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J. Clin. Med., Volume 11, Issue 16 (August-2 2022) – 294 articles

Cover Story (view full-size image): Sudden cardiac arrest is an event primarily caused by ventricular fibrillation. Ventricular fibrillation entails several underlying initiating causes, and a complete diagnostic work-up is essential in order to reveal the cause. This review focuses on the use of multimodality imaging for unraveling structural (or potentially electrical) substrates in patients presenting with a sudden cardiac arrest. The use and role of echocardiography, cardiac magnetic resonance and computed tomography are discussed. In addition, we focus on new techniques such as electrocardiographic characterization with non-invasive electrocardiographic imaging. We specifically focus on patients who are diagnosed with idiopathic ventricular fibrillation, a diagnosis by exclusion, in whom a substrate still needs to be revealed. View this paper
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Review
Pathophysiology of Coagulation and Emerging Roles for Extracellular Vesicles in Coagulation Cascades and Disorders
J. Clin. Med. 2022, 11(16), 4932; https://doi.org/10.3390/jcm11164932 - 22 Aug 2022
Viewed by 708
Abstract
The notion of blood coagulation dates back to the ancient Greek civilization. However, the emergence of innovative scientific discoveries that started in the seventeenth century formulated the fundamentals of blood coagulation. Our understanding of key coagulation processes continues to evolve, as novel homeostatic [...] Read more.
The notion of blood coagulation dates back to the ancient Greek civilization. However, the emergence of innovative scientific discoveries that started in the seventeenth century formulated the fundamentals of blood coagulation. Our understanding of key coagulation processes continues to evolve, as novel homeostatic and pathophysiological aspects of hemostasis are revealed. Hemostasis is a dynamic physiological process, which stops bleeding at the site of injury while maintaining normal blood flow within the body. Intrinsic and extrinsic coagulation pathways culminate in the homeostatic cessation of blood loss, through the sequential activation of the coagulation factors. Recently, the cell-based theory, which combines these two pathways, along with newly discovered mechanisms, emerged to holistically describe intricate in vivo coagulation mechanisms. The complexity of these mechanisms becomes evident in coagulation diseases such as hemophilia, Von Willebrand disease, thrombophilia, and vitamin K deficiency, in which excessive bleeding, thrombosis, or unnecessary clotting, drive the development and progression of diseases. Accumulating evidence implicates cell-derived and platelet-derived extracellular vesicles (EVs), which comprise microvesicles (MVs), exosomes, and apoptotic bodies, in the modulation of the coagulation cascade in hemostasis and thrombosis. As these EVs are associated with intercellular communication, molecular recycling, and metastatic niche creation, emerging evidence explores EVs as valuable diagnostic and therapeutic approaches in thrombotic and prothrombotic diseases. Full article
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Article
Comparison between Carotid Distensibility-Based Vascular Age and Risk-Based Vascular Age in Middle-Aged Population Free of Cardiovascular Disease
J. Clin. Med. 2022, 11(16), 4931; https://doi.org/10.3390/jcm11164931 - 22 Aug 2022
Viewed by 373
Abstract
The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk [...] Read more.
The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction. Full article
(This article belongs to the Special Issue Frontiers in Vascular Stiffness)
Article
The Effects of a Therapeutic Strategy Guided by Lung Ultrasound on 6-Month Outcomes in Patients with Heart Failure: Results from the EPICC Randomized Controlled Trial
J. Clin. Med. 2022, 11(16), 4930; https://doi.org/10.3390/jcm11164930 - 22 Aug 2022
Viewed by 390
Abstract
Background: Pulmonary congestion (PC) is associated with an increased risk of hospitalization and death in patients with heart failure (HF). Lung ultrasound is highly sensitive for detecting PC. The aim of this study is to evaluate whether lung ultrasound-guided therapy improves 6-month outcomes [...] Read more.
Background: Pulmonary congestion (PC) is associated with an increased risk of hospitalization and death in patients with heart failure (HF). Lung ultrasound is highly sensitive for detecting PC. The aim of this study is to evaluate whether lung ultrasound-guided therapy improves 6-month outcomes in patients with HF. Methods: A randomized, multicenter, single-blind clinical trial in patients discharged after hospitalization for decompensated HF. Participants were assigned 1:1 to receive treatment guided according to the presence of lung ultrasound signs of congestion (semi-quantitative evaluation of B lines and the presence of pleural effusion) versus standard of care (SOC). The primary endpoint was the combination of cardiovascular death, readmission, or emergency department or day hospital visit due to worsening HF at 6 months. In September 2020, after an interim analysis, patient recruitment was stopped. Results: A total of 79 patients were randomized (mean age 81.2 +/− 9 years) and 41 patients (51.8%) showed a left ventricular ejection fraction >50%. The primary endpoint occurred in 11 patients (29.7%) in the SOC group and in 11 patients (26.1%) in the LUS group (log-rank = 0.83). Regarding nonserious adverse events, no significant differences were found. Conclusions: LUS-guided diuretic therapy after hospital discharge due to ADHF did not show any benefit in survival or a need for intravenous diuretics compared with SOC. Full article
(This article belongs to the Special Issue Personalized Therapy and Clinical Outcome for Heart Failure)
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Article
Cervical Lymph Node Metastasis Differences in Patients with Unilateral or Bilateral Papillary Thyroid Microcarcinoma: A Multi-Center Analysis
J. Clin. Med. 2022, 11(16), 4929; https://doi.org/10.3390/jcm11164929 - 22 Aug 2022
Viewed by 384
Abstract
Purposes: To quantitatively predict the risk of neck lymph node metastasis for unilateral and bilateral papillary thyroid microcarcinomas (PTMC) that may guide individual treatment strategies for the neck region. Methods: A total of 717 PTMC patients from three medical centers were enrolled [...] Read more.
