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Zusammenfassung Hintergrund Die aktuelle COVID-19-Pandemie stellt, trotz der Verfügbarkeit von Schnelltests und des Starts der Impfkampagne, die Notaufnahme weiterhin vor große Herausforderungen. Die strukturierte Erfassung von demographischen, klinischen sowie therapiebezogenen Daten stellt die Grundlage für die Erstellung evidenzbasierter Prozesse und Behandlungskonzepte dar. Ziel der Arbeit Darstellung der systematischen Erfassung klinischer Parameter bei Patienten mit COVID-19-Verdacht im Notaufnahmeregister ReCovER (Registry for COVID-19 in the Emergency Room) sowie deskriptive Darstellung der ersten 1000 Patienten. Material und Methoden In zentralen Notaufnahmen (ZNA) von 6 Universitätskliniken werden kontinuierlich Daten von Patienten mit COVID-19-Verdacht, unabhängig vom Nachweis einer SARS-CoV-2-Infektion, in ein webbasiertes, anonymisiertes Register eingegeben. Ergebnisse Zwischen dem 19.05.2020 und dem 13.01.2021 wurden 1000 Patienten in das Register eingegeben, hiervon waren 594 Patienten (59,4 %) in der SARS-CoV-2-positiven (PG) und 406 Patienten (40,6 %) in der negativen Gruppe (NG). Patienten der PG hatten signifikant weniger Vorerkrankungen und eine deutlich längere Latenz zwischen Symptombeginn und Vorstellung in der ZNA (Median 5 vs. 3 Tage), litten häufiger unter Husten, Myalgien, Fatigue sowie Geruchs/Geschmacksverlust und hatten einen signifikant höheren Sauerstoffbedarf als die NG-Patienten. Die Rate von schweren Krankheitsverläufen war in der PG signifikant erhöht und es bestanden nach Entlassung häufiger persistierende Symptome (11,1 vs. 4,6 %). Schlussfolgerungen Durch die multizentrische Erfassung von umfangreichen klinischen Daten zu COVID-19-Verdachtsfällen in der Notaufnahme können insbesondere auch für die Situation in Deutschland spezifische Aspekte analysiert werden. Dies ist essenziell für eine gezielte Überprüfung und Adaption international publizierter Strategien.

Background Frequent outbreaks around the globe and endemic appearance in different parts of the world emphasize the substantial risk of hantavirus diseases. Increasing incidence rates, trends of changing distribution of hantavirus species and new insights into clinical courses of hantavirus diseases call for multinational surveillance. Furthermore, evidence-based guidelines for the management of hantavirus diseases and scoring systems, which allow stratification of patients into risk categories, are lacking. Methods Hantavirus registry (HantaReg) is a novel registry platform facilitating multinational research of hantavirus-caused diseases, such as haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HantaReg provides an electronic case report form and uses the General Data Protection Regulation compliant platform clinicalsurveys.net, which can be accessed from any internet browser in the world. Having a modular structure, the registry platform is designed to display or hide questions and items according to the documented case (e.g. patient with HFRS versus HCPS) to facilitate fast, but standardized, data entry. Information categories documented in HantaReg are demographics, pre-existing diseases, clinical presentation, diagnostic and therapeutic approaches, as well as outcome. Conclusions HantaReg is a novel, ready-to-use platform for clinical and epidemiological studies on hantavirus diseases and facilitates the documentation of the disease course associated with hantavirus infections. HantaReg is expected to promote international collaboration and contributes to improving patient care through the analysis of diagnostic and treatment pathways for hantavirus diseases, providing evidence for robust treatment recommendations. Moreover, HantaReg enables the development of prognosis-indicating scoring systems for patients with hantavirus disease.

Objectives Coronavirus disease 2019 (COVID-19) is currently a worldwide major health threat. Recognizing hypoxia in patients early on can have a considerable effect on therapy success and survival rate. Methods We collected data using a standard blood gas analyzer from 50 patients and analyzed measurements of partial pressure of carbon dioxide-pCO2, partial pressure of oxygen-pO2 and oxygen saturation-sO2, bicarbonate concentrations-HCO3− as well as ionized calcium concentrations. We further examined PCR test results for SARS-CoV-2 of the patients and analyzed differences between patients tested positive and those tested negative for the virus. Results Venous pCO2 was significantly higher whereas pO2 and sO2 were significantly lower in patients who tested positive for SARS-CoV-2. The pH, and ionized calcium concentrations of patients tested positive for the virus were significantly lower than in those tested negative. Conclusions Symptomatic SARS-CoV-2-positive patients upon admission to the emergency room exhibit lower venous blood levels of oxygen, pH, and calcium and higher levels of carbon dioxide compared to symptomatic SARS-CoV-2-negative patients. This blood gas analysis constellation could help in identifying SARS-CoV-2-positive patients more rapidly and identifying early signs of hypoxia.

