Meta-analysis of transjugular intrahepatic portosystemic shunt creation with or without intravascular ultrasound guidance.

OBJECTIVE: To conduct a meta-analysis to assess the efficacy of intravascular ultrasound (IVUS) during transjugular intrahepatic portosystemic shunt (TIPS) creation. METHODS: MEDLINE and Embase databases were queried until July 2022 for comparative studies reporting procedure metrics for TIPS creation with or without IVUS guidance. Meta-analysis was performed with random-effects modelling for total procedural time, time to portal venous access, fluoroscopy time, iodinated contrast volume use, air kerma, dose area product, and number of needle passes. Intraoperative procedure-related complications were also reviewed. RESULTS: Of 95 unique records initially identified, 6 were eligible for inclusion. A total of 194 and 240 patients underwent TIPS with and without IVUS guidance. Pooled analyses indicated that IVUS guidance was associated with reduced total procedure time (SMD -0.76 [95% CI -1.02, -0.50] P < .001), time to portal venous access (SMD -0.41 [95% CI -0.67, -0.15] P = .002), fluoroscopy time (SMD, -0.54 [95% CI -1.02, -0.07]; P = .002), contrast volume use (SMD, -0.89 [95% CI -1.16, -0.63]; P < .001), air kerma (SMD, -0.75 [95% CI -1.11, -0.38]; P < .001) and dose area product (SMD, -0.98 [95% CI -1.77, -0.20]; P = .013). A total of 4.2 and 7.8 needle passes were required in the IVUS and non-IVUS group, respectively (SMD, -0.60 [95% CI -1.42, 0.21]; P = .134). Pooled complication rates were 15.2% (12/79) and 21.4% (28/131), respectively. CONCLUSION: IVUS guidance during TIPS creation improves procedural metrics including procedural time, contrast usage, and radiation exposure. ADVANCES IN KNOWLEDGE: (1) The use of IVUS during TIPS is associated with shorter procedural time, lower contrast usage, and radiation exposure. (2)The use of IVUS is not associated with higher complication rates.

Radiology Reports Do Not Accurately Portray the Severity of Cervical Neural Foraminal Stenosis.

STUDY DESIGN: Retrospective study. OBJECTIVE: (1) To compare cervical magnetic resonance imaging (MRI) radiology reports to a validated grading system for cervical foraminal stenosis (FS) and (2) to evaluate whether the severity of cervical neural FS on MRI correlates to motor weakness or patient-reported outcomes. BACKGROUND: Radiology reports of cervical spine MRI are often reviewed to assess the degree of neural FS. However, research looking at the association between these reports and objective MRI findings, as well as clinical symptoms, is lacking. PATIENTS AND METHODS: We retrospectively identified all adult patients undergoing primary 1 or 2-level anterior cervical discectomy and fusion at a single academic center for an indication of cervical radiculopathy. Preoperative MRI was assessed for neural FS severity using the grading system described by Kim and colleagues for each level of fusion, as well as adjacent levels. Neural FS severity was recorded from diagnostic radiologist MRI reports. Motor weakness was defined as an examination grade <4/5 on the final preoperative encounter. Regression analysis was conducted to evaluate whether the degree of FS by either classification was related to patient-reported outcome measure severity. RESULTS: A total of 283 patients were included in the study, and 998 total levels were assessed. There were significant differences between the MRI grading system and the assessment by radio-logists (P< 0.001). In levels with moderate stenosis, 28.9% were classified as having no stenosis by radiology. In levels with severe stenosis, 29.7% were classified as having mild-moderate stenosis or less. Motor weakness was found similarly often in levels of moderate or severe stenosis (6.9% and 9.2%, respectively). On regression analysis, no associations were found between baseline patient-reported outcome measures and stenosis severity assessed by radiologists or MRI grading systems. CONCLUSION: Radiology reports on the severity of cervical neural FS are not consistent with a validated MRI grading system. These radiology reports underestimated the severity of neural foraminal compression and may be inappropriate when used for clinical decision-making. LEVEL OF EVIDENCE: Level III.

