Medicina, Volume 59, Issue 11 (November 2023) – 159 articles

Osteoarthritis (OA) is a prevalent degenerative joint condition characterized by cartilage deterioration, joint inflammation, and functional limitations, particularly impacting the elderly population. Rehabilitation and hyaluronic acid (HA) injections are common therapeutic approaches routinely used in clinical practice, but their synergistic potential is far from being fully characterized. Thus, the aim of this narrative review was to elucidate the multilevel benefits and synergies of integrating these two approaches in multidisciplinary OA rehabilitation. This narrative review follows the scale for the assessment of narrative review articles (SANRA) criteria and involves a comprehensive literature search from July to August 2023. Two independent reviewers screened studies, including those involving human subjects with OA, rehabilitation strategies, and outcomes following HA injection, published in English. Results: HA injections might improve joint biomechanics, reducing friction, absorbing shocks, and potentially regulating inflammation. Rehabilitation plays a pivotal role in strengthening muscles, increasing the range of motion, and enhancing overall function. Optimizing rehabilitation following HA injection might provide additional benefits in joint health. OA management requires a multidisciplinary approach integrating HA injections, rehabilitation, and personalized care. Challenges in patient adherence and healthcare resources currently exist, but emerging technologies offer opportunities to enhance patient engagement and monitoring optimizing sustainability and outcomes of patients with knee, hip, shoulder, and temporomandibular joint OA. Full article

Background and Objectives: Protective equipment, including seatbelts and airbags, have dramatically reduced the morbidity and mortality rates associated with motor vehicle collisions (MVCs). While generally associated with a reduced rate of injury, the effect of motor vehicle protective equipment on patterns of chest wall trauma is unknown. We hypothesized that protective equipment would affect the rate of flail chest after an MVC. Materials and Methods: This study was a retrospective analysis of the 2019 iteration of the American College of Surgeons Trauma Quality Program (ACS-TQIP) database. Rib fracture types were categorized as non-flail chest rib fractures and flail chest using ICD-10 diagnosis coding. The primary outcome was the occurrence of flail chests after motor vehicle collisions. The protective equipment evaluated were seatbelts and airbags. We performed bivariate and multivariate logistic regression to determine the association of flail chest with the utilization of vehicle protective equipment. Results: We identified 25,101 patients with rib fractures after motor vehicle collisions. In bivariate analysis, the severity of the rib fractures was associated with seatbelt type, airbag status, smoking history, and history of cerebrovascular accident (CVA). In multivariate analysis, seatbelt use and airbag deployment (OR 0.76 CI 0.65–0.89) were independently associated with a decreased rate of flail chest. In an interaction analysis, flail chest was only reduced when a lap belt was used in combination with the deployed airbag (OR 0.59 CI 0.43–0.80) when a shoulder belt was used without airbag deployment (0.69 CI 0.49–0.97), or when a shoulder belt was used with airbag deployment (0.57 CI 0.46–0.70). Conclusions: Although motor vehicle protective equipment is associated with a decreased rate of flail chest after a motor vehicle collision, the benefit is only observed when lap belts and airbags are used simultaneously or when a shoulder belt is used. These data highlight the importance of occupant seatbelt compliance and suggest the effect of motor vehicle restraint systems in reducing severe chest wall injuries. Full article

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose–response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose–response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose–response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy. Full article

Most women who menstruate experience various physical, psychological, and behavioral changes during the period between ovulation and menstruation. This study focuses on defining and diagnosing premenstrual disorders, distinguishing between premenstrual symptoms (PS), PMS, and premenstrual dysphoric disorder (PMDD). It highlights the prevalence of these conditions and their impact on women’s quality of life, including social, occupational, and psychological aspects. Furthermore, the study examines the role of physical activity, particularly aerobic exercise, in managing premenstrual symptoms. Several systematic reviews are cited, suggesting that regular physical activity can effectively reduce both physical and psychological symptoms associated with PMS. In conclusion, the management of PMS involves a multifaceted approach, with exercises, dietary modifications, stress management, cognitive-behavioral therapy, and medications all playing roles. Physical activity, especially aerobic exercise, has been found to be an effective non-pharmacological therapy for alleviating PMS symptoms and improving overall well-being. However, more research is needed to determine the optimal type and dosage of exercise for individual women with PMS. Full article

