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Resume Introduction L’expression clinique initiale de la maladie de Whipple (MW) peut mimer un rhumatisme inflammatoire chronique (RIC) et son diagnostic au cours d’un traitement par anti-TNF a ete rapporte dans la litterature depuis plusieurs annees, incluant des formes severes. L’impact de ce type de traitement sur le rapport hote-pathogene est fortement suspecte. La frequence du portage asymptomatique de Tropheryma whipplei dans la population generale complique le diagnostic positif d’une MW devant un RIC non classe. Observations Nous rapportons ici trois observations illustrant des situations redevables d’une recherche de T. whipplei au titre du diagnostic differentiel au cours de la prise en charge d’un rhumatisme inflammatoire. Conclusion L’evaluation clinique individuelle doit guider non seulement l’indication de la recherche de T. whipplei au cours d’un RIC, notamment en cas d’aggravation paradoxale sous traitement, de presentation ou d’evolution atypique, mais egalement l’interpretation des resultats de la biologie moleculaire et de l’anatomopathologie dont la rentabilite peut etre modifiee par les traitements immunomodulateurs. Une strategie de depistage systematique de T. whipplei avant traitement par anti-TNF parait deraisonnable.

Tiermodelle haben unser Verstandnis um die Mechanismen der Atherosklerosebildung und der Bewertung von Therapiemoglichkeiten deutlich verbessert. Der aktuelle Forschungsschwerpunkt liegt auf praventiven Strategien und umfasst pharmakologische und biologische Interventionen, die sich primar gegen die Proliferation von glatten Muskelzellen richten. Zudem werden endovaskulare Techniken zur Rekanalisation und/oder Wirkstoffabgabe sowie integrierte Ansatze mit Geraten und pharmakobiologischen Wirkstoffen intensiv erforscht. Die jahrzehntelange Erfahrung mit Tiermodellen in der Gefasforschung hat gezeigt, dass es kein einzelnes, fur alle Zwecke einsetzbares Modell der Atheroskleroseforschung gibt. Die Spannweite reicht dabei von Grostieren wie dem Schwein bis hin zu Kleintierversuchen mit genetisch veranderten Nagern wie z. B. der ApoE−/−-Maus (Apolipoprotein-E-defiziente Maus) mit entsprechend unterschiedlich stark ausgepragten Veranderungen in ihren Lipid- und Lipoproteinspiegeln. Die Entwicklung transgener Varianten von derzeit verfugbaren Modellen hat unsere Moglichkeiten bereits in der Vergangenheit und auch fur die Zukunft erweitert. Dennoch ist ein Verstandnis der individuellen Merkmale einer Erkrankung bei jeder Tierspezies von Bedeutung, um das Versuchsdesign valide planen und durchfuhren zu konnen.

Die chronische lymphatische Leukamie (CLL) ist die haufigste Leukamie in der westlichen Welt. Das mediane Erkrankungsalter betragt 72 Jahre, und Manner sind mit einem Verhaltnis von 1,7:1 beinahe doppelt so haufig betroffen wie Frauen. Zur Diagnose sind Differentialblutbild, Blutausstrich und eine Durchflusszytometrie zum Nachweis monoklonaler, typischerweise CD5/CD23-positiver B‑Lymphozyten erforderlich. Neben der klinischen Stadieneinteilung nach Binet oder Rai ist insbesondere die genetische Risikoeinteilung von hoher prognostischer Aussagekraft und entscheidend fur die Wahl der geeigneten Therapie. Vor Therapieeinleitung muss daher die Bestimmung des TP53-Mutationsstatus bzw. einer del17p sowie des IGHV-Mutationsstatus („immunoglobulin heavy-chain variable“) erfolgen. Asymptomatische Patienten im fruhen Stadium benotigen keine Therapie. Eine Therapieindikation ergibt sich erst in fortgeschrittenen Stadien, z. B. im Rahmen einer zunehmenden Knochenmarkinsuffizienz oder relevanter B‑Symptomatik. Zielgerichtete Substanzen wie Ibrutinib oder Venetoclax + Obinutuzumab erhalten zunehmend Einzug in die Erstlinienbehandlung, insbesondere bei Patienten mit rascher proliferierender CLL und unmutiertem IgHV-Status. Bei „fitten“ Patienten mit mutiertem IGHV-Status und ohne TP53-Veranderung kann zudem eine Chemoimmuntherapie mit Fludarabin, Cyclophosphamid + Rituximab aufgrund exzellenter Langzeitergebnisse erwogen werden. Bei „unfitten“ Patienten konnen weniger intensive Chemoimmuntherapien eingesetzt werden. Bei Rezidiven >3 Jahre nach der initialen Therapie kann eine Chemoimmuntherapie erneut eingesetzt werden. Im Fall eines Fruhrezidivs sollte ein Wechsel auf eine andere zielgerichtete Substanz angestrebt werden.

