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In diesem Beitrag werden die starken Empfehlungen (Grad A) der AWMF-Leilinien zum Thema „Nationale Versorgungsleitlinie Typ-2-Diabetes: Praventions- und Behandlungsstrategien fur Fuskomplikationen (Version 2.8, Februar 2010)“ fur die Bereiche weiterfuhrende Diagnostik, therapeutische Masnahmen und Amputation zusammengefasst dargestellt und diskutiert. Einschrankend muss erwahnt werden, dass die Gultigkeit der Leitlinien abgelaufen ist. Eine aktuelle Fassung lag bis zur Entstehung dieses Beitrags noch nicht vor, sodass sich die Autoren dieses Artikels an der letzten verfugbaren Fassung orientierten und zusatzlich Empfehlungen der aktuellen ESVS-Leitlinien CLTI berucksichtigten. Die Vergabe der Empfehlungsgrade erfolgte durch ein formales Konsensusverfahren der beteiligten Leitlinienautoren. Auf die Empfehlungen Grad B und Grad 0 wird in diesem Artikel aufgrund des geringen Empfehlungsgrads nicht eingegangen.

Die periphere arterielle Verschlusskrankheit (PAVK) ist die Manifestation der Atherosklerose als vaskulare Systemerkrankung. Weltweit zeigt sich eine steigende Pravalenz bis zu 10 %, die bei einer alter werdenden Bevolkerung bis auf 20 % bei den uber 70-Jahrigen zunimmt. Nur ein Viertel der PAVK-Betroffenen ist symptomatisch. Frauen sind zum Zeitpunkt der Diagnosestellung alter als Manner, dann aber haufiger bereits im Stadium der kritischen Extremitatenischamie (CLI). Neben den funktionellen Beeintrachtigungen stellt die PAVK vor allem eine wichtige Markererkrankung fur kardiovaskulare und zerebrovaskulare Morbiditat und Mortalitat dar. So betragt die 1‑Jahres-Mortalitat bei Patienten mit einer kritischen Extremitatenischamie bis zu 23 %. Eine fruhzeitige Diagnose und evidenzbasierte Behandlung kann den Verlauf dieser Krankheit verlangsamen, die Lebensqualitat verbessern und die Majoramputationsrate reduzieren. Die Kosten fur die ambulante und stationare Behandlung dieser Zielpopulation sind erheblich. In Deutschland wurde zwischen 2007 und 2009 ein Anstieg der Behandlungskosten um 21 % beobachtet. Der Anteil an den stationaren Gesamtkosten betrug 4,9 %. Somit stellt die PAVK vor dem Hintergrund der demografischen Entwicklung mit einer Verdopplung des Anteils der uber 65-Jahrigen in den nachsten 35 Jahren eine medizinische und finanzielle Herausforderung fur das Gesundheitssystem dar.

Gefaschirurgische Patienten uber 80 Jahre sind im klinischen Alltag mittlerweile keine Seltenheit. Die Veranderung in der Demografie stellt die Medizin vor neue Herausforderungen und wird uns auch in Zukunft weiter begleiten. Viele Studien haben in den letzten Jahren den Nutzen einer Revaskularisation bei Vorliegen einer chronisch kritischen Extremitatenischamie nachgewiesen. Aber nicht alles technisch Machbare ist auch sinnvoll fur den Patienten. Endovaskulare und operative Verfahren zu Revaskularisation stehen zur Verfugung. Unter Berucksichtigung der Begleiterkrankungen, der Lebenserwartung und der zu erwartenden Mobilitat des Patienten konnen mit dem geeigneten Verfahren gute Ergebnisse erzielt werden. Dieser Ubersichtsartikel mit selektiver Literaturrecherche soll fur dieses wichtige Thema – Therapieoptionen der kritischer Extremitatenischamie bei Patienten > 80 Jahren – sensibilisieren und zeigt, dass jedes Revaskularisationsverfahren Vor- und Nachteile beinhaltet. Die Therapie muss auf den Patienten individuell abgestimmt werden.

To determine whether sex, age, and body mass index are correlated with active glucagon-like-peptide 1 concentrations and to investigate glucagon-like-peptide 1 reproducibility during repeated oral glucose tolerance tests.Sixty-one healthy volunteers underwent four 2-hour repeated oral glucose tolerance tests approximately 1 week apart. Because this randomized same-subject crossover trial was designed to investigate effects of non-nutritive sweeteners, participants received 355 mL (12 ounces) of water or a beverage containing non-nutritive sweeteners 10 minutes prior to each oral glucose tolerance test. Blood samples were collected 10 minutes before, and 0, 10, 20, 30, 60, 90, and 120 minutes following ingestion of 75 grams of glucose.Basal active glucagon-like-peptide 1, peak glucagon-like-peptide 1, and glucagon-like-peptide 1 area-under-the-curve were higher in men than women (all p ≤0.04), adjusting for body mass index and age. Fasting and stimulated active glucagon-like-peptide 1 results were highly reproducible with little within-subject variability (between-subjects to within-subject variability ratio 4.2 and 3.5 for fasting glucagon-like-peptide 1 and glucagon-like-peptide 1 area-under-the-curve).Men had higher active glucagon-like-peptide 1 concentrations than women. In contrast to considerable inter-individual variability of basal and stimulated active glucagon-like-peptide 1 concentrations, intra-individual variability was low, consistent with tight physiological regulation.

OBJECTIVE This study was designed to demonstrate the predictive ability of quantitative indocyanine green (ICG) fluorescence angiography for the short-term postoperative outcome, the occurrence of delayed graft function (DGF), and long-term graft survival. SUMMARY BACKGROUND DATA DGF is a relevant problem after kidney transplantation; sufficient microperfusion of the allograft is crucial for postoperative organ function. Fluorescence angiography with ICG can serve as an intraoperative quality control of microperfusion. METHODS This prospective diagnostic study, conducted in two German transplantation centers from November 2015 to October 2018, included 128 consecutive kidney transplantations. Intraoperative assessment of the allograft microperfusion was performed by near-infrared fluorescence angiography with ICG; a software was used for quantitative analysis. The associations between perfusion parameters (e.g. ICG Ingress) and donor, recipient, periprocedural, and postoperative characteristics were evaluated. RESULTS DGF occurred in 23 (24%) kidney recipients from deceased donors. ICG Ingress (p = 0.0027), donor age (p = 0.0452), recipient age (p = 0.0139) and recipient body mass index (p = 0.0017) were associated with DGF. ICG Ingress correlated significantly with recipient age (r = -0.27662, p = 0.0016), cold and warm ischemia time (r = -0.25204, p = 0.0082; r = -0.19778, p = 0.0283), operating time (r = -0.32208, p = 0.0002), eGFR on postoperative days 1 (r = +0.22674, p = 0.0104) and 7 (r = +0.33189, p = 0.0001). The cutoff value for ICG Ingress was 106.23 AU with sensitivity of 78.3% and specificity of 80.8% (p < 0.0001) for the prediction of DGF. CONCLUSION Fluorescence angiography with ICG allows intraoperative quantitative assessment of microperfusion during kidney transplantation. The parameter ICG Ingress reflects recipient and procedure characteristics and is able to predict the incidence of DGF. TRIAL REGISTRATION Clinicaltrials.gov: NCT-02775838.

Das Angiosomen-Konzept als eine Entscheidungsgrundlage zur Revaskularisation bei Patienten mit chronisch kritischer Extremitatenischamie und notwendiger Unterschenkelrevaskularisation wird in der Literatur kontrovers diskutiert. Es wurde eine narrative Literatursuche auf PubMed (US National Library of Medicine) durchgefuhrt. Es liegen zahlreiche retrospektiven Studien vor, die eine unterschiedliche Relevanz dieses Konzeptes in Abhangigkeit des gewahlten Therapieverfahrens (offen-chirurgisch vs. endovaskular) zeigen. Ebenso haben Nebenerkrankungen einen Einfluss auf dessen Relevanz. Dieser Artikel gibt eine Ubersicht uber die derzeitige Studienlage zur angiosomenorientierten Revaskularisation in Abhangigkeit vom gewahlten Therapieverfahren sowie eventuell vorliegender Nebenerkrankungen.

