Citations

Abstract Aim Up to 10% of patients who undergo nonurological abdominopelvic operations suffer a ureteral injury. While preoperative ureteral stenting to facilitate identification of the ureter is common, it does not reduce the incidence of intraoperative ureteral injury and is not without risk. As we continue to broaden the application of minimally invasive surgical techniques, a new form of ureteral identification and avoidance that does not rely on tactile feedback is needed. We report our initial experience with intraureteral indocyanine green (ICG) for ureteral identification and avoidance during complex robotic‐assisted colorectal surgery. Method Patients undergoing adjunctive ureteral identification during robotic‐assisted colorectal surgery were prospectively identified. Each patient underwent intraureteral ICG administration using rigid cystoscopy (22 Fr). A 5‐Fr open‐ended ureteral catheter was inserted up to 20 cm and used to inject 5 ml of 2.5 mg/ml ICG as the catheter was withdrawn to the ureteral orifice. Intraureteral ICG was then detected using near‐infrared laser fluorescence technology (Firefly®). Results Successful ICG‐enhanced ureteral identification and avoidance was performed in 15 of 16 (94%) patients undergoing robotic‐assisted colorectal surgery. The median ICG instillation time was 11.5 min (range 4–21 min) and the median operative time with ICG visualization was 489 min (8 h 9 min) [range 268–738 min (4 h 28 min–12 h 18 min)]. No patient experienced intraoperative ureteral injury and there were no adverse sequelae or complications associated with intraureteral ICG administration. Conclusion Intraureteral ICG is a safe and effective method of intraoperative ureteral identification and avoidance during complex robotic‐assisted colorectal surgery. Precise and prolonged ureteral visualization was achieved, allowing for long operative times compatible with complex robotic‐assisted operations.

AbstractFirst‐degree relatives of patients diagnosed with schizophrenia (SZ‐FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First‐degree relatives of patients diagnosed with bipolar disorder (BD‐FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD‐FDRs are inconsistent. Here, we performed a meta‐analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ‐FDRs, 867 BD‐FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ‐FDRs showed a pattern of widespread thinner cortex, while BD‐FDRs had widespread larger cortical surface area. IQ was lower in SZ‐FDRs (d = −0.42,p = 3 × 10−5), with weak evidence of IQ reductions among BD‐FDRs (d = −0.23,p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group‐effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ‐FDRs and more pronounced effects in BD‐FDRs. To conclude, SZ‐FDRs and BD‐FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ‐FDRs and BD‐FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

ObjectiveDeficiency of adenosine deaminase 2 (DADA2) is a monogenic form of vasculitis that can resemble polyarteritis nodosa (PAN). This study was undertaken to identify potential disease‐causing sequence variants in ADA2 in patients with idiopathic PAN, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA).MethodsPatients with idiopathic PAN (n = 118) and patients with GPA or MPA (n = 1,107) were screened for rare nonsynonymous variants in ADA2 using DNA sequencing methods. ADA‐2 enzyme activity was assessed in selected serum samples.ResultsNine of 118 patients with PAN (7.6%) were identified as having rare nonsynonymous variants in ADA2. Four patients (3.4%) were biallelic for pathogenic or likely pathogenic variants, and 5 patients (4.2%) were monoallelic carriers for 3 variants of uncertain significance and 2 likely pathogenic variants. Serum samples from 2 patients with PAN with biallelic variants were available and showed markedly reduced ADA‐2 enzyme activity. ADA‐2 enzyme testing of 86 additional patients revealed 1 individual with strongly reduced ADA‐2 activity without detectable pathogenic variants. Patients with PAN and biallelic variants in ADA2 were younger at diagnosis than patients with 1 or no variant in ADA2, with no other clinical differences noted. None of the patients with GPA or MPA carried biallelic variants in ADA2.ConclusionA subset of patients with idiopathic PAN meet genetic criteria for DADA2. Given that tumor necrosis factor inhibition is efficacious in DADA2 but is not conventional therapy for PAN, these findings suggest that ADA‐2 testing should strongly be considered in patients with hepatitis B virus–negative idiopathic PAN.

AimsTo characterise the clinicopathological features of amyloidosis due to EGF‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1), a newly described amyloid type.Methods and resultsWe identified cases by searching the Mayo Clinic amyloid liquid chromatography and tandem mass spectrometry typing database for specimens with the universal amyloid signature proteins, abundant EFEMP1 spectra and absence of other specific amyloid precursor proteins. We also developed an immunohistochemical stain for EFEMP1 applicable to formalin‐fixed tissue sections and performed electron microscopy in one case. We identified 33 specimens from 32 patients with EFEMP1 amyloid. Most patients were female (91%) with a mean age of 75 years, and most specimens (94%) were from the bowel. EFEMP1 amyloid was incidentally identified in specimens biopsied/resected for a variety of clinical indications. In bowel specimens, EFEMP1 amyloid involved blood vessels and interstitium of the lamina propria, submucosa and/or muscularis propria. Although the EFEMP1 deposits were weakly to moderately Congo red‐positive with absent to weak birefringence, they were strongly positive for EFEMP1 by immunohistochemistry, had the characteristic fibrillar ultrastructure of amyloid and were readily identified by mass spectrometry.ConclusionsEFEMP1 amyloid is a recently described novel amyloid type that predominantly affects the bowel of elderly females. Because EFEMP1 amyloid is only weakly Congo red‐positive, it may be overlooked without a high index of suspicion. However, its characteristic microanatomical distribution is highlighted by immunohistochemistry and its identity is readily confirmed by mass spectrometry. Based on its distinctive features, we propose that EFEMP1 amyloidosis be considered a new amyloid type.

