The effect of peer review on mortality rates.

OBJECTIVE: Lowering of mortality rates in hospitals with mortality rates higher than accepted reference values for acute myocardial infarction (AMI), congestive heart failure (CHF), pneumonia, stroke, mechanical ventilation (MV) and colorectal surgery by using an external peer review process that identifies areas requiring rectification and implements protocols directed at improving these areas. DESIGN: Retrospective, observational, quality management study using administrative data to compare in-hospital mortality rates (pre and post an external peer review process that included adoption of improvement protocols) with reference values. SETTING: German general hospitals of a large, private group. PARTICIPANTS: Hospitals with mortality rates higher than reference values. INTERVENTIONS: Peer review of medical records by experienced, outside physicians triggered by in-hospital mortality rates higher than expected. Inadequacies were identified, improvement protocols enforced and mortality rates subsequently re-examined. MAIN OUTCOME MEASURES: Mortality rates 1 year before and 1 year after peer review and protocol use. RESULTS: For AMI, CHF, pneumonia, stroke, MV and colorectal surgery, the mortality rates 1 year post-peer review were significantly decreased as compared to pre-peer review mortality rates. The standardized mortality ratio for all of the above diagnoses was 1.45, 1 year before peer review, and 0.97, 1 year after peer review. The absolute risk reduction of 7.3% translates into 710 deaths in this population which could have been prevented. CONCLUSIONS: Peer review triggered and conducted in the manner described here is associated with a significant lowering of in-hospital mortality rates in hospitals that previously had higher than expected mortality rates.

Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature.

BACKGROUND: Neuromyelitis optica (NMO, Devic syndrome) and myasthenia gravis (MG) are rare antibody-mediated autoimmune disorders. Concurrent incidence has been reported in only few patients, mostly non-Caucasians. OBJECTIVE: To report on ten Caucasian patients with NMO spectrum disorders (NMOSD) and MG and to provide a comprehensive review of the literature. METHOD: Retrospective study. RESULTS: In total, 26 patients (m:f = 1:12; Caucasian in 12) with MG (generalized in 17) and NMOSD (NMO in 21, longitudinally extensive transverse myelitis in five) were identified from the authors' own files (n = 10) and the previous literature (n = 16). MG preceded NMOSD in 24/25 cases (96%). AQP4-Ab were tested in 20 patients and were positive in 17 (85%). Twenty out of 25 patients (80%) had been treated with thymectomy or thymic irradiation, which preceded NMOSD in all cases (median latency, 12 years; range, 0.3-32). At last follow-up, complete remission of MG was reported in 15/22 (68%), and MG was well controlled with pyridostigmine in three. Co-existing autoimmune disorders or autoimmune antibodies were reported in 17 patients. CONCLUSION: Our study demonstrates that i) AQP4-Ab-positive NMOSD are more commonly associated with MG in Caucasians than previously thought; ii) MG precedes NMOSD in most cases, often by more than a decade; iii) NMOSD almost exclusively occur in females with juvenile or early-onset MG; and iv) MG frequently takes an unusually mild course in patients with NMOSD. A history of thymectomy could be a possible risk factor for the later development of NMOSD. We recommend testing for AQP4-Ab in MG patients presenting with atypical motor or optic symptoms.

Ischemic and hemorrhagic complications after intra-arterial fibrinolysis in vertebrobasilar occlusion.

