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Objective: Fluconazle or posaconazole is a standard of care in antifungal prophylaxis for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). However, many patients need to interrupt standard prophylaxis due to intolerability, drug‐drug interactions, or toxicity. Micafungin has come to prominence for these patients. However, the optimal biological dose of micafungin stays unclear.
Methods: We retrospectively evaluated the efficacy of micafungin as antifungal prophylaxis in HSCT patients. Micafungin was applied as bridging in patients who were not eligible to receive oral posaconazole. Micafungin was either given at a dose of 100 mg or 50 mg SID.
Results: A total of 173 patients received micafungin prophylaxis, 62 in the 100 mg and 111 in the 50 mg dose group. The incidence of probable or proven breakthrough IFDs during the observation period was one in the 100 mg and one in the 50 mg group. Fungal‐free survival after 100 days was 98% and 99% (P = .842), and overall survival after 365 days was 60% and 63% (P = .8) respectively. In both groups, micafungin was well tolerated with no grade 3 or 4 toxicities.
Conclusion: In this retrospective analysis, which was not powered to detect non‐inferiority, micafungin is effective and complements posaconazole as fungal prophylaxis in HSCT.
Review of: Vinzenz Brinkmann, Oliver Primavesi, Max Hollein (eds.), Circumlitio. The Polychromy of Antique and Medieval Sculpture. Proceedings of the Johann David Passavant Colloquium, 10-12 December 2008. Liebighaus Skulpturensammlung, Frankfurt am Main, 2010, 423 pp., 334 colour ill.,ISBN 978-3-7774-2871-0
New scientific methods now being applied to the analysis of traces of pigments and gilding on ancient Greek and Roman marble statuary, and other marble artefacts, have the potential to revolutionise our understanding of the relationship between form and colour in antiquity. At present the enquiry is still in its infancy, but the papers delivered at a conference held in Frankfurt in 2008, reviewed here, provide a general introduction to the subject and to a wide range of work in progress.
Characteristics and clinical outcome of breast cancer patients with asymptomatic brain metastases
(2020)
Simple Summary: The prognosis for patients with breast cancer that has spread to the brain is poor, and survival for these women hasn’t improved over the last few decades. We do not currently test for asymptomatic brain metastases in breast cancer patients, although this does happen in some other types of cancer. In this study we wanted to find out more about breast cancer that has spread to the brain and in particular to see whether there might be any advantage to spotting brain metastases before the development of neurological symptoms. Overall, our results suggest that women could be better off if their brain metastases are diagnosed before they begin to cause symptoms. We now need to carry out a clinical trial to see what happens if we screen high-risk breast cancer patients for brain metastases. This will verify whether doing so could increase survival, symptom control or quality of life.
Abstract: Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80–100%: 68.4% vs. 57%, p < 0.001), a lower number of BM (>1 BM: 56% vs. 70%, p = 0.027), and a slightly smaller diameter of BM (median: 1.5 vs. 2.2 cm, p < 0.001). Asymptomatic patients were more likely to have extracranial metastases (86.7% vs. 81.5%, p = 0.003) but were less likely to have leptomeningeal metastasis (6.3% vs. 10.9%, p < 0.001). Asymptomatic patients underwent less intensive BM therapy but had a longer median overall survival (statistically significant for a cohort of HER2-positive patients) compared to symptomatic patients (10.4 vs. 6.9 months, p < 0.001). Conclusions: These analyses show a trend that asymptomatic patients have less severe metastatic brain disease and despite less intensive local BM therapy still have a better outcome (statistically significant for a cohort of HER2-positive patients) than patients who present with symptomatic BM, although a lead time bias of the earlier diagnosis cannot be ruled out. Our analysis is of clinical relevance in the context of potential trials examining the benefit of early detection and treatment of BM.
