Background: The Seattle heart failure model (SHFM) score is a well-known risk predictor of mortality in patients with heart failure. We validated this score in patients receiving transcatheter aortic valve replacement (TAVR) and aimed to generate further risk discrimination by adding invasive hemodynamics parameters. Methods: Patients who underwent TAVR at our institute between 2015 and 2020 were included and followed for 2 years from index discharge. Patients were randomly assigned to the derivation cohort or the validation cohort. In the derivation cohort, the original SHFM score was modified by adding baseline hemodynamics parameters to evaluate the primary outcomes: 2-year incidence of mortality or readmission from heart failure. The model performance of the modified SHFM score was evaluated in the validation cohort. Results: A total of 217 patients (median age: 86 (83, 88) years old, 64 (29%) men) were included. From the derivation cohort (N = 108), a novel modified SHFM score was constructed: 6 × (original SHFM score < 88.1%) + 5 × (pulmonary capillary wedge pressure > 14 mmHg) + 4 × (cardiac index < 2.26 L/min/m²), which had an improved discrimination compared with the original model (area under the curve: 0.887 vs. 0.679, p = 0.014). In the validation cohort (N = 109), the modified SHFM score showed accurate predictive discrimination of the 2-year cumulative incidence of the primary endpoint into three groups (a low score group with 0–5 points, 3%; an intermediate score group with 6–10 points, 12%; and a high score group with 11–15 points, 43%, p < 0.001). Conclusion: A modified SHFM score consisting of the original SHFM score and invasive hemodynamics parameters predicted mortality and morbidity following TAVR. Evaluation of the external validity of this score in other cohorts needs further investigation. Full article

Introduction: Falls cause 75% of trauma in patients above 65 years of age, and thoracic trauma is the second commonest injury; rib fractures are the most common thoracic injury. These patients have up to 12% mortality, with 31% developing pneumonias. There is wide variation in care. Northumbria Healthcare has a team of respiratory consultants, physiotherapists, specialist nurses and anesthetists for thoracic-trauma management on a respiratory support unit. Methods: With Caldicott approval, basic demographics and clinical outcomes of patients admitted with thoracic trauma between 20 August–21 April were analyzed. A descriptive statistical methodology was applied. Results: A total of 119 patients were identified with a mean age of 71.1 years (range 23–97). Of the 119 patients, 53 were male, 66 females. The main mechanism of injury was falls from standing (65) and falls down stairs/bed or in the bath (18). Length of stay was 7.3 days (range 1–54). In total, 85 patients had more than one co-morbidity, 26 had a full trauma assessment and 75 had pan CTs. The mean number of rib fractures was 3.6 and 31 (26%) patients had a pneumothorax and/or haemothorax. A total of 18 chest drains were inserted (all small bore) and one needle aspiration was performed. No cardiothoracic input was required. Isolated chest trauma was present only in 45 patients. All patients had a pain team review, 22 erector spinae catheters were inserted with 2 paravertebral blocks. Overall, 82 patients did not require oxygen, 1 required CPAP and 1 HFNC. 7 needed intensive care transfer. Furthermore, 20 (17%) developed pneumonias and 16 (14%) deaths occurred within 30 days—all were in those with falls from standing. There was no correlation between number of fractured ribs, length of stay and mortality. Conclusions: High level care for thoracic trauma can be performed by a physician led team. Overall, 42% pneumothoraces/haemothoraces were observed. Further large scale randomised trials are warranted for definitive outcomes. Full article

Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors (TKI). When TKI therapy is discontinued in CML patients in deep, sustained and apparently stable molecular remission, these cells in approximately half of the cases restart to grow, resuming the leukemic process. The elimination of these TKI resistant leukemic stem cells is therefore an essential step in increasing the percentage of those patients who can reach a successful long-term treatment free remission (TFR). The understanding of the biology of the LSCs and the identification of the differences, phenotypic and/or metabolic, that could eventually allow them to be distinguished from the normal hematopoietic stem cells (HSCs) are therefore important steps in designing strategies to target LSCs in a rather selective way, sparing the normal counterparts. Full article

