Contrast-enhanced guided endoscopic ultrasound procedures.

Contrast-enhanced endoscopic ultrasound (CH-EUS) can overcome the limitations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours. Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions, further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS. This review details the knowledge based on the available data on contrast-guided procedures. The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions, which occur in select cases. Additionally, the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage, and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented. Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours, in which case CH-EUS can be used to reveal the incomplete tumour destruction.

Non-vascularized Fibular Autograft and Locking Plate: A Solution to the Resistant Nonunion of a Tibial Metaphyseal Fracture.

The union of tibial fractures often raises concerns. In one such case, a 62-year-old female patient presented in our Emergency Room (ER) with a comminuted tibial metaphyseal fracture resulting from a traffic accident. The patient underwent three surgical procedures in the following two years. The first intervention was open reduction internal fixation (ORIF) with a plate and screws. The second intervention, which took place three months after the first surgery, addressed the union delay through implant removal and closed reduction and internal fixation (CRIF) with an antegrade intramedullary tibial nail. The third intervention addressed the implant failure and oligotrophic nonunion through the removal of the broken tibial nail and ORIF using a proximal tibia locking plate and screws, augmented with fibular shaft and reamed iliac crest autografts. We conducted frequent follow-ups with the patient and performed multiple X-rays to confirm and monitor the fracture union. At the last follow-up, two years after the last surgical intervention, imagistic investigations showed that the patient presented with fracture union, she could support her full body weight on the operated leg, and was able to walk and carry out normal daily activities. As such, we concluded that the surgical method chosen (ORIF with proximal tibia locking plate and screws, augmented with a fibula shaft strut and reamed iliac crest autograft) was a viable option to treat an aseptic oligotrophic nonunion in a high-energy comminuted tibia fracture.

Clinical significance of the anti-Nucleolar Organizer Region 90 antibodies (NOR90) in systemic sclerosis: Analysis of the European Scleroderma Trials and Research (EUSTAR) cohort and a systematic literature review.

BACKGROUND: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain. OBJECTIVES: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort. METHODS: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023. RESULTS: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %. CONCLUSION: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.

Bilateral pheochromocytomas: clinical presentation and morbidity rate related to surgery technique and genetic status.

Background: Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60-90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients. Results: Fourteen patients (12.5%, nine women, five men) had synchronous or metachronous bilateral PHEOs (out of 112 PHEO patients who underwent surgery between 1976 and 2021). The median age at diagnosis was 32 years (9-76) (three were children). Nine patients (64.2%) presented synchronous bilateral tumors, five (35.7%) contralateral metachronous tumors, 2-12 years after the first surgical intervention; three (21.4%) were metastatic. Median follow-up: 5 years (1-41), IQR 19 months. A total of 78.5% had a germline mutation (eight RET gene with MEN2A syndrome, three VHL syndrome, three not tested). Post-surgery recurrence was noted in 16.6% of patients (one with MEN2A syndrome and metastatic PHEOs, one with VHL syndrome), with similar rates after total adrenalectomy or cortical-sparing adrenal surgery. AI was avoided in 40% after cortical-sparing surgery. Conclusion: Bilateral PHEOs are usually associated with genetic syndromes. The surgical technique for patients with hereditary bilateral PHEOs should be chosen based on a personalized approach, as they are at higher risk for developing new adrenal tumors requiring additional surgeries.

The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis-Interstitial Lung Disease in the European Scleroderma Trial and Research Database.

BACKGROUND AND OBJECTIVES: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. METHODS: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. RESULTS: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. CONCLUSIONS: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Integrating Artificial Intelligence in Pediatric Healthcare: Parental Perceptions and Ethical Implications.

