UNASSIGNED: Atypical chronic myeloid leukemia (aCML) is a BCR::ABL1 negative myelodysplastic/myeloproliferative neoplasm with poor overall survival. Some patients can be treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) from suitable donors. The effectiveness of decitabine or azacitidine (AZA) has recently been reported; however, their combined efficacy with selinexor has not yet been reported.
UNASSIGNED: In this study, we report the case of a patient with aCML who was successfully treated with selinexor combined with AZA. A 67-year-old man with a history of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was admitted to the hospital with fatigue and emaciation. He was diagnosed with aCML and no longer responded to decitabine treatment after undergoing seven cycles. The patient was subsequently administered hydroxyurea (HU), selinexor, and AZA. After four courses of combination therapy, his blood cell counts improved; he no longer required transfusions and was able to discontinue HU. The patient continued receiving selinexor and AZA without severe complications. This case is the first to show that combinatorial selinexor and AZA therapy can effectively treat aCML.
UNASSIGNED: Our case sheds light on the importance of selinexor and AZA combined therapy in the exploration of new treatment strategies for aCML. Moreover, this treatment approach offers the possibility of bridging with allo-HSCT.

Overweight and obesity prevalence has increased worldwide. Apart from conventional approaches, people also resort to botanical supplements for reducing body weight, although several adverse events have been associated with these products. In this context, the present study aimed at evaluating the toxicity of Garcinia cambogia-based products and shedding light on the mechanisms involved. The suspected hepatotoxic reactions related to G. cambogia-containing products collected within the Italian Phytovigilance System (IPS) were examined. Then, an in vitro study was performed to evaluate the possible mechanisms responsible for the liver toxicity, focusing on the modulation of oxidative stress and Nrf2 expression. From March 2002 to March 2022, the IPS collected eight reports of hepatic adverse reactions related to G. cambogia, which exclusively involved women and were mostly severe. The causality assessment was probable in three cases, while it was possible in five. In the in vitro experiments, a low cytotoxicity of G. cambogia was observed. However, its combination with montelukast greatly reduced cell viability, increased the intracellular ROS levels, and affected the cytoplasmic Nrf2 expression, thus suggesting an impairment of the antioxidant and cytoprotective defenses. Overall, our results support the safety concerns about G. cambogia-containing supplements and shed light on the possible mechanisms underpinning its hepatotoxicity.

Antibiotic resistance is a serious global threat, and the misuse of antibiotics is considered its main cause. It is characterized by the expression of bacterial defense mechanisms, e.g., β-lactamases, expulsion pumps, and biofilm development. Acinetobacter baumannii and Pseudomonas aeruginosa are antibiotic-resistant species that cause high morbidity and mortality. Several alternatives are proposed to defeat antibiotic resistance, including antimicrobial peptides, bacteriophages, and plant compounds. Terpenes from different plant essential oils have proven antimicrobial action against pathogenic bacteria, and evidence is being generated about their effect against antibiotic-resistant species. That is the case for oregano essential oil (Lippia graveolens), whose antibacterial effect is widely attributed to carvacrol, its main component; however, minor constituents could have an important contribution. The analyzed evidence reveals that most antibacterial evaluations have been performed on single species; however, it is necessary to analyze their activity against multispecies systems. Hence, another alternative is using plant compounds to inactivate hydrolytic enzymes and biofilms to potentiate antibiotics\' effects. Despite the promising results of plant terpenes, more extensive and deep mechanistic studies are needed involving antibiotic-resistant multispecies to understand their full potential against this problem.

This is a preliminary report of the first cases of successful simultaneous use of ulipristal acetate (UPA) and vitamin D3 in uterine fibroid (UF) oral treatment in humans. We present two cases of 37- and 49-year-old females with clinically symptomatic UFs and vitamin D deficiency. Both patients were treated with a standard 3 months of UPA scheme (5 mg daily) with the additional use of vitamin D3 (7000 IU daily orally). In the 37-year-old female all the symptoms (pain, pressure, frequent urination) decreased, total tumor volume after the treatment changed by 47.8%. In the 49-year-old female most symptoms perished, total tumor volume was reduced by 63.3%. UPA and vitamin D share synergistic anti-fibroid properties. Further studies are necessary to show the exact effect of UPA and vitamin D as co-drugs.

BACKGROUND: Dried leaf Artemisia annua (DLA) has shown efficacy against Plasmodium sp. in rodent studies and in small clinical trials. Rodent malaria also showed resiliency against the evolution of artemisinin drug resistance.
OBJECTIVE: This is a case report of a last resort treatment of patients with severe malaria who were responding neither to artemisinin combination therapy (ACT) nor i.v. artesunate.
METHODS: Of many patients treated with ACTs and i.v. artesunate during the 6 mon study period, 18 did not respond and were subsequently treated with DLA Artemisia annua.
METHODS: Patients were given a dose of 0.5g DLA per os, twice daily for 5d. Total adult delivered dose of artemisinin was 55mg. Dose was reduced for body weight under 30kg. Clinical symptoms, e.g. fever, coma etc., and parasite levels in thick blood smears were tracked. Patients were declared cured and released from hospital when parasites were microscopically undetectable and clinical symptoms fully subsided.
RESULTS: All patients were previously treated with Coartem® provided through Santé Rurale (SANRU) and following the regimen prescribed by WHO. Of 18 ACT-resistant severe malaria cases compassionately treated with DLA, all fully recovered. Of the 18, this report details two pediatric cases.
CONCLUSIONS: Successful treatment of all 18 ACT-resistant cases suggests that DLA should be rapidly incorporated into the antimalarial regimen for Africa and possibly wherever else ACT resistance has emerged.

Worldwide, cyanobacterial blooms have been increasing in intensity and frequency, with toxic cyanobacteria sometimes dominant throughout the year in many freshwater bodies. Since the coexistence of more than one type of cyanotoxins in freshwater environments is a common phenomenon, studies on the joint effects of these toxins would be very useful. In this study, the single and combined effects of two cyanotoxins with different modes of action (hepatotoxic and neurotoxic) on the survival (lethal exposure) and feeding (sublethal exposure) of the cladoceran Daphnia magna were investigated. With the single exposures, it was observed that both the survival and feeding activity of the daphnids were impaired by the hepatotoxic and neurotoxic extracts at environmentally relevant concentrations. In the combined exposures, both survival and feeding rate endpoints showed a good fit to the independent action model. For the acute assay and 24h exposure period in the feeding inhibition test, there was no interaction between components of the hepatotoxic and neurotoxic extracts, although a slight tendency to a synergistic deviation could be seen in the feeding rates. On the other hand, for the 4h post-exposure period, a synergistic deviation was found in feeding rates at all mixture concentrations tested. Hence, the combined exposure of hepatotoxins and neurotoxins should also be taken into account in risk assessments of freshwater bodies, since the mixture of these toxins can result in more severe post-exposure effects on the feeding of daphnids than the sum of those expected for single exposures.

OBJECTIVE: To identify possible risk factors and their synergism for cholangiocarcinoma development.
METHODS: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma (ECC) and 83 intrahepatic cholangiocarcinoma (ICC)], diagnosed at a training hospital in Korea between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression and synergism index, respectively.
RESULTS: There was an association between cholangiocarcinoma and hepatitis B virus (HBV) infection, diabetes mellitus (DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios (AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM (AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC (AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC (AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM (OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.
CONCLUSIONS: In this Korean study, HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanisms for such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.