Tim Rahmel

• Dr. med.
• Oberarzt ( Senior Physican) at Universitätsklinikum Knappschaftskrankenhaus Bochum

Background: Sepsis therapy is still limited to treatment of the underlying infection and supportive measures. To date, various sepsis subtypes were proposed, but therapeutic options addressing the molecular changes of sepsis were not identified. With the aim of a future individualized therapy, we used machine learning (ML) to identify clinical phen...

Background Sepsis-associated liver injury (SALI) is associated with poor outcomes and increased mortality. However, effectively stratifying SALI patients according to prognosis remains challenging. This study evaluates laboratory-based clustering filters for stratifying SALI patients by 30-day mortality risk, utilizing data mining techniques for no...

The SARS-CoV-2 pandemic led to significant advancements in treatment and vaccination, contributing to a decline in overall COVID-19-related mortality. However, it remains unclear whether the mortality rate for critical cases treated on intensive care units has also decreased. This multicentric, multinational retrospective observational study analyz...

First steps toward harnessing the complex dynamics of antibiotic resistance are presented. To do this, we first shift down a gear and try to understand the actual driving dynamics behind the development of resistance in a specific clinical department. Analyses are based on the clinical and microbiological data of a German hospital over an observati...

Airway management is a core competency in anesthesiology that has significantly evolved in recent years, primarily due to technological innovations. The 2023 update of the S1 guideline on airway management, published by the German Society for Anesthesiology and Intensive Care Medicine (DGAI), offers evidence-based insights into these advancements a...

Background Sepsis remains a leading cause of mortality in intensive care units. Understanding the dynamics of the plasma proteome of patients with sepsis is critical for improving prognostic and therapeutic strategies. Methods This prospective, multicentre observational cohort study included 363 patients with sepsis recruited from five university...

Introduction In sepsis treatment, achieving and maintaining effective antibiotic therapy is crucial. However, optimal antibiotic dosing faces challenges due to significant variability among patients with sepsis. Therapeutic drug monitoring (TDM), the current gold standard, lacks initial dosage adjustments and global availability. Even with daily TD...

Background The rise in carbapenem-resistant bacteria and the limited number of effective antibiotics pose a major health-care threat. The combination of ceftazidime (CAZ) and avibactam (AVI) represents an approved treatment option for carbapenem-resistant intra-abdominal infections. However, data on the pharmacokinetic profile of AVI in the hepatob...

Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting β1-blocker landiolol. This randomized, open-label, controlled trial was c...

Background Sepsis presents a challenge due to its complex immune responses, where balance between inflammation and anti-inflammation is critical for survival. Glucocorticoid-induced leucine zipper (GILZ) is key protein in achieving this balance, suppressing inflammation and mediating glucocorticoid response. This study aims to investigate GILZ tran...

Background In sepsis, initial resuscitation with fluids is followed by efforts to achieve a negative fluid balance. However, patients with sepsis-associated acute kidney injury (SA-AKI) often need diuretic or renal replacement therapy (RRT). The dilemma is to predict whether early RRT might be advantageous or diuretics will suffice. Both the Furose...

Patients with sepsis experience metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutrition. A ketogenic diet (KD) may offer an immunologically advantageous alternative, although clinical evidence is limited. We conducted a single-center, open-label, randomized controlled trial to assess whether a KD could i...

Purpose There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an imp...

Objective This article describes the statistical analysis plan for the Biomarker-guided intervention to prevent AKI after major surgery (BigpAK-2) trial. Design Adaptive trial design with an interim analysis after enrolment of 618 evaluable patients. Setting The BigpAK.-2 trial is an international, prospective, randomised controlled multicentre s...

Background Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for de...

Introduction: Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb....

Background Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. Methods Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted...

The variability in mortality in sepsis could be a consequence of genetic variability. The glucocorticoid system and the intermediate TSC22D3 gene product—glucocorticoid-induced leucine zipper—are clinically relevant in sepsis, which is why this study aimed to clarify whether TSC22D3 gene polymorphisms contribute to the variance in sepsis mortality....

