J. Clin. Med., Volume 9, Issue 12 (December 2020) – 343 articles

Introduction: A highly pathogenic human coronavirus able to induce severe acute respiratory syndrome (SARS) has been recently recognized as the cause of the coronavirus disease 2019 (COVID-19); the disease became pandemic after a few months. Little is still known about the laboratory prognostic markers in COVID-19 patients. The aim of our study was to describe the prognostic value of clotting parameters for the prediction of severe form of COVID-19 characterized by acute respiratory distress syndrome (ARDS) at hospital admission. Material and Methods: From a large cohort of 152 patients consecutively admitted from February to March 2020 for fever and dyspnea to the emergency departments (ED) of three Italian hospitals, we evaluated 85 patients with confirmed diagnosis of COVID-19 and 67 patients with acute illness. All patients underwent medical history checks, physical examination, and laboratory evaluation. Prothrombin time (PT), activated thromboplastin time (aPTT), fibrinogen and D-dimer tests were performed and compared, first, between COVID-19 and control groups, and then between COVID-19 patients with or without ARDS. Results: COVID-19 patients were more likely to show abnormal baseline levels of PT, aPTT, D-dimer, and fibrinogen at admission compared to the control group. COVID-19 patients with ARDS showed a statistically significant increase in levels of fibrinogen compared to those without ARDS (720 (621–833) vs. 490 (397.5–601.5); p= 1.8653 × 10⁻⁹ (0.0765). A cut-off value of 617 mg/dL had a sensitivity of 76% and a specificity of 79% in identifying COVID-19 patients with ARDS. Conclusion: A serum level of fibrinogen of 617 mg/dL in COVID-19 patients admitted to emergency department may help to identify early those with ARDS. Full article

This observational, cross-sectional, epidemiological analysis investigated relationships of kidney function to urine calcium and other variables. The analyses targeted two population-based samples of adults (Gubbio study and Moli-sani study: n = 3508 and 955, respectively). Kidney function was assessed as estimated glomerular filtration rate (eGFR). Calcium/creatinine ratio (Ca/Cr) was used as index of urinary calcium in timed overnight urine under fed condition (Gubbio study), morning urine after overnight fast (Gubbio study), and first-void morning urine (Moli-sani study). Moli-sani study included also data for glomerular filtered calcium load, tubular calcium handling, and serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, calcium, and 25-hydroxyvitamin D. eGFR positively and independently related to Ca/Cr (p < 0.001). In multivariate analyses, eGFR lower by 10 mL/min × 1.73 m² related to overnight urine Ca/Cr lower by 14.0 mg/g in men and 17.8 mg/g in women, to morning urine Ca/Cr lower by 9.3 mg/g in men and 11.2 mg/g in women, and to first-void urine Ca/Cr lower by 7.7 mg/g in men and 9.6 mg/g in women (p < 0.001). eGFR independently related to glomerular filtered calcium load (p < 0.001) and did not relate to tubular calcium handling (p ≥ 0.35). In reduced eGFR only (<90 mL/min × 1.73 m²), low urine Ca/Cr independently related to low serum 1,25-dihydroxyvitamin D (p = 0.002) and did not relate to hyperphosphatemia, high serum parathyroid hormone, or hypocalcemia (p ≥ 0.14). Population-based data indicated consistent associations of lower kidney function with lower urine calcium due to reduction in glomerular filtered calcium. In reduced kidney function, relative hypocalciuria associated with higher prevalence of low serum 1,25-dihydroxyvitamin D. Full article

Treatment of congenital pseudarthrosis of the tibia remains a major challenge in pediatric orthopedics. Ideal timing and preference of surgical procedures are discussed controversially. A variety of reconstructive treatment strategies have been described in literature, but so far none has proven its superiority. The aim of treatment is to obtain long-term bone union, to prevent refracture, and to correct angular deformities and leg length discrepancies. This study retrospectively evaluates the outcome of different reconstructive strategies. Sixty-nine patients were identified who presented to our outpatient department between 1997 and 2019. Twenty-six of these patients underwent reconstructive surgical treatment and were included in this study. The study cohort was divided into three groups. Excision of the pseudarthrosis was performed in all patients in Group A and B, and in two patients of Group C. Group A (six/26 patients) received subsequent bone transport through external fixation maintaining original length. In Group B (15/26 patients), patients underwent either previous, simultaneous, or subsequent extrafocal lengthening through external fixation to reconstitute length. In Group C (five/26 patients), internal fixation with intramedullary nails was applied. Radiological and clinical evaluation was performed to assess bone union and complication rates. Results varied considerably between the study groups. Overall, the primary bone fusion rate was 69.2%. There were four refractures, all occurring in Group B. The long-term bone union rate without refracture was 53.8%. The overall complication rate was 53.8% and 23.1% showed persistent pseudarthrosis. Two secondary amputations were performed due to failed bone fusion. In conclusion, excision of the pseudarthrosis and extrafocal lengthening achieves a satisfying bone union rate and limb reconstruction, while bone transport does not offer significant advantages but shows higher complication rates. Intramedullary stabilization should be applied to maintain bone union, but shows lower bone union rates when used as a stand-alone treatment regimen. Regardless of the primary bone fusion rates, the probability of long-term bone union remains unpredictable. Full article

