Ulcerative colitis: exceptional consequence after rituximab therapy

Introduction

Possible adverse complications related to rituximab (RTX) are low, some of which are extremely rare. The authors describe one situation visibly waning exceptional treatment with RTX for SLE refractory to conventional therapies.

Comment

The authors report a patient of 34 years followed for months for an illness in its bullous lupus, with cutaneous, articular, hematologic and immunologic. Given a corticosteroid resistance, several therapeutic background based hydroxychloroquine, cyclophosphamide and methotrexate, were initiated without any improvement. Immunomodulatory therapy type RTX was introduced to this form refractory at a rate of 375 mg/m²/week. The waning of the second infusion, the patient presented a sudden intense abdominal pain syndrome, revealing an acute catarrhal appendicitis. At distance from the appendectomy, the consequences of which were favorable, treatment with RTX was resumed. In the aftermath of the third infusion, the patient presented in table tract marked by profuse watery diarrhea whose explorations reveal a morphological endoscopic appearance of erythematous, ulcerative colitis, reversible upon discontinuation of treatment. Histological data revealed important infiltrates composed mainly of CD8 T lymphocytes.

Conclusion

Gastrointestinal immunological consequences to the requirements of the targeted therapies deserved very careful and rigorous monitoring. However, at the slightest sign of digestive, a detailed morphological exploration is essential, to avoid in particular surgical emergency, evolution without treatment could engage in short-term vital prognosis.     

Handiness and acceptability of the new Abak bottle in chronically treated patients. A cross-sectional, retrospective and multicentre study

Background

Difficulty of use of eyedrops is a factor associated with poor patient compliance that reduces treatment efficacy. The aim of this study was to evaluate the handiness and global acceptability of the new Abak^® timolol bottle (multidose preservative-free eyedrops) in comparison with that of other administration systems (classical multidose eyedrops or single-doses) in patients treated for glaucoma or ocular hypertension.

Methods

Cross-sectional, retrospective and multicentre study involving 41 ophthalmologists in France. Selected patients were those who had been treated with the new Abak^® bottle since at least two months, as a replacement for other beta-blocker eyedrops. Handiness and acceptability of the new Abak^® bottle in comparison with other delivery systems were evaluated using a questionnaire filled by the investigator.

Results

Almost all the patients were unanimous regarding the handiness of the new Abak^® bottle: easy to open for 96.5% of them, easy to handle for 96.0%, and easy to get drops for 91.1%. For all these criteria and in a general manner, patients preferred the new Abak^® bottle in comparison with the previous eyedrop container. These results were confirmed in the oldest patients.

Conclusion

The new Abak^® bottle had a greater acceptability compared to preserved multidose eyedrops or to single-doses. Its handiness and the absence of preservative which may improve local tolerance are in favor of a greater compliance in chronically treated patients.     

Durable efficacity and remission after treatment with imatinib mesylate for FIP1L1-PDGFRA transcript negative associated eosinophilic cardiomyopathy

Introduction

The cardiac involvement in hypereosinophilia remains a major cause of morbidity and mortality. Recent advances have identified new molecular mechanisms responsible for the expansion of the eosinophilic lineage, allowing a better classification of the different forms of Hypereosinophilic syndrome (HES) and especially targeted therapy. Since the discovery of the involvement of deregulated tyrosine kinases in the pathophysiology of these diseases, and particularly the identification of the fusion gene FIP1L1–PDGFRA, new molecules inhibiting specifically this signaling pathway (imatinib) were individualized, leading to dramatic therapeutic benefits in proliferative forms of HES considered before that of very poor prognosis.

Case report

We report here the dramatic effectiveness of imatinib used as second line therapy for dilated cardiomyopathy revealing a hypereosinophilic syndrome in a patient in whom the search for FIP1-L1-PDGFRA fusion gene was negative.

Conclusion

If hypereosinophilia has varied clinical and morphological outcome, its clinical consequences, particularly on heart function, are sometimes dreadful, and are not correlated either with blood eosinophil levels or with a specific etiology. We report here a case of HES lacking the FIP1-L1-PDGFRA fusion gene showing that despite the absence of this molecular defect, imatinib mesylate may have therapeutic interest in those cases of HES resistant to first line therapies.     

