Median Arcuate Ligament Compression Associated with Flow-Related Visceral Aneurysms.

PURPOSE: To identify risk factors for rupture, and to determine outcomes of endovascular treatment of median arcuate ligament (MAL) compression-related visceral artery aneurysms (VAAs). METHODS AND MATERIALS: A retrospective review of patients who presented with MALC-related VAAs was performed from 1999 to 2021. A total of 21 patients (12 men) and 39 VAAs associated with MAL compression were encountered (mean age, 59 years). Imaging studies were reviewed for the number, morphology/size, and recurrence of aneurysms. Statistical analysis was performed to identify risk factors for rupture. RESULTS: Ten patients presented with acute rupture, and 12 patients were symptomatic with nonspecific abdominal pain. Twenty-two aneurysms were fusiform in morphology and 17 aneurysms were saccular in morphology. Of the 14 aneurysms that presented with acute hemorrhage, 12 (86%) were fusiform in morphology (odds ratio, 9.0; P < .01). The mean aneurysm size was 1.3 cm, and the mean ruptured size was 0.6 cm. Thirty-one aneurysms were treated by endovascular techniques, and technical success was achieved in all cases. Fourteen patients were found to have an Arc of Buhler. No procedure-related adverse events occurred. No patient underwent surgical ligament release. The mean time of follow-up was 3.2 years, and no aneurysms recurred after endovascular treatment. CONCLUSIONS: MAL compression-associated VAAs are an important clinical entity that should be treated even at small sizes, particularly if they are fusiform in morphology. Endovascular therapy is safe and feasible and results in durable aneurysm exclusion.

Posttranslational Methylation of Arginine in Methyl Coenzyme M Reductase Has a Profound Impact on both Methanogenesis and Growth of Methanococcus maripaludis.

Catalyzing the key step for anaerobic production and/or oxidation of methane and likely other short-chain alkanes, methyl coenzyme M reductase (Mcr) and its homologs play a key role in the global carbon cycle. The McrA subunit possesses up to five conserved posttranslational modifications (PTMs) at its active site. It was previously suggested that methanogenesis marker protein 10 (Mmp10) could play an important role in methanogenesis. To systematically examine its physiological role, mmpX (locus tag MMP1554), the gene encoding Mmp10 in Methanococcus maripaludis, was deleted with a new genetic tool, resulting in the complete loss of the 5-C-(S)-methylarginine PTM of residue 275 in the McrA subunit. When the ΔmmpX mutant was complemented with the wild-type gene expressed by either a strong or a weak promoter, methylation was fully restored. Compared to the parental strain, maximal rates of methane formation by whole cells were reduced by 40 to 60% in the ΔmmpX mutant. The reduction in activity was fully reversed by the complement with the strong promoter. Site-directed mutagenesis of mmpX resulted in a differential loss of arginine methylation among the mutants in vivo, suggesting that activities of Mmp10 directly modulated methylation. R275 was present in a highly conserved PXRR275(A/S)R(G/A) signature sequence in McrAs. The only other protein in M. maripaludis containing a similar sequence was not methylated, suggesting that Mmp10 is specific for McrA. In conclusion, Mmp10 modulates the methyl-Arg PTM on McrA in a highly specific manner, which has a profound impact on Mcr activity.IMPORTANCE Mcr is the key enzyme in methanogenesis and a promising candidate for bioengineering the conversion of methane to liquid fuel. Our knowledge of Mcr is still limited. In terms of complexity, uniqueness, and environmental importance, Mcr is more comparable to photosynthetic reaction centers than conventional enzymes. PTMs have long been hypothesized to play key roles in modulating Mcr activity. Here, we directly link the mmpX gene to the arginine PTM of Mcr, demonstrate its association with methanogenesis activity, and offer insights into its substrate specificity and putative cofactor binding sites. This is also the first time that a PTM of McrA has been shown to have a substantial impact on both methanogenesis and growth in the absence of additional stressors.

Percutaneous retrieval of a Mobin-Uddin inferior vena cava filter 42 years following implantation.

