Citations

ObjectiveTo evaluate the long‐term outcomes and potential predictors of treatment failure after robotic sacrocolpopexy.MethodsWe identified 70 consecutive patients from 2002 to 2012 with symptomatic post‐hysterectomy vaginal vault prolapse that underwent robotic sacrocolpopexy. Multiple clinical and surgical variables were evaluated for potential association with treatment failure, which was defined as any repeat operation for recurrent prolapse or mesh‐related complications.ResultsThe median age at surgery was 67 years (interquartile range 59–74 years) and median follow up was 72 months (interquartile range 39–114 months). Overall, six out of 70 patients (8.6%) underwent a total of six secondary surgeries, including four for recurrent prolapse (two anterior repairs, one posterior repair, one apical) and two mesh complications. No patient‐related factors were associated with the risk of repeat surgery: age (P = 0.45), diabetes mellitus (P = 0.24), tobacco use (P = 0.61) or prior prolapse surgery (P = 0.1) on univariate analysis. Freedom from repeat prolapse surgery or surgery for mesh complication was 98% at 1 year, 95% at 3 years and 90% at 6 years. At last follow up, 80% of patients reported that they would or probably would recommend robotic sacrocolpopexy to a family member or friend.ConclusionsRobotic sacrocolpopexy is associated with excellent long‐term outcomes. Recognition of long‐term success is important for preoperative patient counseling.

AbstractLight chain (AL) amyloidosis is an incurable human disease, where the amyloid precursor is a misfolding‐prone immunoglobulin light‐chain. Here, we identify the role of somatic mutations in the structure, stability and in vitro fibril formation for an amyloidogenic AL‐12 protein by restoring four nonconservative mutations to their germline (wild‐type) sequence. The single restorative mutations do not affect significantly the native structure, the unfolding pathway, and the reversibility of the protein. However, certain mutations either decrease (H32Y and H70D) or increase (R65S and Q96Y) the protein thermal stability. Interestingly, the most and the least stable mutants, Q96Y and H32Y, do not form amyloid fibrils under physiological conditions. Thus, Q96 and H32 are key residues for AL‐12 stability and fibril formation and restoring them to the wild‐type residues preclude amyloid formation. The mutants whose equilibrium is shifted to either the native or unfolded states barely sample transient partially folded states, and therefore do not form fibrils. These results agree with previous observations by our laboratory and others that amyloid formation occurs because of the sampling of partially folded states found within the unfolding transition (Blancas‐Mejia and Ramirez‐Alvarado, Ann Rev Biochem 2013;82:745–774). Here we provide a new insight on the AL amyloidosis mechanism by demonstrating that AL‐12 does not follow the established thermodynamic hypothesis of amyloid formation. In this hypothesis, thermodynamically unstable proteins are more prone to amyloid formation. Here we show that within a thermal stability range, the most stable protein in this study is the most amyloidogenic protein.

Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM). This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI) tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD) revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda-) type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment.

Abstract Using GC/MS in scanning mode as a screening and definitive identification methodology for substance abuse testing, 4500 urine samples have been analyzed. The accuracy and sensitivity of this method was evaluated by the results of 92 proficiency sample analyses, reanalyses by TLC screening with GC confirmation of 125 samples from forensic sources and reanalysis by EMIT screening for seven groups of drugs confirmed by GC/MS of 590 samples from industrial and treatment sources. The results of these studies are presented.

Objectives/HypothesisTo review our experience with endoscopic orbital apex surgery.Study DesignRetrospective review.MethodsAll cases with Current Procedural Terminology codes for endoscopic orbital decompression between 2002 and 2011 at two institutions were reviewed. Patients with a diagnosis of Graves orbitopathy or an orbital complication of sinusitis were excluded. Presenting symptoms, lesion location, pathology, surgical outcomes, and complications were examined.ResultsA total of 27 patients were identified. Seventeen (63%) of the patients were men, and the average age was 56 (range = 14–82) years. Eighteen patients had primary orbital apex lesions, and nine patients had sinonasal lesions that predominantly involved the medial orbital apex. The lesions were found to be on the right in 59% of cases. The etiologies include benign (40.7%), malignant (44%), infectious (7.4%), and metastatic (7.4%) lesions. Obtaining a pathologic diagnosis was successful endoscopically in all but two (7.4%) patients, both with lateral lesions. The two‐surgeon, four‐handed technique and intraoperative image guidance employing fused computed tomography/magnetic resonance imaging were used in the majority of intraconal cases. Complications occurred in three patients (11%) and included myocardial infarction, deep venous thrombosis, and vision loss. There were no cerebrospinal fluid leaks or postoperative hemorrhages. Notably, vision remained stable or improved in all but one patient (3.7% risk of vision decline). Average follow‐up was 4 years (range = 1 month–8 years).ConclusionsThe endoscopic approach to the orbit apex offers significant advantages over traditional external approaches, and should be the preferred approach for all medial and inferior lesions. A two‐surgeon multihanded technique can help facilitate difficult cases.Level of Evidence4. Laryngoscope, 126:20–24, 2016

Endometriosis (EM) is an infrequent cause of peripheral neuropathy, most commonly sciatic. Perineural spread has recently been introduced as an alternate explanation for cases of lumbosacral or sciatic nerve EM. We performed a literature review to collect all reported cases of peripheral and central nervous system EM in search of anatomic patterns of involvement; potentially to support the perineural spread theory. If available, intraneural invasion and presence of peritoneal EM were recorded. The search revealed 83 articles describing 365 cases of somatic peripheral nervous EM and 13 cases of central nervous EM. The most frequently involved site was the sacral plexus (57%,n = 211), followed by the sciatic nerve (39%,n = 140). Other nerves were reported in significantly smaller numbers. Ninety seven percent (97%,n = 355) of peripheral nerve cases presented with pain, 20% (n = 72) reported weakness and 31% (n = 114), numbness. Thirty four percent (34%,n = 38) had solely intraneural EM of which 89% (n = 33) had no peritoneal EM (percentage based on available information). In the central nervous system, the conus medullaris and/or cauda equina constituted the majority of cases with 54% (n = 7). Apart from perineural spread, other discussed mechanisms include retrograde menstruation with peritoneal seeding, hematogenous and lymphogenous spread, stem cell implantation either hematogenously or via retrograde menstruation with subsequent EM differentiation, and coelomic or Müllerian duct metaplasia. We believe this literature review supports perineural spread as an alternate mechanism for EM of nerve, particularly the subgroup with intraneural EM and without peritoneal disease. Clin. Anat. 28:1029–1038, 2015. © 2015 Wiley Periodicals, Inc.