Population-based germline breast cancer gene association studies and meta-analysis to inform wider mainstream testing.

BACKGROUND: Germline genetic testing, previously restricted to familial and young-onset breast cancer, is now offered increasingly broadly to 'population-type' breast cancer patients in mainstream oncology clinics, with wide variation in the genes included. METHODS: Weighted meta-analysis was performed for three population-based case-control studies (BRIDGES, CARRIERS and UK Biobank) comprising in total 101,397 women with breast cancer and 312,944 women without breast cancer, to quantify for 37 putative breast cancer susceptibility genes (BCSGs) the frequency of pathogenic variants (PVs) in unselected, 'population-type' breast cancer cases and their association with breast cancer and its subtypes. RESULTS: Meta-analysed odds ratios (ORs) and frequencies of PVs in population-type breast cancer cases were generated for BRCA1 (OR= 8.73 (95% CI 7.47-10.20), 1 in 101), BRCA2 (OR=5.68 (5.13-6.30), 1 in 68) and PALB2 (OR= 4.30 (95% CI 3.68-5.03), 1 in 187). For both CHEK2 (OR=2.40 (95% CI 2.21-2.62), 1 in 73) and ATM (OR=2.16 (95%CI 1.93-2.41), 1 in 132) subgroup analysis showed stronger association with ER-positive disease. Magnitude of association and frequency of PVs were low for RAD51C (OR=1.53 (95%CI 1.15-2.04), 1 in 913), RAD51D (OR=1.76, (95%CI 1.15-2.41, 1 in 1079) and BARD1 (OR=2.34 (1.85-2.97), 1 in 672); frequencies and associations were moderately higher restricting to triple-negative breast cancers The PV-frequency in 'population-type' breast cancer cases was very low for 'syndromic' BCSGs TP53 (1 in 1844), STK11 (1 in 11,525), CDH1 (1 in 2668), PTEN (1 in 3755) and NF1 (1 in 1470), with metrics of association also modest ranging from OR=3.62 (95%CI 1.98-6.61) for TP53 down to OR=1.60 (95%CI 0.48-5.30) for STK11. CONCLUSIONS: These metrics reflecting 'population-type' breast cancer will be informative to defining the appropriate gene set as we continue to expand to germline testing out to more unselected population-type breast cancer cases.

A scalable and cGMP-compatible autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa.

We present Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a scalable platform producing autologous organotypic iPS cell-derived induced skin composite (iSC) grafts for definitive treatment. Clinical-grade manufacturing integrates CRISPR-mediated genetic correction with reprogramming into one step, accelerating derivation of COL7A1-edited iPS cells from patients. Differentiation into epidermal, dermal and melanocyte progenitors is followed by CD49f-enrichment, minimizing maturation heterogeneity. Mouse xenografting of iSCs from four patients with different mutations demonstrates disease modifying activity at 1 month. Next-generation sequencing, biodistribution and tumorigenicity assays establish a favorable safety profile at 1-9 months. Single cell transcriptomics reveals that iSCs are composed of the major skin cell lineages and include prominent holoclone stem cell-like signatures of keratinocytes, and the recently described Gibbin-dependent signature of fibroblasts. The latter correlates with enhanced graftability of iSCs. In conclusion, DEBCT overcomes manufacturing and safety roadblocks and establishes a reproducible, safe, and cGMP-compatible therapeutic approach to heal lesions of DEB patients.

Social Network Characteristics Associated with More Frequent HIV and STI Prevention Conversations: The N2 Cohort Study in Chicago.