In the situation of a shortage of ventilation beds, ethically justifiable, transparent and comprehensible decisions must be made. This concept proposes that all patients are first intubated depending on necessity and then assessed by a triage team afterwards. In this situation newly admitted COVID patients compete with newly admitted Non-COVID patients as well as patients already treated in intensive care units for a ventilator. The combination of short-term and long-term prognoses should enable the interprofessional triage team to make comprehensible decisions. The aim of the prioritization concept is to save as many human lives as possible and to relieve the treatment team of the difficult decision on prioritization.In der Situation des Beatmungsbettenmangels sind ethisch begründbare, transparente und nachvollziehbare Entscheidungen zu treffen. Dieses Konzept sieht vor, dass zunächst alle Patienten nach Notwendigkeit intubiert und dann von einem Triage-Team beurteilt werden. Dabei stehen neu aufgenommene COVID-Patienten mit neu aufgenommenen Nicht-COVID-Patienten und bereits intensivmedizinisch behandelte Patienten in Konkurrenz um ein Beatmungsgerät. Die Kombination der kurz- und langfristigen Prognose soll dem interprofessionellen Triage-Team ermöglichen, nachvollziehbare Entscheidungen zu treffen. Ziel des Priorisierungskonzeptes ist es, möglichst viele Menschenleben zu retten und die Behandlungsteams von der schwierigen Entscheidung der Priorisierung zu entlasten.

The management of older and multimorbid patients with complex care requires a personalised and comprehensive approach. The main diagnosis is often registered as the cause of hospitalisation, yet poor health-related quality of life (HRQoL) as well as multimorbidity may represent the underlying cause and markedly influence prognosis. To analyse the association of HRQoL and clinical prognosis over time as assessed by a Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI) in older patients admitted to the emergency department (ED). We used data from the prospective MPI–HOPE (Influence of the MPI on the Hospitalisation of Older Patients admitted to the Emergency department) study. Data from 165 patients (≥ 75 years) admitted to the ED of the University Hospital of Cologne, Germany, between Oct 2017 and Jan 2018 were included. Clinical prognosis was calculated by the MPI and HRQoL by the EQ5D-5L. Follow-up interviews assessed HRQoL up to 6 months after discharge. Most patients were multimorbid and presented with several geriatric syndromes. At admission, HRQoL was highest in patients with the best clinical prognosis. The MPI showed a negative correlation with the EQ-Index at admission (rs(86) = − 0.50, p

Short-term dietary restriction (DR) may prevent organ damage from ischemic or toxic insults in animals, but clear evidence in humans is missing. While especially intraarterial administration of contrast media represents a cause of hospital-acquired acute kidney injury (AKI), targeted preventive strategies are not available. This trial investigated the feasibility and effectiveness of pre-interventional DR for preventing AKI in patients undergoing percutaneous coronary intervention (PCI). Patients were randomized to receive a formula diet containing 60% of daily energy requirement (DR group) or ad-libitum food during the 4-day-interval before PCI. Primary endpoint was change of serum creatinine 48 h after PCI (Δcreatinine). Further analyses included incidence of AKI and safety evaluation. Δcreatinine post PCI in the DR group vs. the control group did not show any difference (DR: 0.03(−0.15,0.14)mg/dL vs. control: 0.09(−0.03,0.22)mg/dL;p = 0.797). Subgroup analyses revealed a significant beneficial impact of DR in patients that received ≤100 ml of contrast agent (DR n = 26: Δcreatinine −0.03(−0.20,0.08)mg/dL vs. control n = 24: Δcreatinine 0.10(−0.08,0.24)mg/dL; p = 0.041) and in patients with ≤2 risk factors for AKI (DR: n = 27; Δcreatinine −0.01(−0.18,0.07)mg/dL vs. control n = 31: Δcreatinine 0.09(−0.03,0.16)mg/dl; p = 0.030). Although the primary endpoint was not met, the results of this trial suggest a beneficial impact of DR in low-to-moderate risk patients.

This observational study investigated the impact of hyponatremia resolution on the results of a comprehensive geriatric assessment (CGA) in 150 patients with age ≥70 years and serum sodium 0.2) in the overall analysis for ΔADL and ΔMMSE and moderate (i.e., >0.5) for ΔMMSE in the euvolemic subgroup. Beneficial effects on ΔADL and ΔMMSE were only observed in the subgroup of patients in which [Na+] was raised by >5 mEq/L and multivariable linear regression analysis confirmed [Na+] increase to be an independent predictor of MMSE improvement. Resolution of hyponatremia has a beneficial impact on the geriatric patients’ overall functional status, in particular in euvolemic cases.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents AKI can be prevented effectively through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans) longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, in particular arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Isolation of confirmed or suspected coronavirus disease 2019 (COVID-19) cases is essential but, as symptoms of COVID-19 are non-specific and test results not immediately available, case identification at admission remains challenging. To inform optimization of triage algorithms, patient flow and patient care, we analyzed characteristics of patients admitted to an isolation ward, both severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) positive patients and patients in which initial suspicion was not confirmed after appropriate testing.Data from patients with confirmed or suspected COVID-19 treated in an isolation unit were analyzed retrospectively. Symptoms, comorbidities and clinical findings were analyzed descriptively and associations between patient characteristics and final SARS-CoV-2 status were assessed using univariate regression.Eighty three patients (49 SARS-CoV-2 negative and 34 positive) were included in the final analysis. Of initially suspected COVID-19 cases, 59% proved to be SARS-CoV-2-negative. These patients had more comorbidities (Charlson Comorbidity Index median 5(interquartile range [IQR] 2.5, 7) vs 2.7(IQR 1, 4)), and higher proportion of active malignancy than patients with confirmed COVID-19 (47% vs 15%; P = .004), while immunosuppression was frequent in both patient groups (20% vs 21%; P = .984). Of SARS-CoV-2 negative patients, 31% were diagnosed with non-infectious diseases.A high proportion of patients (59%) triaged to the isolation unit were tested negative for SARS-CoV-2. Of these, many suffered from active malignancy (47%) and were immunosuppressed (20%). Non-infectious diseases were diagnosed in 31%, highlighting the need for appropriate patient flow, timely expert medical care including evaluation for differential diagnostics while providing isolation and ruling out of COVID-19 in these patients with complex underlying diseases.