Despite the proven clinical value of spinal cord stimulation (SCS) for patients with failed back surgery syndrome (FBSS), factors related to a successful SCS outcome are not yet clearly understood. This study aimed to predict responders for high frequency SCS at 10 kHz (HF-10). Data before implantation and the last available data was extracted for 119 FBSS patients treated with HF-10 SCS. Correlations, logistic regression, linear discriminant analysis, classification and regression trees, random forest, bagging, and boosting were applied. Based on feature selection, trial pain relief, predominant pain location, and the number of previous surgeries were relevant factors for predicting pain relief. To predict responders with 50% pain relief, 58.33% accuracy was obtained with boosting, random forest and bagging. For predicting responders with 30% pain relief, 70.83% accuracy was obtained using logistic regression, linear discriminant analysis, boosting, and classification trees. For predicting pain medication decrease, accuracies above 80% were obtained using logistic regression and linear discriminant analysis. Several machine learning techniques were able to predict responders to HF-10 SCS with an acceptable accuracy. However, none of the techniques revealed a high accuracy. The inconsistent results regarding predictive factors in literature, combined with acceptable accuracy of the currently obtained models, might suggest that routinely collected baseline parameters from clinical practice are not sufficient to consistently predict the SCS response with a high accuracy in the long-term. Full article

We investigated prognostic factors associated with refractory left ventricle (LV) failure leading to LV assist device (LVAD), heart transplant or death in patients on an axial flow pump support for cardiogenic shock (CS). Sixty-two CS patients with an Impella^® CP or 5.0 implant were retrospectively enrolled, and clinical, biological, echocardiographic, coronarographic and management data were collected. They were compared according to the 30-day outcome. Patients were mainly male (n = 55, 89%), 58 ± 11 years old and most had no history of heart failure or coronary artery disease (70%). The main etiology of CS was acute coronary syndrome (n = 57, 92%). They presented with severe LV failure (LV ejection fraction (LVEF) 22 ± 9%), organ malperfusion (lactate 3.1 ± 2.1 mmol/L), and frequent use of inotropes, vasopressors, and mechanical ventilation (59, 66 and 30%, respectively). At 24 h, non-recovery was associated with higher total bilirubin (odds ratios (OR) 1.07 (1.00–1.14); p = 0.039), lower LVEF (OR 0.89 (0.81–0.96); p = 0.006) and the number of administrated amines (OR 4.31 (1.30–14.30); p = 0.016). Early evaluation in patients with CS with an axial flow pump implant may enable the identification of factors associated with an unlikely recovery and would call for early screening for LVAD or heart transplant. Full article

Patients receiving mechanical ventilation for coronavirus disease 2019 (COVID-19) related, moderate-to-severe acute respiratory distress syndrome (CARDS) have mortality rates between 76–98%. The objective of this retrospective cohort study was to identify differences in prone ventilation effects on oxygenation, pulmonary infiltrates (as observed on chest X-ray (CXR)), and systemic inflammation in CARDS patients by survivorship and to identify baseline characteristics associated with survival after prone ventilation. The study cohort included 23 patients with moderate-to-severe CARDS who received prone ventilation for ≥16 h/day and was segmented by living status: living (n = 6) and deceased (n = 17). Immediately after prone ventilation, PaO₂/FiO₂ improved by 108% (p < 0.03) for the living and 150% (p < 3 × 10⁻⁴) for the deceased. However, the 48 h change in lung infiltrate severity in gravity-dependent lung zones was significantly better for the living than for the deceased (p < 0.02). In CXRs of the lower lungs before prone ventilation, we observed 5 patients with confluent infiltrates bilaterally, 12 patients with ground-glass opacities (GGOs) bilaterally, and 6 patients with mixed infiltrate patterns; 80% of patients with confluent infiltrates were alive vs. 8% of patients with GGOs. In conclusion, our small study indicates that CXRs may offer clinical utility in selecting patients with moderate-to-severe CARDS who will benefit from prone ventilation. Additionally, our study suggests that lung infiltrate severity may be a better indicator of patient disposition after prone ventilation than PaO₂/FiO₂. Full article