Leitlinien zur Behandlung der Claudicatio intermittens (CI) empfehlen Lebensstilanderung, das Management der Risikofaktoren, die medikamentose Durchblutungsverbesserung, und strukturiertes uberwachtes Gehtraining (SET). Revaskularisationen sollen die Ausnahme bleiben. In Deutschland weicht die Behandlungsrealitat von diesen Leitlinienempfehlungen ab. Die systematische Literaturrecherche fur die S3-Leitlinie PAVK der Deutschen Gesellschaft fur Angiologie (2014) wurde bis 2020 aktualisiert. Bei geeignetem Muster der arteriellen Verschlussprozesse kann die schmerzfreie Gehstrecke durch konsequentes SET signifikant gesteigert werden. Wirksamkeit, Verfugbarkeit, Anwendbarkeit und Therapieadharenz von SET sind aber meist gering. Dagegen fuhren Revaskularisationen bei CI schneller als SET und immer nachhaltiger zur Beschwerdefreiheit. Optimal ist ihre Kombination mit SET. Revaskularisation bei Patienten mit CI haben einen hohen Stellenwert, zumal die konservative Behandlung mittels SET im deutschen Gesundheitssystem nicht erkennbar implementiert ist. Ware SET ausreichend verfugbar, konnte das die Zahl der Revaskularisationen verringern, ihren Erfolg langerfristig sichern, und das kardiovaskulare Risiko senken.

In 2018 and 2020, two meta-analyses using summary-level data from randomized controlled trials reported worse mortality following the application of paclitaxel-coated stents and balloons in femoropopliteal and crural arteries. These results initiated a heated global discussion concerning the validity of this association, while various observational studies using clinical and administrative registries proved the safety of coated devices. This article aimed to summarize the development and adoption of paclitaxel-coated balloons and stents for the treatment of peripheral arterial occlusive disease in clinical practice, research, and practice guidelines. It especially focusses on the European Unionʼs medical device regulation, which has far-reaching implications for the market approval and monitoring of high-risk medical devices.

ZusammenfassungDas diabetische Fußsyndrom (DFS) ist die häufigste Ursache einer Majoramputation in Deutschland. Die meisten Fußläsionen werden durch repetitive Druckbelastung bei diabetischer Polyneuropathie ausgelöst. Die periphere arterielle Verschlusskrankheit (PAVK) verhindert die Wundheilung und ist Hauptrisikofaktor für Amputationen. Bei der Therapie sind die Wund- und Infektionsbehandlung sowie die zeitnahe Revaskularisation entscheidend. Der Einsatz endovaskulärer und gefäßchirurgischer Methoden ist abhängig von Verteilungsmuster und Länge der Verschlussprozesse. Beide Verfahren ergänzen sich. Die Bypasschirurgie hat beim neuroischämischen DFS einen hohen Stellenwert. Multidisziplinäre Zentren, die Revaskularisationen bei DFS anbieten, können in 90 % der Fälle eine Verbesserung der arteriellen Durchblutung erreichen und die Amputationsrate um bis zu 80 % senken. Wegen der hohen Rezidivrate diabetischer Fußläsionen sind Maßnahmen zur Sekundärprophylaxe von herausragender Bedeutung (podologische und orthopädietechnische Betreuung, Fußchirurgie).

Background We do not fully understand how hypercortisolism causes central hypothyroidism or what factors influence recovery of the hypothalamic-pituitary-thyroid axis. We evaluated thyroid function during and after cure of Cushing syndrome (CS). Methods We performed a retrospective cohort study of adult patients with CS seen from 2005 to 2018 (cohort 1, c1, n = 68) or 1985 to 1994 (cohort 2, c2, n = 55) at a clinical research center. Urine (UFC) and diurnal serum cortisol (F: ~8 am and ~midnight [pm]), morning 3,5,3′-triiodothyronine (T3), free thyroxine (FT4), and thyrotropin (TSH) (c1) or hourly TSH from 1500 to 1900 h (day) and 2400 to 04000 h (night) (c2), were measured before and after curative surgery. Results While hypercortisolemic, 53% of c1 had central hypothyroidism (low/low normal FT4 + unelevated TSH). Of those followed long term, 31% and 44% had initially subnormal FT4 and T3, respectively, which normalized 6 to 12 months after cure. Hypogonadism was more frequent in hypothyroid (69%) compared to euthyroid (13%) patients. Duration of symptoms, morning and midnight F, adrenocorticotropin, and UFC were inversely related to TSH, FT4, and/or T3 levels (r = –0.24 to –0.52, P < .001 to 0.02). In c2, the nocturnal surge of TSH (mIU/L) was subnormal before (day 1.00 ± 0.04 vs night 1.08 ± 0.05, P = .3) and normal at a mean of 8 months after cure (day 1.30 ± 0.14 vs night 2.17 ± 0.27, P = .01). UFC greater than or equal to 1000 μg/day was an independent adverse prognostic marker of time to thyroid hormone recovery. Conclusions Abnormal thyroid function, likely mediated by subnormal nocturnal TSH, is prevalent in Cushing syndrome and is reversible after cure.

ZusammenfassungIn Deutschland leben ca. 8 Mio. Menschen mit Diabetes mellitus. Eine Spätfolge dieser Erkrankung ist das diabetische Fußsyndrom (DFS), dessen Prävalenz stark ansteigt. Es umfasst alle Veränderungen am Fuß als Folge der diabetischen Polyneuropathie sowie mikro- und makroangiopathischer (periphere arterielle Verschlusskrankheit, PAVK) Veränderungen. Jährlich entstehen ca. 250.000 neue diabetische Fußulzera. Diese werden oft zu chronischen Wunden. Trotz intensiver Bemühungen um Prävention, frühzeitige Diagnostik und stadiengerechte Wundbehandlung werden in Deutschland jährlich ca. 13.000 Majoramputationen bei Diabetikern durchgeführt. Bei konsequenter Therapie des DFS in interdisziplinären Zentren mit Ausschöpfung aller Möglichkeiten der Wundbehandlung, der Druckentlastung sowie einer arteriellen Revaskularisation kann die Majoramputationsrate um bis zu 80 % gesenkt werden. Durch eine geeignete Präventionsstrategie wäre die große Gefahr der Rezidivulzera geringer.

In den Jahren 2018 und 2020 haben zwei Metaanalysen zu kumulativen Ergebnissen von randomisierten und kontrollierten Studien eine erhohte Sterblichkeit nach der Anwendung Paclitaxel-beschichteter Stents bzw. Ballons in den Gefasen der unteren Extremitaten berichtet. Im Anschluss daran entwickelte sich eine angeregte globale Diskussion uber die Validitat dieser Assoziation, wobei die Ergebnisse zahlreicher Beobachtungsstudien mit klinischen und administrativen Registerdaten die Anwendungssicherheit beschichteter Medizinprodukte nahelegten. Dieser Artikel fasst die Entwicklung und Verbreitung Paclitaxel-beschichteter Ballons und Stents zur Behandlung der peripheren arteriellen Verschlusskrankheit in der klinischen Praxis, in Studien und in Leitlinien zusammen. Hierbei wird ein besonderer Fokus auf die neue Medizinprodukteregulation der Europaischen Union gelegt, die weitreichende Implikationen fur die Marktzulassung und Uberwachung von Hochrisikomedizinprodukten hat.

