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Lymphoceles often occur within several weeks or even months after surgery. Mostly asymptomatic and therefore undiagnosed, they may be self-healing without any treatment. A small percentage of postoperative lymphoceles are symptomatic with significant pain, infection, or compression of vital structures, thus requiring intervention. Many different treatment options are described in the literature, like drainage with or without sclerotherapy, embolization of lymph vessels, and surgical approaches with laparoscopy or laparotomy. Inspired by reports stating that postoperative suction drainage can prevent the formation of lymphoceles, we developed a simple protocol for vacuum-assisted drainage of symptomatic lymphoceles, which proved to be successful and which we would therefore like to present.Between 2008 and 2020, 35 patients with symptomatic postoperative lymphoceles were treated with vacuum-assisted suction drainage (in total 39 lymphoceles). The surgery that caused lymphocele formation had been performed between 8 and 572 days before. All lymphoceles were diagnosed based on biochemical and cytologic findings in aspirated fluid. The clinical and imaging data were collected and retrospectively analyzed.In total, 43 suction drainage catheters were inserted under CT guidance. The technical success rate was 100 %. One patient died of severe preexisting pulmonary embolism, sepsis, and poor conditions (non-procedure-related death). In 94.8 % of symptomatic lymphoceles, healing and total disappearance could be achieved. 4 lymphoceles had a relapse or dislocation of the drainage catheter and needed a second drainage procedure. Two lymphoceles needed further surgery. The complication rate of the procedure was 4.6 % (2/43, minor complications). The median indwelling time of a suction drainage catheter was 8-9 days (range: 1-30 days).The positive effects of negative pressure therapy in local wound therapy have been investigated for a long time. These positive effects also seem to have an impact on suction drainage of symptomatic lymphoceles with a high cure rate.· Suction drainage of lymphoceles is an easy and successful method to cure symptomatic lymphoceles at various locations.. · We believe this to be due to the induction of cavity collapse and surface adherence.. · In most cases rapid clinical improvement could be obtained..· Franke M, Saager C, Kröger J et al. Vacuum-Assisted Suction Drainage as a Successful Treatment Option for Postoperative Symptomatic Lymphoceles. Fortschr Röntgenstr 2022; 194: 384 - 390.ZIEL: Lymphozelen können innerhalb von Wochen oder sogar Monaten nach chirurgischen Eingriffen auftreten. Bleiben diese asymptomatisch, werden sie meist nicht diagnostiziert und heilen von selbst aus. Ein kleiner Prozentsatz der postoperativen Lymphozelen wird jedoch symptomatisch mit Schmerzen, Infektionszeichen oder Kompression von benachbarten Strukturen, was eine Therapie erfordert. Viele verschiedene Behandlungsmethoden sind in der Literatur beschrieben, wie Drainageeinlage mit oder ohne Sklerotherapie, Embolisation von Lymphgefäßen oder chirurgische Operation mit Laparoskopie oder Laparotomie. Inspiriert durch Berichte über postoperative Saugdrainagen, die eine Ausbildung von Lymphozelen verhindern, haben wir ein einfaches Protokoll für eine Vakuum-assistierte Saugdrainage von symptomatischen Lymphozelen entwickelt, welches sich bei uns bewährt hat. Dieses Protokoll möchten wir im Rahmen dieser Studie vorstellen.Von 2008–2020 wurden 35 Patienten mit symptomatischen postoperativen Lymphozelen mit unserer Vakuum-assistierten Saugdrainage behandelt (insgesamt 39 Lymphozelen). Ein vorangegangener chirurgischer Eingriff fand zwischen 8 und 572 Tage zuvor statt. Die Diagnose wurde durch eine Untersuchung des Aspirats biochemisch und zytologisch bestätigt. Die klinischen Daten und Bilddaten wurden gesammelt und retrospektiv analysiert.Insgesamt wurden 43 Saugdrainagen unter CT-Kontrolle eingebracht. Der technische Erfolg lag bei 100 %. Ein Patient starb leider aufgrund einer vorbestehenden Lungenarterienembolie, einer Sepsis und einem schlechten Allgemeinzustand. Bei 94,8 % der Lymphozelen konnte eine komplette Ausheilung erreicht werden. Vier Lymphozelen benötigten eine zweite Drainage aufgrund eines Rezidivs oder einer Drainagedislokation. Zwei Lymphozelen wurden letztendlich bei fehlender Ausheilung operiert. Die Komplikationsrate der Prozedur betrug 4,6 % (minor complications). Die mittlere Einliegedauer der Drainagen betrug 8–9 Tage.Die positiven Effekte der Unterdrucktherapie in lokalen Wunden sind schon seit Langem untersucht. Diese positiven Effekte scheinen auch bei der Saugdrainage von symptomatischen Lymphozelen zu einer hohen Ausheilungsrate zu führen.· Die Saugdrainage ist eine einfache und schnelle Methode zur Ausheilung von symptomatischen Lymphozelen in verschiedenen Körperlokalisationen.. · Wir glauben, dass dies durch die Kollabierung der Lymphozele und Verkleben der Lymphozelenwand zustande kommt.. · In den meisten Fällen konnte durch unsere Methode ein schnelles Abklingen der Beschwerden erreicht werden..