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, have been established. Besides molecular alterations, PDAC tumours show a strong desmoplastic response, resulting in profound metabolic reprogramming involving increased glucose and amino acid consumption, as well as lipid scavenging and biosynthesis. Interestingly, recent works have also revealed the existence of metabolic subtypes with differential prognosis within PDAC, which correlated to defined molecular subclasses in patients: lipogenic subtype correlated with a classical/progenitor signature, while glycolytic tumours associated with the highly aggressive basal/squamous profile. Bioinformatic analyses have demonstrated that the representative genes of each metabolic subtype are up-regulated in PDAC samples and predict patient survival. This suggests a relationship between the genetic signature, metabolic profile, and aggressiveness of the tumour. Considering all this, defining metabolic subtypes represents a clear opportunity for patient stratification considering tumour functional behaviour independently of their mutational background. Full article

A systematic review was conducted to answer the following PICO question: “Can patients diagnosed with oral lichen planus (OLP) be rehabilitated with dental implants as successfully as patients without OLP?”. A systematic review of the literature was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements to gather available and current evidence of oral lichen planus and its relationship with dental implants. The synthesis of results was performed using a Binary Random-Effects Model meta-analysis. Summary measures were odds ratios (ORs), frequencies, and percentages comparing the survival rate of dental implants placed in patients with OLP vs. those in patients without OLP. The electronic search yielded 25 articles, after removing the duplicated ones, 24 articles were selected. Out of the 24 articles, only 15 fulfilled the inclusion criteria. According to the results of the meta-analysis, with a total sample of 48 patients with OLP and 49 patients without OLP, an odds ratio of 2.48 (95% CI 0.34–18.1) was established, with an I² value of 0%. According to the Strength of Recommendation Taxonomy (SORT) criteria, level A can be established to conclude that patients with OLP can be rehabilitated with dental implants. Full article

This study investigated whether intraoperative infusion of magnesium sulphate reduces the incidence of emergence agitation (EA) in paediatric patients who undergo ambulatory ophthalmic surgery using the Paediatric Anaesthesia Emergence Delirium (PAED) scale. Ninety-two paediatric patients who were scheduled for elective ophthalmic surgery were randomly allocated to two groups: control or magnesium. In the magnesium group, patients received an initial intravenous loading dose of 30 mg/kg of 10% solution of magnesium sulphate over 10 min and then a continuous infusion of 10 mg/kg×h during the surgery. In the control group, an equal volume of 0.9% isotonic saline was administered in the same way as in the magnesium group. The PAED scale was assessed at 15-min intervals until the PAED score reached below 10 at the postanaesthetic care unit. EA was defined as a PAED score of 10 or higher. Of the 86 patients recruited, 44 and 42 were allocated to the control and magnesium groups, respectively. The incidence of EA was 77.3% in the control group and 57.1% in the magnesium group (odds ratio, 0.392; 95% confidence interval, 0.154 to 0.997; p = 0.046). The intraoperative infusion of magnesium sulphate significantly reduced the incidence of EA. Full article

Background and aim: Although head and/or neck pain attributed to orthostatic hypotension is included in international guidelines, its mechanisms and relevance remain unknown. This study examined the term’s relevance and aimed to elucidate the associated clinical features. Methods: An active stand test was performed to evaluate fluctuations in systemic and cerebral circulation in children and adolescents reporting complaints in the absence of a confirmed organic disorder. The subjects were categorized based on orthostatic headache presence/absence, and their characteristics and test results were compared. Results: Postural tachycardia syndrome was observed in 50.0% of children with, and 55.1% without, orthostatic headache. For orthostatic hypotension, the respective values were 31.3% and 30.6%. A history of migraine was more prevalent in children with orthostatic headaches (64.1% vs. 28.6%; p < 0.01). The observed decrease in the cerebral oxygenated hemoglobin level was larger in children with orthostatic headaches (Left: 6.3 (3.2–9.4) vs. 4.1 (0.8–6.1); p < 0.01, Right: 5.3 (3.1–8.6) vs. 4.0 (0.8–5.9); p < 0.01). Conclusion: Fluctuations in cerebral blood flow were associated with orthostatic headaches in children, suggesting that the headaches are due to impaired intracranial homeostasis. As orthostatic headache can have multiple causes, the term “head and/or neck pain attributed to orthostatic (postural) hypotension” should be replaced with a more inclusive term. Full article

