The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

Treatment of end-stage peripheral artery disease by neuromodulation.

BACKGROUND: Neuromodulation is a therapeutic option to improve limb salvage in end-stage peripheral arterial disease (PAD), but there is no consensus on its indication for spinal cord stimulation (SCS) in PAD patients. OBJECTIVE: The aim of this study was to present the outcome of end-stage PAD patients treated with SCS. METHODS: This study is a retrospective analysis based on a local prospective registry. Neuromodulation was performed if there was: 1) no revascularisation option, 2) no septicemia, 3) and Rutherford stage 4-6. The primary endpoint of the study was limb salvage. Secondary endpoints were reduction in pain or simply pain reduction pain (assessed using a visual anlog scale/VAS) and improvement in walking distance. RESULTS: Limb salvage was reached in 30/34 patients (88%). Patients reported a significant reduction in pain on the 10-point VAS scale from baseline (median = 7.5, IQR = 7-8) to follow-up at 2 years (median = 0, IQR 0-2.75), p < 0.001. Walking distance also improved from preoperative (median = 50 m, IQR = 20-50 m) to follow-up at 2 years (median = 150 m, IQR 50-272 m), p < 0.001. RESULTS: SCS implantation in patients with end-stage PAD can enable limb salvage in a high percentage of cases and increase mobility due to pain reduction. The role of microcirculation in these improvements needs to be investigated in further studies.

Mid-Term Outcomes of a Hybrid Approach Involving Open Surgery Plus TEVAR of the Descending Aorta in the Treatment of Complex Type A Dissection.

OBJECTIVES: Type A aortic dissection with true lumen collapse and malperfusion downstream is associated with a devastating prognosis. This study compares the clinical outcomes of two operative strategies for this disease: hybrid approach of ascending aorta (and hemiarch replacement) supplemented with retrograde stenting of the descending aorta (thoracic endovascular aortic repair [TEVAR]) and standard ascending aorta (and hemiarch) replacement without stent placement. METHODS: From January 1, 2016 to December 31, 2019, 81 patients with type A aortic dissection were studied. The hybrid technique was applied in 30 patients (group 1), while 51 patients received standard surgical repair (group 2). Patient demographics, clinical and operative findings, postoperative outcome, follow-up interventions, and mid-term survival were analyzed. RESULTS: Baseline characteristics were similar among the groups, except that more preoperative malperfusion was evident in group 1. The postoperative incidence of visceral malperfusion (0 vs. 15.7%, p = 0.02) and low cardiac output syndrome requiring extracorporeal membrane oxygenation support (3.3 vs. 19.6%, p = 0.04) was significantly less in group 1. In-hospital mortality was also significantly lower in group 1 as in group 2 (13.3 vs. 33.3%, p = 0.04). At follow-up, the need for secondary endovascular stenting (3.3 vs. 7.8%, p = 0.65) and surgical aortic reintervention (6.7 vs. 2.0%, p = 0.55) was comparable. One-year, 2-year, and 3-year survival rates were 83.3, 83.3, and 62.5% in group 1, and 58.7, 58.7, and 52.6% in group 2 (p = 0.05), respectively. CONCLUSION: The combination of open surgical replacement of the ascending aorta (and hemiarch) with TEVAR of the descending aorta for true lumen compromise is a feasible treatment option for patients with type A aortic dissection and is associated with a better perioperative outcome and improved mid-term survival rate.

Consensus nomenclature for dyneins and associated assembly factors.

Dyneins are highly complex, multicomponent, microtubule-based molecular motors. These enzymes are responsible for numerous motile behaviors in cytoplasm, mediate retrograde intraflagellar transport (IFT), and power ciliary and flagellar motility. Variants in multiple genes encoding dyneins, outer dynein arm (ODA) docking complex subunits, and cytoplasmic factors involved in axonemal dynein preassembly (DNAAFs) are associated with human ciliopathies and are of clinical interest. Therefore, clear communication within this field is particularly important. Standardizing gene nomenclature, and basing it on orthology where possible, facilitates discussion and genetic comparison across species. Here, we discuss how the human gene nomenclature for dyneins, ODA docking complex subunits, and DNAAFs has been updated to be more functionally informative and consistent with that of the unicellular green alga Chlamydomonas reinhardtii, a key model organism for studying dyneins and ciliary function. We also detail additional nomenclature updates for vertebrate-specific genes that encode dynein chains and other proteins involved in dynein complex assembly.