Die nachvollziehbare Beurteilung von Qualitat in der Medizin gewinnt immer weiter an Bedeutung, so auch bei der Behandlung der peripheren arteriellen Verschlusserkrankung (pAVK). Ziel dieser Arbeit war es, die Spannbreite der derzeitigen Behandlungsrealitat darzustellen sowie Indikatoren fur Ergebnisqualitat in der Behandlung von pAVK-Patienten zu diskutieren. Die Kommission „pAVK und Diabetischer Fus“ der Deutschen Gesellschaft fur Gefaschirurgie und Gefasmedizin e. V. (DGG) hat von 01. Juni 2019 bis 25. Februar 2020 die Literatur zu diesem Thema gesichtet und ausgewertet. Unterschiedliche Indikatoren fur Ergebnisqualitat wurden analysiert und diskutiert. Parallel dazu wurde anhand festgelegter Suchbegriffe eine narrative Literaturrecherche durchgefuhrt und deren Ergebnisse zur Festlegung moglicher Richtwerte fur offen-chirurgische sowie endovaskulare Therapieverfahren genutzt. Anhand der Literatur wurden Zahlen (Mittelwert und Range) fur Qualitatsindikatoren ermittelt. Insgesamt konnten 8 Indikatoren fur Ergebnisqualitat, gultig fur die endovaskulare als auch offen-chirurgische Behandlung, identifiziert werden (Claudicatio intermittens [CI]: Fruhergebnisse [30 Tage]: Fruhverschluss, revisionspflichtige Zugangskomplikationen; Langzeitergebnisse [5 Jahre]: Primare Offenheit, Verschlechterung Rutherford-Stadium; chronisch kritische Extremitatenischamie [CLI]: Fruhergebnisse [30 Tage]: Fruhverschluss, 30-Tages-Major Amputation; Langzeitergebnisse [1 Jahr]: Primare Offenheit, Extremitatenerhalt). Die Kommission „pAVK und Diabetischer Fus“ der DGG hat essenzielle Indikatoren fur Ergebnisqualitat diskutiert und identifiziert. Die Auswertung der Literatur prasentiert dafur Zahlen, welche erreicht werden konnen, zeigt aber auch deren teils grose Ergebnisunterschiede. Ein interdisziplinares Register fur die Behandlung der pAVK ist eine Moglichkeit zur Erhebung von Primardaten, aus denen Richtwerte fur die Indikatoren der Ergebnisqualitat festgelegt werden konnen.

Background Popliteal artery aneurysms (PAAs) are the most common peripheral aneurysms. Although rare and often asymptomatic, there is a significant risk of thrombosis, embolism, and limb loss. The aim of this study was to evaluate the eligibility for endovascular repair of patients treated for symptomatic and asymptomatic PAAs in accordance with the instructions for use (IFU). Methods All patients treated for PAA with open surgical repair between the years 2010 and 2017 were analyzed if suitable for endovascular treatment. Preoperative imaging was reviewed for applicability with an interventional radiologist and 2 vascular surgeons. Evaluation was performed in accordance with the following criteria adopted from the IFU of the Gore ® Viabahn stent graft: at least a single-vessel tibial runoff, proximal and distal landing zone more than 2 cm, no large difference in vessel diameter proximal and distal to the aneurysm, no overstenting of significant collaterals necessary, and no inadequate kinking of the artery. The patients were classified in 3 categories: the patient was eligible, endovascular treatment was feasible, and endovascular treatment was not appropriate. Results 51 patients with 61 symptomatic and asymptomatic PAAs were identified. Forty-five cases were asymptomatic, 11 cases showed clinical symptoms such as claudication, and in 5 cases, the patients presented with acute ischemia. Twenty-four patients were eligible for endovascular intervention, 14 cases were feasible, and in 23 cases, it was not appropriate in accordance with the IFU. Conclusions In this study, more than one-third of the patients with PAA were not eligible for endovascular treatment in accordance with the IFU and another 23 % showed substantial reasons against endovascular treatment. These data suggest that endovascular repair remains a treatment option for selected patients only. Cross-sectional imaging is mandatory for procedure selection.

Background The Matutes score (MS) was proposed to differentiate chronic lymphocytic leukemia (CLL) from other B-cell non-Hodgkin lymphomas (B-NHLs). However, ambiguous immunophenotypes are common and remain a diagnostic challenge. Therefore, we evaluated the diagnostic benefit of measuring CD200 and CD43 expression together with the standard MS antigens. Methods 138 lymphoma patient samples and a validation cohort of 138 additive samples were classified according to the standard MS and further assigned with one or two additional points, for high CD200 and/or CD43 expression levels. The "classical" MS and the "Matutes score-extended" (MS-e) were categorized as high (4-5/6-7), intermediate (2-3/4-5), and low (0-1/0-3). Samples were reclassified into the MS-e with focus on ambiguous cases with an intermediate "classical" MS. Results A total of 35 of 138 (25.4%) patient samples were assigned to the intermediate MS group and confirmed by histopathological reports as CLL (14/40.0%) and B-NHLs other than CLL (21/60%). MS-e analysis identified 13 of 14 (92.9%) of CLL cases (MS-e 4-5) and 18/21 (85.7%) non-CLL cases (MS-e ≤ 3) correctly. Overall, the sensitivity of the CLL diagnosis was significantly increased by application of MS-e compared to the "classical" MS (98.8% vs. 82.7%; p = 0.0009), while specificity of both methods was almost equal (94.7% vs. 98.3%; p = 0.4795). Of note, sole measurement of CD43 and CD200 on B-cells sufficiently differentiated CLL from non-CLL with a test accuracy superior to the "classical" MS (F1 score 96.2 vs. 93.6). Conclusion CD200 and CD43 have a high informative value in diagnostic immunophenotyping and facilitate the separation of CLL from other B-NHLs particularly in ambiguous cases.

In August 2019, 30 attendees at a Nebraska wedding developed mumps after being exposed to one asymptomatic index patient who was fully vaccinated according to Advisory Committee on Immunization Practices (ACIP) recommendations (1), resulting in a multistate outbreak. A public health investigation and response revealed epidemiologic links that extended from the index patient through secondary, tertiary, and quaternary patients and culminated in a measles-mumps-rubella (MMR) booster vaccination campaign in the local community where approximately half of the patients resided.

Summary: Background: To analyze long-term outcomes and possible influencing factors in patients with endstage renal disease (ESRD) and critical limb ischemia (CLI) after major amputation compared to patients with normal renal function and non-dialysis-dependent chronic kidney disease. Patients and methods: Abstraction of single-center medical records of patients undergoing above knee (AKA) and below knee (BKA) amputation over a 10 years period (n = 436; 2009–2018). Excluded were amputations due to trauma or tumor. Patients were subdivided according to renal function in three categories: ESRD patients (n = 98), non-dialysis dependent chronic kidney disease (CKD, n = 98) and normal renal function (NF, n = 240). Predefined endpoints were survival and postoperative complications. Cox-regression models were built to analyze independent risk factors for outcome parameters. Results: In total, 298 AKA, 133 BKA and 5 knee joint exarticulations were performed. ESRD patients showed inferior in-hospital results as to death (ESRD 36.7 % vs. CKD 19.4 % and NF 20.0 %, P = .002). Similarly, long-term survival rates (6 months: ESRD 55.0 % vs. CKD 69.4 %, NF 67.9 % 1 year: ESRD 48.6 %, CKD 60.2 %, NF 60.8 % 5 years: ESRD 9.9 %, CKD 31.8 %, NF 37.1 %, P

Galvanic vestibular stimulation (GVS) has increasingly been used to stimulate the vestibular system in health and disease. While perceptible supra-threshold GVS destabilizes postural control in healthy control (HC) subjects, imperceptible 'noisy' GVS (nGVS) is reported to improve postural control in patients with bilateral vestibulopathy (BV) and therapeutic devices using nGVS are currently under development. We questioned (1) whether perceptible GVS destabilizes postural control of BV patients, expecting any effect to be smaller than in healthy subjects due to the patients' vestibulopathy, and (2) whether imperceptible nGVS improves postural control in comparison to an active sham stimulus in context-dependent conditions, hypothesizing that it fades off once postural control becomes more challenging with respect to its sensory (standing on foam) or cognitive (dual task) complexity. We tested postural responses of 30 BV patients to bimastoidal perceptible (lowGVS, highGVS) or imperceptible (nGVS, sham, noGVS) GVS in comparison to 24 age-matched HC. Perceptible GVS intensities were applied according to the participants' individual motion perception thresholds. Postural sway speed (PSS) was analyzed in a 4-factorial experimental design with the factors group (BV, HC), vision (eyes open/closed), condition (baseline, proprioception, cognition) and stimulation (noGVS, sham, nGVS, lowGVS, highGVS). With eyes open (EO), there were no group-related PSS differences in the baseline and cognition condition in response to either stimulations. With EO on foam and with eye closed (EC) in all conditions, patients showed larger PSS than HC, irrespective of the stimulation type. PSS differed with GVS intensities within each group but not between the groups. PSS under nGVS on EC was only smaller in patients when compared to perceptible GVS, but it was not different from noGVS or sham stimulation. Moreover, this nGVS effect was only found in the baseline but not in the more challenging dual task and foam condition. Almost half of the patients showed higher individual thresholds of motion perception of GVS compared to HC. Interestingly, this high-threshold subgroup showed significantly larger PSS with EC as compared to HC and the low-threshold patient subgroup, although both patient subgroups did not differ in vestibular parameters. We conclude, first, that perceptible GVS is able to destabilize BV patients similarly to HC subjects, suggesting sufficient vestibular afferent processing of GVS during vestibulo-spinal postural control. Second, the effect of the hitherto observed improved postural control by nGVS appears to be small during more demanding postural control conditions (foam, cognitive distraction) that are closer to the patients' everyday life, when active sham stimuli are used as control stimuli. These findings underline the meaning of active control conditions when the efficacy of nGVS is tested, e.g. in portable GVS devices in the attempt to improve postural control in BV patients. However, differential GVS effects on vestibulo-perceptional and vestibulo-spinal thresholds should be taken into account. Finally, our data suggest that individual motion perception thresholds for GVS could potentially serve as a predictor of postural control safety and falling risk in BV.

