Journal of Clinical Medicine

23 pages, 21860 KiB

Open AccessReview

Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy

by Miguel Mateu-Sanz, Juan Tornín, Maria-Pau Ginebra and Cristina Canal

J. Clin. Med. 2021, 10(4), 893; https://doi.org/10.3390/jcm10040893 - 23 Feb 2021

Cited by 42 | Viewed by 7291

Osteosarcoma is the most common primary bone tumor, and its first line of treatment presents a high failure rate. The 5-year survival for children and teenagers with osteosarcoma is 70% (if diagnosed before it has metastasized) or 20% (if spread at the time [...] Read more.

Osteosarcoma is the most common primary bone tumor, and its first line of treatment presents a high failure rate. The 5-year survival for children and teenagers with osteosarcoma is 70% (if diagnosed before it has metastasized) or 20% (if spread at the time of diagnosis), stressing the need for novel therapies. Recently, cold atmospheric plasmas (ionized gases consisting of UV–Vis radiation, electromagnetic fields and a great variety of reactive species) and plasma-treated liquids have been shown to have the potential to selectively eliminate cancer cells in different tumors through an oxidative stress-dependent mechanism. In this work, we review the current state of the art in cold plasma therapy for osteosarcoma. Specifically, we emphasize the mechanisms unveiled thus far regarding the action of plasmas on osteosarcoma. Finally, we review current and potential future approaches, emphasizing the most critical challenges for the development of osteosarcoma therapies based on this emerging technique. Full article

(This article belongs to the Special Issue Novel Pathogenic Mechanisms and Therapeutic Approaches for Sarcomas)

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18 pages, 1411 KiB

Open AccessArticle

Spinal Cord Morphology in Degenerative Cervical Myelopathy Patients; Assessing Key Morphological Characteristics Using Machine Vision Tools

by Kalum Ost, W. Bradley Jacobs, Nathan Evaniew, Julien Cohen-Adad, David Anderson and David W. Cadotte

J. Clin. Med. 2021, 10(4), 892; https://doi.org/10.3390/jcm10040892 - 23 Feb 2021

Cited by 12 | Viewed by 4566

Abstract

Despite Degenerative Cervical Myelopathy (DCM) being the most common form of spinal cord injury, effective methods to evaluate patients for its presence and severity are only starting to appear. Evaluation of patient images, while fast, is often unreliable; the pathology of DCM is [...] Read more.

Despite Degenerative Cervical Myelopathy (DCM) being the most common form of spinal cord injury, effective methods to evaluate patients for its presence and severity are only starting to appear. Evaluation of patient images, while fast, is often unreliable; the pathology of DCM is complex, and clinicians often have difficulty predicting patient prognosis. Automated tools, such as the Spinal Cord Toolbox (SCT), show promise, but remain in the early stages of development. To evaluate the current state of an SCT automated process, we applied it to MR imaging records from 328 DCM patients, using the modified Japanese Orthopedic Associate scale as a measure of DCM severity. We found that the metrics extracted from these automated methods are insufficient to reliably predict disease severity. Such automated processes showed potential, however, by highlighting trends and barriers which future analyses could, with time, overcome. This, paired with findings from other studies with similar processes, suggests that additional non-imaging metrics could be added to achieve diagnostically relevant predictions. Although modeling techniques such as these are still in their infancy, future models of DCM severity could greatly improve automated clinical diagnosis, communications with patients, and patient outcomes. Full article

(This article belongs to the Special Issue Management of Degenerative Cervical Myelopathy and Spinal Cord Injury)

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16 pages, 728 KiB

Open AccessArticle

Quantification of Bacteria in Mouth-Rinsing Solution for the Diagnosis of Periodontal Disease

by Jeong-Hwa Kim, Jae-Woon Oh, Young Lee, Jeong-Ho Yun, Seong-Ho Choi and Dong-Woon Lee

J. Clin. Med. 2021, 10(4), 891; https://doi.org/10.3390/jcm10040891 - 22 Feb 2021

Cited by 4 | Viewed by 3009

Abstract

This study aimed to evaluate the feasibility of diagnosing periodontitis via the identification of 18 bacterial species in mouth-rinse samples. Patients (n = 110) who underwent dental examinations in the Department of Periodontology at the Veterans Health Service Medical Center between 2018 and [...] Read more.

This study aimed to evaluate the feasibility of diagnosing periodontitis via the identification of 18 bacterial species in mouth-rinse samples. Patients (n = 110) who underwent dental examinations in the Department of Periodontology at the Veterans Health Service Medical Center between 2018 and 2019 were included. They were divided into healthy and periodontitis groups. The overall number of bacteria, and those of 18 specific bacteria, were determined via real-time polymerase chain reaction in 92 mouth-rinse samples. Differences between groups were evaluated through logistic regression after adjusting for sex, age, and smoking history. There was a significant difference in the prevalence (healthy vs. periodontitis group) of Aggregatibacter actinomycetemcomitans (2.9% vs. 13.5%), Treponema denticola (42.9% vs. 69.2%), and Prevotella nigrescens (80% vs. 2.7%). Levels of Treponema denticola, Prevotella nigrescens, and Streptococcus mitis were significantly associated with severe periodontitis. We demonstrated the feasibility of detecting periopathogenic bacteria in mouth-rinse samples obtained from patients with periodontitis. As we did not comprehensively assess all periopathogenic bacteria, further studies are required to assess the potential of oral-rinsing solutions to indicate oral infection risk and the need to improve oral hygiene, and to serve as a complementary method for periodontal disease diagnosis. Full article

(This article belongs to the Special Issue Periodontitis: Current Status and the Future)

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13 pages, 988 KiB

Open AccessArticle

Cigarette Smoking, miR-27b Downregulation, and Peripheral Artery Disease: Insights into the Mechanisms of Smoking Toxicity

by Tiago Pereira-da-Silva, Patrícia Napoleão, Marina C. Costa, André F. Gabriel, Mafalda Selas, Filipa Silva, Francisco J. Enguita, Rui Cruz Ferreira and Miguel Mota Carmo

J. Clin. Med. 2021, 10(4), 890; https://doi.org/10.3390/jcm10040890 - 22 Feb 2021

Cited by 16 | Viewed by 3386

Abstract

Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. [...] Read more.

Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. Ninety-four participants were recruited, including 58 individuals without and 36 with PAD, 51 never smokers, 28 prior smokers, and 15 active smokers. The relative expression of six circulating miRNAs with distinct biological roles (miR-21, miR-27b, miR-29a, miR-126, miR-146, and miR-218) was assessed. Cigarette smoking was associated with the presence of PAD in multivariate analysis. Active smokers, but not prior smokers, presented miR-27b downregulation and higher leukocyte, neutrophil, and lymphocyte counts; miR-27b expression levels were independently associated with active smoking. Considering the metabolic and/or inflammatory abnormalities induced by cigarette smoking, miR-27b was independently associated with the presence of PAD and downregulated in patients with more extensive PAD. In conclusion, the atheroprotective miR-27b was downregulated in active smokers, but not in prior smokers, and miR-27b expression was independently associated with the presence of PAD. These unreported data suggest that the proatherogenic properties of cigarette smoking are mediated by a downregulation of miR-27b, which may be attenuated by smoking cessation. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)

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15 pages, 1776 KiB

Open AccessArticle

Medial Prefrontal Transcranial Direct Current Stimulation Aimed to Improve Affective and Attentional Modulation of Pain in Chronic Low Back Pain Patients

by Megan E. McPhee and Thomas Graven-Nielsen

J. Clin. Med. 2021, 10(4), 889; https://doi.org/10.3390/jcm10040889 - 22 Feb 2021

Cited by 10 | Viewed by 3459

Abstract

Chronic low back pain (CLBP) is often without clear underlying pathology. Affective disturbance and dysfunctional pain mechanisms, commonly observed in populations with CLBP, have, therefore, been suggested as potential contributors to CLBP development and maintenance. However, little consensus exists on how these features [...] Read more.

Chronic low back pain (CLBP) is often without clear underlying pathology. Affective disturbance and dysfunctional pain mechanisms, commonly observed in populations with CLBP, have, therefore, been suggested as potential contributors to CLBP development and maintenance. However, little consensus exists on how these features interact and if they can be targeted using non-invasive brain stimulation. In this pilot trial, 12 participants completed two phases (Active or Sham) of high-definition transcranial direct current stimulation (HD-tDCS) to the medial prefrontal cortex, applied for 20 min on three consecutive days. Clinical pain ratings, questionnaires, and sensitivity to painful cuff pressure were completed at baseline, then 4 trials of conditioned pain modulation (CPM; alone, with distraction using a Flanker task, with positive affect induction, and with negative affect induction using an image slideshow) were performed prior to HD-tDCS on Day 1 and Day 4 (24 h post-HD-tDCS). At baseline, attentional and affective manipulations were effective in inducing the desired state (p < 0.001) but did not significantly change the magnitude of CPM-effect. Active HD-tDCS was unable to significantly alter the magnitude of the shift in valence and arousal due to affective manipulations, nor did it alter the magnitude of CPM under any basal, attentional, or affective manipulation trial significantly on Day 4 compared to sham. The CPM-effect was greater across all manipulations on Day 1 than Day 4 (p < 0.02) but also showed poor reliability across days. Future work is needed to expand upon these findings and better understand how and if HD-tDCS can be used to enhance attentional and affective effects on pain modulation. Full article

(This article belongs to the Special Issue Improved Rehabilitation for Patients with Chronic Pain)

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10 pages, 247 KiB

Open AccessArticle

Epidermal Barrier Function and Skin Homeostasis in Skin with Permanent and Adhesive Tattoos: A Cross-Sectional Study

by Jose-Pablo Serrano-Serra, Trinidad Montero-Vilchez, Agustin Buendia-Eisman and Salvador Arias-Santiago

J. Clin. Med. 2021, 10(4), 888; https://doi.org/10.3390/jcm10040888 - 22 Feb 2021

Cited by 4 | Viewed by 8334

Abstract

Tattoos are a current trend, but their impact on skin homeostasis and epidermal barrier function is not well known. So, the aims of this study are (1) to investigate epidermal barrier function and skin homeostasis in skin with permanent tattoos, adhesive temporary tattoos [...] Read more.

Tattoos are a current trend, but their impact on skin homeostasis and epidermal barrier function is not well known. So, the aims of this study are (1) to investigate epidermal barrier function and skin homeostasis in skin with permanent tattoos, adhesive temporary tattoos and non-tattooed skin, and (2) to analyze the effect of petrolatum on skin with permanent and adhesive tattoos. In total, 67 tattoos were enrolled (34 permanent tattoos and 33 adhesive tattoos). Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), erythema and total antioxidant capacity (TAC) were measured in skin with permanent tattoos, adhesive tattoos and non-tattooed skin before and after petrolatum application. The temperature was lower (30.47 °C vs. 31.01 °C; p = 0.001) on skin with permanent tattoos than non-tattooed skin, while SCH (48.24 Arbitrary Units (AU) vs. 44.15 AU; p = 0.008) was higher. Skin with adhesive tattoos showed lower temperature, SCH (21.19 AU vs. 41.31 AU; p < 0.001) and TAC (1.27 microcoulombs (uC) vs. 3.48 uC; p < 0.001), and higher TEWL (8.65 g/h/m² vs. 6.99 g/h/m²; p = 0.003), than non-tattooed skin. After petrolatum application, the temperature decreased on skin with permanent tattoos, and TEWL and SCH decreased on skin with adhesive tattoos. Adhesive tattoos may affect skin barrier function, while permanent tattoos may have a lower impact. Tattooed and non-tattooed skin responds in different ways to moisturizers. Full article

(This article belongs to the Section Dermatology)

11 pages, 1790 KiB

Open AccessArticle

Safety of Catheter Embolization of Pulmonary Arteriovenous Malformations—Evaluation of Possible Cerebrovascular Embolism after Catheter Embolization of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia/Osler Disease by Pre- and Post-Interventional DWI

by Guenther Schneider, Alexander Massmann, Peter Fries, Felix Frenzel, Arno Buecker and Paul Raczeck

J. Clin. Med. 2021, 10(4), 887; https://doi.org/10.3390/jcm10040887 - 22 Feb 2021

Cited by 4 | Viewed by 2840

Abstract

Background. This paper aimed to prospectively evaluate the safety of embolization therapy of pulmonary arteriovenous malformations (PAVMs) for the detection of cerebral infarctions by pre- and post-interventional MRI. Method One hundred and five patients (male/female = 44/61; mean age 48.6+/−15.8; range 5–86) with [...] Read more.

Background. This paper aimed to prospectively evaluate the safety of embolization therapy of pulmonary arteriovenous malformations (PAVMs) for the detection of cerebral infarctions by pre- and post-interventional MRI. Method One hundred and five patients (male/female = 44/61; mean age 48.6+/−15.8; range 5–86) with pre-diagnosed PAVMs on contrast-enhanced MRA underwent embolization therapy. The number of PAVMs treated in each patient ranged from 1–8 PAVMs. Depending on the size and localization of the feeding arteries, either Nester-Coils or Amplatzer vascular plugs were used for embolization therapy. cMRI was performed immediately before, and at the 4 h and 3-month post-embolization therapy. Detection of peri-interventional cerebral emboli was performed via T2w and DWI sequences using three different b-values, with calculation of ADC maps. Results Embolization did not show any post-/peri-interventional, newly developed ischemic lesions in the brain. Only one patient who underwent re-embolization and was previously treated with tungsten coils that corroded over time showed newly developed, small, diffuse emboli in the post-interventional DWI sequence. This patient already had several episodes of brain emboli before re-treatment due to the corroded coils, and during treatment, when passing the corroded coils, experienced additional small, clinically inconspicuous brain emboli. However, this complication was anticipated but accepted, since the vessel had to be occluded distally. Conclusion Catheter-based embolization of PAVMs is a safe method for treatment and does not result in clinically inconspicuous cerebral ischemia, which was not demonstrated previously. Full article

