A Successful Treatment of Broncho-Esophageal Fistula with Esophageal Stenting Using Direct Endoscopic Visualization.

Broncho-esophageal fistula (BEF) is a severe yet relatively rare connection between the bronchus and esophagus usually caused by esophageal and pulmonary malignancies. We present a case report of a 49-year-old man diagnosed with terminal lung carcinoma who developed a BEF. The thoracic computed tomography scan detected a mass in the left bronchi that partially covers and disrupts the bronchial contour in certain regions and extends to the esophageal wall. After thoroughly evaluating alternative treatment approaches, we opt for the stenting procedure due to the advanced stage of the tumor and the significantly diminished quality of life. The treatment involves the use of a partially covered metal stent that is known to exhibit lower potential to migrate. The treatment is highly successful, resulting in a significant enhancement of the patient's quality of life, a lengthening in his survival, and the ability to pursue additional palliative treatment options. In contrast to the typical prosthesis implantation, our procedure uses a direct endoscopic visualization for the proximal deployment of a partially covered stent, offering a cost-effective and radiation-free alternative that can be particularly beneficial for BEF patients in facilities without radiology services.

Recent Updates Regarding the Antiproliferative Activity of Galium verum Extracts on A375 Human Malignant Melanoma Cell Line.

The biological activity of Galium verum herba was exerted on various tumor cell lines with incredible results, but their potential effect on malignant melanoma has not been established yet. Therefore, the current study was structured in two directions: (i) the investigation of the phytochemical profile of diethyl ether (GvDEE) and butanol (GvBuOH) extracts of G. verum L. and (ii) the evaluation of their biological profile on A375 human malignant melanoma cell line. The GvDEE extract showed an FT-IR profile different from the butanol one, with high antioxidant capacity (EC50 of GvDEE = 0.12 ± 0.03 mg/mL > EC50 of GvBuOH = 0.18 ± 0.05 mg/mL). The GvDEE extract also showed antimicrobial potential, especially against Gram-positive bacteria strains, compared to the butanol extract, which has no antimicrobial activity against any bacterial strain tested. The results regarding the antitumor potential showed that both extracts decreased A375 cell viability largely (69% at a dose of 55 µg/mL of the GvDEE extract). Moreover, both extracts induce nuclear fragmentation by forming apoptotic bodies and slight chromatin condensation, which is more intense for GvDEE. Considering the results, one can state that the Galium verum herba possesses antitumor effects on the A375 human malignant melanoma cell line, a promising phytocompound for the antitumor approach to skin cancer.

Preclinical Studies of Canagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, and Donepezil Combined Therapy in Alzheimer's Disease.

The incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), is continuously growing worldwide, which leads to a heavy economic and societal burden. The lack of a safe and effective causal therapy in cognitive decline is an aggravating factor and requires investigations into the repurposing of commonly used drugs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new and efficient class of hypoglycemic drugs and, due to their pleiotropic effects, have indications that go beyond diabetes. There is emerging data from murine studies that SGLT2i can cross the blood-brain barrier and may have neuroprotective effects, such as increasing the brain-derived neurotrophic factor (BDNF), reducing the amyloid burden, inhibiting acetylcholinesterase (AChE) and restoring the circadian rhythm in the mammalian target of rapamycin (mTOR) activation. The current study investigates the effect of an SGLT2i and donepezil, under a separate or combined 21-day treatment on AD-relevant behaviors and brain pathology in mice. The SGLT2i canagliflozin was found to significantly improve the novelty preference index and the percentage of time spent in the open arms of the maze in the novel object recognition and elevated plus maze test, respectively. In addition, canagliflozin therapy decreased AChE activity, mTOR and glial fibrillary acidic protein expression. The results also recorded the acetylcholine M1 receptor in canagliflozin-treated mice compared to the scopolamine group. In the hippocampus, the SGLT2i canagliflozin reduced the microgliosis and astrogliosis in males, but not in female mice. These findings emphasize the value of SGLT2i in clinical practice. By inhibiting AChE activity, canagliflozin represents a compound that resembles AD-registered therapies in this respect, supporting the need for further evaluation in dementia clinical trials.

Cystic Echinococcosis in Hospitalized Adult Patients from Western Romania: 2007-2022.