BackgroundRapid and extensive testing of large parts of the population and specific subgroups is crucial for proper management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decision-making in times of a pandemic outbreak. However, point-of-care (POC) testing in places such as emergency units, outpatient clinics, airport security points or the entrance of any public building is a major challenge. The need for thermal cycling and nucleic acid isolation hampers the use of standard PCR-based methods for this purpose.MethodsTo avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including loop-mediated isothermal amplification (LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK).ResultsWhilst specificity of standard LAMP assays appears to be satisfactory, sensitivity does not reach the current gold-standard quantitative real-time polymerase chain reaction (qPCR) assays yet. We describe a novel multiplexed LAMP approach and validate its sensitivity on primary samples. This approach allows for fast and reliable identification of infected individuals. Primer optimization and multiplexing helps to increase sensitivity significantly. In addition, we directly compare and combine our novel LAMP assays with SHERLOCK.ConclusionIn summary, this approach reveals one-step multiplexed LAMP assays as a prime-option for the development of easy and cheap POC test kits.

Acute kidney injury is a common clinical disorder resulting in significantly increased morbidity and mortality. However, despite extensive research, strategies for prevention or treatment are still lacking in routine clinical practice. Already decades ago, several preconditioning strategies (e. g. ischemic/hypoxic preconditioning and calorie restriction) have been published and their extraordinary effectiveness - especially in rodents - has raised the hope for powerful clinical tools to prevent acute kidney injury. However, the underlying mechanisms are still not completely understood and translation to the clinics has not been successful yet. In this review, the most attractive strategies and the current mechanistic concepts are introduced and discussed. Furthermore, we present clinical trials evaluating the feasibility of preconditioning in the clinical setting.

Eine akzidentielle oder (para)suizidale Intoxikation mit Ethylenglykol kann zu einer schweren Acidose, zu verschiedenen Organsystemschaden und zum Tod fuhren. Wirksame Therapien stellen die Hamodialyse und die sofortige Gabe von Fomepizol bzw. von Ethanol dar. Wir beschreiben einen Patienten nach wiederholter Ethylenglykolintoxikation mit einer schweren metabolischen Acidose und einem akuten Nierenversagen. Durch Hamodialyse mit ethanolhaltigem Dialysat und i. v.-Gabe von Ethanol konnten wir gravierende Folgeschaden verhindern.

Die schwere akute Hyponatriamie ist eine lebensbedrohliche Erkrankung. Wir berichten uber den Fall einer 38-jahrigen Patientin, die im Rahmen einer isovolamischen Hyponatriamie innerhalb kurzer Zeit ein Hirnodem mit letaler Einklemmung entwickelte.

Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, −4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, −11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.

The coronavirus disease (COVID-19) pandemic has caused tremendous pressure on hospital infrastructures such as emergency rooms (ER) and outpatient departments. To avoid malfunctioning of critical services because of large numbers of potentially infected patients seeking consultation, we established a COVID-19 rapid response infrastructure (CRRI), which instantly restored ER functionality. The CRRI was also used for testing of hospital personnel, provided epidemiological data and was a highly effective response to increasing numbers of suspected COVID-19 cases.

Background: Germany is among the countries with the highest numbers of SARS-CoV-2 infections in Europe To slow the spread of SARS-CoV-2 a combination of measur

BackgroundRapid and extensive testing of large parts of the population and specific subgroups is crucial for proper management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decision-making in times of a pandemic outbreak. However, point-of-care (POC) testing in places such as emergency units, outpatient clinics, airport security points or the entrance of any public building is a major challenge. The need for thermal cycling and nucleic acid isolation hampers the use of standard PCR-based methods for this purpose.MethodsTo avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK).ResultsWhilst specificity of standard RT-LAMP assays appears to be satisfactory, sensitivity does not reach the current gold-standard quantitative real-time polymerase chain reaction (qPCR) assays yet. We describe a novel multiplexed RT-LAMP approach and validate its sensitivity on primary samples. This approach allows for fast and reliable identification of infected individuals. Primer optimization and multiplexing helps to increase sensitivity significantly. In addition, we directly compare and combine our novel RT-LAMP assays with SHERLOCK.ConclusionIn summary, this approach reveals one-step multiplexed RT-LAMP assays as a prime-option for the development of easy and cheap POC test kits.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents, AKI can be effectively prevented through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans), longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, particularly arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Background: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Methods: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na+] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH). Results: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na+] change (Δdaily[Na+]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δdaily[Na+] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived. Conclusions: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH.

