Fatty acid binding protein 5 inhibition attenuates pronociceptive cytokine/chemokine expression and suppresses osteoarthritis pain: A comparative human and rat study.

OBJECTIVE: Osteoarthritis (OA) is often accompanied by debilitating pain that is refractory to available analgesics due in part to the complexity of signaling molecules that drive OA pain and our inability to target these in parallel. Fatty acid binding protein 5 (FABP5) is a lipid chaperone that regulates inflammatory pain; however, its contribution to OA pain has not been characterized. DESIGN: This combined clinical and pre-clinical study utilized synovial tissues obtained from subjects with end-stage OA and rats with monoiodoacetate-induced OA. Cytokine and chemokine release from human synovia incubated with a selective FABP5 inhibitor was profiled with cytokine arrays and ELISA. Immunohistochemical analyses were conducted for FABP5 in human and rat synovium. The efficacy of FABP5 inhibitors on pain was assessed in OA rats using incapacitance as an outcome. RNA-seq was then performed to characterize the transcriptomic landscape of synovial gene expression in OA rats treated with FABP5 inhibitor or vehicle. RESULTS: FABP5 was expressed in human synovium and FABP5 inhibition reduced the secretion of pronociceptive cytokines (interleukin-6 [IL6], IL8) and chemokines (CCL2, CXCL1). In rats, FABP5 was upregulated in the OA synovium and its inhibition alleviated incapacitance. The transcriptome of the rat OA synovium exhibited >6000 differentially expressed genes, including the upregulation of numerous pronociceptive cytokines and chemokines. FABP5 inhibition blunted the upregulation of the majority of these pronociceptive mediators. CONCLUSIONS: FABP5 is expressed in the OA synovium and its inhibition suppresses pronociceptive signaling and pain, indicating that FABP5 inhibitors may constitute a novel class of analgesics to treat OA.

Wilms Tumor With Raised Serum Alpha-Fetoprotein: Highlighting the Need for Novel Circulating Biomarkers.

Wilms tumor (WT) is the commonest cause of renal cancer in children. In Europe, a diagnosis is made for most cases on typical clinical and radiological findings, prior to pre-operative chemotherapy. Here, we describe a case of a young boy presenting with a large abdominal tumor, associated with raised serum alpha-fetoprotein (AFP) levels at diagnosis. Given the atypical features present, a biopsy was taken, and histology was consistent with WT, showing triphasic WT, with epithelial, stromal, and blastemal elements present, and positive WT1 and CD56 immunohistochemical staining. During pre-operative chemotherapy, serial serum AFP measurements showed further increases, despite a radiological response, before a subsequent fall to normal following nephrectomy. The resection specimen was comprised of ~55% and ~45% stromal and epithelial elements, respectively, with no anaplasia, but immunohistochemistry using AFP staining revealed positive mucinous intestinal epithelium, consistent with the serum AFP observations. The lack of correlation between tumor response and serum AFP levels in this case highlights a more general clinical unmet need to identify WT-specific circulating tumor markers.

Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption.

BACKGROUND: MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant germ cell tumours (GCTs), regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed sequence 'AAGUGC', determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally. METHODS: We targeted miR-371~373 and/or miR-302/367 clusters in malignant GCT cell lines, using CRISPR-Cas9, gapmer primary miR-302/367 transcript inhibition, and peptide nucleic acid (PNA) or locked nucleic acid (LNA)-DNA inhibition targeting miR-302a-d-3p, and undertook relevant functional assays. RESULTS: MiR-302/367 cluster microRNAs made the largest contribution to AAGUGC seed abundance in malignant GCT cells, regardless of subtype (seminoma/YST/EC). Following the unsuccessful use of CRISPR-Cas9, gapmer, and PNA systems, LNA-DNA-based targeting resulted in growth inhibition in seminoma and YST cells. This was associated with the de-repression of multiple mRNAs targeted by AAGUGC seed-containing microRNAs, with pathway analysis confirming predominant disruption of Rho-GTPase signalling, vesicle organisation/transport, and cell cycle regulation, findings corroborated in clinical samples. Further LNA-DNA inhibitor studies confirmed direct cell cycle effects, with an increase of cells in G0/G1-phase and a decrease in S-phase. CONCLUSION: Targeting of specific miR-371~373 and miR-302/367 microRNAs in malignant GCTs demonstrated their functional significance, with growth inhibition mediated through cell cycle disruption.

