Case Report: Simultaneous Infection with Leishmania (Viannia) braziliensis and L. (V.) lainsoni in a Peruvian Patient with Cutaneous Leishmaniasis

Conventional understanding suggests that simultaneous infection with more than one species of Leishmania is unlikely. In Peru, co-infections are clinically relevant because causative species dictates prognosis, treatment response, and follow-up. We describe a case of Leishmania (Viannia) braziliensis and L. (V.) lainsoni co-infection in a Peruvian patient with cutaneous leishmaniasis.     

Atypical clinical variants in New World cutaneous leishmaniasis: disseminated, erysipeloid, and recidiva cutis due to Leishmania (V.) panamensis

In recent times, there has been an increase in the number of reports for new and rare variants of cutaneous leishmaniasis (CL). Here, we describe three unusual clinical forms of CL identified in Ecuadorian children. A total of 131 patients with CL were diagnosed over a 2-year period of active search. In 3 (2.29%), the lesions were very unusual; these included erysipeloid, recidiva cutis (LRC), and disseminated leishmaniasis (DL). The erysipeloid case is characterized by erythematous and indurated plaque seen on the face of a 5-year-old boy; the LRC one is differentiated by slowly progressing red-brown papules around large scars of healed sores in a 6-year-old girl, and the DL case is characterized by dozens of cutaneous ulcers distributed in the whole body of a 1-year-old girl. Leishmania parasites were isolated by lesion aspirate and analyzed by the technique multilocus enzyme electrophoresis (MLEE). All three isolates were identified as Leishmania (Viannia) panamensis. These distinct clinical variants rarely have been reported previously in the American cutaneous leishmaniasis, and for the first time L. (V.) panamensis was identified as the etiologic agent. Our cases extend the spectrum of clinical presentations in New World leishmaniasis.     

Fractional Exhaled Nitric Oxide Guided-Therapy in Chronic Obstructive Pulmonary Disease: A Stratified,Randomized, Controlled Trial

IntroductionChronic obstructive pulmonary disease (COPD) with eosinophilic airway inflammation represents a distinct phenotype that might respond to treatment with inhaled corticosteroids. Fractional exhaled nitric oxide (FENO) might predict eosinophilic inflammation and guide treatment option. We hypothesized that COPD patients with different baseline levels of FENO might have differentiated response to treatment with salmeterol/fluticasone (SFC) or tiotropium (TIO).MethodsThis open-label, randomized-controlled trial enrolled treatment-naïve COPD patients who were stratified into high- (≥23.5 ppb) and low-FENO group, followed by 12-week treatment with SFC or TIO. A linear mixed model with repeated measures was applied to analyze the changes in FENO (primary outcome), COPD assessment test (CAT) score, FEV₁, and parameters in induced sputum and blood after treatment.Results134 patients were divided into 4 subgroups: low-FENO/SFC (n = 30), low-FENO/TIO (n = 29), high-FENO/SFC (n = 37), and high-FENO/TIO (n = 38). At baseline, FENO 23.5 ppb clearly differentiated between eosinophilic and non-eosinophilic inflammation groups based on the eosinophils in induced sputum and blood. FENO significantly correlated with sputum and blood eosinophils at baseline. High-FENO/SFC (vs. high-FENO/TIO) subgroup had significant reduction in FENO and sputum inflammation profiles (including eosinophils, macrophages, matrix metalloproteinase-9, and interlukin-8) after treatment. These differences were not replicated between low-FENO/SFC and low-FENO/TIO subgroups. The improvement in CAT and FEV₁ after treatment was indiscriminate between SFC and TIO in the low- and high-FENO groups.ConclusionHigh baseline FENO can serve as an indicator of eosinophilic airway inflammation in COPD patients who may respond favorably to treatment with inhaled corticosteroids/long-acting β₂-agonists.Trial registration numberClinicalTrials.gov Identifier: NCT02546349.     

A Parallel-Arm Randomized Controlled Trial to Assess the Effects of a Far-Infrared-Emitting Collar on Neck Disorder

The purpose of this study is to assess the beneficial effects of a far-infrared-emitting collar (FIRC) on the management of neck disorders. A neck disorder is generalized as neck muscle pain and its relative mental disorders because the etiologies of the neck’s multidimensional syndrome are either muscle impairment or psychiatric distress. This is the first study to determine the efficacy of a FIRC by evaluating objective physical evidence and psychometric self-reports using a parallel-arm randomized sham-controlled and single-blinded design. In this trial, 60 participants with neck disorders were observed at baseline and post-intervention. Compared to the placebo group after a 30-min intervention, the FIRC demonstrated a statistically significant biological effect in elevating skin temperature and promoting blood circulation with p-values 0.003 and 0.020, respectively. In addition, FIRC application significantly reduced neck muscle tension, relieved pain, ameliorated fatigue, improved depression, and decreased anxiety. The FIRC could therefore be a potential treatment for neck disorders.     