Cystic echinococcosis (CE) is a neglected parasitic disease caused by the tapeworm Echinococcus granulosus. The aim of this study was to assess the epidemiological features of human cystic echinococcosis in patients from Western Romania. We retrospectively investigated the medical records of patients hospitalized with CE between 1 January 2007 and 1 September 2022. A total of 366 patients (range 18-90 years) were recorded. The number of hospitalized individuals was higher in patients aged 50-59 years (83/366, 22.7%), in females (194/366, 53%), and in residents of rural areas (225/366, 61.5%). The liver was the most common localization of the cysts (302/366, 82.5%). Ninety-eight patients (26.8%) presented complications, including biliary fistula, allergies, and infection of the cyst. Patients with complications had a longer mean hospital stay (15.7 ± 8.3 days) compared to patients without complications (11.5 ± 7.3 days) (p < 0.001). The results of this study revealed that patients diagnosed with CE required hospitalization and extended medical care, indicating that this zoonotic disease remains a significant public health problem in Western Romania. Public health authorities should enhance CE surveillance by implementing control programs and mandatory notification of new cases.

Challenges of Pharyngeal Cancer Screening in Lower-Income Countries during Economic and Social Transitions: A Population-Based Analysis.

Background and Objectives: The rate of head and neck cancer (HNC) is expected to increase by 30% by 2030. However, there are many similarities between the symptomatology of a benign and a malign diagnosis; thus, a protocol for conducting a full head and neck examination is of high importance since the absence of adenopathy does not exclude a malignant diagnosis and also a favorable prognosis. Material and methods: The current study presents a retrospective study on 515 adult patients who underwent a biopsy for possible head and neck tumor pathology. Results: The patients identified with cancer were older than the rest of the group, with a higher developing trend in men than in women. However, the top 10 symptomatology patterns were identical in the malign and benign groups, meaning that new HNC may be missed due to the common symptomatology between benign and malign outcomes. Conclusions: The importance of a full ear, nose, and throat (ENT) examination may be of significant relevance for a proper diagnosis that can improve the overall prognosis of a patient with cancer. The absence of routine screening tests and screening guidelines for oral and pharyngeal cancers represents a significant barrier to secondary HNC prevention.

Experimental Models for Rare Melanoma Research-The Niche That Needs to Be Addressed.

Melanoma, the tumor arising from the malignant transformation of pigment-producing cells-the melanocytes-represents one of the most severe cancer types. Despite their rarity compared to cutaneous melanoma, the extracutaneous subtypes such as uveal melanoma (UM), acral lentiginous melanoma (ALM), and mucosal melanoma (MM) stand out due to their increased aggressiveness and mortality rate, demanding continuous research to elucidate their specific pathological features and develop efficient therapies. Driven by the emerging progresses made in the preclinical modeling of melanoma, the current paper covers the most relevant in vitro, in vivo, and in ovo systems, providing a deeper understanding of these rare melanoma subtypes. However, the preclinical models for UM, ALM, and MM that were developed so far remain scarce, and none of them is able to completely simulate the complexity that is characteristic to these melanomas; thus, a continuous expansion of the existing library of experimental models is pivotal for driving advancements in this research field. An overview of the applicability of precision medicine in the management of rare melanoma subtypes is also provided.

Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity.

Recently, research has greatly expanded the knowledge of the endocannabinoid system (ECS) and its involvement in several therapeutic applications. Cannabinoid receptors (CBRs) are present in nearly every mammalian tissue, performing a vital role in different physiological processes (neuronal development, immune modulation, energy homeostasis). The ECS has an essential role in metabolic control and lipid signaling, making it a potential target for managing conditions such as obesity and diabetes. Its malfunction is closely linked to these pathological conditions. Additionally, the immunomodulatory function of the ECS presents a promising avenue for developing new treatments for various types of acute and chronic inflammatory conditions. Preclinical investigations using peripherally restricted CBR antagonists that do not cross the BBB have shown promise for the treatment of obesity and metabolic diseases, highlighting the importance of continuing efforts to discover novel molecules with superior safety profiles. The purpose of this review is to examine the roles of CB1R and CB2Rs, as well as their antagonists, in relation to the above-mentioned disorders.

UVA/UVB Irradiation Exerts a Distinct Phototoxic Effect on Human Keratinocytes Compared to Human Malignant Melanoma Cells.

Solar ultraviolet radiation (UVR) is responsible for the development of many skin diseases, including malignant melanoma (MM). This study assessed the phototoxic effects of UVA, and UVB radiations on healthy and pathologic skin cells by evaluating the behavior of human keratinocytes (HaCaT) and MM cells (A375) at 24 h post-irradiation. The main results showed that UVA 10 J/cm2 exerted no cytotoxicity on HaCaT and A375 cells, while UVB 0.5 J/cm2 significantly reduced cell viability and confluence, induced cell shrinkage and rounding, generated nuclear and F-actin condensation, and induced apoptosis by modulating the expressions of Bax and Bcl-2. The association of UVA 10 J/cm2 with UVB 0.5 J/cm2 (UVA/UVB) induced the highest cytotoxicity in both cell lines (viability < 40%). However, the morphological changes were different-HaCaT cells showed signs of necrosis, while in A375 nuclear polarization and expulsion from the cells were observed, features that indicate enucleation. By unraveling the impact of different UVR treatments on the behavior of normal and cancer skin cells and describing enucleation as a novel process involved in the cytotoxicity of UVA/UVB irradiation, these findings bridge the gap between the current and the future status of research in the field.

