Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

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 (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

[Heparin-induced thrombocytopenia type II (HIT II) : A medical-economic view]. / Die heparininduzierte Thrombozytopenie (HIT II) : Eine medizinökonomische Betrachtung.

BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. METHODS: In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. RESULTS: HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G­DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. CONCLUSION: The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.

[Medical emergency teams in hospitals]. / Medizinische Notfallteams im Krankenhaus.

BACKGROUND: In-hospital emergencies represent an increasing challenge with regard to risk management in hospitals and until now, no binding recommendations for in-hospital emergency management are available in Germany. Time delays in the detection and treatment of critically ill patients on the wards often lead to serious adverse events. The concept of traditional resuscitation teams is not adequate, because they are initiated only after acute deterioration or cardiac arrest has already occurred. OBJECTIVE: The introduction of a rapid response system with a preventive approach based on a medical emergency team (MET) represents an essential improvement in the management of in-hospital emergencies. However, it is not sufficient to simply rename and restructure the existing resuscitation team to a MET. Rather, the introduction of standardized preventive alarm criteria and structured processes, standardization of training and emergency equipment in the clinic, and the provision of a MET associated with the intensive care unit are required. CONCLUSION: For a hospital with an already established resuscitation team, this represents a fundamental paradigm shift to a sustainable, interdisciplinary, and institutionalized process of rethinking and reorganizing. A clear commitment and ongoing joint efforts of the hospital management and all hospital staff are prerequisite for this.

[Mechanical resuscitation assist devices]. / Mechanische Reanimationshilfen.

In Germany 100,000-160,000 people suffer from out-of-hospital cardiac arrest (OHCA) annually. The incidence of cardiopulmonary resuscitation (CPR) after OHCA varies between emergency ambulance services but is in the range of 30-90 CPR attempts per 100,000 inhabitants per year. Basic life support (BLS) involving chest compressions and ventilation is the key measure of resuscitation. Rapid initiation and quality of BLS are the most critical factors for CPR success. Even healthcare professionals are not always able to ensure the quality of CPR measures. Consequently in recent years mechanical resuscitation devices have been developed to optimize chest compression and the resulting circulation. In this article the mechanical resuscitation devices currently available in Germany are discussed and evaluated scientifically in context with available literature. The ANIMAX CPR device should not be used outside controlled trials as no clinical results have so far been published. The same applies to the new device Corpuls CPR which will be available on the market in early 2014. Based on the current published data a general recommendation for the routine use of LUCAS™ and AutoPulse® CPR cannot be given. The preliminary data of the CIRC trial and the published data of the LINC trial revealed that mechanical CPR is apparently equivalent to good manual CPR. For the final assessment further publications of large randomized studies must be analyzed (e.g. the CIRC and PaRAMeDIC trials). However, case control studies, case series and small studies have already shown that in special situations and in some cases patients will benefit from the automatic mechanical resuscitation devices (LUCAS™, AutoPulse®). This applies especially to emergency services where standard CPR quality is far below average and for patients who require prolonged CPR under difficult circumstances. This might be true in cases of resuscitation due to hypothermia, intoxication and pulmonary embolism as well as for patients requiring transport or coronary intervention when cardiac arrest persists. Three prospective randomized studies and the resulting meta-analysis are available for active compression-decompression resuscitation (ACD-CPR) in combination with an impedance threshold device (ITD). These studies compared ACD-ITD-CPR to standard CPR and clearly demonstrated that ACD-ITD-CPR is superior to standard CPR concerning short and long-term survival with good neurological recovery after OHCA.

ARDS in an HIV-positive patient associated to respiratory syncytial virus.

We describe a clinical case of ARDS in an HIV infected patient. ARDS was associated to a respiratory syncytial virus infection that triggered a suspected Pneumocystis infection that despite missing etiologic proofs was treated with antimycotics. As rather limited information on RSV associated ARDS in HIV patients is available in the current literature, this case is of significant interest.

[Emergency physician and AutoPulse--a good duo in preclinical emergency services?: case example and report on experience]. / Notarzt und AutoPulse--ein gutes Duo im präklinischen Rettungsdienst?: Fallbeispiel und Erfahrungsbericht.

Survival rates after cardiac arrest remain poor despite substantial efforts to advance the cardiopulmonary resuscitation algorithm in the last decades. Recent changes in the resuscitation guidelines in 2005 focused on minimizing interruptions during chest compressions. The aim to provide optimal chest compressions led to the development of automated mechanical chest compression devices, one of which is the AutoPulse resuscitation system. A case of successful use of the AutoPulse system in a 66-year-old patient with sudden cardiac arrest is presented and a review is given of more than 3 years experience in the routine use of this mechanical device for CPR in the emergency medical system in Bonn. Based on this experience, the AutoPulse system is considered to be a safe and effective technical advancement that under certain CPR conditions can be a helpful tool and provide an increased quality of chest compressions.

[Horner's syndrome after fracture of the first rib]. / Horner-Syndrom nach Fraktur der ersten Rippe.

