Heterotopic ossification in right popliteal fossa causing arterial insufficiency.

Heterotopic ossification (HO) is the abnormal formation of extra-skeletal bone in soft tissue, which can occur after trauma or surgery. HO in joints can cause pain, hinder mobility, and compress surrounding nerves and blood vessels. We present an unusual case of arterial insufficiency caused by HO in the right popliteal fossa.

TLR4-Endothelin Axis Controls Syncytiotrophoblast Motility and Confers Fetal Protection in Placental Malaria.

Pregnancy-associated malaria is often associated with adverse pregnancy outcomes. Placental circulatory impairments are an intriguing and unsolved component of malaria pathophysiology. Here, we uncovered a Toll-like receptor 4 (TLR4)-TRIF-endothelin axis that controls trophoblast motility and is linked to fetal protection during Plasmodium infection. In a cohort of 401 pregnancies from northern Brazil, we found that infection during pregnancy reduced expression of endothelin receptor B in syncytiotrophoblasts, while endothelin expression was only affected during acute infection. We further show that quantitative expression of placental endothelin and endothelin receptor B proteins are differentially controlled by maternal and fetal TLR4 alleles. Using murine malaria models, we identified placental autonomous responses to malaria infection mediated by fetally encoded TLR4 that not only controlled placental endothelin gene expression but also correlated with fetal viability protection. In vitro assays showed that control of endothelin expression in fetal syncytiotrophoblasts exposed to Plasmodium-infected erythrocytes was dependent on TLR4 via the TRIF pathway but not MyD88 signaling. Time-lapse microscopy in syncytiotrophoblast primary cultures and cell invasion assays demonstrated that ablation of TLR4 or endothelin receptor blockade abrogates trophoblast collective motility and cell migration responses to infected erythrocytes. These results cohesively substantiate the hypothesis that fetal innate immune sensing, namely, the TRL4-TRIF pathway, exerts a fetal protective role during malaria infection by mediating syncytiotrophoblast vasoregulatory responses that counteract placental insufficiency.

Single- versus multiple-stage catheter-directed thrombolysis for acute iliofemoral deep venous thrombosis does not have an impact on iliac vein stent length or patency rates.

BACKGROUND: Incomplete venous thrombolysis and residual nonstented iliac vein disease are known predictors of recurrent deep venous thrombosis (DVT). Controversy exists as to whether the number of thrombolysis sessions affects total stent treatment length or stent patency. The goal of this study was to evaluate the outcomes of patients who underwent single vs multiple catheter-directed lysis sessions with regard to stent extent and patency. METHODS: Consecutive patients who underwent thrombolysis and stenting for acute iliofemoral DVT between 2007 and 2018 were identified and divided into two groups on the basis of the number of treatments performed (one vs multiple sessions). Operative notes and venograms were reviewed to determine the number of lytic sessions performed and stent information, including size, location, total number, and length treated. End points included total stent length, 30-day and long-term patency, and post-thrombotic syndrome (Villalta score ≥5). The χ2 comparisons, logistic regression, and survival analysis were used to determine outcomes. RESULTS: There were 79 patients who underwent lysis and stenting (6 bilateral interventions; mean age, 45.9 ± 17 years; 48 female). Ten patients (12 limbs) underwent single-stage treatment with pharmacomechanical thrombolysis, and the remaining 69 (73 limbs) had two to four operating room sessions combining pharmacomechanical and catheter-directed thrombolysis. Patients who underwent a single-stage procedure were older and more likely to have a malignant disease. These patients received less tissue plasminogen activator compared with the multiple-stage group (17.2 ± 2.2 mg vs 27.6 ± 11.6 mg; P = .008). Average stent length was 8.8 ± 5.2 cm for the single-stage group vs 9.2 ± 4.6 cm for the multiple-stage group (P = .764). Patients who underwent a single-stage procedure had no difference in average length of stay from that of patients who underwent multiple sessions (8.5 days vs 5.9 days; P = .269). The overall 30-day rethrombosis rate was 7.3%. Two-year patency was 72.2% and 74.7% for the single and multiple stages, respectively (P = .909). The major predictors for loss of primary patency were previous DVT (hazard ratio [HR], 5.99; P = .020) and incomplete lysis (HR, 5.39; P = .014) but not number of procedures (HR, 0.957; P = .966). The overall post-thrombotic syndrome rate was 28.4% at 5 years and was also not associated with the number of treatment sessions. CONCLUSIONS: Single- vs multiple-stage thrombolysis for DVT is not associated with a difference in extent of stent coverage. Patency rates remain high for iliac stenting irrespective of the number of lytic sessions, provided lysis is complete and the diseased segments are appropriately stented.

