Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD.

BACKGROUND AND OBJECTIVE: The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis. METHODS: All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects. RESULTS: Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner. CONCLUSION: The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.

Marked improvement in the success rate of medical management of early pregnancy failure following the implementation of a novel institutional protocol and treatment guidelines: a follow-up study.

PURPOSE: To analyze the success rate, time to passage of tissue and subjective patient experience of a newly implemented protocol for medical management of early pregnancy failure (EPF) over a 2-year period. METHODS: A retrospective chart review of all patients with early pregnancy failure primarily opting for medical management was performed. 200 mg mifepristone were administered orally, followed by a single vaginal dose of 800 mcg misoprostol after 36-48 h. We followed-up with our patients using a written questionnaire. RESULTS: 167 women were included in the present study. We observed an overall success rate of 92 %, defined as no need for surgical management after medication administration. We could not identify predictive values for success in a multivariate regression analysis. Most patients (84 %) passed tissue within 6 h after misoprostol administration. The protocol was well tolerated with a low incidence of side effects. Pain was managed well with sufficient analgesics. Responders to the questionnaire felt adequately informed prior to treatment and rated their overall experience as positive. CONCLUSION: The adaption of the institutional medical protocol resulted in a marked improvement of success rate when compared to the previously used protocol (92 vs. 61 %). We credit this increase to the adjusted medication schema as well as to targeted physician education on the expected course and interpretation of outcome measures. Our results underscore that the medical management of EPF is a safe and effective alternative to surgical evacuation in the clinical setting.

[Contribution of allergen immunotherapy using Phostal in the treatment of seasonal allergic rhinitis (two years of use)]. / Prínos alergenové imunoterapie Phostalem v lécbe sezonní alergické rýmy (dva roky aplikace).

Allergen immunotherapy consists in the administration of the appropriate allergen to which the patient is hypersensitive. The objective is to induce immunological tolerance of the organism. In the present study, the effect of the administration of Phostal on the occurrence of seasonal symptoms of pollinosis in a group of 35 outpatients was observed during two years. The substance was administered according to the regular dosage schedule, all year round. The results of the study have demonstrated a significant effect of the product on the decrease in the occurrence of observed objective symptoms of the disease, starting already from the first year of treatment. This is in correlation with changes in the spirometric functions, selected laboratory parameters and results of the prick tests in the treated group in comparison to the control group.

[Experience with ciclesonide in patients with mild persistent bronchial asthma]. / Zkusenosti s ciclesonidem u dospelých pacientu s lehkou formou astma bronchiale.

Experience with ciclesonide in patients with mild persistent bronchial asthma The study aimed to monitor the effectiveness and safety of the treatment with ciclesonide, administered once a day in a 160 microg dose, over a 3-month period, to a group of 100 patients diagnosed with mild persistent bronchial asthma with deterioration of problems after exercise. The results of the study prove significant positive effects of the preparation used. A significant improvement of FEV1 and PEF values was observed, as well as a statistically significant remission of both day and nocturnal symptoms of the disease, a significantly lower consumption of short-acting beta2-sympathomimetics, and an improvement of all evaluated data relating to the quality of life of the asthmatic patients. No adverse effects were registered.

[Examination of the antioxidative and antidiabetic effect of pomiferin in alloxan-induced diabetes mellitus in an experiment (a pilot study)]. / Sledování antioxidacního a antidiabetického efektu pomiferinu u alloxanem navozeného diabetes mellitus v experimentu--pilotní studie.

The antioxidative and antidiabetic effect of pomiferin was monitored under the experimental conditions of alloxan-induced diabetes mellitus. The animals were divided by random selection into 2 groups (n=7). The treated group was administered pomiferin in peroral doses of 10 mg/kg in Avicel, the placebo group was given only a solution of Avicel, and the last group was intact. Selected laboratory parameters (glucose, urea, cholesterol, antioxidative enzymes, total antioxidative capacity, malondialdehyde in serum: diuresis, total glucose and protein losses through urine) were determined. Kidney tissue and pancreas samples were taken for histopathological analysis. The findings included a statistically significant decrease (p < or = 0.01) in blood glucose level, a significant increase (p < or = 0.01) in glutathione peroxidase, total antioxidative capacity (p < or = 0.05) and a significant decrease (p < or = 0.01) in malondialdehyde level in the treated group compared to the placebo group. A highly significant decrease (p < or = 0.01) in diuresis, glucose and protein losses through urine were identified in the treated group compared to the placebo group. The superoxide dismutase catalytic activity, urea and cholesterol levels involved nonsignificant changes. The results of biochemical examination show a protective antioxidative and antidiabetic effect of pomiferin. The results of histopathological examination correlate with them only partially.

Protective effects of osajin in ischemia-reperfusion of laboratory rat kidney.

