Mechanical power density, spontaneous breathing indexes, and prolonged weaning failure: a prospective cohort study.

A prospective observational study comparing mechanical power density (MP normalized to dynamic compliance) with traditional spontaneous breathing indexes (e.g., predicted body weight normalized tidal volume [VT/PBW], rapid shallow breathing index [RSBI], or the integrative weaning index [IWI]) for predicting prolonged weaning failure in 140 tracheotomized patients.

Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults.

Objectives: T cell immunity is key for the control of viral infections including SARS-CoV-2, in particular with regard to immune memory and protection against arising genetic variants.

Methods: We recently evaluated a peptide-based SARS-CoV-2 T cell activator termed CoVac-1 in a first-in-human trial in healthy adults. Here, we report on long-term safety and efficacy data of CoVac-1 until month 12.

Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency.

T-cell immunity is central for control of COVID-19, particularly in patients incapable of mounting antibody responses. CoVac-1 is a peptide-based T-cell activator composed of SARS-CoV-2 epitopes with documented favorable safety profile and efficacy in terms of SARS-CoV-2-specific T-cell response. We here report a Phase I/II open-label trial (NCT04954469) in 54 patients with congenital or acquired B-cell deficiency receiving one subcutaneous CoVac-1 dose.

The value of walking: a systematic review on mobility and healthcare costs.

Background: The ability to walk is an important indicator of general health and mobility deficits have wide-ranging economic implications. We undertook a systematic review to elucidate the impact of walking parameters on health care costs.  METHODS: Publications reporting on associations between health care costs and walking parameters were identified by a systematic literature search in MEDLINE, Embase, and manual reference screening, following the PRISMA reporting guidelines.

A new tool for bile duct tissue sampling: ex vivo clinical evaluation of intraductal cryobiopsy for cholangioscopy.

Indeterminate biliary strictures represent a major challenge in clinical diagnostics. Diagnostic yield of radiological, endoscopic imaging and histopathological diagnosis is insufficient. The cryobiopsy technique is a new method for tissue extraction already used in different clinical settings.

Mobility endpoints in marketing authorisation of drugs: what gets the European medicines agency moving?

Background: Mobility is defined as the ability to independently move around the environment and is a key contributor to quality of life, especially in older age. The aim of this study was to evaluate the use of mobility as a decisive outcome for the marketing authorisation of drugs by the European Medicines Agency (EMA).

Methods: Fifteen therapeutic areas which commonly lead to relevant mobility impairments and alter the quantity and/or the quality of walking were selected: two systemic neurological diseases, four conditions primarily affecting exercise capacity, seven musculoskeletal diseases and two conditions representing sensory impairments.

The phenotype of adverse drug effects: Do emergency visits due to adverse drug reactions look different in older people? Results from the ADRED study.

Aims: Older patients in particular suffer from adverse drug reactions (ADR) when presenting in the emergency department. We aimed to characterise the phenotype of those ADRs, to be able to recognise an ADR in older patients.

Methods: Cases of ADRs in emergency departments collected within the multicentre prospective observational study (ADRED) were analysed (n = 2215).

Personalising drug safety-results from the multi-centre prospective observational study on Adverse Drug Reactions in Emergency Departments (ADRED).

Purpose: Adverse drug reactions (ADR) account for 5 to 7% of emergency department (ED) consultations. We aimed to assess medication risk profiles for ADRs leading to ED visits.

Methods: We analysed medication intake and patient demographics in a prospective multi-centre observational study collecting ADR cases in four large EDs in Germany.

The Impact of on Tacrolimus Pharmacokinetics and Outcome in Clinical Practice at a Single Kidney Transplant Center.

Although there is evidence that the variant should be considered in tacrolimus dosing in renal transplantation, its impact beyond tacrolimus dose requirements remains controversial. In a cohort of 121 kidney transplant recipients, we analyzed the , , and alleles and the variants , , and for their impact on exposure and dose requirement. Relevant clinical outcome measures such as acute rejection within the first year after transplantation, delayed graft function, and renal function at discharge (estimated glomerular filtration rate) were evaluated.

Tacrolimus Suppositories in Therapy-Resistant Ulcerative Proctitis.

Background: Ulcerative proctitis may often be managed with topical salicylates or steroids alone, but in some patients, symptoms are persistent and severe. We analyzed the efficacy of tacrolimus suppositories in patients who had proven refractory to combined topical and systemic treatment.

Methods: In this retrospective analysis, ulcerative colitis activity index (CAI), side effects, co-medication and drug levels were assessed in 43 patients with distal ulcerative colitis who received suppositories containing 2 mg of tacrolimus b.

Impact of NUDT15 genetics on severe thiopurine-related hematotoxicity in patients with European ancestry.

Purpose: Severe hematotoxicity in patients with thiopurine therapy has been associated with genetic polymorphisms in the thiopurine S-methyltransferase (TPMT). While TPMT genetic testing is clinically implemented for dose individualization, alterations in the nudix hydrolase 15 (NUDT15) emerged as independent determinant of thiopurine-related hematotoxicity. Because data for European patients are limited, we investigated the relevance of NUDT15 in Europeans.

Influence of Variants on ova Treatment Outcome in Crohn's Disease.

A recent randomized study of whipworm ova (TSO) in ileal Crohn's disease failed to demonstrate a clinical benefit compared to placebo after 12 weeks. Nonetheless, it has recently been shown that the spontaneous small intestinal inflammatory changes in (Nucleotide-binding oligomerization domain 2) mice could be substantially ameliorated when these mice were colonized by Those and complementary epidemiologic findings in humans lead to the hypothesis that helminths may be advantageous only in patients carrying defective variants. Thus, 207 participants of the TSO trial were retrospectively genotyped for six functional genetic variants to evaluate whether the treatment outcome differed in patients carrying variants.

Antimicrobial activity of high-mobility-group box 2: a new function to a well-known protein.

The human intestinal tract is highly colonized by a vast number of microorganisms. Despite this permanent challenge, infections remain rare, due to a very effective barrier defense system. Essential effectors of this system are antimicrobial peptides and proteins (AMPs), which are secreted by intestinal epithelial and lymphoid cells, balance the gut microbial community, and prevent the translocation of microorganisms.