW (p = 0.0081), BMI (p = 0.0026), penile circumference (p = 0.0343), and DM (p ≤ 0.001). Multivariate analyses revealed only DM as a statistically significant factor (p < 0.001). Our box–whisker plot revealed no significant difference between the HbA1c level of infection (Hb1Ac = 7.77 ± 1.39) and non-infection groups (Hb1Ac = 6.92 ± 1.84). However, a trend of higher glycemic index in the infection group was observed. Conclusively, DSCD could be an effective and safe alternative to performing circumcision. However, in the population with advanced aging, phimosis, elevated BMI, and DM (HbA1C > 9%), users should be highly cautious due to the increased risk of infection, dehiscence, and hematoma. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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12 pages, 3043 KiB  
Article
DEXA Scan Body Fat Mass Distribution in Obese and Non-Obese Individuals and Risk of NAFLD—Analysis of 10,865 Individuals
by Caitlyn Tan, Kai En Chan, Cheng Han Ng, Michael Tseng, Nicholas Syn, Ansel Shao Pin Tang, Yip Han Chin, Wen Hui Lim, Darren Jun Hao Tan, Nicholas Chew, Elden Yen Hng Ong, Teng Kiat Koh, Jieling Xiao, Douglas Chee, Arun Valsan, Mohammad Shadab Siddiqui, Daniel Huang, Mazen Noureddin, Karn Wijarnpreecha and Mark D. Muthiah
J. Clin. Med. 2022, 11(20), 6205; https://doi.org/10.3390/jcm11206205 - 21 Oct 2022
Cited by 1 | Viewed by 3306
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide yet predicting non-obese NAFLD is challenging. Thus, this study investigates the potential of regional fat percentages obtained by dual-energy X-ray absorptiometry (DXA) in accurately assessing NAFLD risk. Using the United [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide yet predicting non-obese NAFLD is challenging. Thus, this study investigates the potential of regional fat percentages obtained by dual-energy X-ray absorptiometry (DXA) in accurately assessing NAFLD risk. Using the United States National Health and Nutrition Examination Survey (NHANES) 2011–2018, multivariate logistic regression and marginal analysis were conducted according to quartiles of regional fat percentages, stratified by gender. A total of 23,752 individuals were analysed. Males generally showed a larger increase in marginal probabilities of NAFLD development than females, except in head fat, which had the highest predictive probabilities of non-obese NAFLD in females (13.81%, 95%CI: 10.82–16.79) but the lowest in males (21.89%, 95%CI: 20.12–23.60). Increased percent of trunk fat was the strongest predictor of both non-obese (OR: 46.61, 95%CI: 33.55–64.76, p < 0.001) and obese NAFLD (OR: 2.93, 95%CI: 2.07–4.15, p < 0.001), whereas raised percent gynoid and leg fat were the weakest predictors. Ectopic fat deposits are increased in patients with non-obese NAFLD, with greater increases in truncal fat over gynoid fat. As increased fat deposits in all body regions can increase odds of NAFLD, therapeutic intervention to decrease ectopic fat, particularly truncal fat, may decrease NAFLD risk. Full article
(This article belongs to the Special Issue Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Current Concepts and Future Challenges)
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12 pages, 4026 KiB  
Article
Caspase-1 Inhibition Reduces Occurrence of PANoptosis in Macrophages Infected by E. faecalis OG1RF
by Danlu Chi, Yuejiao Zhang, Xinwei Lin, Qimei Gong and Zhongchun Tong
J. Clin. Med. 2022, 11(20), 6204; https://doi.org/10.3390/jcm11206204 - 21 Oct 2022
Cited by 6 | Viewed by 2756
Abstract
To investigate the effect of caspase-1 inhibition on PANoptosis in macrophages infected with Enterococcus faecalis OG1RF. RAW264.7 cells with and without pretreatment by caspase-1 inhibitor were infected with E. faecalis OG1RF at multiplicities of infection (MOIs). A live cell imaging analysis system and [...] Read more.
