Fecal Microbiota Transplantation for Refractory Clostridioides Difficile Infection Is Effective and Well Tolerated Even in Very Old Subjects: A Real-Life Study.

OBJECTIVES: Fecal microbiota transplantation (FMT) is an innovative therapy indicated for the treatment of recurrent Clostridioides difficile infections. Although CDI and its complications are more common in very old patients (≥80 years) due to their comorbidities, frailty and senescence of the immune system, limited data are available for this older patient population. DESIGN: This was a single-center, real-life cohort study with retrospective outcome data registration, conducted at Toulouse, France. SETTING AND PARTICIPANTS: Older people group was compared to the control group aged 18-79 years. MEASUREMENTS: The primary outcome was overall survival at 52 weeks for ≥80 years patients compared to the control group after FMT. Recurrence-free survival at 52 weeks and, the occurrence of adverse events in the short and long term were the secondary endpoints. RESULTS: A total of 58 patients were included, 19 were aged ≥80 years and 39 were aged 18-79 years. Overall survival at 52 weeks after FMT of the very old patients was not different from the control group (78.9% versus 89.7%, p= 0.29). Recurrence-free survival of CDI was not different between groups, with 94.3% in the 18-79-group versus 86.9% in the ≥80 group (p=0.44). The occurrence of short- or long-term adverse events was not statistically different between the two groups (36.8% vs 41%, p=0.45). CONCLUSIONS: FMT is effective and well-tolerated in very old frail patients. This treatment brings a rapid benefit and limits the loss of functions. It also favors their maintenance at home or in a non-medical institution dedicated to dependent subjects and improves their quality of life.

[Gamma heavy chain disease associated with aggressive B lymphoma in the context of myelodysplastic syndrome]. / Maladie des chaînes lourdes de type gamma associée à un lymphome B diffus à grandes cellules dans un contexte de myélodysplasie.

INTRODUCTION: Heavy chain disease is a rare entity characterized by the production of incomplete immunoglobulin heavy chain without associated light chain. It is a B-cell lymphoproliferation, categorized according to the immunoglobulin involved. It is often associated with lymphomas but also with autoimmune diseases. OBSERVATION: We report the case of a 70-year-old patient who presented a gamma-type heavy chain disease, associated with a diffuse large B-cell lymphoma in the context of myelodysplastic syndrome. CONCLUSION: This is the first case of diffuse large B-cell lymphoma associated gamma heavy chain disease described in the context of myelodysplastic syndrome.

Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal--part II.

As reported in a previous paper, the main objective of the new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP) was the harmonisation of approaches for the validation of quantitative analytical procedures. In a series of meetings, members of this Commission have first tried to review the objectives of analytical methods and the objectives of validation methods and to recommend the use of two-sided beta-expectation tolerance intervals for total error of validation samples (accuracy profile) in the acceptance/rejection of analytical method in validation phase. In the context of the harmonization, the other objectives were: (i) to propose a consensus on the norms usually recognized, while widely incorporating the ISO terminology; (ii) to recommend to validate the analytical procedure accordingly to the way it will be used in routine; (iii) to elaborate a rational, practical and statistically reliable strategy to assure the quality of the analytical results generated. This strategy has been formalised in a guide and the three latter objectives made by the Commission are summarised in the present paper which is the second part of summary report of the SFSTP commission. The SFSTP guide has been produced to help analysts to validate their analytical methods. It is the result of a consensus between professionals having expertise in analytical and/or statistical fields. The suggestions presented in this paper should therefore help the analyst to design and perform the minimum number validation experiments needed to obtain all the required information to establish and demonstrate the reliability of its analytical procedure.

Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal--Part I.