The ecological validity of neuropsychological testing (NT) has been questioned in the sports environment. A frequent criticism is that NT, mostly consisting of pen and paper or digital assessments, lacks relevant bodily movement. This study aimed to identify the determinants of a newly developed testing battery integrating both cognitive and motor demands. Twenty active individuals (25 ± 3 years, 11 males) completed the new motor-cognitive testing battery (MC), traditional NT (Stroop test, Trail Making test, Digit Span test) and isolated assessments of motor function (MF; Y-balance test, 20m-sprint, counter-movement jump). Kendal’s tau and partial Spearman correlations were used to detect associations between MC and NT/MF. Except for two items (Reactive Agility A and counter-movement jump; Run-Decide and sprint time; r = 0.37, p < 0.05), MC was not related to MF. Similarly, MC and NT were mostly unrelated, even when controlling for the two significant motor covariates (p > 0.05). The only MC item with (weak to moderate) associations to NT was the Memory Span test (Digit Span backwards and composite; r = 0.43–0.54, p < 0.05). In sum, motor-cognitive function appears to be largely independent from its two assumed components NT and MF and may represent a new parameter in performance diagnostics.
Diverse extracellular signals induce plasma membrane translocation of sphingosine kinase-1 (SphK1), thereby enabling inside-out signaling of sphingosine-1-phosphate. We have shown before that Gq-coupled receptors and constitutively active Gαq/11 specifically induced a rapid and long-lasting SphK1 translocation, independently of canonical Gq/phospholipase C (PLC) signaling. Here, we further characterized Gq/11 regulation of SphK1. SphK1 translocation by the M3 receptor in HEK-293 cells was delayed by expression of catalytically inactive G-protein-coupled receptor kinase-2, p63Rho guanine nucleotide exchange factor (p63RhoGEF), and catalytically inactive PLCβ3, but accelerated by wild-type PLCβ3 and the PLCδ PH domain. Both wild-type SphK1 and catalytically inactive SphK1-G82D reduced M3 receptor-stimulated inositol phosphate production, suggesting competition at Gαq. Embryonic fibroblasts from Gαq/11 double-deficient mice were used to show that amino acids W263 and T257 of Gαq, which interact directly with PLCβ3 and p63RhoGEF, were important for bradykinin B2 receptor-induced SphK1 translocation. Finally, an AIXXPL motif was identified in vertebrate SphK1 (positions 100–105 in human SphK1a), which resembles the Gαq binding motif, ALXXPI, in PLCβ and p63RhoGEF. After M3 receptor stimulation, SphK1-A100E-I101E and SphK1-P104A-L105A translocated in only 25% and 56% of cells, respectively, and translocation efficiency was significantly reduced. The data suggest that both the AIXXPL motif and currently unknown consequences of PLCβ/PLCδ(PH) expression are important for regulation of SphK1 by Gq/11.
Crustal structure at the western end of the North Anatolian Fault Zone from deep seismic sounding
(2001)
The first deep seismic sounding experiment in Northwestern Anatolia was carried out in October 1991 as part of the "German - Turkish Project on Earthquake Prediction Research" in the Mudurnu area of the North Anatolian Fault Zone. The experiment was a joint enterprise by the Institute of Meteorology and Geophysics of Frankfurt University, the Earthquake Research Institute (ERI) in Ankara, and the Turkish Oil Company (TPAO). Two orthogonal profiles, each 120 km in length with a crossing point near Akyazi, were covered in succession by 30 short period tape recording seismograph stations with 2 km station spacing. 12 shots, with charge sizes between 100 and 250 kg, were fired and 342 seismograms out of 360 were used for evaluation. By coincidence an M b = 4.5 earthquake located below Imroz Island was also recorded and provided additional information on Moho and the sub-Moho velocity. A ray tracing method orginally developed by Weber (1986) was used for travel time inversion. From a compilation of all data two generalized crustal models were derived, one with velocity gradients within the layers and one with constant layer velocities. The latter consists of a sediment cover of about 2 km with V p » 3.6 km/s, an upper crystalline crust down to 13 km with V p » 5.9 km/s, a middle crust down to 25 km depth with V p » 6.5 km/s, a lower crust down to 39 km Moho depth with V p » 7.0 km/s and V p » 8.05 km/s below the Moho. The structure of the individual profiles differs slightly. The thickest sediment cover is reached in the Izmit-Sapanca-trough and in the Akyazi basin. Of particular interest is a step of about 4 km in the lower crust near Lake Sapanca and probably an even larger one in the Moho (derived from the Imroz earthquake data). After the catastrophic earthquake of Izmit on 17 August 1999 this significant heterogeneity in crustal structure appears in a new light with regard to the possible cause of the Izmit earthquake. Heterogeneities in structure are frequently also heterogeneities in strength and stress that impede or even lock rupture. The Izmit earthquake is discussed in relation to a large stepover or jog at the North Anatolian Fault.