BACKGROUND AND PURPOSE: To evaluate the incidence and location of hemorrhagic and ischemic lesions after local intra-arterial (IA) fibrinolysis in patients with acute vertebrobasilar occlusion (VBO). METHODS: One hundred forty-three patients with VBO treated with local IA fibrinolysis were retrospectively evaluated. Two different thrombolytic substances, namely urokinase (UK, n = 57 patients) and recombinant tissue plasminogen activator (rtPA, n = 86 patients), were used. Incidence and location of intracranial hemorrhage and ischemic infarction were assessed by means of 403 peri-interventional CT and MR imaging scans. Recanalization success and bleeding rate were correlated with the type and dosage of fibrinolytic agent. Multiple logistic regression was used for statistical analysis. RESULTS: Intracranial hemorrhage was detected in 46 (32%) patients. Bleeding rate was significantly higher for high-dose rtPA than for UK (36% versus 21%, P < .01). Neurologic outcome was worse in patients with postinterventional bleeding (P < .001). Ischemic infarctions were present in 136 (95%) patients. Ischemic lesions of the occipital lobe and thalamus were more frequently seen in the case of successful recanalization than after absent recanalization (P < .005). Occlusion of the postcommunicating segment of the posterior cerebral artery after successful recanalization was seen in 39% of patients. CONCLUSIONS: In acute VBO, bleeding rate after IA rtPA seems to be higher than that using IA UK, especially after high-dose rtPA. Ischemic lesion patterns after successful local IA fibrinolysis are common and correspond to the frequent distal migration of the thrombus. Novel recanalization techniques allowing for endovascular thrombectomy are needed to reduce ischemic and hemorrhagic complications in the treatment of acute VBO.

Outcome of acute vertebrobasilar occlusions treated with intra-arterial fibrinolysis in 180 patients.

BACKGROUND AND PURPOSE: To evaluate predictors of recanalization and a favorable neurologic outcome in patients with acute vertebrobasilar occlusion (VBO) treated with local intra-arterial fibrinolysis (LIF). METHODS: The multicentric data of 180 patients with acute VBO treated with LIF were retrospectively evaluated. The modified Rankin scale (mRS) was used to evaluate the neurologic status before LIF and at the time of discharge. Patient's sex, age, etiology of VBO, recanalization, symptom duration before LIF, and pretreatment mRS were correlated with posttreatment mRS. Multiple logistic regression analysis was used to identify independent variables for recanalization and neurologic outcome. RESULTS: The overall mortality was 43%. Complete recanalization was achieved in 99 (55%) patients and a partial recanalization in 35 (19%) patients, respectively. Recanalization was significantly associated with a favorable outcome (P < .001). The success of recanalization was negatively correlated with the volume of the thrombus (P < .001). No correlation was found between site and etiology of VBO and recanalization. Neurologic outcome correlated strongly with the pretreatment mRS (P < .001) and also with age (P < .02). Coma lasting less than 4.5 hours led to a positive trend toward a better outcome after univariate testing (P < .001). CONCLUSIONS: Success of recanalization and neurologic status before treatment predict neurologic outcome in patients with VBO. Thrombus volume has an adverse effect on the recanalization success.

Plasminogen activation in focal cerebral ischemia and reperfusion.

In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2%+/-8.5% and 19.4%+/-30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8%+/-42.2%, P < 0.05) but not in the cortex (43.0%+/-34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury (r = 0.873, P < 0.001). No such correlation was found in the cortex (r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.

Increased intracellular calpain detection in experimental focal cerebral ischemia.

Calpains are intracellular proteinases whose proteolytic activity is directed mainly against the cytoskeleton and regulatory proteins. We studied the presence of calpain by immunohistochemistry in a rat model of reversible focal cerebral ischemia (3 h) at various times of reperfusion. The numbers of calpain-positive cells on the ischemic side were compared with the non-ischemic side. In controls only 2 +/- 1% cells were positive, whereas the cortex of the ischemic vs the non-ischemic side showed 88 +/- 3% vs 13 +/- 4% calpain-positive cells (p < 0.001), and the basal ganglia 47 +/- 3% vs 13 +/- 4% (p < 0.01) after 3 h ischemia and 24 h reperfusion. This is the first demonstration of elevated intracellular levels of calpains in areas of cerebral ischemia. Longer reperfusion resulted in an increase in calpain positivity.

A gelatin in situ-overlay technique localizes brain matrix metalloproteinase activity in experimental focal cerebral ischemia.