Press Imprint Smear: A Rapid,Simple, and Cheap Method for the Diagnosis of Cutaneous Leishmaniasis Caused by Leishmania (Viannia) braziliensis

A modified imprint method, Press-Imprint-Smear, was compared with histopathology for the diagnosis of cutaneous leishmaniasis. Amastigotes were seen in 69 (92%) of 75 individuals in one or both assays. The Press-Imprint-Smear was positive in 85.3%, and histopathology was positive in 44%. Press-Imprint-Smear is a rapid and relatively sensitive method for the diagnosis of cutaneous leishmaniasis.     

A Controlled Trial to Assess the Effect of Quinine, Chloroquine, Amodiaquine, and Artesunate on Loa loa Microfilaremia

Onchocerciasis control is currently based on mass ivermectin treatment. Unfortunately, this drug can induce serious adverse events (SAEs) in persons with high levels of Loa loa microfilaremia (> 30,000 microfilaria/mL). A means of preventing SAEs would be to treat at risk populations with a drug that would progressively reduce the microfilarial loads before administering ivermectin. Antimalarial drugs are a potential solution because they have shown some activity against various filarial species. A controlled trial was conducted to assess the effect of standard doses of quinine, chloroquine, amodiaquine, and artesunate on L. loa microfilaremia. Ninety-eight patients were randomly allocated into five groups (one for each drug and a control group) after stratification on microfilarial load. Loa loa microfilaremia was monitored on days 0, 3, 7, 15, 30, 60, and 90. No significant change in the loads was recorded in any of the treatment groups. A comprehensive review of the effects of antimalarial drugs against filariae is also provided.     

Controlled Clinical Trial with Sucralfate in the Treatment of Macroscopic Gastritis

The efficacy of sucralfate in the treatment of patients with dyspepsia and macroscopic signs of gastritis was assessed in a double-blind, placebo-controlled study. Treatment was 2g sucralfate or placebo taken 1/2 h before breakfast and at bedtime. Clinical and endoscopic examinations were performed after 6 weeks' treatment, and if mucosal changes and/or symptoms persisted, medication was continued for another 6 weeks. Cumulative healing rates at 6 and 12 weeks were 43% (13 of 30) and 62% (18 of 29) in the sucralfate group versus 37% (11 of 30) and 62% (18 of 29) in the placebo group. Corresponding rates for symptomatic improvement were 80% and 83% for those receiving sucralfate and 73% and 79% for placebo-treated patients. None of the differences between sucralfate and placebo were significant, and sucralfate does not seem to be superior to placebo in the treatment of macroscopic gastritis.     

Randomized,Double-Blinded,Phase 2 Trial of WR 279,396 (Paromomycin and Gentamicin) for Cutaneous Leishmaniasis in Panama

In this randomized, double-blinded Phase 2 trial, 30 patients with Leishmania panamensis cutaneous leishmaniasis were randomly allocated (1:1) to receive once daily topical treatment with WR 279,396 (15% paromomycin + 0.5% gentamicin) or Paromomycin Alone (15% paromomycin) for 20 days. The index lesion cure rate after 6 months follow-up was 13 of 15 (87%) for WR 279,396 and 9 of 15 (60%) for Paromomycin Alone (P = 0.099). When all treated lesions were included, the final cure rate for WR 279,398-treated patients was again 87%, but the final cure rate for Paromomycin Alone-treated patients was 8 of 15 (53.3%; P = 0.046). Both creams were well tolerated with mild application site reactions being the most frequent adverse event. The increased final cure rate in the WR 279,396 group in this small Phase 2 study suggests that the combination product may provide greater clinical benefit than paromomycin monotherapy against L. panamensis cutaneous leishmaniasis.     

Efficacy of Atorvastatin and Antihistamines in Comparison with Antihistamines plus Placebo in the Treatment of Chronic Idiopathic Urticaria: A Controlled Clinical Trial

Chronic Idiopathic Urticaria is defined as recurrent hives occurring for at least 6 weeks. In the majority of cases, there is no identifiable underlying etiology despite extensive evaluation. A subset of these patients is classified as having autoimmune urticaria defined by the presence of a functional IgG antibody to the α subunit of the high-affinity IgE receptor (FceRIa) or to IgE. The aim of this study was to evaluate the effects of the drug atorvastatin in patients with chronic urticaria compared to the placebo.In this single-blind study, 50 patients suffering from chronic urticaria (15-45 years old) were selected and divided into two groups by simple randomization method. The first group was treated with atorvastatin and antihistamines and the second group (control group) was treated with placebo and antihistamines for 3 months. Urticaria severity was measured by score index, before and after the treatment course: ASST (Autologous serum skin test) was performed for all patients and sera were collected to measure cytokines. In cases, IL-5 decreased and IL-10 increased after treatment compared to the time point before treatment (p<0.05). All patients with severe utricaria according our scoring, had positive ASST.The patients with severe urticaria identified by urticaria score and ASST positivity had chronic idiopathic urticaria. By prescribing the Atorvastatin plus antihistamines in severe and resistant forms of urticaria, the use of more toxic medications like cytotoxic drugs may be avoided.     

