Next-generation gene panel testing in adolescents and adults in a medical neuropsychiatric genetics clinic.

Intellectual disability (ID) encompasses a clinically and genetically heterogeneous group of neurodevelopmental disorders that may present with psychiatric illness in up to 40% of cases. Despite the evidence for clinical utility of genetic panels in pediatrics, there are no published studies in adolescents/adults with ID or autism spectrum disorder (ASD). This study was approved by our institutional research ethics board. We retrospectively reviewed the medical charts of all patients evaluated between January 2017 and December 2019 in our adult neuropsychiatric genetics clinic at the McGill University Health Centre (MUHC), who had undergone a comprehensive ID/ASD gene panel. Thirty-four patients aged > 16 years, affected by ID/ASD and/or other neuropsychiatric/behavioral disorders, were identified. Pathogenic or likely pathogenic variants were identified in one-third of our cohort (32%): 8 single-nucleotide variants in 8 genes (CASK, SHANK3, IQSEC2, CHD2, ZBTB20, TREX1, SON, and TUBB2A) and 3 copy number variants (17p13.3, 16p13.12p13.11, and 9p24.3p24.1). The presence of psychiatric/behavioral disorders, regardless of the co-occurrence of ID, and, at a borderline level, the presence of ID alone were associated with positive genetic findings (p = 0.024 and p = 0.054, respectively). Moreover, seizures were associated with positive genetic results (p = 0.024). One-third of individuals presenting with psychiatric illness who met our red flags for Mendelian diseases have pathogenic or likely pathogenic variants which can be identified using a comprehensive ID/ASD gene panel (~ 2500 genes) performed on an exome backbone.

Profilicollis chasmagnathi (Acanthocephala) parasitizing freshwater fishes: paratenicity and an exception to the phylogenetic conservatism of the genus?

Polymorphid acanthocephalans are parasites of marine mammals, waterfowl and ichthyophagous birds. Among these, the genus Profilicollis is known to use exclusively decapods as intermediate hosts. Here, we report the first record of living cystacanths of Profilicollis parasitizing the body cavity of a fish host, Oligosarcus jenynsii, inhabiting the freshwater section of an estuarial system, Mar Chiquita coastal lagoon, in south-east Buenos Aires Province, Argentina. In this environment, cystacanths of Profilicollis chasmagnathi have been previously recorded infecting decapod crabs and as transient accidental infections in the gut of some carcinophagous fishes. In the present study, larvae from the crab Neohelice granulata, from the intestine of the estuarine fish Odontesthes argentinensis and from the body cavity of O. jenynsii were morphologically and genetically compared, confirming their identity as P. chasmagnathi, a species characteristic of estuaries and marine coasts along Argentina, Uruguay and Chile. These findings can be interpreted as a possible case of incipient paratenicity for Profilicollis, and a colonization event of freshwater habitats, probably promoted by the highly variable conditions, typical of ecotonal environments. In addition, cystacanths of the genus Polymorphus were also found in O. jenynsii, representing the first record of this genus in Oligosarcus from Argentina.

Dorsal hippocampal damage disrupts the auditory context-dependent attenuation of taste neophobia in mice.

Rodents exhibit neophobia for novel tastes, demonstrated by an initial reluctance to drink novel-tasting, potentially-aversive solutions. Taste neophobia attenuates across days if the solution is not aversive, demonstrated by increased consumption as the solution becomes familiar. This attenuation of taste neophobia is context dependent, which has been demonstrated by maintained reluctance to drink the novel tasting solution if the subject has to drink it after being brought to a novel environment. This spatial context-dependent attenuation of taste neophobia has been described and likely depends on the integrity of the dorsal hippocampus because this brain area is crucial for representing space and spatial context associations, but is unnecessary for processing taste memories per se. Whether changing the non-spatial auditory context causes a similar effect on attenuation of taste neophobia and the potential role of the dorsal hippocampus in processing this decidedly non-spatial information has not been determined. Here we demonstrate that changing the non-spatial auditory context affects the attenuation of taste neophobia in mice, and investigate the consequence of hippocampal lesion. The results demonstrate that the non-spatial auditory context-dependent attenuation of taste neophobia in mice is lost following NMDA excitotoxic lesions of the CA1 region of the dorsal hippocampus. These findings demonstrate that the dorsal hippocampus is crucial for the modulation non-associative taste learning by auditory context, neither of which provide information about space.

