Pseudotumor Cerebri in the Setting of Differentiation Syndrome in a Patient with Acute Promyelocytic Leukemia Treated with All-trans Retinoic Acid During Induction Therapy

Introduction: Differentiation syndrome, a well-known complication of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APML), can very rarely have ophthalmic manifestations. Pseudotumor cerebri (PC) in the setting of differentiation syndrome (DS) in patients undergoing induction with all-trans retinoic acid has rarely been reported elsewhere. We herein report one such case. Case Presentation: A 28-year-old, non-obese female diagnosed as acute promyelocytic leukemia underwent induction with all- trans retinoic acid and Idarubicin. On day 4 of the treatment, she developed high grade fever (104 – 105 F), dry cough, hypotension, tachycardia, and tinnitus. Chest X ray showed floppy shadows in bilateral lungs. On physical examination, bilateral lower limb edema was noted. She also experienced sudden weight gain of 5 kilogram in 48 hours. After careful exclusion of systemic infection, she was suspected as having DS. She also noticed a reduction in vision in right eye. On eye examination, her best-corrected visual acuity (VA) was 6/60 in the right eye (RE) and 6/6 in the left eye (LE). Fundus evaluation revealed bilateral disc edema with peripapillary hemorrhages along with slight tortuosity of vessels and a yellowish lesion over the fovea in RE. Suspecting DS, she was treated with injection dexamethasone 10 mg twice daily and all- trans retinoic acid was temporarily discontinued. Immediately after its discontinuation, her headache lessened and vision improved gradually. After 2 weeks, her VA was 6/12 in RE and 6/6 in LE which improved to 6/6 in both eyes at 3 months. The patient was also receiving oral voriconazole for fungal prophylaxis and the potentiation effect of all- trans retinoic acid could thus be explained. Conclusion: Pseudotumor cerebri associated with all-trans retinoic acid treatment in acute promyelocytic leukemia, even though frequently reported in pediatric patients, is rare in adults. Ophthalmological evaluation is mandatory in all these patients under all-trans retinoic acid therapy.

Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia

Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.

Combining genetic risk score with artificial neural network to predict the efficacy of folic acid therapy to hyperhomocysteinemia

Artificial neural network (ANN) is the main tool to dig data and was inspired by the human brain and nervous system. Several studies clarified its application in medicine. However, none has applied ANN to predict the efficacy of folic acid treatment to Hyperhomocysteinemia (HHcy). The efficacy has been proved to associate with both genetic and environmental factors while previous studies just focused on the latter one. The explained variance genetic risk score (EV-GRS) had better power and could represent the effect of genetic architectures. Our aim was to add EV-GRS into environmental factors to establish ANN to predict the efficacy of folic acid therapy to HHcy. We performed the prospective cohort research enrolling 638 HHcy patients. The multilayer perception algorithm was applied to construct ANN. To evaluate the effect of ANN, we also established logistic regression (LR) model to compare with ANN. According to our results, EV-GRS was statistically associated with the efficacy no matter analyzed as a continuous variable (OR = 3.301, 95%CI 1.954–5.576, P < 0.001) or category variable (OR = 3.870, 95%CI 2.092–7.159, P < 0.001). In our ANN model, the accuracy was 84.78%, the Youden’s index was 0.7073 and the AUC was 0.938. These indexes above indicated higher power. When compared with LR, the AUC, accuracy, and Youden’s index of the ANN model (84.78%, 0.938, 0.7073) were all slightly higher than the LR model (83.33% 0.910, 0.6687). Therefore, clinical application of the ANN model may be able to better predict the folic acid efficacy to HHcy than the traditional LR model. When testing two models in the validation set, we got the same conclusion. This study appears to be the first one to establish the ANN model which added EV-GRS into environmental factors to predict the efficacy of folic acid to HHcy. This model would be able to offer clinicians a new method to make decisions and individual therapeutic plans.

