Search Results (2,597)

This study was designed to investigate the immunostimulatory and anticancer efficacies of pectic polysaccharides from ginseng leaves treated using the high-pressure extraction method (HPEM). The isolation of polysaccharides using HPEM resulted in 1.35-fold higher polysaccharide yields than those obtained using the commonly used hot water extraction method. In addition, component sugar analysis of ginseng-leaf-derived polysaccharides (GLHP) showed the presence of nine different types of monosaccharides, including galacturonic acid, galactose, rhamnose, and arabinose, which are characteristic of pectic polysaccharides. In addition, GLHP effectively induced activation of the complement system, and macrophages stimulated with GLHP showed enhanced production of cytokines such as IL-6, IL-12, and TNF-α. Intravenous (i.v.) and oral administration (p.o.) of GLHP significantly increased the cancer-cell-killing ability of spleen-derived NK cells. In a lung-cancer-bearing mouse model using Colon26-M3.1 carcinoma, prophylactic i.v. and p.o. GLHP potently inhibited 95.2% and 33.5% of lung cancer, respectively. Furthermore, GLHP showed significant anticancer effects, even in mice with NK cell dysfunction, via the anti-asialo GM1 antibody. These effects may be related to the cancer-cell-killing effects of cytotoxic T lymphocytes (CTL). Therefore, GLHP, a polysaccharide isolated from ginseng leaves using HPEM, has a potent anticancer effect, and these effects are closely related to the stimulation of various immune factors. Full article

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) characterized by complement dysregulation, leading to microvascular thrombosis and multi-organ injury. TMAs are defined by thrombocytopenia, microangiopathic hemolytic anemia and organ dysfunction caused by small-vessel thrombosis. Unlike thrombotic thrombocytopenic purpura, which results from severe ADAMTS13 deficiency, aHUS is driven by uncontrolled activation of the alternative complement pathway. While the kidneys are most frequently affected, other vital organs can also be involved. Genetic susceptibility contributes significantly to disease risk, but a trigger such as infection, pregnancy or autoimmune disease is usually required. Diagnosis is challenging due to overlapping features with other TMAs and relies on exclusion and complement testing. C5 inhibitors, such as eculizumab and ravulizumab, have revolutionized treatment but necessitate prophylactic vaccination and ongoing clinical surveillance. While these therapies provide effective disease control, discontinuing treatment remains complex, especially in patients with complement gene mutations. New therapies targeting various points in the complement cascade are under investigation and may offer safer, more cost-effective options. Progress in genetic profiling and biomarker discovery is essential for earlier diagnosis, individualized therapy and relapse prevention. This review highlights recent advances in the understanding of aHUS pathophysiology, clinical features and evolving therapeutic strategies aimed at improving patient outcomes. Full article

Background/Objectives: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a recently discovered autosomal dominant transmission disease. Patients with this condition have a higher risk of developing gastric cancer. There are numerous questions regarding the natural history of this condition, as well as concerning the diagnostic and therapeutic management of these patients. In this systematic review, we aimed to examine the current literature to determine the role of prophylactic gastrectomy in patients diagnosed with gastric adenocarcinoma and proximal polyposis of the stomach. Additional outcomes are Helicobacter pylori (HP) infection, treatment with proton pump inhibitors (PPI), and colonoscopic examination and abdominal imaging examination, as they are important factors in the therapeutic decision. Methods: We performed a systematic review of the articles published in PubMed and Google Scholar, according to the PRISMA 2020 criteria. Results: We obtained 24 studies that included 83 patients diagnosed with GAPPS, of which 42 underwent prophylactic gastrectomy, 24 benefited from endoscopic follow-up, and 17 were diagnosed with gastric cancer at the first gastroscopic examination. In the prophylactic gastrectomy specimens, malignant gastric disease was confirmed in 10% of cases. GAPPS has been diagnosed more frequently in women. Conclusions: So far, the specialized literature includes a limited number of patients diagnosed with GAPPS. There are also no guidelines yet for the diagnosis and treatment of these patients. Prophylactic gastrectomy or endoscopic surveillance are the only options for patients diagnosed with GAPPS without gastric cancer at the initial examination. For prophylactic gastrectomy, the robotic and laparoscopic approach was preferred. For establishing appropriate lymphadenectomy in prophylactic gastrectomy, future research on gastrectomy specimens is necessary. Most of the included studies were deficient in terms of postoperative follow-up of patients. Thus, we consider it useful to include these patients in a single database. For a comprehensive examination of these and making an appropriate therapeutic decision, we consider it necessary to perform a colonoscopic evaluation, take abdominal imaging, and determine the Helicobacter pylori infection status. Full article