Proposal of a costing method for the provision of sterilization in a public hospital

Introduction

To refine the billing to institutions whose operations of sterilization are outsourced, a sterilization cost approach was developed. The aim of the study is to determine the value of a sterilization unit (one point “S”) evolving according to investments, quantities processed, types of instrumentation or packaging.

Materials and methods

The time of preparation has been selected from all sub-processes of sterilization to determine the value of one point S. The time of preparation of sterilized large and small containers and pouches were raised. The reference time corresponds to one bag (equal to one point S). Simultaneously, the annual operating cost of sterilization was defined and divided into several areas of expenditure: employees, equipments and building depreciation, supplies, and maintenance.

Results

A total of 136 crossing times of containers were measured. Time to prepare a pouch has been estimated at one minute (one S). A small container represents four S and a large container represents 10 S. By dividing the operating cost of sterilization by the total number of points of sterilization over a given period, the cost of one S can be determined.

Discussion/conclusion

This method differs from traditional costing method in sterilizing services, considering each item of expenditure. This point S will be the base for billing of subcontracts to other institutions.     

Study of meta-trajectories of CD4 cells count from taxonomy in the antiretroviral response of efavirenz-based regimen with naive symptomatic patients in Abidjan

Introduction

Sub-Saharan Africa remains the most affected region in the global AIDS epidemic. Côte d’Ivoire is one of the most affected countries by this epidemic. The collective search for deleterious determinants of the evolution of immunological markers (CD4 cells count) may help to optimize the therapeutic efficiency in this resource-limited country.

Patients and methods

We are interested in studying the antiretroviral response of efavirenz-based regimen (treatment of choice in first line) by the nonhierarchical-descendant model by taxonomy of CD4 cells count trajectories. From 87 CD4 cells count trajectories of symptomatic naive patients, classes of similar profiles grouped by the model have formed typical profiles of evolution as meta-trajectories. The analysis of these meta-trajectories was used to study the determinants of CD4 cells count evolution by classes of patients.

Results

Four classes have been determined for an optimal taxonomy with a partition score of 0.72: P1 (n = 27), P2 (n = 15), P3 (n = 24), P4 (n = 21). Our model showed a variation between groups of CD4 cells count trajectories linked to explanatory factors by highlighting the predictive role of certain characteristics on antiretroviral response in Côte d’Ivoire (CD4 cells count baseline [P < 0.01], CD4 percentage baseline [P < 0.05], adherence [P < 0.05]). The multiple correspondence analysis revealed other characteristics that influence the immune response such as the presence of opportunistic infections, bloodless status and weight at the initiation of treatment.

Conclusion

The factors influencing the profile of meta-trajectories of CD4 cells count during efavirenz-based antiretroviral regimen should be considered at the initiation of treatment to optimize performance in the therapeutic monitoring of patients in Abidjan. The model of biomedical indicators meta-trajectories provides a therapeutic decision support provided prior to capitalize sufficient expertise for a better interpretation.     

Accuracy, precision and speed of parenteral nutrition admixture bags manufacturing: comparison between automated and manual methods

Introduction

The parenteral nutrition admixture (PNA) manufacturing in hospital pharmacy is realized by aseptic transfer (AT) or sterilizing filtration (SF). The development of filling systems for PNA manufacturing requires, without standard, an evaluation comparing to traditional methods of SF.

Materials and methods

The filling accuracy of automated AT and SF was evaluated by mass and physical-chemistry tests in repeatability conditions (identical composition of PNA; n = five bags) and reproducibility conditions (different composition of PNA; n = 57 bags). For each manufacturing method, the filling precision and the average time for PNA bags manufacturing were evaluated starting from an identical composition and volume PNA (n = five trials).

Results

Both manufacturing methods did not show significant difference of accuracy. Precision of both methods was lower than limits generally admitted for acceptability of mass and physical-chemistry tests. However, the manufacturing time for SF was superior (five different binary admixtures in five bags) or inferior (one identical binary admixture in five bags) to time recorded for automated AT.

Discussion and conclusions

We show that serial manufacturing of PNA bags by SF with identical composition is faster than automated AT. Nevertheless, automated AT is faster than SF in variable composition of PNA. The manufacturing method choice will be motivate by the nature (i. e., variable composition or not) of the manufactured bags.     