To investigate the effect of caspase-1 inhibition on PANoptosis in macrophages infected with Enterococcus faecalis OG1RF. RAW264.7 cells with and without pretreatment by caspase-1 inhibitor were infected with E. faecalis OG1RF at multiplicities of infection (MOIs). A live cell imaging analysis system and Western blot were applied to evaluate the dynamic curve of cell death and the expression of executor proteins of PANoptosis. The mRNA expression of IL-1β and IL-18 was quantified by RT-qPCR. Morphological changes were observed under scanning electron microscopy. We found that PI-positive cells emerged earlier and peaked at a faster rate in E. faecalis-infected macrophages (Ef-MPs) at higher MOIs. The expression of the N-terminal domain of the effector protein gasdermin D (GSDMD-N), cleaved caspase-3 and pMLKL were significantly upregulated at MOIs of 10:1 at 6 h and at MOI of 1:1 at 12 h postinfection. In Ef-MPs pretreated with caspase-1 inhibitor, the number of PI-positive cells was significantly reduced, and the expression of IL-1β and IL-18 genes and cleaved caspase-1/-3 and GSDMD-N proteins was significantly downregulated (p < 0.05), while pMLKL was still markedly increased (p < 0.05). Ef-MPs remained relatively intact with caspase-1 inhibitor. In conclusion, E. faecalis induced cell death in macrophages in an MOI-dependent manner. Caspase-1 inhibitor simultaneously inhibited pyroptosis and apoptosis in Ef-MPs, but necroptosis still occurred. Full article
(This article belongs to the Special Issue Clinical Updates in Endodontics)
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3 pages, 201 KiB  
Editorial
Post-Intensive Care Syndrome after Critical Illness: An Imperative for Effective Prevention
by Nicolas Paul and Björn Weiss
J. Clin. Med. 2022, 11(20), 6203; https://doi.org/10.3390/jcm11206203 - 21 Oct 2022
Cited by 1 | Viewed by 1855
Abstract
Over the last decades, the importance of intensive care has considerably increased [...] Full article
(This article belongs to the Special Issue Enhancing Recovery after Intensive Care Medicine in Clinical Practice)
13 pages, 754 KiB  
Review
Relationship between Testosterone and Sarcopenia in Older-Adult Men: A Narrative Review
by Kazuyoshi Shigehara, Yuki Kato, Kouji Izumi and Atsushi Mizokami
J. Clin. Med. 2022, 11(20), 6202; https://doi.org/10.3390/jcm11206202 - 20 Oct 2022
Cited by 19 | Viewed by 5431
Abstract
Age-related decline in testosterone is known to be associated with various clinical symptoms among older men and it is possible that the accompanying decline in muscle mass and strength might lead to a decline in motor and physical functions. Sarcopenia is an important [...] Read more.
Age-related decline in testosterone is known to be associated with various clinical symptoms among older men and it is possible that the accompanying decline in muscle mass and strength might lead to a decline in motor and physical functions. Sarcopenia is an important pathophysiological factor associated with frailty in older adults and is diagnosed in older adults as a decrease in muscle strength, muscle mass, and walking speed, which can lead to a significant decline in the quality of life and shortened healthy life expectancy. Testosterone directly interacts with the androgen receptor expressed in myonuclei and satellite cells and is also indirectly associated with muscle metabolism through various cytokines and molecules. Currently, significant correlations between testosterone and frailty in men have been confirmed by numerous cross-sectional studies. Many randomized control studies have also supported the beneficial effect of testosterone replacement therapy (TRT) on muscle volume and strength among men with low to normal testosterone levels. In the world’s aging society, TRT can be a tool for preventing the onset of sarcopenia in older-adult men. This narrative review aims to show the relationship between the decline in testosterone with age, sarcopenia, and frailty, as well as the effects of testosterone replacement therapy on muscle mass and strength. Full article
(This article belongs to the Special Issue Risk Factors, Prevention and Management of Frailty in Elderly)
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15 pages, 2386 KiB  
Review
The Role of Novel Cardiac Imaging for Contemporary Management of Heart Failure
by Frank A. Flachskampf and Tomasz Baron
J. Clin. Med. 2022, 11(20), 6201; https://doi.org/10.3390/jcm11206201 - 20 Oct 2022
Viewed by 2826
Abstract
Heart failure is becoming the central problem in cardiology. Its recognition, differential diagnosis, and the monitoring of therapy are intimately coupled with cardiac imaging. Cardiac imaging has witnessed an explosive growth and differentiation, with echocardiography continuing as the first diagnostic step; the echocardiographic [...] Read more.