Endovascular Repair of Popliteal Artery Injury Post-total Knee Arthroplasty is Safe and Effective: A Case Report and Systematic Review of the Literature.

BACKGROUND: Popliteal artery pseudoaneurysms are a rare but serious complication following total knee arthroplasty that have been traditionally managed with open surgical repair. Endovascular stenting, while relatively new, offers a promising alternative that is less invasive and may reduce the risk of perioperative complications. METHODS: A systematic literature review was conducted, and all clinical reports in the English language from inception to July 2022 were identified. References were manually reviewed to identify additional studies. Demographics, procedural techniques, postprocedural complications, and followup data were extracted and analyzed using STATA 14.1. Additionally, we present a case of a patient with a popliteal pseudoaneurysm treated with a covered endovascular stent. RESULTS: A total of 14 studies (12 case reports, 2 case series; n = 17) were included for review. In all cases, a stent-graft was placed across the popliteal artery lesion. In 5 out of 11 cases, popliteal artery thrombus was present and treated with adjacent modalities (i.e., mechanical thrombectomy, balloon angioplasty, etc.). Procedure success was reported in all cases without perioperative adverse events. Stents remained patent over a median followup of 32 weeks (interquartile range: 36). In all but one case, the patients experienced immediate symptom relief and had an uneventful recovery. For our case, at the 12-month followup the patient was asymptomatic, and ultrasound demonstrated vessel patency. CONCLUSIONS: Endovascular stenting is a safe and effective treatment for popliteal pseudoaneurysms. Future studies should be aimed at evaluating the long-term outcomes of such minimally invasive techniques.

Imaging response assessment for CNS germ cell tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group.

Homogeneous and common objective disease assessments and standardised response criteria are important for better international clinical trials for CNS germ cell tumours. Currently, European protocols differ from those of North America (the USA and Canada) in terms of criteria to assess radiological disease response. An international working group of the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group was therefore established to review existing literature and current practices, identify major challenges regarding imaging assessment, and develop consensus recommendations for imaging response assessment for patients with CNS germ cell tumours. New clinical imaging standards were defined for the most common sites of CNS germ cell tumour and for the definition of locoregional extension. These new standards will allow the evaluation of response to therapy in patients with CNS germ cell tumours to be more consistent, and facilitate direct comparison of treatment outcomes across international studies.

The NHS England 100,000 Genomes Project: feasibility and utility of centralised genome sequencing for children with cancer.

BACKGROUND: Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally. METHODS: Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value. RESULTS: Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36). CONCLUSION: Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.

Advancing clinical and translational research in germ cell tumours (GCT): recommendations from the Malignant Germ Cell International Consortium.

Germ cell tumours (GCTs) are a heterogeneous group of rare neoplasms that present in different anatomical sites and across a wide spectrum of patient ages from birth through to adulthood. Once these strata are applied, cohort numbers become modest, hindering inferences regarding management and therapeutic advances. Moreover, patients with GCTs are treated by different medical professionals including paediatric oncologists, neuro-oncologists, medical oncologists, neurosurgeons, gynaecological oncologists, surgeons, and urologists. Silos of care have thus formed, further hampering knowledge dissemination between specialists. Dedicated biobank specimen collection is therefore critical to foster continuous growth in our understanding of similarities and differences by age, gender, and site, particularly for rare cancers such as GCTs. Here, the Malignant Germ Cell International Consortium provides a framework to create a sustainable, global research infrastructure that facilitates acquisition of tissue and liquid biopsies together with matched clinical data sets that reflect the diversity of GCTs. Such an effort would create an invaluable repository of clinical and biological data which can underpin international collaborations that span professional boundaries, translate into clinical practice, and ultimately impact patient outcomes.