Aim: Fibrosis is observed both in pancreatic cancer (PDAC) and chronic pancreatitis (CP). The main cells involved in fibrosis are pancreatic stellate cells (PSCs), which activate alpha smooth muscle actin (αSMA), which is considered to be the best-known fibrosis marker. The aim of the study was to evaluate the expression of the αSMA in patients with PDAC and CP as the possible differentiation marker. Methods: We enrolled 114 patients undergoing pancreatic resection: 83 with PDAC and 31 with CP. Normal fragments of resected specimen from 21 patients represented the control tissue. The immunoexpressions of αSMA were detected in tissue specimens with immunohistochemistry (Abcam antibodies, GB). Results: Mean cytoplasmatic expression of αSMA protein in PDAC stromal cells was significantly higher compared to CP: 2.42 ± 0.37 vs 1.95 ± 0.45 (p < 0.01) and control group 0.61 ± 0.45 (p < 0.01). Strong immunoexpression of the αSMA protein was found in the vast majority (80.7%) of patients with PDAC, in about half (58%) of patients with CP, and not at all in healthy tissue. The expression of αSMA of different intensity was found in all patients with PDAC and CP, while in healthy tissue was minimal or absent. In PDAC patients, αSMA expression was significantly higher in tumors of diameter higher than 3 cm compared to smaller ones (p = 0.017). Conclusions: Presented findings confirm the significant role of fibrosis in both PDAC and CP; however, they do not confirm the role of αSMA as a marker of differentiation. Full article

JAK2, MPL, and CALR mutations define clonal thrombocytosis in about 90% of patients with sustained isolated thrombocytosis. In the remainder of patients (triple-negative patients) diagnosing clonal thrombocytosis is especially difficult due to the different underlying conditions and possible inconclusive bone marrow biopsy results. The ability to predict patients with sustained isolated thrombocytosis with a potential clonal origin has a prognostic value and warrants further examination. The aim of our study was to define a non-invasive clinical or blood parameter that could help predict clonal thrombocytosis in triple-negative patients. We studied 237 JAK2 V617-negative patients who were diagnosed with isolated thrombocytosis and referred to the haematology service. Sixteen routine clinical and blood parameters were included in the logistic regression model which was used to predict the type of thrombocytosis (reactive/clonal). Platelet count and lactate dehydrogenase (LDH) were the only statistically significant predictors of clonal thrombocytosis. The platelet count threshold for the most accurate prediction of clonal or reactive thrombocytosis was 449 × 10⁹/L. Other tested clinical and blood parameters were not statistically significant predictors of clonal thrombocytosis. The level of LDH was significantly higher in CALR-positive patients compared to CALR-negative patients. We did not identify any new clinical or blood parameters that could distinguish clonal from reactive thrombocytosis. When diagnosing clonal thrombocytosis triple-negative patients are most likely to be misdiagnosed. Treatment in patients with suspected triple negative clonal thrombocytosis should not be delayed if cardiovascular risk factors or pregnancy coexist, even in the absence of firm diagnostic criteria. In those cases the approach “better treat more than less” should be followed. Full article

Maturity to parenthood is essential for taking on parental roles but remains an understudied issue. Still, close relations between maturity and personality dimensions are commonly emphasized. Thus, conducting research on maturity in context of personality seems a valuable research direction. The present research consists of two studies, focusing on the development and validation of Maturity to Parenthood Scale (MPS), in relation to personality, emotional regulation, coping with challenges, and intimate relationship satisfaction. In both studies, childless adults aged 20–35 years took part: (1) 718 participants (M_age = 25.49; SD = 2.89; 479 women), (2) 150 participants (M_age = 23.69; SD = 3.15; 104 women). All the participants had been in an intimate relationship for at least six months at the time of the study, the majority declared their willingness to have children in the future, had higher education, and were professionally active. The results showed that MPS is a reliable, valid measure comprising the following three subscales: valence, behavioral, and cognitive–emotional maturity to parenthood. The findings also confirmed the importance of broad- and narrow-band individual differences and contextual factors for maturity. MPS may be used in psychoeducation, supporting the transition to biological or adoptive/foster parenthood, as well as in medical and psychological care. Full article