Leiomyosarcoma (LMS) in the sinonasal tract (SNT) is a rarity that has been firstly described in 1958. Since then, there have been only a few articles about this entity. Most of the data available about LMS in the SNT is derived from case reports. We believe that our case will support the data set and help guiding the management of this rare condition. A 84-year-old female presented with nasal airway obstruction on the left side. She experienced several episodes of epistaxis from her left nostril, what made her to seek medical care. A rhinoscopy revealed an obstructing mass in the left nasal cavity. Computed tomography (CT) scan of the paranasal sinuses revealed a homogenous mass occupying the left nasal cavity, bone destruction of the left middle, and inferior nasal turbinates. An infiltration of the left nasolacrimal duct was also present. The patient refused to undergo open surgery and the mass was removed during an endoscopic approach. The histopathological analysis combined with immunohistochemistry was consistent with LMS. The resection margins were positive for tumor cells. A staging with CT-neck-thorax, abdomen ultrasound, and MRI of the head ruled out metastases. She underwent a second endoscopic tumor resection surgery with positive resection margins and obtained adjuvant radiotherapy. On 9 months of follow-up, there was no recurrence or metastases.

Ciliopathies comprise a large number of hereditary human diseases and syndromes caused by mutations resulting in dysfunction of either primary or motile cilia. Both types of cilia share a similar architecture. While primary cilia are present on most cell types, expression of motile cilia is limited to specialized tissues utilizing ciliary motility. We characterized protein complexes of ciliopathy proteins and identified the conserved AAA-ATPase Ruvbl1 as a common novel component. Here, we demonstrate that Ruvbl1 is crucial for the development and maintenance of renal tubular epithelium in mice: both constitutive and inducible deletion in tubular epithelial cells result in renal failure with tubular dilatations and fewer ciliated cells. Moreover, inducible deletion of Ruvbl1 in cells carrying motile cilia results in hydrocephalus, suggesting functional relevance in both primary and motile cilia. Cilia of Ruvbl1-negative cells lack crucial proteins, consistent with the concept of Ruvbl1-dependent cytoplasmic pre-assembly of ciliary protein complexes., Cell cilia: Protein crucial for function identified A protein involved in building and maintaining thin protrusions from cell surfaces called cilia is implicated in “ciliopathies”, diseases in which ciliary function is disrupted. These include polycystic kidney disease and disorders collectively known as ciliary dyskinesias. “Primary cilia” perform sensory functions, detecting external chemical and physical signals and initiating responses within cells. In addition, “motile cilia” beat rhythmically to move fluids surrounding cells. Researchers in Germany and the Netherlands, led by Bernhard Schermer and Max C. Liebau at the University of Cologne, studied a protein called Ruvbl1, known to interact with DNA and other proteins. The researchers found it is crucial for the functioning of both types of cilia. Deleting the gene for Ruvbl1 in mice caused kidney failure and a build-up of fluid in the brain known as hydrocephalus. The research could help understand and ultimately treat ciliopathies.

