Longitudinal changes of cytokines and appetite in older hospitalized patients

There are few data on the longitudinal association of cytokine and appetite among older hospitalized patients. We aimed to investigate the impact of the changes of inflammatory cytokines on appetite in older hospitalized patients. A total of 191 patients (mean age 81.3 $\pm$ 6.6 years, 64% women) participated in this prospective longitudinal observational study. Appetite was evaluated using the Edmonton Symptom Assessment System on admission and after seven days. Serum cytokines such as IL-1$\beta$, IL-6, IL-8, IL-10, IL-12p70, IL-17, IL-18, IL-23 and IL-33, IFN-$\alpha$2, IFN-$\gamma$, TNF-$\alpha$ and MCP-1 were measured both times. No significant differences in the mean serum levels of all the cytokines could be detected overtime in relation to appetite changes, except for IL-18. Appetite significantly deteriorated overtime in patients with increasing IL-18 levels and improved in those without significant changes in IL-18 levels. In a stepwise regression analysis, changes of IL-18 levels were the major independent predictor for the changes of patients’ appetite and explained 4% of the variance, whereas other cytokines and variables, such as age, sex, infection and disease, did not show any impact on appetite changes. We conclude that IL-18 seems to exert a significant impact on appetite in acutely ill older hospitalized patients and should, therefore, be considered as a potential target in the diagnosis, prevention and treatment of malnutrition

Challenges associated with pancreas and kidney retransplantation

Simultaneous pancreas and kidney transplantation (SPK) is an accepted treatment for diabetic patients with renal failure, and is associated with increased survival and quality of life for recipients. There are only a few publications on the outcomes of simultaneous pancreas–kidney retransplantation (Re-SPK) after previous SPK and the loss of function of both grafts. A total of 55 patients with type 1 diabetes mellitus underwent pancreas retransplantation at our center between January 1994 and March 2021. Twenty-four of these patients underwent Re-SPK after a previous SPK. All 24 operations were technically feasible. Patient survival rate after 3 months, 1 year, and 5 years was 79.2%, 75%, and 66.7%, respectively. The causes of death were septic arterial hemorrhage ($\it n$ = 3), septic multiorgan failure ($\it n$ = 2), and was unknown in one patient. Pancreas and kidney graft function after 3 months, 1 year, and 5 years were 70.8% and 66.7%, 66.7% and 62.5%, and 45.8% and 54.2%, respectively. Relaparotomy was performed in 13 out of 24 (54.2%) patients. The results of our study show that Re-SPK, after previously performed SPK, is a technical and immunological challenge, associated with a significantly increased mortality and complication rate; therefore, the indication for Re-SPK should be very strict. Careful preoperative diagnosis is indispensable

Inflammation, appetite and food intake in older hospitalized patients

The effect of inflammation on appetite and food intake has been rarely studied in humans. In this study, we examined the association of C-reactive protein (CRP), as an inflammatory marker, with appetite and food intake among older hospitalized patients. A total of 200 older individuals, who were consecutively admitted to a geriatric acute care ward, participated in this prospective observational study. Appetite was evaluated using the Edmonton Symptom Assessment System (ESAS) and the Simplified Nutritional Appetite Questionnaire (SNAQ), respectively. Food intake was measured according to plate diagram method and participants were categorized as having food intake 3.0 (mg/dL) were considered as moderate to severe inflammation. Of total population with mean age 81.4 $\pm$ 6.6 years (62.5% females), 51 (25.5%) had no inflammation and 88 (44.0%) and 61 (30.5%) had mild and moderate to severe inflammation, respectively. According to MNA-SF, 9.0% and 60.0% had normal nutritional status or a risk of malnutrition, respectively, whereas 31.0% were malnourished. Based on the SNAQ-appetite-question, 32.5% of the patients demonstrated poor and very poor appetite whereas 23.5% reported severe loss of appetite according to ESAS. Ninety-five (48.0%) of the participants had food intake <75% of the meals offered. Significant associations between SNAQ-appetite ($\it p$ = 0.003) and ESAS-appetite ($\it p$ = 0.013) scores and CRP levels were observed. In addition, significant differences were observed in CRP levels between intake $\geq$75% and <75% of meals served ($\it p$ < 0.001). Furthermore, there were significant associations between appetite and nutritional status whereas malnourished older patients demonstrated a decreased appetite compared to those with normal nutritional status ($\it p$ = 0.011). In a regression analysis, inflammation was the major independent risk factor for patients' appetite ($\it p$ = 0.003) and food intake ($\it p$ = 0.011) whereas other variables such as infection ($\it p$ = 0.960), chronic inflammatory diseases ($\it p$ = 0.371), age ($\it p$ = 0.679) and gender ($\it p$ = 0.447) do not show any impact on appetite. Our findings confirm that poor appetite and low food intake are associated with inflammation in older hospitalized patients, suggesting that inflammation may contribute an important aspect to the development of malnutrition in these patients

Effects of treatment of asymptomatic hyperuricemia on graft survival and mortality in kidney transplant recipients

$\textbf{Background:}$ Hyperuricemia is very common after renal transplantation. It is associated with an increased risk of cardiovascular events and graft loss. To date, however, treatment is only recommended in symptomatic disease. $\textbf{Material/Methods:}$ We included 503 adult patients who underwent kidney transplantation at the Charité-Universitätsmedizin Berlin in this retrospective study. Patients were followed up for up to 120 months. All-cause mortality, graft survival, changes in level of serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were analyzed. $\textbf{Results:}$ At 12 months post-transplantation, 225 patients had a serum uric acid (SUA) level >7 mg/dl: 52 patients were treated with allopurinol, 37 with benzbromarone, and 136 patients received no medication for hyperuricemia (control). At 12 months, eGFR did not differ between groups (p=0.15) but treated patients had higher SUA levels (p<0.001) compared to the control group. SUA-lowering treatment was associated with a lower risk of allcause mortality (p=0.013) and graft loss (p=0.014) compared to controls. At 120 months, patients in the treatment group had lower SUA levels (p=0.001) and higher eGFR (p<0.001) compared to the control group. $\textbf{Conclusions:}$ Treatment of asymptomatic hyperuricemia was associated with a substantial benefit in patient and graft survival