Purposes: To quantitatively predict the risk of neck lymph node metastasis for unilateral and bilateral papillary thyroid microcarcinomas (PTMC) that may guide individual treatment strategies for the neck region. Methods: A total of 717 PTMC patients from three medical centers were enrolled for analysis. Results: Bilateral PTMCs were demonstrated to be more aggressive with a much higher cervical lymph node metastasis rate including for both central (CLNM) and lateral lymph node metastasis (LLNM) when being compared to unilateral PTMCs. In unilateral PTMC, five (age < 55 years old, male, maximum tumor diameter (MTD) ≥ 0.5 cm, and the presence of thyroid capsular invasion (TCI) and multifocality) and three (maximum diameter of positive CLN (MDCLN) > 0.5 cm, the presence of multifocality and nodular goiter, iNG) factors were identified as independent risk factors for CLNM and LLNM, respectively. In bilateral PTMC, three (age < 55 and presence of TCI and multifocality in at least one side of thyroid lobe) and two (MDCLN > 0.5 cm and presence of nodular goiter (iNG)) factors were identified as independent factors for CLNM and LLNM, respectively. Predictive models of CLNM and LLNM for patients with unilateral disease and of CLNM for patients with the bilateral disease were established based on the described risk factors. Bilateral patients with positive CLNM were also stratified into different subgroups according to the presence and absence of independent risk factors. Conclusion: An evaluation system based on independent factors of CLNM and LLNM for PTMC patients with bilateral and unilateral disease was established. Our newly established evaluation system can efficaciously quantify risks of CLNM and LLNM for PTMC patients with bilateral and unilateral disease and may guide individual treatment strategy including both surgical and postoperative adjuvant treatment of the neck region for these patients. Full article
(This article belongs to the Special Issue Advances in the Treatment of Thyroid Cancer)
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Article
Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma
J. Clin. Med. 2022, 11(16), 4928; https://doi.org/10.3390/jcm11164928 - 22 Aug 2022
Viewed by 408
Abstract
Plasmablastic lymphoma (PBL) is a rare and aggressive form of large B-cell lymphoma (LBCL) most commonly seen in the setting of chronic immunosuppression or autoimmune disease. The prognosis is poor and CHOP-like regimens often fail to produce durable remission; therefore, there is no [...] Read more.
Plasmablastic lymphoma (PBL) is a rare and aggressive form of large B-cell lymphoma (LBCL) most commonly seen in the setting of chronic immunosuppression or autoimmune disease. The prognosis is poor and CHOP-like regimens often fail to produce durable remission; therefore, there is no established standard of care treatment. However, PBL demonstrates substantial morphologic and immunophenotypic overlap with multiple myeloma (MM), suggesting that MM therapeutics might prove useful in treating PBL. We studied the effects of treatment using the first-in-class monoclonal antibody directed against CD38, daratumumab, in combination with chemotherapy in seven patients with advanced-stage LBCL with plasmablastic features. Treatment was safe and well-tolerated. Among six evaluable patients, six patients had complete response after treatment, and four patients who met strict WHO criteria for PBL had durable response (12–31 months and ongoing). Full article
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Article
Sex-Related Differences in Patient Selection for and Outcomes after Pace and Ablate for Refractory Atrial Fibrillation: Insights from a Large Multicenter Cohort
J. Clin. Med. 2022, 11(16), 4927; https://doi.org/10.3390/jcm11164927 - 22 Aug 2022
Viewed by 326
Abstract
Background: A pace and ablate strategy may be performed in refractory atrial fibrillation with rapid ventricular response. Objective: We aimed to assess sex-related differences in patient selection and clinical outcomes after pace and ablate. Methods: In a retrospective multicentre study, patients undergoing AV [...] Read more.
Background: A pace and ablate strategy may be performed in refractory atrial fibrillation with rapid ventricular response. Objective: We aimed to assess sex-related differences in patient selection and clinical outcomes after pace and ablate. Methods: In a retrospective multicentre study, patients undergoing AV junction ablation were studied. Sex-related differences in baseline characteristics, all-cause mortality, heart failure (HF) hospitalizations, and device-related complications were assessed. Results: Overall, 513 patients underwent AV junction ablation (median age 75 years, 50% men). At baseline, men were younger (72 vs. 78 years, p < 0.001), more frequently had non-paroxysmal AF (82% vs. 72%, p = 0.006), had a lower LVEF (35% vs. 55%, p < 0.001) and more frequently had cardiac resynchronization therapy (75% vs. 25%, p < 0.001). Interventional complications were rare in both groups (1.2% vs. 1.6%, p = 0.72). Patients were followed for a median of 42 months in survivors (IQR 22–62). After 4 years of follow-up, the combined endpoint of all-cause death or HF hospitalization occurred more often in men (38% vs. 27%, p = 0.008). The same was observed for HF hospitalizations (22% vs. 11%, p = 0.021) and all-cause death (28% vs. 21%, p = 0.017). Sex category remained an independent predictor of death or HF hospitalization after adjustment for age, LVEF and type of stimulation. Lead-related complications, infections, and upgrade to ICD or CRT occurred in 2.1%, 0.2% and 3.5% of patients, respectively. Conclusions: Pace and ablate is safe with a need for subsequent device-related re-interventions in 5.8% over 4 years. We found significant sex-related differences in patient selection, and women had a more favourable clinical course after AV junction ablation. Full article
(This article belongs to the Section Cardiovascular Medicine)
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Article
Utility of Initial Arterial Blood Gas in Neuromuscular versus Non-Neuromuscular Acute Respiratory Failure in Intensive Care Unit Patients
J. Clin. Med. 2022, 11(16), 4926; https://doi.org/10.3390/jcm11164926 - 22 Aug 2022
Viewed by 403
Abstract
Background: The arterial blood gas (ABG) parameters of patients admitted to intensive care units (ICUs) with acute neuromuscular respiratory failure (NMRF) and non-NMRF have not been defined or compared in the literature. Methods: We retrospectively collected the initial ABG parameters (pH, PaCO2 [...] Read more.
Background: The arterial blood gas (ABG) parameters of patients admitted to intensive care units (ICUs) with acute neuromuscular respiratory failure (NMRF) and non-NMRF have not been defined or compared in the literature. Methods: We retrospectively collected the initial ABG parameters (pH, PaCO2, PaO2, and HCO3) of patients admitted to ICUs with acute respiratory failure. We compared ABG parameter ranges and the prevalence of abnormalities in NMRF versus non-NMRF and its categories, including primary pulmonary disease (PPD) (chronic obstructive pulmonary disease, asthma, and bronchiectasis), pneumonia, and pulmonary edema. Results: We included 287 patients (NMRF, n = 69; non-NMRF, n = 218). The difference between NMRF and non-NMRF included the median (interquartile range (IQR)) of pH (7.39 (7.32–7.43), 7.33 (7.22–7.39), p < 0.001), PaO2 (86.9 (71.4–123), 79.6 (64.6–99.1) mmHg, p = 0.02), and HCO3 (24.85 (22.9–27.8), 23.4 (19.4–26.8) mmol/L, p = 0.006). We found differences in the median of PaCO2 in NMRF (41.5 mmHg) versus PPD (63.3 mmHg), PaO2 in NMRF (86.9 mmHg) versus pneumonia (74.3 mmHg), and HCO3 in NMRF (24.8 mmol/L) versus pulmonary edema (20.9 mmol/L) (all p < 0.01). NMRF compared to non-NMRF patients had a lower frequency of hypercarbia (24.6% versus 39.9%) and hypoxia (33.8% versus 50.5%) (all p < 0.05). NMRF compared to PPD patients had lower frequency of combined hypoxia and hypercarbia (13.2% versus 37.8%) but more frequently isolated high bicarbonate (33.8% versus 8.9%) (all p < 0.001). Conclusions: The ranges of ABG changes in NMRF patients differed from those of non-NMRF patients, with a greater reduction in PaO2 in non-NMRF than in NMRF patients. Combined hypoxemia and hypercarbia were most frequent in PPD patients, whereas isolated high bicarbonate was most frequent in NMRF patients. Full article
(This article belongs to the Section Pulmonology)
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Article
The Effect of Manual Therapy Plus Exercise in Patients with Lateral Ankle Sprains: A Critically Appraised Topic with a Meta-Analysis
J. Clin. Med. 2022, 11(16), 4925; https://doi.org/10.3390/jcm11164925 - 22 Aug 2022
Viewed by 482
Abstract
A high percentage of patients with lateral ankle sprains report poor outcomes and persistent neuromuscular impairment leading to chronic ankle instability and re-injury. Several interventions have been proposed and investigated, but the evidence on manual therapy combined with therapeutic exercise for pain reduction [...] Read more.
