Sapovirus: an emerging pathogen in kidney transplant recipients?

PURPOSE: Diarrhea is an important cause of morbidity and mortality in immunocompromised patients. After including sapovirus to the viral gastroenteritis screening of our institution's laboratory, we noticed an increase in sapovirus infections among kidney transplant recipients. Therefore, we assumed former gastrointestinal tract infections with unidentified pathogens could have been caused by sapovirus. To better understand the characteristics of a sapovirus infection in a high-risk group we initiated this study. METHODS: Over a period of 6 months, all transplant recipients with diarrhea and later identified viral/unknown pathogens were included. Kidney function, levels of immunosuppressants and  c-reactive protein, acid-base balance, onset of symptoms and time of hospitalization were analyzed. RESULTS: Among 13 hospitalized kidney transplant recipients sapovirus was detected in four patients, while in the remaining nine, three were diagnosed with norovirus, one with cytomegalovirus, one with inflammatory bowel disease and in four patients no pathogen was identified. Even though statistically not significant, creatinine levels at admission tended to be higher in sapovirus patients (median: sapovirus: 3.3 mg/dl (1.3; 5.0), non-sapovirus: 2.5 mg/dl (1.1; 4.9), p = 0.710). Also, Tacrolimus levels showed the same trend (sapovirus: 13.6 ng/ml (12.9; 13.6), non-sapovirus: 7.1 ng/ml (2.6; 22.6), p = 0.279). On discharge creatinine levels improved equally in both groups (sapovirus: 1.7 mg/dl (1.4; 3.2), non-sapovirus: 2 mg/dl (1.0; 3.6), p = 0.825). CONCLUSION: In high-risk patients, early symptomatic treatment remains crucial to protect the transplant`s function. In our cohort all patients recovered well. Larger cohorts and longer follow-up times are needed to detect the long-term consequences and a potential need for further research regarding specific treatment. TRIAL REGISTRATION: The study has been registered on DRKS (trialsearch.who.int), Reg. Nr. DRKS00033311 (December 28th 2023).

The somatotroph pituitary gland function in high-aged multimorbid hospitalized patients with IGF-I deficiency.

PURPOSE: It is unclear whether the age-related decline in the somatotropic axis stems from a reduced growth hormone (GH) production in the pituitary gland, or from a peripheral origin akin to an acquired GH resistance. With the help of a GHRH/arginine test, high-aged multimorbid hospitalized patients with IGF-I deficiency are to be tested to determine whether there is primarily a pituitary GH deficiency in the sense of a somatopause. METHODS: Seventeen multimorbid patients (eleven men and six women) with a mean age of 82 years, with IGF-I concentrations below two standard deviations of 30-year-old men and women were identified. Patients suffered from a variety of common age-related stable diseases including coronary artery disease, chronic liver or kidney disease, chronic heart failure as well as acute conditions e.g., urosepsis or endocarditis. To assess the somatotropic axis they underwent a GHRH/arginine test. Results were evaluated using descriptive statistics. RESULTS: In average, the peak concentration of GH after stimulation was 14.8 µg/L with a range from 2.76 to 47.4 µg/L. Taking into account both, gender and BMI (with a mean of 26.5 kg/m²) for each participant, the pituitary gland was adequately stimulated in 16 out of the 17 patients. No patient reported common side effects related to the GHRH/arginine test. CONCLUSION: The somatotroph pituitary gland retains its secretory capacity in the advanced aged. Therefore, age does not seem to be the driving pacemaker for the functional decline of the somatotropic axis within the aged population.

Growth hormone treatment in aged patients with comorbidities: A systematic review.

OBJECTIVE: Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects. DESIGN: A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library. INCLUSION CRITERIA: participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis. RESULTS: The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life. CONCLUSION: Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.

Function outperforms morphology in the assessment of muscular contribution to insulin sensitivity in premenopausal women.

INTRODUCTION: Skeletal muscle contributes significantly to insulin sensitivity in humans. However, which non-invasive measurement best reflects this contribution remains unknown. Consequently, this paper compares morphologic and functional measurements. RESEARCH METHODS AND DESIGN: We conducted a cross-sectional analysis of 144 premenopausal women enrolled in the "Prediction, Prevention, and Sub-classification of Type 2 Diabetes" (PPSDiab) cohort study. For the analysis, we quantified insulin sensitivity by oral glucose tolerance testing and, in a subgroup of 30 women, euglycemic clamp. To assess skeletal muscle, we measured volume by magnetic resonance imaging, intramyocellular lipid content by magnetic resonance spectroscopy, and physical fitness by cardiopulmonary exercise testing. RESULTS: The mean age of the cohort was 35.7 ± 4.1 years and 94 participants (65%) had a history of gestational diabetes mellitus. Of the morphologic and functional muscle parameters, the maximum workload achieved during cardiopulmonary exercise testing associated most closely with insulin sensitivity (standardized beta = 0.39; p < .001). Peak oxygen uptake also demonstrated significant associations, whereas muscle volume and intramyocellular lipid content displayed none. CONCLUSION: Functional measurements provided a better assessment of the muscular contribution to insulin sensitivity than morphologic measurements in premenopausal women. In particular, exercise testing rendered an easy and cost-effective method applicable in clinical settings and other human studies.