Heart failure is becoming the central problem in cardiology. Its recognition, differential diagnosis, and the monitoring of therapy are intimately coupled with cardiac imaging. Cardiac imaging has witnessed an explosive growth and differentiation, with echocardiography continuing as the first diagnostic step; the echocardiographic exam itself has become considerably more complex than in the last century, with the assessment of diastolic left ventricular function and strain imaging contributing important information, especially in heart failure. Very often, however, echocardiography can only describe the fact of functional impairment and morphologic remodeling, whereas further clarification of the underlying disease, such as cardiomyopathy, myocarditis, storage diseases, sarcoidosis, and others, remains elusive. Here, cardiovascular magnetic resonance and perfusion imaging should be used judiciously to arrive as often as possible at a clear diagnosis which ideally enables specific therapy. Full article
(This article belongs to the Special Issue From "Stress Septal Sign" to Global "Heart Remodeling")
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9 pages, 1225 KiB  
Article
Mathematical Estimation of Axial Length Increment in the Control of Myopia Progression
by António Queirós, Ana Amorim-de-Sousa, Paulo Fernandes, Maria Sameiro Ribeiro-Queirós, César Villa-Collar and José M. González-Méijome
J. Clin. Med. 2022, 11(20), 6200; https://doi.org/10.3390/jcm11206200 - 20 Oct 2022
Cited by 8 | Viewed by 2417
Abstract
This study aims to evaluate the existing mathematical approach for the theoretical estimation of axial length (AL) in a cross-sectional study, developing a new mathematical model and testing it in a longitudinal sample. Many professionals do not have a device to measure the [...] Read more.
This study aims to evaluate the existing mathematical approach for the theoretical estimation of axial length (AL) in a cross-sectional study, developing a new mathematical model and testing it in a longitudinal sample. Many professionals do not have a device to measure the AL due to clinic space and cost of equipment. However, this parameter plays an important role in the assessment of myopia progression to monitor treatment effects with myopia control strategies. First, a cross-sectional study based on the mathematical equation proposed by Morgan was performed. The AL was estimated based on the mean values of keratometry and spherical equivalent in 1783 subjects (52% female), aged 14.6 ± 4.6 years (6 to 25 years), of whom 738 were myopic, 770 emmetropic and 275 hyperopic. On average, the AL estimated with the Morgan formula was 0.25 ± 0.48 mm larger than the real AL value (95% limits of agreement: +0.70 to −1.20 mm). The study by gender, ametropia, type of astigmatism and age showed statistically significant differences between the real AL and predicted AL_Morgan (r > 0.750, spearman). Based on the previous sample, a multiple linear regression was applied, and a new mathematical model was proposed. The model was tested on a longitudinal sample of 152 subjects whose mean age was 13.3 ± 3.1 years (9 to 24 years) and of whom 96 were female (64%). The sample consisted of 46 myopes, 82 emmetropes and 24 hyperopes. The longitudinal study of the differences in axial length at one year between the models showed no statistically significant differences and that the mathematical equations are valid for estimating differences in axial increment for ages between 9 and 24 years, despite errors in the predicted value for axial length. Full article
(This article belongs to the Special Issue New Frontiers in Myopia Progression in Children)
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19 pages, 1521 KiB  
Review
Artificial Intelligence and Corneal Confocal Microscopy: The Start of a Beautiful Relationship
by Uazman Alam, Matthew Anson, Yanda Meng, Frank Preston, Varo Kirthi, Timothy L. Jackson, Paul Nderitu, Daniel J. Cuthbertson, Rayaz A. Malik, Yalin Zheng and Ioannis N. Petropoulos
J. Clin. Med. 2022, 11(20), 6199; https://doi.org/10.3390/jcm11206199 - 20 Oct 2022
Cited by 13 | Viewed by 3376
Abstract
Corneal confocal microscopy (CCM) is a rapid non-invasive in vivo ophthalmic imaging technique that images the cornea. Historically, it was utilised in the diagnosis and clinical management of corneal epithelial and stromal disorders. However, over the past 20 years, CCM has been increasingly [...] Read more.
