Carol Davila University of Medicine and Pharmacy

Introduction. Complex childhood trauma (CCT) involves prolonged exposure to severe interpersonal stressors, leading to deficits in executive functioning and self-regulation during adolescence, a critical period for neurodevelopment. While qEEG parameters, particularly alpha oscillations, have been proposed as potential biomarkers for trauma, empirical documentation in developmental samples is limited. Aim. This preregistered study investigated whether adolescents with CCT exhibit qEEG patterns similar to those reported for PTSD, such as reduced posterior alpha power, increased individual alpha peak frequency (iAPF), right-lateralized alpha frequencies, and lower total EEG power (RMS) compared to controls. Materials and Methods. EEG data from 26 trauma-exposed adolescents and 28 controls, sourced from an open database, underwent similar preprocessing. qEEG features, including alpha power, iAPF, alpha asymmetry, and RMS, were extracted from eyes-open and eyes-closed conditions and analyzed using mixed ANOVAs. Results. Significant group differences were found in total EEG power, with trauma-exposed adolescents showing lower RMS than controls. No significant differences were found in posterior absolute alpha power, iAPF, or alpha asymmetry. However, we observed that posterior relative alpha power was higher in the trauma group, though the difference was not statistically significant but showing a small to medium effect size. Additionally, a negative correlation between CPTSD severity and EEG power in the EO condition was observed, suggesting trauma-related cortical hypoactivation. Conclusion. Reduced total EEG power and modified alpha dynamics may serve as candidate neuromarkers of CCT. These findings underscore the need for further research to validate qEEG biomarkers for understanding and diagnosing trauma-related disorders in developmental populations.

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11% in the United States. As for other types of tumors, such as colorectal cancer, aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression. AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid (FA) import into cell. METHODS A gene expression analysis of FASN , CD36 , SLC27A1 , SLC27A2 , SLC27A3 , SLC27A4 , SLC27A5 , ACSL1 , and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection. The genes were considered significantly dysregulated between the groups when the p value was < 0.05 and the fold change (FC) was ≤ 0.5 and ≥ 2. RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue: SLC27A2 (FC = 5.66; P = 0.033), SLC27A3 (FC = 2.68; P = 0.040), SLC27A4 (FC = 3.13; P = 0.033), ACSL1 (FC = 4.10; P < 0.001), and ACSL3 (FC = 2.67; P = 0.012). We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors, including the anatomic location, the lymph node involvement, and the presence of metastasis. A significant difference in the expression of SLC27A3 (FC = 3.28; P = 0.040) was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes. CONCLUSION Despite the low number of patients analyzed, these preliminary results seem to be promising. Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy. Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.

Aim Romania is currently facing a prolonged measles outbreak. The aim of the study was to analyse the circulating human measles virus (HMV) strains by combining whole genome sequencing (WGS) with phylogenetic analysis, with a focus on the haemagglutinin gene. Methods We conducted an observational study in the first five months of 2024, in which 168 patients diagnosed with measles were randomly included. We have evaluated the clinical and epidemiological differences between children and adults. Screening for samples to be sequenced was performed with a commercial kit (PrimerDesign). WGS was done on Illumina MiSeq platform and phylogenetic analysis was performed with ML FastTree. Results No significant epidemiological and clinical differences between patients in the two age groups were identified. WGS was successfully performed for a number of 124 HMV strains. Genotype analysis indicated all the sequences as D8, except one that was B3. Phylogenetic analysis identified two well supported clusters, suggestive for at least two local transmission networks in Romania. One large transmission network (n = 108) consisted of sequences both from adults and children. Only one sequence from outside Romania (reported in Russia in 2023) clustered within this group. Another small transmission cluster was identified (14 sequences of which 11 from patients infected in the spring of 2024 and three in 2022). A few differences between the two co-circulating viral variants/clusters were observed. The median duration of hospitalisation was 2 days longer for patients in smaller cluster compared to those in the larger one (p = 0.019). Furthermore, these two clusters presented different mutation profiles in the hemagglutinin (HA) and neuraminidase (N) genes with implications for molecular surveillance. Conclusion The current measles epidemic in Romania is driven mainly by two D8 genotype variants with different mutation profiles and slightly different severity of the disease, highlighting the usefulness of sustained molecular surveillance.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders. The percentage of CD2⁻, CD25⁺ and/or CD30⁺ MC was considerably lower in patients with indolent SM compared to patients with advanced SM, including aggressive SM and MC leukemia. Whereas CD25 and CD30 expression in MC could not be associated with prognosis, we found that lack of CD2 expression in MC is associated with a significantly reduced overall survival (OS) in patients with SM (p < 0.0001). Lack of CD2 was also associated with the presence of extramedullary involvement affecting the spleen, liver, and/or lymph nodes (odds ratio 2.63 compared to SM with CD2⁺ MC). Together, lack of CD2 expression in MC is a prognostic marker and indicator of reduced OS and extramedullary disease expansion in patients with SM.