Validation of pharmaceutical quality of a [6,6-(2)H(2)]-glucose parenteral solution used for insulin-resistance measurement during human clinical trials

Introduction

Deuterated glucose ([6,6-²H₂]-glucose) is a stable isotopic tracer administered parenterally in healthy volunteers, obese or diabetic patients in clinical trial to study glucose metabolism during euglycemic hyperinsulinemic clamps. In accordance with the Health Authorities on drug safety, we evaluated the pharmaceutical quality of this preparation for biomedical research with a stability study.

Methods

After pharmaceutical qualification of the raw material, the [6,6-²H₂]-glucose was dissolved in water for injection, then sterile, filtered under positive pressure of nitrogen and then autoclaved. Two batch products (500 mg/10 mL and 2 g/15 mL) were sampled to evaluate glucose alteration, isotope shift, limpidity, apyrogenicity and sterility at regular intervals for 2 years. Deuterated glucose solutions were stored in the dark, at +2 °C + 8 °C, in type II glass bottles.

Results

Neither significant decrease of glucose concentration nor pH variation were observed for 2 years. The 5-hydroxymethylfurfural concentration was below the human harmful levels, attesting a non-generation of metabolites during autoclaving. Isotopic enrichment higher than 99% reflected the stability of deuterated label on the 6-carbon of glucose molecules. The non-visible particle concentration below the minimal permissible concentration tolerated by the European Pharmacopoeia and the absence of bacterial endotoxin and bacterial growth attested limpidity, apyrogenicity and sterility of the [6,6-²H₂]-glucose solutions.

Conclusion

After the 2-year study, 500 mg/10 mL and 2 g/15 mL deuterated glucose solutions stored in the dark at +2 °C + 8 °C were stable in aqueous solution, allowing to ensure safety administration for human clinical trials using euglycemic hyperinsulinemic clamps.     

Evaluation of the performance of transfer devices in a closed system using a radioactive solution of [(99m)Tc]

Introduction

The exposure of workers to antineoplastic agents is potentially dangerous in the long term because of the teratogenic, carcinogenic and mutagenic hazardous of these products. These risks could be reduced by individual and collective shield measures. It's recommended to use transfer devices in a closed system for preparation of chemotherapy.

Method

The aim of the survey is to analyse for five devices (four devices in a closed system transfer and a needle equipped with an air intake), the following criteria: transfer performance of a solution of a vial to another one, no leakage of the device and practicality in the use. A method implementing a radioactive solution of sodium pertechnetate [^99mTc] is used.

Results

Teva^® and Cardinal^® devices seem to be more efficient according to the ability to transfer one solution from a vial to another one with a low dead volume and low-level contamination in the around of the manipulation area. The Hospira^® device appears an intermediate solution, while the Phaseal^® device may be irrelevant for the transfer of a solution.

Discussion-Conclusion

Our study could attest that the methodology is simple to implement and cheap to compare devices on multiple selection criteria. This evaluation method is interesting because it allows a classification according to several criteria weighted according to the type of intended use. In addition to economic issues and protection of the worker, the use of such devices should be extended to other areas as the preparation of chemotherapy such as preparation of radiopharmaceuticals drugs.     

Diagnostic value of salivary CRP and IL-6 in patients undergoing anti-TNF-alpha therapy for rheumatic disease

Introduction

Saliva has been increasingly used as a diagnostic medium for disease detection and monitoring. The aim of this observational, prospective, pilot study was to investigate whether salivary concentrations of CRP and IL-6 correlate with those in serum and with the clinical course of a rheumatic disease.

Materials and methods

Nineteen patients with rheumatic disease newly scheduled for anti-TNFα therapy were included. Patients received anti-TNFα treatment (adalimumab, certolizumab, golimumab or infliximab) as per standard protocols. CRP and IL-6 were measured with high-sensitivity immunoassays before and after 12 weeks of therapy, according to standard regimens. The data were analyzed with nonparametric statistics.

Results

Concentrations of CRP in saliva correlated significantly with those in serum (R?=?0.62; p?<?0.0001) and decreased markedly after successful response to treatment. In patients with a limited response to treatment salivary CRP levels increased. In contrast to CRP, the salivary concentrations of IL-6 did not change significantly over the course of therapy and they did not correlate with serum IL-6 concentrations. Salivary levels of neither CRP nor IL-6 corresponded to parameters of oral health and hygiene.