To determine the activity of matrix metalloproteinases (MMP), especially MMP-2 and MMP-9, which play an important role in ischemic stroke and intracerebral hemorrhage, we adapted a simple and rapid method for localizing gelatinase activity to a gelatin film in situ-overlay technique previously used in cancer research. Ten micrometer cryosections of rat brain from controls and animals subjected to 3 h of ischemia and 48 h of reperfusion (suture model for transient cerebral ischemia) were used. After thawing, a gelatin film with a polyester base was put on the slide, incubated for 24 h at 37 degrees C, stained with Ponceau S, and then discolored in bi-distilled water. Non-staining areas on the film corresponded to lysis zones, caused by activated MMPs. This was proven by MMP incubation at various concentrations on the plain gelatin film and pretreatment with EDTA (an MMP inhibitor), which prevents lysis zones in normal and ischemic brains. As confirmatory tests, SDS-PAGE zymography was used to define MMP activity, and also MMP-2 immunohistochemistry to detect the possibly cellular origin of MMPs. Normal rat brain exhibited a low background activity, which was visible as a light halo-like lysis zone over and around the brain. Areas in normal brain with medium MMP activity were within the white matter (corpus callosum, anterior commissure, and cerebellum). Ischemic brain exhibited high activity lysis zones within the infarcted area (detected by microtubuli associated protein-2 staining). These zones consisted of microscopically small lysis holes with a diameter of about 10-20 microm. Immunohistochemistry showed that especially microvessels expressed MMP antigen. SDS-PAGE zymography differentiated between a high level of activated MMPs in the ischemic area and a low level in the non-ischemic basal ganglia. The gelatin film in situ-overlay technique is able to localize MMP activity in ischemic rat brain tissue on a microscopic level.

Plasminogen activation in experimental permanent focal cerebral ischemia.

BACKGROUND: Previous experimental work using in situ zymography has shown very early increased plasminogen activation in ischemic regions after 3 h of ischemia with and without reperfusion. The objective of the present study was to evaluate the time course and extent of plasminogen activation in long-term permanent focal cerebral ischemia. MATERIAL AND METHODS: The middle cerebral artery in male Fisher rats was irreversibly occluded by electrocoagulation. Duration of ischemia was 48, 72, and 168 h. Occlusion was controlled in vivo by MRI at day 2. Plasminogen activation was detected by in situ zymography of 10 microm cryosections with an overlay containing plasminogen and the plasmin substrate caseine. Areas of plasminogen activation were compared to structural lesions (immunohistochemical loss of microtubule-associated protein 2; MAP 2). RESULTS: Compared to controls, increased plasminogen activation was observed in the basal ganglia and the cortex of the ischemic hemisphere after 48, 72, and 168 h (affected area of basal ganglia: 44.5+/-21.9, 70.1+/-2.3 and 66.6+/-2.8%, respectively; affected area of cortex: 63.4+/-9.8, 67.7+/-0.7 and 64.0+/-3.7%, respectively). The duration of ischemia had no significant influence on the extent of plasminogen activation. Areas of increased plasminogen activation significantly overlapped with and exceeded areas of MAP 2 loss (P<0.005). DISCUSSION: Permanent focal cerebral ischemia leads to increased plasminogen activation in ischemic regions. This plasminogen activation remains elevated at persistent levels over days. It may contribute to extracellular matrix (ECM) disruption, secondary hemorrhage, and brain edema in subacute stages of ischemic stroke.

[10 years of Peer Reviewing: improving treatment by quality indicators from administrative data]. / 10 Jahre Peer Review - Verbesserung der medizinischen Behandlung durch Qualitätsindikatoren aus Routinedaten.