Vinblastine monotherapy induction prior to radiotherapy for patients with intracranial germinoma during the COVID-19 pandemic.

BACKGROUND: Patients with localized intracranial germinoma have excellent survival. Reducing treatment burden and long-term sequelae is a priority. Intensive inpatient chemotherapy (e.g., carboPEI = carboplatin/etoposide/ifosfamide) has been effectively employed to reduce radiotherapy treatment volume/dose. Outpatient-based carboplatin monotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology), and successful vinblastine monotherapy induction (with 77% tumor volume reduction after just two weekly vinblastine doses) has recently been reported in an intracranial germinoma patient. METHODS: Adapted UK guidelines for germ cell tumor management were distributed during the COVID-19 pandemic, including nonstandard treatment options to reduce hospital visits and/or admissions. This included vinblastine monotherapy for intracranial germinoma (6 mg/m2 intravenously, or 4 mg/m2 for moderate count suppression, delivered weekly). We describe two such patients treated using this approach. RESULTS: A 30-year-old male with a localized pineal tumor received 12-week vinblastine induction, with >60% volume reduction, prior to definitive radiotherapy. A 12-year-old female with a metastatic suprasellar tumor and progression at all sites of disease whilst awaiting proton radiotherapy received two vinblastine doses with good early response, including 36% primary tumor volume reduction. The patients tolerated vinblastine well. CONCLUSION: Patients with intracranial germinoma have excellent outcomes, and reduction of late effects remains a priority. The description of vinblastine monotherapy in these intracranial germinoma patients warrants further exploration.

Risk taking propensity: Nurse, surgeon and patient preferences for diverting ileostomy.

AIM: The decision-making process to defunction a pelvic colorectal anastomosis involves complex heuristics and is framed by surgeon personality factors. Risk taking propensity may be an important factor in these decisions and patient preferences have not been evaluated alongside surgeons and nurses. METHODS: A prospective cross-sectional study involving a one-off interview and questionnaire assessing how risk taking propensity affects nurse, surgeon and patient preferences for a temporary defunctioning ileostomy (TDI) was performed. The risk taking index (RTI) was employed to evaluate risk taking propensity and the validated prospective measures of preference instruments to evaluate preferences for stoma avoidance in several scenarios by asking the individual to consider trading or gambling years of remaining life expectancy. RESULTS: One hundred and fifty participants met the inclusion criteria, which included 30 (20.0%) surgical nurses, 20 (13.3%) colorectal surgeons and 100 (66.7%) patients. Surgeons had a significantly higher RTI (mean ± SD: 26.8 ± 6.7) than patients (mean ± SD: 20.0 ± 9.8) and nurses (mean ± SD: 23.0 ± 6.6) p = 0.002. Surgeons would consider that it would be in a patient's best interest to have a TDI at an AL rate of 15% or greater, whereas nurses and patients would do so at 28% and 25%, respectively (p = 0.007). CONCLUSION: Surgeons were shown to have a higher risk taking propensity than patients and nurses but a significantly lower threshold of AL where they would consider a TDI is in the best interest of the patient.

Outcomes of adolescent males with extracranial metastatic germ cell tumors: A report from the Malignant Germ Cell Tumor International Consortium.