Objectives To report an unusual complication of pediatric acute maxillary sinusitis: premaxillary abscess. To describe clinical, radiological and biological presentation, treatment strategy and progression. Material and methods A retrospective study included all pediatric patients treated for premaxillary abscess complicating acute maxillary sinusitis in two ENT reference centers between 1999 and 2017. Disease history, clinical presentation, biological and radiological findings, treatment modalities and progression were studied. Results Ten patients were included, with a mean age of 10 ± 4.2 years. All presented with fever, rhinorrhea and premaxillary edema. Contrast-enhanced CT scan systematically found complete opacity of the maxillary sinus, without bone lysis, and extensive effusion along the intersinonasal wall up to the premaxillary region, extending in 3 cases back toward the parapharyngeal space. Bacteriology isolated Streptococcus anginosus most frequently (n = 4; 40%). Treatment comprised intravenous wide-spectrum antibiotics, with surgical drainage of the abscess if > 10 mm (n = 9; 90%). Seven of these 9 patients (78%) had recurrent abscess requiring surgical revision and 3 (33%) required a third drainage. All patients were cured without sequelae at 1 month. Conclusion In case of acute maxillary sinusitis with premaxillary edema, premaxillary abscess should be suspected. The high recurrence rate argues for maximalist surgery associated to close clinical monitoring with radiological examination.

Die Therapieoptionen der peripheren arteriellen Verschlusskrankheit (pAVK) bestehen, abhangig vom Fontaine-Stadium, aus konservativen und revaskularisierenden Verfahren. Ziele der konservativen Therapie sind stadienabhangig die Verhinderung des Krankheitsprogresses, die Steigerung der Gehleistung, die Schmerzreduktion, die Ulkusabheilung und der Beinerhalt. Eine ausreichende Evidenz und Leitlinienempfehlungen existieren in allen Stadien fur den Nikotinverzicht, die medikamentose Einstellung von Blutdruck und -zucker, die Statintherapie sowie fur die Thrombozytenaggregationshemmung, das strukturierte Gehtraining und die Cilostazol- oder Naftidrofurylmedikation ab Stadium IIa. Alternative Verfahren wie die Alprostadilinfusion, die computertomographiegesteuerte lumbale Sympathikolyse, die epidurale Ruckenmarkstimulation, die intermittierende pneumatische Kompression oder die hyperbare Sauerstofftherapie besitzen keine ausreichende Evidenz und sollten nur nach Ausschopfen der Standardtherapie eingesetzt werden.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition.METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed.RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; PCONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.

Das abdominale Aortenaneurysma (AAA) ist eine tagliche klinische Herausforderung fur den Gefaschirurgen. In den letzten Jahren sind viele pathologische Veranderungen der Aneurysmawand im Vergleich zur nativen Aorta gut untersucht und deren Bedeutung in ein Modell zur Aneurysmaprogression eingeordnet worden. Diese modellhafte Theorie wird anhand einer Ubersichtsarbeit vorgestellt. Charakteristische Veranderungen im AAA umfassen eine verbreiterte Tunica media und veranderte Extrazellularmatrix, veranderte Hamodynamik und Krafte auf die Aortenwand, luminale Thrombusbildung, Phanotypwechsel glattmuskularer Zellen, Angiogenese sowie akute und chronische Entzundungsherde. Diese bedingen Veranderungen der Gleichgewichte von Krafteverteilung und Matrixsynthese in der Aortenwand, sodass Areale mit hoher biologischer Aktivitat und reduzierter mechanischer Belastbarkeit entstehen. Die klinisch bekannten Risikofaktoren Nikotinabusus, Dyslipidamie, mannliches Geschlecht, Alter und genetische Pradisposition haben definierte biologische Effekte, die die Gefaswand zusatzlich schwachen. Zum Unterschied zwischen rupturierten und intakten Aneurysmen ist keine klare Aussage moglich. Ebenso ist die initiale Ursache der Aneurysmaentstehung weiterhin unklar. Ein besseres Verstandnis der multifaktoriellen Pathogenese des AAA ist erforderlich um translationale Ansatze zur nichtchirurgischen Therapie und eine patientenindividuelle Risikostratifizierung zu ermoglichen. Die Forschung an humanen Aneurysmaproben ist auch in der endovaskularen Ara notig und erlaubt die Identifikation spezifischer beteiligter Pathomechanismen.

Die chronisch arterielle Ischamie der unteren Extremitaten stellt ein alltagliches Problem in gefaschirurgischen Kliniken dar. In Deutschland sind etwa 3 % aller Hospitalisierungen auf eine periphere arterielle Verschlusskrankheit (PAVK) zuruckzufuhren, wobei vor allem die kritischen Ischamien stark zunehmen. Die Folgen der chronischen Ischamie reichen von eingeschrankter Gehstrecke bis hin zum Verlust der Extremitat. Am Anfang stehen Stressfaktoren wie Hyperlipidamie (LDL), freie Radikale, arterielle Hypertonie, Infektionen oder subklinische Entzundungen, die die Endothelhomoostase storen. Es kommt zu einer Dysfunktion des Endothels mit erhohter Durchlassigkeit. Zellen des Immunsystems werden angelockt und wandern in die Gefaswand ein, wo sie zum Abbau von Matrixkomponenten und zur Destabilisierung des Plaques fuhren. Durch Anderung des Phanotyps von glatten Muskelzellen und Makrophagen entstehen osteoklastenahnliche Zellen, die zu Verhartungen in der Gefaswand fuhren. Ab einer Gefaswandstarke von etwa 100 μm wird durch den Sauerstoffmangel Hypoxie induzierter Faktor (HIF-1α) verstarkt exprimiert, was zu einem Anstieg an Wachstumsfaktoren wie VEGF („vascular endothelial growth factor“) fuhrt. Dadurch wird die Angiogenese als Kapillarenbildner gefordert, reicht aber nicht aus, um eine stenosierte Arterie zu kompensieren. Arteriogenese bezeichnet das Wachstum von bereits vorhandenen Kollateralgefasen. Die treibenden Krafte sind der Druckgradient vor und hinter der Stenose sowie die Scherkrafte, die auf die Gefaswande einwirken. Bei voranschreitender Stenosierung konnen die Kompensationsfahigkeiten uberfordert werden und es kommt zu einer manifesten Hypoxie im Gewebe mit Ruckbildung der gewonnenen Gefasstrukturen/Kollateralkreislaufen und Gewebsatrophie.

