An interprofessional clinic for adults with Turner syndrome: the patient perspective.

OBJECTIVES: This qualitative study assessed the value of a primary care-based interprofessional clinical team for adults with Turner syndrome (TS) utilizing patient perspectives. METHODS: Ten patients within one institution's interprofessional adult TS clinic participated in one of two semi-structured focus groups. Content analysis was used to classify content provided by participants into themes and sub-themes using Dedoose software. RESULTS: Participants found that their quality of care and life were both improved due to the presence of the interprofessional Adults with TS Clinic. Specifically, participants reported that the clinic helped address problems with finding knowledgeable providers and care gaps, made appointments more convenient and improved interprofessional communication. Participants also reported that the clinic helped them find a sense of community and increased personal confidence. Study participants suggested improvements to the clinic by expanding the scope of practice further, simplifying processes to schedule appointments, and potentially creating interprofessional clinics for other rare diseases as well. CONCLUSION: Pursuing avenues to create interprofessional clinics for adults with rare diseases has value from the patient perspective. This value can translate to improved patient outcomes through improvements in patient knowledge of their diagnosis, adherence to evidence-based care and quality of life.

Development of a New Bead Movement-Based Computational Framework Shows that Bacterial Amyloid Curli Reduces Bead Mobility in Biofilms.

Biofilms exist in complex environments, including the intestinal tract, as a part of the gastrointestinal microbiota. The interaction of planktonic bacteria with biofilms can be influenced by material properties of the biofilm. During previous confocal studies, we observed that amyloid curli-containing Salmonella enterica serotype Typhimurium and Escherichia coli biofilms appeared rigid. In these studies, Enterococcus faecalis, which lacks curli-like protein, showed more fluid movement. To better characterize the material properties of the biofilms, a four-dimensional (4D) model was designed to track the movement of 1-µm glyoxylate beads in 10- to 20-µm-thick biofilms over approximately 20 min using laser-scanning confocal microscopy. Software was developed to analyze the bead trajectories, the amount of time they could be followed (trajectory life span), the velocity of movement, the surface area covered (bounding boxes), and cellular density around each bead. Bead movement was found to be predominantly Brownian motion. Curli-containing biofilms had very little bead movement throughout the low- and high-density regions of the biofilm compared to E. faecalis and isogenic curli mutants. Curli-containing biofilms tended to have more stable bead interactions (longer trajectory life spans) than biofilms lacking curli. In biofilms lacking curli, neither the velocity of bead movement nor the bounding box volume was strictly dependent on cell density, suggesting that other material properties of the biofilms were influencing the movement of the beads and flexibility of the material. Taken together, these studies present a 4D method to analyze bead movement over time in a 3D biofilm and suggest curli confers rigidity to the extracellular matrix of biofilms.IMPORTANCE Mathematical models are necessary to understand how the material composition of biofilms can influence their physical properties. Here, we developed a 4D computational toolchain for the analysis of bead trajectories, which laid the groundwork for establishing critical parameters for mathematical models of particle movement in biofilms. Using this open-source trajectory analyzer, we determined that the presence of bacterial amyloid curli changes the material properties of a biofilm, making the biofilm matrix rigid. This software is a powerful tool to analyze treatment- and environment-induced changes in biofilm structure and cell movement in biofilms. The open-source analyzer is fully adaptable and extendable in a modular fashion using VRL-Studio to further enhance and extend its functions.

Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Development of typological classification and its relationship to microdifferentiation in ethnic India.

The history of the racial classification of the people of India can be looked at in three temporal phases: (1) at the national level, the initial studies of racial classification attempted along with the Census of India; (2) at the regional level, studies by anthropologists and statisticians following systematic sampling and statistical procedures were conducted after the initial national-level studies and (3) population-specific studies in different regions across the country including micro-evolutionary studies of individual populations followed the regional studies. Initially the racial classification was part of the Census survey conducted by British anthropologists in some parts of the country among castes and tribes and was based on a few physical traits. This was followed by a systematic anthropometric survey in particulars regions (e.g., UP, Bengal, etc.) by anthropologists and statisticians. This was followed by population specific micro-evolutionary studies across different regions by numerous anthropologists investigating the role of selection, drift, migration and admixture and other population structure variables among endogamous castes and tribes.