Background/Objectives: Obstetric patients undergoing elective cesarean section (CS) with combined spinal–epidural (CSE) anesthesia often experience intraoperative nausea and vomiting (N&V). While prophylactic treatment with antiemetic drugs can be effective, it may also carry potential adverse effects for both the mother and the baby. To address this, we designed a randomized clinical trial to assess the effectiveness of transdermal scopolamine patches and electrical P6 stimulation as preventive measures for N&V in patients scheduled for elective CS under CSE anesthesia. Methods: Following the Institutional Review Board approval and informed consent, a total of 240 patients were randomly allocated into three groups: (1) transdermal scopolamine, (2) P6 stimulation (via a peripheral nerve stimulator), and (3) combined transdermal scopolamine and P6 stimulation, with 80 parturients in each group. The primary outcome was defined as the presence or absence of intraoperative nausea and vomiting during the procedure. Results: The incidences of intraoperative nausea and vomiting were similar across all three treatment groups, with no significant differences observed at any point during the surgery. Additionally, there were no notable differences in overall satisfaction with anesthetic care among the three study groups. Conclusions: These findings indicate that while both transcutaneous P6 acupoint stimulation and transdermal scopolamine are straightforward, safe, and effective methods, combining these two antiemetic strategies does not offer additional benefits in reducing nausea and vomiting. Nevertheless, both approaches may be particularly appealing to patients and obstetric anesthesiologists who prioritize treatments with fewer potential side effects. Full article

Background: Teclistamab (TEC) is the first B-cell maturation antigen-directed bispecific antibody approved in 2022 by the European Medicines Agency and Food and Drug Administration for triple-class exposed relapsed/refractory multiple myeloma (RRMM). Objectives: As TEC is increasingly used in real-world (RW) settings, this study seeks to gather existing RW evidence on effectiveness, safety, healthcare resource utilization, and clinical practices associated with TEC. Methods: A systematic literature review was performed to identify RW observational studies of TEC-treated adults with RRMM from 2023 to June 2024. Results: Sixty-one records representing 41 unique studies were included; sample sizes ranged from 8 to 572 patients. Where reported, median follow-up ranged from 2.3 to 33.6 months, and >65% of the patients would have been ineligible for the pivotal trial of TEC (MajesTEC-1) in all but one study. In eight studies with ≥50 patients and ≥3 months follow-up, overall response rates were 59–66% and cytokine release syndrome (CRS) rates were 18–64%. Tocilizumab use for CRS management was reported in 14 studies, with two indicating CRS rates of 13% and 26% when used prophylactically. Survival and infection outcomes showed wide variability due to short follow-up in most studies. Conclusions: Overall, early RW effectiveness and safety outcomes of TEC were comparable to findings from MajesTEC-1. Full article