(This article belongs to the Special Issue Hereditary Hemorrhagic Telangiectasia: Recent Advances and Future Challenges)

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14 pages, 285 KiB

Open AccessReview

Lipid-Lowering Therapy in Patients with Coronary Heart Disease and Prior Stroke: Mission Impossible?

by Pier Luigi Temporelli, Marcello Arca, Laura D’Erasmo and Raffaele De Caterina

J. Clin. Med. 2021, 10(4), 886; https://doi.org/10.3390/jcm10040886 - 22 Feb 2021

Cited by 6 | Viewed by 3110

Abstract

Hyperlipidemia is a powerful risk factor for coronary heart disease (CHD). It has been known for a long time that lipid-lowering drugs significantly reduce morbidity from CHD, thus proving a causal role for cholesterol in coronary events. Conversely, the relationship between low-density lipoprotein [...] Read more.

Hyperlipidemia is a powerful risk factor for coronary heart disease (CHD). It has been known for a long time that lipid-lowering drugs significantly reduce morbidity from CHD, thus proving a causal role for cholesterol in coronary events. Conversely, the relationship between low-density lipoprotein cholesterol (LDL-C) levels and stroke has been less clear and debated for many years. Recent data conclusively demonstrate not only the inverse epidemiological relationship of blood LDL-C with stroke, but also the efficacy of different strategies to attain cholesterol-lowering on stroke. They also dissipate lingering doubts about the possibility that lipid-lowering is linked to an increase in hemorrhagic stroke. However, despite current international lipid guidelines now strongly recommend aggressive lipid-lowering therapy in patients with atherosclerotic cardiovascular disease, including CHD and cerebrovascular disease (CeVD), secondary prevention patients are often undertreated with lipid-lowering therapies in routine clinical practice. This review highlights that patients with CHD and concomitant CeVD do not receive aggressive lipid-lowering therapy despite being at very high risk and with clear evidence of benefit from lowering LDL-C levels below current targets. Full article

(This article belongs to the Special Issue Treatment and Outcome of Patients with Prior Cerebrovascular Accidents and Coronary Artery Disease)

11 pages, 3920 KiB

Open AccessArticle

Importance of Preoperative Screening Strategies for Coronavirus Disease 2019 in Patients Undergoing Cesarean Sections: A Retrospective, Large Single-Center, Observational Cohort Study

by Ha-Jung Kim, Hyun-Seok Cho, Mi-Young Lee, Hyungtae Kim, Woo-Jong Choi, Hye-Sung Won, Young-Jin Ro and In-Cheol Choi

J. Clin. Med. 2021, 10(4), 885; https://doi.org/10.3390/jcm10040885 - 22 Feb 2021

Cited by 1 | Viewed by 2562

Abstract

During the coronavirus disease 2019 (COVID-19) pandemic, many guidelines have recommended postponing non-emergency operations. However, cesarean sections cannot be indefinitely delayed. Our institution has established a COVID-19 screening strategy for patients undergoing cesarean section. We evaluated the usefulness of this screening strategy. Parturients [...] Read more.

During the coronavirus disease 2019 (COVID-19) pandemic, many guidelines have recommended postponing non-emergency operations. However, cesarean sections cannot be indefinitely delayed. Our institution has established a COVID-19 screening strategy for patients undergoing cesarean section. We evaluated the usefulness of this screening strategy. Parturients undergoing cesarean section at our center during the first peak of the COVID-19 outbreak were retrospectively analyzed. Each parturient underwent a questionnaire survey evaluating epidemiological correlation and symptoms at admission. Reverse transcriptase–polymerase chain reaction (RT–PCR) testing and/or chest radiography were performed. In total, 296 parturients underwent cesarean section. All elective and 37 emergency cesarean sections were performed in general operating rooms because they were considered to have a low risk of COVID-19 infection through the screening process. However, 42 emergency cases were performed in negative-pressure operating rooms with full personal protective equipment (PPE) because the RT–PCR results could not be confirmed in a timely manner. None of them were positive for RT–PCR, and there were no cases of nosocomial infection. A comprehensive preoperative screening strategy, including symptomatic and epidemiological correlation, PCR, and/or imaging test, should be performed in patients undergoing cesarian section. Further, cesarean sections in parturients with unconfirmed COVID-19 status should be performed in a negative-pressure operating room with appropriate PPE. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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14 pages, 1566 KiB

Open AccessArticle

Tear Film Break-Up Time and Dry Eye Disease Severity in a Large Norwegian Cohort

by Mazyar Yazdani, Jørgen Fiskådal, Xiangjun Chen, Øygunn A. Utheim, Sten Ræder, Valeria Vitelli and Tor P. Utheim

J. Clin. Med. 2021, 10(4), 884; https://doi.org/10.3390/jcm10040884 - 22 Feb 2021

Cited by 15 | Viewed by 4831

Abstract

This study evaluated to what extent tear film break-up time (TFBUT) could discriminate pathological scores for other clinical tests and explore the associations between them. Dry eye patients (n = 2094) were examined for ocular surface disease index (OSDI), tear film osmolarity [...] Read more.

This study evaluated to what extent tear film break-up time (TFBUT) could discriminate pathological scores for other clinical tests and explore the associations between them. Dry eye patients (n = 2094) were examined for ocular surface disease index (OSDI), tear film osmolarity (Osm), TFBUT, blink interval, ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test, meibomian expressibility, meibomian quality, and meibomian gland dysfunction. The results were grouped into eight levels of break-up time (≤2, ≥3, ≤5, ≥6, ≤10, ≥11, ≤15, and ≥16) with or without sex stratification. Receiver-operating characteristic curve (ROC) analysis and Pearson’s correlation coefficients were used to study TFBUT’s discriminative power and the associations among the tests, respectively. Above and below each TFBUT’s cut-off, all of the parameters indicated significant difference between groups, except OSDI (cut-off 15 s) and Osm (cut-offs 5 s–15 s). At TFBUT cut-off of 2 s, sex difference could be detected for OSDI, Osm, and OSS. OPI presented the strongest discriminative power and association with TFBUT in sharp contrast to Osm, holding the poorest discriminative power with no significant correlation. The remaining parameters were within the poor to very poor categories, both with regard to discrimination and correlation. In conclusion, patients with lower TFBUT presented with more severe DED parameters at all four defined cut-off values. Full article

(This article belongs to the Section Ophthalmology)

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1 pages, 157 KiB

Open AccessRetraction

RETRACTED: De Vecchis et al. Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea. J. Clin. Med. 2016, 5, 85

by Renato De Vecchis, Cesare Baldi, Carmelina Ariano and JCM Editorial Office

J. Clin. Med. 2021, 10(4), 883; https://doi.org/10.3390/jcm10040883 - 22 Feb 2021

Cited by 4 | Viewed by 2338

Abstract

The journal retracts the article “Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea” by De Vecchis, R [...] Full article

15 pages, 573 KiB

Open AccessReview

Pharmacological Management of Neurogenic Bowel Dysfunction after Spinal Cord Injury and Multiple Sclerosis: A Systematic Review and Clinical Implications

by Jeffery S Johns, Klaus Krogh, Karen Ethans, Joanne Chi, Matthew Querée, Janice J Eng and Spinal Cord Injury Research Evidence Team

J. Clin. Med. 2021, 10(4), 882; https://doi.org/10.3390/jcm10040882 - 22 Feb 2021

Cited by 24 | Viewed by 6305

Abstract

Neurogenic bowel dysfunction (NBD) is a common problem for people with spinal cord injury (SCI) and multiple sclerosis (MS), which seriously impacts quality of life. Pharmacological management is an important component of conservative bowel management. The objective of this study was to first [...] Read more.