Horner's syndrome after trauma is rare. After visual diagnosis, a search for the cause is urgent due to possible life threatening damage. Intracerebral bleeding and carotid dissection must be excluded. Traumatic Horner's syndrome often seems to be, as in the case described here, caused by a fracture of the first rib. As persistent symptoms are not described, conservative therapy is recommended.

[Accidental urban hypothermia. Severe hypothermia of 20.7 degrees C]. / Akzidentelle urbane Unterkühlung. Schwere Hypothermie von 20.7 degrees C.

In emergency medicine accidental hypothermia (<35 degrees C) is a common epiphenomenon of many medical conditions. In contrast, severe hypothermia (<28 degrees C) occurs very seldom and presents a difficult medical situation. Here we present a female patient with severe urban hypothermia (core temperature of 20.7 degrees C) and circulatory arrest. An overview of the emergency treatment, rewarming strategy with extracorporeal circulation and the clinical course will be given. The survival of the patient and the favorable neurological outcome will be discussed considering the current literature. Due to the paucity of treatment guidelines or clear prognostic criteria of withholding or withdrawing treatment in severe hypothermia, the decision of prolonged resuscitation and rewarming strategy is solely dependent on the individual judgement and medical experience of the physician. The positive clinical outcome which can be gleaned from case reports or single retrospective studies should encourage the emergency physician to selectively rewarm a severe hypothermic patient with extracorporeal circulation under prolonged CPR.

[Urosepsis. Current therapy and diagnosis]. / Urosepsis Aktuelle Therapie und Diagnostik.

Urosepsis is defined as sepsis caused by urinary tract infection. This occurs in 25% of all sepsis cases. Because of the increasing incidence of sepsis, this entity will be seen more frequently in medical practice and outpatient units. The immediate identification and treatment of the septic focus is crucial. Depending on severity, early reconstitution of adequate oxygen delivery has parallel priority, therefore necessitating intensive care unit treatment within the first hours. Therapy should consist of eliminating the infectious focus, antimicrobial treatment, supportive therapy, and special sepsis therapy.

[Apoptosis as a pathomechanism in sepsis]. / Apoptose als Pathomechanismus in der Sepsis.

Sepsis is still a leading cause of death in many intensive care patients. The pathophysiology of the disease is dominated by complex immune cascades. Recent research demonstrates that immune cells respond to sepsis with an increased rate of programmed cell death. Up-regulated apoptosis of leukocytes was observed in animal models of sepsis as well as in patients suffering from severe sepsis. The mitochondrial protein Bcl-2 and the caspase cascade play an important role in the regulation of apoptosis. Overexpression of Bcl-2 or inhibition of caspases resulted in an increased survival in animal models of sepsis. Recent reports indicate the relevance of apoptosis in patients with severe sepsis. These results may spawn novel immunomodulatory strategies in the treatment of sepsis.

Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy.

A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE.

Cellular pathology of hilar neurons in Ammon's horn sclerosis.

In addition to functionally affected neuronal signaling pathways, altered axonal, dendritic, and synaptic morphology may contribute to hippocampal hyperexcitability in chronic mesial temporal lobe epilepsies (MTLE). The sclerotic hippocampus in Ammon's horn sclerosis (AHS)-associated MTLE, which shows segmental neuronal cell loss, axonal reorganization, and astrogliosis, would appear particularly susceptible to such changes. To characterize the cellular hippocampal pathology in MTLE, we have analyzed hilar neurons in surgical hippocampus specimens from patients with MTLE. Anatomically well-preserved hippocampal specimens from patients with AHS (n = 44) and from patients with focal temporal lesions (non-AHS; n = 20) were studied using confocal laser scanning microscopy (CFLSM) and electron microscopy (EM). Hippocampal samples from three tumor patients without chronic epilepsies and autopsy samples were used as controls. Using intracellular Lucifer Yellow injection and CFLSM, spiny pyramidal, multipolar, and mossy cells as well as non-spiny multipolar neurons have been identified as major hilar cell types in controls and lesion-associated MTLE specimens. In contrast, none of the hilar neurons from AHS specimens displayed a morphology reminiscent of mossy cells. In AHS, a major portion of the pyramidal and multipolar neurons showed extensive dendritic ramification and periodic nodular swellings of dendritic shafts. EM analysis confirmed the altered cellular morphology, with an accumulation of cytoskeletal filaments and increased numbers of mitochondria as the most prominent findings. To characterize cytoskeletal alterations in hilar neurons further, immunohistochemical reactions for neurofilament proteins (NFP), microtubule-associated proteins, and tau were performed. This analysis specifically identified large and atypical hilar neurons with an accumulation of low weight NFP. Our data demonstrate striking structural alterations in hilar neurons of patients with AHS compared with controls and non-sclerotic MTLE specimens. Such changes may develop during cellular reorganization in the epileptogenic hippocampus and are likely to contribute to the pathogenesis or maintenance of temporal lobe epilepsy.