Therapierefrakt?re Polyarthritis und Fieber

Primary manifestation of an autoinflammatory systemic disease was found in a 15-year-old patient, which initially ran a fulminant course. The course was first controlled by therapy with steroids and cyclosporin A. In the course of the disease, the patient developed a therapy refractory polyarthritis, which failed to respond to a combination of disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors. A good disease control could only be achieved with an interleukin 6 (IL-6) blockade and DMARDs.     

The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.     

Diagnostic criteria in predicting a biliary origin of acute pancreatitis in the era of endoscopic ultrasound: multicentre prospective evaluation of 213 patients.

BACKGROUND: No study on bioclinical criteria predicting a biliary origin for acute pancreatitis has included endosonography as a reference examination. Re-examination of bioclinical parameters deserves consideration in the era where other causes are known (e.g. hereditary, autoimmune). AIM AND METHODS: To determine the performance of bioclinical markers in predicting a biliary origin of acute pancreatitis where the diagnosis of biliary lithiasis was established or ruled out using endosonography. Only patients with a first acute episode of pancreatitis were included. RESULTS: 213 patients (male: 55%; median age: 56 years) were prospectively included in 14 centres. Causes of acute pancreatitis were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset and admission was <48 h in 80%. Endosonography was the sole method establishing the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis, age, female sex, declared alcohol consumption, elevated aspartate and alanine transaminases on admission, gammaglutamyl transferase, alkaline phosphatase, total bilirubin, lipase, mean corpuscular volume were predictive of a biliary origin. Only age (p < 0.0001), sex (p < 0.0008) and alanine transaminase (p < 0.0004) remained significant at multivariate analysis. At age 50, the respective sensitivity and specificity were 73 and 65%. With an elevated alanine transaminase at 2 times the upper limit of normal range, the respective sensitivity and specificity were 74 and 84%. The probability of a biliary origin of acute pancreatitis could be estimated by the following formula: = 1/1 + exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase). CONCLUSION: When endosonography is performed to confirm or exclude a biliary origin of acute pancreatitis, age, sex and alanine transaminase at admission are the only factors predictive of a biliary cause.     

Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.     

Guardianship: A medicolegal review for clinicians

Guardianship may pose an ethical dilemma for physicians, who must balance protecting vulnerable patients from potential safety concerns with respecting their autonomy. Older adults with dementia are particularly susceptible to loss of independence and the ability to participate in medical decision making. To have the capacity for medical decision making, individuals must understand relevant information, appreciate their circumstances, demonstrate reasoning, and express a consistent choice free from coercion. Although capacity assessments are usually task-specific, geriatricians and other specialists may be asked to comment on capacity more globally. These determinations may be used to support a Petition for the Appointment of a Guardian of a Legally Incapacitated Adult, the legal process of pursuing guardianship in probate court. Assigned guardians may be known to the incapacitated individual (e.g., a family member or friend) or may be professional guardians with no prior relationship to the ward. Guardians are encouraged to use substituted decision-making, taking into account the ward's previously expressed values and preferences. Although a number of viable alternatives to guardianship exist, numerous systemic barriers may prevent these from being fully explored. The ongoing need for guardianship should be periodically revisited and reassessed. Data about guardians and wards is shockingly sparse, as there are no centralized databases. Laws and regulations for guardianships vary significantly between states. Physicians can serve as important allies and advocates for patients with cognitive impairment at risk of incapacity, can help preserve their autonomy for as long as possible, and ensure appropriate protections are in place if the patient does lose their decision-making ability.