Background Renal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors. Methods Using Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma. Furthermore, both tumor DNA and DNA from a metastasis are analyzed regarding this mutation. The pathogenic effect of the sequence alteration is confirmed by minigene assays and the biochemical consequences on the protein are examined using TALEN-mediated transgenesis in cultured cells. Results Here we describe an FLCN mutation in a 55-year-old patient who presented himself with progressive weight loss, bilateral kidney cysts and renal tumors. He and members of his family had a history of recurrent pneumothorax during the last few decades. Histology after tumor nephrectomy showed a mixed kidney cancer consisting of elements of a chromophobe renal cell carcinoma and dedifferentiated small cell carcinoma component. Subsequent FLCN sequencing identified an intronic c.1177-5_-3delCTC alteration that most likely affected the correct splicing of exon 11 of the FLCN gene. We demonstrate skipping of exon 11 to be the consequence of this mutation leading to a shift in the reading frame and the insertion of a premature stop codon. Interestingly, the truncated protein was still expressed both in cell culture and in tumor tissue, though it was strongly destabilized and its subcellular localization differed from wild-type FLCN. Both, altered protein stability and subcellular localization could be partly reversed by blocking proteasomal and lysosomal degradation. Conclusions Identification of disease-causing mutations in BHD syndrome requires the analysis of intronic sequences. However, biochemical validation of the consecutive alterations of the resulting protein is especially important in these cases. Functional characterization of the disease-causing mutations in BHD syndrome may guide further research for the development of novel diagnostic and therapeutic strategies. Electronic supplementary material The online version of this article (doi:10.1186/s12881-017-0416-5) contains supplementary material, which is available to authorized users.

Polycystic kidney disease (PKD) is among the leading causes of end-stage renal disease. Increasing evidence exists that molecular therapeutic strategies targeted to cyst formation and growth might be more efficacious in early disease stages, highlighting the growing need for sensitive biomarkers. Here we apply quantitative magnetic resonance imaging techniques of T2 mapping and diffusion-weighted imaging in the jck mouse model for PKD using a clinical 3.0 T scanner. We tested whether kidney T2 values and the apparent diffusion coefficient (ADC) are superior to anatomical imaging parameters in the detection of early cystogenesis, as shown on macro- and histopathology. We also tested whether kidney T2 values and ADC have the potential to monitor early treatment effects of therapy with the V2 receptor antagonist Mozavaptane. Kidney T2 values and to a lesser degree ADC were found to be highly sensitive markers of early cystogenesis and superior to anatomical-based imaging parameters. Furthermore, kidney T2 values exhibited a nearly perfect correlation to the histological cystic index, allowing a clear separation of the two mouse genotypes. Additionally, kidney T2 values and ADC were able to monitor early treatment effects in the jck mouse model in a proof-of-principle experiment. Thus, given the superiority of kidney T2 values and ADC over anatomical-based imaging in mice, further studies are needed to evaluate the translational impact of these techniques in patients with PKD.

Advances in molecular genetics have led to the identification of more than 70 different genes involved in the development of cystic kidney diseases. Most of these diseases are rare, and interpreting the resultant plethora of disease-causing mutations requires a methodical and meticulous approach to differential diagnosis. In this Review we discuss a clinical approach to the diagnosis of cystic kidney diseases in adults, for use by nephrologists. This approach is based upon a thorough clinical evaluation, which considers both kidney phenotype and extrarenal manifestations of the underlying disorder, in combination with genetic testing in selected patients. In our view, cystic kidney disease can (in the majority of patients) be reliably classified on the basis of clinical findings. We therefore propose that defining clinical situations to precipitate the initiation of genetic testing is mandatory and cost-effective. New techniques such as next-generation sequencing will facilitate the diagnosis of cystic kidney diseases in the future, increasing diagnostic safety in a subset of patients. In renal tumour syndromes, genetic testing is warranted.