Tuberculosis (TB) diagnosis is increasingly based on the detection of Mycobacterium tuberculosis complex (MTBC) DNA in sputum using molecular diagnostic tests as the first test for diagnosis. However, sputum can be difficult to obtain in children, patients without productive cough, and the elderly and approaches testing non-sputum samples are needed. We evaluated whether TB can be detected from the oral mucosa of patients with TB. Adults with presumptive TB were examined using culture, Xpert MTB/RIF, smear microscopy and X-Rays. Oral mucosa swabs collected on PrimeStore-MTM, stored at room temperature if tested within 30 days or at −20 °C if examined at a later time. RT-PCR was performed to detect M. tuberculosis DNA. Eighty patients had bacteriologically-confirmed TB, 34 had bacteriologically-negative TB (negative tests but abnormal X-rays) and 152 were considered not to have TB (not TB). Oral swabs RT-PCR were positive in 29/80 (36.3%) bacteriologically-confirmed, 9/34 (26.5%) bacteriologically-negative and 29/152 (19.1%) not TB. The yield varied among samples stored for less and more than 30 days (p = 0.013) from 61% (11/18) and 29% (18/62) among bacteriologically confirmed, and 30.8% (4/13) and 23.8% (5/21) among bacteriologically-negative participants. Among not TB patients, the specificity was 80.9% (123/152), being 78.3% (18/23) among samples stored less than 30 days and 81.4% (105/129) among samples stored for more than 30 days (p = 0.46). The detection of M. tuberculosis in oral mucosa samples is feasible, but storage conditions may affect the yield. Full article

We describe the use of Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in the investigation and diagnosis of Charcot neuroarthropathy (CN) in patients with a hot swollen foot but normal radiographs and clinical suspicion of CN, usually termed Stage 0. This was a retrospective cohort review of 46 diabetes patients who underwent 3 phase bone scintigraphy with “High Resolution” SPECT/CT. The imaging demonstrated that Stage 0 Charcot foot has a distinct bone pathology, which can be classified into three groups: (1) fractures on Computed Tomography (CT) with accompanying focal uptake of tracer on SPECT, (2) bony abnormalities apart from fracture on CT with focal uptake of tracer on SPECT, and (3) normal CT but focal bony uptake of tracer on SPECT. The CT component of SPECT/CT detected bony fractures in 59% of patients. Early treatment with below knee cast and follow-up for 24 months showed only 4 patients who developed Stage 1 Eichenholtz Charcot foot. Our findings support the use of 3 phase bone scintigraphy with SPECT/CT in the characterization and early diagnosis of CN. Stage 0 Charcot foot has a distinct bone pathology which requires urgent treatment to prevent progression to Stage 1 Eichenholtz Charcot foot. If SPECT/CT is unavailable, CT alone will detect bone fracture in 59% patients. Full article

Background: Stromelysins are potential breast cancer biomarkers. The aim of the study was to evaluate if plasma levels of selected metalloproteinases (MMPs) (stromelysin-1 (MMP-3) and stromelysin-10 (MMP-10)) and cancer antigen 15-3 (CA 15-3) used separately and in combination demonstrated diagnostic usefulness in breast cancer (BC). Methods: The study group consisted of 120 patients with BC, while the control group included 40 patients with benign breast cancer and 40 healthy individuals. Concentrations of MMP-3 and MMP-10 were determined by enzyme-linked immunosorbent assay; CA 15-3 was determined by chemiluminescent microparticle immunoassay. Results: In the group of patients with BC, the area under the curve (AUC) was significantly higher for all markers (except MMP-3) and all sets of markers. At the earliest disease stage, only MMP-10 had a significantly higher AUC (AUC = 0.8692, p < 0.001). Moreover, MMP-10 had the highest AUC (0.9166) among parameters tested separately. The highest AUC was observed for the combination of MMP-10 + CA 15-3 and MMP-3 + MMP-10 + CA 15-3 in line with disease progression (stage I 0.8884 and 0.8906, stage II 0.9244 and 0.9308, stages III + IV 0.9919 and 0.9944, respectively, p < 0.001 in all cases). Conclusions: The results suggest that MMP-10 could be a potential marker in early stages of BC. Moreover, plasma concentration of MMP-10 and MMP-3 in combination with CA 15-3 may improve diagnosis of this type of cancer. Full article