High failure rate of 2-stage revision for the infected total elbow arthroplasty: a single institution's experience.

BACKGROUND: Despite 2-stage revision being a common treatment for elbow prosthetic joint infection (PJI), failure rates are high. The purpose of this study was to report on a single institution's experience with 2-stage revisions for elbow PJI and determine risk factors for failed eradication of infection. The secondary purpose was to determine risk factors for needing allograft bone at the second stage of revision in the setting of compromised bone stock. METHODS: We retrospectively analyzed all 2-stage revision total elbow arthroplasties (TEAs) performed for infection at a single institution between 2006 and 2020. Data collected included demographics and treatment course prior to, during, and after 2-stage revision. Radiographs obtained after explantation and operative reports were reviewed to evaluate for partial component retention and incomplete cement removal. The primary outcome was failed eradication of infection, defined as the need for repeat surgery to treat infection after the second-stage revision. The secondary outcome was the use of allograft for compromised bone stock during the second-stage revision. Risk factors for both outcomes were determined. RESULTS: Nineteen patients were included. Seven patients (37%) had either the humeral or ulnar component retained during the first stage, and 10 (53%) had incomplete removal of cement in either the humerus or ulna. Nine patients (47%) had allograft strut used during reimplantation and reconstruction. Nine patients (47%) failed to eradicate the infection after 2-stage revision. Demographic data were similar between the repeat-infection and nonrepeat-infection groups. Six patients (60%) with retained cement failed compared with 3 patients (33%) with full cement removal (P = .370). Two patients (29%) with a retained component failed compared to 7 patients (58%) with full component removal (P = .350). Allograft was used less frequently when a well-fixed component or cement was retained, with no patients with a retained component needing allograft compared to 9 with complete component removal (P = .003). Three patients (30%) with retained cement needed allograft, compared with 6 patients (67%) who had complete cement removal (P = .179). CONCLUSION: Nearly half of the patients failed to eradicate infection after 2-stage revision. The data did not demonstrate a clear association between retained cement or implants and risk of recurrent infection. Allograft was used less frequently when a component and cement were retained, possibly serving as a proxy for decreased bone loss during the first stage of revision. Therefore, the unclear benefit of removing well-fixed components and cement need to be carefully considered as it likely leads to compromised bone stock that complicates the second stage of revision.

Quantitative differences in volumetric calculations for radiation dosimetry in segmental Y90 treatment planning using hybrid angiography-CT compared with anatomic segmentation.

OBJECTIVE: To compare treatment volumes reconstructed from hybrid Angio-CT catheter-directed infusion imaging and Couinaud anatomic model as well as the implied differences in Y-90 radiation dosimetry. METHODS: Patients who underwent transarterial radioembolization (TARE) using Y-90 glass microspheres with pretreatment CT or MRI imaging as well as intraprocedural angiography-CT (Angio-CT) were analysed. Treatment volumes were delineated using both tumoural angiosomes (derived from Angio-CT) and Couinaud anatomic landmarks. Segmental and lobar treatment volumes were calculated via semi-automated contouring software. Volume and dose differences were compared by the two-tailed Student t test or Wilcoxon signed-rank test. Factors affecting volume and dose differences were assessed via simple and/or multiple variable linear regression analysis. RESULTS: From September 2018 to March 2021, 44 patients underwent 45 lobar treatments and 38 patients received 56 segmental treatments. All target liver lobes and all tumours were completely included within the field-of-view by Angio-CT. Tumour sizes ranged between 1.1 and 19.5 cm in diameter. Segmental volumes and treatment doses were significantly different between the Couinaud and Angio-CT volumetry methods (316 vs 404 mL, P < .0001 and 253 vs 212 Gy, P < .01, respectively). Watershed tumours were significantly correlated with underestimated volumes by the Couinaud anatomic model (P < .001). There was a significant linear relationship between tumour diameter and percent volume difference (R2 = 0.44, P < .0001). The Couinaud model overestimated volumes for large tumours that exhibited central hypovascularity/necrosis and for superselected peripheral tumours. CONCLUSIONS: Angio-CT may confer advantages over the Couinaud anatomic model and enable more accurate, personalized dosimetry for TARE. ADVANCES IN KNOWLEDGE: Angio-CT may confer advantages over traditional cross-sectional and cone-beam CT imaging for selective internal radiation therapy planning.