Role of aorto(bi)femoral bypass in treatment of patients with critical limb threatening ischemia.

PURPOSE: To analyse the long-term outcome of open aortic procedures in patients with critical limb threatening ischemia. METHODS: Retrospective analysis of all patients with aortoiliac TransAtlantic Inter-Society Consensus II (TASC II), type D (TASC D) lesions extending to the femoral artery who underwent aortic bypass procedures for critical limb threatening ischemia (CLTI) or intermittent claudication (IC). RESULTS: Over a period of 10 years, 87 patients with IC and 45 patients with CLTI received a total of 56 aortounifemoral and 76 aorto-bi-femoral bypass procedures. After 7 years, overall primary patency (82.2% [CLTI] vs. 80.5% [IC], p = .918) and overall secondary patency (88.9% [CLTI] vs. 88.5% [IC], p = .851) were similar between patients with CLTI and those with IC. Long-term-survival (66.7% vs. 71.3%, p = .356) as well as limb salvage (86.7% vs. 94.3%, p = .104) was considerably lower in the CLTI-group, but the difference was not statistically significant. In the subgroup analysis, patients with CLTI and ischemic lesions (Rutherford class 5-6) had the poorest outcome after 84 months, in terms of secondary patency (92.1% vs. 73.7%, p = .015), limb salvage (97.4% vs. 73.7%, p = .000), and long-term survival (75.0% vs. 26.3%, p = .000) compared to patients with IC. Multivariate analysis revealed significant associations for patients with Rutherford class 5-6 in terms of secondary patency (p = .037) and limb salvage (p = .015). There was a significant difference in primary patency between graft limbs with superficial femoral artery occlusion and graft limbs with patent superficial femoral artery (84.6% vs. 93.0%, p = .017). CONCLUSIONS: Aortic bypass procedures can be used in the treatment of patients with CLTI. Moreover, results are satisfactory in patients with ischemic rest pain. However, less invasive treatments should be considered for patients with ischemic lesions.

Kidney Failure After Occlusion of Accessory Renal Arteries in Endovascular Abdominal Aneurysm Repair.

PURPOSE: To evaluate the incidence of acute renal failure and chronic kidney disease due to occlusion of accessory renal arteries during endovascular aneurysm repair of infrarenal abdominal aortic aneurysm. MATERIAL AND METHODS: We retrospectively reviewed the course of 181 patients (mean age, 71, SD ± 9  years) who underwent EVAR of infrarenal abdominal aortic aneurysm. The renal vessel anatomy was analyzed in all pre- and postoperative CT scans. Diameter and origin of accessory renal arteries were evaluated. Renal function was determined by pre- and postoperative serum creatinine and eGFR levels. Long-term follow-up (>3 months) of patients was available in 121 cases (66.9%). Acute kidney injury and chronic kidney failure were defined according to guidelines of "Kidney Disease: Improving Global Outcomes" (KDIGO). RESULTS: In 65 of 181 patients (33.9%), 82 accessory renal arteries were identified preoperatively. In 19 of 181 patients (10.5%), one or more accessory renal arteries were covered and subsequently occluded by the implanted stent-graft device. Neither acute kidney injury (10.3% vs 12.5%; p = .785) nor chronic kidney disease (10.7% vs 15.38%; p = .452) was detected significantly more often in patients with covered accessory renal artery. The only significant predictor of acute kidney injury was the preoperative serum creatinine level (1.12 mg/dl vs. 0.98 mg/dl; p = .03). Significant predictors for chronic kidney disease were preoperative serum creatinine, eGFR, and impaired renal function (p < .001). CONCLUSION: Coverage of accessory renal artery due to stent-graft does not lead either to temporary acute kidney injury after endovascular aneurysm repair or to chronic kidney disease. LEVEL OF EVIDENCE: Level II b.