Strukturiertes Gehtraining (SGT) zur Verbesserung arterieller Kollateralkreislaufe ist ein wichtiger Baustein in der Therapie und Sekundarprophylaxe der peripheren arteriellen Verschlusskrankheit (PAVK). Trainingsangebote sind deutschlandweit nicht ausreichend. Wir prasentieren die Organisation und Ergebnisse unseres SGT. Die Klinik fur Gefas- und Endovaskularchirurgie des Universitatsklinikums Dusseldorf bietet seit 2014 Patienten mit einer PAVK im Fontaine-Stadium II, einem ankulobrachialen Index (ABI) von ≤0,9 in Ruhe und/oder einem ABI-Abfall von ≥15 % nach Belastung ein SGT an. In Einstiegs‑/Folgeuntersuchungen (0/3/6/12 Monate) werden schmerzfreie/maximale Gehstrecken sowie der ABI vor/nach Belastung erhoben. Verlaufsergebnisse existieren von 37 Patienten (weiblich = 12, Durchschnittsalter = 66 ± 10 Jahre) im Stadium IIa/b (n = 4/33) bzw. 57 Beinen. Nach acht Monaten stieg die schmerzfreie/maximale Gehstrecke, als Zeichen der Bildung von Kollateralkreislaufen, um 63 ± 88 m (75 ± 106 %)/113 ± 212 m (44 ± 78 %) mit uneingeschrankter Gehstrecke bei funf Patienten an. Der ABI hingegen korreliert als Charakteristikum fur Leitungsgefase physiologischerweise nur schwach mit dem Kollateralisierungsgrad und stieg in Ruhe um 0,04 ± 0,13 (11 ± 27 %) und bei zwei Beinen auf >0,9 an. Der Abfall des Belastungs-ABI ging um 2 % zuruck. Drei Beine zeigten keinen pathologischen Belastungs-ABI. 14 Patienten beendeten das Training fruhzeitig. 75 % der Patienten fuhrten das SGT nach der 12-Monats-Kontrolle fort. Unser SGT erzeugt hinsichtlich der schmerzfreien/maximalen Gehstrecken gute Ergebnisse. Der Angebotsmangel erfordert einen bundesweiten Aufbau ahnlicher Trainingsprogramme.

Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective trials for conventional drugs. Opinions of key stakeholders were carefully considered, including those of the biopharmaceutical industry representatives, academic researchers, clinicians, regulatory agency representatives, and—most critically—patients with Alport syndrome. Recommendations were established for preclinical researchers, the use and selection of biomarkers, standards of care, clinical trial designs, trial eligibility criteria and outcomes, pediatric trial considerations, and considerations for patient engagement, recruitment, and treatment. This paper outlines their recommendations.

Increased performance demands have interacted with suboptimal use of technology and contributed to burnout among radiologists. Although the problem of radiologist burnout has been well documented, there is a gap in the literature in terms of how technology can be better utilized to lessen the problem. Informatics-based modifications to existing technology hold the potential to reduce the amount of time radiologists spend on noninterpretive tasks, decrease interruptions, facilitate connections with colleagues, and improve patient care. Examples of successful modifications to technology are presented and discussed in relation to how they contribute to improving workplace engagement among radiologists.

BACKGROUND: Effective co-management of patients with chronic kidney disease (CKD) between primary care physicians (PCPs) and nephrologists is increasingly recognized as a key strategy to ensure the delivery of efficient and high-quality CKD care. However, the co-management of patients with CKD remains suboptimal. OBJECTIVE: We aimed to identify PCPs’ perceptions of key barriers and facilitators to effective co-management of patients with CKD at the PCP-nephrology interface. STUDY DESIGN: Qualitative study SETTING AND PARTICIPANTS: Community-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC; and San Francisco, CA APPROACH: We conducted four focus groups of PCPs. Two members of the research team coded transcribed audio-recorded interviews and identified major themes. KEY RESULTS: Most of the 32 PCPs (59% internists and 41% family physicians) had been in practice for > 10 years (97%), spent ≥ 80% of their time in clinical care (94%), and practiced in private (69%) or multispecialty group practice (16%) settings. PCPs most commonly identified barriers to effective co-management of patients with CKD focused on difficulty developing working partnerships with nephrologists, including (1) lack of timely adequate information exchange (e.g., consult note not received or CKD care plan unclear); (2) unclear roles and responsibilities between PCPs and nephrologists; and (3) limited access to nephrologists (e.g., unable to obtain timely consultations or easily contact nephrologists with concerns). PCPs expressed a desire for “better communication tools” (e.g., shared electronic medical record) and clear CKD care plans to facilitate improved PCP-nephrology collaboration. CONCLUSIONS: Interventions facilitating timely adequate information exchange, clear delineation of roles and responsibilities between PCPs and nephrologists, and greater access to specialist advice may improve the co-management of patients with CKD.

