Who Is at Risk for Diagnostic Discrepancies? Comparison of Pre- and Postmortal Diagnoses in 1800 Patients of 3 Medical Decades in East and West Berlin

<div><h3>Background</h3><p>Autopsy rates in Western countries consistently decline to an average of <5%, although clinical autopsies represent a reasonable tool for quality control in hospitals, medically and economically. Comparing pre- and postmortal diagnoses, diagnostic discrepancies as uncovered by clinical autopsies supply crucial information on how to improve clinical treatment. The study aimed at analyzing current diagnostic discrepancy rates, investigating their influencing factors and identifying risk profiles of patients that could be affected by a diagnostic discrepancy.</p> <h3>Methods and Findings</h3><p>Of all adult autopsy cases of the Charité Institute of Pathology from the years 1988, 1993, 1998, 2003 and 2008, the pre- and postmortal diagnoses and all demographic data were analyzed retrospectively. Based on power analysis, 1,800 cases were randomly selected to perform discrepancy classification (class I-VI) according to modified Goldman criteria. The rate of discrepancies in major diagnoses (class I) was 10.7% (95% CI: 7.7%–14.7%) in 2008 representing a reduction by 15.1%. Subgroup analysis revealed several influencing factors to significantly correlate with the discrepancy rate. Cardiovascular diseases had the highest frequency among class-I-discrepancies. Comparing the 1988-data of East- and West-Berlin, no significant differences were found in diagnostic discrepancies despite an autopsy rate differing by nearly 50%. A risk profile analysis visualized by intuitive heatmaps revealed a significantly high discrepancy rate in patients treated in low or intermediate care units at community hospitals. In this collective, patients with genitourinary/renal or infectious diseases were at particularly high risk.</p> <h3>Conclusions</h3><p>This is the current largest and most comprehensive study on diagnostic discrepancies worldwide. Our well-powered analysis revealed a significant rate of class-I-discrepancies indicating that autopsies are still of value. The identified risk profiles may aid both pathologists and clinicians to identify patients at increased risk for a discrepant diagnosis and possibly suboptimal treatment intra vitam.</p> </div

Histopathologischer Osteomyelitis-Evaluationsscore (HOES) - ein innovativer Ansatz zur histopathologischen Diagnostik und Kartierung der Osteomyelitis