Background The impact of chronic moderate and profound hyponatremia on neurocognitive performance, motor skills, and mood stability has not been investigated systematically so far, and results regarding mild to moderate hyponatremia are inconsistent. Furthermore, it is not known whether treatment has an effect on outcome in these patients. Methods A total of 130 hospitalized patients with confirmed euvolemic hyponatremia ( Results The scores of all tested domains were significantly worse in the hyponatremia group (median serum sodium [Na+] 122 (119-126) mEq/L) as compared to the reference group (P Conclusion We demonstrate a clear association between lower levels of Na+ beyond mild hyponatremia and impairment of neurocognitive and motor performance as well as mood disorders. Our analysis further suggests a causal role of hyponatremia in this context. However, there are apparent differences between the distinct tested domains warranting further investigations.

Hyponatremia is a frequently encountered clinical finding, and by far the most common disorder of electrolyte and water homeostasis throughout the world. Given the complex pathophysiology of hyponatremia as well as its clinical implications, which range from apparently asymptomatic presentations to life-threatening conditions, a comprehensive understanding of its possible causes and of the frequencies of occurrence of the various types of hyponatremia in distinct clinical settings is essential for successful disease management. In this chapter, the diverse etiologies of hyponatremia are summarized, explained, and classified according to the patients' extracellular volume status. An in-depth review of the existing literature on epidemiologic data on incidence and prevalence of hyponatremia is provided covering the general population as well as the patient groups with community-acquired and hospital-acquired hyponatremia. Selected clinical scenarios that are described in detail are: hyponatremia in the geriatric population, in the emergency department, in the postoperative state, and in the intensive care setting. Distinct diseases and circumstances that are often associated with hyponatremia are reviewed briefly, while a more detailed discussion is covered in later chapters.

Background Data are lacking on the relative incidence of thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS) caused by Shiga toxin–producing Escherichia coli (STEC) and atypical HUS (aHUS) in patients presenting with thrombotic microangiopathies (TMAs). Methods This was a prospective, cross-sectional, multicentre and non-interventional epidemiological study. Patients fulfilling criteria for TMAs (platelet consumption, microangiopathic haemolytic anaemia and organ dysfunction) were included in the study. The primary objective was to assess the relative incidence of TTP, STEC-HUS, aHUS and ‘other’ physician-defined diagnoses. The secondary objective was to develop an algorithm to predict a severe deficiency in ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (≤10%) using routine laboratory parameters. A post hoc classification using the recent Kidney Disease: Improving Global Outcomes diagnostic criteria was then undertaken to further classify patient groups. Results aHUS was diagnosed with a relative incidence of 61%, whereas TTP, STEC-HUS and ‘other’ were diagnosed in 13, 6 and 20% of patients, respectively. In the post hoc analysis, 27% of patients with a TMA were classified as ‘primary aHUS’ and 53% as ‘secondary aHUS’. Multivariate analysis revealed that severe deficiency in ADAMTS13 activity (≤10%) was unlikely to underlie TMA if platelet and serum creatinine were above threshold values of 30 × 109/L and 1.8 mg/dL, respectively (negative predictive value of 92.3 and 98.1, respectively, if one or both values were above the threshold). Conclusions In this study, aHUS was the most common single diagnosis among patients presenting with a TMA. In the absence of an ADAMTS13 activity result, platelet count and serum creatinine may aid in the differential diagnosis.

Objectives We investigated the trend in usage of post-exposure prophylaxis (PEP) after HIV-1 risk exposure and evaluated PEP prescription decision making of physicians according to guidelines. Methods All PEP consultations from January 2014 to December 2016 in patients presenting at the University Hospital of Cologne (Germany) were retrospectively analysed. HIV risk contacts included sexual and occupational exposure. The European AIDS Clinical Society (EACS) Guidelines for HIV PEP (version 9.0, 2017) were used for assessment. Results A total of 649 patients presented at the emergency department (ED) or the clinic for infectious diseases (IDC) for PEP consultations. A continuous increase in the number of PEP requests was recorded: 189 in 2014, 208 in 2015 and 252 in 2016. PEP consultations in men who have sex with men (MSM) showed a remarkable increase in 2016 (2014, n = 96; 2015, n = 101; 2016, n = 152). Decisions taken by physicians with a specialization in infectious diseases (n = 547) included 61 (11%) guideline-discordant prescriptions [2014: 14% (n = 22); 2015: 9% (n = 16); 2016: 11% (n = 23)]. Among these, sexual exposure accounted for 45 (74%) cases, including 15 cases of nonconsensual sex, while occupational exposure accounted for 14 (23%) cases and other exposure two cases (3%). The main reason for guideline-discordant PEP prescriptions was emotional stress of the patient (n = 37/61). Conclusions PEP prescriptions are increasing and decision making is influenced by patients' emotional stress, but PEP prescriptions should be strictly administered according to risk assessment.

Lung cancer, in particular small cell lung cancer (SCLC), is a very aggressive solid tumour with limited therapeutic options to date. The majority of patients present, at the time of diagnosis, with extensive disease patterns and reduced performance status. Hyponatraemia is a common finding in SCLC (25%) which can be assigned to a paraneoplastic syndrome termed syndrome of inappropriate ADH secretion (SIADH) in 60% of cases. Hyponatraemia may cause significant and even dramatic neurocognitive deficits, if not treated in an effective manner. Palliative chemo- or radiotherapy is restricted to patients with good performance status and therapeutic adherence. Acute or persistent hyponatraemia may interfere with such treatment options and compromise outcome. This review integrates new diagnostic and therapeutic guidelines to improve the understanding how and when to treat hyponatraemia in thoracic oncology patients Integrating early palliative care in lung cancer patients has a significant impact on prognosis. Correcting hyponatraemia in a supportive and risk stratified fashion may help to improve both prognosis and quality of life and should be a standard in modern palliative care for patients with lung cancer.