Anemia of renal disease is common and is associated with significant morbidity and death. It is mainly caused by a decrease in erythropoietin production in the kidneys and can be partially corrected with erythropoiesis-stimulating agents (ESAs). However, randomized controlled trials have shown that using ESAs to target normal hemoglobin levels can be harmful, and have called into question any benefits of ESA treatment other than avoidance of transfusions.

Copyright ©2016 Simon F. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Volume 1 : Issue 3 Article Ref. #: 1000NPOJ1e004 Kidney Ischemia and Reperfusion Injury – Field of Glory or Warterloo for Erythropoietin?

Chronic ischemia of the lower extremities is an everyday problem in vascular surgery clinics. In Germany, approximately 3% of all hospitalizations are due to peripheral artery disease (PAD), with critical limb ischemia (CLI) in particular showing a rapid increase. The consequences of chronic undersupply range from reduced walking distance to loss of limbs. At the beginning there are stress factors, such as hyperlipidemia (LDL), free radicals, arterial hypertension, infections or subclinical inflammation that interfere with endothelial homeostasis and cause endothelial dysfunction with increased permeability. Cells of the immune system are attracted and migrate into the vascular wall, where they lead to the degradation of matrix components and destabilization of the plaque. By changing the phenotype of smooth muscle cells and macrophages towards osteoclast-like cells, bone-like hardening of the vessel wall takes place. Above a vessel wall thickness of approximately 100 µm, hypoxia-induced factor (HIF-1α) is intensified by the lack of oxygen, which leads to an increase in growth factors, such as vascular endothelial growth factor (VEGF). This promotes angiogenesis, but it is not sufficient to compensate for a stenosed artery. Arteriogenesis refers to the growth of existing collateral vessels. The driving forces are the pressure gradient before and after the stenosis and the shear forces acting on the vessel walls. In the case of progressive stenosis, the compensatory capacities can be overtaxed and a manifest hypoxia in the tissue with regression of the obtained vascular structures and tissue atrophy occurs.Die chronisch arterielle Ischämie der unteren Extremitäten stellt ein alltägliches Problem in gefäßchirurgischen Kliniken dar. In Deutschland sind etwa 3 % aller Hospitalisierungen auf eine periphere arterielle Verschlusskrankheit (PAVK) zurückzuführen, wobei vor allem die kritischen Ischämien stark zunehmen. Die Folgen der chronischen Ischämie reichen von eingeschränkter Gehstrecke bis hin zum Verlust der Extremität. Am Anfang stehen Stressfaktoren wie Hyperlipidämie (LDL), freie Radikale, arterielle Hypertonie, Infektionen oder subklinische Entzündungen, die die Endothelhomöostase stören. Es kommt zu einer Dysfunktion des Endothels mit erhöhter Durchlässigkeit. Zellen des Immunsystems werden angelockt und wandern in die Gefäßwand ein, wo sie zum Abbau von Matrixkomponenten und zur Destabilisierung des Plaques führen. Durch Änderung des Phänotyps von glatten Muskelzellen und Makrophagen entstehen osteoklastenähnliche Zellen, die zu Verhärtungen in der Gefäßwand führen. Ab einer Gefäßwandstärke von etwa 100 μm wird durch den Sauerstoffmangel Hypoxie induzierter Faktor (HIF-1α) verstärkt exprimiert, was zu einem Anstieg an Wachstumsfaktoren wie VEGF („vascular endothelial growth factor“) führt. Dadurch wird die Angiogenese als Kapillarenbildner gefördert, reicht aber nicht aus, um eine stenosierte Arterie zu kompensieren. Arteriogenese bezeichnet das Wachstum von bereits vorhandenen Kollateralgefäßen. Die treibenden Kräfte sind der Druckgradient vor und hinter der Stenose sowie die Scherkräfte, die auf die Gefäßwände einwirken. Bei voranschreitender Stenosierung können die Kompensationsfähigkeiten überfordert werden und es kommt zu einer manifesten Hypoxie im Gewebe mit Rückbildung der gewonnenen Gefäßstrukturen/Kollateralkreisläufen und Gewebsatrophie.