Black cisgender sexually minoritized men (SMM) and transgender women (TW) are subgroups at highest risk of HIV and sexually transmitted infections (STIs) in the US. We sought to identify factors facilitating continued conversations - social reinforcement - surrounding HIV/STI prevention among this subgroup. Participants were recruited in Chicago from 2018 to 2019 from community health spaces. Participants provided information about themselves (level 2) and ⩽5 confidants (level 1). We used multinomial multilevel modeling to identify associations with HIV/STI prevention conversation frequency. A total of 370 participants provided information on 987 confidants (mean = 2.6). We found significantly positive associations between having biweekly or more often HIV/STI prevention conversations and a confidant being a kin family member, older by 15 years or more, racially homophilous, and emotionally close. Future interventions should harness social networks by including components that consider racial homophily, respect for elders, and strong ties, in addition to applying kin family systems interventions approaches and decreasing stigma surrounding HIV/STIs.

A Safety and Feasibility Trial of Ultrasound-Guided Radiofrequency Ablation of Parotid Warthin's Tumor.

OBJECTIVE: To determine if ultrasound-guided (USG) radiofrequency ablation (RFA) of Parotid Warthin's tumor under local anesthesia is a safe and effective procedure. STUDY DESIGN: Safety and feasibility study. SETTING: Tertiary academic medical center. METHODS: This is an IDEAL phase 2a trial in a tertiary referral center. Twenty patients with Parotid Warthin's tumor were recruited. RFA was done between September and December 2021 for all 20 patients using a CoATherm AK-F200 machine with a disposable, 18G × 7 mm radiofrequency electrode. Results and follow-up statistics were compared with a historic sample of patients with parotid Warthin's tumor who underwent parotidectomy between 2019 and 2021 in the same center. RESULTS: Nineteen patients were included in the analysis as 1 patient dropped out after 4 weeks of follow-up. The mean age for the RFA group was 67 years old with most of them being male smokers. At a median of 45 weeks (44-47 weeks) postprocedure there was a 7.48 mL (68.4%) volume reduction compared to baseline. Three patients had transient facial nerve (FN) paresis, 1 recovered within hours, and the other 2 by 12 weeks follow-up. Three patients had great auricular nerve numbness; 1 patient had infected hematoma treated in an out-patient manner. Compared to a historic cohort of parotidectomy patients for Warthin's tumor, there was no significant difference in FN paresis and other minor complications between the 2 treatment modalities. CONCLUSION: The current analysis suggests that USG RFA of Warthin's Tumor is a safe alternative to parotidectomy with shorter operative time and length of stay.

A scalable, GMP-compatible, autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa.

Background: Gene editing in induced pluripotent stem (iPS) cells has been hailed to enable new cell therapies for various monogenetic diseases including dystrophic epidermolysis bullosa (DEB). However, manufacturing, efficacy and safety roadblocks have limited the development of genetically corrected, autologous iPS cell-based therapies. Methods: We developed Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a new generation GMP-compatible (cGMP), reproducible, and scalable platform to produce autologous clinical-grade iPS cell-derived organotypic induced skin composite (iSC) grafts to treat incurable wounds of patients lacking type VII collagen (C7). DEBCT uses a combined high-efficiency reprogramming and CRISPR-based genetic correction single step to generate genome scar-free, COL7A1 corrected clonal iPS cells from primary patient fibroblasts. Validated iPS cells are converted into epidermal, dermal and melanocyte progenitors with a novel 2D organoid differentiation protocol, followed by CD49f enrichment and expansion to minimize maturation heterogeneity. iSC product characterization by single cell transcriptomics was followed by mouse xenografting for disease correcting activity at 1 month and toxicology analysis at 1-6 months. Culture-acquired mutations, potential CRISPR-off targets, and cancer-driver variants were evaluated by targeted and whole genome sequencing. Findings: iPS cell-derived iSC grafts were reproducibly generated from four recessive DEB patients with different pathogenic mutations. Organotypic iSC grafts onto immune-compromised mice developed into stable stratified skin with functional C7 restoration. Single cell transcriptomic characterization of iSCs revealed prominent holoclone stem cell signatures in keratinocytes and the recently described Gibbin-dependent signature in dermal fibroblasts. The latter correlated with enhanced graftability. Multiple orthogonal sequencing and subsequent computational approaches identified random and non-oncogenic mutations introduced by the manufacturing process. Toxicology revealed no detectable tumors after 3-6 months in DEBCT-treated mice. Interpretation: DEBCT successfully overcomes previous roadblocks and represents a robust, scalable, and safe cGMP manufacturing platform for production of a CRISPR-corrected autologous organotypic skin graft to heal DEB patient wounds.

Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations.

BACKGROUND: The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers. METHODS: We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and 'on-tumour' status (established tumour-gene association). RESULTS: Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was <2%. CONCLUSION: Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2, (iii) definition of a set of seven 'most actionable' cancer-susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6 and RET) in which germline follow-up is recommended regardless of tumour type.

Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes.

BACKGROUND: Breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. PATIENTS AND METHODS: We included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. ELIGIBILITY CRITERIA: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (<30 years), and (iv) concomitant ovarian cancer. We undertook exome sequencing of cases and carried out gene-level burden testing of rare damaging variants against those from 51 377 ethnicity-matched population controls from gnomAD. RESULTS: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10-5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10-4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. CONCLUSIONS: This is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes.

PURPOSE: Where multiple in silico tools are concordant, the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework affords supporting evidence toward pathogenicity or benignity, equivalent to a likelihood ratio of ~2. However, limited availability of "clinical truth sets" and prior use in tool training limits their utility for evaluation of tool performance. METHODS: We created a truth set of 9,436 missense variants classified as deleterious or tolerated in clinically validated high-throughput functional assays for BRCA1, BRCA2, MSH2, PTEN, and TP53 to evaluate predictive performance for 44 recommended/commonly used in silico tools. RESULTS: Over two-thirds of the tool-threshold combinations examined had specificity of <50%, thus substantially overcalling deleteriousness. REVEL scores of 0.8-1.0 had a Positive Likelihood Ratio (PLR) of 6.74 (5.24-8.82) compared to scores <0.7 and scores of 0-0.4 had a Negative Likelihood Ratio (NLR) of 34.3 (31.5-37.3) compared to scores of >0.7. For Meta-SNP, the equivalent PLR = 42.9 (14.4-406) and NLR = 19.4 (15.6-24.9). CONCLUSION: Against these clinically validated "functional truth sets," there was wide variation in the predictive performance of commonly used in silico tools. Overall, REVEL and Meta-SNP had best balanced accuracy and might potentially be used at stronger evidence weighting than current ACMG/AMP prescription, in particular for predictions of benignity.

Correction to: A 3i hip fracture liaison service with nurse and physician co-management is cost-effective when implemented as a standard clinical program.

The original version of this article, published on 22 July 2020, unfortunately contained a mistake.

A 3i hip fracture liaison service with nurse and physician co-management is cost-effective when implemented as a standard clinical program.

A hip fracture liaison service that was implemented in 2 hospitals in Alberta, Canada, co-managed by a nurse and physician, was cost-effective and improved initiation of osteoporosis medication following hip fracture. PURPOSE/INTRODUCTION: To determine cost-effectiveness of a 3i hip fracture liaison service (H-FLS) with 12-month follow-up, co-managed by a nurse and physician, when implemented into standard practice. METHODS: The cost-effectiveness analysis compared those receiving the H-FLS to a simulated usual care group using a decision analytic model that incorporated Markov processes. We estimated incremental costs and effectiveness (based on quality-adjusted life years (QALYs) gained) using a lifetime horizon and a healthcare payer perspective. The H-FLS program provided data regarding population at risk, treatment rates, persistence, and intervention costs. We also performed deterministic and probabilistic sensitivity analyses. RESULTS: One thousand two hundred fifty-two patients were included in the H-FLS between June 2015 and March 2018; 69% were female; the average age was 80 ± 11 years. Anti-absorptive treatment following fracture was initiated in 59.6% (95% CI: 55.7-63.5) H-FLS patients relative to 20.9% (95% CI: 13.3-28.5%) receiving usual care (from our published work). Based on modeled cohort simulation cost-effectiveness analysis (CEA), every 1000 H-FLS patients would experience 12 fewer hip fractures and 37 fewer total fragility fractures than patients receiving usual care. Over the study horizon, the H-FLS led to only a $54 incremental cost/patient with a modest gain of 8 QALYs/1000 patients. The incremental cost-effectiveness ratio (ICER) of $6750/QALY gained was less than the $27,000 cost-effectiveness threshold. Eliminating the 9-month follow-up resulted in incremental savings of $218/patient while also reducing 6-month follow-ups increased cost-savings to $378/patient. Probabilistic sensitivity analyses suggested that the H-FLS would either be cost-saving (60%) or cost-effective (40%). CONCLUSION: A H-FLS implemented into standard practice significantly improved anti-absorptive medication use; a cohort simulation cost-effectiveness analysis (CEA) suggested that the H-FLS was cost-effective with potential to become cost-savings.