Objective The aim of this analysis was to evaluate the relationship between the criteria met of the Minimal Disease Activity (MDA) score for psoriatic arthritis (PsA) and patient-perceived disease status. Methods We analysed data from the ReFlaP study ( NCT03119805 ), a cross-sectional international study of adult patients with PsA. Patients self-reported if they felt their PsA was in remission (REM), low disease activity (LDA) or neither. The relationship between patient-reported status and MDA domains met was analysed using point biserial correlation, chi-square test (Χ2), odds ratio, and specificity. Results 88.4% of study patients who met MDA reported good disease status (REM/LDA). Pain was the most commonly missed domain for these patients. A moderate to strong correlation was found between meeting more MDA domains and patient-reported good status irrespective of domain missed. On individual domain testing, MDA state and patient-reported REM/LDA were significantly associated irrespective of domain missed with the exception of enthesitis. Specificity of the MDA score irrespective of domain missed was above 90%. The odds of MDA patients reporting poor disease status was significant only for when pain < 1 was the unmet domain. This significance was not supported by sensitivity analysis. Conclusion This study suggests strong agreement between MDA status and patient-reported good status irrespective of domain missed. Pain < 1 or 2 on a 0-10 numerical rating scale was the hardest domain to meet. The high specificity regardless of the unmet domain suggests patients who feel their disease is active are minimally misclassified by the score.

INTRODUCTION Diagnostic performance of optical coherence tomography (OCT) to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains limited. We aimed to develop a deep‐learning algorithm using OCT to detect AD and MCI. METHODS We performed a cross‐sectional study involving 228 Asian participants (173 cases/55 controls) for model development and testing on 68 Asian (52 cases/16 controls) and 85 White (39 cases/46 controls) participants. Features from OCT were used to develop an ensemble trilateral deep‐learning model. RESULTS The trilateral model significantly outperformed single non‐deep learning models in Asian (area under the curve [AUC] = 0.91 vs. 0.71–0.72, p = 0.022‐0.032) and White (AUC = 0.84 vs. 0.58–0.75, p = 0.056‐ < 0.001) populations. However, its performance was comparable to that of the trilateral statistical model (AUCs similar, p > 0.05). DISCUSSION Both multimodal approaches, using deep learning or traditional statistical models, show promise for AD and MCI detection. The choice between these models may depend on computational resources, interpretability preferences, and clinical needs. Highlights A deep‐learning algorithm was developed to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) using OCT images. The combined model outperformed single OCT parameters in both Asian and White cohorts. The study demonstrates the potential of OCT‐based deep‐learning algorithms for AD and MCI detection.