Editor: We present two cases of symptomatic chronic subclavian artery occlusion in which transbrachial off-label use of the OUTBACK LTD catheter (Cordis Corporation, Miami Lakes, Florida) enabled reentry of the true lumen and stent placement after failure of subintimal wire recanalization. Approval of the local ethics committee was not required because data were retrospectively evaluated. In the first case, a 54-year-old man presented with signs of arm claudication. Magnetic resonance angiography showed chronic occlusion of the left subclavian artery of about 4 cm in length. His medications included acetylsalicylic acid, 100 mg, and clopidogrel, 75 mg. Revascularization was performed using a combined right transfemoral and left transbrachial access. A 5-F sheath (Radifocus Introducer II, 10 cm length; Terumo Europe N.V., Leuven, Belgium) was introduced into the right common femoral artery and into the left brachial artery (Destination, 45 cm length; Terumo Europe N.V.). Heparin 5,000 IU was administered intravenously. With a 100-cm-long 5-F pigtail catheter (Imager II; Boston Scientific Corporation, Natick, Massachusetts) in the ascending aorta, occlusion of the left subclavian artery 1.5 cm away from its take-off from the aorta with the left vertebral artery arising from the aorta was confirmed angiographically (Fig 1a). The long transbrachial 5-F sheath was advanced to the subclavian occlusion. Subintimal recanalization failed with both an 80-cm-long 5-F multipurpose catheter and a 100cm-long 4-F Berenstein catheter (Cordis Corporation) as well as two 0.035-inch hydrophilic wires (one soft and one stiff) with an angled tip (Radifocus Guide Wire M; Terumo Europe N.V.) because reentry of the true lumen was not feasible. The 5-F brachial sheath was exchanged to a 45-cm-long 6-F sheath (Destination), and the 0.035-inch subintimal wire was exchanged to a 0.018-inch wire (SV-5; Cordis Corporation). Although the OUTBACK LTD catheter is intended to be exchanged over a 0.014-inch extra-support wire, it is possible to use 0.018-inch wires. The 6-F compatible 120-cm-long OUTBACK LTD catheter with a hollow 22-gauge needle

Mutations affecting the integrity and function of cilia have been identified in various genes over the last decade accounting for a group of diseases called ciliopathies. Ciliopathies display a broad spectrum of phenotypes ranging from mild manifestations to lethal combinations of multiple severe symptoms and most of them share cystic kidneys as a common feature. Our starting point was a consanguineous pedigree with three affected fetuses showing an early embryonic phenotype with enlarged cystic kidneys, liver and pancreas and developmental heart disease. By genome-wide linkage analysis, we mapped the disease locus to chromosome 17q11 and identified a homozygous nonsense mutation in NEK8/NPHP9 that encodes a kinase involved in ciliary dynamics and cell cycle progression. Missense mutations in NEK8/NPHP9 have been identified in juvenile cystic kidney jck mice and in patients suffering from nephronophthisis (NPH), an autosomal-recessive cystic kidney disease. This work confirmed a complete loss of NEK8 expression in the affected fetuses due to nonsense-mediated decay. In cultured fibroblasts derived from these fetuses, the expression of prominent polycystic kidney disease genes (PKD1 and PKD2) was decreased, whereas the oncogene c-MYC was upregulated, providing potential explanations for the observed renal phenotype. We furthermore linked NEK8 with NPHP3, another NPH protein known to cause a very similar phenotype in case of null mutations. Both proteins interact and activate the Hippo effector TAZ. Taken together, our study demonstrates that NEK8 is essential for organ development and that the complete loss of NEK8 perturbs multiple signalling pathways resulting in a severe early embryonic phenotype.

