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J. Clin. Med., Volume 10, Issue 6 (March-2 2021) – 184 articles

Cover Story (view full-size image): Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease. View this paper
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8 pages, 1035 KiB  
Article
The Effect of Perioperative Blood Transfusions on Microvascular Anastomoses
by Lidia Sanchez-Porro Gil, Xavier Leon Vintro, Susana Lopez Fernandez, Carmen Vega Garcia, Gemma Pons Playa, Manuel Fernandez Garrido and Jaume Masia Ayala
J. Clin. Med. 2021, 10(6), 1333; https://doi.org/10.3390/jcm10061333 - 23 Mar 2021
Cited by 4 | Viewed by 2143
Abstract
Introduction: Perioperative transfusions are associated with complications of free flaps. The purpose of the present study was to find out whether there is a significant relationship between the risk of developing complications in vascular anastomoses and the history of transfusions. Methods: We studied [...] Read more.
Introduction: Perioperative transfusions are associated with complications of free flaps. The purpose of the present study was to find out whether there is a significant relationship between the risk of developing complications in vascular anastomoses and the history of transfusions. Methods: We studied 372 patients retrospectively with microsurgical reconstruction between 2009 and 2017 with regards to the number of red blood cell concentrates transfused. Complications were analyzed relative to flap loss and complications in microvascular anastomoses. Results: 130 patients (34.9%) received blood transfusions. Some 55% of them were transfused between the day of the intervention and the first postoperative day. Ninety-six patients were reoperated on (25.7%). Of those, thirty-six patients (37.5%) corresponded to anastomosis failure. The percentage of patients transfused among those who required reoperation was 55.2%. The percentage of patients transfused among those who were reoperated on within the first 72 h due to an alteration in the anastomosis was 60.6%, while it was 25.6% (Chi square P = 0.0001) for the rest of the patients. Conclusions: Although there is a strong association between transfusion and vascular anastomosis failure, it is not possible to establish the causation between the two. Full article
(This article belongs to the Special Issue Clinical Guidance for Breast Reconstruction)
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18 pages, 1490 KiB  
Article
Whole-Body Pharmacokinetics and Physiologically Based Pharmacokinetic Model for Monomethyl Auristatin E (MMAE)
by Hsuan Ping Chang, Yuen Kiu Cheung and Dhaval K. Shah
J. Clin. Med. 2021, 10(6), 1332; https://doi.org/10.3390/jcm10061332 - 23 Mar 2021
Cited by 21 | Viewed by 5485
Abstract
Monomethyl auristatin E (MMAE) is one of the most commonly used payloads for developing antibody–drug conjugates (ADC). However, limited studies have comprehensively evaluated the whole-body disposition of MMAE. Consequently, here, we have investigated the whole-body pharmacokinetics (PK) of MMAE in tumor-bearing mice. We [...] Read more.
Monomethyl auristatin E (MMAE) is one of the most commonly used payloads for developing antibody–drug conjugates (ADC). However, limited studies have comprehensively evaluated the whole-body disposition of MMAE. Consequently, here, we have investigated the whole-body pharmacokinetics (PK) of MMAE in tumor-bearing mice. We show that while MMAE is rapidly eliminated from the plasma, it shows prolonged and extensive distribution in tissues, blood cells, and tumor. Highly perfused tissues (e.g., lung, kidney, heart, liver, and spleen) demonstrated tissue-to-plasma area under the concentration curve (AUC) ratios > 20, and poorly perfused tissues (e.g., fat, pancreas, skin, bone, and muscle) had ratios from 1.3 to 2.4. MMAE distribution was limited in the brain, and tumor had 8-fold higher exposure than plasma. A physiological-based pharmacokinetic (PBPK) model was developed to characterize the whole-body PK of MMAE, which accounted for perfusion/permeability-limited transfer of drug in the tissue, blood cell distribution of the drug, tissue/tumor retention of the drug, and plasma protein binding. The model was able to characterize the PK of MMAE in plasma, tissues, and tumor simultaneously, and model parameters were estimated with good precision. The MMAE PBPK model presented here can facilitate the development of a platform PBPK model for MMAE containing ADCs and help with their preclinical-to-clinical translation and clinical dose optimization. Full article
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13 pages, 799 KiB  
Article
Multimodal Long-Term Predictors of Outcome in Out of Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management at 36 °C
by Erik Roman-Pognuz, Jonathan Elmer, Frank X. Guyette, Gabriele Poillucci, Umberto Lucangelo, Giorgio Berlot, Paolo Manganotti, Alberto Peratoner, Tommaso Pellis, Fabio Taccone and Clifton Callaway
J. Clin. Med. 2021, 10(6), 1331; https://doi.org/10.3390/jcm10061331 - 23 Mar 2021
Cited by 7 | Viewed by 2461
Abstract
Introduction: Early prediction of long-term outcomes in patients resuscitated after cardiac arrest (CA) is still challenging. Guidelines suggested a multimodal approach combining multiple predictors. We evaluated whether the combination of the electroencephalography (EEG) reactivity, somatosensory evoked potentials (SSEPs) cortical complex and Gray [...] Read more.
Introduction: Early prediction of long-term outcomes in patients resuscitated after cardiac arrest (CA) is still challenging. Guidelines suggested a multimodal approach combining multiple predictors. We evaluated whether the combination of the electroencephalography (EEG) reactivity, somatosensory evoked potentials (SSEPs) cortical complex and Gray to White matter ratio (GWR) on brain computed tomography (CT) at different temperatures could predict survival and good outcome at hospital discharge and six months after the event. Methods: We performed a retrospective cohort study including consecutive adult, non-traumatic patients resuscitated from out-of-hospital CA who remained comatose on admission to our intensive care unit from 2013 to 2017. We acquired SSEPs and EEGs during the treatment at 36 °C and after rewarming at 37 °C, Gray to white matter ratio (GWR) was calculated on the brain computed tomography scan performed within six hours of the hospital admission. We primarily hypothesized that SSEP was associated with favor-able functional outcome at distance and secondarily that SSEP provides independent information from EEG and CT. Outcomes were evaluated using the Cerebral Performance Category (CPC) scale at six months from discharge. Results: Of 171 resuscitated patients, 75 were excluded due to missing data or uninterpretable neurophysiological findings. EEG reactivity at 37 °C has been shown the best single predictor of good out-come (AUC 0.803) while N20P25 was the best single predictor for survival at each time point. (AUC 0.775 at discharge and AUC 0.747 at six months follow up). The predictive value of a model including EEG reactivity, average GWR, and SSEP N20P25 amplitude was superior (AUC 0.841 for survival and 0.920 for good out-come) to any combination of two tests or any single test. Conclusions: Our study, in which life-sustaining treatments were never suspended, suggests SSEP cortical complex N20P25, after normothermia and off sedation, is a reliable predictor for survival at any time. When SSEP cortical complex N20P25 is added into a model with GWR average and EEG reactivity, the predictivity for good outcome and survival at distance is superior than each single test alone. Full article
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16 pages, 326 KiB  
Review
Progression in the Management of Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Diseases, Where Are We Now and Where We Would Like to Be
by Tinne Goos, Laurens J. De Sadeleer, Jonas Yserbyt, Geert M. Verleden, Marie Vermant, Stijn E. Verleden and Wim A. Wuyts
J. Clin. Med. 2021, 10(6), 1330; https://doi.org/10.3390/jcm10061330 - 23 Mar 2021
Cited by 11 | Viewed by 3309
Abstract
A significant proportion of patients with interstitial lung disease (ILD) may develop a progressive fibrosing phenotype characterized by worsening of symptoms and pulmonary function, progressive fibrosis on chest computed tomography and increased mortality. The clinical course in these patients mimics the relentless progressiveness [...] Read more.