Background: A large number of idiosyncratic drug induced liver injury (iDILI) and herb induced liver injury(HILI) cases of variable quality has been published but some are a matter of concern if the cases were not evaluated for causality using a robust causality assessment method (CAM) such as RUCAM (Roussel Uclaf Causality Assessment Method) as diagnostiinjuryc algorithm. The purpose of this analysis was to evaluate the worldwide use of RUCAM in iDILI and HILI cases. Methods: The PubMed database (1993–30 June 2020) was searched for articles by using the following key terms: Roussel Uclaf Causality Assessment Method; RUCAM; Idiosyncratic drug induced liver injury; iDILI; Herb induced liver injury; HILI. Results: Considering reports published worldwide since 1993, our analysis showed the use of RUCAM for causality assessment in 95,885 cases of liver injury including 81,856 cases of idiosyncratic DILI and 14,029 cases of HILI. Among the top countries providing RUCAM based DILI cases were, in decreasing order, China, the US, Germany, Korea, and Italy, with China, Korea, Germany, India, and the US as the top countries for HILI. Conclusion: Since 1993 RUCAM is certainly the most widely used method to assess causality in IDILI and HILI. This should encourage practitioner, experts, and regulatory agencies to use it in order to reinforce their diagnosis and to take sound decisions.
We model the decisions of young individuals to stay in school or drop out and engage in criminal activities. We build on the literature on human capital and crime engagement and use the framework of Banerjee (1993) that assumes that the information needed to engage in crime arrives in the form of a rumour and that individuals update their beliefs about the profitability of crime relative to education. These assumptions allow us to study the effect of social interactions on crime. In our model, we investigate informational spillovers from the actions of talented students to less talented students. We show that policies that decrease the cost of education for talented students may increase the vulnerability of less talented students to crime. The effect is exacerbated when students do not fully understand the underlying learning dynamics.
Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient’s own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF) was compared to standard platelet-rich plasma (PRP) with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× g) for 3 min) were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), collagen1 (COL1) and fibronectin (FN). The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA) levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.
We aim to understand whether Greek and Italian, two null subject languages, differ in the use and interpretation of null subjects, based on evidence from both a production and a comprehension experiment. The results of the two experiments show that the two languages differ in the extent to which they comply with the Position of Antecedent Strategy as formulated by Carminati (2002). In order to account for this difference, we introduce a principle which defines prominence of sentence constituents in terms of hierarchical height, elaborating on a recent proposal by Rizzi (2018). Then we show that the prominence of subject and object constituents in Greek and Italian reflects word-order differences between the two languages (Roussou & Tsimpli 2006). In more general terms, this paper argues in favour of a multi-factorial approach to reference interpretation, in that syntactic factors interact with discourse factors, leading to a gradient variety of reference possibilities.
Background and objectives: Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce.
Materials and methods: To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016.
Results: Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron.
Conclusion: Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.
Aim: To provide distribution information and preliminary conservation assessments for all species of the pineapple family (Bromeliaceae), one of the most diverse and ecologically important plant groups of the American tropics—a global biodiversity hotspot. Furthermore, we aim to analyse patterns of diversity, endemism and the conservation status of the Bromeliaceae on the continental level in the light of their evolutionary history.