Background and Objectives: The surgical treatment of proximal humeral shaft fractures usually considers application of either long straight plates or intramedullary nails. By being able to spare the rotator cuff and avoid the radial nerve distally, the implementation of helical plates might overcome the downsides of common fixation methods. The aims of the current study were (1) to explore the biomechanical competence of different plate designs and (2) to compare their performance versus the alternative treatment option of using intramedullary nails. Materials and Methods: Twenty-four artificial humeri were assigned to the following four groups for simulation of an unstable proximal humeral shaft fracture and instrumentation: Group 1 (Straight-PHILOS), Group 2 (MULTILOC-Nail), Group 3 (45°-Helical-PHILOS), and Group 4 (90°-Helical-PHILOS). All specimens underwent non-destructive, quasi-static biomechanical testing under loading in axial compression, torsion in internal/external rotation, and pure bending in four directions, accompanied by motion tracking. Results: Axial stiffness/displacement in Group 2 was significantly higher/smaller than in all other groups (p ≤ 0.010). Torsional displacement in Group 2 was significantly bigger than in all other groups (p ≤ 0.017). Significantly smaller coronal plane displacement was identified in Group 2 versus all other groups (p < 0.001) and in Group 4 versus Group 1 (p = 0.022). Significantly bigger sagittal plane displacement was detected in Group 4 versus all other groups (p ≤ 0.024) and in Group 1 versus Group 2 (p < 0.001). Conclusions: Intramedullary nails demonstrated higher axial stiffness and smaller axial interfragmentary movements compared with all investigated plate designs. However, they were associated with bigger torsional movements at the fracture site. Although 90°-helical plates revealed bigger interfragmentary movements in the sagittal plane, they demonstrated improved resistance against displacements in the coronal plane when compared with straight lateral plates. In addition, 45°-helical plates manifested similar biomechanical competence to straight plates and may be considered a valid alternative to the latter from a biomechanical standpoint. Full article

Background and Objectives: This prospective, comparative, double-cohort study aimed to compare the efficacy of silver diamine fluoride and potassium iodide (38% SDF+KI; Riva Star^®) with sodium fluoride varnish (5% NaF; Duraphat^®) in hypersensitive carious lesions in primary teeth to evaluate caries arrest and hypersensitivity relief. Materials and Methods: This study included thirty 2–5-year-olds (mean age = 3.67 ± 1.06 years; 16 males and 14 females) who required a desensitizing treatment for hypersensitive carious defects with visible dentin. A total of 15 of the participants were consecutively allocated to treatment with 5% NaF, and they were further compared to an equal number of participants treated with 38% SDF+KI solutions (n = 15). The treatments were performed following clinical evaluation of caries activity using the International Caries Classification and Management System (ICCMS^TM) and the Bjørndal criteria (score of 0–9). Parental-reported hypersensitivity was evaluated using a visual analogue scale (0–10 = no to severe pain). Results: Clinical variables were evaluated at baseline and three months after treatment. Thereafter, a significant decline in hypersensitivity/pain led to lower final scores in the Riva Star^® group (0.40 ± 1.12, p = 0.002) than in the Duraphat^® group (1.40 ± 2.20, p = 0.004). The caries arrest effect was significantly higher in the Riva Star^® group (86.7%) compared to the Duraphat^® group three months after treatment (13.3%, p < 0.001). In both groups, there were no statistically significant differences in the children’s behavior before, during, and after treatment. Conclusions: Ultimately, with both fluoride therapies reducing hypersensitivity/pain significantly, treatment with 38% SDF+KI was clearly more effective in caries arrest than 5% NaF varnish after a 3-month period. Full article

Background and Objectives: Percutaneous left-atrial appendage (LAA) occlusion is an important therapeutic option for preventing cardioembolic stroke in patients with non-valvular atrial fibrillation (AF) at high risk of thromboembolic events and with contraindications for oral anticoagulation (OAC). It is usually performed with transesophageal echocardiography (TOE) guidance under general anesthesia (GA). In this retrospective study, we present a multicenter experience of LAA occlusion performed with conscious sedation (CS) without an anesthesiologist on site. Materials and Methods: All the patients on the waiting list for LAA occlusion procedure at Infermi Hospital, Rivoli, and San Luigi Gonzaga University Hospital, Orbassano, from October 2018 to October 2022 were analyzed. All the procedures were performed with a Watchman/FLX LAA closure device under TOE and fluoroscopic guidance without an anesthesiologist on site. CS was performed with a combination of midazolam and fentanyl as needed. Results: One-hundred fifteen patients were included (age 76.4 ± 7.6 years, median CHA2DS2Vasc 4.4 ± 1.4). CS was performed using midazolam (mean dose 5.9 ± 2.1 mg), adding fentanyl for thirty-nine (33.9%) patients in case of poor tolerance for the procedure despite midazolam. The acute procedural success rate was 99.1%. We observed seven acute severe complications. No patients needed anesthesiological assistance during the procedure, and no cases of respiratory failure necessitating ventilation were reported. In a follow-up after 10 ± 9 months, one case of stroke (0.9%) and one case (0.9%) of transient ischemic attack (TIA) occurred. Conclusions: LAA occlusion performed under CS and without the presence of an anesthesiologist on site appears to be safe and effective. It can be an attractive alternative to general anesthesia (GA), as fewer resources are required. Full article