The aim of this study was to analyze the antioxidative effect of osajin during prophylactic administration. The pathological model for in vivo experiment was the unilateral ischemia-reperfusion of kidney of the laboratory rat. The animals were randomly divided into five groups. Osajin was administrated orally in doses of 5, 10 and 20 mg/kg once a day to three premedicated groups. Placebo--0.5% solution of Avicel--was given to the fourth group and the fifth group was completely intact. The premedication lasted 15 days and subsequently the ischemia of the left kidney was incited in general anaesthesia for 60 min. The reperfusion lasted 10 min and it was finished by blood collection from the left ventricle and the reperfused kidney was recovered. Selected biochemical markers were assessed in blood: superoxide dismutase, glutathion peroxidase, total antioxidative capacity and malondialdehyde. The kidney tissue samples were used for histopathological examination. Laboratory and histopathological results confirmed supposed effects of osajine. The dependence between the effect and the applied dose of osajin was linear. The best biochemical results were reached after administration of osajin at the dose of 5 mg/kg. The best histopathological results were reached after administration of osajin at the dose of 10 mg/kg.

[Protective effects of the flavonoids osajin and pomiferin on heart ischemia-reperfusion]. / Protektivní efekt flavonoidu osajinu a pomiferinu na ischémii-reperfuzi srdce.

The study was undertaken to evaluate the cardioprotective potential of the flavonoids osajin and pomiferin against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based composite therapy. Studies were performed with isolated, modified Langendorff-perfused rat hearts and ischemia of the heart was initiated by stopping the coronary flow for 30 min followed by 60 min of reperfusion (14 ml x min(-1)). Wistar rats were divided into four groups. The treated groups received osajin or pomiferin (5 mg/kg/day in 0.5% Avicel), the placebo group received only 0.5 Avicel; the intact group was left without any applications. Biochemical indicators of oxidative damage--malondialdehyde, superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and the myocardium have been evaluated. We also examined the effect of osajin and pomiferin on cardiac function: left ventricular end-diastolic pressure, left ventricular pressure, and peak positive dP/dt. Our results demonstrate that the flavonoids osajin and pomiferin attenuate the myocardial dysfunction provoked by ischemia-reperfusion. This was confirmed by an increase in both the antioxidant enzyme values and the total antioxidant activity. The cardioprotection provided by osajin and pomiferin treatment results from the suppression of oxidative stress and correlates with the improved ventricular function.

[Morin in the therapy of the ischemia-reperfusion damage model of the rat kidney]. / Morin v terapii ischemicko-reperfuzního poskození ledvinné tkáne laboratorního potkana.

The aim of this study was to analyze the protective effects of morin administered during the therapy of reperfusion injury of the laboratory rat kidney. Animals were randomly divided into five groups (n= 10). One group was left intact. Three medicated groups and one placebo group were subjected to ischemia (60 min) and reperfusion of the left kidney. Morin was suspended in a 2 ml of 0.5% Avicel solution and administered orally by a gastric probe at doses of 5, 10, and 20 mg.kg(-1) once a day for 15 days. The placebo group was given only 2 ml of 0.5% Avicel in the same way. On the 15th day, all the animals were exsanguinated and the reperfused kidneys were recovered. Selected biochemical markers in blood were assessed: superoxide dismutase, glutathion peroxidase, total antioxidative capacity, malondialdehyde, creatinine, urea, and uric acid. Creatinine, urea, and total protein were analyzed in urine, and a 24-hour diuresis was recorded. The kidney tissue samples were used for histopathological examination. Morin supported the organism's own defensive reactions against free radicals and decreased lipid peroxidation in the cell membranes and contributed to the recovery of kidney functions. The histopathological results confirm 20 mg x kg(-1) as the most effective dose.

[Prophylactic administration of homoisoflavonoid in ischemic-reperfusion damage of the renal tissue in the laboratory rat]. / Profylaktické podávání homoizoflavonoidu u ischemicko- reperfuzního poskození ledvinné tkáne laboratorního potkana.

The study aimed to examine the antioxidizing effect of homoisoflavonoid in prophylactic administration under the conditions of renal ischemia-reperfusion in the laboratory rat. The pathological model for the in vivo experiment was unilateral renal ischemia-reperfusion of the laboratory rat. The animals were randomized into 5 groups. Homoisoflavonoid was administered to treated groups orally in doses of 5, 10 and 20 mg/kg once a day in 0.5% Avicel solution. The placebo group received Avicel only, and the intact group was without medication and intervention. On day 15 of the experiment, renal tissue ischemia/reperfusion (60/10 mins) was induced in the treated and placebo groups. Then the animals were exsanguinated, biochemical parameters in the blood (superoxidismutase, glutathionperoxidase, total antioxidizing capacity and malondialdehyde) were assayed, and renal samples were withdrawn for histopathological examination. A biochemical examination demonstrated a dependence of the effect of homoisoflavonoid on the dose administered. An obvious effect was demonstrated in the values of GSHPx, AOC, and MDA. On the other hand, a negative dependence was found between the dose of administered homoisoflavonoid and SOD and GSHPx values. The results of biochemical examination correlate with the histopathological pictures of the renal tissue and support the assumption about a protective effect of homoisoflavonoid under the conditions of artificially induced pathological state--renal tissue ischemia-reperfusion.