Conclusions

Salivary CRP but not IL-6 could be of potential use for monitoring the rheumatic disease activity.

     

Pharmacokinetics and safety of subcutaneous rituximab plus fludarabine and cyclophosphamide for patients with chronic lymphocytic leukaemia

Aims

The aim of the phase Ib, two part SAWYER study (BO25341; {"type":"clinical-trial","attrs":{"text":"NCT01292603","term_id":"NCT01292603"}}NCT01292603) was to investigate the pharmacokinetics and safety of subcutaneous (s.c.) rituximab compared with intravenous (i.v.) rituximab, both in combination with fludarabine and cyclophosphamide (FC), as first line treatment for patients with chronic lymphocytic leukaemia (CLL).

Methods

During part 1 (dose-finding), CLL patients received rituximab i.v. followed by a single dose of rituximab s.c. at one of three fixed doses (1400, 1600 or 1870 mg) in cycle 6. The primary objective was to identify a fixed s.c. dose that would achieve comparable rituximab serum trough concentrations (C_trough) to those achieved with the standard 4 weekly 500 mg m^–2 rituximab i.v. dose.

Results

Fifty-five patients received a fixed dose of rituximab s.c., 16 received 1400 mg, 17 received 1600 mg and 22 received 1870 mg. The 1600 mg dose was predicted to achieve non-inferior C_trough to standard rituximab i.v. treatment. The rituximab s.c. safety profile was comparable with rituximab i.v., except that local administration-related reactions, mainly mild/moderate injection site reactions, occurred more frequently with rituximab s.c., which was not unexpected. Subcutaneous administration was preferred to i.v. administration by >90% of patients and nurses (n = 112).

Conclusions

SAWYER part 1 data predict that rituximab s.c. 1600 mg will achieve non-inferior C_trough concentrations to rituximab i.v. 500 mg m^–2, administered 4 weekly. This fixed s.c. dose is currently undergoing formal non-inferiority assessment in SAWYER part 2. In future, CLL treatment regimens comprising rituximab s.c. and oral FC could substantially reduce i.v. chair time.     

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose

To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost.

Methods

This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated.

Results

A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5–68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2–4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12–30 months) in 69.2 % of patients showing a short-term response. Median cost per patient was € 5,187.5 (IQR € 5,187.5–7,781.3).

Conclusions

In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.     

Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis

Purpose

Analog development of existing drugs and direct drug delivery to the lungs by inhalation as treatments for multiple and extensively drug resistant (MDR and XDR) tuberculosis (TB) represent new therapeutic strategies. Pyrazinamide (PZA) is critical to drug sensitive TB therapy and is included in regimens for MDR TB. However, PZA-resistant Mycobacterium tuberculosis (Mtb) strains threaten its use. Pyrazinoic acid esters (PAEs) are PZA analogs effective against Mtb in vitro, including against the most common PZA resistant strains. However, PAEs require testing for TB efficacy in animal models.

Methods

PAEs were delivered daily as aqueous dispersions from a vibrating mesh nebulizer to Mtb infected guinea pigs for 4 weeks in a regimen including orally administered first-line TB drugs.

Results

PAEs tested as a supplement to oral therapy significantly reduced the organ bacterial burden in comparison to infected, untreated control animals. Thus, PAE aerosol therapy is a potentially significant addition to the regimen for PZA resistant MDR-TB and XDR-TB treatment. Interestingly, low dose oral PZA treatment combined with standard therapy also reduced bacterial burden. This observation may be important for PZA susceptible disease treatment.

Conclusion

The present study justifies further evaluation of PZA analogs and their lung delivery to treat TB.

     

Kortikale Aktivierungen durch Yamamoto Neue Schädelakupunktur (YNSA) in der Behandlung von Schlaganfallpatienten – Eine Sham-kontrollierte Studie mit Hilfe der funktionellen Kernspintomographie (fMRI)

Background

Yamamoto New Scalp Acupuncture was first introduced 35 years ago. Today, it is the most often used microsystem in acupuncture next to auriculotherapy .

Aims

Can the efficacy of YNSA – by means of cortical activation – be visualized in fMRI? The neurological correlates of YNSA were studied with the aid of fMRI in 17 patients with ischemic stroke damage in the right hemi-sphere suffering from residual paresis of the left hand versus 19 healthy volunteers. A new acupuncture needle for magnetic resonance imaging developed by Schockert was used in this study.