Inferior vena cava filters (IVCFs) are an established alternative for protection from thromboembolism when anticoagulation fails or is contraindicated. Before the creation of retrievable IVCFs, patients received filters that were permanent or designed without standardized retrieval options. Although these filters were implanted for prolonged protection, chronic vena caval occlusion and post-thrombotic syndrome are potential sequelae. We present a 53-year-old patient with a Mobin-Uddin permanent IVCF placed 42 years prior complicated by acute iliocaval thrombosis following more than 40 years of filter dwell time. She was successfully treated with thrombolysis, thrombectomy, endobronchial forceps assisted IVCF removal, and iliocaval stent reconstruction.

Accuracy in Referrals to Gynecologic Oncologists Based on Clinical Presentation for Ovarian Mass.

Ovarian cancer is one of the most lethal gynecological cancers in women due to late diagnosis. Despite technological advancements, experienced physicians have high sensitivities and specificities in subjective assessments when combining ultrasound findings and clinical history in analyzing adnexal masses. This study aims to demonstrate general obstetricians and gynecologists' (OB/GYN) appropriateness in gynecologic oncologist referrals for malignant ovarian masses based on history and physical (H&P), imaging, and available tumor markers. Three board certified OB/GYNs were given 148 cases and determined whether or not they would refer them to a gynecologic oncologist. Results showed that OB/GYNs were 81-85% accurate in diagnosing patients with a benign or malignant disease. Among the malignant cases, reviewers had a high sensitivity ranging from 74-81% in appropriately referring a malignancy. In our study, OB/GYNs referred between 23-32% of ovarian masses to a gynecologic oncologist with only 9.5% of cases found to be malignant. Despite the high referral rates, generalists showed a high degree of sensitivity in accurately referring malignant diseases based solely on clinical experience and imaging studies, which could improve survival rates with early intervention by gynecologic oncologists.

Interventional Radiology Image-Guided Suprapubic Cystostomy Using Trocar versus Seldinger Technique: A Comparative Analysis of Outcomes and Complications.

OBJECTIVE: To compare two techniques-trocar and Seldinger-for performing percutaneous suprapubic cystostomy. MATERIALS AND METHODS: 125 patients, mean age 71.8 ± 16.5 years (range, 15-102 years), underwent primary suprapubic cystostomy from January 2013 to December 2018. Trocar access (N = 60) was performed as a single step using a puncture cannula without guidewire access. Seldinger access (N = 65) involved needle puncture, guidewire placement, and serial dilation. A retrospective review of patient records was conducted. RESULTS: All procedures were technically successful. Mean catheter size was 13.1 ± 2.0 and 13.9 ± 2.0 French for trocar and Seldinger, respectively (P = .044). Mean procedure time was significantly reduced using trocar technique, 12.4 ± 7.7 versus 25.7 ± 12.1 minutes (P <.001), and was associated with lower anxiolytic dose, 1.2 ± 0.8 versus 1.9 ± 1.1 mg midazolam (P = .003), and less radiation exposure, 20.2 ± 59.5 versus 100.7 ± 98.5 mGy (P <.001). Catheter occlusion was the most common complication (28.8%), followed by UTI (13.6%) and bladder spasm (8.0%). All but 2 complications were classified as Clavien-Dindo grade I or II. Catheter occlusion was more frequent in the trocar group (41.7% vs 16.9%, P = .003), while bladder spasms were more frequent in the Seldinger group (13.8% vs 1.7%, P = .018). CONCLUSION: Suprapubic cystostomy via trocar is associated with faster procedure time, lower anxiolytic dose, and less radiation. While major complications are rare, catheter occlusion is a common occurrence that may be overlooked. Although we detected more occlusions with trocar technique, this may be confounded by a catheter-tract size discrepancy.

Uterine torsion with necrosis of bilateral adnexa in a postmenopausal woman.

Uterine torsion is an uncommon entity that is defined as a rotation of greater than 45° around the longitudinal axis of the uterus. Although cases of uterine torsion among pregnant patients have been mentioned in the literature, torsion of a non-gravid uterus is a rare occurrence. A 73-year-old nulliparous woman with a known fibroid uterus underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy with frozen section of a 17-18 cm pelvic mass seen on CT imaging. The source of the pelvic mass was unclear on imaging, and benign and malignant possibilities were discussed. During the procedure, necrosis of the uterine fundus and bilateral adnexa were seen due to the fundus being torsed with the uterine fibroid being the pivot point. Uterine torsion, though rare, can be the cause of acute pelvic pain in a postmenopausal woman.