Biosynthetic vascular graft: a valuable alternative to traditional replacement materials for treatment of prosthetic aortic graft infection?

BACKGROUND AND AIMS: To report the experience of a tertiary vascular surgery center using Omniflow II® biosynthetic vascular grafts for treatment of prosthetic aortic graft infection. MATERIALS AND METHODS: Retrospective analysis of all patients with prosthetic graft infections who underwent in situ aortic reconstruction using Omniflow II® grafts or other conduits between March 2015 and May 2017. Early and late mortality, perioperative complications, and reinfection rate were analyzed. RESULTS: Sixteen patients (14 males, median age 68.5, range 57-89) with prosthetic aortic graft infection were treated at our center. Eight patients received an Omniflow II® biosynthetic graft, two patients silver-triclosan coated grafts, three patients bovine pericardial tube grafts, and three patients composite bovine pericardial tube grafts with Omniflow II® graft extensions. Perioperative complications occurred in seven patients (43.8%). Early mortality rate was 18.7% (n = 3). In addition, four patients died during follow-up after a median of 11 months (range 0-34 months). We did not observe any reinfections. Bypass grafts were patent in all patients. No major limb amputations were performed during follow-up. CONCLUSION: Treatment of prosthetic aortic graft infection with Omniflow II® vascular grafts is feasible. Graft material seems to have an excellent resistance to infection and might be a valuable alternative to traditional replacement materials. Especially long-term durability has to be continuously monitored and documented.

Equine parasite control and the role of national legislation - A multinational questionnaire survey.

Experts recommend a change in the control of equine parasites across the world in order to adopt a surveillance-based approach utilizing parasite faecal egg counts (FEC). Several European countries have implemented prescription-only restrictions of anthelmintic usage by law, which is in stark contrast to US, where all anthelmintic products continue to be available over the counter. This study aimed to describe and compare equine parasite control strategies employed in Germany, Austria, the Netherlands, US, and Denmark. An invitation to participate in an online questionnaire survey was published on a large equine news website in each of the participating countries. The main focus of the study was on usage of FEC and anthelmintic treatment intensity in three different equine age groups; foals, 1-3 year-olds and >3 years old. A total of 3092 respondents participated in the study. Danish respondents used significantly more faecal analyses in their parasite control strategies than participants from the other four countries (p < 0.0001). Similarly, Danish participants administered significantly fewer anthelmintic treatments per horse per year (p < 0.0001) independent of the age of the horse, and had been using a selective treatment strategy for a significantly longer time period than their counterparts in other countries (p < 0.0001). Only minor differences were found between respondents from the other four countries. This is remarkable as both Austria and Germany have had prescription-only restrictions for 3-4 decades. Yet, their parasite control strategies were more similar to those employed by American respondents. The Netherlands had only recently introduced prescription-only restrictions by the time this survey was conducted which can explain why Dutch respondents were also similar to their American counterparts. Taken together, this study illustrates substantially different worm control strategies practiced in Denmark, and this difference cannot be explained by legislation alone.

Granulocytic anaplasmosis in 63 dogs: clinical signs, laboratory results, therapy and course of disease.

OBJECTIVES: To describe the clinical signs, laboratory results, therapy and course of disease in dogs with canine granulocytic anaplasmosis in which co-infections had been excluded. METHODS: Medical records of dogs naturally infected with Anaplasma phagocytophilum were retrospectively evaluated with regard to clinical signs and laboratory abnormalities at the time of presentation, therapy and course of disease. RESULTS: Nine hundred and seventy-four dogs with clinical signs suspicious for canine granulocytic anaplasmosis were tested for A. phagocytophilum DNA by modified real-time PCR; 72 dogs had a positive result. Nine of the positive dogs were excluded from further evaluation due to other diseases or lack of data. The most common clinical signs in the 63 A. phagocytophilum-positive dogs included in the study were lethargy and reduced activity (83%), fever (67%) and inappetence (63%). Thrombocytopenia was the most common laboratory abnormality (86%), followed by increased liver enzyme activities and hyperbilirubinaemia (77%), anaemia (70%), hypoalbuminaemia (62%) and leucocytosis (27%). Of 36 thrombocytopenic dogs tested for platelet-bound antibodies, 44% were positive. Of the 63 infected dogs, 59 (97%) recovered, two dogs died (epileptic seizures and immune-mediated haemolytic anaemia) and two were lost to follow-up. CLINICAL SIGNIFICANCE: In areas where it is endemic, canine granulocytic anaplasmosis should be considered as a potential cause of acute nonspecific clinical signs or immune-mediated disease if tick exposure cannot be excluded.