A significant proportion of patients with interstitial lung disease (ILD) may develop a progressive fibrosing phenotype characterized by worsening of symptoms and pulmonary function, progressive fibrosis on chest computed tomography and increased mortality. The clinical course in these patients mimics the relentless progressiveness of idiopathic pulmonary fibrosis (IPF). Common pathophysiological mechanisms such as a shared genetic susceptibility and a common downstream pathway—self-sustaining fibroproliferation—support the concept of a progressive fibrosing phenotype, which is applicable to a broad range of non-IPF ILDs. While antifibrotic drugs became the standard of care in IPF, immunosuppressive agents are still the mainstay of treatment in non-IPF fibrosing ILD (F-ILD). However, recently, randomized placebo-controlled trials have demonstrated the efficacy and safety of antifibrotic treatment in systemic sclerosis-associated F-ILD and a broad range of F-ILDs with a progressive phenotype. This review summarizes the current pharmacological management and highlights the unmet needs in patients with non-IPF ILD. Full article
(This article belongs to the Special Issue The New Perspective in Pulmonary Fibrosis)
13 pages, 1439 KiB  
Article
A Follow-Up Study of a European IgG4-Related Disease Cohort Treated with Rituximab
by Johanna Backhus, Christian Neumann, Lukas Perkhofer, Lucas A Schulte, Benjamin Mayer, Thomas Seufferlein, Martin Müller and Alexander Kleger
J. Clin. Med. 2021, 10(6), 1329; https://doi.org/10.3390/jcm10061329 - 23 Mar 2021
Cited by 19 | Viewed by 4748
Abstract
Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although [...] Read more.
Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. Methods: We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. Results: Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. Conclusion: RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6–9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy. Full article
(This article belongs to the Special Issue Updates on the Treatment of Pancreatic Diseases)
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16 pages, 1813 KiB  
Article
A Novel Combination of Accelerometry and Ecological Momentary Assessment for Post-Stroke Paretic Arm/Hand Use: Feasibility and Validity
by Yi-An Chen, Marika Demers, Rebecca Lewthwaite, Nicolas Schweighofer, John R. Monterosso, Beth E. Fisher and Carolee Winstein
J. Clin. Med. 2021, 10(6), 1328; https://doi.org/10.3390/jcm10061328 - 23 Mar 2021
Cited by 8 | Viewed by 2535
Abstract
Use of the paretic arm and hand is a key indicator of recovery and reintegration after stroke. A sound methodology is essential to comprehensively identify the possible factors impacting daily arm/hand use behavior. We combined ecological momentary assessment (EMA), a prompt methodology capturing [...] Read more.
Use of the paretic arm and hand is a key indicator of recovery and reintegration after stroke. A sound methodology is essential to comprehensively identify the possible factors impacting daily arm/hand use behavior. We combined ecological momentary assessment (EMA), a prompt methodology capturing real-time psycho-contextual factors, with accelerometry to investigate arm/hand behavior in the natural environment. Our aims were to determine (1) feasibility and (2) measurement validity of the combined methodology. We monitored 30 right-dominant, mild-moderately motor impaired chronic stroke survivors over 5 days (6 EMA prompts/day with accelerometers on each wrist). We observed high adherence for accelerometer wearing time (80.3%), EMA prompt response (84.6%), and generally positive user feedback upon exit interview. The customized prompt schedule and the self-triggered prompt option may have improved adherence. There was no evidence of EMA response bias nor immediate measurement reactivity. An unexpected small but significant increase in paretic arm/hand use was observed over days (12–14 min), which may be the accumulated effect of prompting that provided a reminder to choose the paretic limb. Further research that uses this combined methodology is needed to develop targeted interventions that effectively change behavior and enable reintegration post-stroke. Full article
(This article belongs to the Special Issue Post-stroke Intervention)
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4 pages, 166 KiB  
Editorial
Special Issue: Emerging Technologies for Medical Imaging Diagnostics, Monitoring and Therapy of Cancers
by Mohsen Beheshti and Felix M. Mottaghy
J. Clin. Med. 2021, 10(6), 1327; https://doi.org/10.3390/jcm10061327 - 23 Mar 2021
Viewed by 1643
Abstract
Molecular imaging and therapy play an increasingly important role in the field of “precision medicine” as an emergent prospect for management of the cancerous disease [...] Full article
7 pages, 3473 KiB  
Review
Ectopic Fat Accumulation in Pancreas and Heart
by Junji Kozawa and Iichiro Shimomura
J. Clin. Med. 2021, 10(6), 1326; https://doi.org/10.3390/jcm10061326 - 23 Mar 2021
Cited by 13 | Viewed by 3078
Abstract
Ectopic fat is found in liver, muscle, and kidney and is known to accumulate as visceral fat. In recent years, ectopic fat has also been observed in the pancreas, and it has been said that pancreatic fat accumulation is related to the pathophysiology [...] Read more.
Ectopic fat is found in liver, muscle, and kidney and is known to accumulate as visceral fat. In recent years, ectopic fat has also been observed in the pancreas, and it has been said that pancreatic fat accumulation is related to the pathophysiology of diabetes and the onset of diabetes, but the relationship has not yet been determined. In the heart, epicardium fat is another ectopic fat, which is associated with the development of coronary artery disease. Ectopic fat is also observed in the myocardium, and diabetic patients have more fat accumulation in this tissue than nondiabetic patients. Myocardium fat is reported to be related to diastolic cardiac dysfunction, which is one of the characteristics of the complications observed in diabetic patients. We recently reported that ectopic fat accumulation was observed in coronary arteries of a type 2 diabetic patient with intractable coronary artery disease, and coronary artery is attracting attention as a new tissue of ectopic fat accumulation. Here, we summarize the latest findings focusing on the relationship between ectopic fat accumulation in these organs and diabetic pathophysiology and complications, then describe the possibility of future treatments targeting these ectopic fat accumulations. Full article
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11 pages, 2077 KiB  
Article
MicroRNAs in Colon Tissue of Pediatric Ulcerative Pancolitis Patients Allow Detection and Prognostic Stratification
by Petr Jabandziev, Tatsuhiko Kakisaka, Julia Bohosova, Tereza Pinkasova, Lumir Kunovsky, Ondrej Slaby and Ajay Goel
J. Clin. Med. 2021, 10(6), 1325; https://doi.org/10.3390/jcm10061325 - 23 Mar 2021
Cited by 7 | Viewed by 2666
Abstract
Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the [...] Read more.
Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the prediction for standard treatment according to the specific expression of candidate miRNAs. We enrolled consecutive, therapeutically naïve, pediatric UC patients with confirmed pancolitis. We examined formalin-fixed paraffin-embedded specimens of colonic tissue for the expression of 10 selected candidate miRNAs. We performed receiver operating characteristic curve analysis, using area under the curve and a logistic regression model to evaluate the diagnostic and predictive power of the miRNA panels. Sixty patients were included in the final analysis. As a control group, 18 children without macroscopic and microscopic signs of inflammatory bowel disease were examined. The combination of three candidate miRNAs (let-7i-5p, miR-223-3p and miR-4284) enabled accurate detection of pediatric UC patients and controls. A panel of four candidate miRNAs (miR-375-3p, miR-146a-5p, miR-223-3p and miR-200b-3p) was associated with severity of UC in pediatric patients and a combination of three miRNAs (miR-21-5p, miR-192-5p and miR-194-5p) was associated with early relapse of the disease. Nine patients out of the total were diagnosed with primary sclerosing cholangitis (PSC) simultaneously with ulcerative colitis. A panel of 6 candidate miRNAs (miR-142-3p, miR-146a-5p, miR-223-3p, let-7i-5p, miR-192-5p and miR-194-5p) identified those patients with PSC. Specific combinations of miRNAs are promising tools for potential use in precise disease identification and severity and prognostic stratification in pediatric patients with ulcerative pancolitis. Full article
(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)
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14 pages, 2666 KiB  
Article
Chemically-Boosted Corneal Cross-Linking for the Treatment of Keratoconus through a Riboflavin 0.25% Optimized Solution with High Superoxide Anion Release
by Cosimo Mazzotta, Marco Ferrise, Guido Gabriele, Paolo Gennaro and Alessandro Meduri
J. Clin. Med. 2021, 10(6), 1324; https://doi.org/10.3390/jcm10061324 - 23 Mar 2021
Cited by 10 | Viewed by 2582
Abstract
The purpose of this study was to evaluate the effectiveness and safety of a novel buffered riboflavin solution approved for corneal cross-linking (CXL) in progressive keratoconus and secondary corneal ectasia. Following the in vivo preclinical study performed on New Zealand rabbits comparing the [...] Read more.
The purpose of this study was to evaluate the effectiveness and safety of a novel buffered riboflavin solution approved for corneal cross-linking (CXL) in progressive keratoconus and secondary corneal ectasia. Following the in vivo preclinical study performed on New Zealand rabbits comparing the novel 0.25% riboflavin solution (Safecross®) containing 1% hydroxypropyl methylcellulose (HPMC) with a 0.1% riboflavin solution containing 0.10% EDTA, accelerated epithelium-off CXL was performed on 10 patients (10 eyes treated, with the contralateral eye used as control) through UV-A at a power setting of 9 mW/cm2 with a total dose of 5.4 J/cm2. Re-epithelialization was evaluated in the postoperative 7 days by fluorescein dye test at biomicroscopy; endothelial cell count and morphology (ECD) were analyzed by specular microscopy at the 1st and 6th month of follow-up and demarcation line depth (DLD) measured by anterior segment optical coherence tomography (AS-OCT) one month after the treatment. We observed complete re-epithelization in all eyes between 72 and 96 h after surgery (88 h on average). ECD and morphology remained unchanged in all eyes. DLD was detected at a mean depth of 362 ± 50 µm, 20% over solutions with equivalent dosage. SafeCross® riboflavin solution chemically-boosted corneal cross-linking seems to optimize CXL oxidative reaction by higher superoxide anion release, improving DLD by a factor of 20%, without adverse events for corneal endothelium. Full article
(This article belongs to the Special Issue Innovations in Keratoconus Diagnosis and Management)
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20 pages, 3848 KiB  
Article
Preclinical Characterization of the Distribution, Catabolism, and Elimination of a Polatuzumab Vedotin-Piiq (POLIVY®) Antibody–Drug Conjugate in Sprague Dawley Rats
by Victor Yip, M. Violet Lee, Ola M. Saad, Shuguang Ma, S. Cyrus Khojasteh and Ben-Quan Shen
J. Clin. Med. 2021, 10(6), 1323; https://doi.org/10.3390/jcm10061323 - 23 Mar 2021
Cited by 12 | Viewed by 4316
Abstract
Polatuzumab vedotin (or POLIVY®), an antibody–drug conjugate (ADC) composed of a polatuzumab monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable dipeptide linker, has been approved by the United States Food and Drug Administration (FDA) for the treatment of [...] Read more.
Polatuzumab vedotin (or POLIVY®), an antibody–drug conjugate (ADC) composed of a polatuzumab monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable dipeptide linker, has been approved by the United States Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma (DLBCL). To support the clinical development of polatuzumab vedotin, we characterized the distribution, catabolism/metabolism, and elimination properties of polatuzumab vedotin and its unconjugated MMAE payload in Sprague Dawley rats. Several radiolabeled probes were developed to track the fate of different components of the ADC, with 125I and 111In used to label the antibody component and 3H to label the MMAE payload of the ADC. Following a single intravenous administration of the radiolabeled probes into normal or bile-duct cannulated rats, blood, various tissues, and excreta samples were collected over 7–14 days post-dose and analyzed for radioactivity and to characterize the metabolites/catabolites. The plasma radioactivity of polatuzumab vedotin showed a biphasic elimination profile similar to that of unconjugated polatuzumab but different from unconjugated radiolabeled MMAE, which had a fast clearance. The vast majority of the radiolabeled MMAE in plasma remained associated with antibodies, with a minor fraction as free MMAE and MMAE-containing catabolites. Similar to unconjugated mAb, polatuzumab vedotin showed a nonspecific distribution to multiple highly perfused organs, including the lungs, heart, liver, spleen, and kidneys, where the ADC underwent catabolism to release MMAE and other MMAE-containing catabolites. Both polatuzumab vedotin and unconjugated MMAE were mainly eliminated through the biliary fecal route (>90%) and a small fraction (<10%) was eliminated through renal excretion in the form of catabolites/metabolites, among which, MMAE was identified as the major species, along with several other minor species. These studies provided significant insight into ADC’s absorption, distribution, metabolism, and elimination (ADME) properties, which supports the clinical development of POLIVY. Full article
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12 pages, 465 KiB  
Article
Ferric Carboxymatose in Non-Hemodialysis CKD Patients: A Longitudinal Cohort Study
by Roberto Minutolo, Patrizia Berto, Maria Elena Liberti, Nicola Peruzzu, Silvio Borrelli, Antonella Netti, Carlo Garofalo, Giuseppe Conte, Luca De Nicola, Lucia Del Vecchio and Francesco Locatelli
J. Clin. Med. 2021, 10(6), 1322; https://doi.org/10.3390/jcm10061322 - 23 Mar 2021
Cited by 2 | Viewed by 2303
Abstract
No information is available on the efficacy of ferric carboxymaltose (FCM) in real-world CKD patients outside the hemodialysis setting. We prospectively followed 59 non-hemodialysis CKD patients with iron deficient anemia (IDA: hemoglobin <12.0/<13.5 g/dL in women/men and TSAT < 20% and/or ferritin < [...] Read more.