Rationality and safety of acetylsalicylic acid therapy in centenarians

Aim. To assess the presence or absence of indications for taking acetylsalicylic acid (ASA), as well as the safety of therapy among centenarians according to clinical guidelines.Materials and methods. The study included 81 patients (71 women and 10 men). Inclusion criteria: patients 95 years and older (mean age 98.3 ± 1.89) receiving combination therapy, including ASA. In the study, the patients' history data on concomitant diseases and pharmacotherapy were assessed, a comprehensive examination (complete blood count (CBC), echocardiography) was performed. In our work, the results of these studies were analyzed, and statistical calculations were performed.Results. From the total number of patients included in the study, 41.9% regularly take ASA (n=34). In 41.7% (n=14) were taken as secondary prevention of cardiovascular events (the presence of a documented history of cardiovascular disease). According to current recommendations, 58.3% (n=20) of patients had no indications for a prescription. During the analysis among patients for whom according to clinical guidelines ASA therapy was not recommended, groups were identified in which the risk of gastrointestinal bleeding (GIB) was increased: 30% (n=6) patients had a history of gastric ulcer or duodenal ulcer, 20% (n=4) took drugs from the group of non-steroidal anti-inflammatory drugs, 25% (n=3) of patients had thrombocytopenia. In 4 (15.6%) patients from these subgroups, several factors simultaneously increase gastrointestinal bleeding risk.Conclusions. From the total number of patients included in the study and prescribed with ASA, more than half had no indications for therapy; the vast majority of this group had additional risk factors for GIB development. At the same time, a quarter of all participants had indications, but therapy was not prescribed. Summarizing all of the mentioned above, before prescribing and continuing treatment with ASA, clinicians should analyze the therapy's feasibility and safety.

Genetic spectrum and clinical characteristics of 3β-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency in China

Background Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study was to obtain detailed information on the correlation between the genotype and phenotype of HSD3B7 deficiency and to report on responses to primary bile acid therapy. Methods The medical records of a cohort of 39 unrelated patients with genetically and biochemically confirmed HSD3B7 deficiency were examined to determine whether there exist genotype-phenotype relationships in this bile acid synthesis disorder. Results In all, 34 of the 44 variants identified in HSD3B7 were novel. A total of 32 patients presented early with neonatal cholestasis, and 7 presented after 1-year of age with liver failure (n = 1), liver cirrhosis (n = 3), cholestasis (n = 1), renal cysts and abnormal liver biochemistries (n = 1), and coagulopathy from vitamin K1 deficiency and abnormal liver biochemistries (n = 1). Renal lesions, including renal cysts, renal stones, calcium deposition and renal enlargement were observed in 10 of 35 patients. Thirty-three patients were treated with oral chenodeoxycholic acid (CDCA) resulting in normalization of liver biochemistries in 24, while 2 showed a significant clinical improvement, and 7 underwent liver transplantation or died. Remarkably, renal lesions in 6 patients resolved after CDCA treatment, or liver transplantation. There were no significant correlations between genotype and clinical outcomes. Conclusions In what is the largest cohort of patients with HSD3B7 deficiency thus far studied, renal lesions were a notable clinical feature of HSD3B7 deficiency and these were resolved with suppression of atypical bile acids by oral CDCA administration.

A Comparative study between topical 15% potassium hydroxide and 20% Salicylic acid in treatment of multiple palmoplantar warts

Warts are one of the most common benign neoplasms. Warts are induced by over 100 types of human papillomavirus (HPVs) and can affect any race. Various treatments were considered to treat warts, of which topical salicylic acid and KOH are the most commonly used choices. Aim of the study To compare between the efficacy, safety and recurrence rate of topical 15% potassium hydroxide (KOH) and 20% Salicylic acid in the treatment of multiple palm plantar warts. Patients and methods study included 40 patients complaining of multiple palmar and/or planter warts 2 lesions at least. Each patient was treated by: Salicylic acid 20% used on one lesion and topical 15% KOH preparation used on another lesion. Assessment of patients’ response was done through clinical and dermoscopic examination. Results Salicylic acid results revealed that 5% of the treated lesions showed Clinical improvement without dermoscopic clearance, 40% showed Clinical clearance with dermoscopic remnants while 55% showed Clinical and dermoscopic clearance. KOH treated warts showed 5% of the treated lesions had clinical improvement without dermoscopic clearance, 25% showed clinical clearance with dermoscopic remnants while 70% showed clinical and dermoscopic clearance. Conclusion KOH therapy as well as patient satisfaction showed higher significant treatment response compared to salicylic acid therapy with less encountered side effects.