Detection of Strongylus vulgaris in equine faecal samples by real-time PCR and larval culture - method comparison and occurrence assessment.

BACKGROUND: Strongylus vulgaris has become a rare parasite in Germany during the past 50 years due to the practice of frequent prophylactic anthelmintic therapy. To date, the emerging development of resistance in Cyathostominae and Parascaris spp. to numerous equine anthelmintics has changed deworming management and the frequency of anthelmintic usage. In this regard, reliable detection of parasitic infections, especially of the highly pathogenic S. vulgaris is essential. In the current study, two diagnostic methods for the detection of infections with S. vulgaris were compared and information on the occurrence of this parasite in German horses was gained. For this purpose, faecal samples of 501 horses were screened for S. vulgaris with real-time PCR and an additional larval culture was performed in samples of 278 horses. A subset of 26 horses underwent multiple follow-up examinations with both methods in order to evaluate both the persistence of S. vulgaris infections and the reproducibility of each diagnostic method. RESULTS: The real-time PCR revealed S. vulgaris-DNA in ten of 501 investigated equine samples (1.9%). The larval culture demonstrated larvae of S. vulgaris in three of the 278 samples (1.1%). A direct comparison of the two methods was possible in 321 samples including 43 follow-up examinations with the result of 11 S. vulgaris-positive samples by real-time PCR and 4 S. vulgaris-positive samples by larval culture. The McNemar's test (p-value = 0.016) revealed a significant difference and the kappa values (0.525) showed a moderate agreement between real-time PCR and larval culture. CONCLUSIONS: The real-time PCR detected a significantly higher proportion of positives of S. vulgaris compared to larval culture and should thus be considered as a routine diagnostic method for the detection of S. vulgaris in equine samples.

Trends in health surveillance and joint service delivery for pastoralists in West and Central Africa.

In most sub-Saharan African countries, pastoralism represents an important economic resource and contributes significantly to national growth; however, challenges remain, particularly in providing social services to pastoralists (especially health and education) and in avoiding conflict with local sedentary communities and local authorities. All of this takes place while pastoralists try to maintain their mobile lifestyle within a rapidly changing ecosystem. Transdisciplinary approaches, such as 'One Health', which covers both human and animal health, have proven effective in delivering services and reaching mobile pastoralists in remote areas. The pastoralist way of life could be described as being linked to both their livestock and their environment, which makes social science an important element when researching the delivery and adaptation of social services to pastoralists. Early or pre-diagnostic detection of emerging and endemic infectious disease remains a vital aspect of health surveillance targeted at preventing further transmission and spread. Community-based syndromic surveillance, coupled with visual mobile phone technology, adapted to the high levels of illiteracy among nomads, could offer an alternative to existing health surveillance systems. Such an approach could contribute to accelerated reporting, which could in turn lead to targeted intervention among mobile pastoralists in sub-Saharan Africa. Although considerable efforts have been made towards integrating mobile pastoralists into social services, obstacles remain to the adoption of a clear, specific and sustainable policy on pastoralism in sub-Saharan Africa.