Location: The Americas.
Methods: We compiled a dataset of occurrence records for 3,272 bromeliad species (93.4% of the family) and modelled their geographic distribution using either climate‐based species distribution models, convex hulls or geographic buffers dependent on the number of occurrences available. We then combined this data with information on taxonomy and used the ConR software for a preliminary assessment of the conservation status of all species following Criterion B of the International Union for the Conservation of Nature (IUCN).
Results: Our results stress the Atlantic Forest in eastern Brazil, the Andean slopes, Central America and the Guiana Highlands as centres of bromeliad diversity and endemism. Phylogenetically ancient subfamilies of bromeliads are centred in the Guiana highlands whereas the large radiations of the group spread across different habitats and large geographic area. A total of 81% of the evaluated bromeliad species are Possibly Threatened with extinction. We provide range polygons for 3,272 species, as well as newly georeferenced point localities for 911 species in the novel “bromeliad” r package, together with functions to generate diversity maps for individual taxonomic or functional groups.
Main conclusions: Diversity centres of the Bromeliaceae agreed with macroecological patterns of other plant and animal groups, but show some particular patterns related to the evolutionary origin of the family, especially ancient dispersal corridors. A staggering 2/3rds of Bromeliaceae species might be threatened with extinction, especially so in tropical rain forests, raising concerns about the conservation of the family and bromeliad‐dependent animal species.
Colorectal cancer (CRC) is one of the most frequently diagnosed tumor in humans and one of the most common causes of cancer-related death worldwide. The pathogenesis of CRC follows a multistage process which together with somatic gene mutations is mainly attributed to the dysregulation of signaling pathways critically involved in the maintenance of homeostasis of epithelial integrity in the intestine. A growing number of studies has highlighted the critical impact of members of the tripartite motif (TRIM) protein family on most types of human malignancies including CRC. In accordance, abundant expression of many TRIM proteins has been observed in CRC tissues and is frequently correlating with poor survival of patients. Notably, some TRIM members can act as tumor suppressors depending on the context and the type of cancer which has been assessed. Mechanistically, most cancer-related TRIMs have a critical impact on cell cycle control, apoptosis, epithelial–mesenchymal transition (EMT), metastasis, and inflammation mainly through directly interfering with diverse oncogenic signaling pathways. In addition, some recent publications have emphasized the emerging role of some TRIM members to act as transcription factors and RNA-stabilizing factors thus adding a further level of complexity to the pleiotropic biological activities of TRIM proteins. The current review focuses on oncogenic signaling processes targeted by different TRIMs and their particular role in the development of CRC. A better understanding of the crosstalk of TRIMs with these signaling pathways relevant for CRC development is an important prerequisite for the validation of TRIM proteins as novel biomarkers and as potential targets of future therapies for CRC.
Summary
Wild relatives of crops thrive in habitats where environmental conditions can be restrictive for productivity and survival of cultivated species. The genetic basis of this variability, particularly for tolerance to high temperatures, is not well understood. We examined the capacity of wild and cultivated accessions to acclimate to rapid temperature elevations that cause heat stress (HS).
We investigated genotypic variation in thermotolerance of seedlings of wild and cultivated accessions. The contribution of polymorphisms associated with thermotolerance variation was examined regarding alterations in function of the identified gene.
We show that tomato germplasm underwent a progressive loss of acclimation to strong temperature elevations. Sensitivity is associated with intronic polymorphisms in the HS transcription factor HsfA2 which affect the splicing efficiency of its pre‐mRNA. Intron splicing in wild species results in increased synthesis of isoform HsfA2‐II, implicated in the early stress response, at the expense of HsfA2‐I which is involved in establishing short‐term acclimation and thermotolerance.
We propose that the selection for modern HsfA2 haplotypes reduced the ability of cultivated tomatoes to rapidly acclimate to temperature elevations, but enhanced their short‐term acclimation capacity. Hence, we provide evidence that alternative splicing has a central role in the definition of plant fitness plasticity to stressful conditions.