BACKGROUND: Adolescents with extracranial metastatic germ cell tumors (GCTs) are often treated with regimens developed for children, but their clinical characteristics more closely resemble those of young adult patients. This study was designed to determine event-free survival (EFS) for adolescents with GCTs and compared them with children and young adults. METHODS: An individual patient database of 11 GCT trials was assembled: 8 conducted by pediatric cooperative groups and 3 conducted by an adult group. Male patients aged 0 to 30 years with metastatic, nonseminomatous, malignant GCTs of the testis, retroperitoneum, or mediastinum who were treated with platinum-based chemotherapy were included. The age groups were categorized as children (0 to <11 years), adolescents (11 to <18 years), and young adults (18 to ≤30 years). The study compared EFS and adjusted for risk group by using Cox proportional hazards analysis. RESULTS: From a total of 2024 individual records, 593 patients met the inclusion criteria: 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS rate was lower for adolescents (72%; 95% confidence interval [CI], 62%-79%) than children (90%; 95% CI, 81%-95%; P = .003) or young adults (88%; 95% CI, 84%-91%; P = .0002). The International Germ Cell Cancer Collaborative Group risk group was associated with EFS in the adolescent age group (P = .0020). After adjustments for risk group, the difference in EFS between adolescents and children remained significant (hazard ratio, 0.30; P = .001). CONCLUSIONS: EFS for adolescent patients with metastatic GCTs was similar to that for young adults but significantly worse than for that children. This finding highlights the importance of coordinating initiatives across clinical trial organizations to improve outcomes for adolescents and young adults. LAY SUMMARY: Adolescent males with metastatic germ cell tumors (GCTs) are frequently treated with regimens developed for children. In this study, a large data set of male patients with metastatic GCTs across different age groups has been built to understand the outcomes of adolescent patients in comparison with children and young adults. The results suggest that adolescent males with metastatic GCTs have worse results than children and are more similar to young adults with GCTs. Therefore, the treatment of adolescents with GCTs should resemble therapeutic approaches for young adults.

Galectin-3 diminishes Wnt signaling in the postnatal subventricular zone.

Postnatal subventricular zone (pSVZ) stem and progenitor cell proliferation is regulated by several developmental signaling pathways such as Wnt/ß-catenin. However, the molecular regulation of Wnt function in the pSVZ is poorly understood. We previously showed that Wnt signaling is upregulated in an SVZ gliomagenesis in vivo model. As well, the pro-inflammatory molecule Galectin-3 (Gal-3) increases Wnt signaling in cancer cells and is expressed in the SVZ. Therefore, we asked if Gal-3 has a similar function on Wnt signaling in the pSVZ. We interrogated Wnt signaling using a signaling reporter as well as immunohistochemistry and showed that Wnt signaling predominates upstream in the pSVZ lineage but is downregulated in migrating neuroblasts. Biochemical analysis of SVZ cells, in vivo and in neurosphere stem/progenitor cells, showed that Gal-3 physically interacts with multiple forms of ß-catenin, which is a major downstream regulator of Wnt signaling. Functional analyses demonstrated, in vitro and in vivo, that Gal-3 knockdown increases Wnt signaling and conversely that Gal-3 OE inhibits Wnt/ß-catenin signaling in the pSVZ. This latter result suggested that Gal-3, which is consistently increased in brain injury, may decrease pSVZ proliferation. We showed that Gal-3 OE decreased proliferation without altering cell cycle re-entry and that it increased p27Kip1, a molecule which induces cell cycle exit. Our data uncover a novel regulator of Wnt signaling in the SVZ, Gal-3, which does so in a manner opposite to cancer.

Galectin-3 modulates postnatal subventricular zone gliogenesis.

Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3 (Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal-3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation-independent effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis. Gain-of-function of Gal-3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function for Gal-3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.

Continuous vs stepwise anal acoustic reflectometry: An improved technique for physiological measurement of anal sphincter function?