BACKGROUND: Our study aimed to explore the way artificial intelligence (AI) utilization is perceived in pediatric medicine, examining its acceptance among patients (in this case represented by their adult parents), and identify the challenges it presents in order to understand the factors influencing its adoption in clinical settings. METHODS: A structured questionnaire was applied to caregivers (parents or grandparents) of children who presented in tertiary pediatric clinics. RESULTS: The most significant differentiations were identified in relation to the level of education (e.g., aversion to AI involvement was 22.2% among those with postgraduate degrees, 43.9% among those with university degrees, and 54.5% among those who only completed high school). The greatest fear among respondents regarding the medical use of AI was related to the possibility of errors occurring (70.1%). CONCLUSIONS: The general attitude toward the use of AI can be considered positive, provided that it remains human-supervised, and that the technology used is explained in detail by the physician. However, there were large differences among groups (mainly defined by education level) in the way AI is perceived and accepted.

Anastomotic Leakage after Gastrectomy for Gastric Cancer.

Anastomotic leakage (AL) constitutes a prominent cause of significant morbidity following gastrectomy for gastric cancer. The manifestation of AL typically occurs within 7 to 10 days post-surgery, with reported incidence rates of 5.8-6.7% for open gastrectomy and 3.3-4.1% for laparoscopic gastrectomy. Various predisposing risk factors have been identified, including the individual nutritional status (excluding obesity) and preoperative corticotherapy. Interestingly, the administration of neoadjuvant therapies appears to reduce the AL occurrence. In the context of distal gastrectomies, the rates of AL are comparable between laparoscopic, robotic, and open approaches. The total gastrectomies have higher AL rate compared to distal gastrectomies, which are considered the preferred approach. Prophylactic drainage measures have not demonstrated efficacy in preventing AL. As for postoperative management, conservative treatment is indicated for patients presenting with mild clinical symptoms and increased inflammatory blood tests. This approach involves fasting, enteral or parenteral nutrition, administration of antibiotics, and percutaneous drainage. For small AL, endoscopic therapies such as stents, vacuum therapy, clips, suturing devices, and injections are appropriate treatment options. In cases of high-volume fistulas, severe sepsis or failure of previous therapies, surgical reoperation becomes the ultimate solution.

Survival Analysis and Failure Modes of Total Hip Arthroplasty Using a Cemented Semi-Retentive Acetabular Cup.

To reduce the incidence of total hip revisions, there have been continuous efforts to enhance prosthetic materials and designs to optimize implant survival. A primary implant with a constrained acetabular component is often used to minimize the risk of dislocations even though this approach has some drawbacks as reported in the literature. To address these concerns, this study aimed to assess the survivorship and dislocation rate of a semi-retentive cemented acetabular cup when used as a primary implant. The specific cemented cup that we studied was not present in any study that we consulted, so to fill this gap, we conducted a retrospective examination of 527 cemented hip prostheses that utilized the semi-retentive cup between the years 2005 and 2012. We employed Cox multiple regression models for our statistical analysis. The revision due to dislocation occurred in 12.8% of all cases, with a lower incidence of 5% (14 cases) in age groups >70 years than in age groups <70 years (14%-32 cases) (p < 0.001). The survival rates of the semi-retentive cemented acetabular cup were 98.6% (520 cases) at 5 years and 92.2% (487 cases) at 10 years. The survival rates were significantly lower in women than men, with 1.9% (7 cases) toward 0% at 5 years and 8.1% (30 cases) toward 5% (7 cases) at 10 years (p = 0.002). The difference in failure rates between age groups over 70 years (2.3%-10 cases) and age groups under 70 years (11.5%-34 cases) was also statistically significant (p < 0.001). Our study indicates that the semi-constrained design may cause frequent damage to the polyethylene liner due to impingement and wear, which are the primary factors for failure. Also, this implant has a similar risk of revision due to dislocation as reported in studies and may be beneficial as a primary implant in elderly patients with low-demanding lifestyles, muscular insufficiency, and low compliance regarding hip prosthetic behavior, without a major effect on survivorship.

