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.

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.

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.

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.

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.

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.

Live cell imaging reveals differential modifications to cytoplasmic dynein properties by phospho- and dephosphomimic mutations of the intermediate chain 2C S84.

Cytoplasmic dynein is a multisubunit motor protein responsible for intracellular cargo transport toward microtubule minus ends. There are multiple isoforms of the dynein intermediate chain (DYNC1I, IC), which is encoded by two genes. One way to regulate cytoplasmic dynein is by IC phosphorylation. The IC-2C isoform is expressed in all cells, and the functional significance of phosphorylation on IC-2C serine 84 was investigated by using live cell imaging of fluorescent protein-tagged IC-2C wild type (WT) and phospho- and dephosphomimic mutant isoforms in axonal transport model systems. Both mutations modulated dynein functional properties. The dephosphomimic mutant IC-2C S84A had greater colocalization with mitochondria than the IC-2C WT or the phosphomimic mutant IC-2C S84D. The dephosphomimic mutant IC-2C S84A was also more likely to be motile than the phosphomimic mutant IC-2C S84D or the IC-2C WT. In contrast, the phosphomimic mutant IC-2C S84D mutant was more likely to move in the retrograde direction than was the IC-2C S84A mutant. The phosphomimic IC-2C S84D was also as likely as the IC-2C WT to colocalize with mitochondria. Both the S84D phospho- and the S84A dephosphomimic mutants were found to be capable of microtubule minus-end-directed (retrograde) movement in axons. They were also observed to be passively transported in the anterograde direction. These data suggest that the IC-2C S84 has a role in modulating dynein properties.

Dual-energy computed tomography after endovascular aortic aneurysm repair: the role of hard plaque imaging for endoleak detection.

OBJECTIVES: To assess the diagnostic accuracy of dual-energy computed tomography (DECT) for detection of endoleaks and aneurysm sac calcifications after endovascular aneurysm repair (EVAR) using hard plaque imaging algorithms. MATERIALS AND METHODS: One hundred five patients received 108 triple-phase contrast-enhanced CT (non-contrast, arterial and delayed phase) after EVAR. The delayed phase was acquired in dual-energy and post-processed using the standard (HPI-S) and a modified (HPI-M) hard plaque imaging algorithm. The reference standard was determined using the triple-phase CT and contrast-enhanced ultrasound. All images were analysed separately for the presence of endoleaks and calcifications by two independent readers; sensitivity, specificity and interobserver agreement were calculated. RESULTS: Endoleaks and calcifications were present in 25.9 % (28/108) and 20.4 % (22/108) of images. The HPI-S images had a sensitivity/specificity of 54 %/100 % (reader 1) and 57 %/99 % (reader 2), the HPI-M images of 93 %/92 % (reader 1) and 96 %/92 % (reader 2) for detection of endoleaks. For detection of calcifications HPI-S had a sensitivity/specificity of 91 %/99 % (reader 1) and 95 %/97 % (reader 2), the HPI-M images of 91 %/99 % (reader 1) and 91 %/99 % (reader 2), respectively. CONCLUSION: Using HPI-M, DECT enables an accurate diagnosis of endoleaks after EVAR and allows distinguishing between endoleaks and calcifications with high diagnostic accuracy. KEY POINTS: • Dual-energy computed tomography allows the diagnosis of aortic pathologies after EVAR. • Hard plaque imaging algorithms can distinguish between endoleaks and aneurysm sac calcifications. • The modified hard plaque imaging algorithm detects endoleaks with high diagnostic accuracy.

Polytetrafluoroethylene covered stent placement for focal occlusive disease of the infrarenal aorta.