Functional popliteal artery entrapment syndrome: A review of diagnostic and management approaches.

Functional popliteal artery entrapment syndrome (FPAES) presents a challenge for clinicians in the field today. The relative rarity of the disease coupled with its affliction primarily in young, athletic individuals makes it a difficult condition to diagnose. Treatment modalities have been limited to surgical intervention, with more novel methods being developed over the last several years. We present a case report and review the diagnostic and management approaches for FPAES, shedding light on proposed future interventions.

Maternal-Fetal Conflict During Infection: Lessons From a Mouse Model of Placental Malaria.

Infections that reach the placenta via maternal blood can target the fetal-placental barrier and are associated with reduced birth weight, increased stillbirth, miscarriage and perinatal mortality. Malaria during pregnancy can lead to infection of the placental tissue and to adverse effects on the unborn child even if the parasite is successfully cleared, indicating that placental sufficiency is significantly compromised. Human samples and animal models of placental malaria have been used to unravel mechanisms contributing to this insufficiency and have implicated molecular pathways related to inflammation, innate immunity and nutrient transport. Remarkably, fetal TLR4 was found to take part in placental responses that protect the fetus, in contrast to maternal TLR4 responses that presumably preserve the mother's health but result in reduced fetal viability. We propose that this conflict of fetal and maternal responses is a determinant of the clinical outcomes of placental malaria and that fetally derived trophoblasts are on the front lines of this conflict.

Outcomes and predictors of failure of iliac vein stenting after catheter-directed thrombolysis for acute iliofemoral thrombosis.

OBJECTIVE: Iliac vein stenting is recommended to treat venous outflow obstruction after catheter-directed thrombolysis for acute iliofemoral deep venous thrombosis (DVT). Data on the outcome of proximal and distal stent extension are limited. Proximal stent extension to the vena cava may obstruct the contralateral iliac vein, whereas distal extension below the inguinal ligament contradicts common practice for arterial stents. The aim of this retrospective study was to assess outcomes and predictors of failure of iliac vein stents and contralateral iliac vein thrombosis, taking into consideration stent positioning. METHODS: Consecutive patients who underwent thrombolysis and stenting for DVT between May 2007 and September 2017 were identified from a prospectively maintained database. The intraoperative venograms were reviewed for proximal stent placement (covering >50% contralateral iliac vein orifice) and distal placement across the inguinal ligament. End points were ipsilateral DVT recurrence, post-thrombotic syndrome (PTS; Villalta score ≥5), and contralateral DVT. Patients with chronic contralateral DVT or contralateral iliac vein stenting at baseline were excluded from the contralateral DVT outcome evaluation. Survival analysis and Cox regression models were used to determine outcomes. RESULTS: Of 142 patients lysed, 73 patients (12 bilateral DVTs; mean age, 45.8 ± 17.2 years; 46 female patients) were treated with various combinations of thrombolytic techniques and at least one self-expanding iliac stent (77 stented limbs). Thirty-day recurrence developed in nine (12.3%) patients. The 3-year primary patency and secondary patency rates were 75.2% and 82.2%, respectively. The single predictor for loss of primary patency was incomplete thrombolysis (≤50%; hazard ratio [HR], 7.41; P = .002). Overall, 3 of 12 (25%) stents extending below the inguinal ligament occluded at 1 month, 2 months, and 9 months, respectively. The overall rate of PTS (Villalta score ≥5) in the stented cohort was 14.4% at 5 years. This was predicted by incomplete lysis (<50%; HR, 7.09; P = .040), stent extension below the inguinal ligament (HR, 6.68; P = .026), and male sex (HR, 6.02; P = .041). Of the 17 stents that extended into the contralateral common iliac vein and 58 stents that did not, there were 1 (5.9%) and 5 (8.6%) contralateral DVTs (P = .588) at an average follow-up of 27.4 ± 33.7 and 22.2 ± 22.3 months (P = .552), respectively. CONCLUSIONS: Iliac stenting after thrombolysis for acute DVT guarantees high patency and low PTS rates, provided adequate thrombus resolution has been achieved before stent placement. Stent placement below the inguinal ligament does not affect the patency but may be associated with a higher PTS rate. Stenting proximal to the iliocaval confluence, although a precipitating factor, may not independently increase the likelihood of contralateral DVT.