Gastrointestinal factors regulating lipid droplet formation in the intestine.

Cytoplasmic lipid droplets (CLD) are considered as neutral lipid reservoirs, which protect cells from lipotoxicity. It became clear that these fascinating dynamic organelles play a role not only in energy storage and metabolism, but also in cellular lipid and protein handling, inter-organelle communication, and signaling among diverse functions. Their dysregulation is associated with multiple disorders, including obesity, liver steatosis and cardiovascular diseases. The central aim of this review is to highlight the link between intra-enterocyte CLD dynamics and the formation of chylomicrons, the main intestinal dietary lipid vehicle, after overviewing the morphology, molecular composition, biogenesis and functions of CLD.

Abnormal lipid storage related to adipocyte shrinkage in acquired partial lipodystrophy (Barraquer-Simons syndrome).

BACKGROUND: Acquired partial lipodystrophy (APL) is characterized by the gradual symmetrical loss of subcutaneous fat starting from the face, spreading towards the upper part of the body and sparing the lower extremities. OBJECTIVE: We report a 33-year-old woman with facial lipodystrophy, loss of buccal fat pads and breast fat tissue. The subcutaneous fat was preserved in other anatomic regions, and we noted some excess of fat accumulation in the lower abdomen and thighs. She had a low serum level of C3 that was positive for a polyclonal immunoglobulin C3NeF in the serum. She was diagnosed with APL. METHODS: We examined fat from lipoatrophic and healthy areas and compared it to subcutaneous fat samples from a healthy control. RESULTS: Using scanning electron microscopy, we saw shrunken adipocytes with numerous small lipid droplets detaching from the surface of the adipocytes as compared to the classic aspect of adipose tissue in the control subject where the cytoplasm is occupied by one big lipid droplet. A loss of contact between adipocytes was observed in the APL patient when compared to the normal network of adipocytes in the control subject. The healthy fat seemed not affected by lipoatrophy; we observed normal-sized adipocytes, though their surface was not as regular as in the control samples. CONCLUSION: The significance and mechanism of the electron microscopic findings are unknown, but they suggest adipocyte shrinkage related to a defect in the retaining triglycerides, which could contribute to the pathogenesis of this disorder.

Lysosomal dysfunction in the brain of a mouse model with intraneuronal accumulation of carboxyl terminal fragments of the amyloid precursor protein.

Recent data suggest that intraneuronal accumulation of metabolites of the amyloid-ß-precursor protein (APP) is neurotoxic. We observed that transgenic mice overexpressing in neurons a human APP gene harboring the APPE693Q (Dutch) mutation have intraneuronal lysosomal accumulation of APP carboxylterminal fragments (APP-CTFs) and oligomeric amyloid ß (oAß) but no histological evidence of amyloid deposition. Morphometric quantification using the lysosomal marker protein 2 (LAMP-2) immunolabeling showed higher neuronal lysosomal counts in brain of 12-months-old APPE693Q as compared with age-matched non-transgenic littermates, and western blots showed increased lysosomal proteins including LAMP-2, cathepsin D and LC3. At 24 months of age, these mice also exhibited an accumulation of α-synuclein in the brain, along with increased conversion of LC3-I to LC3-II, an autophagosomal/autolysosomal marker. In addition to lysosomal changes at 12 months of age, these mice developed cholinergic neuronal loss in the basal forebrain, GABAergic neuronal loss in the cortex, hippocampus and basal forebrain and gliosis and microgliosis in the hippocampus. These findings suggest a role for the intraneuronal accumulation of oAß and APP-CTFs and resultant lysosomal pathology at early stages of Alzheimer's disease-related pathology.

Revealing the Topology of Quasicrystals with a Diffraction Experiment.