Background and Objectives: To analyze the patient outcome and complication rate of axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients who could not be weaned from cardiopulmonary bypass after cardiothoracic surgery. Materials and Methods: We analyzed the data of 179 patients who were supported with VA-ECMO with femoral–axillary access (FA VA-ECMO) after cardiothoracic surgery between January 2014 and January 2019 in our department. Patients requiring central aortic cannulation and patients with respiratory failure requiring veno-venous ECMO were excluded. Primary outcomes were in-hospital mortality and 1-year survival rate of patients who were weaned from VA-ECMO support. Secondary outcomes were cannulation-related complications at the axillary site, VA-ECMO-related complications, and systemic complications. Results: In our cohort, 60 (33.5%) patients were female. Mean age was 67.0 ± 10.9 years. Overall, 78 (43.5%) patients were operated upon electively, 37 (20.7%) patients underwent urgent surgery, and 64 (35.8%) patients underwent emergency surgical treatment. Sixty-seven patients (37.4%) were resuscitated preoperatively. The mean duration of VA-ECMO support was 8.4 ± 5.1 days. Weaning from VA-ECMO was successful in 87 (48.6%) patients; 62 (34.6%) patients survived the hospital stay. The 1-year survival rate was 74%. Subclavian bleeding occurred in 24 (13.4%) patients, femoral bleeding in 4 (2.2%) patients, ischemia of the upper limb in 11 (6.1%) patients, intracerebral bleeding in 9 (5%) patients, and stroke in 19 (10.6%) patients. Conclusions: In patients with acute LV dysfunction after cardiothoracic surgery who cannot be weaned from cardiopulmonary bypass, right axillary artery cannulation is a safe and reliable method for VA-ECMO support with an acceptable complication rate. Full article

Background and objectives: Implant-related complications leading to implant loss contribute to major morbidity in immediate breast reconstruction (IBR). Various techniques have been advocated to improve rates of reconstruction salvage. The objective of our study was to assess if a peri-prosthetic irrigation system was an effective adjunct to the conventional wash-out technique in improving reconstruction salvage rates. Methods: The study included patients who had immediate implant-based breast reconstruction from January 2015 to November 2020. The conventional technique of reconstruction salvage, using debridement, wash-out, and implant/expander exchange with systemic use of antibiotics, was performed for patients undergoing exploration for infection until May 2019. A simple technique using a continuous peri-prosthetic irrigation system with vancomycin (1 g/L normal saline over 24 h) for 2 days was added as an adjunct to the conventional technique. Treatment details and clinical outcomes were compared between the groups. The study was approved by the Clinical Governance department. Results: During the study period, 335 patients underwent IBR. A total of 65 patients (19.4%) returned to the theatre due to post-operative complications, of which 45 (13.4%) were due to infection. A conventional technique was used in 38 (84.4%) patients, and peri-prosthetic irrigation was used as an adjunct in 7 patients (15.6%). A total of 16 (42.1%) in the conventional group and all 7 (100%) in the irrigation group had successful reconstruction salvage. No patients had complications due to antibiotic irrigation. Conclusions: The peri-prosthetic irrigation system is a simple, safe, and effective adjunct to conventional techniques in improving reconstruction salvage in IBR. Full article

A pseudoaneurysm of the subclavian artery following central venous catheter placement is a rare but potentially fatal complication that often requires surgical intervention. However, surgical repair of the subclavian artery remains challenging. Herein, we report the case of a male patient undergoing hemodialysis who developed a pseudoaneurysm of the subclavian artery after a bedside central vein catheter placement. Hemostasis was successfully achieved by selecting the pseudoaneurysm using a microcatheter. At the 10-month follow-up, the pseudoaneurysm was completely excluded, and the patient was in a stable condition. The patient underwent native arteriovenous fistula creation and hemodialysis. Endovascular treatment could be an effective nonsurgical treatment for subclavian artery pseudoaneurysms and has been attempted as a first-line treatment option. Full article

Background and Objectives: With the increased trend towards digitalization in dentistry, intraoral scanning has, to a certain extent, replaced conventional impressions in particular clinical settings. Trueness and precision are essential traits for optical impressions but have so far been incompletely explored. Materials and Methods: We performed a study to evaluate the differences in the three-dimensional spatial orientations of implant analogs on a stone cast when using an intraoral scanner compared to a dental laboratory scanner. We assessed the deviation of the intraoral scans compared to the laboratory scan for three standardized implant measurement plans and compared these results with control scans of the neighboring natural teeth. Results: We found no statistically significant correlation between the measurements at the scan body level and the landmarks chosen as controls on the neighboring natural teeth (p = 0.198). The values for the implant scans presented wider variation compared to the control scans. The difference between the implant and the control planes ranged from −0.018 mm to +0.267 mm, with a median of −0.011 mm (IQR: −0.001–0.031 mm). While most values fell within a clinically acceptable margin of error of 0.05 mm, 12.5% of the measurements fell outside of this acceptable range and could potentially affect the quality of the resulting prosthetic work. Conclusions: For single-unit implant-supported restorations, intraoral scanning might have enough accuracy. However, the differences that result when scanning with an intraoral scanner may affect the quality of prosthetic work on multiple implants, especially if they are screw-retained. Based on our results, we propose different adaptations of the prosthetic protocol to minimize the potential effect of errors that may occur during the digital workflow. Full article