Defining reference values for the normal tibiofibular syndesmosis in adults using weight-bearing CT.

AIMS: Cone beam CT allows cross-sectional imaging of the tibiofibular syndesmosis while the patient bears weight. This may facilitate more accurate and reliable investigation of injuries to, and reconstruction of, the syndesmosis but normal ranges of measurements are required first. The purpose of this study was to establish: 1) the normal reference measurements of the syndesmosis; 2) if side-to-side variations exist in syndesmotic anatomy; 3) if age affects syndesmotic anatomy; and 4) if the syndesmotic anatomy differs between male and female patients in weight-bearing cone beam CT views. PATIENTS AND METHODS: A retrospective analysis was undertaken of 50 male and 50 female patients (200 feet) aged 18 years or more, who underwent bilateral, simultaneous imaging of their lower legs while standing in an upright, weight-bearing position in a pedCAT machine between June 2013 and July 2017. At the time of imaging, the mean age of male patients was 47.1 years (18 to 72) and the mean age of female patients was 57.8 years (18 to 83). We employed a previously described technique to obtain six lengths and one angle, as well as calculating three further measurements, to provide information on the relationship between the fibula and tibia with respect to translation and rotation. RESULTS: The upper limit of lateral translation in un-injured patients was 5.27 mm, so values higher than this may be indicative of syndesmotic injury. Anteroposterior translation lay within the ranges 0.31 mm to 2.59 mm, and -1.48 mm to 3.44 mm, respectively. There was no difference between right and left legs. Increasing age was associated with a reduction in lateral translation. The fibulae of men were significantly more laterally translated but data were inconsistent for rotation and anteroposterior translation. CONCLUSION: We have established normal ranges for measurements in cross-sectional syndesmotic anatomy during weight-bearing and also established that no differences exist between right and left legs in patients without syndesmotic injury. Age and gender do, however, affect the anatomy of the syndesmosis, which should be taken into account at time of assessment. Cite this article: Bone Joint J 2019;101-B:348-352.

Does histoid leprosy represent a locally hyperimmune variant of lepromatous leprosy?

BACKGROUND: Histoid leprosy is a subtype of leprosy with distinct clinical presentation and histologic features. It accounts for <4% of leprosy cases. The exact location of histoid leprosy along the immune spectrum and its relation to other subtypes is unclear. AIM: To evaluate the local immune phenomenon which define histoid leprosy. DESIGN: Parallel skin biopsies from histoid lesions and from unremarkable skin in patients with histoid leprosy were evaluated and the histologic findings compared. METHODS: Formalin fixed, paraffin embedded tissue sections from lesional and non-lesional biopsies were assessed for changes in epidermis and dermis; type and extent of infiltrate, presence or absence of pseudocapsule and associated reactions. Bacillary index was evaluated using Wade Fite stain for lepra bacilli. RESULTS: Amongst 208 leprosy cases, six cases of histoid leprosy were identified (2.88%). The cases showed presence of nodules, patches and plaques overlying clinically unremarkable skin. Fourteen skin biopsies were evaluated of which the lesional biopsies showed equal proportion of fusocellular, fusocellular epithelioid and fusocellular-vacuolated histology. A greater circumscription was noted in lesional biopsies; however the cellular content of the infiltrate was similar in lesional and non-lesional biopsies. A case of erythema nodosum leprosum in histoid leprosy was also seen. CONCLUSIONS: Ours is the first study comparing normal and lesional skin in histoid leprosy. Though the histoid lesions appear to have a derivation from lepromatous leprosy, the local histologic and clinical alterations may be a result of heightened local immunity or reactive local modifying factors.