Neurogenic bowel dysfunction (NBD) is a common problem for people with spinal cord injury (SCI) and multiple sclerosis (MS), which seriously impacts quality of life. Pharmacological management is an important component of conservative bowel management. The objective of this study was to first assemble a list of pharmacological agents (medications and medicated suppositories) used in current practice. Second, we systematically examined the current literature on pharmacological agents to manage neurogenic bowel dysfunction of individuals specifically with SCI or MS. We searched Medline, EMBASE and CINAHL databases up to June 2020. We used the GRADE System to provide a systematic approach for evaluating the evidence. Twenty-eight studies were included in the review. We found a stark discrepancy between the large number of agents currently prescribed and a very limited amount of literature. While there was a small amount of literature in SCI, there was little to no literature available for MS. There was low-quality evidence supporting rectal medications, which are a key component of conservative bowel care in SCI. Based on the findings of the literature and the clinical experience of the authors, we have provided clinical insights on proposed treatments and medications in the form of three case study examples on patients with SCI or MS. Full article

(This article belongs to the Special Issue Neurogenic Bowel Dysfunction)

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17 pages, 693 KiB

Open AccessReview

Pearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist

by Jason B. Katz, Kent Owusu, Ilisa Nussbaum, Rachel Beekman, Nicholas A. DeFilippo, Emily J. Gilmore, Lawrence J. Hirsch, Mackenzie C. Cervenka and Carolina B. Maciel

J. Clin. Med. 2021, 10(4), 881; https://doi.org/10.3390/jcm10040881 - 22 Feb 2021

Cited by 20 | Viewed by 8001

Abstract

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe [...] Read more.

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe our experience, including the challenges of achieving and maintaining ketosis, in an adult with new onset refractory status epilepticus (NORSE). Case Vignette: A previously healthy 29-year-old woman was admitted with cryptogenic NORSE following a febrile illness; course was complicated by prolonged super-refractory SE. A comprehensive work-up was notable only for mild cerebral spinal fluid (CSF) pleocytosis, elevated nonspecific serum inflammatory markers, and edematous hippocampi with associated diffusion restriction on magnetic resonance imaging (MRI). Repeat CSF testing was normal and serial MRIs demonstrated resolution of edema and diffusion restriction with progressive hippocampal and diffuse atrophy. She required prolonged therapeutic coma with high anesthetic infusion rates, 16 antiseizure drug (ASD) trials, empiric immunosuppression and partial bilateral oophorectomy. Enteral ketogenic formula was started on hospital day 28. However, sustained beta-hydroxybutyrate levels >2 mmol/L were only achieved 37 days later following a comprehensive adjustment of the care plan. KD was challenging to maintain in the intensive care unit (ICU) and was discontinued due to poor nutritional state and pressure ulcers. KD was restarted again in a non-ICU unit facilitating ASD tapering without re-emergence of SE. Discussion: There are inconspicuous carbohydrates in commonly administered medications for SE including antibiotics, electrolyte repletion formulations, different preparations of the same drug (i.e., parenteral, tablet, or suspension) and even solutions used for oral care―all challenging the use of KD in the hospitalized patient. Tailoring comprehensive care and awareness of possible complications of KD are important for the successful implementation and maintenance of ketosis. Full article

(This article belongs to the Special Issue Epileptic Seizures in Critically Ill Patients: Diagnosis, Management, and Outcomes)

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9 pages, 1359 KiB

Open AccessArticle

Effects of the COVID-19 Epidemic on Hospital Admissions for Non-Communicable Diseases in a Large Italian University-Hospital: A Descriptive Case-Series Study

by Caterina Caminiti, Giuseppe Maglietta, Tiziana Meschi, Andrea Ticinesi, Mario Silva and Nicola Sverzellati

J. Clin. Med. 2021, 10(4), 880; https://doi.org/10.3390/jcm10040880 - 21 Feb 2021

Cited by 34 | Viewed by 3645

Abstract

Background: Concern is growing about the negative consequences that response measures to the COVID-19 epidemic may have on the management of other medical conditions. Methods: A retrospective descriptive case-series study conducted at a large University-hospital in northern Italy, an area severely hit by [...] Read more.

Background: Concern is growing about the negative consequences that response measures to the COVID-19 epidemic may have on the management of other medical conditions. Methods: A retrospective descriptive case-series study conducted at a large University-hospital in northern Italy, an area severely hit by the epidemic. Results: Between 23 February and 14 May 2020, 4160 (52%) COVID-19 and 3778 (48%) non-COVID-19 patients were hospitalized. COVID-19 admissions peaked in the second half of March, a period characterized by an extremely high mortality rate (27.4%). The number of admissions in 2020 was similar to 2019, but COVID-19 patients gradually occupied all available beds. Comparison between COVID-19 and non-COVID-19 admissions in 2020 revealed significant differences concerning all age classes and gender. Specifically, COVID-19 patients were older, predominantly male, and exhibited more comorbidities. Overall, admissions for non-communicable diseases (NCDs) in 2020 vs. 2019 dropped by approximately one third. Statistically significant reductions were observed for acute myocardial infarction (−78, −33.9%), cerebrovascular disease (−235, −41.5%), and cancer (−368, −31.9%). While the first two appeared equally distributed between COVID-19 and non-COVID-19 patients, chronic NCDs were statistically significantly more frequent in the former, except cancer, which was less frequent in COVID-19 patients. Conclusions: Prevention of collateral damage to patients with other diseases should be an integral part of epidemic response plans. Prospective cohort studies are needed to understand the long-term impact. Full article

(This article belongs to the Section Epidemiology & Public Health)

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15 pages, 3909 KiB

Open AccessReview

Prognostic Significance of Survivin Expression in Patients with Ovarian Carcinoma: A Meta-Analysis

by Beata Gąsowska-Bajger, Agnieszka Gąsowska-Bodnar, Paweł Knapp and Lubomir Bodnar

J. Clin. Med. 2021, 10(4), 879; https://doi.org/10.3390/jcm10040879 - 21 Feb 2021

Cited by 14 | Viewed by 2794

Abstract

Background: Survivin belongs to the protein family of inhibitors of apoptosis (IAP) and is a regulator of the cell cycle and apoptosis. The aim of this study was to assess the clinical and prognostic significance of expression survivin in patients with ovarian cancer. [...] Read more.