Outcomes of peritoneal dialysis catheter configurations and pelvic fixation.

BACKGROUND: Laparoscopic peritoneal dialysis catheter placement has expanded indications, although a relative paucity of data exists about the best configuration for improving outcomes. The purpose of this study is to investigate the role of different catheter configurations and pelvic fixation on catheter and patient outcomes. METHODS: Retrospective chart review of patients undergoing peritoneal dialysis catheter implantation between January 1, 2013, and December 31, 2016. All procedures were conducted laparoscopically at a single center. Statistical analyses were conducted using Stata/SE 14.2. RESULTS: Buried catheter configuration was a statistically significant predictor of peritonitis compared to unburied configuration (P = 0.008). Buried catheter was exteriorized at 100 days (SD 107.8). A longer length of time to exteriorization significantly correlated with peritonitis, need for revision, and need for revision pelvic fixation (P < 0.05). Additionally, initial pelvic fixation was a significant predictor of revision (HR 3.94). CONCLUSIONS: Peritoneal dialysis catheter placement via a laparoscopic approach can be successfully performed in a diverse patient mix with positive results. However, buried catheter configuration and prophylactic pelvic fixation should be carefully employed in select patients.

Cost-Effectiveness of a Radio Frequency Hemostatic Sealer (RFHS) in Adult Spinal Deformity Surgery.

BACKGROUND: Patients undergoing posterior spinal fusion surgery can lose a substantial amount of blood. This can prolong operative time and require transfusion of allogeneic blood components, which increases the risk of infection and can be the harbinger of serious complications. Does a saline-irrigated bipolar radiofrequency hemostatic sealer (RFHS) help reduce transfusion requirements? METHODS: In an observational cohort study, we compared transfusion requirements in 30 patients undergoing surgery for adult spinal deformity using the RFHS with that of a historical control group of 30 patients in which traditional hemostasis was obtained with bipolar electrocautery and matched them for blood loss-related variables. Total expense to the hospital for the RFHS, laboratory expenses, and blood transfusions was used for cost calculations. The incremental cost-effectiveness ratio was calculated using the number of blood transfusions avoided as the effectiveness payoff. RESULTS: Using a multivariable linear regression model, we found that only estimated blood loss (EBL) was an independent significant predictor of transfusion requirement in both groups. We evaluated the variables of age, EBL, time duration of surgery, preoperative hemoglobin, hemoglobin nadir during surgery, body mass index, length of stay, and number of levels operated on. Mean EBL was greater in the control group (2201 vs. 1416 mL, P = 0.0099). The number of transfusions also was greater in the control group (14.5 vs. 6.5, P = 0.0008). In the cost-effectiveness analysis, we found that the RFHS cost $108 more (compared with not using the RFHS) to avoid 1 unit of blood transfusion. CONCLUSIONS: The cost-effectiveness analysis revealed that if we are willing to pay $108 to avoid 1 unit of blood transfusion, the use of the RFHS is a reasonable choice to use in open surgery for adult spinal deformity.

Fetal and Maternal Innate Immunity Receptors Have Opposing Effects on the Severity of Experimental Malaria in Pregnancy: Beneficial Roles for Fetus-Derived Toll-Like Receptor 4 and Type I Interferon Receptor 1.