Urinary calprotectin and posttransplant renal allograft injury

$\textit {Objective:}$ Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. $\textit {Methods:}$ In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. $\textit {Results:}$ We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r = −0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 $m^{2}$ four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. $\textit {Conclusions:}$ Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation

Epitope similarity cannot explain the pre-formed T cell immunity towards structural SARS-CoV-2 proteins

The current pandemic is caused by the SARS-CoV-2 virus and large progress in understanding the pathology of the virus has been made since its emergence in late 2019. Several reports indicate short lasting immunity against endemic coronaviruses, which contrasts studies showing that biobanked venous blood contains T cells reactive to SARS-CoV-2 S-protein even before the outbreak in Wuhan. This suggests a preformed T cell memory towards structural proteins in individuals not exposed to SARS-CoV-2. Given the similarity of SARS-CoV-2 to other members of the Coronaviridae family, the endemic coronaviruses appear likely candidates to generate this T cell memory. However, given the apparent poor immunological memory created by the endemic coronaviruses, immunity against other common pathogens might offer an alternative explanation. Here, we utilize a combination of epitope prediction and similarity to common human pathogens to identify potential sources of the SARS-CoV-2 T cell memory. Although beta-coronaviruses are the most likely candidates to explain the pre-existing SARS-CoV-2 reactive T cells in uninfected individuals, the SARS-CoV-2 epitopes with the highest similarity to those from beta-coronaviruses are confined to replication associated proteins - not the host interacting S-protein. Thus, our study suggests that the observed SARS-CoV-2 pre-formed immunity to structural proteins is not driven by near-identical epitopes

Dickkopf-3 in the prediction of contrast media induced acute kidney injury

$\bf Background$ Dickkopf-3 (DKK3) has recently been discovered as a urinary biomarker for the prediction of acute kidney injury (AKI) after cardiac surgery. This finding needs to be confirmed for AKI in other clinical settings. The present study investigates whether DKK3 can predict contrast-induced AKI (CI-AKI). $\bf Methods$ We performed a prospective study in 490 patients undergoing coronary angiography. Primary endpoint was an increase in serum creatinine concentration $\geq$ 0.3 mg/dl within 72 h after the procedure. DKK3 was assessed < 24 h before coronary angiography. Predictive accuracy was assessed by receiver operating characteristic (ROC) curves. $\bf Results$ CI-AKI was observed in 30 (6.1%) patients, of whom 27 corresponded to stage I and 3 to stage II according to the Acute Kidney Injury Network (AKIN) criteria. Subjects who developed CI-AKI had a 3.8-fold higher urinary DKK3/creatinine ratio than those without CI-AKI (7.5 pg/mg [interquartile range [IQR] 1.2–1392.0] vs. 2.0 pg/mg [IQR 0.9–174.0]; $\it p$ = 0.047). ROC analysis revealed an area under the curve (AUC) of 0.61. Among subjects without clinically overt chronic kidney disease (estimated glomerular filtration rate [eGFR] > 60 ml/min, urinary albumin creatinine ratio < 30 mg/g), the DKK3/creatinine ratio was 5.4-fold higher in those with subsequent CI-AKI (7.5 pg/mg [IQR 0.9–590.1] vs. 1.38 pg/mg [IQR 0.8–51.0]; $\it p$ = 0.007; AUC 0.62). Coronary angiography was associated with a 43 times increase in the urinary DKK3/creatinine ratio. $\bf Conclusions$ Urinary DKK3 is an independent predictor of CI-AKI even in the absence of overt chronic kidney disease (CKD). The study thereby expands the findings on DKK3 in the prediction of postoperative loss of kidney function to other entities of AKI

Impact of weather changes on hospital admissions for hypertension

Blood pressure (BP) shows a seasonal variation with higher levels at lower temperatures. Many hypertensives, however, report on BP disturbances rather in association with acutely changing weather conditions than with absolute temperatures. To date, the impact of changing meteorological parameters on hypertensive episodes remains elusive. We performed a retrospective time series regression analysis on 203,703 patients in three hospitals in Germany between 2010 and 2018, of whom 7362 patients were admitted for hypertensive disease. Numbers of daily admissions for hypertension were associated with metereological data obtained from three nearby weather stations. Data comprised temperature (mean, maximal, minimal and range within 24 h), athmospheric pressure, and precipitation. Changes of these parameters were calculated over a two and three day period. There was an inverse correlation between maximal daily temperature and the number of admissions for hypertensive disease, which remained significant both after adjustment for seasonality and week day in a spline model and in a constrained distributed lag model. A decrease of maximal temperature by 5 °C was associated with a 3% increase of risk for admission for hypertension and vice versa. There were no significant effects of precipitation and athmospheric pressure on the number of admissions. With regard to all observed metereological parameters, neither the change within two, nor within three days was consistently associated with the number of daily admissions. High temperatures are associated with lower numbers of hypertensive episodes requiring hospital admission. In contrast to the subjective perception of many hypertensive patients, however, acutely changing weather conditions are not associated with a higher risk of hypertensive emergency