Segmental Yttrium-90 Radioembolization Using Glass Microspheres Greater than 400 Gray for the Treatment of Intrahepatic Cholangiocarcinoma: A Preliminary Experience.

Radiation segmentectomy with a dose of >190 Gy using yttrium-90 (90Y) glass microspheres for intrahepatic cholangiocarcinoma (iCCA) has been shown to be safe and effective. The present study further increased the dose to >400 Gy for treatment of iCCA as complete pathologic necrosis has been shown in hepatocellular carcinoma using this ablative approach. A total of 10 patients with 13 tumors (median size, 5.3 cm; range, 1.5-13.6 cm) at a single institution underwent >400-Gy segmental radioembolization. Objective response was achieved in all tumors (13 of 13, 100%). One patient developed a Grade 3 or greater major adverse event (stroke and hepatic decompensation). One patient was bridged to transplant (>95% pathologic necrosis), whereas another underwent resection (>99% necrosis). Contralateral hypertrophy was observed in 6 out of 6 patients treated with modified lobectomy dosing, with a functional liver reserve increase from a median of 31.5% to 57.1%. The present report suggests that segmental transarterial radioembolization with >400 Gy is feasible in terms of safety and effectiveness for treating iCCA.

Do Magnets Have the Potential to Serve as a Stabilizer for the Shoulder Joint in Massive Rotator Cuff Tears?: A Biomechanical Cadaveric Study.

Background: Disruption of the rotator cuff muscles compromises concavity compression force, which leads to superior migration of the humeral head and loss of stability. A novel idea of using the magnetic force to achieve shoulder stabilization in massive rotator cuff tears (MRCTs) was considered because the magnets can stabilize two separate entities with an attraction force. This study aimed to investigate the biomechanical effect of the magnetic force on shoulder stabilization in MRCTs. Methods: Seven fresh frozen cadaveric specimens were used with a customized shoulder testing system. Three testing conditions were set up: condition 1, intact rotator cuff without magnets; condition 2, an MRCT without magnets; condition 3, an MRCT with magnets. For each condition, anterior-posterior translation, superior translation, superior migration, and subacromial contact pressure were measured at 0°, 30°, and 60° of abduction. The abduction capability of condition 2 was compared with that of condition 3. Results: The anterior-posterior and superior translations increased in condition 2; however, they decreased compared to condition 2 when the magnets were applied (condition 3) in multiple test positions and loadings (p < 0.05). Abduction capability improved significantly in condition 3 compared with that in condition 2, even for less deltoid loading (p < 0.05). Conclusions: The magnet biomechanically played a positive role in stabilizing the shoulder joint and enabled abduction with less deltoid force in MRCTs. However, to ensure that the magnet is clinically applicable as a stabilizer for the shoulder joint, it is necessary to thoroughly verify its safety in the human body and to conduct further research on technical challenges.

The biomechanical effects of acromial fracture angulation in reverse total shoulder arthroplasty.