Interhemispheric subdural hematoma (ISH) poses significant challenges in neurosurgical practice owing to its deep localization within the cerebral hemispheres. Despite the widespread adoption of advanced neurosurgical technologies, adverse patient outcomes hinder progress in enhancing overall prognosis. This review seeks to evaluate the etiology, clinical manifestations, treatment modalities, and outcomes associated with ISHs, thereby informing clinical decision-making and improving patient care. Databases such as PubMed, Scopus, and Google Scholar were systematically searched from 1964 to 2024. The search was limited to studies involving human subjects and published in English. Keywords such as "interhemispheric subdural hematoma" and "parafalcine subdural hematoma" were used in various combinations to identify relevant articles. Our search identified 167 individuals (87 females and 80 males) ranging in age from 6 weeks to 93 years. Trauma emerged as the leading risk factor, accounting for 86.8% of cases. Nausea and vomiting were the most frequent symptoms (14.7%), followed by headache (11.8%). Most patients (22.8%) had a Glasgow Coma Scale score of 13 to 16, indicating moderate severity. Radiological analysis showed that

The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA's blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

Background Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is a haematological malignancy which may occur in patients with textured breast implant history. While typically diagnosed at an early stage with good prognosis, it may present with local residual disease due to incomplete surgical excision. Case presentation We describe the case of a 42 year-old woman with a history of bilateral breast augmentation for cosmetic purposes 21 years prior, who developed recurring seroma of the left side. She sought help from her first surgeon who performed 2 breast implant exchange procedures placing textured devices and finally a bilateral breast implant removal over the course of two decades. The patient did not receive capsulectomies in the previous implant exchanges, and received sampling from the anterior capsule in the last procedure, where BIA-ALCL was diagnosed on the left side. She was referred to a tertiary cancer center where preoperative workup confirmed presence of local residual disease. Following multidisciplinary team management, she underwent revision of en-bloc capsulectomy of the left side without need for additional treatments. Post-operative course was uneventful with no signs of local recurrences at 18 months follow-up. Conclusion Residual disease in BIA-ALCL may be caused not only by tumor characteristics or extent, but also by misdiagnosis or late diagnosis. This case highlights the critical importance of thorough surgical excision in BIA-ALCL. The existence of guidelines and clinical practice recommendations direct surgeons on how to appropriately recognize and manage symptomatic patients in order to treat suspicious cases in a timely manner.

Introduction CPVT is a rare inherited channelopathy which predisposes patients to malignant ventricular arrhythmias during exercise or stress. Although exceptionally rare, the diagnosis can be made in individuals over 40 years. Case presentation A 58-year-old male with persistent atrial fibrillation was evaluated for exercise prescription. He was keen on low-intensity skill sports and medium-intensity endurance sports. He reported no symptoms and had no relevant family history. The ECG showed atrial fibrillation without other abnormalities. The transthoracic echocardiogram demonstrated severe left atrial dilatation but nothing else of note. The exercise test revealed a poorly controlled ventricular rate with effort, with frequent monomorphic PVC and a 4-beat NSVT. The CTCA and CMR excluded significant coronary artery disease or an underlying cardiomyopathy. The bisoprolol dose was increased, and the patient was advised to limit his training to moderate-intensity exercise. In the meantime, the patient’s 25-year-old daughter suffered a sudden cardiac arrest and was found to harbor a pathogenic RYR2 mutation, later identified in our patient through predictive genetic testing. The patient was reassessed considering the genetic result. An exercise test revealed bi-directional PVCs. He was switched on a non-selective beta-blocker. Specific exercise prescription and lifestyle changes were discussed. Conclusion Genetic testing in CPVT is crucial for diagnosis and prognosis of affected individuals, as well as for identifying family members at risk, even in the absence of a characteristic phenotype.