The management of hyponatremia has evolved in recent years, particularly with the introduction of tolvaptan for hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This commentary presents a summary of recent international recommendations in the form of a series of didactic 'dos and don'ts', in order to provide concise, practical guidance for practising clinicians focused on the investigation and management of euvolemic hyponatremia (SIADH).A multidisciplinary group of international experts reviewed existing guidelines and the evidence cited within to summarize the recommendations in a practical method for use in clinical practice.The 'dos and don'ts' are presented under topic headings that include diagnosis and diagnostic tests, specific causes, correction of acute hyponatremia, correction rates for chronic hyponatremia, management of SIADH including fluid restriction, hypertonic saline and pharmacological strategies, and management of overcorrection. Within each topic, the authors summarize the published recommendations on managing hyponatremia and the use of specific agents for the treatment of SIADH.Practising clinicians can use these 'dos and don'ts' to provide clear, up-to-date guidance on how to manage hyponatremia and the use of tolvaptan in SIADH.

Background Acute kidney injury is a frequent complication after cardiac surgery and is associated with adverse outcomes. Although short‐term calorie restriction (CR) has proven protective in rodent models of acute kidney injury, similar effects have not yet been demonstrated in humans. Methods and Results CR _KCH (Effect of a Preoperative Calorie Restriction on Renal Function After Cardiac Surgery) is a randomized controlled trial in patients scheduled for cardiac surgery. Patients were randomly assigned to receive either a formula diet containing 60% of the daily energy requirement (CR group) or ad libitum food (control group) for 7 days before surgery. In total, 82 patients were enrolled between April 16, 2012, and February 5, 2015. There was no between‐group difference in the primary end point of median serum creatinine increment after 24 hours (control group: 0.0 mg/dL [−0.1 – (+0.2) mg/dL]; CR group: 0.0 mg/dL [−0.2 – (+0.2) mg/dL]; P =0.39). CR prevented a rise in median creatinine at 48 hours (control group: +0.1 mg/dL [0.0 – 0.3 mg/dL]; CR group: −0.1 mg/dL [−0.2 – (+0.1) mg/dL]; P =0.03), with most pronounced effects observed in male patients and patients with a body mass index >25. This benefit persisted until discharge: Median creatinine decreased by 0.1 mg/dL (−0.2 – 0.0 mg/dL) in the CR group, whereas it increased by 0.1 mg/dL (0.0 – 0.3 mg/dL; P =0.0006) in the control group. Incidence of acute kidney injury was reduced by 5.8% (41.7% in the CR group compared with 47.5% in the control group). Safety‐related events did not differ between groups. Conclusions Despite disappointing results with respect to creatinine rise within the first 24 hours, the benefits observed at later time points and the subgroup analyses suggest the protective potential of short‐term CR in patients at risk for acute kidney injury, warranting further investigation. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01534364.

Acute kidney injury (AKI) is an important risk factor for a number of adverse outcomes including end-stage renal disease and cardiovascular morbidity and mortality. Whilst many clinical situations that can induce AKI are known—e.g. drug toxicity, contrast agent exposure or ischemia during surgery—targeted preventive or therapeutic measures are still lacking. As to renoprotective strategies, remote ischemic preconditioning (RIPC) is one of the most promising novel approaches and has been examined by a number of clinical trials. The aim of this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate parameter to assess the effect of RIPC in healthy volunteers. In this IRB-approved, prospective study, 40 healthy volunteers were stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a transient ischemia of the right arm, and 20 undergoing a sham procedure. Before and after the procedure, both kidneys of all participants were scanned using a 12-echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180 ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2* values, which have an inverse correlation with the oxygenation level of tissue, were averaged for the RIPC and control groups. Following intervention, mean R2* values significantly decreased in the RIPC group in both the cortex (18.6 ± 2.3 vs. 17.5 ± 1.7 Hz; p = 0.0047) and medulla (34 ± 5.2 vs. 32.2 ± 4.2 Hz; p = 0.0001). However, no significant differences were observed in the control group. RIPC can be non-invasively assessed in healthy volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney tissue. This study presents a first-in-man trial establishing a quantifiable readout of RIPC and its effects on kidney physiology. BOLD measurements may advance clinical trials in further evaluating RIPC for future clinical care.

SUMMARY: Hyponatremia is the most common electrolyte disorder and can lead to a wide spectrum of symptoms, from apparently asymptomatic to life-threatening. Severe symptoms are usually a consequence of cerebral edema and should prompt immediate treatment with hypertonic fluid. In less severe cases, or after resolution of severe symptoms thorough clinical examination of volume status, additional laboratory tests are needed in order to identify the underlying cause and to classify the hyponatremia as hypo-, eu- or hyper-volemic. Although most cases of hyponatremia are attributed to an excessive action of antidiuretic hormone (vasopressin), optimal therapy regimes differ. While hypovolemic hyponatremia is treated appropriately with the administration of isotonic saline, eu- and hyper-volemic hyponatremia are classically treated with fluid restriction. In recent years a new class of drugs, vasopressin receptor-2 antagonists, called vaptans, have emerged as a potent and safe choice for the treatment of fluid r...