Methods

The study was performed in a 1.5 tesla Philips MRI system (TR 3000 ms, TE 50 ms, FA 90°) in a box-car design. Patients were instructed via video goggles to open or close their left hand for five seconds. The data were analyzed by the SPM 2 evaluation program. All patients and volunteers were first subjected to sham acupressure and then YNSA. The sham acupuncture consisted of a single application of pressure by a finger nail in the centre of an imaginary line between SJ 23 and Gb 14. In the verum YNSA, needles were applied to the yin points of the basal ganglia, cerebellum and basic point C.

Results

Of the 17 patients, only five measurements could be evaluated due to motion artefacts. It was not possible to make a group analysis because of the inhomogeneous lesions. The cortical activations were different in each patient. In contrast to the sham acupuncture, verum acupuncture displayed significant cortical activation in the motor, premotor and supplemental motor cortex of the patients.It was possible to evaluate the measurements of the volunteers as a group analysis. In contrast to the patients, the volunteers displayed a decrease in cortical activation during YNSA.

Conclusions

Eight patients in this study experienced a perceptible improvement in mobility and a reduction of spasticity as a result of stroke treatment with YNSA. These motor improvements positively correlate to cortical activity which can be visualized by functional magnetic resonance imaging.Further more extensive clinical and fMRI studies are necessary in order to investigate YNSA-induced cortical activation in stroke patients in deeper detail.     

Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B: A European multicenter study

Background and aims

The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in patients with chronic hepatitis B (CHB).

Methods

Seventy eight consecutive CHB patients from five European centers were included. All started a TDF + FTC combination between October 2005 and March 2010. Virological, biochemical, and clinical data were recorded during follow-up. Tolerance was also monitored. Patients were classified into either treatment simplification (TS), where efficacy of the previous treatment was obtained at TDF + FTC initiation, and treatment intensification (TI), where the previous line of therapy had failed.

Results

TDF + FTC was given as a TI to 54 patients (69%) and as a TS to 24 (31%). Among patients with TI, 83% were males. The median baseline HBV-DNA was 4.4 log₁₀ IU/mL, and median alanine-transaminase (ALT) was 1.10 × ULN. Sixty percent were HBeAg positive, 47% had significant fibrosis (?F3 Metavir equivalent), and 29% had confirmed cirrhosis. Median treatment duration was 76 weeks (interquartile range 60–116). Kaplan–Meier analysis showed that, 48 weeks after TI, the probability of being HBV-DNA becoming undetectable was 76%, and reached 94% at week 96. No viral breakthrough occurred. Patients with TS (87% males, median baseline HBV-DNA 1.1 log₁₀ IU/mL, median ALT 0.79 × ULN, 33% HBeAg positive, 61% with significant fibrosis) were treated for a median duration of 76 weeks. In this subgroup, all patients but one remained HBV-DNA undetectable and no ALT flare-up occurred during follow-up. Creatinine levels did not show kidney-function deterioration in either group of patients.

Conclusions

After a median follow-up of >76 weeks, the TDF + FTC combination showed encouraging antiviral efficacy and a good safety profile in all patients with CHB. TDF + FTC may represent an interesting clinical option to simplify therapy and increase the barrier to resistance, which should be assessed in the long term.     

Colchicine in chronic hepatitis B: a pilot study

Rationale:

Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. Early in vitro studies have demonstrated that colchicine blocks mitosis in the metaphase and inhibits DNA synthesis.

Aim:

A pilot study of hepatitis B virus (HBV)-related/HBV-DNA+ve chronic liver disease.

Patients:

Nine biopsy-proven chronic hepatitis patients (three with cirrhosis) entered the study. Two of them were HBeAg+ve and seven were antiHBe+. All patients were HBV-DNA+ve/antiHBc IgM+ve (index values of anti-HBc IgM ranged from 0.370 to 1.200). All of them had a major contraindication to interferon therapy or refused antiviral treatment. The known persistence of positive HBsAg ranged from 2 to 21 years.

Methods:

After informed consent, the patients received 1 mg colchicine a day orally for 5 days-a-week over 6 months. Testing for liver enzymes and viral markers was performed at the baseline and after 3 and 6 months.