Background: Transplant centers commonly evaluate split renal function (SRF) with MAG3-scintigraphy (MAG3) in living kidney donation. Alternatively, the kidney volume can be measured based on pre-donation CT-scans. The aim of this study was to identify the most accurate CT-volumetry technique for SRF[for full text, please go to the a.m. URL], 133. Kongress der Deutschen Gesellschaft für Chirurgie

Objective The aim of the study reported here was to evaluate patients’ satisfaction with implantation of venous access devices under local anesthesia (LA) with and without additional oral sedation. Materials and methods A total of 77 patients were enrolled in the prospective descriptive study over a period of 6 months. Subcutaneous implantable venous access devices through the subclavian vein were routinely implanted under LA. Patients were offered an additional oral sedative (lorazepam) before each procedure. The level of anxiety/tension, the intensity of pain, and patients’ satisfaction were evaluated before and immediately after the procedure using a visual analog scale (ranging from 0 to 10) with a standardized questionnaire. Results Patients’ satisfaction with the procedure was high (mean: 1.3±2.0) with no significant difference between the group with premedication and the group with LA alone (P=0.54). However, seven out of 30 patients (23.3%) in the group that received premedication would not undergo the same procedure without general anesthesia. There was no significant influence of lorazepam on the intensity of pain (P=0.88). In 12 out of 30 patients (40%) in the premedication group, the level of tension was higher than 5 on the visual analog scale during the procedure. In 21 out of 77 patients (27.3%), the estimate of the level of tension differed between the interventionist and the patient by 3 or more points in 21 out of 77 patients (27.3%). Conclusion Overall patient satisfaction is high for implantation of venous access devices under LA. A combination of LA with lorazepam administered orally might not be adequate for patients with a high level of anxiety and tension. The level of tension is often underestimated by the interventionist. Pre-procedural standardized questionnaires could be used to identify patients for whom a gradual approach of individualized sedation may be more effective.

De-Hua Chang,1 Sonja Hiss,1 Lena Herich,2 Ingrid Becker,2 Kamal Mammadov,1 Mareike Franke,1 Anastasios Mpotsaris,1 Robert Kleinert,3 Thorsten Persigehl,1 David Maintz,1 Christopher Bangard1 1Department of Radiology, 2Institute of Medical Statistics, Informatics and Epidemiology, 3Department of Surgery, University Hospital of Cologne, Cologne, Germany Objective: The aim of the study reported here was to evaluate patients’ satisfaction with implantation of venous access devices under local anesthesia (LA) with and without additional oral sedation.Materials and methods: A total of 77 patients were enrolled in the prospective descriptive study over a period of 6 months. Subcutaneous implantable venous access devices through the subclavian vein were routinely implanted under LA. Patients were offered an additional oral sedative (lorazepam) before each procedure. The level of anxiety/tension, the intensity of pain, and patients’ satisfaction were evaluated before and immediately after the procedure using a visual analog scale (ranging from 0 to 10) with a standardized questionnaire.Results: Patients’ satisfaction with the procedure was high (mean: 1.3±2.0) with no significant difference between the group with premedication and the group with LA alone (P=0.54). However, seven out of 30 patients (23.3%) in the group that received premedication would not undergo the same procedure without general anesthesia. There was no significant influence of lorazepam on the intensity of pain (P=0.88). In 12 out of 30 patients (40%) in the premedication group, the level of tension was higher than 5 on the visual analog scale during the procedure. In 21 out of 77 patients (27.3%), the estimate of the level of tension differed between the interventionist and the patient by 3 or more points in 21 out of 77 patients (27.3%).Conclusion: Overall patient satisfaction is high for implantation of venous access devices under LA. A combination of LA with lorazepam administered orally might not be adequate for patients with a high level of anxiety and tension. The level of tension is often underestimated by the interventionist. Pre-procedural standardized questionnaires could be used to identify patients for whom a gradual approach of individualized sedation may be more effective. Keywords: patient satisfaction, pain, supportive care, chemotherapy, central venous port implantation