Summary. The term “microcirculation” refers to the terminal vascular network of the body, which includes arterioles, capillaries, venules as well as initial lymphatic vessels. Additionally, it insinuates to their unique function in thermoregulation, fluid balance, maintenance of cellular exchange, and metabolism. Disturbances of microvascular function were identified to precede macrovascular involvement in the presence of cardiovascular risk factors and is the hallmark of terminal disease stages like critical limb or acral ischemia. Nevertheless, despite its obvious significance in vascular medicine assessment of microvascular function became increasingly neglected in the clinical institutions during the last decades and seems to play a subordinary role in medical education. We therefore provide an overview over relevant and clinically practicable methods to assess microcirculation in vascular medicine with critical estimations of their pros and cons and their perspectives in the future.

We examined the effect of galvanic vestibular stimulation (GVS) on resting state brain activity using fMRI (rs‐fMRI) in patients with bilateral vestibulopathy. Based on our previous findings, we hypothesized that GVS, which excites the vestibular nerve fibers, (a) increases functional connectivity in temporoparietal regions processing vestibular signals, and (b) alleviates abnormal visual–vestibular interaction. Rs‐fMRI of 26 patients and 26 age‐matched healthy control subjects was compared before and after GVS. The stimulation elicited a motion percept in all participants. Using different analyses (degree centrality, DC; fractional amplitude of low frequency fluctuations [fALFF] and seed‐based functional connectivity, FC), group comparisons revealed smaller rs‐fMRI in the right Rolandic operculum of patients. After GVS, rs‐fMRI increased in the right Rolandic operculum in both groups and in the patients' cerebellar Crus 1 which was related to vestibular hypofunction. GVS elicited a fALFF increase in the visual cortex of patients that was inversely correlated with the patients' rating of perceived dizziness. After GVS, FC between parietoinsular cortex and higher visual areas increased in healthy controls but not in patients. In conclusion, short‐term GVS is able to modulate rs‐fMRI in healthy controls and BV patients. GVS elicits an increase of the reduced rs‐fMRI in the patients' right Rolandic operculum, which may be an important contribution to restore the disturbed visual–vestibular interaction. The GVS‐induced changes in the cerebellum and the visual cortex were associated with lower dizziness‐related handicaps in patients, possibly reflecting beneficial neural plasticity that might subserve visual–vestibular compensation of deficient self‐motion perception.

Background: The pathophysiologic mechanisms underlying painful symptoms in diabetic polyneuropathy (DPN) are poorly understood.They may be associated with MRI characteristics, which have not yet been investigated.Purpose: To investigate correlations between nerve structure, load and spatial distribution of nerve lesions, and pain in patients with DPN.Materials and Methods: In this prospective single-center cross-sectional study, participants with type 1 or 2 diabetes volunteered between June 2015 and March 2018. Participants underwent 3-T MR neurography of the sciatic nerve with a T2-weighed fat-suppressed sequence, which was preceded by clinical and electrophysiologic tests. For group comparisons, analysis of variance or the Kruskal-Wall is test was performed depending on Gaussian or non-Gaussian distribution of data. Spearman correlation coefficients were calculated for correlation analysis.Results: A total of 131 participants (mean age, 62 years +/- 11 [standard deviation]; 82 men) with either type 1 (n = 45) or type 2 (n = 86) diabetes were evaluated with painful (n = 64), painless (n = 37), or no (n = 30) DPN. Participants who had painful diabetic neuropathy had a higher percentage of nerve lesions in the full nerve volume (15.2% +/- 1.6) than did participants with nonpainful DPN (10.4% +/- 1.7, P = .03) or no DPN (8.3% +/- 1.7; P

Background : Various imaging modalities can be used in addition to white light (WL) to improve detection of bladder cancer (BC). Objective : To use real-time multispectral imaging (rMSI) during urethrocystoscopy to combine different imaging modalities to achieve multiparametric cystoscopy (MPC). Design, setting, and participants : The rMSI system consisted of a camera with a spectral filter, a multi-LED light source, a microcontroller, and a computer for display and data acquisition. MSI with this system was achieved via temporal multiplexing. Surgical procedure : MPC was performed in ten patients with a diagnosed bladder tumor. Measurements : We gathered evidence to prove the feasibility of our approach. In addition, experienced urologists performed post-interventional evaluation of images of individual lesions. Images were independently rated in a semiquantitative manner for each modality. A statistical model was built for pairwise comparisons across modalities. Results and limitations : Overall, 31 lesions were detected using the rMSI set-up. Histopathology revealed malignancy in 27 lesions. All lesions could be visualized simultaneously in five modalities: WL, enhanced vascular contrast (EVC), blue light fluorescence, protoporphyrin IX fluorescence, and autofluorescence. EVC and photodynamic diagnosis images were merged in real time into one MP image. Using the recorded images, two observers identified all malignant lesions via MPC, whereas the single modalities did not arouse substantial suspicion for some lesions. The MP images of malignant lesions were rated significantly more suspicious than the images from single imaging modalities. Conclusions : We demonstrated for the first time the application of rMSI in endourology and we established MPC for detection of BC. This approach allows existing imaging modalities to be combined, and it may significantly improve the detection of bladder cancer. Patient summary : Real-time multispectral imaging was successfully used to combine different imaging aids for more comprehensive illustration of bladder tumors for surgeons. In the future, this technique may allow better detection of bladder tumors and more complete endoscopic resection in cases of cancer.

Imaging plays a central role in the evaluation of patients following cardiothoracic surgery, both for monitoring in the early postoperative period and for assessing for suspected complications. Patients with postsurgical complications can develop a range of signs and symptoms, from hypotension and tachycardia, as the result of severe bleeding, to fever and leukocytosis because of infection. The radiologist is an important member of the care team in the postoperative period, helping identify and manage complications of cardiothoracic surgery. This article reviews the common complications of cardiothoracic surgery focusing on the role of imaging and clues to diagnosis.

Maternal obesity greatly affects next generations, elevating obesity risk in the offspring through perinatal programming and flawed maternal and newborn nutrition. The exact underlying mechanisms are poorly understood. Interleukin-6 (IL-6) mediates its effects through a membrane-bound receptor or by trans-signaling (tS), which can be inhibited by the soluble form of the co-receptor gp130 (sgp130). As IL-6 tS mediates western-style diet (WSD) effects via chronic low-grade inflammation (LGI) and LGI is an important mediator in brain–adipose tissue communication, this study aims at determining the effects of maternal obesity in a transgenic mouse model of brain-restricted IL-6tS inhibition (GFAPsgp130) on offspring’s short- and long-term body composition and epigonadal white adipose tissue (egWAT) metabolism. Female wild type (WT) or transgenic mice were fed either standard diet (SD) or WSD pregestationally, during gestation, and lactation. Male offspring received SD from postnatal day (P)21 to P56 and were metabolically challenged with WSD from P56 to P120. At P21, offspring from WT and transgenic dams that were fed WSD displayed increased body weight and egWAT mass, while glucose tolerance testing showed the strongest impairment in GFAPsgp130WSD offspring. Simultaneously, egWAT proteome reveals a characteristic egWAT expression pattern in offspring as a result of maternal conditions. IL-6tS inhibition in transgenic mice was in tendency associated with lower body weight in dams on SD and their respective offspring but blunted by the WSD. In conclusion, maternal nutrition affects offspring’s body weight and egWAT metabolism predominantly independent of IL-6tS inhibition, emphasizing the importance of maternal and newborn nutrition for long-term offspring health.