Topological properties of crystals and quasicrystals is a subject of recent and growing interest. This Letter reports an experiment where, for certain quasicrystals, these properties can be directly retrieved from diffraction. We directly observe, using an interferometric approach, all of the topological invariants of finite-length Fibonacci chains in their diffraction pattern. We also quantitatively demonstrate the stability of these topological invariants with respect to structural disorder.

Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer.

The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose-limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160 mg/m(2) biweekly. Efficacy was evaluated in 15 patients with irinotecan-refractory colorectal cancer. The median time of disease control was 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13 of 19 patients. Matched pre- and posttreatment tumor biopsies showed decreased eIF4E mRNA levels in five of nine patients. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in seven of 15 (47%) patients who were progressing before study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre- and posttherapy tumor biopsies penetration of the ASO into the site of metastasis.

Longitudinal circulating concentrations of long-chain polyunsaturated fatty acids in the third trimester of pregnancy in gestational diabetes.

AIM: Gestational diabetes mellitus is a common complication of pregnancy. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for fetal neurodevelopment. Docosahexaenoic acid (DHA) is the predominant n-3 LCPUFA in the brain and retina. Circulating absolute concentrations of total n-3 and n-6 LCPUFAs rise during normal pregnancy. It remains unclear whether gestational diabetes may affect the normal rise in circulating concentrations of LCPUFAs in the third trimester of pregnancy - a period of rapid fetal neurodevelopment. This study aimed to address this question. METHODS: In a prospective singleton pregnancy cohort, fatty acids in fasting plasma total lipids were measured at 24-28 and 32-35 weeks of gestation in women with (n = 24) and without gestational diabetes mellitus (n = 116). Fatty acid desaturase activity indices were estimated by relevant product-to-precursor fatty acid ratios. Dietary nutrient intakes were estimated by a food frequency questionnaire. RESULTS: Plasma absolute concentrations of total n-6 LCPUFAs rose significantly between 24-28 and 32-35 weeks of gestation in women with or without gestational diabetes, whereas total n-3 LCPUFAs and DHA concentrations rose significantly only in women without gestational diabetes (all P < 0.01). Delta-5 desaturase indices (20:4n-6/20:3n-6) were similar, but delta-6 desaturase indices (18:3n-6/18:2n-6) were significantly lower in women with gestational diabetes at 32-35 weeks of gestation. Dietary intakes of all fatty acids were comparable. CONCLUSION: The normal rise in circulating absolute concentrations of DHA and total n-3 LCPUFAs in the third trimester of pregnancy may be compromised in gestational diabetes, probably due to impaired synthesis or mobilization rather than dietary intake difference.

[Stevens-Johnson syndrome and Hodgkin's disease: A fortuitous association or paraneoplastic syndrome?]. / Syndrome de Stevens-Johnson et maladie de Hodgkin : association fortuite ou syndrome paranéoplasique ?

BACKGROUND: Hodgkin's disease has been associated with a variety of cutaneous symptoms. We report two cases of Stevens-Johnson syndrome (SJS) associated with Hodgkin's disease. PATIENTS AND METHODS: Case 1: a 22-year-old man was hospitalized for a second erythematous vesicular eruption with intense mucosal involvement. Histopathological examination confirmed the diagnosis of Stevens-Johnson syndrome. He also developed enlarged cervical lymph nodes that revealed Hodgkin's disease. The latter diagnosis was followed by two recurrent rashes. Treatment consisted of systemic chemotherapy. Complete remission was obtained with no signs of cutaneous recurrence after 24 months of regular follow-up. Case 2: a 29-year-old man was admitted for a generalized erythematous and bullous rash with intense mucosal involvement. Histopathological examination confirmed the diagnosis of Stevens-Johnson syndrome. He then developed muco-cutaneous icterus that was secondary to Hodgkin's disease. Under specific hematologic treatment, no cutaneous relapse was noticed. DISCUSSION: These cases illustrate the rare association of SSJ revealing Hodgkin's disease. In these cases, no evidence was found of infectious disease or drug-induced cutaneous effects. Only one case of toxic epidermal necrolysis associated with Hodgkin's disease had previously been reported. The link between both diseases may be immunosuppression induced by Hodgkin's disease, which could favor infection inducing SJS or secretion by tumor cells granulysin, a mediator responsible for damage to keratinocytes.

