Hyponatremia in the emergency department: an overview of diagnostic and therapeutic approach.

INTRODUCTION: Hyponatremia, defined as a serum sodium concentration <135 mmol/l, is a frequent electrolyte disorder in patients presenting to an emergency department (ED). In this context, appropriate diagnostic and therapeutic management is rarely performed and challenging due to complex pathophysiologic mechanisms and a variety of underlying diseases. OBJECTIVE: To implement a feasible pathway of central diagnostic and therapeutic steps in the setting of an ED. METHODS: We conducted a narrative review of the literature, considering current practice guidelines on diagnosis and treatment of hyponatremia. Underlying pathophysiologic mechanisms and management of adverse treatment effects are outlined. We also report four cases observed in our ED. RESULTS: Symptoms associated with hyponatremia may appear unspecific and range from mild cognitive deficits to seizures and coma. The severity of hyponatremia-induced neurological manifestation and the risk of poor outcome is mainly driven by the rapidity of serum sodium decrease. Therefore, emergency treatment of hyponatremia should be guided by symptom severity and the assumed onset of hyponatremia development, distinguishing acute (<48 hours) versus chronic hyponatremia (>48 hours). CONCLUSIONS: Especially in moderately or severely symptomatic patients presenting to an ED, the application of a standard management approach appears to be critical to improve overall outcome. Furthermore, an adequate work-up in the ED enables further diagnostic and therapeutic evaluation during hospitalization.

SARS-CoV-2 antigen rapid immunoassay for diagnosis of COVID-19 in the emergency department.

BACKGROUND: In the emergency department (ED) setting, rapid testing for SARS-CoV-2 is likely associated with advantages to patients and healthcare workers, for example, enabling early but rationale use of limited isolation resources. Most recently, several SARS-CoV-2 rapid point-of-care antigen tests (AGTEST) became available. There is a growing need for data regarding their clinical utility and performance in the diagnosis of SARS-CoV-2 infection in the real life setting EDs. METHODS: We implemented AGTEST (here: Roche/SD Biosensor) in all four adult and the one paediatric EDs at Charité - Universitätsmedizin Berlin in our diagnostic testing strategy. Test indication was limited to symptomatic suspected COVID-19 patients. Detailed written instructions on who to test were distributed and testing personnel were trained in proper specimen collection and handling. In each suspected COVID-19 patient, two sequential deep oro-nasopharyngeal swabs were obtained for viral tests. The first swab was collected for nucleic acid testing through SARS-CoV-2 real-time reverse transcriptase (rt)-PCR diagnostic panel (PCRTEST) in the central laboratory. The second swab was collected to perform the AGTEST. Analysis of routine data was prospectively planned and data were retrieved from the medical records after the inclusion period in the adult or paediatric ED. Diagnostic performance was calculated using the PCRTEST as reference standard. False negative and false positive AGTEST results were analysed individually and compared with viral concentrations derived from the calibrated PCRTEST. RESULTS: We included n = 483 patients including n = 202 from the paediatric ED. N = 10 patients had to be excluded due to missing data and finally n = 473 patients were analysed. In the adult cohort, the sensitivity of the AGTEST was 75.3 (95%CI: 65.8/83.4)% and the specificity was 100 (95%CI: 98.4/100)% with a SARS-CoV-2 prevalence of 32.8%; the positive predictive value was 100 (95%CI: 95.7/100)% and the negative predictive value 89.2 (95%CI: 84.5/93.9)%. In the paediatric cohort, the sensitivity was 72.0 (95%CI: 53.3/86.7)%, the specificity was 99.4 (95%CI:97.3/99.9)% with a prevalence of 12.4%; the positive predictive value was 94.7 (95%CI: 78.3/99.7)% and the negative predictive value was 96.2 (95%CI:92.7/98.3)%. Thus, n = 22 adult and n = 7 paediatric patients showed false negative AGTEST results and only one false positive AGTEST occurred, in the paediatric cohort. Calculated viral concentrations from the rt-PCR lay between 3.16 and 9.51 log10 RNA copies/mL buffer. All false negative patients in the adult ED cohort, who had confirmed symptom onset at least seven days earlier had less than 5 × 105 RNA copies/mL buffer. CONCLUSIONS: We conclude that the use of AGTEST among symptomatic patients in the emergency setting is useful for the early identification of COVID-19, but patients who test negative require confirmation by PCRTEST and must stay isolated until this result becomes available. Adult patients with a false negative AGTEST and symptom onset at least one week earlier have typically a low SARS-CoV-2 RNA concentration and are likely no longer infectious.