A high percentage of patients with lateral ankle sprains report poor outcomes and persistent neuromuscular impairment leading to chronic ankle instability and re-injury. Several interventions have been proposed and investigated, but the evidence on manual therapy combined with therapeutic exercise for pain reduction and functional improvement is still uncertain. The purpose was to study the effectiveness of adding manual therapy to therapeutic exercise in patients with lateral ankle sprains through a critically appraised topic. The literature search was performed in PubMed, PEDro, EMBASE and CINAHL databases, and only randomized clinical trials were included according to following criteria: (1) subjects with acute episodes of lateral ankle sprains, (2) administered manual therapy plus therapeutic exercise, (3) comparisons with therapeutic exercise alone and (4) reported outcomes for pain and function. Three randomized clinical trials (for a total of 180 patients) were included in the research. Meta-analyses revealed that manual therapy plus exercise was more effective than only exercises in improving dorsal (MD = 8.79, 95% CI: 6.81, 10.77) and plantar flexion (MD = 8.85, 95% CI 7.07, 10.63), lower limb function (MD = 1.20, 95% CI 0.63, 1.77) and pain (MD = −1.23; 95% IC −1.73, −0.72). Manual therapy can be used with therapeutic exercise to improve clinical outcome in patients with lateral ankle sprains. Full article
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Review
Occult Neck Metastases in Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis
J. Clin. Med. 2022, 11(16), 4924; https://doi.org/10.3390/jcm11164924 - 22 Aug 2022
Viewed by 502
Abstract
Introduction: Adenoid cystic carcinoma (AdCC) is a rare tumor whose clinical course is burdened by local recurrence and distant dissemination. Lymph node metastasis is not believed to be common and its clinical impact is controversial. The aim of this study was to determine: [...] Read more.
Introduction: Adenoid cystic carcinoma (AdCC) is a rare tumor whose clinical course is burdened by local recurrence and distant dissemination. Lymph node metastasis is not believed to be common and its clinical impact is controversial. The aim of this study was to determine: (1) the prevalence of occult metastasis at diagnosis in cN0 head and neck AdCC, (2) its prognostic role, and (3) the consequent need to perform elective neck dissection (END). Material and Methods: A systematic review and meta-analyses following PRISMA guidelines was performed. PubMed, Embase, and Central databases were questioned up to July 2021 to identify studies reporting on the prevalence of occult neck metastases in head and neck AdCC. A single-arm meta-analysis was then performed to determine the pooled prevalence of occult lymph node metastases among the retained studies. Results: Of the initial 6317 studies identified, 16 fulfilled the inclusion criteria, and they were included in the meta-analysis. Of a population of 7534 patients, 2530 cN0 patients were treated with END, which revealed 290/2530 cases of occult metastases (pN+/cN0). Meta-analysis of the results of END in the 16 studies estimated an overall prevalence of occult metastases at diagnosis of 17%. No further subgroup analysis was possible to identify factors influencing lymph node involvement and the prognostic role of END. Conclusions: Taking 20% as an historically proposed cut off, a 17% prevalence of occult metastases represents a borderline percentage to get a definitive conclusion about the indication to END for head and neck AdCC. A more advanced UICC stage, an oropharyngeal minor salivary glands origin, and a high-grade transformation are factors to be considered in a comprehensive patient’s tailored therapeutic strategy. Multicenter prospective studies are the key to finding stronger recommendations on this topic. Full article
(This article belongs to the Special Issue New Advances in the Diagnosis and Treatment of Salivary Gland Tumors)
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Article
Predictive Modeling of Injury Risk Based on Body Composition and Selected Physical Fitness Tests for Elite Football Players
J. Clin. Med. 2022, 11(16), 4923; https://doi.org/10.3390/jcm11164923 - 22 Aug 2022
Viewed by 351
Abstract
Injuries are one of the most significant issues for elite football players. Consequently, elite football clubs have been consistently interested in having practical, interpretable, and usable models as decision-making support for technical staff. This study aimed to analyze predictive modeling of injury risk [...] Read more.
Injuries are one of the most significant issues for elite football players. Consequently, elite football clubs have been consistently interested in having practical, interpretable, and usable models as decision-making support for technical staff. This study aimed to analyze predictive modeling of injury risk based on body composition variables and selected physical fitness tests for elite football players through a sports season. The sample comprised 36 male elite football players who competed in the First Portuguese Soccer League in the 2020/2021 season. The models were calculated based on 22 independent variables that included players’ information, body composition, physical fitness, and one dependent variable, the number of injuries per season. In the net elastic analysis, the variables that best predicted injury risk were sectorial positions (defensive and forward), body height, sit-and-reach performance, 1 min number of push-ups, handgrip strength, and 35 m linear speed. This study considered multiple-input single-output regression-type models. The analysis showed that the most accurate model presented in this work generates an error of RMSE = 0.591. Our approach opens a novel perspective for injury prevention and training monitorization. Nevertheless, more studies are needed to identify risk factors associated with injury prediction in elite soccer players, as this is a rising topic that requires several analyses performed in different contexts. Full article
(This article belongs to the Special Issue Advancements in Sports Medicine)
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Article
Prognostic Factors of Survival in Patients with Peritoneal Metastasis from Colorectal Cancer
J. Clin. Med. 2022, 11(16), 4922; https://doi.org/10.3390/jcm11164922 - 22 Aug 2022
Viewed by 338
Abstract
Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was [...] Read more.
Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 ± 12 years (range: 32–92 years), and 114 patients were female (47.5%). The mean follow-up was 20 ± 13 months (median 12 months). The Kaplan–Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p < 0.001), N0 stage (30% vs. 19%; p < 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p > 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1–10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11–20 (8%) or a PCI of >20 (0%) (p < 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294–3.077), KRAS mutation (HR 1.751; 95% CI: 1.188–2.581), PCI 11–20 (HR: 9.935; 95% CI: 5.204–18.966) and PCI > 20 (HR: 4.011; 95% CI: 2.291–7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Peritoneum Cancer)
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Article
High PEEP Levels during CPR Improve Ventilation without Deleterious Haemodynamic Effects in Pigs
J. Clin. Med. 2022, 11(16), 4921; https://doi.org/10.3390/jcm11164921 - 22 Aug 2022
Viewed by 278
Abstract
Background: Invasive ventilation during cardiopulmonary resuscitation (CPR) is very complex due to unique thoracic pressure conditions. Current guidelines do not provide specific recommendations for ventilation during ongoing chest compressions regarding positive end-expiratory pressure (PEEP). This trial examines the cardiopulmonary effects of PEEP application [...] Read more.
Background: Invasive ventilation during cardiopulmonary resuscitation (CPR) is very complex due to unique thoracic pressure conditions. Current guidelines do not provide specific recommendations for ventilation during ongoing chest compressions regarding positive end-expiratory pressure (PEEP). This trial examines the cardiopulmonary effects of PEEP application during CPR. Methods: Forty-two German landrace pigs were anaesthetised, instrumented, and randomised into six intervention groups. Three PEEP levels (0, 8, and 16 mbar) were compared in high standard and ultralow tidal volume ventilation. After the induction of ventricular fibrillation, mechanical chest compressions and ventilation were initiated and maintained for thirty minutes. Blood gases, ventilation/perfusion ratio, and electrical impedance tomography loops were taken repeatedly. Ventilation pressures and haemodynamic parameters were measured continuously. Postmortem lung tissue damage was assessed using the diffuse alveolar damage (DAD) score. Statistical analyses were performed using SPSS, and p values <0.05 were considered significant. Results: The driving pressure (Pdrive) showed significantly lower values when using PEEP 16 mbar than when using PEEP 8 mbar (p = 0.045) or PEEP 0 mbar (p < 0.001) when adjusted for the ventilation mode. Substantially increased overall lung damage was detected in the PEEP 0 mbar group (vs. PEEP 8 mbar, p = 0.038; vs. PEEP 16 mbar, p = 0.009). No significant differences in mean arterial pressure could be detected. Conclusion: The use of PEEP during CPR seems beneficial because it optimises ventilation pressures and reduces lung damage without significantly compromising blood pressure. Further studies are needed to examine long-term effects in resuscitated animals. Full article
(This article belongs to the Special Issue Sudden Cardiac Death: Clinical Updates and Perspectives)
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Reply
Reply to Fabbris et al. A Viable Alternative. Comment on “Kohmer et al. Self-Collected Samples to Detect SARS-CoV-2: Direct Comparison of Saliva, Tongue Swab, Nasal Swab, Chewed Cotton Pads and Gargle Lavage. J. Clin. Med. 2021, 10, 5751”
J. Clin. Med. 2022, 11(16), 4920; https://doi.org/10.3390/jcm11164920 - 22 Aug 2022
Viewed by 185
Abstract
We thank Fabbris et al. for their remarks [...] Full article
(This article belongs to the Topic Infectious Diseases)
Article
New Insights on the Minimal-Invasive Therapy of Cervical Cancer
J. Clin. Med. 2022, 11(16), 4919; https://doi.org/10.3390/jcm11164919 - 22 Aug 2022
Viewed by 380
Abstract
Objective: The ideal management of early-stage cervical cancer has become the subject of a global controversy following the publication of a prospective study in 2018 that reported a worse oncologic outcome when comparing the minimally invasive approach to the laparotomy approach. The discussion [...] Read more.
Objective: The ideal management of early-stage cervical cancer has become the subject of a global controversy following the publication of a prospective study in 2018 that reported a worse oncologic outcome when comparing the minimally invasive approach to the laparotomy approach. The discussion involves both prospective and retrospective data and general and theoretical considerations. We wanted to look at the data available today and review the different opinions, offering an impartial assessment of the ongoing controversy. Methods: The available literature was reviewed, focusing on articles arguing for and against minimally invasive surgery in cervical cancer. We tried to avoid any fundamental bias, as is often evident in the available reviews on the subject. Literature both before and after the 2018 publication was taken into consideration. Results: As is usual in discussions of concepts, the literature that is now available provides arguments for both sides of this challenging issue, depending on one’s standpoint. Science-related writing is not immune to trends. There is a curious shift in opinion seen before and after 2018. One must question whether there was a prejudice in favor of minimally invasive surgery prior to the publication of the NEJM articles and a bias against it afterward. Conclusion: Whether further minimally invasive surgery for cervical cancer is invariable is tied to the more pressing question of how this surgery will have to be centralized in the future. Unless these questions are linked, no satisfactory solution can be found. Full article
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Review
Artificial Intelligence-Assisted Renal Pathology: Advances and Prospects
J. Clin. Med. 2022, 11(16), 4918; https://doi.org/10.3390/jcm11164918 - 22 Aug 2022
Viewed by 535
Abstract
Digital imaging and advanced microscopy play a pivotal role in the diagnosis of kidney diseases. In recent years, great achievements have been made in digital imaging, providing novel approaches for precise quantitative assessments of nephropathology and relieving burdens of renal pathologists. Developing novel [...] Read more.
Digital imaging and advanced microscopy play a pivotal role in the diagnosis of kidney diseases. In recent years, great achievements have been made in digital imaging, providing novel approaches for precise quantitative assessments of nephropathology and relieving burdens of renal pathologists. Developing novel methods of artificial intelligence (AI)-assisted technology through multidisciplinary interaction among computer engineers, renal specialists, and nephropathologists could prove beneficial for renal pathology diagnoses. An increasing number of publications has demonstrated the rapid growth of AI-based technology in nephrology. In this review, we offer an overview of AI-assisted renal pathology, including AI concepts and the workflow of processing digital image data, focusing on the impressive advances of AI application in disease-specific backgrounds. In particular, this review describes the applied computer vision algorithms for the segmentation of kidney structures, diagnosis of specific pathological changes, and prognosis prediction based on images. Lastly, we discuss challenges and prospects to provide an objective view of this topic. Full article
(This article belongs to the Special Issue Recent Advances in Kidney Disease Imaging)
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Article
The Role of TSHR, PTEN and RASSF1A Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
J. Clin. Med. 2022, 11(16), 4917; https://doi.org/10.3390/jcm11164917 - 21 Aug 2022
Viewed by 439
Abstract
Aim: We investigated whether a difference exists between TSHR, PTEN and RASSF1A methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and [...] Read more.