Subtle Changes in Myocardial Work Indices Assessed by 2D-Speckle Tracking Echocardiography Are Linked with Pathological LV Remodeling and MACEs Following an Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

The goal of this study was to assess whether subtle changes in myocardial work indices may predict left ventricular (LV) remodeling and major cardiac events (MACEs) in patients with a first ST-elevation acute myocardial infarction (STEMI) and preserved LVEF after successful myocardial revascularization with PCI. Methods. Consecutive STEMI patients in sinus rhythm and with an LV ejection fraction ≥ 50% following a successful PCI were recruited. Conventional and two-dimensional speckle tracking echocardiography (2D-STE) was conducted within 36 h of the PCI and 3 months later. Patients having an increase of more than 20% in LV diastolic volume were included in the LV remodeling group. MACEs were noted throughout a four-year period of follow-up. Results: The study comprised 246 STEMI patients with a mean age of 66; 72% of whom were men. In 24% (58) of the patients, LV remodeling developed. These patients were older, more frequently hypertensive, and had a smoking history. They also exhibited significantly lower baseline and 3-month values for the myocardial global index (GWI), global constructive work (GCW), and global myocardial efficiency (GWE). The cut-off values of 1670 mmHg% for GWI and 83% for GWE were predictive of LV remodeling (p < 0.0001). During the four-year follow-up period, 19% of STEMI patients experienced a MACE, involving 15% from non-LV remodelers and 34% from LV remodelers (p = 0.01). The cut-off values for baseline GWI of 1680 mmHg% and baseline GWE of 84% had the best accuracy in predicting MACEs. In conclusion, non-invasive myocardial work indices offered a reproducible and accurate method to predict post-MI LV remodeling and MACEs.

An Insight on the Possible Association between Inflammatory Bowel Disease and Biologic Therapy with IL-17 Inhibitors in Psoriasis Patients.

Psoriasis is a chronic, inflammatory, multisystemic disease which affects approximately 2-3% of the population globally, whose onset is triggered by genetic and environmental factors which activate both dendritic cells and keratinocytes, resulting in the production of proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 17, interleukin 23, interleukin 22, and interleukin 1ß. An in-depth understanding of the pathophysiology of psoriasis led to significant advances in the development of safe and efficient novel therapeutic options, with four classes of biologic therapy being approved for the management of moderate to severe psoriasis: tumor necrosis factor alpha inhibitors, interleukin 23 inhibitors, anti-interleukin 12/23 agents, anti-interleukin 17 agents, as well as small-molecule inhibitors, such as apremilast. Psoriasis is associated with comorbid conditions, namely psoriatic arthritis, cardiovascular disease, metabolic syndrome, psychiatric disorders, malignancy, as well as inflammatory bowel disease. For patients affected by both psoriasis and inflammatory bowel disease, there is a strong recommendation to avoid IL-17 inhibitors since they may play a part in the exacerbation of the gastrointestinal disease. Our aim was to perform a thorough literature review regarding the development of inflammatory bowel disease lesions in psoriasis patients treated with IL-17 inhibitors, along with a case presentation to emphasize the need for close follow-up of these patients.

Myocardial Work Evaluation-A Useful Non-Invasive Method to Predict Coronary Artery Sub-Occlusion in a Patient with Unstable Angina and Multiple Myocardial Revascularization Interventions.