Despite the existence of therapeutic and prophylactic measures, gastrointestinal parasites are common in pets. Due to the zoonotic potential of some species, parasitic protozoa and helminths are of great importance to public health. In this study, we investigated the occurrence of the main gastrointestinal parasites in domestic dog puppies in the city of Araçatuba, São Paulo, Brazil. One hundred fecal samples were collected from dogs up to six months of age. Parasites were diagnosed using Willis’, Faust’s and malachite green coproparasitological techniques. Parasite prevalence as determined by Willis and/or Faust diagnostic techniques was as follows: Toxocara spp. 34%, Cystoisospora spp. 28%, Ancylostomatidae 22% and Giardia spp. 8%. These prevalence rates were calculated by considering an animal to be positive if Willis’ or Faust’s or both tests returned a positive result. Cryptosporidium diagnosis with malachite green was negative for all samples. Infection with Toxocara spp., the most prevalent pathogen in this survey, was not limited to dogs with abnormal fecal consistency. The occurrence of asymptomatic parasitized dogs increases the risk of zoonotic transmission. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse event with unclear mechanisms and limited treatment alternatives. This study aimed to investigate the efficacy of two alkalizing agents, a mixture of potassium citrate and sodium citrate (K/Na citrate) or sodium bicarbonate (NaHCO₃), in preventing and treating paclitaxel (PTX)-induced mechanical allodynia in rodents. The results from rodent models demonstrated that repeated prophylactic administration of K/Na citrate or NaHCO₃ could inhibit the development of PTX-induced mechanical allodynia. Moreover, K/Na citrate was effective in preventing the PTX-induced exacerbation of mechanical allodynia, even when treatment was initiated immediately after the onset of allodynia. K/Na citrate also reduced the levels of the plasma complement component anaphylatoxin C3a in a PTX-induced CIPN rat model. Complement activation, resulting in the production of C3a, has been implicated in the pathogenesis of this model. Additionally, pretreatment with Na citrate significantly prevented the reduction in neurite outgrowth caused by PTX. Furthermore, K/Na citrate inhibited spontaneous and mechanical stimuli-induced firing in spinal dorsal horn neurons. These findings indicate that K/Na citrate may regulate the development of PTX-induced mechanical allodynia by modulating complement activation and providing neuroprotection against PTX-induced peripheral nerve injury. This study implies that alkalization could help prevent PTX-induced peripheral neuropathy and mitigate its exacerbation. Full article

Spontaneous bacterial peritonitis (SBP) is the most common bacterial infection in cirrhotic patients. Historically, the bacterial spectrum was dominated by Gram-negative bacteria. However, recent studies showed that fluoroquinolone (FQ)-based prophylaxis promotes the intestinal overgrowth of Gram-positive bacteria and contributes to the selection of quinolone-resistant Gram-negative bacteria, increasing multidrug-resistant (MDR) organism infections. FQ resistance rates reach up to nearly one-third in community-acquired cases and 50% in hospital-acquired cases, raising concerns about FQ efficacy. Moreover, rare but serious side effects further limit FQ use. Predictive factors of FQ treatment failure have been identified, guiding management strategies. Rifaximin has emerged as a promising alternative for SBP prophylaxis, with encouraging results. This review aims to explore the shifting role of FQ-based SBP prophylaxis, focusing on the emerging concerns, side effects, and alternative strategies. While norfloxacin remains a first-line prophylactic in cirrhotic patients with low ascitic protein levels, its efficacy appears to be reduced in those with advanced liver failure or additional risk factors for MDR organisms. In these subgroups, alternative prophylactics, such as trimethoprim–sulfamethoxazole or rifaximin, may be preferable. We propose a risk-stratification approach to guide treatment selection, with further studies needed to refine these criteria. Full article

Background: Oxidative stress, inflammation, and endothelial dysfunction are important processes in the progression of atherosclerosis and the occurrence of acute coronary syndromes (ACSs). Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are present in marine organisms and have the capacity to reduce all these processes and, at the same time, the progression of atherosclerosis and the emergence of ACSs. Aim: To evaluate the role of Omega-3 PUFAs therapy on parameters of oxidative stress, inflammatory syndrome, endothelial dysfunction, and long-term prognosis in acute coronary syndromes. Methods: One thousand one hundred forty patients were admitted to Clinic County Emergency Hospital Brasov with ACS and were enrolled in a prospective study. The study was divided into four groups related to the type of ACS and treatment with Omega-3 PUFAs added to the optimal medical therapy (OMT). The effect of Omega-3 PUFAs therapy associated with the OMT was determined by measuring the dynamics of the following parameters: (a) oxidative stress—total antioxidant status (TAS), oxidated low density lipoprotein cholesterol antibodies (Ab anti-ox-LDL), IgG anti-Myeloperoxidase antibodies (IgG type Ab anti-MPO); (b) inflammatory syndrome—C-reactive protein and fibrinogen; (c) endothelial dysfunction—flow mediated dilation (FMD) and von Willebrand factor (vWf) activity, from baseline to 6 months of follow-up. Clinical events followed at 5 years were cardiovascular and sudden death, Non-ST and ST segment elevation ACS, in stent thrombosis and restenosis, stroke, readmission in hospital for ACS and for heart failure. Results: In ACS groups, treatment with Omega-3 PUFAs added to the OMT significantly decreased the parameters of oxidative stress, inflammatory syndrome, and endothelial dysfunction at 6 months of follow-up. Regarding the clinical events, a significant reduction in the risk of cardiovascular and sudden death and a decreased incidence of Non-ST and ST segment elevation ACS, in-stent restenosis, readmission for ACS and heart failure, was observed in Omega-3 PUFA-treated groups in comparison to control groups. Conclusions: In acute coronary syndromes, therapy with Omega-3 PUFAs added to the OMT resulted in a significant decrease of parameters of oxidative stress, inflammation, and endothelial dysfunction at 6 months and also a significant improvement in the long-term prognosis. Full article