国产注射用醋酸奥曲肽治疗食管胃底静脉曲张破裂出血的多中心随机对照临床研究

背景：生长抑素及其类似物可降低门静脉压力，减少奇静脉血流，临床上广泛应用于门静脉高压所致食管胃底静脉曲张破裂出血的治疗。目的：评价国产注射用醋酸奥曲肽治疗急性食管胃底静脉曲张破裂出血的疗效和安全性。方法：采用多中心、随机、单盲、阳性药物平行对照试验设计，以善宁醋酸奥曲肽注射液作为对照．疗程5天。首剂0．1mg加入5％葡萄糖20ml静脉推注，随后以0．025mg／h的速度连续静脉滴注72h．如出血停止，则继续皮下注射0．1mg1次／8h，连续2天。疗效评价指标包括呕血量和便血量，安全性评价指标包括实验室检查结果、患者生命体征以及治疗中的不良反应。结果：共129例患者人组，其中试验组64例，对照组65例。按全分析集（FAS）评价，试验组临床显效率为78．1％．总有效率为93．8％，对照组临床显效率为83．1％．总有效率为96．9％，两组相比差异无统计学意义（P〉0．05）。试验组2例（3．1％）患者出现发热的不良事件，对照组无不良事件和不良反应发生。两组均未发生严重不良事件。结论：国产注射用醋酸奥曲肽用于治疗食管胃底静脉曲张破裂出血安全、有效，与同剂量善宁醋酸奥曲肽注射液疗效相近。     

Clinical Efficacy of Vitamin D3 Adjuvant Therapy in Allergic Rhinitis: A Randomized Controlled Trial

Background: Vitamin D supplementation has been proven to be effective in the treatment of allergic rhinitis (AR). Objective: We conducted the present study to explore the role and efficacy of vitamin D adjuvant therapy for the treatment of inflammation in patients with AR. Methods: Out of 127 patients with potential eligible AR, 60 were randomly assigned into two groups and were finally included in our analysis (n=30 for each intervention). The patients with potential eligible AR were randomly allocated to intervention with desloratadine citrate disodium (DCD, 8.8 mg/day) without and with vitamin D3 nasal drops (1.5х106 IU, once/week) for four weeks. Thirty healthy control subjects were included in our study. We assessed the changes in the serum 25(OH)D, peripheral blood eosinophils, interleukin (IL)-4 levels, and nasal symptoms. Serum 25(OH)D, peripheral blood eosinophils, and IL-4 levels were detected respectively with liquid chromatography-tandem mass spectrometry (LC-MS/MS), a blood detector, and enzyme-linked immunosorbent assay. Results: Our patients who received vitamin D3 adjuvant therapy had a higher serum 25(OH)D level (47.57 ± 2.83 vs. 31.51 ± 2.95 ng/ml, p=0.000) and lower AR symptoms score (2.07 ± 1.89 vs. 3.37 ± 1.50, p=0.005), serum IL-4 (10.38 ± 3.41 vs. 12.79 ± 5.40 pg/ml, p=0.043), and peripheral blood eosinophils (0.34 ± 0.09 vs. 0.41 ± 0.10 109/l, p=0.003) compared with DCD single treatment. The efficacy rates of DCD with and without vitamin D3 in AR were 97% and 84%, respectively. Conclusion: Nasal vitamin D3 combined with DCD could improve the clinical symptoms of AR. Vitamin D3 adjunct therapy showed significant effects on inhibiting inflammation in patients with AR. We concluded that vitamin D3 supplementation could be an effective adjuvant therapy in AR patients.     

Treatment Adherence in a Randomized Controlled Trial of Pirfenidone in HFpEF: Determinants and Impact on Efficacy

ObjectivesMedication adherence in patients with heart failure with preserved ejection fraction is unclear. This study sought to evaluate treatment adherence in the Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction (PIROUETTE) trial.Methods and ResultsAdherence was evaluated through pill counts and diary cards. Univariable and multivariable regression models were used to assess the relationship between adherence and baseline characteristics. Instrumental variable regression was used to estimate the causal effect of pirfenidone treatment duration on myocardial fibrosis. Complete adherence data were available in 54 of 80 participants completing the trial. Mean adherence to study medication was 94.7% and 96.9% in the pirfenidone and placebo groups, respectively. Each additional day of treatment with pirfenidone resulted in a significant decrease in myocardial extracellular volume (–0.004%; 95% confidence interval: -0.007% to -0.001%; P = 0.007). Associations with adherence included older age, higher symptom burden, lower body weight, and smaller right ventricular size.ConclusionAdherence to study medication in the PIROUETTE trial was very high among patients for whom complete adherence data were available. Importantly, each additional day of treatment reduced myocardial fibrosis. Potential predictors of adherence were identified. Implementation of improved methods for assessing adherence is required.