Aim: We investigated whether a difference exists between TSHR, PTEN and RASSF1A methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in TSHR, PTEN and RASSF1A genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of TSHR was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (p = 0.040). TSHR methylation levels in the PTC group plasma samples were significantly higher compared to HC (p = 0.022). After surgery, PTC plasma samples showed lower TSHR and PTEN methylation levels compared to the levels before surgery (p = 0.003, p = 0.031, respectively). The TSHR methylation level was significantly higher in PTC with larger tumor size (>2 cm) (p < 0.001), and lymph node metastases (p = 0.01), lymphovascular invasion (p = 0.02) and multifocality (p = 0.013) 0ROC analysis revealed that the TSHR methylation level provides high accuracy in distinguishing PTC from HC (p = 0.022, AUC of 0.616). Conclusion: TSHR methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Review
Pulmonary Embolism Presenting with Pulmonary Infarction: Update and Practical Review of Literature Data
J. Clin. Med. 2022, 11(16), 4916; https://doi.org/10.3390/jcm11164916 - 21 Aug 2022
Viewed by 461
Abstract
Pulmonary infarction (PI) is a possible consequence of pulmonary embolism (PE). The real incidence of PI could be underestimated considering only non-fatal PE presentation. However, following postmortem examination, the prevalence of PI is considerably higher. This evidence suggests the necessity of proper diagnostic [...] Read more.
Pulmonary infarction (PI) is a possible consequence of pulmonary embolism (PE). The real incidence of PI could be underestimated considering only non-fatal PE presentation. However, following postmortem examination, the prevalence of PI is considerably higher. This evidence suggests the necessity of proper diagnostic protocol for identifying PI. Unfortunately, PI diagnosis can sometimes be challenging, due to the overlapping of symptoms with other diseases. Nowadays, the diagnosis is mainly based on radiological evaluation, although the combination with emerging imaging techniques such as ultrasound and nuclear scanning might improve the diagnostic algorithm for PI. This review aims to summarize the available data on the prevalence of PI, the main predisposing factors for the development of PI among patients with PE, to resume the possible diagnostic tools, and finally the clinical and prognostic implications. Full article
(This article belongs to the Section Emergency Medicine)
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Graphical abstract

Case Report
Primary Epstein–Barr Virus-Positive Mucocutaneous Ulcer of Esophagus: A Rare Case Report
J. Clin. Med. 2022, 11(16), 4915; https://doi.org/10.3390/jcm11164915 - 21 Aug 2022
Viewed by 425
Abstract
Primary EBV-positive mucocutaneous ulcer (EBVMCU) is a rare and indolent disorder occurring in the oropharynx, skin, and gastrointestinal tract, with remission after removal of the immunosuppressive causes. We present a 69-year-old woman with heartburn, regurgitation of gastric acid, enlarged lymph nodes, and parotid [...] Read more.
Primary EBV-positive mucocutaneous ulcer (EBVMCU) is a rare and indolent disorder occurring in the oropharynx, skin, and gastrointestinal tract, with remission after removal of the immunosuppressive causes. We present a 69-year-old woman with heartburn, regurgitation of gastric acid, enlarged lymph nodes, and parotid glands. The endoscopic examination showed a circumscribed ulcer in the lower esophagus. A biopsy pathology indicated an esophageal EBV-associated lymphoproliferative disorder and a parotid gland/lymph node indolent B-cell lymphoma. Interestingly, the patient did not undergo any treatment, but the endoscopic ulcer improved significantly after more than 2 months. The last pathology showed EBV negativity, and EBVMCU was considered in combination with clinical and endoscopic manifestations. We followed up with the patient at 6 months, and the symptoms of acid reflux and heartburn had disappeared. Our case demonstrates that EBVMCU may occur in the esophagus with spontaneous regression. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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Article
Cystoid Macular Edema after Rhegmatogenous Retinal Detachment Repair with Pars Plana Vitrectomy: Rate, Risk Factors, and Outcomes
J. Clin. Med. 2022, 11(16), 4914; https://doi.org/10.3390/jcm11164914 - 21 Aug 2022
Viewed by 425
Abstract
(1) Background: The aim was to describe the rate and outcomes of cystoid macular edema (CME) after pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD) and to identify risk factors and imaging characteristics. (2) Methods: A retrospective consecutive case study was [...] Read more.
(1) Background: The aim was to describe the rate and outcomes of cystoid macular edema (CME) after pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD) and to identify risk factors and imaging characteristics. (2) Methods: A retrospective consecutive case study was conducted over a 5-year period among adult patients who underwent PPV for primary RRD repair. The main outcome measure was the rate of CME at 12 months following PPV. (3) Results: Overall, 493 eyes were included. The CME rate was 28% (93 patients) at 12 months. In multivariate analysis, eyes with worse presenting visual acuity (VA) (odds ratio [OR], 1.55; 95% CI, 1.07–2.25; p = 0.02) and grade C proliferative vitreoretinopathy (PVR) (OR, 2.88; 95% CI, 1.04–8.16; p = 0.04) were more at risk of developing CME 1 year after PPV. Endolaser retinopexy was associated with a greater risk of CME than cryotherapy retinopexy (OR, 3.06; 95% CI, 1.33–7.84; p = 0.01). Eyes undergoing cataract surgery within 6 months of the initial RRD repair were more likely to develop CME at 12 months (OR, 1.96; 95% CI, 1.06–3.63; p = 0.03). (4) Conclusions: CME is a common complication after PPV for primary RRD repair. Eyes with worse presenting VA, severe PVR at initial presentation, endolaser retinopexy, and cataract surgery within 6 months of initial RRD repair were risk factors for postoperative CME at 12 months. Full article
(This article belongs to the Special Issue Current Challenges in the Management of Vitreoretinal Conditions)
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Article
Mechanical Unloading of the Left Ventricle before Coronary Reperfusion in Preclinical Models of Myocardial Infarction without Cardiogenic Shock: A Meta-Analysis
J. Clin. Med. 2022, 11(16), 4913; https://doi.org/10.3390/jcm11164913 - 21 Aug 2022
Viewed by 566
Abstract
Aim: to compare a conventional primary reperfusion strategy with a primary unloading approach before reperfusion in preclinical studies. Methods: we performed a meta-analysis of preclinical studies. The primary endpoint was infarct size (IS). Secondary endpoints were left ventricle end-diastolic pressure (LVEDP), mean arterial [...] Read more.