Bien que le pastoralisme constitue une ressource économique majeure dans la plupart des pays d'Afrique subsaharienne et qu'il contribue significativement à la croissance des économies nationales, il se heurte encore à de nombreuses difficultés liées notamment à l'accès aux services sociaux, en particulier dans les domaines de la santé et de l'éducation, et à la prévention des conflits avec les communautés sédentaires et les autorités locales. Ce constat intervient à un moment où les pasteurs eux-mêmes essayent de préserver leur mode de vie nomade au sein d'un écosystème soumis à de rapides transformations. Les approches transdisciplinaires, en particulier celles relevant du concept « Une seule santé ¼ qui recouvre à la fois la santé humaine et la santé animale ont fait leurs preuves pour améliorer la fourniture de services et la couverture des pasteurs nomades dans les régions éloignées. Le mode de vie des pasteurs pouvant se définir comme entretenant à la fois des relations avec le bétail et avec leur environnement, les sciences sociales ont un rôle important à jouer pour étudier les modalités de fourniture de services sociaux et leur adaptation aux communautés pastorales. La capacité de procéder à la détection précoce (pré-diagnostic) des maladies émergentes ou endémiques demeure un aspect crucial de la surveillance sanitaire visant à prévenir les risques de transmission et de propagation. L'exercice d'une surveillance syndromique par les communautés, en recourant aux technologies de l'imagerie transmise par téléphonie mobile selon des modalités adaptées à cette population majoritairement illettrée constitue une alternative prometteuse aux systèmes actuels de surveillance sanitaire. Une telle approche permettrait d'accélérer le rythme des notifications et donc de cibler les interventions à destination des pasteurs nomades en Afrique subsaharienne. Bien que des efforts considérables aient été déployés pour faire bénéficier les pasteurs nomades des services sociaux, nombre d'obstacles s'opposent encore à la mise en place d'une politique claire, spécifique et durable en faveur du pastoralisme en Afrique subsaharienne.

Aunque en la mayoría de los países del África subsahariana el pastoreo constituye un importante recurso económico y contribuye sensiblemente al crecimiento nacional, quedan aún problemas por resolver, sobre todo a la hora de prestar servicios sociales a las comunidades de pastores, en particular de salud y educación, y de evitar situaciones de conflicto con las comunidades sedentarias y administraciones locales. Todo ello sucede mientras las sociedades pastorales tratan de preservar su modo de vida nómada dentro de un ecosistema sujeto a rápidas transformaciones. Se ha comprobado que los planteamientos transdisciplinares, como el de «Una sola salud¼, que abarca a la vez la salud humana y la sanidad animal, resultan eficaces para prestar servicios y llegar a las comunidades de pastores nómadas de zonas aisladas. Cabría describir el pastoreo como un modo de vida vinculado a la vez al ganado y al medio natural, lo que hace de las ciencias sociales un elemento importante a la hora de investigar la prestación y adaptación de servicios sociales a estas poblaciones. La detección pronta o previa al diagnóstico de enfermedades infecciosas emergentes o endémicas sigue siendo un aspecto central de la vigilancia sanitaria, destinado a impedir que el agente pueda transmitirse o propagarse. La vigilancia sindrómica a escala comunitaria, combinada con la tecnología de la telefonía móvil visual, perfectamente adaptada a los elevados niveles de analfabetismo existentes entre los nómadas, podría ofrecer una alternativa a los sistemas vigentes de vigilancia sanitaria. Semejante método podría ayudar a comunicar con mayor presteza episodios sanitarios, lo que a su vez podría traducirse en intervenciones específicas entre los pastores nómadas del África subsahariana. Aunque se han hecho considerables esfuerzos para integrar en los servicios sociales a las comunidades pastorales móviles, subsisten obstáculos que dificultan la adopción en el África subsahariana de una política clara, específica y sostenible con respecto al pastoreo.

The Influence of Preoperative Aneurysmal Thrombus Quantity and Distribution on the Development of Type II Endoleaks with Aneurysm Sac Enlargement After EVAR of AAA.