BACKGROUND: The biomechanical changes and treatment guidelines on acromial fracture after reverse shoulder arthroplasty (RSA) are still not well understood. The purpose of our study was to analyze the biomechanical changes with respect to acromial fracture angulation in RSA. METHODS: RSA was performed on 9 fresh-frozen cadaveric shoulders. An acromial osteotomy was performed on the plane extending from the glenoid surface to simulate an acromion fracture. Four conditions of acromial fracture inferior angulation were evaluated (0°, 10°, 20°, and 30° angulation). The middle deltoid muscle loading origin position was adjusted based on the position of each acromial fracture. The impingement-free angle and capability of the deltoid to produce movement in the abduction and forward flexion planes were measured. The length of the anterior, middle, and posterior deltoid was also analyzed for each acromial fracture angulation. RESULTS: There was no significant difference in the abduction impingement angle between 0° (61.8° ± 2.9°) and 10° angulation (55.9° ± 2.8°); however, the abduction impingement angle of 20° (49.3° ± 2.9°) significantly decreased from 0° and 30° angulation (44.2° ± 4.6°), and 30° angulation significantly differed from 0° and 10° (P < .01). On forward flexion, 10° (75.6° ± 2.7°), 20° (67.9° ± 3.2°), and 30° angulation (59.8° ± 4.0°) had a significantly decreased impingement-free angle than 0° (84.2° ± 4.3°; P < .01), and 30° angulation had a significantly decreased impingement-free angle than 10°. On analysis of glenohumeral abduction capability, 0° significantly differed (at 12.5, 15.0, 17.5, and 20.0N) from 20° and 30°. For forward flexion capability, 30° angulation showed a significantly smaller value than 0° (15N vs. 20N). As acromial fracture angulation increased, the middle and posterior deltoid muscles of 10°, 20°, and 30° became shorter than those of 0°; however, no significant change was found in the anterior deltoid length. CONCLUSIONS: In acromial fractures at the plane of glenoid surface, 10° inferior angulation of the acromion did not interfere with abduction and abduction capability. However, 20° and 30° of inferior angulation caused prominent impingement in abduction and forward flexion and reduced abduction capability. In addition, there was a significant difference between 20° and 30°, suggesting that not only the location of the acromion fracture after RSA but also the degree of angulation are important factors for shoulder biomechanics.

Biomechanical consequences of glenoid and humeral lateralization in reverse total shoulder arthroplasty.

BACKGROUND: The objective of our study was to quantify the biomechanical effectiveness of lateralization in RTSA with respect to glenoid and humeral component configurations. METHODS: Eight cadaveric shoulders were tested in a custom shoulder testing system. Three parameters, including the glenosphere thickness, humeral tray offset, and insert thickness, were assessed by implanting 8 configurations on each specimen. Humeral position, maximum internal rotation, and maximum external rotation (ER) before impingement were quantified at 0° and 30° glenohumeral abduction. The adduction angle at which the humeral component contacted the inferior scapular neck and the abduction angle where acromial notching occurred were also measured. The simulated active range of motion, including ER and abduction capability, was tested by increasing the load applied to the remaining posterior cuff and middle deltoid, respectively. Stability was evaluated by the forces that induced anterior dislocation at 30° abduction. RESULTS: The thicker glenosphere affected only lateralization, whereas the centric humeral tray and thicker insert significantly affected humeral lateralization and distalization simultaneously. Greater adduction and ER angles were found in more lateralized humerus. A significant positive correlation between humeral lateralization and ER capability was observed; however, lateralization did not significantly improve implant stability in this cadaveric testing system. CONCLUSION: Lateralization is achievable at both the glenoid and humeral sides but has different effects; therefore, lateralized implant options should be selected according to patients' needs. Lateralization is an effective strategy for reducing adduction notching while increasing ER capability. Thicker glenospheres only affected humeral lateralization. The centric humeral tray would be selected for less distalization to avoid overlengthening, whereas an eccentric humeral tray is the most effective for distalization and medialization in reducing abduction notching to the acromion and for patients with pseudoparalysis.

2022 Bernard Morrey Award: the elbow ulnar collateral ligament complex demonstrates region specific stretching and recovery characteristics with valgus loading.