Differential leukocyte counts on admission predict outcomes in patients with acute ischaemic stroke treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: To determine the association of differential leukocyte counts on admission with efficacy and safety outcomes in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS: Consecutive patients with AIS receiving IVT were evaluated at two stroke centers. Differential leukocyte counts and neutrophil:lymphocyte ratio (NLR) were determined during the initial 12 h of admission. Efficacy outcomes were favorable functional outcome (FFO) (modified Rankin Scale scores of 0-1) and functional independence (FI) (modified Rankin Scale scores of 0-2) at 3 months, whereas safety outcomes were symptomatic intracranial hemorrhage and 3-month mortality. RESULTS: Among 657 IVT-treated patients with AIS, the mean age was 64 ± 14 years, 50% were female and median National Institutes of Health Stroke Scale score was 7 points (interquartile range, 4-13). Lower neutrophil and leukocyte counts and NLR counts were observed in patients with 3-month FFO and FI, whereas higher counts were observed in patients who died at 3 months. The best discriminative factors for 3-month FFO and FI were NLR < 2.2 (sensitivity 51.4%, specificity 63.1%) and leukocyte count <8100/µL (sensitivity 57.5%, specificity 55.1%), respectively. After adjustment for potential confounders, NLR < 2.2 was associated with higher odds of FFO [odds ratio (OR), 1.56; 95% confidence interval (CI), 1.08-2.24; P = 0.018], whereas leukocyte count <8100/µL demonstrated higher odds of 3-month FI (OR, 1.69; 95% CI, 1.11-2.57; P = 0.014) and lower odds of 3-month mortality (OR, 0.31; 95% CI, 0.16-0.60; P = 0.001). Combined neutrophil (<6800/µL) and leukocyte (<8100/µL) counts demonstrated a strong interaction for 3-month FI (OR, 1.73; 95% CI, 1.13-2.67; P interaction = 0.012). CONCLUSIONS: Differential leukocyte counts on admission were independently associated with clinical outcomes in patients with AIS treated with IVT. These inflammatory biomarkers are potential targets for adjunctive neuroprotection in this stroke subgroup.

Prevalence of isolated gastrocnemius tightness in patients with foot and ankle pathology: a population-based study.

Aims: Gastrocnemius tightness predisposes to musculoskeletal pathology and may require surgical treatment. However, it is not clear what proportion of patients with foot and ankle pathology have clinically significant gastrocnemius tightness. The aim of this study was to compare the prevalence and degree of gastrocnemius tightness in a control group of patients with a group of patients with foot and ankle pathology. Patients and Methods: This prospective, case-matched, observational study compared gastrocnemius tightness, as assessed by the lunge test, in a control group and a group with foot and ankle pathology. Gastrocnemius tightness was calculated as the difference in dorsiflexion of the ankle with the knee extended and flexed. Results: A total of 291 controls were paired with 97 patients with foot and ankle pathology (FAP). The mean gastrocnemius tightness was 6.0° (sd 3.5) in controls and 8.0° (sd 5.7) in the FAP group (p < 0.001). Subgroup analysis showed a mean gastrocnemius tightness of 10.3° (sd 6.0) in patients with forefoot pathology versus 6.9° (sd 5.3) in patients with other pathology (p = 0.008). A total of 12 patients (37.5%) with forefoot pathology had gastrocnemius tightness of > two standard deviations of the control group (> 13°). Conclusion: Gastrocnemius tightness of > 13° may be considered abnormal. Most patients with foot and ankle pathology do not have abnormal degrees of gastrocnemius tightness compared with controls, but it is present in over a third of patients with forefoot pathology. Cite this article: Bone Joint J 2018;100-B:945-52.

Everolimus-associated Acute Kidney Injury in Patients with Metastatic Breast Cancer.