BACKGROUND: Arterial insufficiency is rarely caused by isolated infrarenal aortic occlusive lesions. Endovascular treatment options include plain balloon angioplasty and bare metal stent placement. In this study the feasibility and efficacy of polytetrafluoroethylene (PTFE) covered balloon expandable stents were evaluated. MATERIAL AND METHODS: Consecutive patients from two centers were prospectively collected in a database and retrospectively analyzed. Results were evaluated by clinical examination, ankle-brachial indices (ABI), duplex ultrasound, and plain abdominal radiography. RESULTS: Thirty-six consecutive patients were treated between November 2008 and June 2013. Indication for treatment was Rutherford 3 (n = 29), 4 (n = 3), and 5 (n = 4). Technical success was always achieved and there were no distal embolizations or vessel wall ruptures. The median follow-up was 22 months (range 0-60). All patients improved clinically and the ABI increased significantly from 0.73 ± 0.18 to 1.01 ± 0.14 (p < .01). One patent covered stent was removed surgically because of infection. Primary patency rates were 100% at 1 and 2 years without stent fractures. CONCLUSION: The use of PTFE covered stents for the treatment of isolated infrarenal aortic occlusive disease is safe and very effective. Patency rates are excellent and complications including distal embolization and vessel wall rupture are extremely rare.

Outcomes of fenestrated/branched endografting in post-dissection thoracoabdominal aortic aneurysms.

OBJECTIVES: Fenestrated/branched thoracic endovascular repair (F/Br-TEVAR) is increasingly applied for atherosclerotic thoracoabdominal aortic aneurysm (TAAA); however, use in post-dissection TAAAs is still very limited. Experience with F/Br-TEVAR in the treatment of post-dissection TAAA is presented. METHODS: Data were analysed from prospectively maintained databases including all patients with post-dissection TAAAs that underwent F/Br-TEVAR within the period January 2010 to July 2013 in two vascular institutions. Evaluated outcomes included initial technical success, operative mortality and morbidity, late survival, endoleak, aneurysm diameter regression, renal function, and reintervention during follow-up (FU). RESULTS: A total of 31 patients (25 male, mean age 65 ± 11.4 years) were treated. Technical success was 93.5% and 30-day mortality 9.6%. Temporary spinal cord ischaemia occurred in four (12.6%) patients, with no case of permanent paraplegia. Mean FU was 17.0 ± 10 months. There were seven late deaths, all aneurysm unrelated. Estimated overall survival rates were 83.9 ± 6.7, 76.4 ± 7.9 and 71.6 ± 8.7% at 6, 12, and 18 months, respectively. Impairment of renal function occurred in two (6.4%) patients. Endoleaks were diagnosed in 12 patients during FU, including six type IB endoleaks and six type II endoleaks. Reintervention was required in seven (22.5%) patients. Mean aneurysm sac regression was 9.3 ± 8.7 mm, with a false lumen thrombosis rate of 66.7% and 88.2% for patients with a FU longer than 6 and 12 months respectively. CONCLUSIONS: F/Br-EVAR is feasible for patients with a post-dissection TAAA. Although associated with additional technical challenges, and a significant need for reintervention, it leads to favourable aneurysm morphologic changes, and may play a more prominent role in the future for this type of pathology if long-term results confirm the good initial outcome.

Editor's choice--Temporary aneurysm sac perfusion as an adjunct for prevention of spinal cord ischemia after branched endovascular repair of thoracoabdominal aneurysms.

OBJECTIVE: To report experience with the concept of temporary aneurysm sac perfusion (TASP) and second stage side branch completion to prevent severe spinal cord ischemia (SCI) after branched endovascular aortic repair (bEVAR) for thoracoabdominal aortic aneurysm (TAAA). METHODS: Patients were treated for TAAA with bEVAR between January 2009 and September 2012. TASP was performed by non-completion of side branches to one of the reno-visceral arteries, distal aortic or iliac extensions with secondary side branch completion. Primary endpoints of the study were overall technical success, side branch patency, perioperative mortality, and the rate of severe SCI. RESULTS: Eighty-three patients were treated for TAAA with branched aortic stent grafts with (n = 40) or without (n = 43) TASP. Overall technical success, including aneurysm exclusion, absence of persistent type I or III endoleak, TASP side branch patency, and secondary side branch completion was 35/40 (88%). Secondary TASP side branch completion was performed after a median of 48 days (range 1-370 days). The rate of early re-interventions for reno-visceral side branch complications was 8/283 (3%) and 6/83 (7%) for perioperative mortality, with three patients in both groups. Severe SCI or paraplegia was observed in 11/83 (13%) of the patients and reduced in the TASP group (2/40) compared with the non-TASP group (9/43; p = .03), especially in Crawford I-III aneurysms (1/29 vs. 7/24; p = .01). However, one TASP patient died 4 months after bEVAR during the TASP interval from suspected aorto-bronchial fistula. CONCLUSION: The concept of TASP after bEVAR for TAAA is feasible and seems to reduce the risk of SCI. Early side TASP branch completion within 4 weeks is recommended to reduce the risk of rupture, although, according to the individual clinical presentation, a longer TASP interval might improve neurological rehabilitation from SCI.