This paper is the first part of a summary report of a new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the harmonization of approaches for the validation of quantitative analytical procedures. Indeed, the principle of the validation of theses procedures is today widely spread in all the domains of activities where measurements are made. Nevertheless, this simple question of acceptability or not of an analytical procedure for a given application, remains incompletely determined in several cases despite the various regulations relating to the good practices (GLP, GMP, ...) and other documents of normative character (ISO, ICH, FDA, ...). There are many official documents describing the criteria of validation to be tested, but they do not propose any experimental protocol and limit themselves most often to the general concepts. For those reasons, two previous SFSTP commissions elaborated validation guides to concretely help the industrial scientists in charge of drug development to apply those regulatory recommendations. If these two first guides widely contributed to the use and progress of analytical validations, they present, nevertheless, weaknesses regarding the conclusions of the performed statistical tests and the decisions to be made with respect to the acceptance limits defined by the use of an analytical procedure. The present paper proposes to review even the bases of the analytical validation for developing harmonized approach, by distinguishing notably the diagnosis rules and the decision rules. This latter rule is based on the use of the accuracy profile, uses the notion of total error and allows to simplify the approach of the validation of an analytical procedure while checking the associated risk to its usage. Thanks to this novel validation approach, it is possible to unambiguously demonstrate the fitness for purpose of a new method as stated in all regulatory documents.

Pharmacokinetics of ketoprofen in rabbit after a single topical application.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by topical application in management of joint pain and inflammation. Little is known, however, about their pharmacokinetics, especially in the synovial compartment versus the plasma compartment, following topical administration. Ketoprofen, a NSAID, was delivered by a single topical application (KETUM 2.5% gel) on the rabbit knee-joint region of one hind limb. Concentrations of ketoprofen were measured in plasma, synovial fluid, joint capsule and synovial fat tissue at 2, 4, 6 and 12 hours after application. Whatever the time period after application, ketoprofen concentrations in synovial fluid were much higher than in plasma. The time-course of the decrease in ketoprofen plasma concentrations was more rapid than that in synovial fluid. Similarly, concentrations in joint capsule were higher than those found in synovial fat tissue. Finally, while ketoprofen concentrations decreased rapidly in plasma and in synovial fat tissue, concentrations in joint capsule and particularly in synovial fluid were more sustained. The increase in residence time of ketoprofen in synovial fluid could be in favour of its efficiency in the management of joint pain and inflammation.

Aging of cylinders excised from pulp tissues of the ;golden delicious' apple.

Aging cylinders excised from ;Golden Delicious' apple (Pyrus malus L.) pulp, like the intact fruit, exhibit some characteristic phenomena such as rise in respiration (climacteric), ethylene synthesis, enzymic changes, and increase in ribosomes and mRNA. Aging of cylinders of pulp tissues may offer a useful physiological tool for the study of maturation and senescence.

Polyribosomes from aging apple and cherry fruit.

The sequence of events which occurs during the ripening of the Passe-Crassane pear fruit have been previously studied. In this work, we have investigated the ripening of another climacteric fruit (Pyrus malus L. cv Golden Delicious) and of a nonclimacteric fruit (Prunus avium L. cv Bigarreau Napoléon). We show that both climacteric fruits exhibit the same preclimacteric sequence of events. Differences exist, however, between the Golden Delicious apple and the Passe-Crassane pear in that the protein synthesis capacity of the two fruits is not the same during the over-ripening period. On the other hand, a nonclimacteric fruit, the Bigarreau Napoléon cherry, does not show an increase in its protein synthesis capacity during the over-ripening period.

Plasmodium falciparum: one-step growth in a semi-defined medium and the stimulatory effect of human seric lipoproteins and liposomes.

The ring stages of Plasmodium falciparum within red blood cells cultured with complete medium stop growing when transferred to a basic medium containing RPMI plus fatty acid-free bovine serum albumin and dialyzable factors from human serum. Growth and multiplication can be partially restored by the addition of lipoprotein fractions prepared from human serum. No specificity was observed with subclasses of lipoproteins. Synthetic liposomes containing lecithin, oleic acid, and cholesterol mimic the effect of lipoproteins.