BACKGROUND AND OBJECTIVES: In-hospital mortality of myocardial infarction, heart failure and pneumonia within a private hospital chain were compared with the German average since 2000. METHODS: Increased in-hospital mortalities based on diagnosis coding with ICD-10 benchmarked with German average values induced peer reviews in concern hospitals. From 2000 until 2010, peer reviews as performed by at least 2 peers compared retrospectively case management and treatment with best care, classified the treatment and discussed it with responsible physicians. The classification consisted of category 1 for improvement potential, category 2 for miscoding and category 3 for sufficient treatment. Based on the improvement potential an operational plan of treatment improvement for the single hospital was produced which was to be realized by this hospital and supported by concern activities for knowledge improvement. RESULTS: In 2000, the indicators in-hospital mortality of myocardial infarction, heart failure and pneumonia of the hospital chain exceeded German average whereas in 2008 these values were lower (i. e. better) than German average. The peer reviews detected large improvement potentials in treatment processes and helped to improve them. CONCLUSION: Peer reviews as triggered by quality indicators supported improvement of treatment and likely outcomes.

[White matter lesions as a risk factor for stroke and dementia. A population-based study in 85-year-olds]. / Marklagerläsionen als Risikofaktor für Schlaganfälle und Demenzen. Ergebnisse einer populationsbasierten Studie bei 85-Jährigen.

AIM: This study was performed to determine whether white matter lesions on cranial computed tomography (cCT) are associated with increased prevalence and incidence of stroke, dementia, and mortality. METHODS: A representative sample of 239 85-year-olds living in Gothenburg, Sweden, was examined in a population-based study. Stroke was defined by information from patient reports, key informants, and an inpatient register system. Dementia was diagnosed according to DSM-III-R. White matter lesions (WML) and infarcts were determined by cCT. Follow-up examinations were performed 3 years later. RESULTS: White matter lesions doubled the odds of previous stroke (OR 1.8, 95% CI 1.03-3.3). Individuals with WML and stroke showed higher prevalence of dementia (OR 16.5, 95% CI 6.5-41.8) and mortality (OR 12.4, 95% CI 5.1-30.0) than those without WML and stroke. CONCLUSION: White matter lesions are common in the elderly, and these changes have clinical consequences increasing the risk of stroke. Whether preventive mechanisms could lead to risk reduction should be clarified in further studies.

[Congenital fistulas of the coronary arteries. A review with case presentations]. / Kongenitale Fisteln der Koronararterien. Eine Ubersicht mit Falldemonstrationen.

Coronary artery fistulas are rare atypical communications between a coronary artery and a cardiac chamber or other great vascular structure and usually congenital in origin. Many are detected accidentally by the use of coronary angiography. These fistulas often have minor hemodynamical significance and the course is primarily from the proximal left coronary artery to the pulmonary artery. Though symptoms are rare they should be observed carefully in aspect of possible complications. In contrast sometimes coronary artery fistulas are found when searching for the cause of cardiac murmurs or clinical symptoms. Great amounts of shunted blood can result in cardiac volume overload and myocardial ischemia may occur by coronary steal. Surgical closure of these fistulas is the treatment of choice. In our laboratory we found in a series of 3,000 coronary angiographies a 53 year old man with an abnormal communication from the right coronary artery to the right atrium and a 68 year old woman with a fistula from the proximal left anterior descending artery to the pulmonary artery.

[Reproducible ventricular flutter during programming of a DDD pacemaker]. / Reproduzierbares Kammerflattern bei Programmierung eines DDD-Schrittmachers.

A bipolar DDD pacemaker system was implanted in a 51-year-old woman with a 2 degrees (Mobitz type) atrioventricular block. The first postimplantation control was unremarkable, but she collapsed 9 weeks later with dyspnoea, tachycardia and profound perspiration. Ventricular flutter occurred twice during routine ambulatory pacemaker function tests one week later. The first episode was terminated by a precordial blow with a fist, but the second required electrical defibrillation. During the subsequent hospitalization abnormal electrolyte balance and digitalis intoxication were excluded. Left-heart catheterization with coronary angiography showed normal left-ventricular function at rest and normal coronary arteries. There was no evidence for an arrhythmogenic right ventricle. Electrophysiological testing with programmed ventricular stimulation provoked ventricular tachycardia with torsade de pointes and transition to ventricular fibrillation. Antiarrhythmic treatment with sotalol, 160 mg twice daily by mouth, failed to suppress the episodes of torsade de pointes. But further programmed ventricular stimulation was uneventful after the sotalol dosage had been increased to 160 mg three times daily.