Implementation of an in-patient hip fracture liaison services to improve initiation of osteoporosis medication use within 1-year of hip fracture: a population-based time series analysis using the RE-AIM framework.

A hip fracture liaison service that was implemented in 2 hospitals in Alberta, Canada, co-managed by a nurse and physician, was effective for improving initiation of osteoporosis medication following hip fracture. PURPOSE: To examine implementation of an in-patient hip fracture liaison service (H-FLS) to improve osteoporosis medication use after hip fracture using the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance). METHODS: Using population-based administrative data from 7 quarters before and up to 7 quarters after H-FLS implementation, we examined new starts, continued use, and overall use (new starts + continued use) of osteoporosis medication after hip fracture. A total of 1427 patients 50 years and older that underwent hip fracture surgery at 1 of 2 tertiary hospitals in a Canadian province and survived to 12 months post-fracture were included. We also compared treatment initiation rates by sex and hospital. RESULTS: Of the 1427 patients, 1002 (70.2%) were female (mean age = 79.3 ± 11.9 years) and 425 (29.8%) were male (mean age = 73.8 ± 13.8 years). Based on pre-fracture residence within the health zone, 1101 (69%) were considered eligible (Reach). New starts of osteoporosis medication increased from 24.7% pre- to 43.9% post-implementation of the H-FLS (p < 0.001) (effectiveness). The proportion of patients prescribed osteoporosis medication prior to a hip fracture remained consistent (15.1% pre-; 14.7% post-implementation; p = 0.88) with a resultant improvement in overall medication use from 39.8% pre- to 58.6% post-implementation (p < 0.001). Both sites significantly improved medication initiation (site 1: 27.9% pre- to 40.3% post-implementation; site 2: 19.6% pre- to 50.0% post-implementation; p < 0.001 for both) (adoption). Medication initiation in females improved from 26.0% pre- to 43.4% post-implementation while initiation in males improved from 21.7% pre- to 45.1% post-implementation (p < 0.001[females]; p = 0.001[males]) (implementation). Post-implementation, elevated initiation rates were retained over the 7 quarters (p = 0.81) (maintenance). CONCLUSIONS: An H-FLS based in two tertiary hospital sites significantly improved use of osteoporosis medications after hip fracture in both males and females.

Germline-focussed analysis of tumour-only sequencing: recommendations from the ESMO Precision Medicine Working Group.

It is increasingly common in oncology practice to perform tumour sequencing using large cancer panels. For pathogenic sequence variants in cancer susceptibility genes identified on tumour-only sequencing, it is often unclear whether they are of somatic or constitutional (germline) origin. There is wide-spread disparity regarding both the extent to which systematic 'germline-focussed analysis' is carried out upon tumour sequencing data and for which variants follow-up analysis of a germline sample is carried out. Here we present analyses of paired sequencing data from 17 152 cancer samples, in which 1494 pathogenic sequence variants were identified across 65 cancer susceptibility genes. From these analyses, the European Society of Medical Oncology Precision Medicine Working Group Germline Subgroup has generated (i) recommendations regarding germline-focussed analyses of tumour-only sequencing data, (ii) indications for germline follow-up testing and (iii) guidance on patient information-giving and consent.