BACKGROUND: The objective of this study was to quantify the valgus laxity and strain of the elbow ulnar collateral ligament (UCL) complex after repeated valgus stretching and subsequent recovery. Understanding these changes may have important implications in improving strategies for injury prevention and treatment. The hypothesis was that the UCL complex will demonstrate a permanent increase in valgus laxity and region-specific increase in strain as well as region-specific recovery characteristics. METHODS: Ten cadaveric elbows (7M, 3F, 61.7 ± 2.7 years) were used. Valgus angle and strain of the anterior and posterior bands of the anterior bundle and the posterior bundle were measured at 1 Nm, 2.5 Nm, 5 Nm, 7.5 Nm, and 10 Nm of valgus torque at 70° of flexion for: (1) intact UCL, (2) stretched UCL, and (3) rested UCL. To stretch the UCL, elbows were cycled with increasing valgus torque at 70° of flexion (10 Nm-20 Nm in 1 Nm increments) until the valgus angle increased 8° from the intact valgus angle measured at 1Nm. This position was held for 30 minutes. Specimens were then unloaded and rested for 2 hours. Linear mixed effects model with Tukey's post hoc test was used for statistical analysis. RESULTS: Stretching significantly increased valgus angle compared to the intact condition 3.2° ± 0.2° (P < .001). Strains of both the anterior and posterior bands of the anterior bundle were significantly increased from intact by 2.8% ± 0.9% (P = .015) and 3.1% ± 0.9% (P = .018), respectively at 10 Nm. Strain in the distal segment of the anterior band was significantly higher than the proximal segment with loads of 5 Nm and higher (P < .030). After resting, the valgus angle significantly decreased from the stretched condition by 1.0° ± 0.1° (P < .001) but failed to recover to intact levels (P < .004). After resting, the posterior band had a significantly increased strain compared to the intact state of 2.6% ± 1.4% (P = .049) while the anterior band was not significantly different from intact. CONCLUSION: After repeated valgus loading and subsequent resting, the UCL complex demonstrated permanent stretching with some recovery but not to intact levels. The anterior band demonstrated increased strain in the distal segment compared to the proximal segment with valgus loading. The anterior band was able to recover to strain levels similar to intact after resting, while the posterior band did not.

Latissimus dorsi and teres major tendon transfer for irreparable anterosuperior rotator cuff tear improves kinematics and internal rotation compared to latissimus dorsi tendon transfer.

INTRODUCTION: Latissimus dorsi and teres major (LDTM) tendon transfer has demonstrated better clinical outcomes compared to Latissimus dorsi (LD) transfer for irreparable anterosuperior cuff (subscapularis/supraspinatus) tears; however, the biomechanical effects of these procedures are unknown. Therefore, the objective of this study was to compare kinematics and internal rotation of LDTM transfer to LD transfer for anterosuperior cuff tear. METHODS: Eight cadaveric shoulders were tested in four conditions; (1) intact, (2) anterosuperior rotator cuff tear, (3) LDTM transfer, and (4) LD transfer. Glenohumeral kinematics and internal rotation at 0°, 30°, and 60° of glenohumeral abduction in the scapular plane were measured. Muscle loading was applied based on physiological cross-sectional area ratios with three muscle loading conditions to simulate potentially increased tension due to the advanced insertion site of the transferred tendons. RESULTS: The anterosuperior rotator cuff tear leads to a significant superior shift of the humeral head compared to intact at 0° and 30° abduction (p < 0.039). Both the LDTM (p < 0.047) and LD transfers (p < 0.032) significantly shifted the humeral head inferiorly compared to the tear condition.; however, the LDTM transfer shifted the head in the anteroinferior direction compared to the LD transfer at 60° abduction and 30° ER (p < 0.045). Both LDTM and LD transfer significantly increased internal resting rotation (p < 0.008) and maximum internal rotation (p < 0.008) compared to anterosuperior rotator cuff tear and intact at 30° and 60° abduction. LDTM transfer resulted in a significant internal resting rotation compared with the LD transfer at 30° abduction with double muscle loading (p = 0.02). At 0° abduction, the LDTM transfer (p < 0.027) significantly increased maximum internal rotation compared to anterosuperior rotator cuff tear and intact. CONCLUSION: Although both LDTM and LD tendon transfer improved the abnormal humeral head apex position and internal rotation compared with the tear condition, the LDTM transfer was biomechanically superior to the LD transfer in a cadaveric model.