BACKGROUND: Anal acoustic reflectometry (AAR) is a technique for measuring the physiological profile of the anal canal, primarily the internal anal sphincter. Evaluation of a new continuous method, recently developed for the urethra, would enable its future application for investigation of rectal reflexes. METHODS: Patients aged 18 and over with fecal incontinence (FI) were included. Stepwise AAR parameters were compared with continuous opening pressure (Op, cmH2 O), opening elastance (Oe, cmH2 O/mm2 ), closing pressure (Cp, cmH2 O), closing elastance (Ce, cmH2 O/mm2 ), hysteresis (Hys, [%]), squeeze opening pressure (SqOp, cmH2 O), and squeeze opening elastance (SqOe, cmH2 O/mm2 ). Vaizey incontinence and Manchester Health Questionnaire scores were also collected. RESULTS: Thirty-two patients, 26 females were analyzed. Median age: 60 (range, 32-75). Median AAR parameters of Op (37.50 vs 35.15, P = .031), Oe (1.31 vs 0.84, P < .0001), Ce (1.11 vs 0.88, P < .0001), Hys (37.75 vs 19.04, P < .0001), and SqOe (1.27 vs 1.06, P = .005) were significantly higher with the continuous method. Cp (22.70 vs 27.22, P = .003) is lower and SqOp (96.87 vs 59.47, P = .71) not significantly different. The continuous technique had superior repeatability between cycles for all AAR parameters except Oe, which was equivalent and continuous SqOp had a stronger negative correlation with Vaizey score than stepwise (-0.46, P = .009 vs -0.37, P = .038). CONCLUSIONS: The differences seen between the two techniques are likely to be related to the rate of stretch. The continuous technique appears to represent a more physiological measurement of anal sphincter function than the stepwise technique particularly in the assessment of voluntary squeeze function.

Trends in phenotype in the English paediatric neurofibromatosis type 2 cohort stratified by genetic severity.

Childhood onset neurofibromatosis type 2 can be severe and genotype dependent. We present a retrospective phenotypic analysis of all ascertained children in England 1.0). Focal cortical dysplasia occurred in 26% group 3 and 4% 2A. A total of 48% of group 3 underwent ≥1 major intervention (intracranial/spinal surgery/Bevacizumab/radiotherapy) compared to 35% of 2A; with 23% group 3 undergoing spinal surgery (schwannoma/ependymoma/meningioma resection) compared to 4% of 2A. Mean age starting Bevacizumab was 12.7 in group 3 and 14.9 years in 2A. In conclusion, group 3 phenotype manifests earlier with greater tumour load, poorer visual outcomes and more intervention.

Recurrent ovarian immature teratoma in a 12-year-old girl: Implications for management.

Immature teratomas (IT) are rare and recurrences uncommon. A 12-year-old female with grade 3 (high-grade) ovarian IT underwent surgical resection but experienced early recurrences; the first was treated with surgery but the second was metastatic and managed with chemotherapy, resulting in growing-teratoma-syndrome and need for further surgery. She now remains well in uneventful clinical follow-up. We believe chemotherapy could be reserved for very carefully selected recurrent IT cases, which may alter the natural history of disease.

Canadian patterns of practice for intracranial germ cell tumors in adolescents and young adults.

INTRODUCTION: The study objectives were to describe patterns of practice for intracranial germ cell tumors (IGCT) in adolescents and young adults (AYA) and to determine factors associated with practice patterns. METHODS: A survey was written containing questions on the management of two 17-year old males, one with localized pineal germinoma and the other with localized pineal non-germinomatous germ cell tumor (NGGCT). An invitation to participate anonymously in the survey was e-mailed to 119 oncologists who treat brain tumors across Canada. RESULTS: Seventy-two (61%) of the 119 oncologists participated in the study. For the germinoma case, the most common treatment approaches were whole ventricular radiotherapy (WVRT) and chemotherapy (CH) (56%), WVRT alone (15%), and craniospinal radiotherapy (CSRT) alone (10%); for physicians recommending WVRT + CH, most frequently selected whole ventricular doses were 24 Gy (57%) and 18 Gy (20%). Chemotherapy was included in the treatment of germinoma by 96% of pediatric physicians vs. 54% of adult physicians (P = 0.001). The most common treatment approaches for NGGCT were CSRT + CH (44%), WVRT + CH (21%), and pineal gland RT + CH (15%). The selection of craniospinal vs. smaller-volume RT was not associated with the physicians' specialty, percentage of practice treating brain tumors, number of IGCTs seen, or size of institution. CONCLUSIONS: There is wide variation in the management of IGCT in AYA across Canada. A 17-year old male with a localized pineal germinoma is highly likely to receive chemotherapy if managed by a pediatric oncologist, while the same patient is much less likely to receive chemotherapy if managed by an adult oncologist.