The mRNA- and DNA-based “genetic” COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on the timing and data analysis methods used. Focusing only on lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces the evolution of statistical conclusions on the prevalence of AEs and incidents associated with these vaccines, from initial underestimation of atypical, severe toxicities to recent claims suggesting the possible contribution of COVID-19 vaccinations to the excess deaths observed in many countries over the past few years. Among hundreds of different AEs listed in Pfizer’s pharmacovigilance survey, the present analysis categorizes the main symptoms according to organ systems, with nearly all of them being affected. Using data from the US Vaccine Adverse Event Reporting System and a global vaccination dataset, a comparison of the prevalence and incidence rates of AEs induced by genetic versus flu vaccines revealed an average 26-fold increase in AEs with the use of genetic vaccines. The difference is especially pronounced in the case of severe ‘Brighton-listed’ AEs, which are also observed in COVID-19 and post-COVID conditions. Among these, the increases in incidence rates relative to flu vaccines, given as x-fold rises, were 1152x, 455x, 226x, 218x, 162x, 152x, and 131x for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, and hypertension, respectively. The review delineates the concept that genetic vaccines can be regarded as prophylactic immuno-gene therapies and that the observed chronic disabling AEs might be categorized as iatrogenic orphan diseases. It also examines the unique vaccine characteristics that could be causally related to abnormal immune responses which potentially lead to adverse events and complications. These new insights may contribute to improving the safety of this platform technology and assessing the risk/benefit balance of various products. Full article

In pediatric dentistry, antibiotics are currently prescribed for both therapeutic and prophylactic purposes. Antibiotic therapy can be prescribed for the treatment of diffuse dental or oral cavity infections, always as a complement to the most suitable dental procedure for the specific case. The aim of this study was to investigate the knowledge regarding the use and prescribing practices of antibiotics in pediatric patients in a sample of Italian dentists by using an anonymous and telematic questionnaire. Methods: A specially prepared questionnaire was electronically transmitted to a cohort of Italian dentists. The questionnaire consisted of two parts: demographic information and general knowledge of antibiotic prescription in pediatric dentistry. The statistical analysis of the obtained data was performed. Results: The study sample consisted of 242 Italian dentists. Poor statistically significant differences emerged between specialists in Pediatric Dentistry and dentists without specialization or specialists in other branches, as well as between dentists who, in their clinical activity, mainly treat children/adolescents or adults. For the complementary treatment of dental or oral cavity infections, Amoxicillin was the antibiotic indicated as the first choice for pediatric patients with no allergy to penicillins by most of the sample, while more than 20% of dentists would prescribe Clindamycin in patients with an allergy to penicillin. The knowledge regarding the dosage of administration of the chosen antibiotic appeared not to be sufficient. Conclusions: An improvement in the knowledge of the Guidelines in Pediatric Dentistry appeared necessary regarding the posology of the antibiotic of choice. More information about the adverse effects of Clindamycin is needed. Full article

Introduction: Bronchopulmonary Neuroendocrine Neoplasms (NEN) occur in 2–7% of patients with multiple endocrine neoplasia type 1 (MEN1). Precursor lesions have been identified for MEN1-related pancreatic, duodenal, and gastric NEN. The aim of the current study using a MEN1 mouse model was to define the precursor lesions of bronchopulmonary NEN and evaluate the potential prophylactic antitumor effects of somatostatin analogues in a transgenic MEN1 mouse model. Methods: Fifteen mice, germline heterozygous for Men1(+/T), were treated with subcutaneous injections of lanreotide autogel (Somatuline Autogel^®, IPSEN Pharma), while 15 mice were treated with subcutaneous injections of physiologic sodium chloride as the control group. Five mice from each group were euthanized after 12, 15, and 18 months, respectively. The complete lungs were resected and evaluated after hematoxylin and eosin staining and immunohistochemistry for synaptophysin and chromogranin A. Results: In the lungs of the 30 evaluated mice, whether treated or placebo treated, no bronchopulmonary neuroendocrine cell hyperplasia nor neuroendocrine neoplasia was detected through histopathology. However, pulmonary adenocarcinoma developed in 2 (13%) of the 15 untreated mice and in 1 (7%) of the 15 lanreotide-treated mice. Conclusions: Heterozygous Men1(+/T) knockout mice do not develop bronchopulmonary NEN or precursor lesions, but pulmonary adenocarcinoma. This surprising result needs to be investigated in more detail. Full article