Background and Objectives: Cryoablation is an established treatment method for atrial fibrillation (AF). We present the long-term results of cryoablation in 94 patients with paroxysmal and persistent AF treated in our center. Materials and Methods: This was an observational, retrospective study of 94 patients who underwent a cryoablation procedure for paroxysmal or persistent AF from 2015 to 2017. The follow up was 51 ± 3 months. The absence of arrhythmia was checked at 6, 12, 24, and 48 months after the procedure with 24 h Holter monitoring. We evaluated echocardiography parameters before and 48 months after cryoablation. The quality of life was assessed by calculating EHRA scores at each visit. Results: The mean history of pre-procedural AF duration was 55.3 ± 8.6 months. Paroxysmal AF was present in 42% of patients and persistent AF in 58%. Comparing the EHRA classes, a statistically significant difference was observed between the score assessed before the procedure and the score after one year, as well as when comparing the rates before the procedure and four years after the procedure (p < 0.000). The recurrence of AF was observed in 22.3% of patients 1 year after the procedure, in 26.6% of patients 2 years after the procedure, and in 34% of patients 4 years after the procedure; 9.3% of them were left in permanent AF. During the observation period, 28% of patients underwent a repeated pulmonary vein isolation procedure, and 6% of patients had a permanent pacemaker implanted. Five hematomas (5%) and one instance of phrenic nerve palsy (1%) were observed during the procedure. Conclusions: The rate of arrhythmia recurrence increased every year after cryoablation. Quality of life improved after the procedure, despite the recurrence of AF. A quarter of patients had to undergo a repeat pulmonary vein isolation procedure. Full article

Background and Objectives: Esophageal stenting with self-expandable metallic stents (SEMS), for both benign and malignant reasons, has been widely practiced for decades, but migration still remains the most common complication of the procedure. In this report we aim to review our experience and results in stent fixation with clips. Materials and Methods: We present 18 patients who underwent esophageal stenting for both benign and malignant reasons. The SEMSs used were partially covered and were fixated with two to four through the scope hemostatic clips in the proximal end of the prothesis. The procedure was performed only on patients with a high risk of migration of the stent. Results: Migration occurred in only one of the above-mentioned patients and was treated with stent repositioning. The other adverse events that occurred were related to tumor growth in patients with malignant diseases. Conclusions: Clip fixation of an esophageal self-expandable metallic stent in cases considered high-risk for migration is a safe procedure. It reduces the migration rate significantly for both benign and malignant indications. Full article

Background and Objectives: Impaired cognition and pain after surgery contribute to prolonged hospital stays and increased mortality rates. Thus, the development of preemptive algorithms for reducing their impact should be prioritized. The main objectives of the present study were to evaluate the efficiency of using virtual reality (VR) to treat postoperative cognitive decline and pain perception. Materials and Methods: The study was a prospective, monocentric, clinical study that included 51 patients who have undergone major abdominal surgery. The patients were divided into two groups: Control (n = 25) and VR (n = 26). The VR sessions consisted of 5–8 min exposure at 24–48 h after surgery. We considered the outcome variables, the mini-mental state examination, and visual analogue scale at 24–48 h after surgery. The dependent variables were age, social status, educational level, and duration of surgery. Results: We did not observe any differences in postoperative cognition deficit with regard to VR. The VR, however, successfully reduced postoperative pain intensity. Moreover, the patients’ age, surgery duration, level of education, and social status influenced the MMSE score at 24–48 h after surgery. Conclusions: Even if using VR does not alleviate short-term postoperative cognitive impairments, it could affect pain perception. Further studies are needed to support the use of VR in perioperative contexts. Full article

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed^®, Web of Science™, and Scopus^®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: “miRNA”, “non-coding RNA”, “small RNA”, “Testicular Cancer”, “seminomatous testicular germ cell”, “non-seminomatous testicular germ cell”. Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90–99%) and sensitivity (84–89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools. Full article