Malaria in pregnancy (MiP) is a distinctive clinical form of Plasmodium infection and is a cause of placental insufficiency leading to poor pregnancy outcomes. Maternal innate immunity responses play a decisive role in the development of placental inflammation, but the action of fetus-derived factors in MiP outcomes has been overlooked. We investigated the role of the Tlr4 and Ifnar1 genes, taking advantage of heterogenic mating strategies to dissect the effects mediated by maternally and fetally derived Toll-like receptor 4 (TLR4) or type I interferon receptor 1 (IFNAR1). Using a mouse infection system displaying severe MiP outcomes, we found that the expressions of TLR4 and IFNAR1 in the maternal compartment take part in deleterious MiP outcomes, but their fetal counterparts patently counteract these effects. We uncovered that fetal TLR4 contributes to the in vitro uptake of infected erythrocytes by trophoblasts and to the innate immune response in the placenta, offering robust protection of fetus viability, but had no sensible impact on the placental parasite burden. In contrast, we observed that the expression of IFNAR1 in the fetal compartment was associated with a reduced placental parasite burden but had little beneficial effect on fetus outcomes. Furthermore, the downregulation of Ifnar1 expression in infected placentas and in trophoblasts exposed to infected erythrocytes indicated that the interferon-IFNAR1 pathway is involved in the trophoblast response to infection. This work unravels that maternal and fetal counterparts of innate immune pathways drive opposing responses in murine placental malaria and implicates the activation of innate receptors in fetal trophoblast cells in the control of placental infection and in the protection of the fetus.

Cost of coils for intracranial aneurysms: clinical decision analysis for implementation of a capitation model.

OBJECTIVE The price of coils used for intracranial aneurysm embolization has continued to rise despite an increase in competition in the marketplace. Coils on the US market range in list price from $500 to $3000. The purpose of this study was to investigate potential cost savings with the use of a price capitation model. METHODS The authors built a clinical decision analytical tree and compared their institution's current expenditure on endovascular coils to the costs if a capped-price model were implemented. They retrospectively reviewed coil and cost data for 148 patients who underwent coil embolization from January 2015 through September 2016. Data on the length and number of coils used in all patients were collected and analyzed. The probabilities of a treated aneurysm being ≤/> 10 mm in maximum dimension, the total number of coils used for a case being ≤/> 5, and the total length of coils used for a case being ≤/> 50 cm were calculated, as was the mean cost of the currently used coils for all possible combinations of events with these probabilities. Using the same probabilities, the authors calculated the expected value of the capped-price strategy in comparison with the current one. They also conducted multiple 1-way sensitivity analyses by applying plausible ranges to the probabilities and cost variables. The robustness of the results was confirmed by applying individual distributions to all studied variables and conducting probabilistic sensitivity analysis. RESULTS Ninety-five (64%) of 148 patients presented with a rupture, and 53 (36%) were treated on an elective basis. The mean aneurysm size was 6.7 mm. A total of 1061 coils were used from a total of 4 different providers. Companies A (72%) and B (16%) accounted for the major share of coil consumption. The mean number of coils per case was 7.3. The mean cost per case (for all coils) was $10,434. The median total length of coils used, for all coils, was 42 cm. The calculated probability of treating an aneurysm less than 10 mm in maximum dimension was 0.83, for using 5 coils or fewer per case it was 0.42, and for coil length of 50 cm or less it was 0.89. The expected cost per case with the capped policy was calculated to be $4000, a cost savings of $6564 in comparison with using the price of Company A. Multiple 1-way sensitivity analyses revealed that the capped policy was cost saving if its cost was less than $10,500. In probabilistic sensitivity analyses, the lowest cost difference between current and capped policies was $2750. CONCLUSIONS In comparison with the cost of coils from the authors' current provider, their decision model and probabilistic sensitivity analysis predicted a minimum $407,000 to a maximum $1,799,976 cost savings in 148 cases by adapting the capped-price policy for coils.

Structure and characterisation of hydroxyethylcellulose-silica nanoparticles.