TFAP2C- and p63-Dependent Networks Sequentially Rearrange Chromatin Landscapes to Drive Human Epidermal Lineage Commitment.

Tissue development results from lineage-specific transcription factors (TFs) programming a dynamic chromatin landscape through progressive cell fate transitions. Here, we define epigenomic landscape during epidermal differentiation of human pluripotent stem cells (PSCs) and create inference networks that integrate gene expression, chromatin accessibility, and TF binding to define regulatory mechanisms during keratinocyte specification. We found two critical chromatin networks during surface ectoderm initiation and keratinocyte maturation, which are driven by TFAP2C and p63, respectively. Consistently, TFAP2C, but not p63, is sufficient to initiate surface ectoderm differentiation, and TFAP2C-initiated progenitor cells are capable of maturing into functional keratinocytes. Mechanistically, TFAP2C primes the surface ectoderm chromatin landscape and induces p63 expression and binding sites, thus allowing maturation factor p63 to positively autoregulate its own expression and close a subset of the TFAP2C-initiated surface ectoderm program. Our work provides a general framework to infer TF networks controlling chromatin transitions that will facilitate future regenerative medicine advances.

Comparative effectiveness of one versus two-stage sacral neurostimulation device placement.

OBJECTIVE: Sacral neurostimulation (SNS) is an effective third-line treatment for overactive bladder. We sought to compare the cost of standard two-stage SNS device placement to that of a combined one-stage placement using a Markov chain model. METHODS: Costs were defined using Medicare outpatient reimbursement rates. The model was developed as follows: With the two-stage approach, patients underwent initial lead placement with fluoroscopy and those who converted to stage two underwent permanent generator placement week later. Patients who did not convert underwent lead removal. Patients undergoing a one-stage procedure had initial lead and generator placement at the same time. Patients with success underwent no further procedure. Patients without success could opt for generator and lead removal. Cost effectiveness of one versus two-stage placement depended on successful conversion rate. RESULTS: Reimbursement included physician, anesthesia, facility and device fees. In a two-stage procedure, initial cost of lead placement was $6170. With successful conversion, cost of a second procedure with permanent lead and generator placement was $18,474. Patients who failed test phase underwent lead removal for a cost of $2879. In a one-stage procedure approach, initial cost of permanent lead and generator placement was $18,474. Patients with a successful outcome had no additional costs. Patients with an unsuccessful outcome could have the lead and generator removal for a cost of $5758. If the conversion rate from testing phase to permanent placement was greater than 71%, a one-stage approach proved to be cost effective. CONCLUSIONS: Identifying patients with favorable risk factors for success may predict those patients who warrant a one-stage approach.

Sertoli-Leydig Cell Tumour and DICER1 Mutation: A Case Report and Review of the Literature.

Sertoli-Leydig cell tumours of the ovary (SLCT) are rare tumours predominantly caused by mutations in the DICER1 gene. We present a patient with a unilateral SLCT who had an underlying germline DICER1 gene mutation. We discuss the underlying pathology, risks, and screening opportunities available to those with a mutation in this gene as SLCT is only one of a multitude of other tumours encompassing DICER1 syndrome. The condition is inherited in an autosomal dominant fashion. As such, genetic counselling is a key component of the management of women with SLCT.

Outbreak of non-tuberculous mycobacteria skin or soft tissue infections associated with handling fish - New York City, 2013-2014.