[Pseudolymphoma of the skin: ambiguous terminology: a survey among dermatologists and pathologists]. / Le pseudolymphome cutané: une sémantique ambiguë. Enquête auprès des dermatologues et des pathologistes.

BACKGROUND: Cutaneous pseudolymphomas (CPL) are diseases that simulate cutaneous lymphomas both clinically and histologically but have a benign course. It can be very difficult, if not impossible, to differentiate pseudolymphoma from lymphoma and there is some semantic ambiguity about the term pseudolymphoma. The aim of this study was to determine the exact meaning attributed to the term pseudolymphoma by a representative sample of French dermatologists and pathologists. MATERIALS AND METHODS: We designed two types of questionnaire, one for dermatologists and the other for pathologists, and sent them out to 274 dermatologists and to 110 pathologists. RESULTS: We received responses from 122 dermatologists (44.5%) and 64 pathologists (58.1%). In the dermatologist group, 56% consider that CPL is not a clearly defined entity, while 58% consider it a benign disease and only 18% feel that most CPLs are related to a precise cause; 72% of dermatologists perform a routine checkup, 58% initiate treatment and 84% conduct follow-up in the case of CPL. Among pathologists, 61% consider that CPL is not a clearly defined entity, 82% feel that cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia and cutaneous lymphocytoma are the same entity, and 75% consider that CPL are benign; 92% perform routine immunohistochemistry studies and only 26% screen for clonality. Bivariate statistical analysis showed that pathologists consider pseudolymphomas as benign entities frequently than dermatologists (χ(2) test: P=0.02; Fisher's exact test: P=0.01) and that there are more pathologists than dermatologists who see more than four pseudolymphomas per year (χ(2) test: P<0.001; Fisher's exact test: P<0.001). Multivariate analysis clearly identified a tendency among doctors viewing pseudolymphomas as a distinct entity to also consider them benign (Odds Ratio 0.29, CI 97.5% 0.14-0.58), irrespective of speciality or type of practice (hospital practice, private practice or both). DISCUSSION: This study demonstrates that, in France, the term pseudolymphoma is an ambiguous notion. We believe that cases in which it is impossible to differentiate pseudolymphoma from cutaneous lymphoma should be referred to as lymphoproliferations of undetermined significance, since more than 50% of physicians consider that the term pseudolymphoma designates a resolutely benign entity.

Estimation of the prevalence of uterine infertility and its different causes in France according to data from a literature review.

INTRODUCTION: Uterine infertility (UI) is defined as the complete absence of a uterus (absolute uterine infertility or AUI) or the presence of a non functional uterus (non-absolute uterine infertility or NAUI). The exact prevalence of uterine infertility is currently unknown. Our aim was to assess the number of French women concerned by Uterine Infertility according to a recent literature review. MATERIALS AND METHODS: We have previously conducted a systematic review of the literature on UI and its various causes in the world. Based on these study and demographic data of 2022 from INSEE (Institut National de la Statistique et des Études Économiques), we attempted to estimate the number of women under 40 years of age in France affected by potential UI using direct standardization. RESULTS AND DISCUSSION: Based on the estimation from INSEE data, approximately 2066 women of childbearing age would have MRKH syndrome in France, 380 the Androgen Insensitivity Syndrome and 3700 had an haemostasis hysterectomy in France. We did not find data on the prevalence of hysterectomies before the age of 40 in France. For the following pathologies: uterine malformations, radiation uterus, synechiae, myomas and adenomyosis there was a huge amount of missing data, which does not allow us to estimate the number of potentially infertile patients. CONCLUSION: Prevalence of UI is poorly known. UI probably concerns several thousand patients in France. The creation of a UI registry would make enable to assess the number of patients potentially eligible for adoption, uterus transplantation or even surrogacy.

Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

Association between genetic variants in the HNF4A gene and childhood-onset Crohn's disease.