18F-FDG PET/MRI Imaging in a Preclinical Rat Model of Cardiorenal Syndrome-An Exploratory Study.

Cardiorenal syndrome (CRS) denotes the bidirectional interaction of chronic kidney disease and heart failure with an adverse prognosis but with a limited understanding of its pathogenesis. This study correlates biochemical blood markers, histopathological and immunohistochemistry features, and 2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) metabolic data in low-dose doxorubicin-induced heart failure, cardiorenal syndrome, and renocardiac syndrome induced on Wistar male rats. To our knowledge, this is the first study that investigates the underlying mechanisms for CRS progression in rats using 18F-FDG PET. Clinical, metabolic cage monitoring, biochemistry, histopathology, and immunohistochemistry combined with PET/MRI (magnetic resonance imaging) data acquisition at distinct points in the disease progression were employed for this study in order to elucidate the available evidence of organ crosstalk between the heart and kidneys. In our CRS model, we found that chronic treatment with low-dose doxorubicin followed by acute 5/6 nephrectomy incurred the highest mortality among the study groups, while the model for renocardiac syndrome resulted in moderate-to-high mortality. 18F-FDG PET imaging evidenced the doxorubicin cardiotoxicity with vascular alterations, normal kidney development damage, and impaired function. Given the fact that standard clinical markers were insensitive to early renal injury, we believe that the decreasing values of the 18F-FDG PET-derived renal marker across the groups and, compared with their age-matched controls, along with the uniform distribution seen in healthy developing rats, could have a potential diagnostic and prognostic yield in cardiorenal syndrome.

A rare encounter with two cases of Budd­Chiari syndrome in the Emergency Department: A case report.

Budd-Chiari syndrome (BCS) is a rare disorder clinically characterized by abdominal pain, hepatomegaly and ascites. The condition is often related to thrombosis of the hepatic veins or the terminal portion of the inferior vena cava. A myeloproliferative disorder is the most identified underlying prothrombotic risk factor, although almost one-half of affected patients are now recognized as having multiple underlying prothrombotic risk factors. Doppler ultrasound may be enough to confirm the diagnosis of BCS; however, computed tomography or magnetic resonance imaging is often employed. Anticoagulant therapy is the cornerstone of BCS treatment, but most patients also need additional treatment strategies. Most patients with BCS are now treated by endovascular intervention, which has improved survival rate in those afflicted by this disease. The long-term course of the disease can be complicated by progression or recurrence of the underlying myeloproliferative disorder. The present study reports the cases of two patients with BCS with the aim of alerting healthcare workers in Emergency Departments of this less common diagnosis in patients presenting with frequent complaints of abdominal pain.

True Brachial Artery Aneurysm in Patients with Previous Arterio-Venous Fistula Ligation and Immunosuppressant Therapy for Renal Transplantation: Case Report and Literature Review.

BACKGROUND/OBJECTIVE: Brachial artery aneurysm (BAA) is a serious complication in patients with previous arterio-venous fistula (AVF), renal transplantation (RT), and immunosuppressive regimens. Until now, there has been no standard of care for these patients, especially for patients undergoing chronic dialysis and immunosuppressive treatment. The aim of this study was to investigate data from the literature regarding these patients and to suggest recommendations for the best approach to their treatment. METHODS: A review of the literature was performed by searching the PubMed database in the English language. The review was accompanied by two case reports. A total of 24 articles with different variables-demographics, renal transplantation, aneurysm size, and type of surgery-were subjected to the review. In addition, two cases are reported. CONCLUSION: This review suggests that the best treatment for these patients is open surgery, with aneurysmectomy and graft interposition. RESULTS: All patients had RT. The age of patients ranged from 26-77 yo, with a male predominance. The majority had an AVF ligated after RT. The main clinical symptoms were pain, swelling, and pulsatile mass (66%). All patients, except one, were treated through open surgery. The first option for treatment was reversed saphenous vein graft interposition (36%), followed by ePTFE graft (16%).

Eugenol Induces Apoptosis in Tongue Squamous Carcinoma Cells by Mediating the Expression of Bcl-2 Family.