Recently, everolimus (Evl) has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

Can a urine dipstick test be used to assess smoking status in patients undergoing planned orthopaedic surgery? a prospective cohort study.

AIMS: Smoking is associated with post-operative complications but smokers often under-report the amount they smoke. Our objective was to determine whether a urine dipstick test could be used as a substitute for quantitative cotinine assays to determine smoking status in patients. PATIENTS AND METHODS: Between September 2013 and July 2014 we conducted a prospective cohort study in which 127 consecutive patients undergoing a planned foot and ankle arthrodesis or osteotomy were included. Patients self-reported their smoking status and were classified as: 'never smoked' (61 patients), 'ex-smoker' (46 patients), or 'current smoker' (20 patients). Urine samples were analysed with cotinine assays and cotinine dipstick tests. RESULTS: There was a high degree of concordance between dipstick and assay results (Kappa coefficient = 0.842, p < 0.001). Compared with the quantitative assay, the dipstick had a sensitivity of 88.9% and a specificity of 97.3%. Patients claiming to have stopped smoking just before surgery had the highest rate of disagreement between reported smoking status and urine testing. CONCLUSION: Urine cotinine dipstick testing is cheap, fast, reliable, and easy to use. It may be used in place of a quantitative assay as a screening tool for detecting patients who may be smoking. A positive test may be used as a trigger for further assessment and counselling. Cite this article: Bone Joint J 2016;98-B:1418-24.

The relationship between spinopelvic measurements and patient-reported outcome scores in patients with multiple myeloma of the spine.

AIMS: Patients with multiple myeloma (MM) develop deposits in the spine which may lead to vertebral compression fractures (VCFs). Our aim was to establish which spinopelvic parameters are associated with the greatest disability in patients with spinal myeloma and VCFs. PATIENTS AND METHODS: We performed a retrospective cross-sectional review of 148 consecutive patients (87 male, 61 female) with spinal myeloma and analysed correlations between spinopelvic parameters and patient-reported outcome scores. The mean age of the patients was 65.5 years (37 to 91) and the mean number of vertebrae involved was 3.7 (1 to 15). RESULTS: The thoracolumbar region was most commonly affected (109 patients, 73.6%), and was the site of most posterior vertebral wall defects (47 patients, 31.8%). Poorer Oswestry Disability Index scores correlated with an increased sagittal vertical axis (p = 0.006), an increased number of VCFs (p = 0.035) and sternal involvement (p = 0.012). Poorer EuroQol visual analogue scale scores correlated with posterior vertebral wall defects in the thoracolumbar region (p = 0.012). The sagittal vertical axis increased with the number of fractures and kyphosis in the thoracolumbar (p = 0.009) and lumbar (p < 0.001) regions. CONCLUSIONS: In MM, patients with VCFs have poorer clinical scores at presentation in the presence of sagittal imbalance. Outcome is particularly affected by multiple fractures in the thoracolumbar and lumbar regions and by failure to prevent kyphosis. Patients with MM should be screened for spinal lesions early. Cite this article: Bone Joint J 2016;98-B:1234-9.

Safety of venous thromboembolism prophylaxis with fondaparinux in ischemic stroke.