O ciclismo é um esporte que tem atraído vários adeptos pelo mundo. A prática do ciclismo exige grandes adaptações neuroimunoendócrinas e cardiovasculares, de tal modo que o corpo mantenha a homeostase. Nesse contexto, biomarcadores de estresse miocárdico parecem sofrer alterações secundárias ao esforço físico do ciclista. O objetivo desse trabalho foi avaliar, em ciclistas, os valores de BNP, NT-proBNP e Troponina ultrassensível, relacionando alterações nesses biomarcadores à presença de lesões miocárdicas em exercícios de longa duração. Realizou-se uma revisão narrativa, que realizou busca ativa nas bases de dados Bireme, Pubmed, MedLine, SciELO e LILACS. Foram analisados 7 artigos que atenderam aos critérios metodológicos do estudo. Os estudos demonstram que os atletas de ciclismo estão predispostos a valores mais elevados de BNP, NT-proBNP e Troponina ultrassensível durante o exercício que os indivíduos não praticantes de exercícios de resistência; contudo, não se evidenciam alterações no músculo cardíaco em curto prazo.

BACKGROUND We characterized and quantified peripheral nerve damage in alcohol-dependent patients (ADP) by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. METHODS Thirty-one adult patients with a history of excessive alcohol consumption and age-/sex-matched healthy controls were prospectively examined. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into ADP with alcohol-related polyneuropathy (ALN) and without ALN (Non-ALN). 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was performed using dual-echo 2-dimensional relaxometry sequences with spectral fat saturation. Detailed quantification of nerve injury by morphometric (cross-sectional area [CSA]) and microstructural MRN markers (proton spin density [ρ], apparent T2-relaxation-time [T2app ]) was conducted in all study participants. RESULTS MRN detected nerve damage in ADP with and without ALN. A proximal-to-distal gradient was identified for nerve T2-weighted (T2w)-signal and T2app in ADP, indicating a proximal predominance of nerve lesions. While all MRN markers differentiated significantly between ADP and controls, microstructural markers were able to additionally differentiate between subgroups: tibial nerve ρ at thigh level was increased in ALN (p

Introduction: The results of kidney transplants have improved dramatically in recent years, leading to reduced morbidity and mortality. Despite continuous improvements, urological complications occur at a rate of 2.6%–15%. Ureteral stenosis of graft ureters is the most common complication, with a probability of 0.5%–6.3%. This study aimed to determine the incidence of ureteral stenosis after kidney transplantation and identify risk factors that distinguish transplant patients with and without ureteral stenosis. Methods: This study retrospectively analyzed patients who had undergone kidney transplantation at the Department of Urology of the Friedrich-Alexander University Erlangen-Nuremberg between 2001 and 2015. Forty-seven patients developed ureteral stenosis during the operation. Most of the ureteral stenosis cases occurred in the first 4 months after transplantation. Kaplan-Meier analysis and the log-rank test were used to calculate the cumulative risk, and the Mann-Whitney U test was used nonparametrically. The significance level was set at p < 0.05. Results: Statistical analysis showed that residual diuresis (p = 0.008), cold ischemia time (CIT) (p = 0.040), the body mass index (p = 0.027), and donor serum creatinine value (p = 0.039) showed a significantly different distribution between recipients with or without ureteral stenosis after kidney transplantation. In multivariate Cox’s regression modeling, residual diuresis and the donor serum creatinine level were identified as the only independent predictors of patients’ stenosis-free survival. Conclusion: Urological complications not diagnosed and treated in time endanger the success of kidney transplantation. After evaluating the kidney transplantation data of the patients at the Transplant Center Erlangen-Nuremberg from 2001 to 2015, residual diuresis, CIT, the body mass index, and donor serum creatinine value were found to influence the development of ureteral stenosis.

Summary Sodium-glucose co-transporter-2 (SGLT2) inhibitors have several beneficial effects in patients with type 2 diabetes, including glucose lowering, weight loss, blood pressure lowering, and a reduced risk of major adverse cardiovascular events. To address high unmet medical need via improved glycaemic control, several clinical trials have been done to assess the efficacy and safety of SGLT2 inhibitors in combination with insulin therapy in patients with type 1 diabetes. In this Personal View, we summarise data from eight clinical trials of canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin in patients with type 1 diabetes. HbA1c-lowering efficacy was greatest at 8–12 weeks of therapy, but the magnitude of HbA1c lowering waned with longer duration of treatment (up to 52 weeks). Data are not yet available to establish for how long glycaemic efficacy could be sustained during long-term therapy in patients with type 1 diabetes. Moreover, SGLT2 inhibitor therapy induces serious adverse events, including a roughly six-times increased risk of diabetic ketoacidosis. The US Food and Drug Administration estimated that one additional case of ketoacidosis will occur for every 26 patient-years of exposure of patients with type 1 diabetes to sotagliflozin therapy. Assuming a case mortality of 0·4%, this estimate translates into 16 additional deaths per year per 100 000 patients with type 1 diabetes undergoing treatment. These considerations raise important questions about the risk-to-benefit profile of SGLT2 inhibitors when used as adjunctive therapy in patients with type 1 diabetes.

Background Free tissue transfer has become a routine procedure with low failure. In case of a compromised vascular pedicle, flap survival is time dependantly possible due to flap autonomization. However it remains unknown at what time and to which degree different factors influence flap autonomization. Methods We investigated 16 patients after free flap reconstruction at different anatomic locations who eventually presented for other medical reasons. To assess the perfusion pattern we performed Indocyanine Green angiography. Results The mean follow-up after free flap reconstruction was 58,1 month. A total of 16 flaps were examined at different anatomic locations. In 2 cases digital subtraction angiography demonstrated an occlusion of the anastomosis after arteriovenous loop despite vital flaps. Indocyanine Green angiography showed no signs of mal-perfusion or non-perfusion in the transplanted flaps and capillaries across the flap borders in 9 cases. Conclusion Flap autonomization is possible even in patients with problem wounds and poorly vascularized wound beds independent from the anatomic localization. Multiple factors exist, that influence the autonomization process over time. Indocyanine Green angiography seems to be a promising tool to visualize and study the skin perfusion pattern of free flaps over longer periods.

Die zystoskopische Weislicht- (WL-)Diagnostik von Harnblasentumoren kann durch moderne Bildgebungsmodalitaten wie der photodynamischen Diagnostik (PDD) oder dem „narrow band imaging“ (NBI) optimiert werden. Durch den Einsatz einer Multispektralbildgebung ist eine simultane Visualisierung mehrerer Modalitaten in Echtzeit moglich („real-time multispectral imaging“, rMSI). Wir erzeugten durch eine digitale Uberlagerung mehrerer Modalitaten (WL, „enhanced vascular contrast“ [EVC], Gesamtfluoreszenz, Protoporphyrin IX und Autofluoreszenz [AF]) ein multiparametrisches Endoskopiebild. Die technische Entwicklung und die nachfolgende klinische Implementierung der rMSI erforderte eine strukturierte praklinische Evaluation sowohl ex vivo als auch in vivo, bevor die Technologie bei Patienten angewendet werden kann. In dieser Ubersichtsarbeit beschreiben wir den Prozess der Testung, Validierung und ersten klinischen Anwendung der rMSI in der urologischen Endoskopie.