AbstractObjectivesThe purpose of this study was to investigate the influence of simulated reduced‐dose three‐dimensional angiography (3DA) on the accuracy and precision of linear measurements derived from 3DA datasets.BackgroundThree‐dimensional angiography is performed during X‐ray guided interventional procedures to aid diagnosis and inform treatment strategies for children and adults with congenital heart disease. However, 3DA contributes substantially to patient radiation dose and may lead to an increased radiation‐induced cancer risk.MethodsReduced‐dose patient 3DA images were simulated by adding quantum noise to the 2D projection angiograms, then reconstructing the projection angiograms into the 3DA dataset. Dose reduction in the range 33–72% was simulated. Five observers performed 46 vessel diameter measurements along prespecified axes within 23 vessel segments from 11 patient 3DA datasets. Statistical tests were performed to assess the influence of radiation dose reduction on the accuracy and precision of vessel diameter measurements.ResultsVessel diameter measurements were in the range 5.9– 22.7 mm. Considering all vessel segments and observers, the influence of dose level on the accuracy of diameter measurements was in the range 0.02 – 0.15 mm (p .05–.8). Interobserver variability increased modestly with vessel diameter, but was not influence by dose level (p = .52). The statistical test for observer recall bias was negative (p = .51).ConclusionsSimulated dose reduction up to 72% did not affect the accuracy or precision of the diameter measurements acquired from 3DA images. These findings may embolden 3DA radiation dose reduction for pediatric and congenital heart disease patients.

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1–6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

ObjectivesUrine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin‐exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin‐tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP.MethodsA retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund‐Mackay CT score, spirometry and lab values) were collected.ResultsAmong the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P< .001), aspirin sensitivity (P< .001), worse Lund‐Mackay CT scores (P= .002) and other objective markers of disease severity including serum IgE (P= .05), presenting blood eosinophil level (P< .001), and the highest recorded eosinophil level (P< .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (Rrange 0.31–0.52) than the aspirin tolerant CRSwNP group (Rrange −0.30–0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores).ConclusionElevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient‐reported symptom measures.Level of Evidence3Laryngoscope, 131:961–966, 2021

Abstract Background Self-assembly of the amyloid-β (Aβ) peptide into aggregates, from small oligomers to amyloid fibrils, is fundamentally linked with Alzheimer’s disease (AD). However it is clear that not all forms of Aβ are equally harmful, and that linking a specific aggregate to toxicity also depends on the assays and model systems used [1, 2]. Though a central postulate of the amyloid cascade hypothesis, there remain many gaps in our understanding regarding the links between Aβ deposition and neurodegeneration. Methods In this study, we examined familial mutations of Aβ that increase aggregation and oligomerization, E22G and DE22, and induce cerebral amyloid angiopathy, E22Q and D23N. We also investigated synthetic mutations that stabilize dimerization, S26C, and a phospho-mimetic, S8E, and non-phospho-mimetic, S8A. To that end, we utilized BRI2-Aβ fusion technology and rAAV2/1 based somatic brain transgenesis in mice to selectively express individual mutant Aβ species in vivo. In parallel we generated PhiC31-based transgenic Drosophila melanogaster expressing wild type (WT) and Aβ40 and Aβ42 mutants, fused to the Argos signal peptide to assess the extent of Aβ42-induced toxicity as well as to interrogate the combined effect of different Aβ40 and Aβ42 species.Results When expressed in the mouse brain for 6 months, Aβ42 E22G, Aβ42 E22Q/D23N, and Aβ42WT formed amyloid aggregates consisting of some diffuse material as well as cored plaques, whereas other mutants formed predominantly diffuse amyloid deposits. Moreover, while Aβ40WT showed no distinctive phenotype, Aβ40 E22G and E22Q/D23N formed unique aggregates that accumulated in mouse brains. This is the first evidence that mutant Aβ40 overexpression leads to deposition under certain conditions. Interestingly, we found that mutant Aβ42 E22G, E22Q, and S26C, but not Aβ40, were toxic to the eye of Drosophila. In contrast, flies expressing a copy of Aβ40 (WT or mutants) in addition to Aβ42WT, showed improved phenotypes, suggesting possible protective qualities for Aβ40. Conclusions These studies suggest that while some Aβ40 mutants form unique amyloid aggregates in mouse brains, they do not exacerbate Aβ42 toxicity in Drosophila, which highlights the significance of using different systems for a better understanding of AD pathogenicity and more accurate screening for new potential therapies.