Ocular color-coded sonography - a promising tool for neurologists and intensive care physicians.

Ocular color-coded duplex sonography (OCCS), when performed within the safety limits of diagnostic ultrasonography, is an easy noninvasive technique with high potential for diagnosis and therapy in diseases with raised intracranial pressure and vascular diseases affecting the eye. Despite the capabilities of modern ultrasound systems and its scientific validation, OCCS has not gained widespread use in neurological practice. In this review, the authors describe the technique and main parameter settings of OCCS systems to reduce potential risks as thermal or cavitational effects for sensitive orbital structures. Applications of OCCS are the determination of intracranial pressure in emergency medicine, and follow-up evaluations of idiopathic intracranial hypertension and ventricular shunting by measuring the optic nerve sheath diameter. A diameter of 5.7 - 6.0 mm corresponds well with symptomatically increased intracranial pressure (> 20 cmH2O). OCCS also helps to discriminate between different etiologies of central retinal artery occlusion - by visualization of a "spot sign" and Doppler flow analysis of the central retinal artery - and aids the differential diagnosis of papilledema. At the end perspectives are illustrated that combine established ultrasound methods such as transcranial color-coded sonography with OCCS.

[The significance of contrast-enhanced ultrasound in vascular surgery]. / Stellenwert der Kontrastmittelsonografie in der Gefäßchirurgie.

BACKGROUND: Vascular contrast-enhanced ultrasound (CEUS) is a special ultrasound application without the harmful side effects of nephrotoxicity and radiation exposure. CEUS can be used for advanced diagnosis of carotid stenosis and follow-up checks of endovascular repair of abdominal aortic aneurysms (EVAR). Low-flow phenomenon in peripheral vascular disease can easily be detected by enhanced colour-coded duplex sonography (CCDS). METHODS: The technical requirements of CEUS are explained here for the aorta, carotid, and peripheral arteries. The benefits and risks compared to computed tomography (CT), magnetic resonance (MR) and angiography are evaluated. Based on a selective review of the literature and the authors' personal experiences, CEUS is recommended for routine surveillance after EVAR. RESULTS: CEUS is a safe method using SonoVue® (Bracco) as the only approved agent for vascular examination. Special equipment and training is necessary. In prospective studies and meta-analyses the detection and characterisation of endoleaks is comparable to that of CT imaging. Neovascularisation as a sign of carotid plaques at risk can be seen without the need for invasive treatment. Imaging of crural vessels with enhanced CCDS is a promising but rarely needed option in diabetic and renally insufficient patients. CONCLUSION: CEUS in vascular medicine should be performed prior to other methods to avoid nephrotoxic contrast agents for the patients, especially in follow-up checks after EVAR. The time and effort required are still limiting its practical breakthrough.

[Control of bovine hypodermosis in Switzerland; looking back]. / Die erfolgreiche Bekämpfung der Hypodermose in der Schweiz: Ein Blick zurück.

For many years, hypodermosis control - which started in the 1920's - was unsatisfactory, partly due to a lack of efficacy or a too high toxicity of the available products. An improved control became possible with the introduction (1957) of the organophosphate Metrifonate (Neguvon®, Bayer AG). Subsequent large-scale campaigns according to the Federal Ordinance on epizootic diseases (1967) quite reduced hypodermosis in Switzerland. However, due to a limited use of the product (only young and alpine-grazing cattle were allowed to be treated, administratively indicated maximum dose, side-effects) and its incomplete efficacy, a full control was not possible. The decision to maintain hypodermosis as a "notifiable" disease then allowed further epidemiological studies. In 2000/2001 a concerted action in close cooperation with the cantonal veterinarians allowed a consequent and systematic treatment of all cattle in all endemic areas by the large-scale use of Eprinomectin (Eprinex®, Merial Inc.) for dairy cattle and of Ivermectin (Merial Inc.) as microdose "off-label" for young cattle has led to a rapid and sustainable success.