In Berlin sind im Jahr 2016 funf Kinderschutzambulanzen (KSA) mit der Aufgabe der elektiven und ambulanten medizinischen Abklarung bei Verdachtsfallen von Kindeswohlgefahrdungen im Rahmen eines Modellprojektes betraut worden und stehen seitdem involvierten nicht klinikgebundenen Einrichtungen des Landes Berlin wie Jugendamtern oder den Kinder- und Jugendgesundheitsdiensten mit ihrer medizinischen Kompetenz beratend zur Seite. Das Vorgehen der KSA ist vollumfanglich in die Datenschutzgesetzgebung des Landes Berlin eingebunden. Zum Ende des Modellprojektes wird die Arbeit fur die Bewertung des Modellprojektes seitens des Senates anonymisiert evaluiert werden. Eine dieser KSA ist an der Klinik fur Kinder- und Jugendmedizin des Klinikums Neukolln angesiedelt. Dargestellt werden die Ergebnisse der KSA in Neukolln des Jahres 2017 unter Auflistung der Einweisergruppen, der Vorstellungsgrunde und der abschliesenden Wertung. Im Jahr 2017 wurden 145 Kinder in der KSA vorgestellt, grostenteils von offentlichen Zuweisern oder aus der Kinderklinik selbst zur vertieften Abklarung bei zuvor unklaren, aber nicht akut bedrohlichen Konstellationen. In 67 Fallen lag tatsachlich eine Kindeswohlgefahrdung vor; bei 34 Kindern lag keine Kindeswohlgefahrdung vor: Somit konnte in 70 % der Vorstellungen eine eindeutige Einschatzung erreicht werden. Bei 40 Patienten konnte eine Kindeswohlgefahrdung nicht ausgeschlossen werden; in 4 Fallen konnte keine vertiefte Diagnostik stattfinden. Neben der Padiatrie und der Kinderchirurgie war die Kinder- und Jugendpsychiatrie das am haufigsten involvierte Fachgebiet. In der KSA-Arbeit konnte eine intensivierte Zusammenarbeit mit den offentlichen Einrichtungen etabliert werden. Die KSA hat sich als ein sehr taugliches Instrument in der Klarung moglicher Kindeswohlgefahrdungen erwiesen, die in der engen Kooperation mit den offentlichen Einrichtungen geeignet ist, diese mit medizinisch fundierten Befunden in der Entscheidungsfindung zu unterstutzen.

Objective We conducted a prospective evaluation of microperfusion parameters after tibial bypass surgery was performed. Differences between grafts with occlusions during follow-up and patent grafts were analyzed in relation to the pedal arch quality. Methods Patients receiving tibial bypass grafts for chronic limb-threatening ischemia from 2019 to 2020 were included. Assessment of microcirculation (parameters: hemoglobin oxygen saturation [sO2] and flow) was done by laser Doppler flowmetry and white light spectrometry (oxygen-to-see), supine and in elevation, whereas the macrocirculation was evaluated by the ankle-brachial index and duplex ultrasound examination. The quality of run-off was graded for each patient. Measurements were performed preoperatively, 1 day postoperatively, and after 6 months. Patients with graft occlusions during follow-up (OCCLUDED) and patients without occlusions (OPEN) were compared. Results We included 42 patients (13 women, 29 men; mean age, 76.1 years; range, 60-89 years) were included. The patency of all grafts 1 day after the operation was confirmed by ultrasound examination. The overall analysis of the microcirculation showed significant changes in both the supine and elevated leg position between measurements taken preoperatively, 1 day after the operation, and after 6 months for the parameters sO2 and FLOW (sO2 supine, P = .001; sO2 elevated, P Conclusions Significantly poorer microperfusion was detected postoperatively in patients with later occurrence of graft occlusions despite patent grafts on the first postoperative day. Microperfusion measurements might be a possible tool for the prediction of graft failure.

Objectives Respiratory failure is the major cause of death in coronavirus disease 2019 (COVID-19). Autopsy-based reports describe diffuse alveolar damage (DAD), organizing pneumonia, and fibrotic change, but data on early pathologic changes and during progression of the disease are rare. Methods We prospectively enrolled three patients with COVID-19 and performed full clinical evaluation, including high-resolution computed tomography. We took transbronchial biopsy (TBB) specimens at different time points and autopsy tissue samples for histopathologic and ultrastructural evaluation after the patients’ death. Results Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed by reverse transcription polymerase chain reaction and/or fluorescence in situ hybridization in all TBBs. Lung histology showed reactive pneumocytes and capillary congestion in one patient who died shortly after hospital admission with detectable virus in one of two lung autopsy samples. SARS-CoV-2 was detected in two of two autopsy samples from another patient with a fulminant course and very short latency between biopsy and autopsy, showing widespread organizing DAD. In a third patient with a prolonged course, autopsy samples showed extensive fibrosis without detectable virus. Conclusions We report the course of COVID-19 in paired biopsy specimens and autopsies, illustrating vascular, organizing, and fibrotic patterns of COVID-19–induced lung injury. Our results suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.

BackgroundAcute respiratory distress syndrome (ARDS) is the major cause of death in coronavirus disease 2019 (COVID-19). Multiple autopsy-based reports of COVID-19 lung pathology describe diffuse alveolar damage (DAD), organizing pneumonia (OP) and fibrotic change, but data on early pathological changes as well as during progression of the disease are rare.Research questionComparison of histopathological and ultrastructural findings in paired transbronchial biopsies (TBBs) and autopsy material from three patients with confirmed SARS-CoV-2-infection.MethodsWe prospectively enrolled 3 patients with confirmed SARS-CoV-2 infection. Full clinical evaluation was performed including high-resolution computed tomography (HR-CT). We took TBBs at different time points during the disease and autopsy tissue samples after the patients’ death.ResultsSARS-CoV-2 was detected by RT-PCR and/or FISH in all TBBs. Lung histology revealed pneumocyte hyperplasia and capillary congestion in one patient who died short after hospital admission with detectable virus in 1/2 autopsy samples from the lung. SARS-CoV-2 was detected in 2/2 autopsy samples from a patient with a fulminant course of the disease and very short latency between biopsy and autopsy, both showing widespread DAD. In a third patient with a prolonged course, i.e. five weeks of ICU treatment with ECMO, autopsy samples showed extensive interstitial fibrosis without detectable virus by RT-PCR and/or FISH.InterpretationWe report the course of COVID-19 in paired TBB and autopsy samples from three patients at an early stage, in rapidly progressive and in a prolonged disease course. Our findings illustrate vascular, organizing and fibrotic patterns of COVID-19-induced lung injury and suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.

Zusammenfassung Einleitung Der Einfluss einer SARS-CoV-2-Infektion auf chronisch entzündliche Darmerkrankungen (CED) ist bislang nicht gut charakterisiert, und es ist unklar, ob diese eine Anpassung der immunsuppressiven Therapie erfordert. Methodik Für die retrospektive Dokumentation klinischer Parameter und Veränderungen einer immunsuppressiven Therapie von mit SARS-CoV-2 infizierten CED-Patienten wurde ein nationales Melderegister etabliert. Ergebnisse Insgesamt wurden nur 3 von 185 CED-Patienten (1,6 %) wegen abdomineller Symptome auf eine SARS-CoV-2-Infektion getestet. Im COVID-19-Krankheitsverlauf entwickelten 43,5 % Durchfall, abdominelle Schmerzen oder Hämatochezie (Hospitalisierungsrisiko mit vs. ohne abdominelle Symptome: 20,0 % vs. 10,6 %, p Diskussion Bei mit SARS-CoV-2 infizierten CED-Patienten traten häufig neue abdominelle Symptome bei Infektion auf. Diese führten aber nur selten zur SARS-CoV-2-Testung. Eine hohe CED-Aktivität zum Zeitpunkt des SARS-CoV-2-Nachweises war mit einem erhöhten Hospitalisierungsrisiko assoziiert.