Introduction An increasing amount of longitudinal health data is available on critically ill septic patients in the age of digital medicine, including daily sequential organ failure assessment (SOFA) score measurements. Thus, the assessment in sepsis focuses increasingly on the evaluation of the individual disease’s trajectory. Machine learning (ML...

Purpose Excessive tachycardia in resuscitated septic shock can impair hemodynamics and worsen patient outcome. We asked whether heart rate (HR) control can be achieved without increased vasopressor requirements by using a titrated highly selective, ultra-short acting β1-blocker landiolol. Methods This randomized, open-label, controlled trial was c...

Immunometabolism is a fascinating field of research that investigates the interactions between metabolic processes and the immune response. This intricate connection plays a pivotal role in regulating inflammatory reactions and consequently exerts a significant impact on the course of sepsis. The proinflammatory response during an immune reaction i...

Sepsis is a common life-threatening disease caused by dysregulated immune response and metabolic acidosis which lead to organ failure. An abnormal expression of aquaporins plays an important role in organ failure. Additionally, genetic variants in aquaporins impact on the outcome in sepsis. Thus, we investigated the polymorphism (rs17553719) and ex...

OBJECTIVE Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term co...

Sepsis involves an immunological systemic response to a microbial pathogenic insult, leading to a cascade of interconnected biochemical, cellular, and organ–organ interaction networks. Potential drug targets can depict aquaporins, as they are involved in immunological processes. In immune cells, AQP3 and AQP9 are of special interest. In this study,...

Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 (Aqp5) knockdown provided enhanced sepsis survival in a murine sepsis model. Potential AQP5 inhibitors provide sulfonamides and their derivatives. In this s...

Background Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. Methods We determined the HCMV serostatus (...

Abstract The use of extracorporeal membrane oxygenation (ECMO) is discussed to improve patients’ outcome in severe COVID-19 with respiratory failure, but data on ECMO remains controversial. The aim of the study was to determine the characteristics of patients under invasive mechanical ventilation (IMV) with or without veno-venous ECMO support and t...

Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader...

Abstract Background The COVID-19 pandemic has taken a toll on health care systems worldwide, which has led to increased mortality of different diseases like myocardial infarction. This is most likely due to three factors. First, an increased workload per nurse ratio, a factor associated with mortality. Second, patients presenting with COVID-19-like...

Clonal hematopoiesis of indeterminate potential (CHIP) leads to higher mortality, carries a cardiovascular risk and alters inflammation. All three aspects harbor overlaps with the clinical manifestation of COVID-19. This study aimed to identify the impact of CHIP on COVID-19 pathophysiology. 90 hospitalized patients were analyzed for CHIP. In addit...

The quantity of aquaporin 5 protein in neutrophil granulocytes is associated with human sepsis-survival. The C-allele of the aquaporin (AQP5)-1364A/C polymorphism was shown to be associated with decreased AQP5 expression, which was shown to be relevant in this context leading towards improved outcomes in sepsis. To date, the underlying mechanism of...

Clinical success of Toll-Like receptor-4 (TLR-4) antagonists in sepsis therapy has thus far been lacking. As inhibition of a receptor can only be useful if the receptor is active, stratification of patients with active TLR-4 would be desirable. Our aim was to establish an assay to quantify phosphorylated TLR-4 using the proximity ligation assay (PL...

Postoperative nausea and vomiting (PONV) are one of the most adverse events after general anesthesia, a distressing experience, and pose a risk to the patient. Despite advances in drug prophylaxis and PONV treatment, the incidence remains high and additional non-pharmacological treatments are needed. In this post hoc analysis of a recently publishe...

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both...

Midazolam is a widely used short-acting benzodiazepine. However, midazolam is also criticized for its deliriogenic potential. Since delirium is associated with a malfunction of the neurotransmitter acetylcholine, midazolam appears to interfere with its proper metabolism, which can be triggered by epigenetic modifications. Consequently, we tested th...

Background A profound inflammation-mediated lung injury with long-term acute respiratory distress and high mortality is one of the major complications of critical COVID-19. Immunoglobulin M (IgM)-enriched immunoglobulins seem especially capable of mitigating the inflicted inflammatory harm. However, the efficacy of intravenous IgM-enriched preparat...

Importance: Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality. Objective: To deter...