Objective To evaluate transrenal reversible ureteral occlusion with detachable balloons in patients with treatment-refractory urinary tract fistulas. Methods From September 2009 to September 2013, reversible occlusion of 18 ureters (7 men, 3 women; 27-74 years) with treatment-refractory urinary leakage mostly because of tumor disease or iatrogenic surgical injury was performed. Nephrostomy was exchanged fluoroscopically into an 8F or 9F sheath, which was introduced into the ureter to the point of intended balloon inflation. The prepared semicompliant balloon on a special microcatheter was introduced into the sheath, inflated, and detached. A nephrostomy tube was placed in the pelvicalyceal system. After healing of the fistulas, urinary flow was restored by transureteral removal or computed tomography–guided percutaneous puncture of the balloons. Results Hundred percent successful placement of the balloons and initial urinary fistula occlusion was achieved (18 of 18 ureters). One patient was lost during follow-up. Six of the remaining 9 patients needed reocclusion because of balloon dislocation or deflation (secondary technical success 83%; 5 of 6 ureters). A z-shaped ureter made reocclusion unsuccessful. Mean duration of ureteral occlusion was 74 days (5-250 days). After healing of the fistulas, intentional ureteral recanalization by percutaneous puncture or transureteral balloon removal was feasible. Anterograde urination was achieved in 5 of 9 patients (clinical success rate 55%). Four fistulas did not heal. Two patients died from their underlying disease. Conclusion Transrenal reversible off-label ureteral occlusion with semicompliant detachable balloons is feasible with a high technical success rate. Long-term ureteral occlusion can be achieved in nearly all patients with a moderate clinical success rate in heavily diseased patients.

Purpose Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT). Patients and Methods The analysis set consisted of 739 patients with residues ≥ 2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkin's disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkin's disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression. Results In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P = .022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P = .9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%). Conclusion Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse.

To introduce a novel percutaneous technique to stop blood entry at the lesser aortic arch curvature by coil embolisation in type Ia endoleak after TEVAR. A 61-year-old Marfan patient presented with type Ia endoleak of the aortic arch and a growing aortic arch pseudoaneurysm after TEVAR. Multiple preceding operations and interventions made an endovascular approach unsuccessful. Direct percutaneous puncture of the aneurysmal sac would have cured the sign, but not the cause of blood entry at the lesser curvature of the aortic arch. Direct CT-guided percutaneous puncture of the blood entry site in the aortic arch with fluoroscopically guided coil embolisation using detachable extra-long coils was successfully performed. Three weeks after the intervention, the patient developed fever because of superinfection of the pseudoaneurysm. The blood cultures and CT-guided mediastinal aspirate were sterile. After intravenous administration of antibiotics, the fever disappeared and the patient recovered. Six-month follow-up showed permanent closure of the endoleak and a shrinking aneurysmal sac. Direct percutaneous puncture of the aortic arch at the blood entry site of a thoracic type Ia endoleak after TEVAR and double-chimney stent-grafts with coil embolisation of the wedge-shaped space between the lesser aortic curvature and the stent-graft is possible. • Endoleaks after thoracic endovascular aortic repair are common in 15-30 %. • Most endoleaks can be treated by endovascular means. • Direct percutaneous endoleak repair is described as a bail-out option. • Direct percutaneous aortic arch coil embolisation of type 1a endoleak is possible. • Antibiotic prophylaxis should be administered case by case, considering individual risk factors.