The serotonin transporter (5-HTT) is a key molecule of serotoninergic neurotransmission and target of many anxiolytics and antidepressants. In humans, 5-HTT gene variants resulting in lower expression levels are associated with behavioral traits of anxiety. Furthermore, functional magnetic resonance imaging (fMRI) studies reported increased cerebral blood flow (CBF) during resting state (RS) and amygdala hyperreactivity. 5-HTT deficient mice as an established animal model for anxiety disorders seem to be well suited for investigating amygdala (re-)activity in an fMRI study. We investigated wildtype (5-HTT+/+), heterozygous (5-HTT+/-), and homozygous 5-HTT-knockout mice (5-HTT-/-) of both sexes in an ultra-high-field 17.6 Tesla magnetic resonance scanner. CBF was measured with continuous arterial spin labeling during RS, stimulation state (SS; with odor of rats as aversive stimulus), and post-stimulation state (PS). Subsequently, post mortem c-Fos immunohistochemistry elucidated neural activation on cellular level. The results showed that in reaction to the aversive odor CBF in total brain and amygdala of all mice significantly increased. In male 5-HTT+/+ mice amygdala RS CBF levels were found to be significantly lower than in 5-HTT+/- mice. From RS to SS 5-HTT+/+ amygdala perfusion significantly increased compared to both 5-HTT+/- and 5-HTT-/- mice. Perfusion level changes of male mice correlated with the density of c-Fos-immunoreactive cells in the amygdaloid nuclei. In female mice the perfusion was not modulated by the 5-Htt-genotype, but by estrous cycle stages. We conclude that amygdala reactivity is modulated by the 5-Htt genotype in males. In females, gonadal hormones have an impact which might have obscured genotype effects. Furthermore, our results demonstrate experimental support for the tonic model of 5-HTTLPR function.

Background Even though tumours are considered to occur frequently in pet hamsters, there is only a small number of scientific reports in current literature. Methods Pathological reports from 177 hamsters were evaluated. Results Of these, 78 were male and 75 were female. Median age of affected hamsters was 12 months (range 2-34). Integumental tumours were the most common neoplasms (62%, 109/177). As far as species was known, the number of Syrian hamsters (52%, 30/58) affected by tumours seemed to be lower than the number of affected dwarf hamsters (85%, 47/55). Tumours of the hematopoietic system were the second most frequently neoplasms (17%, 30/177). Relative number of neoplasms of the endocrine system, tumours of the digestive system (1.7%, 3/177) and other tumours (4%, 7/177 each) was low. The majority of integumental tumours were epithelial (66%; 91/126). Conclusion This study aimed to analyze data from veterinary surgeries and pathological institutes about the occurrence of spontaneous tumours in Syrian hamsters and dwarf hamsters to give information about the frequency of tumours, prognosis and survival time. This is the first study about tumours in pet hamsters in Germany so far.

Context Lipodystrophy syndromes cause hypertriglyceridemia that improves with leptin treatment using metreleptin. Mechanisms causing hypertriglyceridemia and improvements after metreleptin are incompletely understood. Objective Determine relationship of circulating lipoprotein lipase (LPL) modulators with hypertriglyceridemia in healthy controls and in patients with lipodystrophy before and after metreleptin. Methods Cross-sectional comparison of patients with lipodystrophy (generalized lipodystrophy n = 3; partial lipodystrophy n = 11) vs age/sex-matched healthy controls (n = 28), and longitudinal analyses in patients before and after 2 weeks and 6 months of metreleptin. The study was carried out at the National Institutes of Health, Bethesda, Maryland. Outcomes were LPL stimulators apolipoprotein (apo) C-II and apoA-V and inhibitors apoC-III and angiopoietin-like proteins (ANGPTLs) 3, 4, and 8; ex vivo activation of LPL by plasma. Results Patients with lipodystrophy were hypertriglyceridemic and had higher levels of all LPL stimulators and inhibitors vs controls except for ANGPTL4, with >300-fold higher ANGPTL8, 4-fold higher apoC-III, 3.5-fold higher apoC-II, 1.9-fold higher apoA-V, 1.6-fold higher ANGPTL3 (P < .05 for all). At baseline, all LPL modulators except ANGPLT4 positively correlated with triglycerides. Metreleptin decreased apoC-II and apoC-III after 2 weeks and 6 months, and decreased ANGPTL8 after 6 months (P < 0.05 for all). Plasma from patients with lipodystrophy caused higher ex vivo LPL activation vs hypertriglyceridemic control plasma (P < .0001), which did not change after metreleptin. Conclusion Elevations in LPL inhibitors apoC-III and ANGPTL8 may contribute to hypertriglyceridemia in lipodystrophy, and may mediate reductions in circulating and hepatic triglycerides after metreleptin. These therefore are strong candidates for therapies to lower triglycerides in these patients.

ZusammenfassungHintergrundEs gibt Hinweise auf geschlechterspezifische Unterschiede bei der Entwicklung, Diagnostik und Behandlung der symptomatischen peripheren arteriellen Verschlusskrankheit (PAVK). Obwohl Frauen in der Literatur etwa 50 % der behandelten Kohorten ausmachen, ist deren Anteil in kontrollierten randomisierten Studien zur PAVK gering. Leitlinien enthalten bisher kaum geschlechtersensitive Empfehlungen, und die Ergebnisse retrospektiver Beobachtungsstudien widersprechen sich. Diese systematische Literaturrecherche soll verfügbare Beobachtungsstudien zu Geschlechterunterschieden bei der endovaskulären Behandlung der symptomatischen PAVK identifizieren.Material und MethodenEs wurde eine systematische Literaturanalyse auf der Basis einer PubMed-Recherche mit dem Schwerpunkt auf retrospektive Beobachtungsstudien zum Vergleich der Behandlungsergebnisse zwischen Männern und Frauen durchgeführt.ErgebnisseInsgesamt konnten 37 Publikationen identifiziert werden, die eine Kohorte von 5.489.558 Patientinnen und Patienten (40,3 % Frauen) beschreiben. Fünf Studien nutzten Propensity Score Matching zur Kontrolle von Störfaktoren. In 23 Studien wurden Behandlungsergebnisse nach der Dauer des Krankenhausaufenthalts bzw. nach 30 Tagen berichtet. Während 10 Studien einen Behandlungsnachteil bei Frauen identifizieren konnten, berichteten 6 Studien über einen Behandlungsnachteil bei Männern. Die weiteren 21 Studien konnten keine eindeutigen Unterschiede zeigen.SchlussfolgerungenDie verfügbare Real-World-Evidenz lässt aufgrund der methodischen Limitationen der eingeschlossenen Studien und deren unzureichender Vergleichbarkeit keine eindeutige Aussage zu geschlechterspezifischen Unterschieden bei der endovaskulären Behandlung der PAVK zu.

Background and Objectives: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and lung manifestations of connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory-failure. Methods: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence (IIF) and immunoblot (IB). Fifteen COVID-19 patients underwent high-resolution computed tomography (HR-CT). Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from disease. ANA titers ≥1:320 and/or positive ENA immunoblot were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p=0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p=0.039). Detection of AABs was significantly associated with a need for intensive care (ICU) treatment (83.3% vs. 10%; p=0.002) and occurrence of severe complications (75% vs. 20%, p=0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation and deposition of collagen fibrils. Conclusions: We are the first to report overlapping clinical, serological and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.

Diabetic neuropathy (DPN) is one of the most severe and yet most poorly understood complications of diabetes mellitus. In vivo imaging of dorsal root ganglia (DRG), a key structure for the understanding of DPN, has been restricted to animal studies. These have shown a correlation of decreased DRG volume with neuropathic symptom severity. Our objective was to investigate correlations of DRG morphology and signal characteristics at 3 Tesla (3T) magnetic resonance neurography (MRN) with clinical and serological data in diabetic patients with and without DPN. In this cross-sectional study, participants underwent 3T MRN of both L5 DRG using an isotropic 3D T2-weighted, fat-suppressed sequence with subsequent segmentation of DRG volume and analysis of normalized signal properties. Overall, 55 diabetes patients (66 ± 9 years; 32 men; 30 with DPN) took part in this study. DRG volume was smaller in patients with severe DPN when compared to patients with mild or moderate DPN (134.7 ± 21.86 vs 170.1 ± 49.22; p = 0.040). In DPN patients, DRG volume was negatively correlated with the neuropathy disability score (r = −0.43; 95%CI = −0.66 to −0.14; p = 0.02), a measure of neuropathy severity. DRG volume showed negative correlations with triglycerides (r = −0.40; 95%CI = −0.57 to −0.19; p = 0.006), and LDL cholesterol (r = −0.33; 95%CI = −0.51 to −0.11; p = 0.04). There was a strong positive correlation of normalized MR signal intensity (SI) with the neuropathy symptom score in the subgroup of patients with painful DPN (r = 0.80; 95%CI = 0.46 to 0.93; p = 0.005). DRG SI was positively correlated with HbA1c levels (r = 0.30; 95%CI = 0.09 to 0.50; p = 0.03) and the triglyceride/HDL ratio (r = 0.40; 95%CI = 0.19 to 0.57; p = 0.007). In this first in vivo study, we found DRG morphological degeneration and signal increase in correlation with neuropathy severity. This elucidates the potential importance of MR-based DRG assessments in studying structural and functional changes in DPN.

Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic β-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.

IntroductionCompression therapy is highly effective in the treatment of many venous diseases, including leg edema. However, its relevance in patients with peripheral arterial disease (PAD) or diabetes mellitus is critically discussed. The aim of the present study was to assess the influence of compression therapy on microperfusion and its safety in patients with PAD or diabetes mellitus.Research design and methodsA prospective analysis of 94 consecutive patients (44 patients with diabetes, 45 patients with PAD and 5 healthy controls) undergoing medical compression therapy was performed. Microperfusion was assessed by a combined method of white light tissue spectrometry and laser Doppler flowmetry under medical compression therapy (classes I and II), in different body positions (supine, sitting, standing and elevated position of the leg) and at different locations (great toe, lateral ankle and calf).ResultsDuring the entire study, no compression-related adverse events occurred. Evaluation of microcirculation parameters (oxygen saturation of hemoglobin and flow) at the different locations and in sitting and standing positions (patients with diabetes and PAD) under compression therapy classes I and II revealed no tendency for reduced microperfusion in both groups. In contrast, in the elevated leg position, all mean perfusion values decreased in the PAD and diabetes groups. However, the same effect was seen in the healthy subgroup.ConclusionsIn consideration of the present inclusion criteria, use of medical compression stockings is safe and feasible in patients with diabetes or PAD. This study did not find relevant impairment of microperfusion parameters under compression therapy in these patient subgroups in physiologic body positions.Trial registration numberNCT03384758.

Background Limited data on the prevalence and medical care of sickle cell disease (SCD) in Germany are available. Here, we make use of a patient registry to characterize the burden of disease and the treatment modalities for patients with SCD in Germany. Procedure A nationwide German registry for patients with SCD documents basic data on diagnosis and patient history retrospectively at the time of registration. A prospective annual documentation provides more details on complications and treatment of SCD. For the current analyses, data of 439 patients were available. Results Most patients had homozygous SCD (HbSS 75.1%, HbS/�����thalassemia 13.2%, and HbSC 11.3%). The median age at diagnosis was 1.9 years (interquartile range, 0.6���4.4 years), most patients were diagnosed when characteristic symptoms occurred. Sepsis and stroke had affected 3.2% and 4.2% of patients, respectively. During the first year of observation, 48.3% of patients were admitted to a hospital and 10.1% required intensive care. Prophylactic penicillin was prescribed to 95.6% of patients with homozygous SCD or HbS/�� thalassemia below the age of six and hydroxycarbamide to 90.4% of patients above the age of two years. At least one annual transcranial Doppler ultrasound was documented for 74.8% of patients between 2 and 18 years. Conclusion With an estimated number of at least 2000, the prevalence of SCD in Germany remains low. Prospectively, we expect that the quality of care for children with SCD will be further improved by an earlier diagnosis after the anticipated introduction of a newborn screening program for SCD., publishedVersion

Background During the past decades, the use of vascular closure devices (VCDs) has been established due to the increasing number of interventions. Of particular concern is the perceived risk of VCDs for development of implant-induced vascular major complications. Therefore, the aim of this analysis was to report the variety of vascular access side complications after the use of VCDs, and to analyze the referred risk factors. Methods All cases of vascular complications associated with VCD use requiring surgical repair from 2010 to 2016 were retrospectively analyzed in a single center trial. Systemic and local complications, risk factors as pre-existing diseases and their influence on the surgical outcome were evaluated. Results A total of 46 individuals were included in this study (male/female: 16/30). The total number of interventions in the involved departments of the study center during the same period was 9754 Therefore the complication rate after VCD implantation was 0.47%. The detected complications ranged from symptomatic claudication (N.=24) to acute leg ischemia (N.=19) and major bleeding (N.=3). Surgical reconstruction was performed by direct suture (N.=4), transverse arteriotomy with thrombectomy (N.=2), endarterectomy with patchplasty (N.=35), inguinal graft interposition or bypass (N.=3) and primary major amputation (N.=2). In regard to the risk factors, the study has concluded that atherosclerosis, female gender and diabetes mellitus are correlated with major vascular complications (bleeding and limb ischemia). However, in cases with therapeutic anticoagulation the rate of major bleeding was significantly elevated (P=0.028). Conclusions Reported complication rates associated with femoral VCD implantation are low. However, in some cases VCD implantation may account for severe complications including limb losses. Therefore, an adequate patient selection is necessary to detect those cases at higher risk for complications.

The real impact of specific sites of metastasis on prognosis of metastatic pancreatic cancer (MPC) is unknown. To evaluate the association of specific metastatic sites and survival outcomes in MPC a systematic literature review was performed including prospective randomized trials of systemic treatments in metastatic pancreatic cancer indexed in PubMed, Embase and Web of Science. Data regarding systemic treatment regimens, progression free survival and overall survival were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Of 1,052 abstracts, 7 randomized trials were considered eligible with a combined sample size of 2,975 MPC patients. Combining the studies with meta-analysis, we could see that patients with liver metastasis had a HR for death of 1.53 with 95% CI of 1.15 to 2.02 (p-value 0.003) and HR for risk of progression of 1.96 with 95% CI of 1.28 to 2.99 (p-value 0.002), without significant heterogeneity. Having two or more sites of metastasis comparing to one site did not have impact on overall survival; RR of 1.05 with 95% CI 0.91 to 1.23 (p-value 0.493). In conclusion, liver metastasis confers worse outcomes among patients with MPC. Apparently, multiple metastatic sites do not present worse prognosis when compared with only one organ involved, therefore, demonstrating the severity of this disease. Prospective studies evaluating other treatments are necessary to address the impact of local treatments in liver metastasis in MPC.

Summary: Background: Morbidity, lesion pattern, management and short-term outcomes of civilian vascular trauma are rarely evaluated. Therefore, analysis of in hospital results in patients with non-iatrogenic vascular trauma in a tertiary referral hospital was performed. Patients and methods: Retrospective evaluation of patients with vascular trauma from 2007–2017 was done. 48 patients (34 male, 14 females, mean age 56 years) were included. Excluded were patients with iatrogenic vascular complications. Major cause of vascular trauma were traffic accidents in 43.8 %, fall from great heights in 27.1 %, sport and home related injuries in 16.8 %, suicidal injuries in 4.2 % and gunshot wounds in 2.1 % (other 6.3 %). 60.4 % of patients presented with blunt, 39.6 % of patients with penetrating vascular trauma. More than half of the cases included polytraumatized patients (54.4 %). Results: Most commonly affected were the popliteal (25.0 %) and the axillar artery (18.8 %). Aortic injuries were present in 14.6 % of cases, whereas the femoral and subclavian artery were involved in 12.6 % and 10.4 %. Vascular reconstruction was performed by interposition graft in 45.9 %, direct suture in 18.8 %, patchplasty in 10.4 %, ligation in 12.4 %, and implantation of stentgraft in 12.5 %. Postoperative complication rate was 54.2 %. Rate of in-hospital major amputation was 14.6 % and in-hospital mortality was 14.6 % as well. Comparison between blunt and penetrating trauma as to postoperative complication (p = 0.322), blood transfusion (p = 0.452) and amputation (p = 0.304) showed no significant differences, whereas lethality in blunt trauma was 20.6 % vs. 5.2 % in penetrating trauma. Injury severity score (ISS) was significantly elevated for blunt trauma patients (mean ISS Score blunt 32 vs 21 penetrating, p = 0.043). Conclusions: The majority of vascular lesions is caused by blunt trauma. Blunt lesions do also show a severe injury pattern, compared to penetrating trauma, and the complication rate remains high. However, by means of vascular reconstruction, limb salvage is feasible in a high percentage of cases.