Hepatocyte nuclear 4 alpha (HNF4α), involved in glucose and lipid metabolism, has been linked to intestinal inflammation and abnormal mucosal permeability. Moreover, in a genome-wide association study, the HNF4A locus has been associated with ulcerative colitis. The objective of our study was to evaluate the association between HNF4α genetic variants and Crohn's disease (CD) in two distinct Canadian pediatric cohorts. The sequencing of the HNF4A gene in 40 French Canadian patients led to the identification of 27 single nucleotide polymorphism (SNP)s with a minor allele frequency >5%. To assess the impact of these SNPs on disease susceptibility, we first conducted a case-control discovery study on 358 subjects with CD and 542 controls. We then carried out a replication study in a separate cohort of 416 cases and 1208 controls. In the discovery cohort, the genotyping of the identified SNPs revealed that six were significantly associated with CD. Among them, rs1884613 was replicated in the second CD cohort (odds ratio (OR): 1.33; P<0.012) and this association remained significant when both cohorts were combined and after correction for multiple testing (OR: 1.39; P<0.004). An 8-marker P2 promoter haplotype containing rs1884613 was also found associated with CD (P<2.09 × 10(-4) for combined cohorts). This is the first report showing that the HNF4A locus may be a common genetic determinant of childhood-onset CD. These findings highlight the importance of the intestinal epithelium and oxidative protection in the pathogenesis of CD.

[Post-thymus transplant vitiligo in a child with Foxn1 deficiency]. / Vitiligo post-greffe thymique chez un enfant porteur d'un déficit en Foxn1.

BACKGROUND: Foxn1 transcription factor deficit leads to immune deficiency, with hair and nail abnormalities. We report the case of a patient also presenting localized leucoderma. CASE REPORT: A 3-year-old boy underwent thymus transplantation at the age of 9 months for Foxn1 deficiency. He had developed urticaria and autoimmune hypothyroidism after thymus grafting. On examination, he had universal non-scarring alopecia, nail changes (atrophy, partial onycholysis and longitudinal grooves) and leucoderma on both big toes. DISCUSSION: This is the first description of leucoderma occurring in a patient with Foxn1 deficiency, as well as the first report of this pigment abnormality following thymus transplantation. The pathogenic hypotheses discussed were post-graft vitiligo and leucoderma induced by Foxn1 deficiency.

Inferior turbinate reduction: comparing post-operative bleeding between different surgical techniques.

OBJECTIVE: Post-operative bleeding is one of the most common and severe complications of turbinate surgery. This study compared post-operative bleeding following partial turbinectomy, submucosal turbinate reduction and endoscopic turbinoplasty. METHODS: Post-operative bleeding was assessed in patients who underwent inferior turbinate intervention by partial turbinectomy, submucosal turbinate reduction or endoscopic turbinoplasty between January 2016 and November 2017 and had completed at least one month of follow up. RESULTS: Of 1035 patients who underwent inferior turbinate surgery during the study period, 751 were included. Of these, 56 (7.5 per cent) presented to the emergency room with post-operative bleeding; 31 (8.4 per cent) had undergone partial turbinectomy, 19 (10.7 per cent) had undergone submucosal turbinate reduction and 6 (3.0 per cent) had undergone endoscopic turbinoplasty. The odds ratio of requiring an intervention to control bleeding was significantly lower in the endoscopic turbinoplasty group than in the submucosal turbinate reduction group (odds ratio = 3.26, 95 per cent confidence interval = 1.02-10.43). CONCLUSION: Endoscopic turbinoplasty had the lowest rate of post-operative bleeding and the lowest rate of patients requiring intervention.

Acoustic signalling and behaviour of Antarctic minke whales (Balaenoptera bonaerensis).

Acoustic signalling is the predominant form of communication among cetaceans. Understanding the behavioural state of calling individuals can provide insights into the specific function of sound production; in turn, this information can aid the evaluation of passive monitoring datasets to estimate species presence, density, and behaviour. Antarctic minke whales are the most numerous baleen whale species in the Southern Ocean. However, our knowledge of their vocal behaviour is limited. Using, to our knowledge, the first animal-borne audio-video documentation of underwater behaviour in this species, we characterize Antarctic minke whale sound production and evaluate the association between acoustic behaviour, foraging behaviour, diel patterns and the presence of close conspecifics. In addition to the previously described downsweep call, we find evidence of three novel calls not previously described in their vocal repertoire. Overall, these signals displayed peak frequencies between 90 and 175 Hz and ranged from 0.2 to 0.8 s on average (90% duration). Additionally, each of the four call types was associated with measured behavioural and environmental parameters. Our results represent a significant advancement in understanding of the life history of this species and improve our capacity to acoustically monitor minke whales in a rapidly changing Antarctic region.