Author(s): Sperati, C John; Soman, Sandeep; Agrawal, Varun; Liu, Yang; Abdel-Kader, Khaled; Diamantidis, Clarissa J; Estrella, Michelle M; Cavanaugh, Kerri; Plantinga, Laura; Schell, Jane; Simon, James; Vassalotti, Joseph A; Choi, Michael J; Jaar, Bernard G; Greer, Raquel C; National Kidney Foundation Education Committee | Abstract: BackgroundGiven the high prevalence of chronic kidney disease (CKD), primary care physicians (PCPs) frequently manage early stage CKD. Nonetheless, there are challenges in providing optimal CKD care in the primary care setting. This study sought to understand PCPs' perceptions of barriers and facilitators to the optimal management of CKD.Study designMixed methods study.Settings and participantsCommunity-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC and San Francisco, CA.MethodologyWe used a self-administered questionnaire and conducted 4 focus groups of PCPs (n = 8 PCPs/focus group) in each city to identify key barriers and facilitators to management of patients with CKD in primary care.Analytic approachWe conducted descriptive analyses of the survey data. Major themes were identified from audio-recorded interviews that were transcribed and coded by the research team.ResultsOf 32 participating PCPs, 31 (97%) had been in practice for g10 years, and 29 (91%) practiced in a non-academic setting. PCPs identified multiple barriers to managing CKD in primary care including at the level of the patient (e.g., low awareness of CKD, poor adherence to treatment recommendations), the provider (e.g., staying current with CKD guidelines), and the health care system (e.g., inflexible electronic medical record, limited time and resources). PCPs desired electronic prompts and lab decision support, concise guidelines, and healthcare financing reform to improve CKD care.ConclusionsPCPs face substantial but modifiable barriers in providing care to patients with CKD. Interventions that address these barriers and promote facilitative tools may improve PCPs' effectiveness and capacity to care for patients with CKD.

Die akute Extremitatenischamie (AEI) gefahrdet sowohl die betroffene Gliedmase als auch das Leben des Patienten und stellt eine haufige Ursache fur eine Extremitatenamputation dar. Deshalb ist die AEI ein vaskularer Notfall, der einer raschen Revaskularisation bedarf. Die Ursachen sind kardiale Embolien, lokale Thrombosen, postrekonstruktive thrombotische Gefasverschlusse, embolisierende Aneurysmen, Aortendissektionen und Gefasverletzungen. Das 30-Tage-Major-Amputationsrisiko betragt 10–30 % und die 30-Tage-Mortalitat 15–30 %. Die Auspragung des Krankheitsbilds ist abhangig von der peripheren Restperfusion. Die Einteilung nach Rutherford und die 6 Ps nach Pratt beschreiben die Klinik. Man unterscheidet eine komplette Ischamie mit voller Auspragung der Symptomatik und eine inkomplette Form mit Erhalt der Sensibilitat und Motorik. Als Folgeereignis kann es zu einem Reperfusions- oder einem Kompartmentsyndrom kommen. Bei komplexer Vorgeschichte ist eine CTA fur die Therapieplanung hilfreich. Mittel der Wahl zur Diagnostik ist die Duplexsonographie und Angiographie. Als Therapieoptionen stehen die offen chirurgische Therapie, die endovaskulare Therapie oder eine Kombination aus beidem (Hybridverfahren) zur Verfugung. Mittlerweile haben die endovaskulare und die offenchirurgische Methode einen vergleichbaren Stellenwert bei der Behandlung einer AEI.

Die akute Ischamie einer Extremitat stellt einen Notfall dar. Um rationale Schritte bei der Behandlung einzuleiten, sind Kenntnisse der zugrundeliegenden Pathophysiologie hilfreich. Wahrend einer Ischamie kommt es zu einem Abfall des Blutsauerstoffs, der benotigt wird, um die physiologische Energiegewinnung zu ermoglichen. Durch die Hemmung der mitochondrialen oxidativen Phosphorylierung kommt es zu einem Verlust zellularer Energietrager und einer Funktionsbeeintrachtigung mikrosomaler Membranpumpen. Dies fuhrt zu veranderten intrazellularen Elektrolytspiegeln. Es entsteht eine Azidose sowie ein Zellodem. Durch die Beeintrachtigung des endoplasmatischen Retikulums kommt es zu einer anhaltenden Fehlproduktion von Proteinen, was die Zellfunktion nachhaltig stort. Der wahrend der Reperfusion frisch einstromende Sauerstoff bringt durch die Bildung freier Radikale Schaden mit sich. Zudem werden Leukozyten eingeschwemmt, die eine Entzundungsreaktion vorantreiben und zusatzlich reaktive Sauerstoffradikale bilden. Stickstoffmonoxid (NO) fungiert als physiologischer Radikalfanger und reguliert den Gefastonus. In den ischamisch geschadigten Gefasen spricht die endothelvermittelte Relaxation auf NO aber nicht mehr an. Zudem zeigt sich eine gesteigerte Filtration von Flussigkeit ins Interstitium und eine Rarefizierung des perfundierten kapillaren Gefasbettes. Es kommt zu Vasospasmen und durch den erhohten Widerstand zu einer weiteren Verschlechterung der Perfusion. Wahrend der Reperfusionsphase kommt es zudem zu einer Einschwemmung von Metaboliten in den Gesamtorganismus sowie von inflammatorischen Zytokinen, was zu Entzundungen in weiteren Organen wie der Lunge fuhren kann. Die akute Extremitatenischamie ist ein multifaktorielles Geschehen, das je nach Auspragung und Dauer zu unterschiedlich stark ausgepragten Folgeschaden fuhren kann.