The new Surviving Sepsis Campaign (SSC) guideline was substantially revised in 2021. These updated recommendations are intended to guide intensivists in providing adequate care to adult patients with sepsis or septic shock. In particular, the current SSC guideline emphasizes early recognition and stringent management in the first hours after the on...

Background Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predic...

Background Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods We i...

Introduction: In case of a contamination of water-supplying systems in hospitals with legionella, usually chemical disinfection measures are used for remediation. Unfortunately, it is reported, that these methods may not be sustainable, have an impact on water quality, and can even fail. As an alternative, the superheat and flush method does not n...

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Background: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score...

Very-low-carbohydrate diet triggers the endogenous production of ketone bodies as alternative energy substrates. There are as yet unproven assumptions that ketone bodies positively affect human immunity. We have investigated this topic in an in vitro model using primary human T cells and in an immuno-nutritional intervention study enrolling healthy...

Background. Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predi...

Background Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. Objective To...

Infections with cytomegalovirus (CMV) are one of the most frequent opportunistic infections in kidney transplant recipients. Current risk-adapted CMV chemoprophylaxis regimens are based almost solely on the donor and recipient CMV serostatus. Of note, the NFKB1 -94ins/delATTG promoter polymorphism was recently associated with a higher risk of CMV i...

Objective To investigate the effect of therapeutic suggestions played to patients through earphones during surgery on postoperative pain and opioid use. Design Blinded randomised controlled study. Setting Five tertiary care hospitals in Germany. Participants 385 of 400 patients consecutively recruited from January to December 2018 who were to un...

Sepsis is characterized by a dysregulated immune response, metabolic derangements and bioenergetic failure. These alterations are closely associated with a profound and persisting mitochondrial dysfunction. This however occurs despite increased expression of the nuclear-encoded transcription factor A (TFAM) that normally supports mitochondrial biog...

Mitochondrial DNA (mtDNA) plays a vital role as a damage-associated molecular pattern in sepsis being able to shape the immune response. Since pathogen recognition receptors of innate immune cells are activated by demethylated DNA only, we set out to investigate the amount of DNA methyltransferase 1 (DNMT1) in mitochondria and the extent of mtDNA m...

Purpose The approach to limit therapy in very old intensive care unit patients (VIPs) significantly differs between regions. The focus of this multicenter analysis is to illuminate, whether the Clinical Frailty Scale (CFS) is a suitable tool for risk stratification in VIPs admitted to intensive care units (ICUs) in Germany. Furthermore, this invest...

Introduction Sepsis is defined as detrimental immune response to an infection. This overwhelming reaction often abolishes a normal reconstitution of the immune cell homeostasis that in turn increases the risk for further complications. Recent studies revealed a favourable impact of ketone bodies on resolution of inflammation. Thus, a ketogenic diet...

Major complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and we explored the effect of AQP3 polymorphism on imm...

Since the functionally important AQP5 -1364A/C single nucleotide promoter polymorphism alters key mechanisms of inflammation and survival in sepsis, it may affect the risk of an acute kidney injury. Accordingly, we tested the hypothesis in septic patients that this AQP5 polymorphism is associated with major adverse kidney events and also validated...

Patients with severe infections and especially sepsis have a high in-hospital mortality, but even hospital survivors face long-term sequelae, decreased health-related quality of life, and high risk of death, suggesting a great need for specialized aftercare. However, data regarding a potential benefit of post-discharge rehabilitation in these patie...

Objectives: Pharmacokinetic-pharmacodynamic (PK-PD) considerations are at the heart of defining susceptibility breakpoints for antibiotic therapy. However, current approaches follow a fragmented workflow. The aim of this study was to develop an integrative pharmacometric approach to define MIC-based breakpoints for killing and suppression of resis...

Altered aquaporin 5 (AQP5) expression in immune cells impacts on key mechanisms of inflammation and is associated with sepsis survival. Since epigenetic regulation via DNA methylation might contribute to a differential AQP5 expression in sepsis, we tested the hypotheses that DNA methylation of the AQP5 promotor (1) influences AQP5 expression, (2) i...