BACKGROUND: While lifestyle changes, management of coronary artery disease (CAD) risk factors, myocardial revascularization procedures, and medication can improve a patient's prognosis, de novo native coronary lesions and in-stent restenosis (ISR) remain significant clinical concerns. ISR is more frequent with a bare-metal stent than with a drug-eluting stent and has been documented in around 12% of DES patients. Acute coronary syndrome (ACS) manifests as unstable angina in about 30% to 60% of ISR patients. Myocardial work imaging is a modern, non-invasive technique able to identify individuals with critical coronary artery lesions with high sensitivity and specificity. CASE REPORT: We present the case of a 72-year-old Caucasian gentleman with multiple cardiovascular risk factors, admitted to the Cardiology Clinic of Timișoara Municipal Hospital with unstable angina. From 1999 to 2021, the patient experienced two myocardial infarctions, a double aortocoronary bypass graft, and multiple percutaneous coronary interventions with 11 stent implantations, including 6 for ISR. Using two-dimensional speckle-tracking echocardiography and myocardial work assessment, we detected that the lateral wall of the left ventricle had a severely impaired deformation pattern. Angio-coronarography was performed, and sub-occlusion of the posterolateral branch of the right coronary artery was found. Angioplasty was performed and a DES was inserted, with a good final angiographic result and complete release of symptoms. CONCLUSION: In patients with a history of multiple myocardial revascularization interventions and ISR, it is challenging to identify the critical ischemia region by non-invasive methods. Myocardial work imaging was beneficial in the detection of the altered deformation patterns indicating significant ischemia, its accuracy being superior to that of LV strain, as proven by coronary angiography. Urgent coronary angiography followed by angioplasty and stent implantation resolved the issue.

Determination of Phosphodiesterase Type-5 Inhibitors (PDE-5) in Dietary Supplements.

This study proposed a high-performance thin-layer chromatography (HPTLC) screening method to detect phosphodiesterase 5 (PDE-5) inhibitors as possible adulterant agents in various dietary supplements. Chromatographic analysis was performed on silica gel 60F254 plates using a mixture of ethyl acetate:toluene:methanol:ammonia in a volume ratio of 50:30:20:0.5 as a mobile phase. The system provided compact spots and symmetrical peaks of sildenafil and tadalafil with retardation factor values of 0.55 and 0.90, respectively. The analysis of products purchased from the internet or specialized stores demonstrated the presence of sildenafil, tadalafil, or both compounds in 73.3% of products, highlighting inadequacies and inconsistencies in the labeling, as all dietary supplements were declared to be natural. The results were confirmed using ultra-high-performance liquid chromatography coupled with a positive electrospray ionization high-resolution tandem mass spectrometry (UHPLC-HRMS-MS) method. Furthermore, in some samples, vardenafil and various analogs of PDE-5 inhibitors were detected using a non-target HRMS-MS approach. The results of the quantitative analysis revealed similar findings between the two methods, with adulterant quantities found to be similar to or higher than those in approved medicinal products. This study demonstrated that the HPTLC method is a suitable and economical method for screening PDE-5 inhibitors as adulterants in dietary supplements intended for sexual activity enhancement.

The regional evolution of job insecurity during the first COVID-19 wave in relation to the pandemic intensity.

As the COVID-19 pandemic hit the European continent at the beginning of 2020, one of the most significant socio-economic effects that immediately become the central focus of media and governing bodies was the unemployment and the sudden transformations suffered by the job market. This effect created major concerns for citizens and governing structures, as the pandemic generated a new and unparalleled economic context, where the short and medium-term future of several sectors seemed unpredictable. The concern acted upon the job insecurity of individuals, a perceived threat to the continuity and stability of their employment. Based on a self-reported survey covering the first pandemic wave, our study classifies the regions (NUTS2 level) from six EU countries according to their performance in terms of job insecurity, but also the shock intensity (death rates and case fatality ratio), and identifies the overall over and under performers. The results show that the regional evolution of the job insecurity could be linked to the pandemic evolution, especially in the stronger economies. However, the model does not follow a classic economic core-periphery pattern. The model is challenged especially by a stronger performance of several less performant regions from Italy, Romania, or France. Supplementary Information: The online version contains supplementary material available at 10.1007/s12076-023-00337-9.

Genome editing using Staphylococcus aureus Cas9 in a canine model of glycogen storage disease Ia.