Dialysis care is an integral part of the practice of nephrology. Despite this, education of fellows in providing dialysis often remains rudimentary, relying on a combination of didactics and learning through experience. This runs the risk of training nephrologists who can provide dialysis care without truly being experts on the subject. In this article, a collection of novel or innovative teaching methods is presented that are meant to provide training programs with additional tools with which to improve the training of their fellows in dialysis.

The renal patient is best served when the nephrologist familiar with the case performs the urine microscopy

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART).We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059.Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause).After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients.Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

Background Median arcuate ligament syndrome is a rare condition with abdominal symptoms. Accepted treatment options are open release of median arcuate ligament, laparoscopic release of edian arcuate ligament, robot-assisted release of median arcuate ligament and open vascular treatment. Here we aimed to evaluate the central priority of open vascular therapy in the treatment of median arcuate ligament syndrome. Methods We conducted a monocentric retrospective study between January 1996 and June 2016. Thirty-one patients with median arcuate ligament syndrome underwent open vascular surgery, including division of median arcuate ligament in 17 cases, and vascular reconstruction of the celiac artery in 14 cases. Results In a 20-year period, 31 patients (n = 26 women, n = 5 men) were treated with division of median arcuate ligament (n = 17) or vascular reconstruction in combination with division of median arcuate ligament (n = 14). The mean age of patients was 44.8 ± 15.13 years. The complication rate was 16.1% (n = 5). Revisions were performed in 4 cases. The 30-day mortality rate was 0%. The mean in-hospital stay was 10.7 days. Follow-up data were obtained for 30 patients. The mean follow-up period was 52.2 months (range 2–149 months). Patients were grouped into a decompression group (n = 17) and revascularisation group (n = 13). The estimated Freedom From Symptoms rates were 93.3, 77.8, and 69.1% for the decompression group and 100, 83.3, and 83.3% for the revascularisation group after 12, 24 and 60 months respectively. We found no significant difference in the Freedom From Re-Intervention CA rates of the decompression (100% at 12, 24 and 60 months post-surgery) and revascularisation (100% at 12 months, and 91.7% at 24 and 60 months post-surgery) groups during follow-up (p = 0.26). Conclusions Open vascular treatment of median arcuate ligament syndrome is a safe, low mortality-risk procedure, with low morbidity rate. Treatment choice depends on the clinical and morphological situation of each patient.

Spinal cord ischemia (SCI) is a clinical complication following aortic repair that significantly impairs the quality and expectancy of life. Despite some strategies, like cerebrospinal fluid drainage, the occurrence of neurological symptoms, such as paraplegia and paraparesis, remains unpredictable. Beside the major blood supply through conduit arteries, a huge collateral network protects the central nervous system from ischemia—the paraspinous and the intraspinal compartment. The intraspinal arcades maintain perfusion pressure following a sudden inflow interruption, whereas the paraspinal system first needs to undergo arteriogenesis to ensure sufficient blood supply after an acute ischemic insult. The so-called steal phenomenon can even worsen the postoperative situation by causing the hypoperfusion of the spine when, shortly after thoracoabdominal aortic aneurysm (TAAA) surgery, muscles connected with the network divert blood and cause additional stress. Vessels are a conglomeration of different cell types involved in adapting to stress, like endothelial cells, smooth muscle cells, and pericytes. This adaption to stress is subdivided in three phases—initiation, growth, and the maturation phase. In fields of endovascular aortic aneurysm repair, pre-operative selective segmental artery occlusion may enable the development of a sufficient collateral network by stimulating collateral vessel growth, which, again, may prevent spinal cord ischemia. Among others, the major signaling pathways include the phosphoinositide 3 kinase (PI3K) pathway/the antiapoptotic kinase (AKT) pathway/the endothelial nitric oxide synthase (eNOS) pathway, the Erk1, the delta-like ligand (DII), the jagged (Jag)/NOTCH pathway, and the midkine regulatory cytokine signaling pathways.

L’hypereosinophilie sanguine est une anomalie biologique definie par la presence de plus de 0,5 G/L. Les causes les plus frequentes en zones tropicales en sont les helminthoses. Les effets secondaires de medicaments et les phenomenes atopiques sont plus rares que dans les pays industrialises. Parfois satellite d’une affection systemique patente, sa decouverte impose une enquete etiologique pragmatique, des actions therapeutiques d’epreuve et un suivi axe sur le depistage des hemopathies chroniques et celui des lesions viscerales graves liees a l’eosinotoxicite tissulaire chronique.

Background There are several options for treating patients suffering from chronic mesenteric ischemia (CMI). One possibility contains bypass grafting following a left renal route to avoid inter alia kinking of the bypass. This study reviews the results of 16 patients suffering from CMI treated with this bypass technique, called “French Bypass” (FB). Methods A retrospective study conducted between June 1, 2002, and December 31, 2015. Sixteen patients were included with an average age of 54.6 years (10 women) who were treated with FB. Risk factors, surgical course, and follow-up were evaluated. Results Average stay in hospital took 28.4 days, with mostly minor complications occurring. Overall, 4 cases of FB occlusion were diagnosed in between 30 days after surgery, of which 3 made interventions necessary. Primary patency rates were 75%/56%/56% after 12/24/60 months. Overall survival rate after 60 month was 78%. Conclusions The FB is a sufficient option for treatment of CMI combining advantages of anterograde and retrograde bypass grafting, with comparable outcome to established techniques in visceral vessel reconstruction.