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.

Trk activation of the ERK1/2 kinase pathway stimulates intermediate chain phosphorylation and recruits cytoplasmic dynein to signaling endosomes for retrograde axonal transport.

The retrograde transport of Trk-containing endosomes from the axon to the cell body by cytoplasmic dynein is necessary for axonal and neuronal survival. We investigated the recruitment of dynein to signaling endosomes in rat embryonic neurons and PC12 cells. We identified a novel phosphoserine on the dynein intermediate chains (ICs), and we observed a time-dependent neurotrophin-stimulated increase in intermediate chain phosphorylation on this site in both cell types. Pharmacological studies, overexpression of constitutively active MAP kinase kinase, and an in vitro assay with recombinant proteins demonstrated that the intermediate chains are phosphorylated by the MAP kinase ERK1/2, extracellular signal-regulated kinase, a major downstream effector of Trk. Live cell imaging with fluorescently tagged IC mutants demonstrated that the dephosphomimic mutants had significantly reduced colocalization with Trk and Rab7, but not a mitochondrial marker. The phosphorylated intermediate chains were enriched on immunoaffinity-purified Trk-containing organelles. Inhibition of ERK reduced the amount of phospho-IC and the total amount of dynein that copurified with the signaling endosomes. In addition, inhibition of ERK1/2 reduced the motility of Rab7- and TrkB-containing endosomes and the extent of their colocalization with dynein in axons. NGF-dependent survival of sympathetic neurons was significantly reduced by the overexpression of the dephosphomimic mutant IC-1B-S80A, but not WT IC-1B, further demonstrating the functional significance of phosphorylation on this site. These results demonstrate that neurotrophin binding to Trk initiates the recruitment of cytoplasmic dynein to signaling endosomes through ERK1/2 phosphorylation of intermediate chains for their subsequent retrograde transport in axons.

Epidermal growth factor stimulates extracellular-signal regulated kinase phosphorylation of a novel site on cytoplasmic Dynein intermediate chain 2.

Extracellular-signal regulated kinase (ERK) signaling is required for a multitude of physiological and patho-physiological processes. However, the identities of the proteins that ERK phosphorylates to elicit these responses are incompletely known. Using an affinity purification methodology of general utility, here we identify cytoplasmic dynein intermediate chain 2 (DYNC1I-2, IC-2) as a novel substrate for ERK following epidermal growth factor receptor stimulation of fibroblasts. IC-2 is a subunit of cytoplasmic dynein, a minus-end directed motor protein necessary for transport of diverse cargos along microtubules. Emerging data support the hypothesis that post-translational modification regulates dynein but the signaling mechanisms used are currently unknown. We find that ERK phosphorylates IC-2 on a novel, highly conserved Serine residue proximal to the binding site for the p150Glued subunit of the cargo adapter dynactin. Surprisingly, neither constitutive phosphorylation nor a phosphomimetic substitution of this Serine influences binding of p150Glued to IC-2. These data suggest that ERK phosphorylation of IC-2 regulates dynein function through mechanisms other than its interaction with dynactin.

Defining the concept of 'tick repellency' in veterinary medicine.

Although widely used, the term repellency needs to be employed with care when applied to ticks and other periodic or permanent ectoparasites. Repellency has classically been used to describe the effects of a substance that causes a flying arthropod to make oriented movements away from its source. However, for crawling arthropods such as ticks, the term commonly subsumes a range of effects that include arthropod irritation and consequent avoiding or leaving the host, failing to attach, to bite, or to feed. The objective of the present article is to highlight the need for clarity, to propose consensus descriptions and methods for the evaluation of various effects on ticks caused by chemical substances.

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.

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.