Glycogen storage disease type Ia (GSD Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), associated with life-threatening hypoglycemia and long-term complications, including hepatocellular carcinoma formation. Gene replacement therapy fails to stably reverse G6Pase deficiency. We attempted genome editing using two adeno-associated virus vectors, one that expressed Staphylococcus aureus Cas9 protein and a second containing a donor transgene encoding G6Pase, in a dog model for GSD Ia. We demonstrated donor transgene integration in the liver of three adult-treated dogs accompanied by stable G6Pase expression and correction of hypoglycemia during fasting. Two puppies with GSD Ia were treated by genome editing that achieved donor transgene integration in the liver. Integration frequency ranged from 0.5% to 1% for all dogs. In adult-treated dogs, anti-SaCas9 antibodies were detected before genome editing, reflecting prior exposure to S. aureus. Nuclease activity was low, as reflected by a low percentage of indel formation at the predicted site of SaCas9 cutting that indicated double-stranded breaks followed by non-homologous end-joining. Thus, genome editing can integrate a therapeutic transgene in the liver of a large animal model, either early or later in life, and further development is warranted to provide a more stable treatment for GSD Ia.

The Role of Fascial Tissue Layer in Electric Signal Transmission from the Forearm Musculature to the Cutaneous Layer as a Possibility for Increased Signal Strength in Myoelectric Forearm Exoprosthesis Development.

Myoelectric exoprostheses serve to aid in the everyday activities of patients with forearm or hand amputations. While electrical signals are known key factors controlling exoprosthesis, little is known about how we can improve their transmission strength from the forearm muscles as to obtain better sEMG. The purpose of this study is to evaluate the role of the forearm fascial layer in transmitting myoelectrical current. We examined the sEMG signals in three individual muscles, each from six healthy forearms (Group 1) and six amputation stumps (Group 2), along with their complete biometric characteristics. Following the tests, one patient underwent a circumferential osteoneuromuscular stump revision surgery (CONM) that also involved partial removal of fascia and subcutaneous fat in the amputation stump, with re-testing after complete healing. In group 1, we obtained a stronger sEMG signal than in Group 2. In the CONM case, after surgery, the patient's data suggest that the removal of fascia, alongside the fibrotic and subcutaneous fat tissue, generates a stronger sEMG signal. Therefore, a reduction in the fascial layer, especially if accompanied by a reduction of the subcutaneous fat layer may prove significant for improving the strength of sEMG signals used in the control of modern exoprosthetics.

Radiotherapy in aggressive or dopamine agonists resistant prolactinomas; is it still worthwhile?

Radiotherapy, conventional or radiosurgery, has been used to control prolactin secretion and tumour growth in prolactinomas both as part of multimodal therapy or rarely as primary treatment. However, considering the radiotherapy side effects, notably hypopituitarism, as opposed to the high efficacy and low toxicity of dopamine agonists (DA) treatment and neurosurgery, radiotherapy is recommended mostly for patients with aggressive or high-risk prolactinomas or in those resistant or intolerant to medical therapy, usually after surgical failure. We provide an overview of the published literature on the efficacy and toxicity of radiotherapy (conventional fractionated or radiosurgery), in aggressive, high-risk, or DA resistant prolactinomas. Radiotherapy has shown a good efficacy and a reasonable toxicity profile in prolactinomas where other treatment modalities failed. In aggressive and high-risk prolactinomas, the cumulative percentage for tumour control (reduction plus stable) ranged from 68% to 100%. Most studies reported global hormonal control rates over 50%. In resistant prolactinomas, the global secretion control rate (on, but also off DA) ranged from 28% to 89%-100%; in most studies over 80%. The 5-year rate of hypopituitarism was around 12%-25%. To date there are no controlled study on the use of radiotherapy as a prophylactic treatment in patients with clinical, radiological or pathological markers of aggressiveness. In conclusion, our review supports the use of radiotherapy in patients with growing, clinically aggressive or truly DA resistant prolactinomas. In patients with high-risk or invasive prolactinomas or in those harboring pathological markers of aggressiveness, the prophylactic use of radiotherapy should be individualized.