Nutcracker syndrome: diagnosis and therapy.

Nutcracker syndrome (NCS) is an extrinsic compression of the left renal vein (LRV) by the superior mesenteric artery (SMA) anteriorly and aorta posteriorly resulting in renal vascular congestion manifesting as hematuria, proteinuria, orthostatic hypotension, pain, or even renal dysfunction. Long-standing venous compression can encourage collateral drainage pathways through gonadal and pelvic veins, which may explain reported symptom and syndrome overlap with pelvic congestion syndrome. Diagnosis can be challenging and variable, frequently involving a combination of ultrasound Doppler, cross-sectional, and invasive imaging. Often, intravascular pressure measurements are required to prove a renocaval pressure gradient to aid in a definitive diagnosis. Conservative management is appropriate, especially in children, who tend to outgrow the disorder. In the interim, medical management with angiotensin converting enzyme inhibitors (ACEIs) is a useful therapy to manage orthostatic hypotension in the pediatric population. In adults, invasive therapies are more frequently pursued. These are aimed at relieving the extrinsic compression on the LRV. The standard of care is renal vein transposition, with renal autotransplantation reserved for recalcitrant cases. Endovascular stenting is a less invasive option. Laparoscopic placement of an exovascular stent is a newer therapy intended to minimize trauma to the LRV. In this review, we will discuss the clinical manifestations, diagnostic criterion, imaging features, and conservative and surgical therapies for this condition.

Venous popliteal entrapment syndrome.

Popliteal entrapment syndrome (PES) describes a set of symptoms related to compression of the neurovascular bundle in the popliteal fossa, with popliteal artery involvement the most widely recognized variation. Popliteal vein entrapment is a rare variation which can easily go undiagnosed. This is most commonly due to an anomaly of the medial head of the gastrocnemius muscle, but other etiologies include excess adipose tissue or cysts within the popliteal fossa, popliteal artery aneurysm, fibrous bands, thickened perivenous fascia, compression by the popliteus muscle or muscular hypertrophy independent of anomalous anatomy, or variant origin of the short saphenous vein. However, with improving awareness, it is a condition which should be increasingly considered in patients presenting with unexplained lower extremity swelling or other symptoms of lower extremity thrombosis. The initial test of choice is typically ultrasound with flexion and extension maneuvers. Venography is the gold standard for diagnosis, but MRI offers a noninvasive option for both diagnosis and evaluation of etiology and should be considered in the work-up of popliteal venous entrapment. Management is based on severity and type of symptoms, ranging from conservative management with compression stockings to surgical management if there is popliteal artery involvement or more severe symptoms. Endovascular therapy such as angioplasty or stenting has also been reported with good results.

Observation time after outpatient non-arterial interventional procedures: standards, safety, and outcomes.

PURPOSE: To evaluate the impact of standardized reduced post-procedure observation time on subsequent healthcare encounters such as emergency department (ED) visits, hospital admissions, and clinic visits. METHODS: 800 consecutive patients undergoing outpatient non-arterial interventional radiologic procedures within the vascular interventional department between 1 June 2013 and 21 July 2014 were included in this IRB-approved, HIPAA-compliant single center observational retrospective study. Electronic medical records were reviewed for subsequent healthcare encounters, such as ED visits, hospital admissions, and clinic visits. An attending interventional radiologist and radiology resident reviewed, in consensus, medical records for relevance of the encounter to the index procedure. Procedure-related encounters were analyzed to determine relationship to length of observation time, using Matlab for statistical analysis. RESULTS: 397 and 403 patients were in the pre- and post-standardization groups, respectively. Median observation time decreased overall from 1.67 h [interquartile range (IQR) 1.17-2.17] to 1.42 h (IQR 1.08-1.92), p < 0.001. There was no significant change in either overall or procedure-related ED visits (16.6% [66/397] and 1.0% [4/397] pre-standardization vs. 20.1% [81/403] and 2.2% [9/403] post-standardization, p = 0.24 and 0.26), hospital admissions (27.7% [110/397] and 4.0% [16/397] prestandardization vs. 28.3% [114/403] and 2.7% [11/403] post-standardization, p = 0.88 and 0.33), or clinic visits (41.3% [164/397] and 1.0% [4/397] pre-standardization vs. 39.5% [159/403] and 2.2% [9/403] post-standardization, p = 0.61 and 0.26). CONCLUSION: Proposed standardized shortened observation times after outpatient interventional radiologic procedures are safe, without change in either total or procedure-related ED visits, hospital admissions, or clinic visits.

Cofilin-induced changes in F-actin detected via cross-linking with benzophenone-4-maleimide.

Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family of proteins. It plays a key role in actin dynamics by promoting disassembly and assembly of actin filaments. Upon its binding, cofilin has been shown to bridge two adjacent protomers in filamentous actin (F-actin) and promote the displacement and disordering of subdomain 2 of actin. Here, we present evidence for cofilin promoting a new structural change in the actin filament, as detected via a switch in cross-linking sites. Benzophenone-4-maleimide, which normally forms intramolecular cross-linking in F-actin, cross-links F-actin intermolecularly upon cofilin binding. We mapped the cross-linking sites and found that in the absence of cofilin intramolecular cross-linking occurred between residues Cys374 and Asp11. In contrast, cofilin shifts the cross-linking by this reagent to intermolecular, between residue Cys374, located within subdomain 1 of the upper protomer, and Met44, located in subdomain 2 of the lower protomer. The intermolecular cross-linking of F-actin slows the rate of cofilin dissociation from the filaments and decreases the effect of ionic strength on cofilin-actin binding. These results are consistent with a significant role of filament flexibility in cofilin-actin interactions.

Multiple forms of Spire-actin complexes and their functional consequences.

Spire is a WH2 domain-containing actin nucleator essential for establishing an actin mesh during oogenesis. In vitro, in addition to nucleating filaments, Spire can sever them and sequester actin monomers. Understanding how Spire is capable of these disparate functions and which are physiologically relevant is an important goal. To study severing, we examined the effect of Drosophila Spire on preformed filaments in bulk and single filament assays. We observed rapid depolymerization of actin filaments by Spire, which we conclude is largely due to its sequestration activity and enhanced by its weak severing activity. We also studied the solution and crystal structures of Spire-actin complexes. We find structural and functional differences between constructs containing four WH2 domains (Spir-ABCD) and two WH2 domains (Spir-CD) that may provide insight into the mechanisms of nucleation and sequestration. Intriguingly, we observed lateral interactions between actin monomers associated with Spir-ABCD, suggesting that the structures built by these four tandem WH2 domains are more complex than originally imagined. Finally, we propose that Spire-actin mixtures contain both nuclei and sequestration structures.

Cofilin-linked changes in actin filament flexibility promote severing.

The actin regulatory protein, cofilin, increases the bending and twisting elasticity of actin filaments and severs them. It has been proposed that filaments partially decorated with cofilin accumulate stress from thermally driven shape fluctuations at bare (stiff) and decorated (compliant) boundaries, thereby promoting severing. This mechanics-based severing model predicts that changes in actin filament compliance due to cofilin binding affect severing activity. Here, we test this prediction by evaluating how the severing activities of vertebrate and yeast cofilactin scale with the flexural rigidities determined from analysis of shape fluctuations. Yeast actin filaments are more compliant in bending than vertebrate actin filaments. Severing activities of cofilactin isoforms correlate with changes in filament flexibility. Vertebrate cofilin binds but does not increase the yeast actin filament flexibility, and does not sever them. Imaging of filament thermal fluctuations reveals that severing events are associated with local bending and fragmentation when deformations attain a critical angle. The critical severing angle at boundaries between bare and cofilin-decorated segments is smaller than in bare or fully decorated filaments. These measurements support a cofilin-severing mechanism in which mechanical asymmetry promotes local stress accumulation and fragmentation at boundaries of bare and cofilin-decorated segments, analogous to failure of some nonprotein materials.

Prevalence and predictors of ocular complications associated with cataract surgery in United States veterans.

PURPOSE: To investigate the prevalence and predictors of intraoperative and 90-day postoperative ocular complications associated with cataract surgery performed in the United States Veterans Health Administration (VHA) system. DESIGN: Retrospective cohort study. PARTICIPANTS: Forty-five thousand eighty-two veterans who underwent cataract surgery in the VHA. METHODS: The National Patient Care Database was used to identify all VHA patients who underwent outpatient extracapsular cataract surgery and who underwent only 1 cataract surgery within 90 days of the index surgery between October 1, 2005, and September 30, 2007. Data collected include demographics, preoperative systemic and ocular comorbidities, intraoperative complications, and 90-day postoperative complications. Adjusted odds ratios (ORs) of factors predictive of complications were calculated using logistic regression modeling. MAIN OUTCOME MEASURES: Intraoperative and postoperative ocular complications within 90 days of cataract surgery. RESULTS: During the study period, 53786 veterans underwent cataract surgery; 45082 met inclusion criteria. Common preoperative systemic and ocular comorbidities included diabetes mellitus (40.6%), chronic pulmonary disease (21.2%), age-related macular degeneration (14.4%), and diabetes with ophthalmic manifestations (14.0%). The most common ocular complications were posterior capsular tear, anterior vitrectomy, or both during surgery (3.5%) and posterior capsular opacification after surgery (4.2%). Predictors of complications included: black race (OR, 1.38; 95% confidence interval [CI], 1.28-1.50), divorced status (OR, 1.10; 95% CI, 1.03-1.18), never married (OR, 1.26; 95% CI, 1.14-1.38), diabetes with ophthalmic manifestations (OR, 1.33; 95% CI, 1.23-1.43), traumatic cataract (OR, 1.80; 95% CI, 1.40-2.31), previous ocular surgery (OR, 1.29; 95% CI, 1.02-1.63), and older age. CONCLUSIONS: In a cohort of United States veterans with a high preoperative disease burden, selected demographic factors and ocular comorbidities were associated with greater risks of cataract surgery complications. Further large-scale studies are warranted to investigate cataract surgery outcomes for non-VHA United States patient populations.