Novel path to apoptosis: small transmembrane pores created by staphylococcal alpha-toxin in T lymphocytes evoke internucleosomal DNA degradation.

Peripheral-blood human T lymphocytes were treated with Staphylococcus aureus alpha-toxin. Membrane permeabilization was assessed by measuring efflux of K+ and Rb+ and influx of Na+, Ca2+, and propidium iodide. Cellular ATP and [3H]thymidine incorporation following lectin stimulation were measured as parameters for cell viability. Internucleosomal cleavage characteristic of programmed cell death was assessed by agarose gel electrophoresis and by quantifying low-molecular-weight, [3H]thymidine-labeled DNA fragments. Nanomolar concentrations of alpha-toxin evoked protracted, irreversible ATP depletion in both activated and resting T lymphocytes. Toxin-damaged cells also lost their ability to incorporate [3H]thymidine upon subsequent stimulation with phytohemagglutinin. These cells carried toxin hexamers, and their plasma membranes became permeable for monovalent ions but not for Ca2+ and propidium iodide. The permeabilization event was followed by internucleosomal DNA degradation characteristic of programmed cell death. Membranes of cells treated with high toxin doses (> 300 nM) became permeable to both Ca2+ and propidium iodide. In this case, ATP depletion occurred within minutes and no DNA degradation was observed. When cells were suspended in Na(+)-free buffer, alpha-toxin applied at low doses still bound and formed hexamers. However, these cells displayed neither DNA degradation nor loss of viability. The data indicate that formation of very small but not of large alpha-toxin pores may trigger programmed cell death in lymphocytes and that uncontrolled flux of Na+ ions may be an important event precipitating the suicide cascade.

[Nocturnal gastroesophageal reflux as a cause of refractory chronic laryngitis--pathophysiology and management]. / Nächtlicher gastroösophagealer Reflux als Ursache der therapierefraktären chronischen Laryngitis--Mechanismen und Management.

Chronic laryngitis is a common disease with a multifactoral genesis. One of the known causal factors is gastrolaryngeal acid reflux as a consequence of gastroesophageal reflux disease (GERD). 10 to 30% of the patients do not show an adequate response to the standard treatment with proton pump inhibitors, which could not be well explained in the past. Our own observations indicate, that sleep related gastroesophageal reflux may play an important role. The special physiological conditions in sleep can impair the reflux, and an increased nocturnal breathing effort in snoring or sleep apnea induces an intensive gastrolaryngeal reflux. This paper explains the pathophysiological background and the diagnostics and differential treatment.

Combined cerebellar and bilateral cervical posterior spinal artery stroke demonstrated on MRI.

Combined cerebellar and spinal ischemic stroke is a rare, critical condition. We report a patient with combined cerebellar and bilateral posterolateral cervical spinal cord infarction due to bilateral stenosis of the vertebral arteries. MRI is the method of choice for imaging this condition; diffusion-weighted imaging of the spinal cord gives reliable results.

[Gliomatosis cerebri: two case reports with atypical clinical and neuroradiologic findings]. / Gliomatosis cerebri. Zwei Fallberichte mit atypischer klinischer und neuroradiologischer Befundkonstellation.

The diagnosis of the rare disease Gliomatosis cerebri requires the correlation of clinical, radiological, and pathological findings. We report on two patients with intravitally diagnosed gliomatosis cerebri. Due to the unusually high malignancy of the tumor cells, diagnosis was complicated by atypical findings such as gadolinium enhancement in MRI and raised intracranial pressure. The clinical course, differential diagnosis, and literature are summarized briefly.