PURPOSE: To determine the influence of preoperative aneurysmal thrombus quantity and distribution on the development of type II endoleak with aneurysm sac enlargement after endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: We retrospectively analyzed the pre- and postoperatively performed CT scans of 118 patients who had follow-up imaging for at least 1 year after EVAR available. We assessed preoperative thrombus perimeter (T Peri), diameter (T Dia), cross-sectional area (T CSA), and volume (T Vol). The preoperative thrombus distribution was classified into no thrombus, semilunar-shaped (anterior, right side, left side, posterior) thrombus, and circumferential type thrombus. The number of preoperative patent aortic side branches (ASB) was identified. Endpoint was type II endoleak with aneurysm volume (A Vol) increase of ≥5 % during follow-up. RESULTS: During follow-up (2 years, range 1-9 years), 17 patients with type II endoleak had significant A Vol increase. Less preoperative T Peri, T Dia, T CSA, and T Vol were associated with A Vol increase. A circumferential thrombus distribution significantly protected against aneurysm enlargement (p = 0.028). The variables with the strongest significance for A Vol increase were preoperative T Vol/A Vol ratio (OR 0.95; p = 0.037) and number of patent ASB (OR 3.52; p < 0.001). CONCLUSION: A low preoperative T Vol/A Vol ratio and a high number of patent ASB were associated with aneurysm sac enlargement after EVAR.

Ultrasound diagnostics of renal artery stenosis: Stenosis criteria, CEUS and recurrent in-stent stenosis.

BACKGROUND AND PURPOSE: As a non-invasive, side effect-free and cost-effective method, ultrasonography represents the method of choice for the diagnosis of renal artery stenosis. Four different criteria in total, including two direct criteria in peak systolic velocity (PSV) and renal aortic ratio (RAR) and two indirect criteria in resistance index (RI) and acceleration time (AT) for the measurement of relevant renal artery stenosis are described, each demonstrating highly variable accuracy in studies. Furthermore, there is controversy over the degree beyond which stenosis becomes therapeutically relevant and which ultrasound PSV is diagnostically relevant in terms of stenosis grading. MATERIAL AND METHODS: This article gives a critical review based on a selective literature search on measurement methodology and the validity of ultrasound in renal artery stenosis. A critical evaluation of methods and a presentation of measurement principles to establish the most precise measurement method possible compared with the gold standard angiography, as well as an evaluation of the importance of computed tomography angiography (CTA) and magnetic resonance angiography (MRA). RESULTS AND CONCLUSIONS: The PSV provides high sensitivity and specificity as a direct measurement method in stenosis detection and grading. Most studies found sensitivities and specificities of 85-90 % for > 50 % stenosis at a PSV > 180-200 cm/s in ROC curve analysis. Other methods, such as the ratio of the PSV in the aorta to the PSV in the renal artery (RAR) or indirect criteria, such as side to side differences in RI (dRI) or AT can be additionally used to improve accuracy. Contrast-enhanced ultrasound improves accuracy by means of echo contrast enhancement. Although in the past only high-grade stenosis was considered relevant for treatment, a drop in pressure of > 20 mmHg in > 50 % stenosis (PSV 180 cm/s) is classified as relevant for increased renin secretion. Stenosis in fibromuscular dysplasia can be reliably graded according to the continuity equation. Although the available studies on the grading of in-stent restenosis are the subject of controversy, there is a tendency to assume higher cut-off values for PSV and RAR. Whilst MRA and CTA demonstrate an accuracy of > 90 %, this is at the cost of possible side effects for patients, particularly in the case of pre-existing renal parenchymal damage. ADDITIONAL ONLINE MATERIAL: This article includes two additional video sequences on visualizing renal artery stenosis. This supplemental material can be found under: dx.doi.org/10.1007/s00772-015-0060-3.

Live cell imaging of cytoplasmic dynein movement in transfected embryonic rat neurons.

Live cell imaging of the movement of various membrane-bounded organelle cargos has enhanced our understanding of their function. Eukaryotic cells utilize microtubules and two classes of microtubule-based motor proteins, cytoplasmic dynein and members of the kinesin family, to deliver a variety of membrane-bounded organelles and other cargos to their appropriate locations. In order to better understand the functions and regulation of cytoplasmic dynein, we developed a method to study its location and motility in living cells. The technique takes advantage of the long thin axons of cultured hippocampal neurons. We use calcium phosphate to transfect fluorescent-tagged dynein intermediate chain (IC) subunits (DYNC1I) into cultured neurons. When the ICs are expressed at low levels, they are effective probes for the location of the cytoplasmic dynein complex in axons when living cells are imaged with fluorescence microscopy. The fluorescent subunit probes can be used to identify specific cargos of dynein complexes with different IC isoforms as well as the kinetic properties of cytoplasmic dynein.