[The abdominal pain unit as a treatment pathway : Structured care of patients with atraumatic abdominal pain in the emergency department]. / Die Abdominal Pain Unit als Behandlungspfad : Strukturierte Versorgung von Patient*innen mit atraumatischen Bauchschmerzen in der Notaufnahme.

BACKGROUND: Patients with atraumatic abdominal pain are common in the emergency department and have a relatively high hospital mortality, with a very wide spectrum of different causes. Rapid, goal-directed diagnosis is essential in this context. METHODS: In a Delphi process with representatives of different disciplines, a diagnostic treatment pathway was designed, which is called the Abdominal Pain Unit (APU). RESULTS: The treatment pathway was designed as an extended event process chain. Crucial decision points were specified using standard operating procedures. DISCUSSION: The APU treatment pathway establishes a consistent treatment structure for patients with atraumatic abdominal pain. It has the potential to improve the quality of care and reduce intrahospital mortality over the long term.

Point-of-care lung ultrasound in COVID-19 patients: inter- and intra-observer agreement in a prospective observational study.

With an urgent need for bedside imaging of coronavirus disease 2019 (COVID-19), this study's main goal was to assess inter- and intraobserver agreement in lung ultrasound (LUS) of COVID-19 patients. In this single-center study we prospectively acquired and evaluated 100 recorded ten-second cine-loops in confirmed COVID-19 intensive care unit (ICU) patients. All loops were rated by ten observers with different subspeciality backgrounds for four times by each observer (400 loops overall) in a random sequence using a web-based rating tool. We analyzed inter- and intraobserver variability for specific pathologies and a semiquantitative LUS score. Interobserver agreement for both, identification of specific pathologies and assignment of LUS scores was fair to moderate (e.g., LUS score 1 Fleiss' κ = 0.27; subpleural consolidations Fleiss' κ = 0.59). Intraobserver agreement was mostly moderate to substantial with generally higher agreement for more distinct findings (e.g., lowest LUS score 0 vs. highest LUS score 3 (median Fleiss' κ = 0.71 vs. 0.79) or air bronchograms (median Fleiss' κ = 0.72)). Intraobserver consistency was relatively low for intermediate LUS scores (e.g. LUS Score 1 median Fleiss' κ = 0.52). We therefore conclude that more distinct LUS findings (e.g., air bronchograms, subpleural consolidations) may be more suitable for disease monitoring, especially with more than one investigator and that training material used for LUS in point-of-care ultrasound (POCUS) should pay refined attention to areas such as B-line quantification and differentiation of intermediate LUS scores.

Risk stratification for renal transplantation after cardiac or lung transplantation: single-center experience and review of the literature.