Background: The risk of palatally displaced canines (PDCs) rises in patients with tooth agenesis. The orthodontic extrusion and alignment of PDCs require adequate anchorage to enable tooth movement and control the side effects. There is no paper presenting treatment in the case of severe oligodontia with simultaneous PDCs and the use of mini-implants (MIs) for their orthodontic extrusion. Case presentation: A 15-year-old patient presented with non-syndromic oligodontia and bilateral PDCs. Cone beam computed tomography revealed that both PDCs were in proximity to the upper incisors’ roots. There was no evident external root resorption of the incisors. The “canines first” approach was chosen. MIs were used both as direct and indirect anchorage. First, the extrusive forces of cantilevers were directed both occlusally and distally. Next, the buccal directions of forces were implemented. Finally, fixed appliances were used. PDCs were extruded, aligned, and torqued. Proper alignment and occlusion were achieved to enable further prosthodontic restorations. Conclusions: The use of MIs made it possible to avoid collateral effects, reduce the risk of complications, and treat the patient effectively. MIs provide adequate anchorage in demanding cases. The use of MIs for the extrusion of PDCs made it possible to offer this treatment option to patients with severe oligodontia. The presented protocol was effective and served to circumvent treatment limitations associated with an inadequate amount of dental anchorage and a high risk of root resorption. Full article

Background and Objectives: Diverticulosis affects a significant portion of the elderly population, with age and lifestyle being established risk factors. Additionally, genetic predisposition is gaining recognition as a contributing factor. This pilot study sought to explore the frequency of genetic variants in matrix metalloproteinases (MMPs) 3, 9, and 12 in a population of colonic diverticulosis patients. Materials and Methods: The study encompassed 134 participants: 59 diagnosed with colon diverticulosis during colonoscopy and 75 healthy controls. The cases and controls were meticulously matched in terms of age and gender. We assessed the distribution of genetic variants MMP3 rs3025058, MMP9 rs3918242, and MMP12 rs2276109 using the polymerase chain reaction–restriction fragments length polymorphism technique. Results: The MMP9 rs3918242 allele T was notably more frequent in individuals with diverticulosis when compared with the control group (p < 0.03). Furthermore, it was associated with dominant (OR = 2.62; 95% CI: 1.24–5.56; p < 0.01) and co-dominant (OR = 2.10; 95% CI: 1.06–4.13; p < 0.03) genetic models. The MMP3 rs3025058 5A/5A genotype was nearly twice as frequent in patients with diverticulosis, while the 6A/6A genotype was only half as common in this group. Conversely, no significant correlation was established between MMP12 rs2276109 and colonic diverticulosis. Conclusions: Our study offers the first insight into a potential connection between genetic variants in MMPs and colon diverticulosis. Specifically, allele T of MMP9 rs3918242 and allele 5A of MMP3 rs3025058 appear to be linked to this condition. These findings indirectly suggest a role for extracellular matrix proteins in the pathogenesis of diverticulosis. Full article

Background and Objective: The aim of this retrospective cohort study is to evaluate the impact of assisted reproductive treatment (ART) on adverse maternal outcomes and the rate of hospitalization in maternal intensive care (MIC) in a tertiary university center in Liege, Belgium. Materials and Methods: This is a retrospective cohort study comparing two groups, 6557 patients who achieved pregnancy spontaneously and 330 patients who achieved pregnancy after ART, between January 2020 and December 2022. These patients were followed in the academic obstetrics department of Citadelle Hospital, Liège. The database of the ART center was compared with the database of the delivery unit to determine the cohort of patients who conceived after ART. Adverse maternal outcomes and MIC hospitalization rates were compared with between spontaneous pregnancies and ART groups. ART groups were also compared with each other. Results: The rate of hospitalization in maternal intensive care for patients who achieved pregnancy spontaneously was 12.1%, compared to 17.3% after ART. Comparing the rate of pre-eclampsia, 3.5% of spontaneous pregnancies were complicated by pre-eclampsia, while after ART, 10.9% of patients developed this complication during pregnancy. This rate was higher after IVF (12%) compared to intrauterine insemination and particularly after frozen embryo transfer (FET) in artificial cycle (17.9%). The birthweight of newborns after ART was also analyzed. A significant difference was obtained when comparing fresh embryo transfer with FET. Conclusions: Our study confirmed that FET in artificial cycle is a risk factor for pre-eclampsia and that fresh embryo transfer is associated with a higher rate of newborns with a lower percentile of birthweight. Our data showed that the rate of MIC hospitalization was significantly higher after ART but did not differ between groups. Full article