Corneal confocal microscopy (CCM) is a rapid non-invasive in vivo ophthalmic imaging technique that images the cornea. Historically, it was utilised in the diagnosis and clinical management of corneal epithelial and stromal disorders. However, over the past 20 years, CCM has been increasingly used to image sub-basal small nerve fibres in a variety of peripheral neuropathies and central neurodegenerative diseases. CCM has been used to identify subclinical nerve damage and to predict the development of diabetic peripheral neuropathy (DPN). The complex structure of the corneal sub-basal nerve plexus can be readily analysed through nerve segmentation with manual or automated quantification of parameters such as corneal nerve fibre length (CNFL), nerve fibre density (CNFD), and nerve branch density (CNBD). Large quantities of 2D corneal nerve images lend themselves to the application of artificial intelligence (AI)-based deep learning algorithms (DLA). Indeed, DLA have demonstrated performance comparable to manual but superior to automated quantification of corneal nerve morphology. Recently, our end-to-end classification with a 3 class AI model demonstrated high sensitivity and specificity in differentiating healthy volunteers from people with and without peripheral neuropathy. We believe there is significant scope and need to apply AI to help differentiate between peripheral neuropathies and also central neurodegenerative disorders. AI has significant potential to enhance the diagnostic and prognostic utility of CCM in the management of both peripheral and central neurodegenerative diseases. Full article
(This article belongs to the Special Issue Corneal Confocal Microscopy and the Nervous System)
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4 pages, 179 KiB  
Editorial
Flow Cytometry, a Unique Biotechnology in Medical Applications
by Claude Lambert
J. Clin. Med. 2022, 11(20), 6198; https://doi.org/10.3390/jcm11206198 - 20 Oct 2022
Cited by 1 | Viewed by 1769
Abstract
It is good to see that the Journal of Clinical Medicine has recently published several good papers, highlighting the special input of cell analysis using flow cytometry [...] Full article
(This article belongs to the Section Clinical Laboratory Medicine)
8 pages, 853 KiB  
Article
Invasive Diagnostic and Therapeutic Management of Cerebral VasoSpasm after Aneurysmal Subarachnoid Hemorrhage (IMCVS)—A Phase 2 Randomized Controlled Trial
by Hartmut Vatter, Erdem Güresir, Ralph König, Gregor Durner, Rolf Kalff, Patrick Schuss, Thomas E. Mayer, Jürgen Konczalla, Elke Hattingen, Volker Seifert and Joachim Berkefeld
J. Clin. Med. 2022, 11(20), 6197; https://doi.org/10.3390/jcm11206197 - 20 Oct 2022
Cited by 11 | Viewed by 5761
Abstract
Cerebral vasospasm (CVS) is associated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). The most frequently used form of rescue therapy for CVS is invasive endovascular therapy. Due to a lack of prospective data, we performed a prospective randomized multicenter trial [...] Read more.
Cerebral vasospasm (CVS) is associated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). The most frequently used form of rescue therapy for CVS is invasive endovascular therapy. Due to a lack of prospective data, we performed a prospective randomized multicenter trial (NCT01400360). A total of 34 patients in three centers were randomized to invasive endovascular treatment or conservative therapy at diagnosis of relevant CVS onset. Imaging data was assessed by a neuroradiologist blinded for treatment allocation. Primary outcome measure was development of DCI. Secondary endpoints included clinical outcome at 6 months after SAH. A total of 18 of the 34 patients were treated conservatively, and 16 patients were treated with invasive endovascular treatment for CVS. There was no statistical difference in the rate of cerebral infarctions either at initial or at the follow-up MRI between the groups. However, the outcome at 6 months was better in patients treated conservatively (mRs 2 ± 1.5 vs. 4 ± 1.8, p = 0.005). Invasive endovascular treatment for CVS does not lead to a lower rate of DCI but might lead to poorer outcomes compared to induced hypertension. The potential benefits of endovascular treatment for CVS need to be addressed in further studies, searching for a subgroup of patients who may benefit. Full article
(This article belongs to the Special Issue Clinical Advances in Cerebral Aneurysm Treatment)
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