No information is available on the efficacy of ferric carboxymaltose (FCM) in real-world CKD patients outside the hemodialysis setting. We prospectively followed 59 non-hemodialysis CKD patients with iron deficient anemia (IDA: hemoglobin <12.0/<13.5 g/dL in women/men and TSAT < 20% and/or ferritin < 100 ng/mL) who were intolerant or non-responders to oral iron. Patients received ferric carboxymaltose (FCM) (single dose of 500 mg) followed by additional doses if iron deficiency persisted. We evaluated efficacy of FCM in terms of increase of hemoglobin, ferritin, and TSAT levels. Direct and indirect costs of FCM were also analyzed in comparison with a hypothetical scenario where same amount of iron as ferric gluconate (FG) was administered intravenously. During the 24 weeks of study, 847 ± 428 mg of FCM per patient were administered. IDA improved after four weeks of FCM and remained stable thereafter. At week-24, mean change (95%CI) from baseline of hemoglobin, ferritin and TSAT were +1.16 g/dL (0.55–1.77), +104 ng/mL (40–168) and +9.5% (5.8–13.2), respectively. These changes were independent from ESA use and clinical setting (non-dialysis CKD, peritoneal dialysis and kidney transplant). Among ESA-treated patients (n = 24), ESA doses significantly decreased by 26% with treatment and stopped either temporarily or persistently in nine patients. FCM, compared to a FG-based scenario, was associated with a cost saving of 288 euros/patient/24 weeks. Saving was the same in ESA users/non-users. Therefore, in non-hemodialysis CKD patients, FCM effectively corrects IDA and allows remarkable cost savings in terms of societal, healthcare and patient perspective. Full article
(This article belongs to the Special Issue Management of the Progression and Complications of CKD)
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12 pages, 976 KiB  
Article
Pain Sensitivity, Negative Affect, and Alcohol Use Disorder Status: A Moderated Mediation Study of Emotion Dysregulation
by Maciej Kopera, Elisa M. Trucco, Hubert Suszek, Paweł Kobyliński, Paweł Wiśniewski, Marcin Wojnar and Andrzej Jakubczyk
J. Clin. Med. 2021, 10(6), 1321; https://doi.org/10.3390/jcm10061321 - 23 Mar 2021
Cited by 8 | Viewed by 2879
Abstract
Previous work suggests that the association between pain and emotional processes among individuals with alcohol use disorder (AUD) may differ from healthy controls. This study investigates whether pain sensitivity mediates the association between negative affect and emotional dysregulation and whether this association differs [...] Read more.
Previous work suggests that the association between pain and emotional processes among individuals with alcohol use disorder (AUD) may differ from healthy controls. This study investigates whether pain sensitivity mediates the association between negative affect and emotional dysregulation and whether this association differs across AUD status using moderated mediation. The sample included 165 individuals diagnosed with AUD and 110 healthy controls. Of interest was pain sensitivity, as assessed with the Pain Sensitivity Questionnaire, negative affect, as assessed with the Beck Depression Inventory, and emotional dysregulation, as assessed with the Difficulties in Emotional regulation Scale. Age, biological sex, and current pain severity were included as covariates. The results support a moderated partial mediation model that explained 44% of the variance in emotional dysregulation. The findings indicate that negative affect is related to higher pain sensitivity across groups. Moreover, pain sensitivity partially mediated the association between negative affect and emotional dysregulation, but in opposite directions depending on AUD status. Among healthy controls, greater pain sensitivity was related to better emotional regulation, while greater pain sensitivity led to greater emotional dysregulation among individuals with AUD. The potential parallels in the underlying neurobiological mechanisms of emotionality, pain, and AUD suggest that interventions targeting pain may improve adaptive affect regulation skills, which in turn could reduce negative affect and its effect on pain sensitivity among individuals with AUD. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Mental Disorders)
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14 pages, 407 KiB  
Article
Association of Barriers, Fear of Falling and Fatigue with Objectively Measured Physical Activity and Sedentary Behavior in Chronic Stroke
by M. Luz Sánchez-Sánchez, Anna Arnal-Gómez, Sara Cortes-Amador, Sofía Pérez-Alenda, Juan J. Carrasco, Assumpta Climent-Toledo, Gemma Victoria Espí-López and Maria-Arantzazu Ruescas-Nicolau
J. Clin. Med. 2021, 10(6), 1320; https://doi.org/10.3390/jcm10061320 - 23 Mar 2021
Cited by 3 | Viewed by 2915
Abstract
Understanding the fostering factors of physical activity (PA) and sedentary behavior (SB) in post-stroke chronic survivors is critical to address preventive and health interventions. This cross-sectional study aimed to analyze the association of barriers to PA, fear of falling and severity of fatigue [...] Read more.
Understanding the fostering factors of physical activity (PA) and sedentary behavior (SB) in post-stroke chronic survivors is critical to address preventive and health interventions. This cross-sectional study aimed to analyze the association of barriers to PA, fear of falling and severity of fatigue encountered by stroke chronic survivors with device-measured PA and SB. Ambulatory community-dwelling post-stroke subjects (≥six months from stroke onset) were evaluated and answered the Barriers to Physical Activity after Stroke Scale (BAPAS), Short Falls Efficacy Scale-International (Short FES-I) and Fatigue Severity Scale (FSS). SB and PA were measured with an Actigraph GT3X+ accelerometer for ≥seven consecutive days. Stepwise multiple linear regression analysis was employed to identify factors associated with PA and SB. Fifty-seven participants (58.2 ± 11.1 years, 37 men) met the accelerometer wear–time criteria (three days, ≥eight h/day). The physical BAPAS score explained 28.7% of the variance of the prolonged sedentary time (β = 0.547; p < 0.001). Additionally, the walking speed (β = 0.452) together with physical BAPAS (β = −0.319) explained 37.9% of the moderate-to-vigorous PA time (p < 0.001). In chronic post-stroke survivors, not only the walking speed but, also, the perceived physical barriers to PA are accounted for the SB and PA. Interventions to reverse SB and to involve subjects post-stroke in higher levels of PA should consider these factors. Full article
(This article belongs to the Special Issue Post-stroke Intervention)
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11 pages, 2611 KiB  
Article
Factors Associated with Increased Risk of Early Severe Neonatal Morbidity in Late Preterm and Early Term Infants
by Tesfaye S. Mengistu, Veronika Schreiber, Christopher Flatley, Jane Fox and Sailesh Kumar
J. Clin. Med. 2021, 10(6), 1319; https://doi.org/10.3390/jcm10061319 - 23 Mar 2021
Cited by 7 | Viewed by 2278
Abstract
Although the risk of neonatal mortality is generally low for late preterm and early term infants, they are still significantly predisposed to severe neonatal morbidity (SNM) despite being born at relatively advanced gestations. In this study, we investigated maternal and intrapartum risk factors [...] Read more.