Aim: to compare a conventional primary reperfusion strategy with a primary unloading approach before reperfusion in preclinical studies. Methods: we performed a meta-analysis of preclinical studies. The primary endpoint was infarct size (IS). Secondary endpoints were left ventricle end-diastolic pressure (LVEDP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO). We calculated mean differences (MDs) and associated 95% confidence intervals (CIs). Sensitivity and subgroup analyses on the primary and secondary endpoints, as well as a meta-regression on the primary endpoint using the year of publication as a covariate, were also conducted. Results: 11 studies (n = 142) were selected and entered in the meta-analysis. Primary unloading reduced IS (MD −28.82, 95% CI −35.78 to −21.86, I2 96%, p < 0.01) and LVEDP (MD −3.88, 95% CI −5.33 to −2.44, I2 56%, p = 0.02) and increased MAP (MD 7.26, 95% CI 1.40 to 13.12, I2 43%, p < 0.01) and HR (MD 5.26, 95% CI 1.97 to 8.55, I2 1%, p < 0.01), while being neutral on CO (MD −0.11, 95% CI −0.95 to 0.72, I2 88%, p = 0.79). Sensitivity and subgroup analyses showed, overall, consistent results. The meta-regression on the primary endpoint demonstrated a significant influence of the year of publication on effect estimate. Conclusions: in animal models of myocardial infarction, a primary unloading significantly reduces IS and exerts beneficial hemodynamic effects compared to a primary reperfusion. Full article
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Article
Dermoscopy Use Leads to Earlier Cutaneous Melanoma Diagnosis in Terms of Invasiveness and Size? A Single-Center, Retrospective Experience
J. Clin. Med. 2022, 11(16), 4912; https://doi.org/10.3390/jcm11164912 - 21 Aug 2022
Viewed by 326
Abstract
Background: The incidence of cutaneous melanoma has risen in recent years. The aim of this study was to compare cutaneous melanomas diagnosed at the Dermatology Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, from 2006 to 2020 and between two [...] Read more.
Background: The incidence of cutaneous melanoma has risen in recent years. The aim of this study was to compare cutaneous melanomas diagnosed at the Dermatology Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, from 2006 to 2020 and between two specific biennia, i.e., 2006–2007 and 2019–2020. Methods: Retrospective chart review, with dermoscopic image collection, of cutaneous melanomas diagnosed at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, from 1 January 2006 to 31 December 2020 Results: A statistically significant increase was shown in the proportions of in situ melanoma and melanoma measuring less than 6 mm, i.e., small-diameter melanoma (SDM), across the studied period (p < 0.001). Moreover, in the biennium 2006–2007, among 220 melanoma diagnoses, 6 were in situ (2.7%), as compared with 68 melanomas in situ out of a total of 236 (28.8%) melanomas diagnosed in the biennium 2019–2020. A statistically significant difference in the proportion of in situ melanoma between the two biennia was demonstrated (p < 0.001). Furthermore, during the first biennium, 27/220 (12.3%) SDM were identified, as compared with 61/236 (25.9%) in the last. A statistically significant difference was shown in the proportion of SDM between the two (p < 0.001). Conclusions: The percentage of in situ melanomas and those that can be detected at a diameter <6 mm has increased. The latter has been shown to be around one-third of excised lesions, thus undermining the practicality of the ABCD mnemonic. Dermoscopic criteria for SDM are needed to help further refine melanoma diagnosis. Full article
(This article belongs to the Special Issue Update on Skin Cancers: Non-invasive Diagnostic Tools and Treatment)
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Article
Recent Increases in Influenza-Related Hospitalizations, Critical Care Resource Use, and In-Hospital Mortality: A 10-Year Population-Based Study in South Korea
J. Clin. Med. 2022, 11(16), 4911; https://doi.org/10.3390/jcm11164911 - 21 Aug 2022
Viewed by 396
Abstract
Background: Long-term trends in influenza-related hospitalizations, critical care resource use, and hospital outcomes since the 2009 H1N1 influenza pandemic season have been rarely studied for adult populations. Materials and Methods: Adult patients from the Korean Health Insurance Review and Assessment Service who were [...] Read more.
Background: Long-term trends in influenza-related hospitalizations, critical care resource use, and hospital outcomes since the 2009 H1N1 influenza pandemic season have been rarely studied for adult populations. Materials and Methods: Adult patients from the Korean Health Insurance Review and Assessment Service who were hospitalized with influenza over a 10-year period (2009–2019) were analyzed. The incidence rates of hospitalization, critical care resource use, and in-hospital death were calculated using mid-year population census data. Results: In total, 300,152 hospitalized patients with influenza were identified (men, 35.7%; admission to tertiary hospitals, 9.4%). Although the age-adjusted hospitalization rate initially decreased since the 2009 H1N1 pandemic (52.61/100,000 population in 2009/2010), it began to increase again in 2013/2014 and reached a peak of 169.86/100,000 population in 2017/2018 (p < 0.001). The in-hospital mortality rate showed a similar increasing trend as the hospitalization, with a peak of 1.44/100,000 population in 2017/2018 (vs. 0.35/100,000 population in 2009/2010; p < 0.001). The high incidence rates of both hospitalization and in-hospital mortality were mainly attributable to patients aged ≥60 years. The rate of intensive care unit admission and the use of mechanical ventilation, continuous renal replacement therapy and vasopressors have also increased from the 2013/2014 season. The incidence of heart failure was the most frequent complication investigated, with a three-fold increase in the last two seasons since 2009/2010. In multivariate analysis adjusted for covariates, among hospitalized patients, type of hospitals and 2009 H1N1 pandemic season were associated with in-hospital mortality. Conclusions: We confirmed that the rates of hospitalization, critical care resource use, and in-hospital mortality by influenza have increased again in recent years. Therefore, strategies are needed to reduce infections and optimize resource use with a greater focus on older people. Full article
(This article belongs to the Section Infectious Diseases)
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Article
The Effect of Roux-en-Y Gastric Bypass on Non-Alcoholic Fatty Liver Disease Fibrosis Assessed by FIB-4 and NFS Scores—An 11.6-Year Follow-Up Study
J. Clin. Med. 2022, 11(16), 4910; https://doi.org/10.3390/jcm11164910 - 21 Aug 2022
Viewed by 396
Abstract
Severe obesity is a strong risk factor for non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass (RYGB) surgery effectively induces weight loss, but few studies have described the long-term effects of RYGB on NAFLD-related fibrosis. Data from 220 patients with severe obesity operated [...] Read more.