Background: The aquaporin 5 (AQP5) −1364A/C promoter single nucleotide polymorphism affects key mechanisms of inflammation and immune cell migration. Thus, it could be involved in the pathogenesis of cytomegalovirus infection. Accordingly, we tested the hypothesis that the AQP5 promoter −1364A/C polymorphism is associated with the risk of cytomegal...

Background: For an effective antimicrobial treatment, it is crucial that antibiotics reach sufficient concentrations in plasma and tissue. Currently no data exist regarding moxifloxacin plasma concentrations and exposure levels in tissue under septic conditions. Objectives: To determine the pharmacokinetics of moxifloxacin in plasma and intersti...

Background Propofol is a widely used anaesthetic drug with advantageous operating conditions and recovery profile. However, propofol could have long term effects on neuronal cells and is associated with post-operative delirium (POD). In this context, one of the contributing factors to the pathogenesis of POD is a reduction of cholinesterase activit...

What we already know about this topic: Acute respiratory distress syndrome is defined according to clinical criteria, but lack of precise characterization may contribute to negative trials and impede personalized care. Polymorphisms of aquaporin-5, a key mediator of inflammation, may impact outcome. What this article tells us that is new: In acu...

Introduction The inhalative administration of drugs is a non-invasive application form that is regularly used in the treatment of ventilated patients in critical care setting. However, assessment of effectiveness or distribution of nebulised drugs is one of the lacking cornerstones of modern intensive care monitoring. Electrical impedance tomograph...

Background Aquaporin 5 (AQP5) expression impacts on cellular water transport, renal function but also on key mechanisms of inflammation and immune cell migration that prevail in sepsis and ARDS. Thus, the functionally relevant AQP5 -1364A/C promoter single nucleotide polymorphism could impact on the development and resolution of acute kidney injury...

Mean cumulative fluid balance with 95% CI stratified for patients with AKI (AKI stage ≥ 1) and without AKI until ICU day 30. Measurements on day 1, 5, 10, 15, 20, 25, and 30. (PDF)

Proportion of all patients stratified for AKI stage 1, 2, and 3 according to KDIGO criteria. Measurements on day 1, 5, 10, 15, 20, 25, and 30. (PDF)

Background In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospective...

Background: Acute liver injury in patients with ARDS decreases survival but early stages may be easily missed due to the lack of sufficient biomarkers signalling its onset. Accordingly, we tested in ARDS patients the hypotheses that microRNA-122, the foremost liver-related microRNA (miR), 1) is an sensitive and specific early predictor for potenti...

Background Sepsis is now operationally defined as life-threatening organ dysfunction caused by an infection, identified by an acute change in SOFA-Score of at least two points, including clinical chemistry such as creatinine or bilirubin concentrations. However, little knowledge exists about organ-specific microRNAs as potentially new biomarkers. A...

Baseline characteristics of the control group (infection without sepsis) and patients with sepsis according sepsis-3 criteria. (DOCX)

Cycle Threshold [CT] of cel-miR-54 expression in control patients, sepsis survivors, and sepsis non-survivors. Cel-miR-54 levels are presented in scatter plots. Data are shown as median with interquartile range. (PDF)

Zusammenfassung Die neue Leitlinie der Surviving Sepsis Campaign wurde im Jahr 2016 überarbeitet und im Jahr 2017 veröffentlicht. Darüber hinaus änderte sich durch „Sepsis-3“ die Definition der Sepsis im Jahr 2016 grundlegend, von einer Inflammation mit Infektion hin zu einer „lebensbedrohlichen Organ-Dysfunktion, die durch eine fehlregulierte Wirt...

Background: We tested the hypothesis that moxifloxacin monotherapy is equally effective and safe as a betalactam antibiotic based combination therapy in patients with acute respiratory distress syndrome (ARDS) evoked by severe community acquired pneumonia (CAP). Methods: In a retrospective chart review study of 229 patients with adult respirator...

Beta-cell-regeneration is considered as a future option for the therapy of diabetes, but the detection of beta-cell replication in human pancreas is still challenging. Therefore, the expression of Ki67, PCNA and MCM-7 in human pancreatic tissue was quantified in order to validate their use as beta-cell replication markers. Human pancreatic tissue s...