Although the risk of neonatal mortality is generally low for late preterm and early term infants, they are still significantly predisposed to severe neonatal morbidity (SNM) despite being born at relatively advanced gestations. In this study, we investigated maternal and intrapartum risk factors for early SNM in late preterm and early term infants. This was a retrospective cohort study of non-anomalous, singleton infants (34+0–38+6 gestational weeks) born at the Mater Mother’s Hospital in Brisbane, Australia from January 2015 to May 2020. Early SNM was defined as a composite of any of the following severe neonatal outcome indicators: admission to neonatal intensive care unit (NICU) in conjunction with an Apgar score <4 at 5 min, severe respiratory distress, severe neonatal acidosis (cord pH < 7.0 or base excess <−12 mmol/L). Multivariable binomial logistic regression analyses using generalized estimating equations (GEE) were used to identify risk factors. Of the total infants born at 34+0–38+6 gestational weeks, 5.7% had at least one component of the composite outcome. For late preterm infants, pre-existing diabetes mellitus, instrumental birth and emergency caesarean birth for non-reassuring fetal status were associated with increased odds for early SNM, whilst for early term infants, pre-existing and gestational diabetes mellitus, antepartum hemorrhage, instrumental, emergency caesarean and elective caesarean birth were significant risk factors. In conclusion, we identified several risk factors contributing to early SNM in late preterm and early term cohort. Our results suggest that predicted probability of early SNM decreased as gestation increased. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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7 pages, 403 KiB  
Brief Report
Reduced Flow-Mediated Dilatation Is Not Related to COVID-19 Severity Three Months after Hospitalization for SARS-CoV-2 Infection
by Marianne Riou, Walid Oulehri, Cedric Momas, Olivier Rouyer, Fabienne Lebourg, Alain Meyer, Irina Enache, Cristina Pistea, Anne Charloux, Christophe Marcot, Frederic de Blay, Olivier Collange, Michel Mertes, Emmanuel Andrès, Samy Talha and Bernard Geny
J. Clin. Med. 2021, 10(6), 1318; https://doi.org/10.3390/jcm10061318 - 23 Mar 2021
Cited by 21 | Viewed by 3662
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide, with more than two million deaths. Evidence indicates the critical role of the vascular endothelium in its pathophysiology but, like potential changes in functional vasodilation, the vascular effect of SARS-CoV-2 at a given [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide, with more than two million deaths. Evidence indicates the critical role of the vascular endothelium in its pathophysiology but, like potential changes in functional vasodilation, the vascular effect of SARS-CoV-2 at a given distance from the acute infection is largely unknown. We assessed brachial artery flow-mediated dilatation (FMD) in 27 COVID-19 patients needing conventional or intensive care unit hospitalization, three months after SARS-CoV-2 infection diagnosis and in nine age- and sex- matched control subjects. Interestingly, the FMD was lower in COVID-19 patients as compared to controls (8.2 (7.2–8.9) vs. 10.3 (9.1–11.7)); p = 0.002, and half of the hospitalized COVID-19 survivors presented with a reduced FMD < 8% at three months of COVID-19 onset. Impaired FMD was not associated with severe or critical SARS-CoV-2 infection, reflected by ICU hospitalization, total hospitalization duration, or severity of lung damage. In conclusion, reduced FMD is often observed even three months after hospitalization for SARS-CoV-2 infection, but such alteration predominantly appears to not be related to COVID-19 severity. Longer and larger follow-up studies will help to clarify the potential prognosis value of FMD among COVID-19 patients, as well as to further determine the mechanisms involved. Full article
(This article belongs to the Special Issue Vascular Damage and Coagulopathy during COVID-19 Infections)
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7 pages, 2032 KiB  
Article
Inappropriate Heart Rate Response to Hypotension in Critically Ill COVID-19-Associated Acute Kidney Injury
by Charles Verney, David Legouis, Guillaume Voiriot, Muriel Fartoukh and Vincent Labbé
J. Clin. Med. 2021, 10(6), 1317; https://doi.org/10.3390/jcm10061317 - 23 Mar 2021
Cited by 1 | Viewed by 1805
Abstract
Angiotensin-converting enzyme 2 (ACE2) receptor of severe acute respiratory syndrome coronavirus 2 is involved in baroreflex control mechanisms. We hypothesize that severe coronavirus infectious disease 2019 (COVID-19) patients may show an alteration in baroreflex-mediated heart rate changes in response to arterial hypotension. A [...] Read more.
Angiotensin-converting enzyme 2 (ACE2) receptor of severe acute respiratory syndrome coronavirus 2 is involved in baroreflex control mechanisms. We hypothesize that severe coronavirus infectious disease 2019 (COVID-19) patients may show an alteration in baroreflex-mediated heart rate changes in response to arterial hypotension. A pilot study was conducted to assess the response to hypotension in relation to continuous venovenous hemodiafiltration (CVVHDF) in critically ill patients with PCR-confirmed COVID-19 (from February to April 2020) and in critically ill non-COVID-19 patients with sepsis (from February 2018 to February 2020). The endpoint was a change in the heart rate in response to CVVHDF-induced hypotension. The association between COVID-19 status and heart rate change was estimated using linear regression. The study population included 6 COVID-19 patients (67% men; age 58 (53–64) years) and 12 critically ill non-COVID-19 patients (58% men; age 67 (51–71) years). Baseline characteristics, laboratory findings, hemodynamic parameters, and management before CVVHDF-induced hypotension were similar between the two groups, with the exception of a higher positive end-expiratory pressure and doses of propofol and midazolam administered in COVID-19 patients. Changes in the heart rate were significantly lower in COVID-19 patients as compared to critically ill non-COVID-19 patients (−7 (−9; −2) vs. 2 (2;5) bpm, p = 0.003), while the decrease in mean arterial blood pressure was similar between groups. The COVID-19 status was independently associated with a lower change in the heart rate (−11 (−20; −2) bpm; p = 0.03). Our findings suggest an inappropriate heart rate response to hypotension in severe COVID-19 patients compared to critically ill non-COVID-19 patients. Full article
(This article belongs to the Section Intensive Care)
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11 pages, 1041 KiB  
Article
Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation
by Johan Noble, Antoine Metzger, Hamza Naciri Bennani, Melanie Daligault, Dominique Masson, Florian Terrec, Farida Imerzoukene, Beatrice Bardy, Gaelle Fiard, Raphael Marlu, Eloi Chevallier, Benedicte Janbon, Paolo Malvezzi, Lionel Rostaing and Thomas Jouve
J. Clin. Med. 2021, 10(6), 1316; https://doi.org/10.3390/jcm10061316 - 23 Mar 2021
Cited by 16 | Viewed by 2791
Abstract
Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor [...] Read more.
Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15–51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients. Full article
(This article belongs to the Special Issue New Advances in Kidney Transplantation)
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9 pages, 1042 KiB  
Article
Association between Visceral or Subcutaneous Fat Accumulation and B-Type Natriuretic Peptide among Japanese Subjects: A Cross-Sectional Study
by Yoshinori Hayashi, Hirohide Yokokawa, Hiroshi Fukuda, Mizue Saita, Taiju Miyagami, Yuichi Takahashi, Teruhiko Hisaoka and Toshio Naito
J. Clin. Med. 2021, 10(6), 1315; https://doi.org/10.3390/jcm10061315 - 23 Mar 2021
Cited by 2 | Viewed by 1676
Abstract
Background: Some previous studies have shown reduced levels of plasma B-type natriuretic peptide (BNP) in individuals with obesity. We aimed to estimate the relationship between BNP and abdominal fat distribution, adjusted for confounding factors. Methods: This cross-sectional study included 1806 Japanese individuals (981 [...] Read more.