Inflammatory abdominal aortic aneurysms (IAAAs) are rare clinical entities with an exaggerated inflammatory component. The aim of this study is to report outcomes of a single-center 10-year experience in open surgical management of IAAA and to compare the results with noninflammatory, atherosclerotic abdominal aortic aneurysms (non-IAAAs).We retrospectively reviewed the medical records of 18 patients with IAAA selected out of patients with AAA who underwent open surgery in the Department of Vascular and Endovascular Surgery at the University Hospital Dusseldorf from January 2006 to December 2015. These patients were matched with controls, selected from a prospectively retained database of patients with AAA undergoing open surgery during the study period. A 1:2 case-control match regarding age, gender, and year of treatment was performed. We analyzed both groups for preoperative parameters, intraoperative findings, and early postoperative outcomes.The 2 groups showed considerable similarities with no significant differences in the clinical features. Both groups outlined comparable aneurysm size (62 vs. 56 mm); however, the mean preoperative C-reactive protein was found to be significantly elevated in the study group (mean value: 2.6 vs. 0.9 mg/dL, P 0.05). Most patients were operated using a standard transperitoneal median laparotomy approach; only 1 patient of each group was operated using a left retroperitoneal approach. There was no significant difference in operation time (190 vs. 194 min) and 30-day mortality 0%. The in-hospital mortality was 11% in the study group and 0% in the control group. We found a significant higher complication rate in the study group 10 (56%) vs. 12 (33%). The major complications were also more frequent in the study group 4 (22%) vs. 6 (16.7%). IAAA showed a statistically significant longer length of intensive care unit and hospital stay when compared with non-IAAA (7 and 20 days vs. 2 and 14 days, P 0.05). IAAAs outlined a significantly greater transfusion requirement for erythrocytes and fresh frozen plasma than non-IAAA.Open surgical treatment of IAAA guarantees a regression of the inflammatory process in most patients, which was detected through ultrasound in follow-up examination, although the approach to the surgical site is highly demanding. IAAA exhibits clear gender predominance and is associated with significantly higher transfusion requirement, early morbidity, and length of stay.

Resume La pandemie a VIH est due aux virus de type 1 groupe M (VIH-M). A cote de ces virus majoritaires, il existe de nombreux variants divergeant genetiquement, ayant conduit a la definition des VIH-2 et des groupes N, O et P au sein du VIH-1. Ces derniers sont le resultat de passages inter-especes independants de virus presents chez les chimpanzes et les gorilles des plaines de l’Ouest de l’Afrique centrale. Ces sources simiennes et la necessaire adaptation a l’espece humaine sont a l’origine de caracteristiques genomiques, phylogenetiques, et de proprietes virales, propres a chaque groupe. L’histoire naturelle des infections associees a ces variants semble neanmoins similaire a celle des VIH-M, avec une forte replication virale in vivo associee a une immunodepression continue. Ces variants non-M ont tous ete decrits pour la premiere fois chez des patients d’origine camerounaise. L’ouest de l’Afrique centrale est ainsi l’epicentre des epidemies a variants non-M, et la circulation hors de cette region est anecdotique, en dehors de la France. Au Cameroun, berceau de tous les groupes decrits actuellement, les infections VIH-O representent 1 % des infections VIH, tandis que seuls 15 cas d’infections VIH-N et deux infections VIH-P ont ete rapportes a ce jour. Si la diversite genetique importante de ces variants necessite l’utilisation d’outils specifiques d’identification serologique et de caracterisation moleculaire, le diagnostic et le suivi virologique de ces infections apparaissent desormais possibles avec les trousses commerciales actuelles ; en revanche, tres peu de donnees sont disponibles sur la reponse au traitement antiretroviral et la conduite a tenir en cas d’echec. Malgre l’amelioration des connaissances sur ces variants rares, il persiste de nombreuses et fascinantes questions sur leur origine, leur evolution genetique et les raisons de leur faible diffusion epidemiologique. Leur decouverte, ainsi que la description ces dernieres annees de nombreux virus simiens, demontre une dynamique de transmission a l’homme, rendant probable l’existence d’autres variants ; il convient donc de poursuivre une veille sanitaire, en particulier devant toute discordance dans l’algorithme de depistage et de prise en charge therapeutique des infections a VIH.

Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta, iliac arteries and extends into the retroperitoneum to envelop neighboring structures such as the ureters. We present two cases with multisystem disease involving retroperitoneal fibrosis, renal failure, pulmonary infiltrates and skeletal abnormalities. The unifying diagnosis of Erdheim–Chester disease (ECD) is a non-Langerhans cell histiocytosis (NLH) characterized by bilateral metaphyseal sclerosis of long bones, retroperitoneal fibrosis and multiple organ dysfunction due to the infiltrative process.