The use of biomaterials in treating and managing chronic wounds represents a significant challenge in global healthcare due to the complex nature of these wounds, which are slow to heal and can lead to complications such as frequent infections and diminished quality of life for patients. Chronic wounds, which can arise from conditions like diabetes, poor circulation, and pressure sores, pose distinct challenges in wound care, necessitating the development of specialized dressings. The pathophysiology of chronic wounds is thoroughly examined in this article, with particular attention paid to the cellular and molecular defects at work and the therapeutic guidelines. It also identifies key issues in the field, such as biocompatibility, cost-effectiveness, immune reactions, and regulatory obstacles, while suggesting future research focuses on improving biocompatibility, integrating drug delivery systems, and exploring cellular treatments. Ethical implications, such as patient safety, informed consent, and equitable access to technology, are also discussed. Finally, this review highlights the transformative potential of biomaterials in chronic wound management, urging for continued research and clinical integration to fully harness their capabilities in improving patient care.

Background: Bupropion, an atypical antidepressant and smoking cessation aid, is known for its potential to cause seizures, cardiotoxicity and neurotoxicity in overdose scenarios. However, overdoses may present variably, and muscular and renal complications, such as rhabdomyolysis and acute kidney injury (AKI), can emerge in unexpected ways. Previous reports have shown that severe overdoses can lead to a spectrum of complications, but the precise mechanisms linking bupropion overdose with rhabdomyolysis remain poorly understood. Clinical presentation: This paper presents the management of a severe rhabdomyolysis case following deliberate ingestion of 4 g of immediate-release bupropion. The report highlights the unexpected presentation of bupropion overdose, including a lack of typical neurotoxic or muscular symptoms, and the subsequent involvement of multiple factors in the decision to initiate early renal replacement therapy, despite the absence of overt acute kidney injury (AKI). Conclusions: This case underscores the importance of individualized patient assessment and the challenges of managing rare and complex drug overdoses. Early intervention with renal replacement therapy, despite the absence of acute kidney injury, may be justified in cases of significant rhabdomyolysis and potential renal complications. Clinicians should maintain a high degree of suspicion for complications like rhabdomyolysis in overdose scenarios and consider early renal support in patients at risk of renal failure, even in the absence of overt kidney injury. The findings also point to the need for a more nuanced approach to diagnosing and treating bupropion overdose in critically ill patients.

The management of multiple intracranial aneurysms presents significant clinical challenges, particularly when complicated by underlying conditions such as cerebral atherosclerosis. This case report highlights the successful treatment of a 66-year-old female diagnosed with three intracranial aneurysms located in the right middle cerebral artery (MCA), pericallosal artery, and M2 segment. The patient also had a history of systemic atherosclerosis and right-sided breast cancer, factors that increased the complexity of surgical intervention. The aim of this report is to demonstrate the efficacy of single-stage microsurgical clipping in managing multiple aneurysms with favorable outcomes in a complex patient profile. Methods: The patient underwent right-sided pterional craniotomy for microsurgical clipping of all three aneurysms during a single-stage procedure. Two aneurysms in the MCA were clipped using Yasargil clips, and a third aneurysm located at the bifurcation of the pericallosal artery was also secured with a clip. The procedure was performed under microscopic visualization, with meticulous dissection of the atherosclerotic vessels and careful intraoperative hemostasis. Postoperative care involved proactive perioperative management, including blood pressure control and vigilant neurological monitoring. Results: Postoperative imaging at three months confirmed proper clip placement with no evidence of residual aneurysm filling or ischemic complications. The patient exhibited a full neurological recovery, with no deficits or further complications, highlighting the effectiveness of the surgical approach in managing multiple aneurysms concurrently. Conclusions: This case supports the use of single-stage microsurgical clipping as an effective treatment for patients with multiple intracranial aneurysms, even in the presence of complicating factors such as atherosclerosis. A meticulous surgical technique and perioperative management are critical to achieving favorable outcomes and reducing the risk of delayed ischemia or other postoperative complications.