Background: The aim of this study is to determine the effect of three doses of intra-articular injection of platelet-rich plasma (PRP) into the osteoarthritic (OA) knee joint on the functional status and on the changes in the levels of specific OA biomarkers in blood serum. Methods: Forty patients with unilateral primary knee osteoarthritis were enrolled in this single center, prospective clinical trial. For each patient, three intra-articular PRP injections were administered one week apart. Clinical and laboratory assessment was performed before the first PRP injection (baseline), and 3 months after the third PRP application (3-month follow up). Pain in the affected knee joint was assessed with the Visual Analog Scale for Pain (VAS). Change in clinical status was evaluated with the Western Ontario and McMaster Universities Arthritis Index Questionnaire (WOMAC). Concentrations of 19 biomarkers (EGF, Eotaxin, FGF-2, GRO, IL-10, IL-1RA, IL-8, IP-10, MCP-1, PDGF-AB/BB, RANTES, MMP-3, MMP-13, Collagen type 2, BMP-2, TIMP-1, TIMP-2, TGF beta 1, and COMP) in the serum of studied patients were quantified. Results: At 3-month follow up, there was a significant decrease in the VAS score and significant improvement in the WOMAC score. There was a significant decrease in the levels of Eotaxin, MCP-1, MMP-1, IL-10, EGF, PDGF-AB/BB, TGF- β1 compared to baseline levels. A significant increase in markers BMP-2, COMP, Collagen type 2 and GRO was found at the same time point. There was no significant change in the concentrations of other biomarkers (FGF-2, IL-1RA, IL-8, IL-10, MMP-3, RANTES, TIMP-1, TIMP-3). Conclusions: We found an increase in specific pro-anabolic and anti-inflammatory biomarkers with a concomitant decrease in pro-inflammatory biomarkers at 3 months after three intra-articular applications of PRP. Significant improvement in VAS and WOMAC scores was observed. Treatment with PRP may be an effective therapeutic option with anti-inflammatory and regenerative potential in patients with primary knee OA. Full article

Previous literature has provided conflicting results regarding the associations between early surgery and postoperative outcomes in elderly patients with distal femur fractures. Using data from the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2019, we identified elderly patients who underwent surgery for distal femur fracture within two days of hospital admission (early surgery group) or at three or more days after hospital admission (delayed surgery group). Of 9678 eligible patients, 1384 (14.3%) were assigned to the early surgery group. One-to-one propensity score matched analyses showed no significant difference in 30-day mortality between the early and delayed groups (0.5% versus 0.5%; risk difference, 0.0%; 95% confidence interval, −0.7% to 0.7%). Patients in the early surgery group had significantly lower proportions of the composite outcome (death or postoperative complications), shorter hospital stays, and lower total hospitalization costs than patients in the delayed surgery group. Our results showed that early surgery within two days of hospital admission for geriatric distal femur fracture was not associated with a reduction in 30-day mortality but was associated with reductions in postoperative complications and total hospitalization costs. Full article

Coronavirus disease 2019 (COVID-19) is a multisystem illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can manifest with a multitude of symptoms in the setting of end-organ damage, though it is predominantly respiratory. However, various symptoms may remain after acute SARS-CoV-2 infection, and this condition is referred to as “Long COVID” (LC). Patients with LC may develop multi-organ symptom complex that remains 4–12 weeks after the acute phase of illness, with symptoms intermittently persisting over time. The main symptoms are fatigue, post-exertional malaise, cognitive dysfunction, and limitation of functional capacity. Pediatric patients developed the main symptoms of LC like those described in adults, although there may be variable presentations of LC in children. The underlying mechanisms of LC are not clearly known, although they may involve pathophysiological changes generated by virus persistence, immunological alterations secondary to virus–host interaction, tissue damage of inflammatory origin and hyperactivation of coagulation. Risk factors for developing LC would be female sex, more than five early symptoms, early dyspnea, previous psychiatric disorders, and alterations in immunological, inflammatory and coagulation parameters. There is currently no specific treatment for LC, but it could include pharmacological treatments to treat symptoms, supplements to restore nutritional, metabolic, and gut flora balance, and functional treatments for the most disabling symptoms. In summary, this study aims to show the scientific community the current knowledge of LC. Full article