Biomechanical comparison of combined latissimus dorsi and teres major tendon transfer vs. latissimus dorsi tendon transfer in shoulders with irreparable anterosuperior rotator cuff tears.

BACKGROUND: Irreparable anterosuperior rotator cuff tears (IASRCTs) can result in a gradual loss of active elevation and internal rotation, superior and anterior translation of the humeral head, and cuff tear arthropathy. Joint-preserving treatment options for IASRCTs in young and high-demand elderly patients remain a subject of ongoing debate. The aim of the study was to evaluate the biomechanical efficacy of the combined latissimus dorsi and teres major tendon (LDTM) transfer and compare it to an isolated latissimus dorsi (LD) transfer in a cadaveric IASRCT model. METHODS: Eight cadaveric shoulders (mean age, 68.3 ± 5.2 years; range 58-71) were tested with a custom shoulder testing system. All specimens were tested at 0°, 30°, and 60° of glenohumeral abduction in the scapular plane under 4 conditions: (1) intact, (2) IASRCT, (3) combined LDTM transfer, and (4) isolated LD transfer. The superior and anteroinferior translation and subacromial contact pressure were measured. The effects of 3 different LD and LDTM muscle loading conditions were investigated to determine the effectiveness of the muscle transfer conditions. A linear mixed effect model was used for statistical analysis, followed by a Tukey post hoc test. RESULTS: IASRCTs significantly increased superior translation, anteroinferior translation, and subacromial peak contact pressure. Combined LDTM transfer significantly decreased superior and anteroinferior translation compared with IASRCTs in all positions and muscle loadings. Isolated LD transfer did not significantly decrease superior (P > .115) and anteroinferior translation (P > .151) compared to IASRCT at any abduction and muscle loads except superior translation at 60° abduction and 90° of external rotation (ER) (P < .036). LDTM transfer also significantly decreased peak contact pressure from the IASRCT condition at every abduction angle (P < .046). However, isolated LD transfer significantly decreased subacromial peak contact pressure only at 30° abduction and 0° and 30° of ER with triple loading (P < .048), as well as at 60° abduction and 90° of ER (P < .003). CONCLUSIONS: Combined LDTM transfer decreased superior translation, anteroinferior translation, and subacromial contact pressure compared with the IASRCT condition. Isolated LD transfer did not improve glenohumeral translation and subacromial contact pressure. Combined LDTM transfer may be a more reliable treatment option than isolated LD transfer in patients with an IASRCT.

Risk Factors for Abscess Development Following Percutaneous Microwave Ablation Therapy of Hepatic Tumors.