Methodologic Validation of a Faster Pelvic Floor Test: Two Randomized Studies in Anal Acoustic Reflectometry.

BACKGROUND: Anal acoustic reflectometry investigates the opening and closing function of the anal canal using reflected sound waves to measure a cross-sectional area at different pressures. Anal acoustic reflectometry is reliable and repeatable, distinguishes between continence and incontinence and between subgroups of incontinence, correlates with symptom severity, and does not distort the anal canal during investigation. OBJECTIVE: The purpose of this study was to validate anal acoustic reflectometry methodology by asking 2 questions: can anal acoustic reflectometry be used alongside manometry (order study) and can anal acoustic reflectometry be performed faster (filling study). The secondary aim was to assess the response of the anal canal to stretch using anal acoustic reflectometry. DESIGN: This research included 2 prospective randomized studies. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: Patients undergoing investigation for fecal incontinence were included. INTERVENTION: For the order study, patients were prospectively randomized to anal acoustic reflectometry, manometry, 2-minute rest and then manometry, anal acoustic reflectometry, or vice versa. For the filling study, patients were prospectively randomized to fast rate anal acoustic reflectometry (5 cm H2O/1 s), manometry, 2-minute rest and then manometry, normal rate anal acoustic reflectometry (5 cm H2O/3 s), or vice versa. MAIN OUTCOME MEASURES: The primary outcome was no difference in anal acoustic reflectometry or manometry variables. Demographic and clinical data were recorded. RESULTS: The order study included 30 patients with a median age of 63 years (range, 30-84 y); 77% were women. No difference was found among all of the variables of anal acoustic reflectometry and manometry regardless of which test was performed first. The filling study included 50 patients with a median age of 62 years (range, 30-78 y); 80% were women. No difference was found between fast and normal rates of anal acoustic reflectometry and manometry in any order. LIMITATIONS: This study was limited by its comparison with water-perfused manometry. CONCLUSIONS: Anal acoustic reflectometry and manometry can be performed at the normal or fast rate of anal acoustic reflectometry in any order. A fast rate of anal acoustic reflectometry did not augment the response of the anal canal to stretch as measured by anal acoustic reflectometry and manometry. This study validates a faster anal acoustic reflectometry technique and vindicates previous data. See Video Abstract at http://links.lww.com/DCR/A821.

Severity of heterotopic ossification in patients following surgery for hip fracture: a retrospective observational study.

BACKGROUND: Heterotopic ossification (HO) is a relatively common complication following hip surgery treated with open reduction and internal fixation, total arthroplasty or hemiarthroplasty. Development of HO after hip surgery is an important clinical issue as it can affect functional status. We aimed to determine whether there was association between severity of heterotopic ossification about the hip and the interval between the time of hip fracture and surgery. MATERIALS AND METHODS: Our retrospective study included 151 patients (age range 33-95 years) treated for hip fractures by hemiarthroplasty. Medical records were reviewed for time interval to surgery, laterality, surgical approach, and patient age. Patients who had any post-operative complications were excluded. Radiographs were semiquantitatively assessed for the degree of heterotopic ossification based on Brooker Classification (5-point scale). Statistical analysis was performed utilizing Chi-square, Kruskal-Wallis, and Score tests, and also a proportional odds model (significance level set at 0.05). RESULTS: Thirty eight patients had no heterotopic ossification, 43 had class 1, 55 had class 2, and 15 had class 3 or greater heterotopic ossification. The majority of patients (59.6%) had surgery within 2 days of acute injury. Severe heterotopic ossification (HO 3+) was associated with the longer interval between the time of acute hip fracture and surgery (median 6 days) vs. median 2 days in all other groups (HO classes 0-2) (p = 0.0015). The odds ratio and 95% CI for one level higher HO class was 1.296 (1.152, 1.459), which meant that the odds of having HO class one level higher increased by about 29.6% for every one-day increase in the days to surgery. No significant association was found for other variables. CONCLUSION: Class 3 or greater HO was associated with longer time interval between time of acute hip fracture and surgery compared to all other groups (HO class 0-2).