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease among children. In some patients, cervical spine arthritis remains a serious and chronic manifestation of JIA. The aim of this study was to assess the frequency of cervical spine lesions on radiographs and MRI in JIA patients with clinical signs of cervical spine involvement and to verify if with the addition of MRI, the use of radiographs could be abandoned. Methods: This retrospective study evaluated consecutive 34 children (25 girls; aged 6–18 years, median 15.5 years) with JIA and with clinical involvement of cervical spine. In each patient, both radiographs and MRI of the cervical spine were performed. Imaging findings were correlated with clinical and laboratory data. Results: The cervical spine was affected in 35% of patients. The most frequent lesions were subaxial subluxations (SAS; 24%), apophyseal joint ankylosis (9%), and C1/C2 joint lesions (9%). Anterior atlanto-axial subluxation (AAS) was diagnosed only by radiography, and most of the SAS were seen on radiography, whereas only a few on MRI. Reversely, C1/C2 soft tissue involvement were seen on MRI only. Cervical spine involvement was associated with raised ESR (p = 0.012) and CRP (p = 0.014). Conclusions: The cervical spine lesions are still frequent complication of JIA affecting up to 35% of JIA patients. Most of them develop serious complications, such as AAS and ankylosis. Despite advantages of MRI in terms of the imaging of the atlanto-axial region radiography shows superiority in diagnosis of AAS and SAS. Full article

Mounting evidence indicates an association between adipokines and inflammation-related atherosclerosis. Here, we sought to investigate the association of vaspin and omentin with clinical characteristics and outcomes of patients with acute cerebral ischemia (ACI). Consecutive ACI patients were evaluated within 24 h from symptom-onset. Stroke aetiology was classified using TOAST criteria. Adipokines were assayed using quantikine enzyme immunoassay commercially available kits. Stroke severity was assessed by NIHSS-score, and ipsilateral carotid stenosis (≥50% by NASCET criteria) by ultrasound and CT/MR angiography. Major cerebrovascular events were assessed at three months. We included 135 ACI patients (05 (78%) and 30 (22%) with acute ischemic stroke and transient ischemic attack, respectively; mean age ± SD: 59 ± 10 years; 68% men; median NIHSS-score: 3 (IQR:1–7)). Omentin was strongly correlated to admission stroke severity (Spearman rho coefficient: +0.303; p < 0.001). Patients with ipsilateral carotid stenosis had higher omentin levels compared to patients without stenosis (13.3 ± 8.9 ng/mL vs. 9.5 ± 5.5 ng/mL, p = 0.014). Increasing omentin levels were independently associated with higher stroke severity (linear regression coefficient = 0.290; 95%CI: 0.063–0.516; p = 0.002) and ipsilateral carotid stenosis (linear regression coefficient = 3.411; 95%CI: 0.194–6.628; p = 0.038). No association of vaspin with clinical characteristics and outcomes was found. Circulating omentin may represent a biomarker for the presence of atherosclerotic plaque, associated with higher stroke severity in ACI patients. Full article

It is well known that some pathological conditions, especially of autoimmune etiology, are associated with the HLA (human leukocyte antigen) phenotype. Among these diseases, we include celiac disease, inflammatory bowel disease, autoimmune enteropathy, autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cholangitis. Immunoglobulin G4-related diseases (IgG4-related diseases) constitute a second group of autoimmune gastrointestinal, hepatobiliary and pancreatic illnesses. IgG4-related diseases are systemic and rare autoimmune illnesses. They often are connected with chronic inflammation and fibrotic reaction that can occur in any organ of the body. The most typical feature of these diseases is a mononuclear infiltrate with IgG4-positive plasma cells and self-sustaining inflammatory response. In this review, we focus especially upon the hepatopancreatobiliary system, autoimmune pancreatitis and IgG4-related sclerosing cholangitis. The cooperation of the gastroenterologist, radiologist, surgeon and histopathologist is crucial for establishing correct diagnoses and appropriate treatment, especially in IgG4 hepatopancreatobiliary diseases. Full article