Background: Some previous studies have shown reduced levels of plasma B-type natriuretic peptide (BNP) in individuals with obesity. We aimed to estimate the relationship between BNP and abdominal fat distribution, adjusted for confounding factors. Methods: This cross-sectional study included 1806 Japanese individuals (981 men and 825 women) who underwent a medical health check-up. Analyzed data included age, sex, visceral fat area (VFA), and subcutaneous fat area (SFA) as obtained from computed tomography, blood pressure, and blood test results including BNP. Multiple linear regression analysis was used to examine the association between BNP, VFA, and SFA after adjusting for age, sex, comorbidities, and body mass index. Results: In the models analyzed separately for VFA and SFA, BNP correlated independently with VFA in multiple linear regression analysis among all subjects and in both men and women, while SFA correlated inversely with BNP in all subjects and women but not in men. In the model that included both VFA and SFA, BNP correlated independently with VFA, but SFA and BNP were not correlated in any models. Conclusion: Higher VFA showed an independent, significant association with lower BNP. In addition, the inverse correlation with BNP was stronger for VFA than for SFA. Full article
(This article belongs to the Special Issue Clinical Update on Metabolic Syndrome)
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12 pages, 1499 KiB  
Article
Premature STEMI in Men and Women: Current Clinical Features and Improvements in Management and Prognosis
by Rebeca Lorca, Isaac Pascual, Andrea Aparicio, Alejandro Junco-Vicente, Rut Alvarez-Velasco, Noemi Barja, Luis Roces, Alfonso Suárez-Cuervo, Rocio Diaz, Cesar Moris, Daniel Hernandez-Vaquero and Pablo Avanzas
J. Clin. Med. 2021, 10(6), 1314; https://doi.org/10.3390/jcm10061314 - 23 Mar 2021
Cited by 5 | Viewed by 2063
Abstract
Background: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical [...] Read more.
Background: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical characteristics and prognosis of men and women with premature STEMI. Methods: A total 1404 consecutive patients were referred to our institution for emergency cardiac catheterization due to STEMI suspicion (1 January 2014–31 December 2018). Patients with confirmed premature (<55 years old in men and <60 in women) STEMI (366 patients, 83% men and 17% women) were included (359 atherothrombotic and 7 spontaneous coronary artery dissection (SCAD)). Results: Premature STEMI patients had a high prevalence of classical cardiovascular risk factors. Mean follow-up was 4.1 years (±1.75 SD). Mortality rates, re-hospitalization, and hospital stay showed no significant differences between sexes. More than 10% of women with premature STEMI suffered SCAD. There were no significant differences between sexes, neither among cholesterol levels nor in hypolipemiant therapy. The global survival rates were similar to that expected in the general population of the same sex and age in our region with a significantly higher excess of mortality at 6 years among men compared with the general population. Conclusion: Our results showed a high incidence of cardiovascular risk factors, a high prevalence of SCAD among young women, and a generally good prognosis after standardized treatment. During follow-up, 23% suffered a major cardiovascular event (MACE), without significant differences between sexes and observed survival at 1, 3, and 6 years of follow-up was 96.57% (95% CI 94.04–98.04), 95.64% (95% CI 92.87–97.35), and 94.5% (95% CI 91.12–97.66). An extra effort to prevent/delay STEMI should be invested focusing on smoking avoidance and optimal hypolipemiant treatment both in primary and secondary prevention. Full article
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13 pages, 710 KiB  
Review
Management of Dyspepsia and Gastroparesis in Patients with Diabetes. A Clinical Point of View in the Year 2021
by Silvia Bonetto, Gabriella Gruden, Guglielmo Beccuti, Arianna Ferro, Giorgio Maria Saracco and Rinaldo Pellicano
J. Clin. Med. 2021, 10(6), 1313; https://doi.org/10.3390/jcm10061313 - 23 Mar 2021
Cited by 9 | Viewed by 4516
Abstract
Diabetes mellitus is a widespread disease, and represents an important public health burden worldwide. Together with cardiovascular, renal and neurological complications, many patients with diabetes present with gastrointestinal symptoms, which configure the so-called diabetic enteropathy. In this review, we will focus on upper [...] Read more.
Diabetes mellitus is a widespread disease, and represents an important public health burden worldwide. Together with cardiovascular, renal and neurological complications, many patients with diabetes present with gastrointestinal symptoms, which configure the so-called diabetic enteropathy. In this review, we will focus on upper gastrointestinal symptoms in patients with diabetes, with particular attention to dyspepsia and diabetic gastroparesis (DG). These two clinical entities share similar pathogenetic mechanisms, which include autonomic neuropathy, alterations in enteric nervous system and histological abnormalities, such as interstitial cells of Cajal depletion. Moreover, the differential diagnosis may be challenging because of overlapping clinical features. Delayed gastric emptying should be documented to differentiate between DG and dyspepsia and it can be assessed through radioactive or non-radioactive methods. The clinical management of dyspepsia includes a wide range of different approaches, above all Helicobacter pylori test and treat. As regards DG treatment, a central role is played by dietary modification and glucose control and the first-line pharmacological therapy is represented by the use of prokinetics. A minority of patients with DG refractory to medical treatment may require more invasive therapeutic approaches, including supplemental nutrition, gastric electric stimulation, pyloromyotomy and gastrectomy. Full article
(This article belongs to the Special Issue Gastrointestinal Tract Disorders)
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8 pages, 462 KiB  
Article
The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns
by Eleni Rebelos, Miikka-Juhani Honka, Laura Ekblad, Marco Bucci, Jarna C. Hannukainen, Lilian Fernandes Silva, Kirsi A. Virtanen, Lauri Nummenmaa and Pirjo Nuutila
J. Clin. Med. 2021, 10(6), 1312; https://doi.org/10.3390/jcm10061312 - 23 Mar 2021
Cited by 1 | Viewed by 2069
Abstract
The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the MC4R gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers [...] Read more.
The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the MC4R gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers of the mutant allele have decreased cerebrocortical response to insulin. Thus, in this study, we addressed whether rs17782313 associates with brain glucose uptake (BGU). Here, [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 113 Finnish subjects scanned under insulin clamp conditions who also had the rs17782313 determined were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. Statistical analysis was performed with statistical parametric mapping. There was no difference in age, BMI, and insulin sensitivity as indexed by the M value between the rs17782313-C allele carriers and non-carriers. Brain glucose uptake during insulin clamp was not different by gene allele, and it correlated with the M value, in both the rs17782313-C allele carriers and non-carriers. The obesity risk SNP rs17782313 near the MC4R gene is not associated with brain glucose uptake during insulin clamp in humans, and this frequent mutation cannot explain the enhanced brain glucose metabolic rates in insulin resistance. Full article
(This article belongs to the Special Issue New Trends in Brain Glucose Metabolism, Morphology and Function)
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12 pages, 634 KiB  
Article
The Temporal Relationships and Associations between Cutaneous Manifestations and Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study
by Yi-Teng Hung, Puo-Hsien Le, Chia-Jung Kuo, Yu-Chuan Tang, Meng-Jiun Chiou, Cheng-Tang Chiu, Chang-Fu Kuo and Yu-Huei Huang
J. Clin. Med. 2021, 10(6), 1311; https://doi.org/10.3390/jcm10061311 - 22 Mar 2021
Cited by 9 | Viewed by 2919
Abstract
The temporal relationships between inflammatory bowel disease (IBD)-associated cutaneous manifestations and IBD remain uncertain, with existing evidence mostly from separate cross-sectional studies. We sought to determine the risks of IBD-related dermatologic diseases before and after the diagnosis of IBD. We identified 2847 cases [...] Read more.