Background and Objectives: In patients with peripheral artery disease, there is insufficient understanding of characteristics that predict successful revascularization of the lower extremity (LE) chronic total occlusions (CTOs) and baseline differences in demographic, clinical, and angiographic characteristics in patients with LE CTO vs. non-CTO. We aim to explore these differences and predictors of successful revascularization among CTO patients. Materials and Methods: Two vascular centers enrolled LE-CTO patients who underwent endovascular revascularization. Data on demographics, clinical, angiographic, and interventional characteristics were collected. LE non-CTO arterial stenosis patients were compared. A total of 256 patients with LE revascularization procedures were studied; among them, 120 had CTOs and 136 had LE stenosis but no CTOs. Results: Aspirin use (Odds ratio, OR: 3.43; CI 1.32–8.88; p = 0.011) was a positive predictor whereas a history of malignancy (OR: 0.27; CI 0.09–0.80; p = 0.018) was a negative predictor of successful crossing in the CTO group. The CTO group had a higher history of myocardial infarction (29.2 vs. 18.3%, p = 0.05), end-stage renal disease (19.2 vs. 9.6%, p = 0.03), and chronic limb-threatening ischemia as the reason for revascularization (64.2 vs. 22.8%, p < 0.001). They were more likely to have advanced TransAtlantic Inter-Society Consensus (TASC) stages, multi-vessel revascularization procedures, longer lesions, and urgent treatment. Conclusions: The use of aspirin is a positive predictor whereas a history of malignancy is a negative predictor for successful crossing in CTO lesions. Additionally, LE-CTO patients have a higher incidence of comorbidities, which is expected given their higher disease burden. Successful endovascular re-vascularization can be associated with baseline clinical variables. Full article

Background and Objectives: This study evaluated the in vitro anti-adipogenic and anti-inflammatory properties of black cumin (Nigella sativa L.) seed extract (BCS extract) as a potential candidate for developing herbal formulations targeting metabolic disorders. Materials and Methods: We evaluated the BCS extract by assessing its 2,2-diphenyl-1-picrohydrazyl (DPPH) radical scavenging activity, levels of prostaglandin E₂ (PGE₂) and nitric oxide (NO), and mRNA expression levels of key pro-inflammatory mediators. We also quantified the phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPK) signaling molecules. To assess anti-adipogenic effects, we used differentiated 3T3-L1 cells and BCS extract in doses from 10 to 100 μg/mL. We also determined mRNA levels of key adipogenic genes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/BEPα), adipocyte protein 2 (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), and sterol-regulated element-binding protein 1c (SREBP-1c) using real-time quantitative polymerase chain reaction (qPCR). Results: This study showed a concentration-dependent DPPH radical scavenging activity and no toxicity at concentrations up to 30 μg/mL in Raw264.7 cells. BCS extract showed an IC₅₀ of 328.77 ± 20.52 μg/mL. Notably, pre-treatment with BCS extract (30 μg/mL) significantly enhanced cell viability in lipopolysaccharide (LPS)-treated Raw264.7 cells. BCS extract treatment effectively inhibited LPS-induced production of PGE₂ and NO, as well as the expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), interleukin (IL)-1β and IL-6, possibly by limiting the phosphorylation of p38, p65, inhibitory κBα (I-κBα), and c-Jun N-terminal kinase (JNK). It also significantly attenuated lipid accumulation and key adipogenic genes in 3T3-L1 cells. Conclusions: This study highlights the in vitro anti-adipogenic and anti-inflammatory potential of BCS extract, underscoring its potential as a promising candidate for managing metabolic disorders. Full article

This narrative review aims to report the main clinical manifestations, therapeutic strategies, outcomes, and complications of acute SARS-CoV-2 infection in childhood and to summarize the data relating the SARS-CoV-2 vaccination efficacy and safety in pediatric age. SARS-CoV-2 infection mostly occurs asymptomatically in the pediatric population, while multisystem inflammatory syndrome in children (MIS-C) represents the most severe coronavirus disease 2019 (COVID-19)-related illness, a life-threatening event with a high morbidity rate. After the development of SARS-CoV-2 vaccines and their subsequent approval in children, the rate of infection as well as the number of its related complications have shown a drastic decrease. Fully vaccinated children are protected from the risk of developing a severe disease and a similar protective role has been observed in the reduction of complications, in particular MIS-C. However, long-lasting immunity has not been demonstrated, booster doses have been required, and reinfection has been observed. With regards to vaccine safety, adverse events were generally mild to moderate in all age groups: local adverse events were the most commonly reported. Nevertheless, a potential association between SARS-CoV-2 vaccine and the subsequent development of inflammatory manifestations has been suggested. Myocarditis has rarely been observed following vaccination; it appeared to be more frequent among adolescent males with a mild clinical course leading to a complete recovery. SARS-CoV-2 vaccine-related MIS-C cases have been described, although a univocal definition and an exact time interval with respect to vaccination has not been reported, thus not establishing a direct causal link. Current evidence about COVID-19 vaccination in children and adolescents suggest that benefits outweigh potential risks. Long-term data collection of the post-authorization safety surveillance programs will better define the real incidence of SARS-CoV-2 vaccine-related complications in the pediatric population. Full article