PURPOSE: To investigate risk factors associated with post-microwave ablation (MWA) abscess development. MATERIALS AND METHODS: A retrospective case-control analysis was conducted to identify hepatic MWA performed at a single tertiary medical center between January 2010 and January 2022. Case and control patients were defined as those who did or did not develop intrahepatic abscess within 3 months following MWA, respectively. Correlations between risk factors and post-MWA abscess development were assessed by Fisher's exact test. RESULTS: Between 2010 and 2022, 253 patients underwent 376 MWA sessions with post-ablation abscess complication rate of 1.1% (4/376). Complications associated with intrahepatic abscess included bacteremia, empyema, pleural abscess, subcutaneous abscess, cholangitis, bile leak, biliocutaneous and arterio-biliary fistulae, and pseudoaneurysm. One patient expired from septic shock 5 days post-ablation. All abscesses were treated by percutaneous drainage and antibiotics. One patient required concomitant placement of a biliary stent and embolization of a biliocutaneous tract. History of Sphincter of Oddi manipulation (p < 0.01), cholangiocarcinoma (p < 0.05), transarterial radioembolization (TARE) to the index lesion (p < 0.05), and abnormal serum alkaline phosphatase levels (p < 0.05) were significantly correlated with post-MWA abscess. The risk of developing post-MWA abscesses for patients with a history of cholangiocarcinoma or a history of Sphincter of Oddi manipulation were 20.0% and 27.2%, respectively. CONCLUSION: Patients with prior Sphincter of Oddi manipulation, cholangiocarcinoma, or TARE are at greater risk of developing post-MWA abscess.

Hybrid CT-angiography (Angio-CT) for combined CT and fluoroscopic procedures in interventional radiology enhances utilization.

PURPOSE: To investigate the utilization of an angiography-CT (Angio-CT) system and its advantages for single patient encounters. METHODS: Interventions utilizing both CT and fluoroscopy to perform multiple procedures in a single encounter or single interventions using both were identified. Cases were stratified by complexity (defined by RVUs). Comparative analyses of room (TRoom) and total encounter (TEncounter) times were performed between non-complex bundled cases and controls. RESULTS: Between June 2018 and August 2019, 1108 procedures were performed via the Angio-CT system; 10% (114/1108) used both fluoroscopy and CT. 21% (24/114) Involved more than one procedure in a single encounter that required a CT-only and fluoroscopy-only bundled procedure. 59% (67/114) were non-complex, and 70% (80/114) were non-oncologic. 82.5% (14/17) of non-complex bundled procedures demonstrated TRoom below the mean of their respective controls; 52.8% (9/17) were 2 standard deviations below the control means. Pleural catheter placement following post-lung biopsy pneumothorax was the most common non-complex bundled case with a significant reduction in TRoom when performed via Angio-CT compared to control (99 vs. 163 min, p < 0.0001). There was a significant reduction in TEncounter for abdominopelvic drain placement procedures bundled with either (1) percutaneous nephrostomy tube evaluation with or without replacement, or (2) central venous catheter placement (211 min vs. 344 min, p < 0.001 and 231 min vs. 347 min, p < 0.05, respectively). CONCLUSION: The primary use for the hybrid Angio-CT system was to perform non-oncologic and non-complex cases with potential reduction in TRoom and TEncounter for specific non-complex bundled cases.

A case of hyperpigmentation induced by hydroxychloroquine and quinacrine in a patient with systemic lupus erythematosus and review of the literature.

Hydroxychloroquine (HQ) and quinacrine are widely used antimalarials for systemic lupus erythematosus (SLE) and other autoimmune diseases. We report a case of antimalarial-induced hyperpigmentation in a 57-year old African-American woman. The patient had a long-standing history of SLE that was treated with HQ and quinacrine in varying doses for 16 years. The disease improved considerably and entered remission; however, the patient subsequently developed severe, disseminated hyperpigmentation on her face, trunk, upper and lower extremities. A malar facial biopsy revealed numerous perivascular and scattered interstitial, heavily pigment laden dark brown to black macrophages. The Fontana Masson staining was positive for melanin, and Perl's stain for iron was negative. This staining pattern, to our knowledge, has only been reported once before in the literature. Our patient represents a rare case of severe recalcitrant hyperpigmentation induced by combination HQ and quinacrine therapy for SLE.

Analyzing Radiation Use during Transjugular Intrahepatic Portosystemic Shunt Creation.