Background: Survivin belongs to the protein family of inhibitors of apoptosis (IAP) and is a regulator of the cell cycle and apoptosis. The aim of this study was to assess the clinical and prognostic significance of expression survivin in patients with ovarian cancer. Methods: We systematically searched for articles in PubMed, the American Chemical Society (Publications), Medline, the Royal Society of Chemistry, Scopus and the Web of Science. Patient clinical data, overall survival (OS), disease-free survival (DFS), and survivin expression were extracted from individual studies. We performed statistical analysis using the STATA 16 package. Eighteen publications containing data from 2233 patients with ovarian cancer were included in this meta-analysis. Results: We found an adverse effect of survivin expression on OS (risk ratio (HR): 1.60; 95% confidence interval (CI): 1.33–1.93, p = 0.00) but this was not observed on DFS (HR: 1.06; 95% CI: 0.55–2.05, p = 0.87). The analysis of clinicopathological parameters showed that survivin expression was associated with the histological grades (G1–2 vs. G3) (odds ratio (OR) = 0.53, 95% CI: 0.34–0.83, p = 0.01) and: International Federation Gynecology and Obstetrics (FIGO) stage (I–II vs. III–IV) (OR = 0.22, 95% CI: 0.09–0.55, p = 0.00), but it was not significantly correlated with the histological subtype (OR = 1.14, 95% CI: 0.83–1.58, p = 0.42). Conclusions: Our meta-analysis suggests that survivin expression may be a marker of poor prognosis in ovarian cancer. Survivin expression was associated with parameters of greater aggressiveness of ovarian cancer. Prospective studies are needed to confirm our results indicating that survivin expression can be used as an ovarian cancer biomarker. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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11 pages, 325 KiB

Open AccessArticle

Exploring the Role of Interleukin-6 Receptor Inhibitor Tocilizumab in Patients with Active Rheumatoid Arthritis and Periodontal Disease

by Codrina Ancuța, Rodica Chirieac, Eugen Ancuța, Oana Țănculescu, Sorina Mihaela Solomon, Ana Maria Fătu, Adrian Doloca and Cristina Iordache

J. Clin. Med. 2021, 10(4), 878; https://doi.org/10.3390/jcm10040878 - 20 Feb 2021

Cited by 20 | Viewed by 2946

Abstract

Background: The aim of our study was to explore the influence of weekly subcutaneous administration of interleukin-6 (IL-6) receptor inhibitor tocilizumab (TCZ) on periodontal status in a local longitudinal study of patients with rheumatoid arthritis (RA) and periodontal disease (PD). Methods: We performed [...] Read more.

Background: The aim of our study was to explore the influence of weekly subcutaneous administration of interleukin-6 (IL-6) receptor inhibitor tocilizumab (TCZ) on periodontal status in a local longitudinal study of patients with rheumatoid arthritis (RA) and periodontal disease (PD). Methods: We performed a 6-month prospective study in 51 patients with chronic periodontitis and moderate-to-severe RA starting TCZ in accordance with local recommendations. Extensive rheumatologic (clinical activity, inflammatory, serological biomarkers) and periodontal (visible plaque index, gingival index, bleeding on probing, probing pocket depth, clinical attachment loss) assessments were done. Changes in RA activity and periodontal status were reassessed after 3 and 6 months. Results: We demonstrated significant correlations between periodontal status, disease activity, and serologic biomarkers (p < 0.05). Tocilizumab significantly improved the gingival index scores and decreased the number of sites with bleeding on probing after only 3 months (p < 0.05), while the probing pocket depth significantly decreased after 6 months; overall, clinical attachment loss presented only slight changes without any statistical significance as well as teeth count and plaque levels (p > 0.05). Conclusion: IL-6 inhibition is able to improve periodontal outcomes in patients with RA and concomitant PD, which is essentially related to a dramatic decrease in serum inflammatory mediators. Full article

(This article belongs to the Special Issue Prevention and Treatment of Periodontitis)

33 pages, 722 KiB

Open AccessReview

Thrombocytopenia in Virus Infections

by Matthijs Raadsen, Justin Du Toit, Thomas Langerak, Bas van Bussel, Eric van Gorp and Marco Goeijenbier

J. Clin. Med. 2021, 10(4), 877; https://doi.org/10.3390/jcm10040877 - 20 Feb 2021

Cited by 82 | Viewed by 19072

Abstract

Thrombocytopenia, which signifies a low platelet count usually below 150 × 10⁹/L, is a common finding following or during many viral infections. In clinical medicine, mild thrombocytopenia, combined with lymphopenia in a patient with signs and symptoms of an infectious disease, [...] Read more.

Thrombocytopenia, which signifies a low platelet count usually below 150 × 10⁹/L, is a common finding following or during many viral infections. In clinical medicine, mild thrombocytopenia, combined with lymphopenia in a patient with signs and symptoms of an infectious disease, raises the suspicion of a viral infection. This phenomenon is classically attributed to platelet consumption due to inflammation-induced coagulation, sequestration from the circulation by phagocytosis and hypersplenism, and impaired platelet production due to defective megakaryopoiesis or cytokine-induced myelosuppression. All these mechanisms, while plausible and supported by substantial evidence, regard platelets as passive bystanders during viral infection. However, platelets are increasingly recognized as active players in the (antiviral) immune response and have been shown to interact with cells of the innate and adaptive immune system as well as directly with viruses. These findings can be of interest both for understanding the pathogenesis of viral infectious diseases and predicting outcome. In this review, we will summarize and discuss the literature currently available on various mechanisms within the relationship between thrombocytopenia and virus infections. Full article

(This article belongs to the Special Issue The Latest Clinical Advances in Thrombocytopenia)

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9 pages, 233 KiB

Open AccessArticle

Relationship between Tooth Loss and the Medications Used for the Treatment of Rheumatoid Arthritis in Japanese Patients with Rheumatoid Arthritis: A Cross-Sectional Study

by Hiroko Hashimoto, Shimpei Hashimoto and Yoshihiro Shimazaki

J. Clin. Med. 2021, 10(4), 876; https://doi.org/10.3390/jcm10040876 - 20 Feb 2021

Cited by 11 | Viewed by 3065

Abstract

Background: There is limited information regarding the association between tooth loss and the medications used for the treatment of rheumatoid arthritis (RA). Here, we examined the association between tooth loss, disease severity, and drug treatment regimens in RA patients. Method: This study recruited [...] Read more.