Results:

None of the patients experienced side-effects during the treatment. The two HBeAg+ve patients seroconverted to anti-HBe with a normalization of AST/ALT during therapy. Among the seven antiHBe+ve patients, four had a complete normalization of transaminases (one patient cleared the HBsAg with seroconversion to anti-HBs). Six of the nine patients were HBV-DNA-ve at the end of therapy and were still negative after 12 months of follow-up.

Conclusion:

These preliminary results suggest that colchicine might have an antiviral activity in HBV-DNA+ve chronic liver disease, and it could be regarded as an alternative therapy to interferon.

     

A clinical prediction model for infusion-related reactions to rituximab in patients with B cell lymphomas

Background Infusion-related reactions (IRRs) are a major adverse event of rituximab. Objective To develop a prediction model for IRRs to rituximab among patients with B cell non- Hodgkin’s lymphomas (B-NHL). Setting A 1000-bed university hospital in Tokyo. Methods Patients with B-NHL treated with rituximab at our institution from 2004 to 2014 were retrospectively analysed. Chills, fever, rash, nausea, asthenia, headache, cardiovascular symptoms, and respiratory symptoms of any grade, in association with rituximab infusion, were identified as IRRs. Risk factors for IRRs to rituximab found in the intergroup analysis were subsequently evaluated by using multivariate analysis. Main outcome measure Occurrence of IRRs to rituximab. Results A total of 140 patients with various types of B-NHL, including 74% with diffuse large Bcell lymphoma, were analysed. Among them, 55 and 85 patients were assigned to the IRR group and the non-IRR group, respectively. Indolent histological subtypes, bulky disease (>10 cm), B symptoms, higher serum soluble interleukin-2 receptor concentration, and bone marrow involvement were more common in the IRR group. The multivariate logistic regression analysis identified low-grade lymphomas [odds ratio (OR) 2.81, p = 0.017] and bulky disease (OR 2.52, p = 0.037) as independent risk factors for IRRs to rituximab. The incidence rates of IRRs to rituximab among patients with neither, one, or both of these risk factors were 26, 54, and 78%, respectively (χ² = 16.4, p < 0.001). Conclusions A simple combination of histopathological subtype and bulkiness of disease could predict the risk of IRRs to rituximab among patients with B-NHL.     

Effects of intranasal xylometazoline,alone or in combination with ipratropium,in patients with common cold

Abstract

Background:

Common cold is one of the most prevalent conditions that family doctors encounter. One of the first symptoms to occur is nasal congestion, which can have a negative impact on daily life and prompts many patients to seek treatment for relief. Xylometazoline nasal spray (Otrivin^*) is a topical decongestant that has been used successfully for many years and is generally recognized as an effective and safe therapy. However, most studies have investigated its clinical efficacy in healthy patients and few have included patients with common cold.     

Biomimetic Delivery Strategies at the Urothelium: Targeted Cytoinvasion in Bladder Cancer Cells via Lectin Bioconjugates

Purpose

Urothelial cells, including bladder cancer (BCa) cells, represent a highly valuable but challenging target for localized antineoplastic therapy. This study describes a novel, biomimetic approach to improve intravesical drug delivery, based on glycan-specific targeting. In direct analogy to the invasion mechanism used by uropathogenic bacteria, we evaluate the potential of lectin bioconjugates to facilitate binding and uptake of large payload molecules at this penetration-hostile barrier.

Methods

Wheat germ agglutinin (WGA) served as a targeting ligand and was covalently coupled to fluorescein-labeled bovine serum albumin (fBSA), yielding multivalent protein bioconjugates. Cytoadhesion, uptake and intracellular processing were characterized on a panel of urothelial cell lines of non-malignant and malignant origin.

Results

Conjugation to WGA rendered the fBSA payload protein strongly cytoadhesive, with a clear preference in binding to cancerous cells. The highly specific, lectin-mediated recognition process was followed by rapid internalization, and extensive but non-exclusive accumulation in acid and LAMP-2-positive compartments. Stage of malignancy and mechano-structural cell configuration were important determinants for the sorting between different processing pathways.

Conclusion

Lectin-bioconjugates allow for triggering endogenous uptake routes and influencing the intracellular distribution in BCa cells. They hold considerable promise for enhancing the delivery of small molecule drugs and complex biomolecules in intravesical therapy.