Aim: Predicting future changes in species richness in response to climate change is one of the key challenges in biogeography and conservation ecology. Stacked species distribution models (S‐SDMs) are a commonly used tool to predict current and future species richness. Macroecological models (MEMs), regression models with species richness as response variable, are a less computationally intensive alternative to S‐SDMs. Here, we aim to compare the results of two model types (S‐SDMS and MEMs), for the first time for more than 14,000 species across multiple taxa globally, and to trace the uncertainty in future predictions back to the input data and modelling approach used.
Location: Global land, excluding Antarctica.
Taxon: Amphibians, birds and mammals.
Methods: We fitted S‐SDMs and MEMs using a consistent set of bioclimatic variables and model algorithms and conducted species richness predictions under current and future conditions. For the latter, we used four general circulation models (GCMs) under two representative concentration pathways (RCP2.6 and RCP6.0). Predicted species richness was compared between S‐SDMs and MEMs and for current conditions also to extent‐of‐occurrence (EOO) species richness patterns. For future predictions, we quantified the variance in predicted species richness patterns explained by the choice of model type, model algorithm and GCM using hierarchical cluster analysis and variance partitioning.
Results: Under current conditions, species richness predictions from MEMs and S‐SDMs were strongly correlated with EOO‐based species richness. However, both model types over‐predicted areas with low and under‐predicted areas with high species richness. Outputs from MEMs and S‐SDMs were also highly correlated among each other under current and future conditions. The variance between future predictions was mostly explained by model type.
Main conclusions: Both model types were able to reproduce EOO‐based patterns in global terrestrial vertebrate richness, but produce less collinear predictions of future species richness. Model type by far contributes to most of the variation in the different future species richness predictions, indicating that the two model types should not be used interchangeably. Nevertheless, both model types have their justification, as MEMs can also include species with a restricted range, whereas S‐SDMs are useful for looking at potential species‐specific responses.
In 2010, the Conference of the Parties of the Convention on Biological Diversity agreedon the Strategic Plan for Biodiversity 2011–2020 in Aichi Prefecture, Japan. As this planapproaches its end, we discussed whether marine biodiversity and prediction studieswere nearing the Aichi Targets during the 4th World Conference on Marine Biodiversityheld in Montreal, Canada in June 2018. This article summarises the outcome of a five-day group discussion on how global marine biodiversity studies should be focusedfurther to better understand the patterns of biodiversity. We discussed and reviewedseven fundamental biodiversity priorities related to nine Aichi Targets focusing onglobal biodiversity discovery and predictions to improve and enhance biodiversitydata standards (quantity and quality), tools and techniques, spatial and temporal scaleframing, and stewardship and dissemination. We discuss how identifying biodiversityknowledge gaps and promoting efforts have and will reduce such gaps, including via theuse of new databases, tools and technology, and how these resources could be improvedin the future. The group recognised significant progress toward Target 19 in relationto scientific knowledge, but negligible progress with regard to Targets 6 to 13 whichaimed to safeguard and reduce human impacts on biodiversity.
Cardiac reactions to emotional words in adolescents and young adults with PTSD after child abuse
(2019)
Post‐traumatic stress disorder (PTSD) is associated with alterations in cardiac reactivity to threat cues. Meta‐analyses have summarized that adults with PTSD have increased heart rates in response to trauma‐related stimuli. However, the opposite effect (i.e., cardiac hyporeactivity) has recently been reported in subgroups of PTSD patients. In children and adolescents with PTSD, reports of cardiac alterations are rare and ambiguous. So far, most studies in adolescents and young adults are restricted to victims of accidents, even though PTSD is highly prevalent in victims of child maltreatment. The present study aimed at investigating cardiac reactions in adolescents and young adults with PTSD after child abuse. Cardiac responses to standardized emotional words were studied in 39 adolescent and young adult PTSD patients after childhood sexual and/or physical abuse as compared to 39 healthy control subjects (age range: 15–20 years). The experimental paradigm consisted of a passive reading task with neutral, positive, physically threatening, and socially threatening (swear) words. Results showed that cardiac reactions to negative stimuli, particularly physically threatening stimuli, were less pronounced in PTSD patients than in controls. Moreover, cardiac reactions in response to socially threatening words were less variable in the PTSD group. No differences between and within groups were present in reaction to neutral or positive stimuli. Findings suggest that a physiologically blunted subtype of PTSD may already manifest during adolescence and young adulthood. Moreover, the results of the present study emphasize the relevance of individual trauma history for physiological reactions.