Hypothesizing Nutrigenomic-Based Precision Anti-Obesity Treatment and Prophylaxis: Should We Be Targeting Sarcopenia Induced Brain Dysfunction?

Background: The United States Centers for Disease Control and Prevention (CDC) estimates a total obesity rate of 30% for 12 states and a 20% obesity rate nationwide. The obesity epidemic continues to increase in spite of preventative measures undertaken worldwide. Pharmacological treatments promise to reduce total fat mass. However, medications may have significant side effects and can be potentially fatal. Data Retrieval: This brief review, based on a PUBMED search of the key terms “Obesity” and” Sarcopenia,” will present evidence to corroborate the existence of Reward Deficiency Syndrome (RDS) in obesity and the involvement of catecholaminergic pathways in substance seeking behavior, particularly as it relates to carbohydrates cravings. Expert Opinion: The genetic basis and future genetic testing of children for risk of aberrant generalized craving behavior are considered a prevention method. Here we present evidence supporting the use of precursor amino acid therapy and modulation of enkephalinase, MOA, and COMT inhibition in key brain regions. Such treatments manifest in improved levels of dopamine/norepinephrine, GABA, serotonin, and enkephalins. We also present evidence substantiating insulin sensitivity enhancement via Chromium salts, which affect dopamine neuronal synthesis regulation. We believe our unique combination of natural ingredients will influence many pathways leading to the promotion of well-being and normal healthy metabolic functioning. Sarcopenia has been shown to reduce angiogenesis and possible cerebral blood flow. Exercise seems to provide a significant benefit to overcome this obesity-promoting loss of muscle density. Conclusion: Utilization of proposed nutrigenomic formulae based on coupling genetic obesity risk testing promotes generalized anti-craving of carbohydrates and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and relapse prevention.

Rapid response to leptin therapy in a FPLD patient with a novel PPARG missense variant

Summary Familial partial lipodystrophy (FPLD) syndromes are rare heterogeneous disorders especially in women characterized by selective loss of adipose tissue, reduced leptin levels and severe metabolic abnormalities. Here we report a 34-year-old female with a novel heterozygotic c.485 thymine>guanine (T>G) missense variant (p.phenylalanine162cysteine; (Phe162Cys)) in exon 4 of the peroxisome proliferator-activated receptor gamma (PPARG) gene, developing a non-ketotic diabetes and severe hypertriglyceridemia with triglyceride concentrations >50 mmol/L. In this case, a particular interesting feature in comparison to other known PPARG mutations in FPLD is that while glycaemic control could be achieved through standard anti-diabetic medication, hypertriglyceridemia did neither respond to fibrate nor to omega-3-fatty acid therapy. This might suggest a lipid metabolism driven phenotype of the novel PPARG c.485T>G missense variant. Notably, recombinant leptin replacement therapy (metreleptin (Myalepta®)) was initiated showing a rapid and profound effect on triglyceride levels as well as on liver function tests and satiety feeling. Unfortunately, severe allergic skin reactions developed at the side of injection which could be covered by anti-histaminc treatment. We conclude that the heterozygous PPARG c.485T>G variant is a yet undescribed molecular basis underlying FPLD with difficulties predominantly to control hypertriglyceridemia and that recombinant leptin therapy may be effective in affected subjects. Learning points Heterozygous c.485T>G variant in PPARG is most likely a cause for FPLD in humans. This variant results in a special metabolic phenotype with a predominant dysregulation of triglyceride metabolism not responding to standard lipid lowering therapy. Recombinant leptin therapy is effective in rapidly improving hypertriglyceridemia.