Despite being the most common electrolyte disturbance encountered in clinical practice, the diagnosis and treatment of hyponatremia (defined as a serum sodium concentration

Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It may cause a variety of symptoms and is associated with longer hospitalizations and higher mortality. However, to date, only little is known about the extent of hyponatremia in patients with incurable diseases and whether it is associated with physical symptoms in this patient group. This study aims to describe the prevalence of hyponatremia, associated symptoms, and symptom intensity in inpatients with hyponatremia receiving specialist palliative care (SPC). This is a retrospective study. Demographic and clinical data as well as symptoms, scored symptom intensity, and laboratory values were collected. All inpatients of a large German University Hospital receiving SPC in 2013 with documented sodium values were included. In 2013, 789 inpatients received SPC of which 710 had documented sodium values. The prevalence of hyponatremia was 38.7% (275/710). A mild degree showed 220 (31,0%), 44 (6.2%) had a moderate, and 11 (1.6%) a severe form. Hyponatremia patients experienced significantly more symptoms than normonatremic patients (mean = 7.71 vs 6.63; p

Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney.

Background Endogenous bone marrow-derived cells are known to incorporate into renal epithelium at a low rate. Haematopoietic stem cells (HSCs) rather than mesenchymal stem cells (MSC) are responsible for this phenomenon. MSCs have the potential to ameliorate kidney function after acute kidney injury (AKI) without directly repopulating the tubules. However, little is known about the short-term effect of HSCs. Methods In this article, we analysed the survival rate and organ distribution of isolated rat HSCs injected into the renal artery after ischaemic renal injury, using quantitative real-time PCR, as well as their impact on renal function and histomorphology. Results Intra-arterially injected Lin(-)CD90(+) HSCs were detected in the kidney at significant amounts only within the first 24 h after injection and were virtually absent by Day 2. Compared with control animals, no differences were seen after HSC administration with respect to kidney function or histomorphologic changes of AKI. At Day 7 HSCs were again readily detectable in the kidney suggesting a redistribution of cells at later time points. Of note, HSCs did not seem to have an exclusive tropism for the injured kidney but were detectable in the lungs, liver, spleen, heart and brain at all time points. Conclusions Injected HSCs do not appear to significantly contribute to tubular repair or ameliorate renal damage in ischaemic AKI although they may show considerable engraftment in various organs. These data further challenge the concept that injection of HSCs may be used as a therapeutic approach in treating AKI.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the most common cause of euvolaemic hyponatraemia. However, although first described over 50 years ago, the management of hyponatraemia secondary to SIADH is not always straightforward. Some of the issues surrounding the management of hyponatraemia secondary to SIADH were explored in the European Hyponatraemia Survey completed by attendees of the European Hyponatraemia Network Academy Meeting 2011. This article describes the findings of this survey and the specific issues raised regarding the management of hyponatraemia secondary to SIADH in Europe. Some of these issues - including awareness, education, diagnosis, management and cost considerations of the condition - were common to countries across Europe.

Background/Aims: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are common causes of nephrotic syndrome (NS) in adults. However, induction of remission and sustained control of proteinuria is often difficult. Recently, B cell-directed therapy using the anti-CD20 antibody rituximab has been suggested as induction regimen in pediatric FSGS and MCD patients. Data on rituximab use in adults are still limited. Methods: We report on rituximab use in five consecutively treated adult patients (mean age 42.2 ± 9.9 years) with FSGS or relapsing MCD (2 FSGS, 3 MCD) who failed to respond to standard immunosuppressive treatment. Median follow-up was 8 months (3–25). Results: Rituximab induced complete remission in 2 MCD patients and partial remission in 3 patients. Proteinuria was reduced by 86.8% (42.9–95.2) 3 months and by 73.0% (60.1–95.5) 6 months after therapy. In 1 patient with severe FSGS, partial remission was not evident before 6 months after rituximab treatment. Relapses occurred in 2 patients. No severe adverse events related to rituximab were observed. Conclusion: Our findings suggest that B cell-directed therapies are novel treatment options for adults with refractory NS. Response to rituximab varied, with MCD patients exhibiting a faster and more pronounced response compared to FSGS patients.

Background: Although renal tubular epithelium has a great capacity for repair it has been suggested that the administration of mesenchymal stem cells may accelerate the recovery following severe ischemic injury. Methods: Here we analyzed the survival rate and organ distribution of transplanted mesenchymal stem cells as well as their contribution to kidney regeneration after ischemic renal injury using functional tests, histological examination as well as quantitative real-time PCR. Results: Intravenously injected stem cells were mainly trapped in lungs and liver. One hour after injection, less than 1% of the injected stem cells could be detected in the injured kidneys. These cells disappeared within the first few days and did not replace renal epithelial cells precluding substantial transdifferentiation. To clarify whether reinforced stem cell delivery might promote sustained survival or conversion to tubular epithelia, stem cells were directly injected into the injured kidneys. Although these grafted cells also did not show sustained survival or contribute to structural renal repair, stem cell injection was associated with a significant but transient initial decrease in serum creatinine. Conclusion: These data suggest that mesenchymal stem cells do not significantly contribute to epithelial renewal after ischemic injury, promoting the idea that the major impact of cell-based therapy for acute kidney injury may result from paracrine or endocrine effects unrelated to stem cell transdifferentiation.