High Resolution Strain Analysis Comparing Aorta and Abdominal Aortic Aneurysm with Real Time Three Dimensional Speckle Tracking Ultrasound.

OBJECTIVE/BACKGROUND: Ultrasound measurement of aortic diameter for aneurysm screening allows supervision of aneurysm growth. Additional biomechanical analysis of wall motion and aneurysm deformation can supply information about individual elastic properties and the pathological state of the aortic wall. Local aortic wall motion was analyzed through imaged aortic segments according to age and pathology. METHODS: Sixty-five patients were examined with a commercial four dimensional ultrasound system (4D-US). Three groups were defined: patients with normal aortic diameter and younger than 60 years of age (n = 21); those with normal aortic diameter and older than 60 years of age (n = 25); and those with infrarenal aortic aneurysm (n = 19). A diastolic reference shape of aortic wall segments was obtained and local and temporally resolved wall strain was determined. Indices characterizing the resulting wall strain distribution were determined. RESULTS: The analysis of biomechanical properties displayed increasing heterogeneous and dyssynchronous circumferential strain with increasing patient age. Young patients exhibited higher mean strain amplitude. The distribution of the spatial heterogeneity index and local strain ratio was inversely proportional to age. The maximum local strain amplitude was significantly higher in the young (0.26 ± 0.17) compared with the old (0.16 ± 0.07) or aneurysmal aorta (0.16 ± 0.10). Temporal dyssynchrony significantly differed between young (0.13 ± 0.10) and old (aneurysmal 0.31 ± 0.04, non-aneurysmal 0.29 ± 0.05), regardless of aortic diameter. The spatial heterogeneity index and local strain ratio differentiate non-aneurysmal and aneurysmal aorta, regardless of age. CONCLUSIONS: 4D-US strain imaging enables description of individual wall motion (kinematics) of the infrarenal aorta with high spatial and temporal resolution. Functional differences between young, old, and aneurysmal aorta can be described by mean (circumferential) strain amplitude, the spatial heterogeneity index, and the local strain ratio. Further investigation is required to refine this new perspective of patient individualized characterization of the pathological AAA wall and eventually to rupture risk stratification.

Inferior Mesenteric Artery Side Branch for Selected Patients with Endovascular Aortic Aneurysm Repair.

OBJECTIVE/BACKGROUND: To report on our experience of the treatment of aortic aneurysms by custom-made, branched stent-grafts with an additional inferior mesenteric artery (IMA) side branch to preserve IMA perfusion in patients at risk for colon ischemia. METHODS: Three male patients (mean age 60 years) with a thoracoabdominal, pararenal, and infrarenal aortic aneurysm (AA), respectively, were treated by endovascular aneurysm exclusion using custom-made, branched stent-grafts with a side branch to the IMA for prevention of colon ischemia. Indications for selective IMA side branch perfusion were occlusions or high-grade stenosis of the visceral or hypogastric arteries. RESULTS: No colon ischemia and no neurological deficit were observed. All three IMA side branches were perfused and patent, as documented by computed tomography scan and duplex ultrasound postoperatively and after 12 months. Patency after 24 months was documented as 2/3. CONCLUSION: Custom-made, branched stent-grafts are an endovascular option to preserve the IMA perfusion in selected, electively treated patients with an increased risk for insufficient colon perfusion due to stenosis or occlusions of visceral or hypogastric arteries.

Ultrasound diagnostics of the abdominal aorta: English version.