Health economics of Patient Blood Management: a cost‐benefit analysis based on a meta‐analysis
(2019)
Background and Objectives: Patient Blood Management (PBM) is the timely application of evidence‐based medical and surgical concepts designed to improve haemoglobin concentration, optimize haemostasis and minimize blood loss in an effort to improve patient outcomes. The focus of this cost‐benefit analysis is to analyse the economic benefit of widespread implementation of a multimodal PBM programme.
Materials and Methods: Based on a recent meta‐analysis including 17 studies (>235 000 patients) comparing PBM with control care and data from the University Hospital Frankfurt, a cost‐benefit analysis was performed. Outcome data were red blood cell (RBC) transfusion rate, number of transfused RBC units, and length of hospital stay (LOS). Costs were considered for the following three PBM interventions as examples: anaemia management including therapy of iron deficiency, use of cell salvage and tranexamic acid. For sensitivity analysis, a Monte Carlo simulation was performed.
Results: Iron supplementation was applied in 3·1%, cell salvage in 65% and tranexamic acid in 89% of the PBM patients. In total, applying these three PBM interventions costs €129·04 per patient. However, PBM was associated with a reduction in transfusion rate, transfused RBC units per patient, and LOS which yielded to mean savings of €150·64 per patient. Thus, the overall benefit of PBM implementation was €21·60 per patient. In the Monte Carlo simulation, the cost savings on the outcome side exceeded the PBM costs in approximately 2/3 of all repetitions and the total benefit was €1 878 000 in 100·000 simulated patients.
Conclusion: Resources to implement a multimodal PBM concept optimizing patient care and safety can be cost‐effectively.
Objective: Novel treatments are needed to control treatment‐resistant status epilepticus (SE). We present a summary of clinical cases where oral topiramate (TPM) was used in refractory SE (RSE) and superrefractory SE (SRSE).
Methods: A review of medical records was carried out to detect TPM administration in SE patients treated in Frankfurt and Marburg between 2011 and 2016. The primary outcome question concerned SE resolution after TPM initiation.
Results: In total, TPM was used in 106 of 854 patients having a mean age of 67.4 ± 18.1 years, 61 of whom were female (57.5%). The median latency from SE onset to TPM initiation was 8.5 days. Patients with SE had previously failed a median of five other antiepileptic drugs. The median initial TPM dose was 100 mg/d, which was uptitrated to a median maintenance dose of 400 mg/d. Treatment with TPM was continued for a median time of 12 days. TPM was the last drug provided to 42 of 106 (39.6%) patients, with a resultant response attributed to TPM observed in 29 of 106 (27.4%) patients. A response was attributed to TPM in 21 (31.8%) of 66 RSE cases and eight (20%) of 40 SRSE cases. Treatment‐emergent adverse events were attributed to TPM usage in two patients, one each with pancreatitis and hyperchloremic acidosis, and in 38 patients (35.8%), hyperammonemia was seen. Thirty‐four of these patients received a combination of TPM and valproate and/or phenobarbital. The intrahospital mortality rate was 22.6% (n = 24).
Significance: The rate of SE cessation attributed to TPM treatment (27.4%) represents a relevant response given the late treatment position of TPM and the treatment latency of more than 8 days. Based on these results and in line with the findings of other case series, TPM can be considered an alternative option for treating RSE and SRSE.