Background: There is limited information regarding the association between tooth loss and the medications used for the treatment of rheumatoid arthritis (RA). Here, we examined the association between tooth loss, disease severity, and drug treatment regimens in RA patients. Method: This study recruited 94 Japanese patients with RA. The severity of RA was assessed using the Steinbrocker classification of class and stage. Data on RA medications were obtained from medical records. We examined the associations between tooth loss, RA severity, and drug treatment regi mens using multinomial logistic regression analyses. Results: Patients with 1–19 teeth had significantly higher odds ratios (ORs) of taking methotrexate (MTX) (OR, 8.74; 95% confidence interval (CI), 1.11–68.8) and biologic disease-modifying antirheumatic drugs (bDMARDs) (OR, 21.0; 95% CI, 1.3–339.1) compared to those with 27–28 teeth when adjusted for RA severity (class). Furthermore, patients with 1–19 teeth had significantly higher ORs of taking MTX (OR, 9.71; 95% CI, 1.22–77.1) and bDMARDs (OR, 50.2; 95% CI, 2.55–990.6) compared to those with 27–28 teeth when adjusted for RA severity (stage). Conclusion: RA patients with fewer teeth were more likely to take stronger RA therapies, independent of RA severity and other factors. Full article

(This article belongs to the Collection Systemic Manifestations and Complications of Rheumatoid Arthritis)

19 pages, 1242 KiB

Open AccessArticle

Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

by Kawaljit Kaur, Shahram Vaziri, Marcela Romero-Reyes, Avina Paranjpe and Anahid Jewett

J. Clin. Med. 2021, 10(4), 875; https://doi.org/10.3390/jcm10040875 - 20 Feb 2021

Cited by 1 | Viewed by 2884

Abstract

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of [...] Read more.

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood. Full article

(This article belongs to the Special Issue Periodontitis: Current Status and the Future)

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15 pages, 887 KiB

Open AccessArticle

Predictors of Progression and Mortality in Patients with Prevalent Rheumatoid Arthritis and Interstitial Lung Disease: A Prospective Cohort Study

by Natalia Mena-Vázquez, Marta Rojas-Gimenez, Carmen María Romero-Barco, Sara Manrique-Arija, Espildora Francisco, María Carmen Aguilar-Hurtado, Isabel Añón-Oñate, Lorena Pérez-Albaladejo, Rafaela Ortega-Castro, Francisco Javier Godoy-Navarrete, Inmaculada Ureña-Garnica, Maria Luisa Velloso-Feijoo, Rocio Redondo-Rodriguez, Francisco Gabriel Jimenez-Núñez, Blanca Panero Lamothe, María Isabel Padin-Martín and Antonio Fernández-Nebro

J. Clin. Med. 2021, 10(4), 874; https://doi.org/10.3390/jcm10040874 - 20 Feb 2021

Cited by 51 | Viewed by 4842

Abstract

Objectives: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. Patients and methods: We performed a multicenter, prospective, observational study of patients with [...] Read more.

Objectives: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. Patients and methods: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving disease-modifying antirheumatic drugs (DMARDs) between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main endpoint was “Progression to ILD at the end of follow-up” in terms of the following outcomes: (1) improvement (i.e., improvement in forced vital capacity (FVC) ≥10% or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥15% and absence of radiological progression); (2) nonprogression (stabilization or improvement in FVC ≤10% or diffusing capacity of the lungs for carbon monoxide (DLCO) <15% and absence of radiological progression); (3) progression (worsening of FVC >10% or DLCO >15% and radiological progression); or (4) death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with the worsening of ILD. Results: After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months after diagnosis of ILD. The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (hazard ratio (HR), 2.6 (95%CI, 1.0–6.7)), FVC <80% (HR, 3.8 (95%CI, 1.5–6.7)), anticitrullinated protein antibody titers (HR, 2.8 (95%CI, 1.1–6.8)), smoking (HR, 2.5 (95%CI, 1.1–6.2)), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 (95%CI, 0.2–0.8)). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%). Infection was fatal in 10/18 patients (55.5%) during follow-up. Conclusions: Lung function is stable in most patients with RA-ILD receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs), although one-third worsened or died. Identifying factors associated with worsening in RA-ILD is important for clinical management. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis and Other Inflammatory Diseases: From Pathogenesis through Therapeutic Targets to Personalized Medicine)

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9 pages, 1091 KiB

Open AccessArticle

Is Neoadjuvant Treatment Justified in Clinical T1 Pancreatic Ductal Adenocarcinoma?

by Hyung Sun Kim, Kenji Nakagawa, Takahiro Akahori, Kota Nakamura, Tadataka Takagi, Masayuki Sho, Joon Seong Park and Dong Sup Yoon

J. Clin. Med. 2021, 10(4), 873; https://doi.org/10.3390/jcm10040873 - 20 Feb 2021

Cited by 3 | Viewed by 2836

Abstract

Introduction: Studies on neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. However, neoadjuvant treatment effectiveness, especially in clinical T1 stage patients, still needs to be determined. We comparatively evaluated the oncologic benefit of preoperative neoadjuvant treatment in clinical [...] Read more.

Introduction: Studies on neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. However, neoadjuvant treatment effectiveness, especially in clinical T1 stage patients, still needs to be determined. We comparatively evaluated the oncologic benefit of preoperative neoadjuvant treatment in clinical T1 stage pancreatic cancer. Methods: Data from two centers were included in the comparative analysis, with overall and recurrence-free survival as primary outcomes, between January 2010 and December 2017. Results: In total, 45 patients were retrospectively reviewed in this study. Two patients in the neoadjuvant group were excluded because of distant metastasis during neoadjuvant treatment. Finally, 43 patients underwent a pancreatectomy for clinical T1 pancreatic cancer, of whom, 35 and 8 patients underwent upfront surgery and neoadjuvant treatment, respectively. Overall survival was similar in the two study groups (5-year overall survival rate: neoadjuvant group, 75%; upfront surgery group, 43.9%, p = 0.066). Conclusions: In our study on patients with clinical T1 stage pancreatic cancer, no significant differences were reported in the oncological outcome in the neoadjuvant therapy group. Large-scale prospective studies are needed to determine the survival benefits of neoadjuvant treatment for early-stage pancreatic cancer. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Challenges and Breakthroughs)

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8 pages, 529 KiB

Open AccessCommunication

A Cognitive Behavioral Therapy-Informed Self-Management Program for Acute Respiratory Failure Survivors: A Feasibility Study

by Megan M. Hosey, Stephen T. Wegener, Caroline Hinkle and Dale M. Needham

J. Clin. Med. 2021, 10(4), 872; https://doi.org/10.3390/jcm10040872 - 20 Feb 2021

Cited by 8 | Viewed by 4831

Abstract

Background: The number of people surviving critical illness is rising rapidly around the globe. Survivorship comes at a cost, with approximately half of patients with acute respiratory failure (ARF) experiencing clinically significant symptoms of anxiety, and 32–40% of survivors having substantial anxiety symptoms [...] Read more.