BACKGROUND AND OBJECTIVES: The ideal method for screening investigations is one which is as free as possible from side effects, is easily learnt, and can therefore be broadly used to detect abdominal aortic aneurysms (AAA) with a high degree of certainty. Although ultrasonography fulfils these criteria, the measurement method is not standardized. Different measurement methods are used in ultrasonography as well as in computed tomography (CT) studies and the measurement method is actually described sufficiently in only 57 % of cases. METHODS: This article provides a critical review of the current literature on measurement methods and the validity of ultrasonography for the determination of aortic diameter, particularly in AAA, and presents the measurement principles for making measurements as precisely as possible. RESULTS AND CONCLUSION: The most precise determination of aortic diameter is carried out by electrocardiogram (ECG) gating according to the leading-edge method with orthogonal slicing. Within the framework of screening investigations, sufficient measurement precision can be achieved by adherence to orthogonal slicing. Using these standardized measurement methods, ultrasonography shows valid and reproducible results even compared with CT and is the method of choice in screening investigations for AAA.

Distinct functional roles of cytoplasmic dynein defined by the intermediate chain isoforms.

The motor protein, cytoplasmic dynein is responsible for the movement of a variety of cargoes toward microtubule minus ends in cells. Little is understood about how dynein is regulated to specifically transport its various cargoes. In vertebrates, the dynein motor domain (DYNC1H) is encoded by a single gene; while there are two genes for the five smaller subunits that comprise the cargo binding domain of the dynein complex. The isoforms of the intermediate chain (DYNC1I) provide a good model system with which to study the roles the different isoforms of the cargo domain subunits have in designating specific dynein functions. The intermediate chains (DYNC1I) play a key scaffold role in the dynein complex. In neurons, dynein complexes with different intermediate chain isoforms have distinct roles, including cargo binding and transport. Some of the phospho-isoforms of the intermediate chain also specify binding to specific cargo. These data support the model that cytoplasmic dynein can be specifically regulated through the different isoforms of the subunits.

Acaricide treatment prevents adrenocortical hyperplasia as a long-term stress reaction to psoroptic mange in cattle.

In cattle, infestation with Psoroptes ovis mites may cause severe dermatitis (psoroptic mange) which compromises the health and welfare of the animals and may lead to significant economic losses. To investigate yet undocumented effects of psoroptic mange mite infestations and how successful therapy promotes animal health, the present study examined alterations of the skin, lymph nodes and adrenal glands of P. ovis infested Fleckvieh (Simmental) bulls treated with either ivermectin long-acting injection (IVM LAI; IVOMEC(®) GOLD, Merial; 3.15% ivermectin w/v) or saline (n=16 each). Approximately 8 weeks subsequent to experimental infestation with P. ovis, the bulls had developed mange and were administered either IVM LAI or saline once at 1 mL/50 kg body weight by subcutaneous injection. Mite counts were conducted in weekly intervals for determination of efficacy of treatment, and following humane euthanasia of the animals 8 weeks after treatment, skin samples from affected (mangy or previously mangy) and unaffected areas, prescapular lymph nodes and adrenal glands were collected for gross and pathohistological examination. In addition, four age-matching, uninfested Simmental bulls were sampled as controls for comparison. No P. ovis mites were detected on any IVM LAI-treated bull after 28 days following treatment whereas saline-treated bulls maintained infestation throughout the study. At sampling (approximately 16 weeks after experimental infestation and 8 weeks following saline or IVM LAI treatment), saline-treated bulls displayed a severe, exsudative dermatitis with significantly increased skin thickness and inflammatory cell infiltration, significantly enlarged, hyperplastic prescapular lymph nodes, as well as significantly increased adrenal gland weights and volumes as compared to P. ovis-infested, IVM LAI-treated bulls and uninfested controls. Quantitative stereological analysis revealed that the adrenal gland enlargement in P. ovis-infested, saline-treated bulls was due to a selective increase of the volume of the zona fasciculata in the adrenal cortex. Compared to uninfested controls and P. ovis-infested, IVM LAI-treated bulls, the number of epithelial cells in the zona fasciculata was significantly increased in P. ovis-infested, saline-treated bulls, while the zona fasciculata cell volumes did not differ between the three groups of cattle. While the single point determination of serum cortisol concentrations did not reveal significant differences between the three groups of cattle at tissue sampling, the hyperplastic growth of the adrenal cortex in the P. ovis-infested, saline-treated bulls provides morphologic evidence that a chronic stress reaction is one consequence of mange mite infestations that can be prevented by efficacious acaricidal treatment.