Background/Aims: Lenvatinib was recently approved as a first-line oral multikinase inhibitor for unresectable hepatocellular carcinoma (HCC). In this study, we aimed to compare the efficacy and safety of lenvatinib and sorafenib for the treatment of unresectable HCC in patients with prior failure of transarterial treatment. Methods: Between January 2019 and September 2020, 98 unresectable HCC patients treated with lenvatinib or sorafenib as salvage therapy were enrolled from five Korean university-affiliated hospitals. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate were calculated to assess the antitumor response. Results: A total of 43 and 55 patients were treated with lenvatinib and sorafenib, respectively, as salvage therapy after the failure of transarterial treatments. The median PFS was 4.97 months in the lenvatinib group and 2.47 months in the sorafenib group (p = 0.001, log-rank test). The ORR was significantly higher in the lenvatinib group (25.6%) than in the sorafenib group (3.6%, p = 0.002). Use of lenvatinib over sorafenib (hazard ratio: 0.359, 95% confidence interval: 0.203–0.635, p < 0.001) was the most significant factor for a favorable PFS after the failure of transarterial treatments in all enrolled patients. For favorable OS, achieving objective response was the significant factor (hazard ratio 0.356, 95% confidence interval: 0.132–0.957, p = 0.041). There were no significant differences in the safety profile between the two groups. Conclusions: In this real-world study, lenvatinib was demonstrated to be more efficacious than sorafenib as a salvage therapy for transarterial treatments in unresectable HCC. Full article

The possibility that the cerebral ventricles can dilate without any increase in the pressure of the cerebrospinal fluid (CSF) was recognized in 1935 by Penfield who reported a patient in whom “…the cerebrospinal fluid spaces are closed and the ventricles progressively enlarge without the measured intraventricular pressure rising above 150 to 200 mm of water” [...] Full article

Individual cutting guides for the reconstruction of lower jaw defects with fibular grafts are often used. However, the application of these osteotomy tools is costly and time intensive. The aim of this study was to compare the precision of osteotomies using a 3D-printed guide with those using a universal, reusable, and more cost-efficient Multi-Use Cutting Jig (MUC-Jig). In this non-blinded experimental study, 10 cranio-maxillofacial surgeons performed four graft removals each in a randomized order using the same osteotomy angle, both proximally (sagittal cut) and distally (coronal cut), of a graft (45°, 30°, 15°, or 0°), first with the MUC-Jig then with the 3D-printed cutting guide. The 40 fibula transplants (Tx) of each method (n = 80) were then analyzed concerning their Tx length and osteotomy angles and compared to the original planning data. Furthermore, the surgeons’ subjective perception and the duration of the two procedures were analyzed. The mean relative length and mean relative angle deviation between the MUC-Jig (−0.08 ± 1.12 mm; −0.69° ± 3.15°) and the template (0.22 ± 0.90 mm; 0.36° ± 2.56°) group differed significantly (p = 0.002; p = < 0.001), but the absolute deviations did not (p = 0.206; p = 0.980). Consequently, clinically comparable osteotomy results can be achieved with both methods, but from an economic point of view the MUC-Jig is a more cost-efficient solution. Full article

Background: Cerebral embolic protection devices (CEPDs) have emerged as a mechanical barrier to prevent debris from reaching the cerebral vasculature, potentially reducing stroke incidence. Bovine aortic arch (BAA) is the most common arch variant and represents challenge anatomy for CEPD insertion during transcatheter aortic valve replacement (TAVR). Methods: Cohort study reporting the Sentinel^TM Cerebral Protection System insertion’s feasibility and safety in 165 adult patients submitted to a transfemoral TAVR procedure from April 2019 to April 2020. Patients were divided into 2 groups: (1) BAA; (2) non-BAA. Results: Median age, EuroScore II, and STS score were 79 years (74–84), 2.9% (1.7–6.2), and 2.2% (1.6–3.2), respectively. BAA was present in 12% of cases. Successful two-filter insertion was 86.6% (89% non-BAA vs. 65% BAA; p = 0.002), and debris was captured in 95% (94% non-BAA vs. 95% BAA; p = 0.594). No procedural or vascular complications associated with Sentinel insertion and no intraprocedural strokes were reported. There were two postprocedural non-disabling strokes, both in non-BAA. Conclusion: This study demonstrated Sentinel insertion feasibility and safety in BAA. No procedural and access complications related to Sentinel deployment were reported. Being aware of the bovine arch prevalence and having the techniques to navigate through it allows operators to successfully use CEPDs in this anatomy. Full article