Portal vein access during transjugular intrahepatic portosystemic shunt creation was examined in 11 patients. Radiation metrics (kerma area product, reference point air kerma, and fluoroscopy times) during portal vein access were significantly greater for conventional versus intravascular US-guided transjugular intrahepatic portosystemic shunt (54.8 mGy ∙ cm2 ± 27.6 vs 8.4 mGy ∙ cm2 ± 5.0, P = .009; 210.4 mGy ± 109.1 vs 29.5 mGy ± 18.4, P = .009; 19.1 min ± 8.6 vs 8.9 min ± 4.6, P = .04). Wedged hepatic venography is a major contributor to radiation exposure. Intravascular US guidance is associated with significantly reduced radiation use.

Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators.

Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognate diol, eliminating a proresolving signal that potently suppresses IL-8-driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF.

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites.

UNLABELLED: Serratia marcescens generates secondary metabolites and secreted enzymes, and it causes hospital infections and community-acquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressed crp mutant phenotypes. Evidence supports that the putative response regulator eepR was directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin- and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promoters in vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes. IMPORTANCE: This study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacterium Serratia marcescens to produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allow S. marcescens to compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science.

Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation.

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1ß production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation.

The effect of hyperoxia on reactive oxygen species (ROS) in rat petrosal ganglion neurons during development using organotypic slices.

Hyperoxia, during development in rats, results in hypoxic chemosensitivity ablation, carotid body hypoplasia, and reduced chemoafferents. We hypothesized that hyperoxia increases reactive oxygen species (ROS) in cell bodies of chemoafferents. Organotypic slices of petrosal-nodose ganglia from rats at day of life (DOL) 5-6 and 17-18 were exposed to 8%, 21%, or 95% O(2) for 4 h in the presence or absence of the ROS-sensitive fluorescent indicator, CM-H(2)DCFDA, and propidium iodide was used to determine the relationship between cell death and oxygen tension. In tissue slices from DOL 5-6 rats, fluorescence intensity was 182.5 +/- 2.9 for hypoxia, 217.5 +/- 3.3 for normoxia, and 336.6 +/- 3.8 for hyperoxia, (mean +/- SEM, p < 0.001, ANOVA). Normoxia increased ROS levels by 19.2% from hypoxia (p < 0.01) with a further increase of 54.8% from normoxia to hyperoxia (p < 0.001). In tissue slices from DOL 17-18 rats, ROS levels increased with increasing oxygen tension but were less than in younger animals (p < 0.01, ANOVA). The antioxidants, NAC and TEMPO-9-AC, attenuated ROS levels and cell death. Electron microscopy demonstrated that hyperoxia damages the ultrastructure within petrosal ganglion neurons. Hyperoxic-induced increased levels of ROS in petrosal ganglion neurons may contribute to loss of hypoxic chemosensitivity during early postnatal development.

Maturation of peripheral arterial chemoreceptors in relation to neonatal apnoea.

Apnoea and periodic breathing are the hallmarks of breathing for the infant who is born prematurely. Sustained respiration is obtained through modulation of respiratory-related neurons with inputs from the periphery. The peripheral arterial chemoreceptors, uniquely and reflexly change ventilation in response to changes in oxygen tension. The chemoreflex in response to hypoxia is hyperventilation, bradycardia and vasoconstriction. The fast response time of the peripheral arterial chemoreceptors to changes in oxygen and carbon dioxide tension increases the risk of more periodicity in the breathing pattern. As a result of baseline hypoxaemia, peripheral arterial chemoreceptors contribute more to baseline breathing in premature than in term infants. While premature infants may have an augmented chemoreflex, infants who develop bronchopulmonary dysplasia have a blunted chemoreflex at term gestation. The development of chemosensitivity of the peripheral arterial chemoreceptors and environmental factors that might cause maldevelopment of chemosensitivity with continued maturation are reviewed in an attempt to help explain the physiology of apnoea of prematurity and the increased incidence of sudden infant death syndrome (SIDS) in infants born prematurely and those who are exposed to tobacco smoke.