Functionalising nanoparticles with polymers has gained much interest in recent years, as it aids colloidal stability and manipulation of surface properties. Here, polymer-coated thiolated silica nanoparticles were synthesised by self-condensation of 3-mercaptopropyltrimethoxysilane in the presence of hydroxyethylcellulose. These nanoparticles were characterised by dynamic light scattering, small angle neutron scattering, Nanoparticle Tracking Analysis, Raman spectroscopy, FT-IR spectroscopy, thermogravimetric analysis, Ellman's assay, transmission electron microscopy and cryo-transmission electron microscopy. It was found that increasing the amount of hydroxyethylcellulose in the reaction mixture increased the nanoparticle size and reduced the number of thiol groups on their surface. Additionally, by utilising small angle neutron scattering and dynamic light scattering, it was demonstrated that higher concentrations of polymer in the reaction mixture (0.5-2% w/v) resulted in the formation of aggregates, whereby several silica nanoparticles are bridged together with macromolecules of hydroxyethylcellulose. A correlation was identified between the aggregate size and number of particles per aggregate based on size discrepancies observed between DLS and SANS measurements. This information makes it possible to control the size of aggregates during a simple one-pot synthesis; a prospect highly desirable in the design of potential drug delivery systems.

Movement-related dynamics of cortical oscillations in Parkinson's disease and essential tremor.

Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson's disease (n = 11), with essential tremor (n = 9) and without a movement disorder (n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson's disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson's disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson's disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson's disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson's disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases.

Petrous bone cholesteatoma: classification, management and review of the literature.

OBJECTIVE: To discuss the classification of petrous bone cholesteatoma (PBC) and add a subclassification; to review the existing literature and to propose the ideal surgical management of PBC based upon the experience of the largest series published in the literature until now. STUDY DESIGN: Retrospective analysis. SETTING: Quaternary referral neuro-otologic private practice. MATERIALS AND METHODS: The data of 129 patients who underwent surgery for PBC between 1979 and 2008 were analyzed with respect to the classification, type of the approach used, facial nerve lesion and its management, recurrences and outcome. RESULTS: Out of the 129 PBC cases 64 were supralabyrinthine, 9 infralabyrinthine, 7 infralabyrinthine-apical, 48 massive and 1 apical. The facial nerve was involved in 95% of the cases. Hearing could not be preserved in 82% of the cases due to the extent of the lesions and the surgical approaches used. The internal carotid artery, jugular bulb and the lower cranial nerves were infrequently involved, but demanded careful identification and meticulous care to avoid complications. Obliteration of the cavities provided a safe solution for protection of the exposed dura and the vital neurovascular structures. Recurrences were observed in 5 cases. CONCLUSION: The classification of PBC is fundamental to choose the appropriate surgical approach; the facial nerve is involved in almost all the cases, radical removal takes priority over hearing preservation and cavity obliteration is important to protect the vital neurovascular structures which may be exposed.

Management of complex cases of petrous bone cholesteatoma.

OBJECTIVES: In a retrospective analysis of a quaternary referral neuro-otologic private practice, we identify complex cases of petrous bone cholesteatoma (i.e., cases with encasement of vital structures such as the internal carotid artery, jugular bulb, and sigmoid sinus, with further extension to the clivus, sphenoid sinus, or rhinopharynx), review surgical approaches and techniques of management of vital structures, and propose the ideal surgical management. METHODS: We performed a retrospective case study of 130 cases of petrous bone cholesteatoma submitted to surgery between 1979 and 2009 to identify the complex cases and their classification, approach used, outcomes, and recurrences. RESULTS: Of 130 cases. 13 were complex. Facial palsy was the presenting feature in 11 cases, 7 of which presented with grade VI palsy. A long duration of facial palsy (more than 3 years) was seen in 5 cases. Clival involvement was seen in 6 cases; 1 case extended to the sphenoid sinus, and 1 to the rhinopharynx. The internal carotid artery was encased in 11 cases in the vertical and the horizontal parts. The jugular bulb was involved in 7 cases. Modified transcochlear approaches or infratemporal fossa approaches were used in all cases. There were no recurrences. CONCLUSIONS: Classification is fundamental to choosing the right surgical approach. Transotic and modified transcochlear approaches hold the key to treating complex cases. Infratemporal fossa approach type B has to be used for extension into the clivus, sphenoid sinus, or rhinopharynx. Internal carotid artery, jugular bulb, and sigmoid sinus involvement should be identified before operation.