Background and Objectives: The purpose of this study was to apply histopathological and immunohistochemical methods to compare the protective efficacy of melatonin and N-acetylcysteine (NAC) application in rats with experimental brain ischemia/reperfusion (I/R) injury induced through occlusion of the middle cerebral artery (MCA), and to evaluate the protective effect of their combined use. Materials and Methods: Forty-one young adult male Wistar albino rats were divided into five groups—control (n = 8), I/R group (n = 8), melatonin (n = 8), NAC (n = 8), and melatonin + NAC (n = 9). Results: All scores differed between the groups, apart from vascular congestion (p < 0.05). At two-way comparisons, all histological scores were significantly higher in the I/R group than in the control group (p < 0.05). No change occurred in the vascular congestion scores with the administration of melatonin, although decreases were determined in all other scores. These decreases were statistically significant for cellular eosinophilic pyknotic degeneration, vacuolization, and edema (p < 0.05). All histopathological scores in the group administered NAC together with melatonin were significantly lower than in the I/R group (p < 0.05). Conclusions: The combined use of NAC and melatonin, the neuroprotective efficacy of which on histopathological parameters is shown in this study, now needs to be supported by further research. Full article

Background and Objectives: An understanding of the anatomical complexity of teeth is a significant factor for a successful endodontic treatment outcome. The aim of this study was to explore the frequency and pattern of distribution of radix entomolaris (RE) in mandibular first molars (MFMs) of a Saudi Arabian subpopulation using CBCT scans. Materials and Methods: This study was conducted at dental clinics of Qassim University from February to May 2023 by evaluating CBCT scans that were previously obtained for diagnostic purposes. Scans of Saudi national patients with bilaterally present MFMs and fully formed root apices were included. Conversely, scans with one/or two missing MFMs, MFMs with incomplete root apices, full- or partial-coverage prosthesis, endodontic treatment, and associated radicular resorption were excluded from study. A total of 303 CBCT scans with 606 bilateral MFMs were analyzed by two calibrated evaluators for the presence of, and type according to Song’s typolgy of RE. The data were analyzed using SPPS-24. The descriptive variables were documented as frequencies and percentages. The chi-square test was used to determine the association between the prevalence of RE with the gender, jaw side and age group. Both inter-rater and intra-rater agreements were estimated for detecting and classifying RE using Cohen’s kappa test. Results: The sample had 63.7% males and 36.3% females. The prevalence of RE was 6.6%, with Song’s type III (57.5%) as the most common variant. Absolute agreement was noted between the raters about the presence of RE and very strong agreement was noted for the classification of the RE. Conclusions: RE is an uncommon finding among the mandibular first molars of the Saudi population without any gender and quadrant predilection. The clinicians’ knowledge of the presence and Song’s type of RE may contribute towards the enhancement of endodontic treatment outcomes. Full article

Background and Objectives: The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods: The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results: Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5–84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia <3.7 × 10⁹/L (AUC 0.95), and low CRP levels < 1.66 mg/dL (AUC 0.98) (p < 0.001 for each factor). Conclusions: Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic. Full article

Background and Objectives: The assessment of sexual dysfunction among psoriatic patients still remains a great diagnostic difficulty due to its subjective and embarrassing character. Various questionnaires have been used to assess sexual dysfunctions associated with skin conditions; however, none of them have been approved as a gold standard. The aim of our study was to create and validate the Skin-Related Sexual Life Questionnaire (SRSLQ) for the assessment of possible sexual dysfunction and related psychological burdens in patients with skin diseases. Materials and Methods: A total of 109 patients, including 45 women and 64 men (1:1.4) suffering from psoriasis and aged between 18 and 73 years (mean 48.0 ± 13.4 years), were included in the study. All subjects completed the 11-item SRSLQ and the Dermatology Life Quality Index (DLQI). In addition, all men were asked to fulfil the five-item version of the International Index of Erectile Dysfunction (IIEF-5) at the time of examination and 7 days after enrollment. The disease severity was assessed via the PASI scale. Results: The statistical analysis of internal consistency of SRSLQ showed very good integrity, with a Cronbach α coefficient of 0.94. The reproducibility level assessed with intraclass correlation coefficient (ICC) amounted to 0.96. A significant correlation between the total score of the 11-item SRSDQ and the DLQI (r = 0.39; p < 0.001) was found, confirming congruent validity. Conclusions: The validated 11-item Skin-Related Sexual Life Questionnaire can be successfully implemented in daily clinical practice as well as in clinical research. Full article

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case–control study comparing CLE patients retrospectively assigned to three subgroups based on 3–6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40–80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients. Full article