Wingless binding integration site proteins (Wnt) have an important role in normal kidney development and in various kidney diseases. They are required for complete epithelial differentiation and normal nephron formation. Changes in these proteins could also have important role in carcinogenesis. This study included 185 patients with clear cell renal carcinoma (ccRCC) in whom immunohistochemical expression of Wnt-4 protein in healthy and tumorous tissue after surgery was investigated. There was higher expression of Wnt-4 in healthy than in tumor tissue. No difference between Fuhrman’s grade and Wnt-4 expression was found. A poor negative correlation between tumor size and Wnt-4 expression was found. Patients with suspected metastatic diseases had higher Wnt-4 expression. There was no difference in survival rates between Wnt-4 negative and positive groups. In our study we have shown that high Wnt-4 expression in healthy tissue decreases in low-grade tumors but then increases in high-grade tumors, suggesting that tumor progression requires Wnt-4 activation or reactivation. Full article

(1) Background: The aim of the present pilot study was to study the effect of a new oral gonadotropin-releasing hormone antagonist on adenomyosis. (2) Methods: Eight premenopausal women, aged between 37 and 45 years, presenting with heavy menstrual bleeding, pelvic pain, and dysmenorrhea due to diffuse and disseminated uterine adenomyosis, confirmed by magnetic resonance imaging (MRI), received 200 mg linzagolix once daily for a period of 12 weeks, after which they were switched to 100 mg linzagolix once daily for another 12 weeks. The primary efficacy endpoint was the change in volume of the adenomyotic uterus from baseline to 24 weeks, evaluated by MRI. Secondary efficacy endpoints included the change in uterine volume from baseline to 12 and 36 weeks by MRI, and also weeks 12, 24, and 36 assessed by transvaginal ultrasound (TVUS). Other endpoints were overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain, dyspareunia, amenorrhea, quality of life measures, bone mineral density (BMD), junctional zone thickness, and serum estradiol values. (3) Results: Median serum estradiol was suppressed below 20 pg/mL during the 12 weeks on linzagolix 200 mg, and maintained below 60 pg/mL during the second 12 weeks on linzagolix 100 mg. At baseline, the mean ± SD uterine volume was 333 ± 250 cm³. After 24 weeks of treatment, it was 204 ± 126 cm³, a reduction of 32% (p = 0.0057). After 12 weeks, the mean uterine volume was 159 ± 95 cm³, a reduction of 55% from baseline (p = 0.0001). A similar pattern was observed when uterine volume was assessed by TVUS. Improvements in overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain, dyspareunia, and dyschezia, as well as quality of life measured using the EHP-30 were also observed. Mean percentage BMD loss at 24 weeks was, respectively, −2.4%, −1.3%, and −4.1% for the spine, femoral neck, and total hip. The most common adverse events were hot flushes, which occurred in 6/8 women during the first 12 weeks, and 1/8 women between 12 and 24 weeks. (4) Conclusions: Linzagolix at a dose of 200 mg/day reduced uterine volume, and improved clinically relevant symptoms. Treatment with 100 mg thereafter retains the therapeutic benefits of the starting dose while minimizing side effects. This ‘hit hard first and then maintain’ approach may be the optimal way to treat women with symptomatic adenomyosis. Full article

There are several premises that the body composition of kidney transplant recipients may play a role in tacrolimus metabolism early after transplantation. The present study aimed at analyzing the relationship between the body composition parameters assessed by bioimpedance analysis (BIA) and initial tacrolimus metabolism. Immediately prior to transplantation, BIA using InBody 770 device was performed in 122 subjects. Tacrolimus concentration-to-dose (C/D) ratio was calculated based on the first blood trough level measurement. There was no difference in phase angle, visceral fat area, lean body mass index (LBMI) and the proportion of lean mass as a percentage of total body mass between the subgroups of slow and fast metabolizers. However, subjects with LBMI ≥ median value of 18.7 kg/m², despite similar initial tacrolimus dose per kg of body weight, were characterized by a significantly lower tacrolimus C/D ratio (median 1.39 vs. 1.67, respectively; p < 0.05) in comparison with the subgroup of lower LBMI. Multivariate regression analysis confirmed that age (r_partial = 0.322; p < 0.001) and LBMI (r_partial = −0.254; p < 0.01) independently influenced the tacrolimus C/D ratio. A LBMI assessed by BIA may influence the tacrolimus metabolism in the early post-transplant period and can be a useful in the optimization of initial tacrolimus dosing. Full article