Spatial variation of plastic debris on important turtle nesting beaches of the remote Chagos Archipelago, Indian Ocean.

We report Anthropogenic Marine Debris (AMD) in Chagos Archipelago in the Indian Ocean, globally amongst the most isolated island groups. AMD on 14 island beaches in five atolls were surveyed in 2019 using two techniques: Marine Debris Tracker (MDT) along littoral vegetation and photoquadrats in open beach. Over 60 % of AMD in both beach zones was composed of plastics, especially bottles and fragments (mean = 44.9 %, 27.2 %, range = 16.5-73.2 %, 4.8-55.9 % respectively in vegetation; mean = 28.7 %, 31.5 %, range = 17.7-40.7 %, 11.6-60.0 % respectively in open beach). The density of plastic debris in littoral vegetation (MDT data: 1995 bottles, 3328 fragments per 100 m2) was 10-fold greater than in open beach (photoquadrat data: 184 bottles, 106 fragments per 100 m2). Significant latitudinal variation in vegetation AMD occurred (8-fold greater in southern atolls, p = 0.006). AMD varied within island zones: most debris observed on oceanside beaches (oceanside vs lagoon, W = 365, p < 0.001; ocean vs island tip, W = 107, p = 0.034). Standardisation of surveys using the open-source MDT App is recommended. Debris accumulation hotspots overlapped with sea turtle nesting habitat, guiding future beach clean-up prioritisation.

Learning Curve for Flow Diversion of Posterior Circulation Aneurysms: A Long-Term International Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Flow diversion has gradually become a standard treatment for intracranial aneurysms of the anterior circulation. Recently, the off-label use of the flow diverters to treat posterior circulation aneurysms has also increased despite initial concerns of rupture and the suboptimal results. This study aimed to explore the change in complication rates and treatment outcomes across time for posterior circulation aneurysms treated using flow diversion and to further evaluate the mechanisms and variables that could potentially explain the change and outcomes. MATERIALS AND METHODS: A retrospective review using a standardized data set at multiple international academic institutions was performed to identify patients with ruptured and unruptured posterior circulation aneurysms treated with flow diversion during a decade spanning January 2011 to January 2020. This period was then categorized into 4 intervals. RESULTS: A total of 378 procedures were performed during the study period. Across time, there was an increasing tendency to treat more vertebral artery and fewer large vertebrobasilar aneurysms (P = .05). Moreover, interventionalists have been increasingly using fewer overlapping flow diverters per aneurysm (P = .07). There was a trend toward a decrease in the rate of thromboembolic complications from 15.8% in 2011-13 to 8.9% in 2018-19 (P = .34). CONCLUSIONS: This multicenter experience revealed a trend toward treating fewer basilar aneurysms, smaller aneurysms, and increased usage of a single flow diverter, leading to a decrease in the rate of thromboembolic and hemorrhagic complications.

Managing finances of shipping living donor kidneys for donor exchanges.

Kidney donor exchanges enable recipients with immunologically incompatible donors to receive compatible living donor grafts; however, the financial management of these exchanges, especially when an organ is shipped, is complex and thus has the potential to impede the broader implementation of donor exchange programs. Representatives from transplant centers that utilize the National Kidney Registry database to facilitate donor exchange transplants developed a financial model applicable to paired donor exchanges and donor chain transplants. The first tenet of the model is to eliminate financial liability to the donor. Thereafter, it accounts for the donor evaluation, donor nephrectomy hospital costs, donor nephrectomy physician fees, organ transport, donor complications and recipient inpatient services. Billing between hospitals is based on Medicare cost report defined costs rather than charges. We believe that this model complies with current federal regulations and effectively captures costs of the donor and recipient services. It could be considered as a financial paradigm for the United Network for Organ Sharing managed donor exchange program.