Background and objectives. The mesangial deposition of IgA is rarely described with proliferative glomerulonephritis associated with Staphylococcus infection. Recently, this association has been increasingly recognized possibly due to the increased rate of Staphylococcus infection. Design setting, participants and measurements. We report two cases of methicillin-sensitive Staphylococcus aureus bacteremia associated with acute proliferative glomerulonephritis with dominant mesangial deposit of IgA. We searched MEDLINE (1960–2009) for similar reports. We pooled individual patient data and reported descriptive statistics of all published cases. Results. Forty-six cases were included in the final analysis. The mean age of presentation was 59, with a male predominance (84%). Clinical presentation was notable for rapidly progressive glomerulonephritis with nephrotic-range proteinuria and normal complement levels in 52 and 72%, respectively. Methicillin-resistant S. aureus (68%) was the most common pathogen isolated with a latent period ranging from 1 to 16 weeks. Diffuse mesangial proliferation was commonly found with crescentic lesions noted in 35% of the cases. Antimicrobial treatment was associated with renal recovery in 58% of the cases. Need for renal replacement therapy was significantly associated with pre-existing diabetes, hypertension and interstitial fibrosis seen on kidney biopsy. Conclusions. IgA-dominant post-Staphylococcus glomerulonephritis is a rare clinical entity with certain unique clinical and morphologic features. It is difficult to differentiate from primary IgA nephropathy in cases where the infection is not apparent. An acute onset of rapidly progressive glomerulonephritis, with normal complement levels and deposition of mesangial IgA in an elderly patient should raise suspicion for this rare form of glomerulonephritis.

As several equations have been developed for estimating the glomerular filtration rate (GFR), many laboratories are now reporting the GFR automatically, and primary care providers are left trying to interpret the results and put them into the context of patient care. Therefore, it is important that health care professionals understand how to interpret the estimated GFR value and how to recognize when the estimate may not be accurate.

Traumatic rupture of the descending aorta is an acute life-threatening event. The most common cause is deceleration trauma resulting in a sudden stretching of the aortic isthmus as for example in car and motorcycle accidents and falls from a great height. Exemplified by a case report of a multiply injured 57-year-old male the diagnostic pathways, therapy and postoperative complications are presented.

Summary Background and objectives Chronic kidney disease (CKD) is increasing, and outcomes-related research from diverse health care settings is needed to target appropriate efforts and interventions. We developed an electronic health record (EHR)-based CKD registry at the Cleveland Clinic and validated comorbid conditions. Design, setting, participants, & measurements Patients who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider and (1) had two estimated GFR values 90 days apart as of January 1, 2005 and/or (2) were patients with International Classification of Diseases-9 (ICD-9) diagnosis codes for kidney disease were included. Results Our registry includes 57,276 patients (53,399 patients met estimated GFR criteria and 3877 patients met ICD-9 diagnosis code criteria) as of March 2010. Mean age was 69.5 ± 13.4 years, with 55% women and 12% African Americans. Medicare is the primary insurer for more than one half of the study cohort. The κ statistics to assess the extent of agreement between the administrative dataset extracted from the EHR and actual EHR chart review showed substantial agreement (>0.80) for all conditions except for coronary artery disease and hypertension, which had moderate agreement ( Conclusions Development of an EHR-based CKD registry is feasible in a large health system, and the comorbid conditions included in the registry are reliable. In addition to conducting research studies, such a registry could help to improve the quality of care delivered to CKD patients and complement the ongoing nationwide efforts to develop a CKD surveillance project.

Background Despite the perspective of vaccination against herpes zoster, there are few recent data available on the incidence of this disease, the proportion of postherpetic neuralgia cases, and associated disease management costs. This study was performed to evaluate these parameters in a representative sample of French physicians. Methods It was a retrospective, declarative study conducted from the medical files of patients who presented with herpes zoster and consulted in 2005, based on a random sample of GPs, dermatologists, neurologists, and physicians in pain clinics, weighted by demographic departmental distribution of patients aged 50 years and above. The analysis was performed on cases diagnosed by physicians themselves (incident cases). Results The annual incidence of herpes zoster was estimated at 8.99/1000 [8.34–9.64], all types of physicians pooled and at 8.67/1000 for GPs. This represents about 182,500 cases of herpes zoster in France in 2005 in patients aged 50 years and above. Incidence was slightly higher amongst women (1.3 times) and increased with age. Amongst the 777 cases of incident herpes zoster, 343 were complicated by postherpetic neuralgia one month after diagnosis. The proportion of patients presenting postherpetic neuralgia at 3 and 6 months was 32.1% and 17.6%, respectively. The annual cost of management of herpes zoster and postherpetic neuralgia was estimated at 170 [109–249] million euros, of which 61.0 million euros were covered by the national health insurance. Conclusion In this study, the incidence of herpes zoster observed in France in subjects aged 50 years and above is close to that already estimated in France and Europe. The proportion of postherpetic neuralgia is high and this painful complication may persist for several months after diagnosis of herpes zoster. To our knowledge, EPIZOD is the first study conducted in France to assess the cost of herpes zoster and of postherpetic neuralgia, the most frequent complication of this viral disease.