Background: GATA2-related myelodysplastic syndrome (GATA2-MDS) is a unique predisposition syndrome with a high risk of leukemic transformation. This systematic review synthesizes current literature and presents two illustrative pediatric GATA2-MDS cases. Methods: Data retrieval from eight cohort and case–control studies provides comprehensive analysis on disease features, diagnostic complexities, management, and outcomes related to hematopoietic stem cell transplantation (HSCT) in GATA2-related myeloid malignancies. Additionally, two pediatric cases are included to exemplify clinical and therapeutic challenges in real-world setting. Results: The literature data demonstrates high incidence of monosomy 7, and recurrent infections as the most common clinical feature, followed by immunodeficiency and lymphedema. Prognosis clearly worsens with age and HSCT remains the only curative treatment. GATA2 patients undergoing HSCT experience high rates of graft versus host disease (GvHD) as well as unique neurological, thrombotic, and infectious complications. Transplant-related mortality (TRM) is linked to GvHD and infections. Post-transplant cyclophosphamide (PT/Cy) strategies seem to improve survival by reducing GvHD incidence. Overall survival (OS) remains variable across groups. The first case presents rapid disease progression to pulmonary alveolar proteinosis (PAP) and leukemic transformation, further developing severe HSCT complications. The second case addresses novel GATA2 mutation and raises concerns regarding alternative prophylactic and therapeutic strategies in transplant setting. Conclusions: Collaborative efforts aim to enhance understandings of GATA2-related myeloid malignancies and guide towards more effective management approaches. Full article

Skin aging is significantly influenced by glycation processes, leading to the formation of Advanced Glycation End-products (AGEs) that compromise dermal structure and function. This study evaluated the protective effects of a novel injectable product based on a combination of two different ranges of Molecular Weights of Hyaluronic Acid (MWHA: LMWHA-Low MWHA, MMWHA-Mid MWHA, and HMWHA-High MWHA) and trehalose against glycation in human skin explants. Using human skin explants with methylglyoxal-induced glycation stress, we assessed the product’s impact on carboxymethyllysine (CML) formation and cell viability in the reticular dermis. The product was administered prophylactically one day before methylglyoxal exposure, and samples were analyzed after six days. Results demonstrated that the product significantly reduced CML formation by 45% (p < 0.01) compared to untreated controls under baseline conditions and maintained a 30% reduction (p < 0.05) in CML formation under methylglyoxal-induced stress. Importantly, the product preserved cell viability throughout the experimental period and maintained CML levels comparable to physiological baseline despite glycation stress. These findings suggest that the synergistic action of hyaluronic acid and trehalose provides effective protection against both baseline and induced glycation in human skin, indicating potential applications in preventing glycation-related skin aging. Full article

We present the case of a 46-year-old man with a history of complex ventricular arrhythmias preceding the development of asymptomatic mild left ventricular dysfunction, who presented with acute-onset heart failure and was ultimately diagnosed with dilated cardiomyopathy. Genetic testing identified a novel, likely pathogenic mutation in exon 4 of the BAG3 gene (NM_004281, c.1128del, (p.(Ser377AlafsTer47)), not previously reported in the literature. Given the presence of multiple clinical features indicative of a poor prognosis, he underwent prophylactic placement of a subcutaneous implantable cardioverter-defibrillator. The clinical presentation of this novel BAG3 mutation suggests that it may be associated with a significant arrhythmic phenotype. This case underscores the importance of close follow-up and genetic testing in patients presenting with mild left ventricular dysfunction and ventricular arrhythmias. Full article