The syndrome of inappropriate antidiuretic hormone secretion is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and outcomes in patients with syndrome of inappropriate antidiuretic hormone secretion are not well understood. The objective of the Hyponatremia Registry was to assess the current state of management of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion in diverse hospital settings, specifically which diagnostic and treatment modalities are currently used and how rapidly and reliably they result in an increase in serum sodium concentration ([Na(+)]). A secondary objective was to determine whether treatment choices and outcomes differ across the United States and the European Union.The Hyponatremia Registry recorded selected diagnostic measures and use, efficacy, and outcomes of therapy for euvolemic hyponatremia diagnosed clinically as syndrome of inappropriate antidiuretic hormone secretion in 1524 adult patients with [Na(+)] ≤130 mEq/L (1034 from 146 US sites and 490 from 79 EU sites). A subgroup of patients with more rigorously defined syndrome of inappropriate antidiuretic hormone secretion via measurement of relevant laboratory parameters was also analyzed.The most common monotherapy treatments for hyponatremia in syndrome of inappropriate antidiuretic hormone secretion were fluid restriction (48%), isotonic (27%) or hypertonic (6%) saline, and tolvaptan (13%); 11% received no active agent. The mean rate of [Na(+)] change (mEq/L/d) was greater for all active therapies than no active treatment. Hypertonic saline and tolvaptan produced the greatest mean rate of [Na(+)] change (interquartile range, both 3.0 [6.0] mEq/L/d) compared with lower interquartile range rates of [Na(+)] change for isotonic saline (1.5 [3.0] mEq/L/d) and fluid restriction (1.0 [2.3] mEq/L/d). The general pattern of responses was similar in both the US and EU cohorts. At discharge, [Na(+)] was135 mEq/L in 75% of patients and ≤130 mEq/L in 43% of patients. Overly rapid correction occurred in 10.2% of patients.Current treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion often uses therapies with limited efficacy; the most commonly chosen monotherapy treatments, fluid restriction and isotonic saline, failed to increase the serum [Na(+)] by ≥5 mEq/L in 55% and 64% of monotherapy treatment episodes, respectively. Appropriate laboratory tests to diagnose syndrome of inappropriate antidiuretic hormone secretion were obtained in50% of patients; success rates in correcting hyponatremia were significantly higher when such tests were obtained. Few outcome differences were found between the United States and the European Union. A notable exception was hospital length of stay; use of tolvaptan was associated with significantly shorter length of stay in the European Union but not in the United States. Despite the availability of effective therapies, most patients with syndrome of inappropriate antidiuretic hormone secretion were discharged from the hospital still hyponatremic.

Bone marrow cells are used with promising results for cell therapy after myocardial infarction (MI). We determined the survival and organ distribution of transplanted mononuclear (MNC) or mesenchymal (MSC) bone marrow cells, and the influence of cell type, cell number and application time. MNC and MSC (male Fischer 344 rats) were injected into the border zone of MI (syngeneic females) immediately or 7 days after LAD ligation (10(5) or 10(6) cells, 50 microl). After 0 h, 48 h, 5 days, 3 weeks and 6 weeks, DNA of heart, lung, liver, spleen, kidney, blood, bone marrow, brain and skeletal muscle was isolated and the number of donor cells determined by quantitative real-time PCR with Y-chromosome specific primers (each n>or=4). The percentage of donor-cells in the heart decreased rapidly from 34-80% of injected cells (0 h) to 0.3-3.5% (6 weeks) independent from cell type, number and application time. The absolute number increased after increasing injected cell number (10(6) vs. 10(5)). In the lung, MNC and MSC were found at 0 h (126+/-48 and 140+/-3 per million organ cells), but in liver and kidney, only few. At 48 h and 6 weeks, an increasing number of MNC, but not MSC, were detected in the spleen (6 weeks, 602+/-173 per million organ cells vs. 95+/-50 in the heart, P=0.02). In all other organs, only few or no grafted cells of either cell type were detected at these times. Organ distribution was independent from injection time. The low survival of grafted cells may limit their therapeutic impact, while their distribution to other organs must be considered in all cell therapy applications.

We thank the authors for their interest in our study on the impact of remote ischemic preconditioning on contrast medium–induced acute kidney injury (CI-AKI).1 The incidence of CI-AKI varies substantially among several studies because of the lack of a uniform definition of CI-AKI.2 Rates of CI-AKI may be as high as 50% or even higher, depending on the presence of risk factors such as chronic renal insufficiency and diabetes mellitus. Although the definition of CI-AKI varies across the trials, the most commonly used definition includes an absolute increase in serum creatinine of 0.5 mg/dL or a 25% relative increase in …