Background/Objectives: Despite its low incidence, complete postoperative abdominal evisceration represents a complication requiring an urgent solution. We aimed to present a rare case of an abdominal evisceration of the omentum and small-bowel loops after a total abdominal hysterectomy and review the literature regarding this condition’s diagnosis and therapeutic management. Case report: On the sixth postoperative day for a uterine fibroid, a 68-year-old patient presented with an abdominal evisceration of the omentum and small bowel that occurred two hours before. An emergency laparotomy was performed to correct the evisceration and restore the integrity of the abdominal wall structure. The literature review was carried out in the PubMed, Embase, and Web of Science databases using the terms “abdominal wall dehiscence”, “abdominal evisceration”, “open abdomen”, “burst abdomen”, “abdominal fascial dehiscence”, “abdominal dehiscence post-hysterectomy”, and “hysterectomy complications” by identifying all-time articles published in English. Results: Seven studies were included in this electronic search. The early diagnosis of abdominal evisceration, the identification of risk factors and comorbidities, followed by the choice of surgical technique, and postoperative follow-up were parts of the standard algorithm for managing this life-threatening case. Conclusions: Abdominal evisceration, as a surgical emergency, requires the diagnosis and treatment of this complication alongside the identification of the risk factors that can lead to its occurrence, as well as careful postoperative monitoring adapted to each case.

In several studies, hyperprolactinemia has been associated with increased breast cancer risk. Evidence shows that prolactin (PRL) is linked to mammary tumorigenesis, especially in postmenopausal patients, but the data remain controversial. We present a case of a 67 year-old patient with a resistant PRL-secreting PitNET who subsequently developed breast cancer. The patient was known to have persistent high PRL levels despite multimodal treatment (surgery, radiotherapy, and high doses of cabergoline). The tumor specimens obtained after transsphenoidal intervention were histologically and immunohistochemically examined for the following parameters: anterior pituitary hormones, the ki-67 labeling index, CAM 5.2 expression, ER ∝ expression, and somatostatin receptors, which revealed a densely granulated tumor with intense positivity for PRL and ER ∝ , a ki-67 labeling index of 6% and negative MGMT expression. Years later, the patient was diagnosed with breast carcinoma. Histopathological and immunohistochemical examination of the tumor specimen obtained after radical mastectomy confirmed ductal invasive breast cancer with negative immunostaining for prolactin receptors (PLRr) but positive immunostaining for estrogen (ER) and progesterone receptors (PGR) and a ki-67 labeling index of 8%. PRL is involved in mammary development and differentiation, which leads to lactation, the major driver during pregnancy, by regulating ovarian progesterone production. On the basis of the physiological actions of PRL, a role for this hormone in breast cancer has been suggested. Few cases of different types of breast carcinoma associated with hyperprolactinemia due to a pituitary tumor have been reported in the literature. The association between hyperprolactinemia and the risk of breast carcinoma is not well understood. Immunohistochemistry evaluation of PLRr can be helpful to provide information in these cases.

Introduction Chronic nausea and vomiting are symptoms of a wide range of gastrointestinal and non‐gastrointestinal conditions. Diagnosis can be challenging and requires a systematic and well‐structured approach. If the initial investigation for structural, toxic and metabolic disorders is negative, digestive motility and gut‐brain interaction disorders should be assessed. United European Gastroenterology (UEG) and the European Society for Neurogastroenterology and Motility (ESNM) identified the need for an updated, evidence‐based clinical guideline for the management of chronic nausea and vomiting. Methods A multidisciplinary team of experts in the field, including European specialists and national societies, participated in the development of the guideline. Relevant questions were addressed through a literature review and statements were developed and voted on according to a Delphi process. Results Ninety‐eight statements were identified and voted following the Delphi process. Overall agreement was high, although the grade of scientific evidence was low in many areas. Disagreement was more evident for some pharmacological treatment options. A diagnostic algorithm was developed, focussing on the differentiating features between gastrointestinal motility and gut‐brain interaction disorders with predominant nausea and vomiting. Conclusion These guidelines provide an evidence‐based framework for the evaluation and treatment of patients with chronic nausea and vomiting.