Mycobacterium marinum, a bacterium found in freshwater and saltwater, can infect persons with direct exposure to fish or aquariums. During December 2013, the New York City Department of Health and Mental Hygiene learned of four suspected or confirmed M. marinum skin or soft tissue infections (SSTIs) among persons who purchased whole fish from Chinese markets. Ninety-eight case-patients with non-tuberculous mycobacteria (NTM) SSTIs were identified with onset June 2013-March 2014. Of these, 77 (79%) were female. The median age was 62 years (range 30-91). Whole genome sequencing of clinical isolates revealed two main clusters and marked genetic diversity. Environmental samples from distributors yielded NTM though not M. marinum. We compared 56 case-patients with 185 control subjects who shopped in Chinese markets, frequency-matched by age group and sex. Risk factors for infection included skin injury to the finger or hand (odds ratio [OR]: 15·5; 95% confidence interval [CI]: 6·9-37·3), hand injury while preparing fish or seafood (OR 8·3; 95% CI 3·8-19·1), and purchasing tilapia (OR 3·6; 95% CI 1·1-13·9) or whiting (OR 2·7; 95% CI 1·1-6·6). A definitive environmental outbreak source was not identified.

Qualitative Insights from the Osteoporosis Research: A Narrative Review of the Literature.

Purpose. Much of the research on osteoporosis has been generated quantitatively. However, the qualitative osteoporosis literature provides valuable information on patient and clinician experiences and perspectives, informing the design and implementation of health research and healthcare services. To identify knowledge gaps and inform the design of future qualitative research, a narrative review was conducted to consolidate and synthesize the existing insights available within the qualitative osteoporosis research. Methods. Search terms reflecting the domains of osteoporosis and qualitative research were entered into the Scopus database to generate a comprehensive survey of qualitative research in the area of osteoporosis. Articles were thematically analysed and the results are presented in the form of a narrative review. Results. Forty-four articles were included in the narrative review. Qualitative research in the field of osteoporosis research can be summarized by 3 thematic areas: the meaning of osteoporosis for patients and the public, the lived experience of an osteoporosis diagnosis, and the programmatic approach to osteoporosis prevention and treatment. Conclusions. Qualitative studies provide clinically valuable insights in how osteoporosis is conceptualized and managed and programmatic aspects of osteoporosis treatment. The findings of this narrative review suggest the need for balance between presenting osteoporosis as a serious health condition and producing unwarranted anxiety and inactivity so as to ensure the best possible outcomes for individuals with osteoporosis.

Retroperitoneal hemorrhage after ureteroscopy without laser lithotripsy: an extreme example of an underreported event?

Retroperitoneal hemorrhage and an associated hematoma are uncommon but potentially serious complications following ureteroscopy with laser lithotripsy. However, no reports of serious bleeding complications have been published regarding ureteroscopy without laser lithotripsy in the management of stone disease. We report of such a case here and then review the current literature in order to discuss the incidence, risk factors, and management of such events.

Movers and stayers: how residential selection contributes to the association between female body mass index and neighborhood characteristics.

BACKGROUND/OBJECTIVES: To examine how a woman's current body mass index (BMI) is associated with nonrandom residential migration that is based on the average BMI of her origin and destination neighborhoods. SUBJECTS/METHODS: Among women having at least two children, all birth certificates from Salt Lake county from 1989 to 2010 (n=34 010) were used to obtain prepregnancy weights before the first and second births, residential location and sociodemographic information. Census data were used for measures of walkability of neighborhoods. RESULTS: After adjustments for age, education, race/ethnicity and marital status, obese women living in the leanest neighborhoods are found to be three times more likely (odds ratio (OR)=3.03, 95% confidence interval (CI) 2.06-4.47) to move to the heaviest neighborhoods relative to women with healthy weight (BMI between 18 and 25 kg m(-2)). Conversely, obese women in the heaviest neighborhoods are 60% less likely (OR=0.39, 95% CI 0.22-0.69) to move to the leanest neighborhoods relative to healthy weight women. Indicators of relatively greater walkability (older housing, greater proportion of residents who walk to work) and higher median family income characterize leaner neighborhoods. CONCLUSIONS: The findings are consistent with the hypothesis that nonrandom selection into and out of neighborhoods accounts for some of the association between BMI and neighborhood characteristics.