Background— Contrast medium–induced acute kidney injury is associated with substantial morbidity and mortality. The underlying mechanism has been attributed in part to ischemic kidney injury. The aim of this randomized, double-blind, sham-controlled trial was to assess the impact of remote ischemic preconditioning on contrast medium–induced acute kidney injury. Methods and Results— Patients with impaired renal function (serum creatinine >1.4 mg/dL or estimated glomerular filtration rate −1 · 1.73 m −2 ) undergoing elective coronary angiography were randomized in a 1:1 ratio to standard care with (n=50) or without ischemic preconditioning (n=50; intermittent arm ischemia through 4 cycles of 5-minute inflation and 5-minute deflation of a blood pressure cuff). Overall, both study groups were at high risk of developing contrast medium–induced acute kidney injury according to the Mehran risk score. The primary end point was the incidence of contrast medium–induced kidney injury, defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dL above baseline at 48 hours after contrast medium exposure. Contrast medium–induced acute kidney injury occurred in 26 patients (26%), 20 (40%) in the control group and 6 (12%) in the remote ischemic preconditioning group (odds ratio, 0.21; 95% confidence interval, 0.07–0.57; P =0.002). No major adverse events were related to remote ischemic preconditioning. Conclusions— Remote ischemic preconditioning before contrast medium use prevents contrast medium–induced acute kidney injury in high-risk patients. Our findings merit a larger trial to establish the effect of remote ischemic preconditioning on clinical outcomes. Clinical Trial Registration— URL: http://www.germanctr.de . Unique identifier: U1111-1118-8098.

Background: ABO-incompatible (ABOi) kidney transplantation is an established procedure relying on the removal of donor-specific isoagglutinine antibodies as part of the recipient preconditioning. At present, current protocols using immunoadsorption apply a single-use selective carbohydrate isoagglutinine adsorber. A regenerative and selective immunoglobulin immunoadsorption could be an alternative but has not been reported for ABOi transplantation. Methods: Eight patients were treated with the commonly used isoagglutinine carbohydrate epitope adsorber and seven with a regenerative polyclonal sheep anti-immunoglobulin adsorber as part of the preconditioning for ABOi kidney transplantation. An IgG-isoagglutinine titer of less or equal 1:4 qualified for transplantation. Treatment safety, efficiency, length of desensitization, number of postoperative immunoadsorptions, and allograft outcome were retrospectively compared. Results: With the use of the immunoglobulin adsorber the median initial isoagglutinine IgG titers of 1:64 (range 1:32–1:256) were lowered to the target of 1:4 preoperatively with a mean of 6.2 immunoadsorptions (range 5–11). Mean IgG/IgM titer step reduction per IA was 1.98/1.21 for (range 0–4/0–4) and mean titer step rebound 1.31/0.82 (range 0–4/0–3), respectively. The number of immunoadsorptions and length of desensitization was not different from the use of the specific isoagglutinine adsorbers. After transplantation, no rejection occurred and only one postoperative immunoadsorption was necessary. No adverse events in relation to immunoadsorption were observed. Graft function was comparable to the isoagglutinine adsorber group. Conclusion: These data suggest that ABOi kidney transplantation can be performed safely and effectively with a selective regenerative immunoglobulin immunoadsorber. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.

Cardiovascular disease is the most prevalent cause of death in patients with chronic kidney disease (CKD), even at an early stage of the disease and is considered a coronary heart disease risk equivalent. Therefore, therapeutic efforts to control modifiable additional cardiovascular risk factors such as dyslipidemia in this population seems reasonable. Indeed, abnormalities of lipid metabolism are often encountered in patients with CKD, end stage renal disease or after kidney transplantation. In this review we will summarize the currently available data on etiology, epidemiology, and impact on cardiovascular morbidity in patients with CKD, renal pathologies like the nephrotic syndrome and after kidney transplantation and give a brief overview of the existing guidelines on treating dyslipidemia.

Leflunomide, an inhibitor of the dihydroorotase dehydrogenase and thereby pyrimidine synthesis, was introduced and licensed for the treatment of rheumatoid arthritis in 1998. In the following years, its antiviral properties were discovered and the drug was used in solid organ transplantation for polyomavirus type BK or cytomegalovirus infection. Owing to its long half-life and weak interaction with the cytochrome system, special considerations apply in the use of this drug. This article summarizes the clinical experience with leflunomide in rheumatology and in the evolving field of transplantation.

Bone marrow cells are used for cell therapy after myocardial infarction (MI) with promising results. However, cardiac persistence of transplanted cells is rather low. Here, we investigated strategies to increase the survival and cardiac persistence of mononuclear (MNC) and mesenchymal (MSC) bone marrow cells transplanted into infarcted rat hearts. MNC and MSC (male Fischer 344 rats) were treated with different doses of PDGF-BB prior to intramyocardial injection into border zone of MI (syngeneic females, permanent LAD ligation) and hearts were harvested after 5 days and 3 weeks. In additional experiments, untreated MNC and MSC were injected immediately after permanent or temporary LAD ligation and hearts were harvested after 48 h, 5 days, 3 weeks, and 6 weeks. DNA of the hearts was isolated and the number of donor cells was determined by quantitative real-time PCR with Y chromosome-specific primers. There was a remarkable though not statistically significant ( p = 0.08) cell loss of ~46% between 5 days and 3 weeks in the control group, which was completely inhibited by treatment with high dose of PDGF-BB. Forty-eight hours after reperfusion only 10% of injected MSC or 1% for MNC were found in the heart, decreasing to 1% for MSC and 0.5% for MNC after 6 weeks. These numbers were lower than after permanent LAD ligation for both MNC and MSC at all time points studied. Treatment with PDGF-BB seems to prevent loss of transplanted bone marrow cells at later times presumably by inhibition of apoptosis, while reperfusion of the occluded artery enhances cell loss at early times putatively due to enhanced early wash-out. Further investigations are needed to substantially improve the persistence and survival of grafted bone marrow cells in infarcted rat hearts, in order to fully explore the therapeutic potential of this novel treatment modality for myocardial repair.