Cultural competence training has been criticized for reinforcing existing stereotypes, ignoring intersectionality and inadvertently marginalizing some individuals and groups. In contrast, cultural humility offers the possibility of transformational learning, requiring individuals to pursue a lifelong course of self-examination. This approach makes authentic engagement with others possible. We review the premises underlying cultural competence and cultural humility, as well as proposed models for the integration of cultural humility into the clinical context. We propose a new model for the integration of cultural humility into clinical research: CARE, signifying Curiosity, Attentiveness, Respect and Responsiveness, and Embodiment. We conclude that the concept of cultural humility can be integrated into the conduct of clinical research. Full article

Background and Objectives: The aim of this study was to assess the relationship between habitual physical activity, body composition, serum myokine concentration, and all-cause mortality in chronic hemodialysis patients. Materials and Methods: A prospective cohort study with a 7-year follow-up was conducted in a group of 38 patients (24 men, 14 women, mean age 65.6 ± 13.9 years, dialysis vintage 1.17 ± 1.25 years). Baseline serum concentrations of myokines—follistatin and myostatin—were assessed along with a measurement of physical activity with multidimensional accelerometery, body composition, and the force of forearm muscle contraction. Survival analysis was performed using the Kaplan–Meier method for tertiles of follistatin, serum myostatin, body composition, and physical activity expressed in metabolic equivalents (MET). Results: The mean physical activity among patients was 81 min/24 h (median 38.5 min), and the mean weekly 3MET activity was 493 min (median 218 min). The probability of survival of patients was significantly lower in the subgroup with 3MET/24 h less than 26 min/24 h and 3METt less than 148 min per week compared to the other subgroup (p = 0.006 and p = 0.006, respectively). During the 70-month follow-up, the subgroup with the lowest baseline follistatin concentration showed a significantly lower risk of death (p = 0.02). Baseline myostatin levels were not significant risk factors for mortality, nor were BMI or lean and fat tissue index categories. Conclusions: Physical activity and low plasma follistatin, but not body composition indexes or plasma myostatin, could serve as predictors of all-cause mortality in hemodialysis patients. Full article

Background and Objectives: Although the importance of sarcopenia control has been suggested, there are no minimal detectable change (MDC) studies of older adults with sarcopenia, to our knowledge, and the criteria for determining the effectiveness of interventions are unknown. The purpose of this study was to calculate the MDC in the five times sit-to-stand test (FTSST) in older Japanese adults with sarcopenia and use it as an index to determine the effectiveness of future interventions. Materials and Methods: This was a cross-sectional study conducted in January and February 2023. The participants of this study were older Japanese adults using daycare rehabilitation. Thirty-eight participants performed the FTSST twice a week. Grip strength, walking speed, and skeletal muscle mass were measured to determine the presence of sarcopenia. The diagnosis of sarcopenia was defined as low skeletal muscle mass and low muscle strength and/or low physical function, based on the Asian Working Group for Sarcopenia 2019 diagnostic criteria. Participants were further classified as sarcopenic or non-sarcopenic. Intraclass correlation coefficients (ICCs) and MDCs were calculated for the overall, sarcopenia, and non-sarcopenia groups using the two FTSST measures. The average and difference of the two variables were used to calculate the MDC. Results: Overall, the ICC (1,1) was 0.94, MDC was 2.87 s, and MDC% was 23.3%. The sarcopenia group had an ICC (1,1) of 0.93, MDC of 3.12 s, and MDC% of 24.0%. The non-sarcopenia group had an ICC (1,1) of 0.95, MDC of 2.25 s, and MDC% of 19.2%. Conclusions: Despite the limitation of the data being only from this study population, we found that a change of ≥3.12 s or ≥24.0% in the FTSST of older adults with sarcopenia was clinically meaningful and may help to determine the effectiveness of sarcopenia treatment. The improvement or decline in older Japanese adults with sarcopenia should be determined by changes in the FTSST over a longer period of time than that for other conditions. Full article

Background and Objectives: Due to their specific morphology, the regeneration of intrabony defects (IBDs) represents one of the greatest challenges for clinicians. Based on the specific properties of a magnesium membrane, a new approach for the surgical treatment of IBD was developed. The surgical procedure was described using a series of three cases. Materials and Methods: The patients were healthy individuals suffering from a severe form of periodontitis associated with IBD. Based on radiographic examination, the patients had interproximal bone loss of at least 4 mm. Due to its good mechanical properties, it was easy to cut and shape the magnesium membrane into three different shapes to treat the specific morphology of each IBD. In accordance with the principles of guided bone regeneration, a bovine xenograft was used to fill the IBD in all cases. Results: After a healing period of 4 to 6 months, successful bone regeneration was confirmed using radiological analysis. The periodontal probing depth (PPD) after healing showed a reduction of 1.66 ± 0.29 mm. Conclusions: Overall, the use of the different shapes of the magnesium membrane in the treatment of IBD resulted in a satisfactory functional and esthetic outcome. Full article