Aneurysmal subarachnoid haemorrhage (aSAH) is a serious condition with a high mortality and high permanent disability rate for those who survive the initial haemorrhage. The purpose of this study was to investigate markers specific to the central nervous system as potential in-hospital mortality predictors after aSAH. In patients with an external ventricular drain, enolase, S100B, and GFAP levels were measured in the blood and cerebrospinal fluid (CSF) on days 1, 2, and 3 after aSAH. Compared to survivors, non-survivors showed a significantly higher peak of S100B and enolase levels in the blood (S100B: 5.7 vs. 1.5 ng/mL, p = 0.031; enolase: 6.1 vs. 1.4 ng/mL, p = 0.011) and the CSF (S100B: 18.3 vs. 0.9 ng/mL, p = 0.042; enolase: 109.2 vs. 6.1 ng/mL, p = 0.015). Enolase showed the highest level of predictability at 1.8 ng/mL in the blood (AUC of 0.873) and 80.0 ng/mL in the CSF (AUC of 0.889). The predictive ability of S100B was also very good with a threshold of 5.7 ng/mL in the blood (AUC 0.825) and 4.5 ng/mL in the CSF (AUC 0.810). In conclusion, enolase and S100B, but not GFAP, might be suitable as biomarkers for the early prediction of in-hospital mortality after aSAH. Full article

Crohn’s disease (CD) is associated with bone loss and increased fracture risk. TX-Analyzer™ is a new fractal-based technique to evaluate bone microarchitecture based on conventional radiographs. The aim of the present study was to evaluate the TX-Analyzer™ of the thoracic and lumbar spine in CD patients and healthy controls (CO) and to correlate the parameters to standard imaging techniques. 39 CD patients and 39 age- and sex-matched CO were analyzed. Demographic parameters were comparable between CD and CO. Bone structure value (BSV), bone variance value (BVV) and bone entropy value (BEV) were measured at the vertebral bodies of T7 to L4 out of lateral radiographs. Bone mineral density (BMD) and trabecular bone score (TBS) by dual energy X-ray absorptiometry (DXA) were compared to TX parameters. BSV and BVV of the thoracic spine of CD were higher compared to controls, with no difference in BEV. Patients were further divided into subgroups according to the presence of a history of glucocorticoid treatment, disease duration > 15 years and bowel resection. BEV was significantly lower in CD patients with these prevalent risk factors, with no differences in BMD at all sites. Additionally, TBS was reduced in patients with a history of glucocorticoid treatment. Despite a not severely pronounced bone loss in this population, impaired bone quality in CD patients with well-known risk factors for systemic bone loss was assessed by TX-Analyzer™. Full article

Background: Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is related to iron–dopamine dysregulation and immune system alteration. We aimed to assess the effects of serum hepcidin, an iron-regulating hormone, in drug-naive RLS patients compared to healthy controls and to evaluate its role in helping to predict clinical improvement after treatment with dopamine agonist. Methods: Nonanemic and drug-naive RLS patients (n = 18) and healthy controls (n = 15) were enrolled. The serum hepcidin and iron-related values in the serum were measured upon the first visit in both groups and 12 weeks later after dopaminergic treatment in 12 patients. Information about sociodemographic characteristics, sleep-related profiles, mood and anxiety was obtained upon the first visit in all participants as well as after treatment in RLS patients. Results: Serum hepcidin levels exhibited no significant differences between patients with drug-naïve RLS and healthy controls at diagnosis (7.1 ± 2.4 vs. 7.0 ± 3.2 ng/mL, p = 0.357). Decreased hepcidin levels were significantly associated with decreased RLS severity (β = 0.002, 95% CI = 0.00−0.00, p = 0.005) and improved quality of life (β = 0.002, 95% CI = 0.00−7.01, p = 0.044) in a dose-dependent manner after 12 weeks of treatment with a dopamine agonist. This association was independent of age, sex, inflammatory markers, sleep quality, insomnia, daytime sleepiness, depression and anxiety. Conclusions: This study demonstrates the role of hepcidin in evaluating the positive therapeutic response in RLS. Full article

There is an increasing incidence, prevalence, and burden of knee osteoarthritis due to a global increase in obesity and an aging population. The aim of the present study was to compare the effectiveness of the addition of aerobic exercises performed in an unloaded or loaded position to a conventional exercise program in overweight subjects with knee osteoarthritis. Twenty-four subjects were randomly allocated to receive 36 sessions of 30-min duration of either sitting aerobic exercises (experimental group) or standing aerobic exercises (control group). Pain intensity, knee disability, and quality-of-life data were collected at baseline and at 12, 24, and 36 sessions. Generalized linear mixed models (GLMMs) were constructed for the analysis of the differences. Significant differences were found in the experimental group for self-reported pain and knee pain and disability at 24 and 36 sessions (p < 0.05). Significant between-group differences were observed in change in self-reported knee pain and disability and quality of life from baseline to 24th- and 36th-session measurements in favor of the experimental group. Adherence to treatment was higher in the experimental group. Adding aerobic exercises in an unloaded position to a conventional exercise program produced superior effects over time for self-reported knee pain, knee pain and disability and quality of life compared to loaded aerobic exercises in overweight subjects with knee osteoarthritis. Full article

Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49–16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2–8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65–11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates. Full article

Background: The negative impact of a high-fat diet on the course of gastroesophageal reflux disease (GERD) has been previously reported. Free fatty acid receptors (FFARs) may be mediators of this phenomenon. The aim of this study was to characterize the role of FFARs in the course of nonerosive (NERD) and erosive (ERD) reflux disease. Methods: Collectively, 73 patients (62 with GERD and 11 healthy controls (HCs)) were recruited to the study. Esophageal biopsies were drawn from the lower third of the esophagus and kept for further experiments. Quantitative, real-time polymerase chain reaction was used to assess the expression of FFAR1, FFAR2, FFAR3, and FFAR4 in biopsies. Histological evaluation of dilated intracellular spaces (DISs) was also performed. Results: FFAR3 exhibited the highest expression, and FFAR4 exhibited the lowest expression in all esophageal samples. Higher relative expression of FFAR1 and FFAR2 and significantly higher expression of FFAR3 (p = 0.04) was noted in patients with GERD compared to respective HCs. Patients with nonerosive GERD (NERD) presented higher expression of all FFARs compared to patients with erosive GERD (ERD) and respective HCs. Interestingly, in patients with ERD, the expression of FFAR3 was lower than in HCs. Significant, weak, positive correlation was found for FFAR3 and FFAR4 expression and DIS scores (r = 0.36, p < 0.05 for FFAR 3, and r = 0.39, p < 0.05 for FFAR4). Conclusions: In this study, we show that FFARs may play a role in GERD pathogenesis, particularly in the NERD type. It may be assumed that FFARs, in particular FFAR3 and FFAR4, may have diagnostic and therapeutic potential in GERD. Full article

The (pro)renin receptor ((P)RR), which evokes renin activity with prorenin, is secreted extracellularly as soluble (P)RR (s(P)RR) and may participate in tissue renin-angiotensin system (RAS) activity in severe heart failure (HF) patients. The aim of this study was to determine whether s(P)RR is an adequate marker in severe HF patients treated with RAS inhibitors, beta-blockers, and tolvaptan. We enrolled 11 patients with severe HF between May 2013 and June 2014. First of all, furosemide of all patients was changed to tolvaptan with hydrochlorothiazide and then the treatment had been changed according to the patient’s condition. After 1, 3, 6, and 12 months, the variance of s(P)RR, plasma renin activity (PRA), plasma renin concentration (PRC), brain natriuretic peptide (BNP) and their association was investigated. Furosemide was restarted in five patients and two patients suffered cardiac death. PRA/PRC and s(P)RR were unchanged (PRA: 10.7 ± 13.9 to 12.8 ± 8.5 ng/mL/h; PRC: 347.1 ± 577.5 to 148.3 ± 123.8 pg/mL; s(P)RR: 28.2 ± 19.3 to 33.4 ± 22.4 ng/mL) and had no significant correlations (PRA and s(P)RR: p = 0.36; PRC and s(P)RR: p = 0.35). There was a significant positive correlation with a high correlation coefficient (CC) between PRA and PRC (p < 0.0001, CC = 0.76), and a negative correlation with weak CC between BNP and s(P)RR (p = 0.01, CC = −0.45). In conclusion, s(P)RR was always high and had no correlations with disease state and PRA/PRC in severe HF patients. Full article

The discontinuation of recommended therapy after myocardial infarction predisposes patients to serious thrombotic complications. The aim of this study was a comprehensive analysis of permanent as well as short- and long-term discontinuation of pharmacotherapy, taking into consideration the basic groups of medications and nonadherence determinants in a one-year follow-up in post-myocardial infarction (MI) patients. Material and methods: The study was a single center cohort clinical trial with a one-year follow-up including 225 patients (73.3% men, 26.7% women) aged 62.9 ± 11.9 years. In eight cases (3.6%), the follow-up duration was less than one year due to premature death. The following factors were analyzed: lack of post-discharge therapy initiation; short-term therapy discontinuation (<30 days); long-term therapy discontinuation (≥30 days); and permanent cessation of therapy. The analysis of therapy discontinuation was performed based on prescription filling data. Results: Occupational activity (Odds Ratio (OR) 5.15; 95% Confidence interval (CI) 1.42–18.65; p = 0.013) and prior MI (OR 5.02; 95% CI 1.45–16.89; p = 0.009) were found to be independent predictors of a lack of post-discharge therapy initiation with P2Y₁₂ receptor inhibitors. We found no independent predictors of lack of post-discharge therapy initiation with other medications, whether analyzed separately or together. Age above 65 years (Hazard Ratio (HR)—1.59; 95% CI 1.15–2.19; p = 0.0049) and prior revascularization (HR—1.44; 95% CI 1.04–2.19; p = 0.0273) were identified as independent predictors of therapy discontinuation. Multilogistic regression analysis showed no independent predictors of the cessation of any of the medications as well as the permanent or temporary simultaneous discontinuation of all medications. Conclusions: The vast majority of post-MI patients discontinue, either temporarily or permanently, one of the essential medications within one year following myocardial infarction. The most likely medication class to be discontinued are statins. Older age and prior cardiac revascularization are independent determinants of therapy discontinuation. Full article