Head and neck squamous cell carcinoma is highly aggressive type of cancer for which the available treatment often causes patients severe side effects. Eugenol (Eug) is the major active constituent of clove essential oil and is known to possess antitumor properties. The present study aimed to assess the in vitro cytotoxicity of eugenol in SCC-4, tongue squamous carcinoma cells, and also in HGF, human gingival fibroblasts. Both cell lines were treated with five concentrations of Eug (0.1-1 mM) for 72 h. Cellular viability was assessed, followed by cellular morphological evaluation and by staining of the nuclei and cytoskeleton. RT-PCR was conducted in order to find the effect eugenol had on the expression on Bad, Bax, and Bcl-2 genes. Eugenol induced a dose-dependent decrease in viability in both cell lines, with the SCC-4 cells being significantly more affected. HGF cells detached from the plate at the highest concentrations used, while SCC-4 cells changed their morphology in a dose-dependent manner, with rounding, floating cells, and confluency loss being observed. Apoptotic-like signs such as chromatin and actin filaments condensation were clearly seen in SCC-4 cells, while RT-PCR revealed a significantly increased expression of pro-apoptotic genes Bax and Bad. Therefore, eugenol exerts its cytotoxic effect in tongue squamous cell carcinoma through inducing apoptosis.

Relevance of Surface Neuronal Protein Autoantibodies as Biomarkers in Seizure-Associated Disorders.

The detection of neuronal surface protein autoantibody-related disorders has contributed to several changes in our understanding of central nervous system autoimmunity. The clinical presentation of these disorders may be associated (or not) with tumors, and often patients develop an inexplicable onset of epilepsy, catatonic or autistic features, or memory and cognitive dysfunctions. The autoantigens in such cases have critical roles in synaptic transmission and plasticity, memory function, and process learning. For months, patients with such antibodies may be comatose or encephalopathic and yet completely recover with palliative care and immunotherapies. This paper reviews several targets of neuronal antibodies as biomarkers in seizure disorders, focusing mainly on autoantibodies, which target the extracellular domains of membrane proteins, namely leucine-rich glioma-inactivated-1 (LGI1), contactin-associated protein-like 2 (CASPR2), the N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid receptor-B (GABABR), the glycine receptor (GlyR), and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). In order to restore health status, limit hospitalization, and optimize results, testing these antibodies should be done locally, using internationally certified procedures for a precise and rapid diagnosis, with the possibility of initiating therapy as soon as possible.

Alzheimer's Disease Pharmacotherapy in Relation to Cholinergic System Involvement.

Alzheimer's disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer's disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer's disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer's disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.

The utility of indirect imagistic signs in the diagnosis of anterior cruciate ligament ruptures.

We conducted a retrospective study, between 2013 and 2018. The study was conducted by analyzing the comparative imaging of two groups of patients. The two groups comprise 42 patients, 14 women and 28 men aged between 17 and 70 years old, to whom objective variables of statistical relevance were tracked. The results of this study show that there is a significant correlation between an angle value of less than 45° and the rupture of the anterior crossed ligament.

The Use of Circulating miRNAs as Biomarkers for Oxidative Stress in Critically Ill Polytrauma Patients.

BACKGROUND: The diversity of primary and secondary traumatic injuries specific for the critically ill polytrauma patient is complicating the therapeutic management in the absence of a strict assessment of the biological changes. Inflammation, redox imbalance, and immunosuppression can be quantified by various biochemical parameters; however, they do not fully respond to the current requirements. Another phenomenon responsible for worsening the clinical status and for the development of complications in such patients is oxidative stress. Its aggressiveness combined with biochemical and physiological imbalances leads to increased morbidity and mortality. To minimize the effects induced by free radicals, various substances are administered with high antioxidant capacity. However, the dosage optimization for each patient is difficult without strict monitoring of oxidative stress. In this paper we will summarize and present the pathophysiology of oxidative stress, as well as the specificity of miRNAs for a series of molecular changes at the cellular level. METHODS: For this study the available literature on specific databases such as PubMed, Embase and Scopus was thoroughly analyzed. Each article has been carefully reviewed, extracting useful information for this study. The keywords used to select the relevant articles were "oxidative stress", "antioxidant therapy", "microRNAs biomarkers", and "critically ill patients". RESULTS: For this study, 121 scientific articles relevant to our topic were analyzed. Currently, quantification of oxidative stress is achieved through indirect correlations with plasma levels of specific biomarkers. For a more specific evaluation of the redox status, numerous studies were conducted on the use of circulating miRNAs as biomarkers in this regard. CONCLUSIONS: Introducing miRNAs can revolutionize both monitoring and therapy modulation in these patients, adapting to the organic damage.