BACKGROUND: Long-term survival after heart (HTx) or lung (LuTx) transplantation increases the risk for end-stage renal disease (ESRD). After HTx ESRD was reported to enhance mortality, and kidney transplantation (KTx) was shown to improve survival. However, prognostic factors in ESRD after HTx or LuTx are largely unknown. METHODS: Single-center observational study in HTx and LuTx patients who accessed the KTx waiting list; baseline characteristics were correlated with mortality. RESULTS: KTx was performed in 15 of 65 study patients. Survival was comparable on the KTx waiting list and in reference patients from the same center without ESRD. KTx significantly improved survival (5 years' survival 84.6% with KTx vs. 56.5% on the KTx waiting list, p = 0.030). None of the baseline parameters predicted mortality in the KTx group. Only on the KTx waiting list BMI (median 24.7 vs. 20.7; p < 0.05) and left ventricular ejection fraction (LVEF, median 63 vs. 53%, p < 0.008) significantly correlated with survival. CONCLUSIONS: The risk for mortality after HTx or LuTx is not increased by ESRD, provided that patients meet access criteria for the KTx waiting list. KTx improves survival in ESRD after HTx or LuTx. BMI and LVEF may predict outcome in HTx/LuTx patients on the KTx waiting list.

Short-term immunosuppressive treatment of the donor ameliorates consequences of ischemia/ reperfusion injury and long-term graft function in renal allografts from older donors.

BACKGROUND: Grafts from so-called "marginal donors" are increasingly used for organ transplantation. The combination of reduced organ quality and additional inflammatory damages may be particularly detrimental in these grafts. In a previous study, we showed the beneficial effects on long-term graft outcome of "suboptimal" grafts by the induction of heme oxygenase-1. Here we tested the impact of short-term donor treatment with established immunosuppressants. METHODS: Twelve-month-old Fischer 344 donor rats either were treated with prednisolone, mycophenolate mofetil, RAD, or FK506 24 hr and 1 hr before organ harvesting or remained untreated. Renal allografts were perfused with University of Wisconsin solution and kept at 4 degrees C for an ischemic period of 2 hr. Morphologic, immunohistologic, and real time reverse transcriptase-polymerase chain reaction analyses for relevant markers were performed at serial intervals and at the end of the observation period (6 months). RESULTS: All animals survived the observation period, although the ischemic time resulted in accelerated chronic graft dysfunction. Grafts from donors treated with prednisolone or FK506 demonstrated significantly improved graft function and structure by 6 months. Mononuclear infiltrates were significantly reduced by the end of the observation period, whereas intragraft mRNA levels of tumor necrosis factor-alpha and interleukin-10 were significantly altered during the early period after transplantation. Minor improvements in graft function and histologic alterations of suboptimal grafts were observed after pretreatment with mycophenolate mofetil and RAD. CONCLUSION: Donor treatment with approved immunosuppressants, in particular prednisolone or FK506, represents a novel therapeutic strategy of clinical relevance, most importantly when using grafts from marginal donors.

Alterations of the immune response with increasing recipient age are associated with reduced long-term organ graft function of rat kidney allografts.

BACKGROUND: Clinically, an increasing number of older recipients are listed for transplantation. We examined recipient age-associated alterations of the immune response and their effects on graft function. METHODS: Three- and 18-month-old Lewis (LEW) rats received kidneys from 3- and 18-month-old Fischer 344 (F344) rats (1.5 mg/kg/d cyclosporine A for 10 days; n=6/group) and were observed for 180 days. In additional groups, double kidney transplantations were performed to determine the impact of nephron mass and recipient age on graft outcome. RESULTS: All young recipients but only 66% of old recipients survived the observation period. Increasing recipient age resulted in a significant decrease in renal allograft function (P<0.001), more advanced morphologic evidence of chronic allograft damage (P<0.001), and greater cellular infiltration (P<0.05) and major histocompatibility complex expression (P<0.01) within grafts. Additional in vitro studies examined age-related changes in the cellular immune response by enzyme-linked immunosorbent assay, fluorescence-activated cell sorter analysis, and alloreactive enzyme-linked immunospot: splenocytes from old LEW rats produced significantly more interleukin (IL)-2 (P<0.0001), IL-4 (P<0.05), interferon (IFN)-gamma (P<0.0001), and tumor necrosis factor-alpha (P<0.05). IFN-gamma-producing memory-type T cells were significantly elevated in older rats (P<0.0001). Moreover, they revealed significantly more alloreactive T cells directed against F344 (146 +/- 64.2 and 512 +/- 277/10(6) T cells; P<0.05). Double renal allografts from young donors into old recipients confirmed an independent effect of recipient age on the acceleration of chronic graft deterioration. CONCLUSIONS: The enhanced cellular immune responsiveness in elderly recipients was associated with advanced chronic graft injury. Clinically, older recipients may need a modified immunosuppression.

Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1.

Today, the major problem in organ transplantation is not acute graft rejection but chronic graft deterioration. In addition to alloantigen-specific events, alloantigen independent factors like donor age, previous diseases, consequences of brain death, and perioperative events of ischemia/reperfusion injury have a major impact on long-term graft function. The induction of the stress protein heme oxygenase-1 (HO-1) protects cells from injury and apoptosis. Here, we tested the protective effects of HO-1 induction in a clinically relevant kidney transplant model. Induction of HO-1 expression following cobalt-protoporphyrin (CoPP) treatment in organ donors prolonged graft survival and long-term function remarkably following extended periods of ischemia. Positive effects were observed with both optimal and marginal grafts from old donor animals. Structural changes characteristic for chronic rejection, as well as graft infiltration by monocytes/macrophages and CD8+ T cells, were substantially reduced following HO-1 induction. Up-regulation of HO-1 expression before organ transplantation was also associated with reduced levels for tumor necrosis factor (TNF)-alpha mRNA, increased levels for interferon (IFN)-gamma, and bcl-x, and insignificant differences for CD25, interleukin (IL)-2, IL-4, IL-6, and IL-10 mRNA levels. The significant improvement of long-term graft function following induction of HO-1 expression in donor organs suggests that this strategy may be a novel clinical treatment option with particular relevance for transplantation of marginal organs.

Combination of bortezomib-based chemotherapy and extracorporeal free light chain removal for treating cast nephropathy in multiple myeloma.

Besides amyloidosis and light chain deposition disease, the most common histological type of renal lesion is cast nephropathy in 30% of patients with multiple myeloma [2]. In contrast to amyloidosis, cast nephropathy is believed to be potentially reversible when circulating light chains are rapidly reduced. We report on three patients with multiple myeloma and cast nephropathy treated with a bortezomib-based chemotherapy in addition to a newly developed high-cutoff polyflux® haemofilter. Reduction in serum free light chain levels was achieved within 10-12 days, with all three patients improving their renal function.

The impact of immune-activating processes following transplantation on chronic allograft nephropathy.

BACKGROUND: The long-term success of organ transplantation is influenced by numerous alloantigen-dependent and -independent risk factors. However, only very little information is presently available on the influence of systemic immune-activating processes following organ engraftment. METHODS: To simulate the clinical situation of sequential organ transplantation, rat renal allograft recipients received additional immune activating stimuli (secondary donor-specific and third-party skin grafts) after transplantation at serial time intervals (4 and 8 weeks). The overall observation period was 16 weeks. RESULTS: All control animals survived the observation period. In contrast, recipients receiving additional third-party or donor-specific skin grafts were beginning to die 12 weeks after organ engraftment with only few animals surviving 16 weeks. Systemic immune activation by additional third-party and in particular by additional donor-specific skin grafts resulted in significant temporary and long-term functional deterioration. Morphologic changes progressed significantly, particularly after a secondary challenge with donor-specific skin grafts. ED1+ monocytes/macrophages, T-cell infiltrates, and intragraft mRNA expression for CD25 were significantly elevated by 16 weeks, following an additional immune challenge. Analysis of early intragraft events showed strong up-regulation of CD25 transcripts, suggesting fast stimulation of intragraft immune processes. CONCLUSION: Both alloantigen-specific and -unspecific systemic immune activation processes, following experimental organ transplantation, contribute to chronic graft deterioration. Those results seem relevant for long-term immunosuppressive protocols and clinical situations of sequential organ transplantation.