Background: The number of people surviving critical illness is rising rapidly around the globe. Survivorship comes at a cost, with approximately half of patients with acute respiratory failure (ARF) experiencing clinically significant symptoms of anxiety, and 32–40% of survivors having substantial anxiety symptoms in the months or years after hospitalization. Methods: This feasibility study reports on 11 consecutive ARF patients receiving up to six sessions of a psychological intervention for self-management of anxiety. Results: All 11 patients accepted and received the psychological intervention. Four patients did not fully complete all 6 sessions due to death (n = 1, 2 sessions completed), and early hospital discharge (n = 3, patients completed 2, 3 and 5 sessions). The median (IQR) score (range: 0–100; minimal clinically important difference: 13) for the Visual Analog Scale-Anxiety (VAS-A) pre-intervention was 70 (57, 75) points. During the intervention, all 11 patients had a decrease in VAS-A, with a median (IQR) decrease of 44 (19, 48) points. Conclusions: This self-management intervention appears acceptable and feasible to implement among ARF patients during and after an ICU stay. Full article

(This article belongs to the Special Issue Post-intensive Care Syndrome: Prevention, Current Status and Future Challenges)

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9 pages, 604 KiB

Open AccessArticle

CD28 Gene Polymorphisms in the Promoter Region Are Associated with Transfusion Reactions: A Functional Study

by Ying-Hao Wen, Wei-Tzu Lin, Wei-Ting Wang and Ding-Ping Chen

J. Clin. Med. 2021, 10(4), 871; https://doi.org/10.3390/jcm10040871 - 20 Feb 2021

Cited by 2 | Viewed by 2609

Abstract

Transfusion reactions are mainly induced by the interaction of an antigen and antibody. However, transfusion reactions still occur with the implementing of crossmatching and usage of pre-storage leukoreduced blood products. The roles of CD28 and CTLA4 gene polymorphisms in transfusion reaction have been [...] Read more.

Transfusion reactions are mainly induced by the interaction of an antigen and antibody. However, transfusion reactions still occur with the implementing of crossmatching and usage of pre-storage leukoreduced blood products. The roles of CD28 and CTLA4 gene polymorphisms in transfusion reaction have been shown, and subjects with certain single nucleotide polymorphisms (SNPs) of the CD28 or CTLA4 gene had a significantly higher risk of transfusion reactions. In total, 40 patients with transfusion reactions after receiving pre-storage leukoreduced blood products were enrolled in this study. We focused on the SNPs located in the CD28 promoter region (rs1879877, rs3181096, rs3181097, and rs3181098) to find out the significant SNP. A luciferase reporter assay was used to investigate the expression level of protein affected by promoter SNP variation. We found that the polymorphism of rs3181097 was associated with transfusion reactions (p = 0.003 in additive model and p = 0.015 in dominant model). Consequently, we investigated the biological function in the CD28 promoter polymorphisms (rs1879877 G > T, rs3181096 C > T, rs3181097 G > A, and rs3181098 G > A) by using dual-spectral luciferase reporter assay. The results showed that the ex-pression level of CD28 was decreased under the effect of rs3181097 with A-allele. This suggested that rs3181097 may regulate immune response through decreasing CD28 protein expression and then lead to development of transfusion reactions. Full article

(This article belongs to the Section Hematology)

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11 pages, 2936 KiB

Open AccessArticle

Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature

by Bruno Fattizzo, Marta Ferraresi, Juri Alessandro Giannotta and Wilma Barcellini

J. Clin. Med. 2021, 10(4), 870; https://doi.org/10.3390/jcm10040870 - 20 Feb 2021

Cited by 8 | Viewed by 3545

Abstract

Hemophagocytic lymphohistocytosis (HLH) is a rare hyperinflammatory condition which may be primary or secondary to many diseases, including hematologic malignancies. Due to its life-threatening evolution, a timely diagnosis is paramount but challenging, since it relies on non-specific clinical and laboratory criteria. The latter [...] Read more.

Hemophagocytic lymphohistocytosis (HLH) is a rare hyperinflammatory condition which may be primary or secondary to many diseases, including hematologic malignancies. Due to its life-threatening evolution, a timely diagnosis is paramount but challenging, since it relies on non-specific clinical and laboratory criteria. The latter are often altered in other diseases, including autoimmune cytopenias (AIC), which in turn can be secondary to infections, systemic autoimmune or lymphoproliferative disorders. In the present article, we describe two patients presenting at the emergency department with acute AICs subsequently diagnosed as HLH with underlying diffuse large B cell lymphoma. We discuss the diagnostic challenges in the differential diagnosis of acute cytopenias in the internal medicine setting, providing a literature review of secondary HLH and AIC. Full article

(This article belongs to the Section Hematology)

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21 pages, 385 KiB

Open AccessReview

Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art

by Kilian Vomstein, Katharina Feil, Laura Strobel, Anna Aulitzky, Susanne Hofer-Tollinger, Ruben-Jeremias Kuon and Bettina Toth

J. Clin. Med. 2021, 10(4), 869; https://doi.org/10.3390/jcm10040869 - 20 Feb 2021

Cited by 64 | Viewed by 9364

Abstract

Around 1–5% of all couples experience recurrent pregnancy loss (RPL). Established risk factors include anatomical, genetic, endocrine, and hemostatic alterations. With around 50% of idiopathic cases, immunological risk factors are getting into the scientific focus, however international guidelines hardly take them into account. [...] Read more.

Around 1–5% of all couples experience recurrent pregnancy loss (RPL). Established risk factors include anatomical, genetic, endocrine, and hemostatic alterations. With around 50% of idiopathic cases, immunological risk factors are getting into the scientific focus, however international guidelines hardly take them into account. Within this review, the current state of immunological risk factors in RPL in international guidelines of the European Society of Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine (ASRM), German/Austrian/Swiss Society of Obstetrics and Gynecology (DGGG/OEGGG/SGGG) and the Royal College of Obstetricians and Gynecologists (RCOG) are evaluated. Special attention was drawn to recommendations in the guidelines regarding diagnostic factors such as autoantibodies, natural killer cells, regulatory T cells, dendritic cells, plasma cells, and human leukocyte antigen system (HLA)-sharing as well as treatment options such as corticosteroids, intralipids, intravenous immunoglobulins, aspirin and heparin in RPL. Finally, the current state of the art focusing on both diagnostic and therapeutic options was summarized. Full article

(This article belongs to the Special Issue Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy)

14 pages, 2356 KiB

Open AccessArticle

Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

by Katarzyna Kapica-Topczewska, François Collin, Joanna Tarasiuk, Agata Czarnowska, Monika Chorąży, Anna Mirończuk, Jan Kochanowicz and Alina Kułakowska

J. Clin. Med. 2021, 10(4), 868; https://doi.org/10.3390/jcm10040868 - 19 Feb 2021

Cited by 16 | Viewed by 3715

Abstract

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), [...] Read more.