(1) Background: Mitral regurgitation (MR) is the second most prevalent valvular heart disease in developed countries. Mitral valve (MV) disease is a common cause of heart failure and a leading cause of morbidity and mortality in the U.S.A. and Europe. (2) Methods: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2001–2015. We included patients that had surgical mitral valve replacement (SMVR) listed as a procedure in their discharge report. We sought to (i) examine trends in incidence of SMVR among women and men in Spain, (ii) compare in-hospital outcomes for mechanical and bioprosthetic SMVR by sex, and (iii) identify factors associated with in-hospital mortality (IHM) after SMVR. (3) Results: We identified 44,340 hospitalizations for SMVR (84% mechanical, 16% bioprosthetic). The incidence of SMVR was higher in women (IRR 1.51; 95% CI 1.48–1.54). The use of mechanical SMVR decreased over time in both sexes and the use of bioprosthetic valves increased over time in both sexes. Men who underwent mechanical and bioprosthetic SMVR had higher comorbidity than women. IHM was significantly lower in women who underwent SMVR than in men (10% vs. 12% p < 0.001 for mechanical and 14% vs. 16% p = 0.025 for bioprosthetic valve, respectively). Major adverse cardiovascular and cerebrovascular events (MACCE) were also significantly lower in women who underwent mechanical and bioprosthetic SMVR. A significant reduction in both in-hospital MACCEs and IHM was observed over the study period regardless of sex. After multivariable logistic regression, male sex was associated with increased IHM only in bioprosthetic SMVR (OR 1.28; 95% CI 1.1–1.5). (4) Conclusions: This nationwide analysis over 15 years of sex-specific outcomes after SMVR showed that incidences are significantly higher in women than men for mechanical and bioprosthetic SMVR. IHM and MACCE have improved over time for SMVR in both sexes. Male sex was independently associated with higher mortality after bioprosthetic SMVR. Full article

Lymph node involvement has been shown to be one of the most relevant prognostic factors in a variety of malignancies; this is also true of endometrial cancer. The determination of the lymph node status is crucial in order to establish the tumor stage, and to consider adjuvant treatment. A wide range of surgical staging practices are currently used for the treatment of endometrial cancer. The necessity and extent of lymph node dissection is an ongoing controversial issue in gynecological oncology. Lymph node surgery in endometrial cancer is technically challenging, and can be time consuming because of the topographic complexity of lymphatic drainage as such, and the fact that the lymph nodes are directly adjacent to both blood vessels and nerves. Therefore, profound and exact knowledge of the anatomy is essential. Sentinel lymph node mapping was recently introduced in surgical staging with the aim of reducing morbidity, whilst also obtaining useful prognostic information from a patient’s lymph node status. The present review summarizes the current evidence on the role of lymph node surgery in endometrial cancer, focusing on the embryological, anatomical, and technical aspects. Full article

Fibromyalgia (FM), chronic fatigue syndrome (CFS) and multiple chemical sensitivity (MCS) are some of the central sensitization syndromes (CSSs). The complexity of their diagnosis, the high interindividual heterogeneity and the existence of multi-syndromic patients requires a multifaceted treatment. The scientific literature is contradictory regarding the role of food in CSS, and evidence on the role of nutrition in MCS is particularly scarce. This review consists in gathering information about the current status of dietary recommendations (i.e., special dietary interventions, the role of additives, presence of micronutrient deficiencies, nutritional supplements and elimination of other nutrients and substances) and discussing the scientific evidence in depth to shed light on appropriate nutritional treatment managements for CSS patients. Current indications show that dietary modifications may vastly improve the patients’ quality of life at a low cost. We suggest personalized treatment, taking into consideration the severity of the disease symptoms, quality of life, coexistence with other diseases, pharmacological treatment, changing clinical characteristics, nutritional status, energy requirements and food tolerances, among others, as the best ways to tailor specific dietary interventions. These approaches will partially overcome the lack of scientific and clinical research on MSC. Patients should also be advised on the serious consequences of following dietary guidelines without a dietitian’s and clinician’s supervision. Full article

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06−0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12–0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer. Full article