Severe obesity is a strong risk factor for non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass (RYGB) surgery effectively induces weight loss, but few studies have described the long-term effects of RYGB on NAFLD-related fibrosis. Data from 220 patients with severe obesity operated by RYGB in Central Norway were analysed. Variables incorporated in NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4) index and anthropometric data were collected before surgery and a mean of 11.6 years postoperatively. FIB-4 > 1.3 or NFS > 0.675 were used as cut-off values for advanced fibrosis. Proportions with advanced fibrosis decreased from 24% to 14% assessed by FIB-4 and from 8.6% to 2.3% using NFS, with resolution rates of advanced fibrosis of 42% and 73%, respectively. The shift towards lower fibrosis categories was significant (NFS p < 0.0001; FIB-4 p = 0.002). NFS decreased from −1.32 (IQR −2.33–−0.39) to −1.71 (IQR −2.49–−0.95, p < 0.001) 11.6 years after surgery, whereas FIB-4 did not change: 0.81 (IQR 0.59–1.25) to 0.89 (IQR 0.69–1.16, p = 0.556). There were weak correlations between change in fibrosis scores and weight loss. In conclusion, the majority of patients with advanced fibrosis at baseline had improvement after 11.6 years. Factors associated with reduction in fibrosis were not identified. Full article
(This article belongs to the Topic Liver Fibrosis and Cirrhosis)
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Case Report
The Management of Portal Vein Thrombosis after Adult Liver Transplantation: A Case Series and Review of the Literature
J. Clin. Med. 2022, 11(16), 4909; https://doi.org/10.3390/jcm11164909 - 21 Aug 2022
Viewed by 367
Abstract
Background: Portal vein thrombosis (PVT) after adult liver transplantation (LT) is a rare but serious complication with no consensus on the ideal treatment. We report a case series and a comprehensive review of the literature on PVT after LT to discuss the therapeutic [...] Read more.
Background: Portal vein thrombosis (PVT) after adult liver transplantation (LT) is a rare but serious complication with no consensus on the ideal treatment. We report a case series and a comprehensive review of the literature on PVT after LT to discuss the therapeutic options. Methods: The clinical data of 360 adult patients (≥18 years of age) who underwent LT from January 2017 to January 2020 were reviewed, and a comprehensive search of PubMed and Web of Science was conducted. Patients diagnosed with PVT after LT were identified, and relevant risk factors and therapies were analyzed. Results: Among the 360 patients, 7 (1.94%) developed PVT after LT. Onset of PVT within one week after LT was found in six patients (85.71%). Four of the seven patients with PVT received systemic anticoagulation (low molecular weight heparin and warfarin) therapy. Minimally invasive interventional therapies combined with systemic anticoagulation (heparin and warfarin) were applied for three patients, two of whom died because of severe abdominal hemorrhage and liver failure. Of the 33 cases reported in the literature, minimally invasive interventional therapy combined with systematic anticoagulation or sclerotherapy were the most-used methods (20/33). Systemic anticoagulation was administered to four patients, and surgical operation (thrombectomy; portosystemic shunt and retransplantation) was performed for nine patients. Among these 33 patients, 4 eventually died. Conclusions: Interventional therapy combined with systemic anticoagulation is a good choice for the management of PVT after LT, and in our experience, systemic anticoagulation alone can also have a positive effect for early PVT patients. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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Review
Myeloid-Derived Suppressor Cells: New Insights into the Pathogenesis and Therapy of MDS
J. Clin. Med. 2022, 11(16), 4908; https://doi.org/10.3390/jcm11164908 - 21 Aug 2022
Viewed by 687
Abstract
Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by the clonal expansion of hematopoietic stem cells, bone marrow failure manifested by cytopenias, and increased risk for evolving to acute myeloid leukemia. Despite the fact that the acquisition of somatic mutations is considered key for [...] Read more.
Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by the clonal expansion of hematopoietic stem cells, bone marrow failure manifested by cytopenias, and increased risk for evolving to acute myeloid leukemia. Despite the fact that the acquisition of somatic mutations is considered key for the initiation of the disease, the bone marrow microenvironment also plays significant roles in MDS by providing the right niche and even shaping the malignant clone. Aberrant immune responses are frequent in MDS and are implicated in many aspects of MDS pathogenesis. Recently, myeloid-derived suppressor cells (MDSCs) have gained attention for their possible implication in the immune dysregulation associated with MDS. Here, we summarize the key findings regarding the expansion of MDSCs in MDS, their role in MDS pathogenesis and immune dysregulation, as well their potential as a new therapeutic target for MDS. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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Systematic Review
Uterine Factor Infertility, a Systematic Review
J. Clin. Med. 2022, 11(16), 4907; https://doi.org/10.3390/jcm11164907 - 21 Aug 2022
Viewed by 400
Abstract
Uterine factor infertility (UFI) is defined as a condition resulting from either a complete lack of a uterus or a non-functioning uterus due to many causes. The exact prevalence of UFI is currently unknown, while treatments to achieve pregnancy are very limited. To [...] Read more.
Uterine factor infertility (UFI) is defined as a condition resulting from either a complete lack of a uterus or a non-functioning uterus due to many causes. The exact prevalence of UFI is currently unknown, while treatments to achieve pregnancy are very limited. To evaluate the prevalence of this condition within its different causes, we carried out a worldwide systematic review on UFI. We performed research on the prevalence of UFI and its various causes throughout the world, according to the PRISMA criteria. A total of 188 studies were included in qualitative synthesis. UFI accounted for 2.1 to 16.7% of the causes of female infertility. We tried to evaluate the proportion of the different causes of UFI: uterine agenesia, hysterectomies, uterine malformations, uterine irradiation, adenomyosis, synechiae and Asherman syndrome, uterine myomas and uterine polyps. However, the data available in countries and studies were highly heterogenous. This present systematic review underlines the lack of a consensual definition of UFI. A national register of patients with UFI based on a consensual definition of Absolute Uterine Factor Infertility and Non-Absolute Uterine Factor Infertility would be helpful for women, whose desire for pregnancy has reached a dead end. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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Systematic Review
Use of the Thyromental Height Test for Prediction of Difficult Laryngoscopy: A Systematic Review and Meta-Analysis
J. Clin. Med. 2022, 11(16), 4906; https://doi.org/10.3390/jcm11164906 - 21 Aug 2022
Viewed by 360
Abstract
The thyromental height test (TMHT) has been proposed as a novel single clinical test for predicting difficult laryngoscopy (DL), though consequent studies have put forward various estimates when verifying its reliability. This systematic review and meta-analysis aimed to provide a comprehensive evaluation of [...] Read more.