IDO1 in cancer: a Gemini of immune checkpoints.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan (Trp) into downstream catabolites known as kynurenines. Coincidently, numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer. Preclinical studies have further introduced an interesting paradox: while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden, approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival. Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy, these data suggest that there is a more complex mechanism of action than previously appreciated. Similar to the dual faces of the astrological Gemini, we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism, as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects. The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration, but the lack of a universal prognostic significance among all cancer subtypes. Finally, ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients.

IDO1 Inhibition Synergizes with Radiation and PD-1 Blockade to Durably Increase Survival Against Advanced Glioblastoma.

Purpose: Glioblastoma is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating glioblastoma have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, nivolumab (anti-PD-1), which failed to improve recurrent glioblastoma patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for glioblastoma, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents.Experimental Design: Here, we investigated immunocompetent orthotopic mouse models of glioblastoma treated with the potent CNS-penetrating IDO1 enzyme inhibitor, BGB-5777, combined with anti-PD1 mAb, as well as radiotherapy, based on our recent observation that tumor-infiltrating T cells directly increase immunosuppressive IDO1 levels in human glioblastoma, the previously described reinvigoration of immune cell functions after PD-1 blockade, as well as the proinflammatory effects of radiation.Results: Our results demonstrate a durable survival benefit from this novel three-agent treatment, but not for any single- or dual-agent combination. Unexpectedly, treatment efficacy required IDO1 enzyme inhibition in non-glioblastoma cells, rather than tumor cells. Timing of effector T-cell infiltration, animal subject age, and usage of systemic chemotherapy, all directly impacted therapy-mediated survival benefit.Conclusions: These data highlight a novel and clinically relevant immunotherapeutic approach with associated mechanistic considerations that have formed the basis of a newly initiated phase I/II trial for glioblastoma patients. Clin Cancer Res; 24(11); 2559-73. ©2018 AACR.

Identification and localization of Myxococcus xanthus porins and lipoproteins.

Myxococcus xanthus DK1622 contains inner (IM) and outer membranes (OM) separated by a peptidoglycan layer. Integral membrane, ß-barrel proteins are found exclusively in the OM where they form pores allowing the passage of nutrients, waste products and signals. One porin, Oar, is required for intercellular communication of the C-signal. An oar mutant produces CsgA but is unable to ripple or stimulate csgA mutants to develop suggesting that it is the channel for C-signaling. Six prediction programs were evaluated for their ability to identify ß-barrel proteins. No program was reliable unless the predicted proteins were first parsed using Signal P, Lipo P and TMHMM, after which TMBETA-SVM and TMBETADISC-RBF identified ß-barrel proteins most accurately. 228 ß-barrel proteins were predicted from among 7331 protein coding regions, representing 3.1% of total genes. Sucrose density gradients were used to separate vegetative cell IM and OM fractions, and LC-MS/MS of OM proteins identified 54 ß-barrel proteins. Another class of membrane proteins, the lipoproteins, are anchored in the membrane via a lipid moiety at the N-terminus. 44 OM proteins identified by LC-MS/MS were predicted lipoproteins. Lipoproteins are distributed between the IM, OM and ECM according to an N-terminal sorting sequence that varies among species. Sequence analysis revealed conservation of alanine at the +7 position of mature ECM lipoproteins, lysine at the +2 position of IM lipoproteins, and no noticable conservation within the OM lipoproteins. Site directed mutagenesis and immuno transmission electron microscopy showed that alanine at the +7 position is essential for sorting of the lipoprotein FibA into the ECM. FibA appears at normal levels in the ECM even when a +2 lysine is added to the signal sequence. These results suggest that ECM proteins have a unique method of secretion. It is now possible to target lipoproteins to specific IM, OM and ECM locations by manipulating the amino acid sequence near the +1 cysteine processing site.