Background: Treatment and diagnosis of osteomyelitis are still a challenging problem for surgeons, microbiologists and histopathologists. A direct microbiological detection of bacteria in tissues is still gold standard, but it is not always successful for example in chronic osteomyelitis and/or when an antibiotic treatment has already been started or in cases of low virulent bacteria. The goal of this study was to define diagnostic criteria of osteomyelitis, the inflammatory regression of osteomyelitis ("osteomyelitis score") under specific therapy by the correlation of histopathological and microbiological and clinical standard tests. Methods: In this retrospective analysis patients with medical history and clinically clear signs of bacterial infection and osteomyelitis underwent surgery between 01.01.2013 and 31.12.2012. Their formal consent was given. Tissue samples were taken during surgery according to defined criteria including surgical interventions. Histopathological diagnosis was carried out by conventional techniques based on defined criteria of bacterial infection in connective tissue, peri-implant membrane and bone. These results were carried out in tables by numbers representing the histopathological criteria of acute osteomyelitis (A1 to A3) as well as the chronic criteria (C1 and C2) in a semiquantitative way (scale 0 to 3). On the other hand a notational, graduated histopathological report was performed.Preoperative clinical diagnosis, perioperative macroscopic diagnosis, histopathological and microbiological findings were correlated.Results: Histopathological samples of 52 surgical interventions based on the preoperative diagnosis "osteomyelitis" (AOM, ECOM or COM) were included. 37 times preoperatively signs of a chronic osteomyelitis (COM), 10 times preoperatively acute osteomyelitis (AOM) was diagnosed. Another 5 patients were preoperatively diagnosed as acute exacerbated osteomyelitis (ECOM). The correlation of the histopathological infection including the inflammatory activity and microbiological detection of bacteria was 57%. The correlation between preoperative diagnosis and histopathological findings was 68%.Conclusion: The relatively small 68% correlation between clinical preoperative and histopathological diagnosis and 57% correlation between preoperative clinical diagnosis and microbiological findings indicates: Clinical findings are not sufficient for the diagnosis "osteomyelitis". Clinical findings are not sufficient for the differentiation between AOM, ECOM and COM. Histopathological analysis is the critical factor for the diagnosis ("osteomyelitis") and differential diagnosis (AOM vs. COM). Histopathological analysis represents the basis for further treatment. HOES facilitates the classification of the histopathological findings. HOES is a sufficient tool for the treating physician in order to define the further treatment.Grundlegende Überlegung: Diagnose und Therapie der Osteomyelitis fordern auch heute Chirurgen, Mikrobiologen und Pathologen gleichermaßen. Der direkte mikrobiologische Nachweis des krankheitsverursachenden Erregers stellt einen "Gold Standard" in der Diagnostik der Knocheninfektion dar. Leider gelingt der Keimnachweis nicht in allen Fällen, speziell bei chronischen Krankheitsverläufen, laufender Antibiotikatherapie oder im Falle der "low grade Infektion". Die histopathologische Analyse ist insofern eine Condotio sine qua non. Nur anhand dieser Ergebnisse lässt sich zweifelsfrei das Vorliegen einer Osteomyelitis detektieren und eine Aussage zu ihrer Akuität machen. Ziel dieser Studie ist die Vorstellung eines standardisierten histopathologischen Scores, anhand dessen analog zum TMN-System bei Tumorerkrankungen eine valide Kartierung einer Osteomyelitis möglich ist. Weiterhin wurde die Korrelation zwischen histopathologischen Ergebnissen und der klinischen Diagnose ebenso wie dem positiven Keimnachweis überprüft.Methode: In einer retrospektiven Analyse wurden die histopathologischen und mikrobiologischen Befunde von Patienten mit den eindeutigen klinischen Symptomen einer Osteomyelitis untersucht. Alle in die Studie eingeschlossenen Patienten wurden zwischen dem 01.01.2013 und dem 31.12.2013 operiert. Sämtliche Gewebsproben wurden während der operativen Eingriffe gewonnen. Die histologischen Untersuchungen basierten auf den Standardtechniken für bakterielle Infektionen im Bindegewebe, periimplantär und im Knochen. Die Ergebnisse wurden erfasst: in einer tabellarischen Form durch Zahlen, welche die Ausprägung von akuten (A1 bis A3) und chronischen (C1 und C2) Osteomyelitis-Kriterien semiquantitativ (Scala 0-3) in einer getrennten Form für akute und chronische Veränderungen darstellt (Histopathologischer Osteomyelitis-Evaluationsscore), in einer schriftlichen, abgestuften Form, welche sich durch die Summation der tabellarischen Werte ergibt. Die präoperative und die perioperative Diagnose, das histologische Ergebnis und die Mikrobiologie wurden hinsichtlich ihrer Übereinstimmung korreliert (dabei war nicht die Keimtypisierung, sondern der Keimnachweis an sich relevant). Ergebnisse: 52 chirurgische Proben wurden ausgewertet. Sie alle stammten von Patienten mit der präoperativen Diagnose "Osteomyelitis" (akute Osteomyelitis = AOM; akute Exazerbation einer chronischen Osteomyelitis = ECOM; chronische Osteomyelitis = COM). Es fanden sich: COM n=37, AOM n=10, ECOM n=5. Die Korrelation zwischen dem histopathologischen Bild inklusive der inflammatorischen Reaktion und einem positiven Erregernachweis betrug 57%. Die Korrelation zwischen der präoperativen Diagnose und der histologischen Analyse betrug 68%.Schlussfolgerung: Die relative geringe Übereinstimmung von präoperativer Diagnose, histopathologischem Ergebnis und der Mikrobiologie legt Folgendes nahe: Die klinische Vermutung allein ist nicht ausreichend für die Diagnose "Osteomyelitis". Die klinische Vermutung allein ist nicht ausreichend zur Differenzierung zwischen AOM, ECOM und COM. Die histopathologische Analyse ist das entscheidende Kriterium. Einerseits für die Diagnose "Osteomyelitis" an sich und andererseits für deren Akuität. Die histopathologische Analyse ist die Basis für die Therapie. HOES ist ein brauchbares Instrument zur standardisierten Kartierung der histopathologischen Ergebnisse

Inhibition of human vascular smooth muscle cell proliferation by lovastatin: the role of isoprenoid intermediates of cholesterol synthesis

Restenosis remains the largest single obstacle to the long‐term success of invasive vascular interventions. Lovastatin, an HMG‐CoA reductase inhibitor, has been shown to reduce myointimal hyperplasia in animal models of restenosis and in one clinical coronary restenosis trial. We have assessed the effect of lovastatin on the growth of cultured human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses. Lovastatin (2 μM) inhibited proliferation over 14 days in saphenous vein (and graft stenoses) derived vascular smooth muscle cells by 42% and 32%, respectively: this was not significantly different. Lovastatin (10 μM) reduced [methyl 3H]‐thymidine uptake by 51% in saphenous vein‐derived cells. These concentrations were significantly higher than those achieved in plasma during therapeutic dosage. Lovastatin‐induced inhibition of vascular smooth muscle cell proliferation and [methyl 3H]‐thymidine uptake was completely reversed by adding mevalonate (100 μM) but cholesterol (10–40 μl‐1) had no effect. Isopentenyl adenine (25–50 μM) did not affect the inhibition of [methyl 3H]‐thymidine uptake by lovastatin (10 μM), but farnesol (20 μM), another isoprenoid precursor of cholesterol synthesis, reversed the antiproliferative effect