The thyromental height test (TMHT) has been proposed as a novel single clinical test for predicting difficult laryngoscopy (DL), though consequent studies have put forward various estimates when verifying its reliability. This systematic review and meta-analysis aimed to provide a comprehensive evaluation of the predictive value of TMHT for DL. A computerized search of CNKI, CQVIP, EBSCO, PubMed, SinoMed, and Wanfang Data was conducted on 1 June 2022. Prospective cohort studies reporting diagnostic properties of TMHT in relation to Cormack and Lehane grading in patients aged more than 16 years, either sex, scheduled for surgery under general anesthesia, requiring tracheal intubation with direct laryngoscopy were included in this analysis. Data was extracted or calculated, and meta-analysis was done by the Stata MIDAS module. A total of 23 studies with 5896 patients were included in this analysis. Summary estimates of all included studies are as follows: sensitivity 74% (95% CI, 68–79%); specificity 88% (95% CI, 81–92%); diagnostic odd ratio, 20 (95% CI, 10–40); positive likelihood ratio, 5.9 (95% CI, 3.6–9.6); and negative likelihood ratio, 0.30 (95% CI, 0.23–0.39). Summary sensitivity and specificity for studies with a prespecified threshold were 82% (95% CI, 71–89%) and 94% (95% CI, 87–98%), respectively. The estimated area under curve (AUC) was 85% (95% CI, 81–88%). There was no significant threshold effect but significant heterogeneity in both sensitivity and specificity. Heterogeneity in sensitivity became insignificant after removing two outliers of sensitivity analysis. It is concluded that THMT has an overall optimal predictive value for DL in adult patients with diverse ethnicity and various risk factors, displaying better predictive values in a large patient population comparing to other recent reported bedside assessments and a previous meta-analysis. As significant heterogeneity brought by un-standardized application of external laryngeal manipulations in the included studies may have biased the results of this meta-analysis, the actual predictive value of TMHT for DL still awaits further studies with good designs and large sample sizes for better determination. Full article
(This article belongs to the Special Issue Anesthetic Management in Perioperative Period)
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Article
Dual Targeting of the EGFR/HER2 Pathway in Combination with Systemic Chemotherapy in Refractory Pancreatic Cancer—The CONKO-008 Phase I Investigation
J. Clin. Med. 2022, 11(16), 4905; https://doi.org/10.3390/jcm11164905 - 21 Aug 2022
Viewed by 347
Abstract
Background: Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF. [...] Read more.
Background: Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF. Methods: We conducted a phase I trial using an accelerated dose escalation design in patients with refractory pancreatic cancer. Lapatinib was given on days 1 to 42 in combination with folinic acid 200 mg/m2 day + 5-fluorouracil 2000 mg/m2 (24 h) on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m2 days 8 and 22 of a 43-day cycle (OFF). Toxicity and efficacy were evaluated. Results: In total, eighteen patients were enrolled: dose level 1 (1000 mg) was assigned to seven patients, dose level 2 (1250 mg), five patients; and dose level 3 (1500 mg), six patients. Dose-limiting toxicities were diarrhea and/or neutropenic enterocolitis observed in two of six patients: one diarrhea III°, one diarrhea IV°, as well as neutropenic enterocolitis. The maximum tolerable dose of lapatinib was 1250 mg OD. Conclusions: The combination of lapatinib 1250 mg OD with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation. Full article
(This article belongs to the Special Issue Challenges in Treatment of Pancreatic Ductal Adenocarcinoma)
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Article
Normal References of Peak Oxygen Uptake for Cardiorespiratory Fitness Measured with Cardiopulmonary Exercise Testing in Chinese Adults
J. Clin. Med. 2022, 11(16), 4904; https://doi.org/10.3390/jcm11164904 - 21 Aug 2022
Viewed by 345
Abstract
Introduction: This study aims to establish normal reference values of peak oxygen uptake (VO2peak) for cardiorespiratory fitness (CRF) in Chinese adults using cardiorespiratory exercise testing (CPET). Methods: A cross-sectional study was done in four communities, two in the North (Beijing) and [...] Read more.
Introduction: This study aims to establish normal reference values of peak oxygen uptake (VO2peak) for cardiorespiratory fitness (CRF) in Chinese adults using cardiorespiratory exercise testing (CPET). Methods: A cross-sectional study was done in four communities, two in the North (Beijing) and two in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, with one urban and one rural in each region. Out of 1642 participants screened, 1114 were eligible and completed CPET using a cycle ergometer (Ergosana320F) without abnormal ECG and were included in the analysis. The 2nd and 98th percentiles of V·O2peak were used as the lower and upper limits of the normal reference values. Results: Significant difference in mean V·O2peak was shown between men (27.0 mL·min−1·kg−1) and women (23.7 mL·min−1·kg−1). The mean V·O2peak decreased with age in both sexes, from 35.8 mL·min−1·kg−1 in age 20–29 years to 20.5 mL·min−1·kg−1 in 70–79 years in men and from 29.2 mL·min−1·kg−1 to 17.0 mL·min−1·kg−1 in women. Thus, the age- and sex-specific normal reference values of V·O2peak were presented for each 10-year age group by men and women separately. Conclusions: This first community-based study in China provides age- and sex-specific normal references of V·O2peak as a measure of CRF in Chinese adults, which differed significantly from those established in Western populations. Future studies with national representative samples should be warranted. Full article
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Article
Platelet-to-Lymphocyte Ratio (PLR) Is Not a Predicting Marker of Severity but of Mortality in COVID-19 Patients Admitted to the Emergency Department: A Retrospective Multicenter Study
J. Clin. Med. 2022, 11(16), 4903; https://doi.org/10.3390/jcm11164903 - 21 Aug 2022
Viewed by 438
Abstract
(1) Introduction: In the present study, we investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) as a marker of severity and mortality in COVID-19 infection. (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients [...] Read more.
(1) Introduction: In the present study, we investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) as a marker of severity and mortality in COVID-19 infection. (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate to severe coronavirus 19 (COVID-19), all of whom were hospitalized after being admitted to the emergency department (ED). (3) Results: A total of 1035 patients were included in our study. Neither lymphocytes, platelets or PLR were associated with disease severity. Lymphocyte count was significantly lower and PLR values were significantly higher in the group of patients who died, and both were associated with mortality in the univariate analysis (OR: 0.524, 95% CI: (0.336–0.815), p = 0.004) and (OR: 1.001, 95% CI: (1.000–1.001), p = 0.042), respectively. However, the only biological parameter significantly associated with mortality in the multivariate analysis was platelet count (OR: 0.996, 95% CI: (0.996–1.000), p = 0.027). The best PLR value for predicting mortality in COVID-19 was 356.6 (OR: 3.793, 95% CI: (1.946–7.394), p < 0.001). (4) Conclusion: A high PLR value is however associated with excess mortality. Full article
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