The temporal relationships between inflammatory bowel disease (IBD)-associated cutaneous manifestations and IBD remain uncertain, with existing evidence mostly from separate cross-sectional studies. We sought to determine the risks of IBD-related dermatologic diseases before and after the diagnosis of IBD. We identified 2847 cases of IBD and 14,235 matched controls from the Taiwan National Health Insurance Research Database between 2003 and 2014. The risks of cutaneous manifestations before and after the diagnosis of IBD were estimated with multivariable-adjusted analyses. At diagnosis, IBD was associated with atopic dermatitis (odds ratio (OR) = 1.61; 95% confidence interval (CI), 1.14–2.28), erythema nodosum (OR = 7.44; 95%CI, 3.75–14.77), aphthous stomatitis (OR = 2.01; 95%CI, 1.72–2.35), polyarteritis nodosa (OR = 5.67; 95%CI, 2.69–11.98), rosacea (OR = 1.67, 95%CI = 1.19–2.35), and cutaneous T cell lymphoma (OR = 21.27; 95%CI, 2.37–191.00). IBD was associated with the subsequent development of pyoderma gangrenosum (hazard ratio (HR) = 17.79; 95%CI, 6.35–49.86), erythema nodosum (HR = 6.54; 95%CI, 2.83–15.13), polyarteritis nodosa (HR = 2.69; 95%CI, 1.05–6.90), hidradenitis suppurativa (HR = 2.48; 95%CI, 1.03–5.97), psoriasis (HR = 2.19; 95%CI, 1.27–3.79), rosacea (HR = 1.92; 95%CI, 1.39–2.65), and aphthous stomatitis (HR = 1.45; 95%CI, 1.22–1.72). This study clarified the associations and temporal relationships between cutaneous manifestations and IBD, highlighting the need for interdisciplinary care in the patient with specific dermatologic diseases presenting with abdominal symptoms, or the IBD patients with cutaneous lesions. Full article
(This article belongs to the Special Issue Skin Disease and Comorbidities)
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12 pages, 419 KiB  
Article
DNA Fragmentation in Human Spermatozoa and Pregnancy Rates after Intrauterine Insemination. Should the DFI Threshold Be Lowered?
by Anne Sofie Rex, Chunsen Wu, Jørn Aagaard and Jens Fedder
J. Clin. Med. 2021, 10(6), 1310; https://doi.org/10.3390/jcm10061310 - 22 Mar 2021
Cited by 10 | Viewed by 2014
Abstract
Sperm DNA fragmentation index (DFI) can be analyzed by a flow cytometric assay after treatment with acid and acridine orange. In this prospective, cohort study, the value of DFI was determined in a semen analysis collected before fertility treatment (baselineDFI) in 146 couples [...] Read more.
Sperm DNA fragmentation index (DFI) can be analyzed by a flow cytometric assay after treatment with acid and acridine orange. In this prospective, cohort study, the value of DFI was determined in a semen analysis collected before fertility treatment (baselineDFI) in 146 couples and during 1–3 intrauterine inseminations (IUI) in 211 couples (511 cycles). The pregnancy rate (PR)/cycle was 9.9% if baselineDFI was >10 and 21.7% if baselineDFI was ≤10, (p < 0.005). The live birth rate (LBR)/cycle was 5% if baselineDFI was >10 and 14.2% if baselineDFI was ≤10 (p < 0.005). PR/patient was 23.1% if baselineDFI was >10 and 45.5% if baselineDFI was ≤10 (p < 0.005). LBR/patient was 12.4% if baselineDFI was >10 and 34% if baselineDFI was ≤10 (p < 0.005). When isolating non-stimulated IUI cycles and couples with female age < 35, a significant difference in PR and LBR between couples with high DFI and low DFI was seen. Results suggest that DFI > 10 could advice against timed coitus and non-stimulated IUI cycles. Analysis for DFI performed before treatment provides information about PR and LBR after IUI. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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8 pages, 247 KiB  
Article
Macrolide-Resistant and Macrolide-Sensitive Mycoplasma pneumoniae Pneumonia in Children Treated Using Early Corticosteroids
by Hye Young Han, Ki Cheol Park, Eun-Ae Yang and Kyung-Yil Lee
J. Clin. Med. 2021, 10(6), 1309; https://doi.org/10.3390/jcm10061309 - 22 Mar 2021
Cited by 7 | Viewed by 1781
Abstract
We have found that early corticosteroid therapy was effective for reducing morbidity during five Korea-wide epidemics. We evaluated the clinical and laboratory parameters of 56 children who received early corticosteroid treatment for pneumonia that was caused by macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae [...] Read more.
We have found that early corticosteroid therapy was effective for reducing morbidity during five Korea-wide epidemics. We evaluated the clinical and laboratory parameters of 56 children who received early corticosteroid treatment for pneumonia that was caused by macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae) or macrolide-sensitive M. pneumoniae between July 2019 and February 2020. All subjects had dual positive results from a PCR assay and serological test, and received corticosteroids within 24–36 h after admission. Point mutation of residues 2063, 2064, and 2067 was identified in domain V of 23S rRNA. The mean age was 6.8 years and the male:female ratio was 1.2:1 (31:25 patients). Most of the subjects had macrolide-resistant M. pneumoniae (73%), and all mutated strains had the A2063G transition. No significant differences in clinical and laboratory parameters were observed between macrolide-resistant and macrolide-sensitive M. pneumoniae groups that were treated with early dose-adjusted corticosteroids. Higher-dose steroid treatment may be needed for patients who have fever that persists for >48 h or increased biomarkers such as lactate dehydrogenase concentration at follow-up despite a usual dose of steroid therapy. Full article
(This article belongs to the Section Pulmonology)
13 pages, 1594 KiB  
Article
Application of a Genus-Specific LAMP Assay for Schistosome Species to Detect Schistosoma haematobium x Schistosoma bovis Hybrids
by Beatriz Crego-Vicente, Pedro Fernández-Soto, Begoña Febrer-Sendra, Juan García-Bernalt Diego, Jérôme Boissier, Etienne K. Angora, Ana Oleaga and Antonio Muro
J. Clin. Med. 2021, 10(6), 1308; https://doi.org/10.3390/jcm10061308 - 22 Mar 2021
Cited by 4 | Viewed by 2739
Abstract
Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions caused by different species of parasitic flatworms of the genus Schistosoma. The emergence of natural hybrids of schistosomes indicate the risk of possible infection to humans and [...] Read more.
Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions caused by different species of parasitic flatworms of the genus Schistosoma. The emergence of natural hybrids of schistosomes indicate the risk of possible infection to humans and their zoonotic potential, specifically for Schistosoma haematobium and S. bovis. Hybrid schistosomes have the potential to replace existing species, generate new resistances, pathologies and extending host ranges. Hybrids may also confuse the serological, molecular and parasitological diagnosis. Currently, LAMP technology based on detection of nucleic acids is used for detection of many agents, including schistosomes. Here, we evaluate our previously developed species-specific LAMP assays for S. haematobium, S. mansoni, S. bovis and also the genus-specific LAMP for the simultaneous detection of several Schistosoma species against both DNA from pure and, for the first time, S. haematobium x S. bovis hybrids. Proper operation was evaluated with DNA from hybrid schistosomes and with human urine samples artificially contaminated with parasites’ DNA. LAMP was performed with and without prior DNA extraction. The genus-specific LAMP properly amplified pure Schistosoma species and different S. haematobium-S. bovis hybrids with different sensitivity. The Schistosoma spp.-LAMP method is potentially adaptable for field diagnosis and disease surveillance in schistosomiasis endemic areas where human infections by schistosome hybrids are increasingly common. Full article
(This article belongs to the Special Issue Epidemiology, Immunology, and Control of Schistosomiasis)
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4 pages, 189 KiB  
Editorial
Special Issue: Diagnosis and Management of Addiction and Other Mental Disorders (Dual Disorders)
by Ana Adan and Marta Torrens
J. Clin. Med. 2021, 10(6), 1307; https://doi.org/10.3390/jcm10061307 - 22 Mar 2021
Cited by 12 | Viewed by 3088
Abstract
The term “dual disorder” (DD) refers to the coexistence or concurrence of at least one substance use disorder (SUD) and another mental disorder in the same person, as the World Health Organization established in its lexicon of alcohol and drug terms [...] Full article
22 pages, 900 KiB  
Review
Inhaled Anesthetics: Environmental Role, Occupational Risk, and Clinical Use
by Mariana Gaya da Costa, Alain F. Kalmar and Michel M. R. F. Struys
J. Clin. Med. 2021, 10(6), 1306; https://doi.org/10.3390/jcm10061306 - 22 Mar 2021
Cited by 40 | Viewed by 7924
Abstract
Inhaled anesthetics have been in clinical use for over 150 years and are still commonly used in daily practice. The initial view of inhaled anesthetics as indispensable for general anesthesia has evolved during the years and, currently, its general use has even been [...] Read more.
Inhaled anesthetics have been in clinical use for over 150 years and are still commonly used in daily practice. The initial view of inhaled anesthetics as indispensable for general anesthesia has evolved during the years and, currently, its general use has even been questioned. Beyond the traditional risks inherent to any drug in use, inhaled anesthetics are exceptionally strong greenhouse gases (GHG) and may pose considerable occupational risks. This emphasizes the importance of evaluating and considering its use in clinical practices. Despite the overwhelming scientific evidence of worsening climate changes, control measures are very slowly implemented. Therefore, it is the responsibility of all society sectors, including the health sector to maximally decrease GHG emissions where possible. Within the field of anesthesia, the potential to reduce GHG emissions can be briefly summarized as follows: Stop or avoid the use of nitrous oxide (N2O) and desflurane, consider the use of total intravenous or local-regional anesthesia, invest in the development of new technologies to minimize volatile anesthetics consumption, scavenging systems, and destruction of waste gas. The improved and sustained awareness of the medical community regarding the climate impact of inhaled anesthetics is mandatory to bring change in the current practice. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics)
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16 pages, 20054 KiB  
Article
Clinical Phase I/II Study: Local Disease Control and Survival in Locally Advanced Pancreatic Cancer Treated with Electrochemotherapy
by Francesco Izzo, Vincenza Granata, Roberta Fusco, Valeria D'Alessio, Antonella Petrillo, Secondo Lastoria, Mauro Piccirillo, Vittorio Albino, Andrea Belli, Salvatore Tafuto, Antonio Avallone, Renato Patrone and Raffaele Palaia
J. Clin. Med. 2021, 10(6), 1305; https://doi.org/10.3390/jcm10061305 - 22 Mar 2021
Cited by 27 | Viewed by 2610
Abstract
Objective. To assess local disease control rates (LDCR) and overall survival (OS) in locally advanced pancreatic cancer (LAPC) treated with electrochemotherapy (ECT). Methods. Electrochemotherapy with bleomycin was performed in 25 LAPC patients who underwent baseline Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) [...] Read more.
Objective. To assess local disease control rates (LDCR) and overall survival (OS) in locally advanced pancreatic cancer (LAPC) treated with electrochemotherapy (ECT). Methods. Electrochemotherapy with bleomycin was performed in 25 LAPC patients who underwent baseline Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and Position Emission Tomography (PET) scans before ECT and 1 and 6 months post ECT. LDCR were assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Choi criteria. Needle electrodes with fixed linear (N-30-4B) or fixed hexagonal configurations (N-30-HG or I-40-HG or H-30-ST) or variable geometry (VGD1230 or VGD1240) (IGEA S.p.A., Carpi, Italy) were used to apply electric pulses. Pain evaluation was performed pre-ECT, after 1 month and after 6 months with ECT. Overall survival estimates were calculated by means of a Kaplan-Meier analysis. Results. At 1 month after ECT, 76% of patients were in partial response (PR) and 20% in stable disease (SD). Six months after ECT, 44.0% patients were still in PR and 12.0% in SD. A LDCR of 56.0% was reached six months after ECT: 13 patients treated with fixed geometry had a LDCR of 46.1%, while for the 12 patients treated with variable geometry, the LDCR was 66.7%. The overall survival median value was 11.5 months: for patients treated with fixed geometry the OS was 6 months, while for patients treated with variable geometry it was 12 months. Electrochemotherapy was well-tolerated and abdominal pain was rapidly resolved. Conclusions. Electrochemotherapy obtained good results in terms of LDCR and OS in LAPC. Multiple needle insertion in a variable geometry configuration optimized by pre-treatment planning determined an increase in LDCR and OS compared to a fixed geometry configuration. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)
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14 pages, 277 KiB  
Article
Effect of Sleep Bruxism Intensity on Blood Pressure in Normotensives
by Monika Michalek-Zrabkowska, Mieszko Wieckiewicz, Pawel Gac, Joanna Smardz, Rafal Poreba, Anna Wojakowska, Katarzyna Goslawska, Grzegorz Mazur and Helena Martynowicz
J. Clin. Med. 2021, 10(6), 1304; https://doi.org/10.3390/jcm10061304 - 22 Mar 2021
Cited by 8 | Viewed by 2286
Abstract
The present research aimed to investigate the influence of sleep bruxism (SB) intensity on blood pressure parameters in normotensive subjects by using an ambulatory blood pressure device. The study group included 65 normotensive individuals suspected of having SB. All participants underwent one-night video-polysomnography, [...] Read more.
The present research aimed to investigate the influence of sleep bruxism (SB) intensity on blood pressure parameters in normotensive subjects by using an ambulatory blood pressure device. The study group included 65 normotensive individuals suspected of having SB. All participants underwent one-night video-polysomnography, and ambulatory blood pressure monitoring was performed the next day; 86.15% of them were diagnosed with SB. Statistical analysis included correlation and regression analysis. The obtained results showed that systolic blood pressure variability during sleep significantly increased in individuals with BEI > 4 (bruxism episodes index; episodes/hour) compared to those with BEI ≤ 4 (8.81 ± 3.36 versus 10.57 ± 3.39, p = 0.05). Multivariable regression analysis showed that systolic blood pressure variability at nighttime was also associated with the following independent risk factors: higher apnea-to-bruxism index, male gender, BEI > 4 episodes/hour, body mass index (BMI) ≥ 25 kg/m2, higher arousal index, and shorter total sleep time. In summary, sleep bruxism intensity was associated with increased systolic blood pressure variability during sleep. Coincidental apnea, male gender, severe sleep bruxism (SB intensity with BEI > 4/hour), excess weight and obesity, higher arousal index, and shorter sleep time seem to be the main determinants that influence blood pressure in normotensive sleep bruxers. Full article
(This article belongs to the Section Epidemiology & Public Health)
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