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and progression independent of relapses and brain MRI Activity (PIRMA). Data from the Therapeutic Program Monitoring System were analyzed. Three panels of patients were identified: R0, no relapse during treatment, and R1 and R2 with the occurrence of relapse during the first and the second year of treatment, respectively. In the R0 panel, we detected 4.6% PIRA patients at 24 months (p < 0.001, 5.0% at 36 months, 5.6% at 48 months, 6.1% at 60 months). When restricting this panel to patients without brain MRI activity, we detected 3.0% PIRMA patients at 12 months, 4.5% at 24 months, and varying from 5.3% to 6.2% between 36 and 60 months of treatment, respectively. In the R1 panel, RAW was detected in 15.6% patients at 12 months and, in the absence of further relapses, 9.7% at 24 months and 6.8% at 36 months of treatment. The R2 group was associated with RAW significantly more frequently at 24 months compared to the R1 at 12 months (20.7%; p < 0.05), but without a statistical difference later on. In our work, we confirmed that disability progression was independent of relapses and brain MRI activity. Full article

(This article belongs to the Section Clinical Neurology)

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16 pages, 2118 KiB

Open AccessArticle

Aberrant Expression of TLR2, TLR7, TLR9, Splicing Variants of TLR4 and MYD88 in Chronic Lymphocytic Leukemia Patients

by Katarzyna Skorka, Paulina Wlasiuk, Agnieszka Karczmarczyk and Krzysztof Giannopoulos

J. Clin. Med. 2021, 10(4), 867; https://doi.org/10.3390/jcm10040867 - 19 Feb 2021

Cited by 8 | Viewed by 3103

Abstract

Functional toll-like receptors (TLRs) could modulate anti-tumor effects by activating inflammatory cytokines and the cytotoxic T-cells response. However, excessive TLR expression could promote tumor progression, since TLR-induced inflammation might stimulate cancer cells expansion into the microenvironment. Myd88 is involved in activation NF-κB through [...] Read more.

Functional toll-like receptors (TLRs) could modulate anti-tumor effects by activating inflammatory cytokines and the cytotoxic T-cells response. However, excessive TLR expression could promote tumor progression, since TLR-induced inflammation might stimulate cancer cells expansion into the microenvironment. Myd88 is involved in activation NF-κB through TLRs downstream signaling, hence in the current study we provided, for the first time, a complex characterization of expression of TLR2, TLR4, TLR7, TLR9, and MYD88 as well as their splicing forms in two distinct compartments of the microenvironment of chronic lymphocytic leukemia (CLL): peripheral blood and bone marrow. We found correlations between MYD88 and TLRs expressions in both compartments, indicating their relevant cooperation in CLL. The MYD88 expression was higher in CLL patients compared to healthy volunteers (HVs) (0.1780 vs. 0.128, p < 0.0001). The TLRs expression was aberrant in CLL compared to HVs. Analysis of survival curves revealed a shorter time to first treatment in the group of patients with low level of TLR4(3) expression compared to high level of TLR4(3) expression in bone marrow (13 months vs. 48 months, p = 0.0207). We suggest that TLRs expression is differentially regulated in CLL but is similarly shared between two distinct compartments of the microenvironment. Full article

(This article belongs to the Section Hematology)

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11 pages, 260 KiB

Open AccessArticle

Associations of MDM2 and MDM4 Polymorphisms with Early-Stage Breast Cancer

by Agnė Bartnykaitė, Aistė Savukaitytė, Rasa Ugenskienė, Monika Daukšaitė, Erika Korobeinikova, Jurgita Gudaitienė and Elona Juozaitytė

J. Clin. Med. 2021, 10(4), 866; https://doi.org/10.3390/jcm10040866 - 19 Feb 2021

Cited by 11 | Viewed by 3734

Abstract

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed [...] Read more.

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I–II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment. Full article

(This article belongs to the Special Issue New Therapeutic Approaches, Biomarkers for Diagnosis, Prognosis and Therapy Prediction in Breast Cancer and Breast Cancer Recurrence)

99 pages, 518 KiB

Open AccessEditorial

Acknowledgment to Reviewers of Journal of Clinical Medicine in 2020

by Journal of Clinical Medicine Editorial Office

J. Clin. Med. 2021, 10(4), 865; https://doi.org/10.3390/jcm10040865 - 19 Feb 2021

Viewed by 8908

Abstract

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Journal of Clinical Medicine maintains its standards for the high quality of its published papers [...] Full article

12 pages, 950 KiB

Open AccessArticle

Influence of COVID-19 on Health-Related Quality of Life and the Perception of Being Vaccinated to Prevent COVID-19: An Approach for Community Pharmacists from Romania and Bulgaria

by Adina Turcu-Stiolica, Maria Bogdan, Mihaela-Simona Subtirelu, Andreea-Daniela Meca, Adriana-Elena Taerel, Irina Iaru, Maria Kamusheva and Guenka Petrova

J. Clin. Med. 2021, 10(4), 864; https://doi.org/10.3390/jcm10040864 - 19 Feb 2021

Cited by 16 | Viewed by 5663

Abstract

Community pharmacists are essential front-line health workers, involved in relieving the COVID-19 burden. Their health-related quality of life status needs to be assessed, as lower levels could affect their functioning. In order to evaluate the current status of community pharmacists’ quality of life [...] Read more.

Community pharmacists are essential front-line health workers, involved in relieving the COVID-19 burden. Their health-related quality of life status needs to be assessed, as lower levels could affect their functioning. In order to evaluate the current status of community pharmacists’ quality of life from Romania and Bulgaria during the COVID-19 pandemic, and to identify factors associated with their decision on being vaccinated to prevent COVID-19, an online survey involving 395 community pharmacists was conducted from 15th July 2020 to 15th August 2020. The 15D instrument was used for quality-of-life assessment. The pharmacists’ recommendations for vitamin C and D intake during the COVID-19 pandemic were also analyzed in order to promote future training programs for community pharmacists. Descriptive statistics, comparative analyses between pharmacists from Romania and Bulgaria, and multiple correlation analyses were performed on the collected data. Significant differences were observed for the level of quality of life between the two groups of pharmacists according to their age; smaller values, directly correlated with their age (total 15D score and age: Spearman r = 0.168, p = 0.022), were obtained for Bulgarian pharmacists regarding sleeping, usual activities, mental function, discomfort and symptoms, depression, distress. The perception of being vaccinated did not differ between Romanian and Bulgarian pharmacists, as almost 50% agreed to vaccination (p = 0.7542). Their willingness to vaccinate was correlated with vitamin D usage (p = 0.0134), rather than with vitamin C (p = 0.4157). No other significant associations were found between willingness to get vaccinated to prevent COVID-19 and other characteristics (age, gender, income, quality-of-life markers). Evidence-based interventions are required to enhance the health-related quality of life of community pharmacists involved in the first line of the COVID-19 pandemic. Full article

(This article belongs to the Special Issue The Impact of the COVID-19 Emergency on the Quality of Life of the General Population)

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