Nephronophthisis (NPH) is a genetically heterogenous kidney disease and represents the most common genetic cause for end-stage renal disease in children. It is caused by the mutation of genes encoding for the nephrocystin proteins (NPHPs) which localize to primary cilia or centrosomes, classifying this disease as a 'ciliopathy'. Recently, it has been shown that NPHP4 acts as a potent negative regulator of mammalian Hippo signalling by interacting with the Lats protein kinase and controlling the phosphorylation of the oncogenic transcriptional activator TAZ. Here, we demonstrate that NPHP9, another NPH family member, also controls TAZ activity by a distinct mechanism. NPHP9, which is also called NEK8, directly interacted with TAZ and induced nuclear translocation of the TAZ/NPHP9 protein complex. Binding of NPHP9 to TAZ was enhanced in a TAZ mutant that lost its ability to bind 14-3-3, suggesting that 14-3-3 and NPHP9 may compete for TAZ binding, with 14-3-3 favouring cytoplasmic retention and NPHP9 mediating nuclear delivery. Consistently, co-expression of NPHP4, which inhibits TAZ phosphorylation at the 14-3-3 binding site through the inhibition of Lats kinase activity, induced efficient nuclear delivery of the TAZ/NPHP9 protein pair. Consistent with a role for TAZ in controlling proliferation and tumorigenesis, the downregulation of NPHP9 inhibited the TAZ-dependent proliferation of hippo-responsive normal epithelial and also breast cancer cells. As NPHP9 has been shown to be upregulated in breast cancer, these data do not only support a critical role for TAZ/hippo signalling in the pathogenesis of NPH but may also imply a possible role for NPHP9 in TAZ-mediated tumorigenesis.

A 69-year-old man presented with pneumogenic sepsis. A chest radiograph showed bilateral extensive infiltrates that did not respond to broad-spectrum antibiotic treatment. Progressive respiratory failure necessitated invasive mechanical ventilation (bilevel positive airway pressure, 0.5 inspiratory oxygen saturation; peak inspiratory pressure, 24 cm H2O; positive end-expiratory pressure, 8 cm H2O). Chest computed tomography (CT) revealed inflammatory infiltrates with caverns and bilateral pleural effusions. Blood and bronchoalveolar cultures remained sterile. Therefore, computed tomography-guided lung biopsy was performed with an 18-gauge core needle with the patient in prone position (Figure, A). A control computed tomography scan (Figure, B) revealed massive systemic air embolism. Shortly thereafter, the patient developed cardiorespiratory failure. Cardiopulmonary resuscitation remained unsuccessful. Figure. A , Computed tomography-guided lung biopsy of infiltrates was performed with an 18-gauge needle and the patient in prone position. B , Air embolism after lung biopsy involving intercostal arteries (arrow), coronary arteries (arrowheads), and the aorta (white asterisk). Percutaneous computed tomography-guided lung biopsy is a frequently performed procedure for histological and microbiological analyses of pulmonary …

Meeting abstract Genetic cystic kidney diseases, including autosomal recessive polycystic kidney disease (ARPKD), are among the most common causes of end stage renal disease in children and in adolescents. While the detailed biological events resulting in cyst formation remain incompletely understood, nowadays there is wide agreement that dysfunction of a specialized cellular organelle, the primary cilium, underlies genetic cystic kidney disease. In addition to cystic kidney disease, phenotypes resulting from impaired ciliary function can affect nearly every organ of the human body and are nowadays termed ciliopathies. We recently identified the AAA ATPase RUVBL1 as part of various ciliopathy-associated renal protein complexes and could show that loss of Ruvbl1 in the renal tubule leads to a severe ARPKD-like cystic kidney phenotype in mice. RUVBL1 has previously been linked to regulation of cilia-associated signaling pathways. To obtain novel insights into the cellular function of RUVBL1 and its partner protein RUVBL2, we generated stable murine cell lines with single genomic integration of coding sequences for fluorescence-tagged Ruvbl1 and Ruvbl2. Out of these cell lines we performed protein interaction screens by repetitive and independent immunoprecipitations followed by quantitative mass spectrometry. Along with multiple known interaction partners we identified novel candidates including proteins that had already been linked to ciliary function. In addition to the important role of RUVBL1 in the renal tubule our data point to a more general function of the RUVBL proteins and the RUVBLs-containing chaperone-like R2TP protein complex for ciliary function. Novel murine in vivo data strongly supports this concept. In summary, we obtained novel functional insights into the cell biological link of the AAA ATPases RUVBL1 and RUVBL2 to primary cilia. Our data suggest a role of the RUVBL proteins in the cytosolic pre-assembly of ciliary protein complexes.