INTRODUCTION: Unfractionated heparin (UFH), low molecular weight heparin or fondaparinux are recommended for venous thromboembolism (VTE) prophylaxis in acutely ill medical patients. There are limited data on the safety of fondaparinux for VTE prophylaxis in ischemic stroke. We examined adverse event frequency in hospitalized patients with ischemic stroke who received VTE prophylaxis with fondaparinux versus UFH. MATERIALS AND METHODS: We performed a propensity score matched analysis on a retrospective cohort of 644 consecutive patients with acute ischemic stroke receiving fondaparinux (n=322) or UFH (n=322) for VTE prophylaxis. Patients who received intravenous tPA and continuous intravenous infusions of UFH were excluded. The primary outcome was major hemorrhage (intracranial or extracranial) and the secondary outcome was total hemorrhage (major and minor hemorrhage) during hospitalization. We also examined the rate of symptomatic VTE. RESULTS: Mean age of the matched cohort was 71.3±14.1 years, median NIHSS score was 4 (IQR 1-11), median duration of anticoagulant exposure was 5 (IQR 3-8) days, and 98.1% received antiplatelet medications. In the matched cohort, there were less observed major hemorrhages in the fondaparinux group 1.2% (4/322) compared to UFH 3.7% (12/322), but this difference was not significant (OR=0.33, 95% CI 0.08-1.10, p=0.08). There were also no significant differences in total hemorrhage (p=0.15), intracranial hemorrhage (p=0.48), major extracranial hemorrhage (p=0.18) and symptomatic VTE (p=1.00) between the groups. CONCLUSIONS: Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups.

"Snacks are not food". Low-income, urban mothers' perceptions of feeding snacks to their preschool-aged children.

Snacking has become more frequent among US preschool-aged children in recent decades and represents a significant proportion of daily energy intake. Social influences on snacking among children, however, are not well understood. This qualitative research described low-income, urban mothers' perceptions of feeding snacks to their preschool-aged children using data from 7 focus groups with 32 participants. Focus group transcripts were analyzed using a constant comparative method to identify themes. Mothers described snacks as involving less preparation, balance, and sustenance than meals (Theme 1). Mothers also made reference to some snacks as not being "real food" (Theme 2). At the same time, snacks had significant hedonic value as reflected in mothers' enjoyment of those foods (Theme 3), the effectiveness of snacks to manage children's behavior (Theme 4), and the variety of restrictions that mothers placed on children's access to snacks, such as locking cabinets, offering small servings, and reducing the number of snacks in sight (Theme 5). Two overarching themes highlighted distinctions mothers made in feeding children snacks vs. meals as well as the powerful hedonic appeal of snacks for both mother and child. These observations suggest that low-income, urban mothers of preschool-aged children may perceive snacks as serving a more important role in managing children's behavior than in providing nutrition. Child feeding interventions should address non-food related ways of managing children's behavior as well as encouraging caregivers to see snacks as structured opportunities for nutrition and connecting with their children.

Profile of gynecologic malignancies reported at a tertiary care center in India over the past decade: comparative evaluation with international data.

OBJECTIVE: Comprehensive statistics on gynecologic malignancies reported from India are deficient. This study was performed to ascertain the profile of gynecologic cancers reported at our center regarding incidence, histologic subtypes, frequency of involvement at various sites and stage at presentation. We endeavored to compare our data with gynecologic cancers reported at other national and international centers. MATERIALS AND METHODS: Retrospective review of records of gynecologic cancers obtained from Departments of Pathology and Gynecology, at a tertiary care center, Delhi from January 2000 to December 2009 was performed. Comparison with international data was performed using Fishcher's exact test and chi square tests. RESULTS: A total of 1315 gynecologic cancers were reported. Cervical malignancies were the commonest at our center as compared to uterine malignancies in data from Surveillance, Epidemiology, and End Results (SEER) Program of United States and European Union. All malignancies except cervical cancers affected a younger age group at our center than in the US population. Cervical cancer presented at a relatively more advanced stage, ovarian cancers at more localized stages, whereas uterine cancers presented at similar stages as compared to Western data. CONCLUSIONS: Our registry presents composite data from North India. Higher age and advanced stage at presentation of cervical cancers suggests lacunae in screening programs available. Ovarian malignancies were more localized at presentation than in the Western population for which environmental or genetic factors may be causative.

Migration of central lines from the superior vena cava to the azygous vein.

AIM: To report 11 cases of central venous access catheters migrating from the superior vena cava to the azygos vein in order to raise radiologists' awareness of this possibility. MATERIALS AND METHODS: This is a retrospective review of the clinical history and imaging of 11 patients whose central line migrated from the superior vena cava to the azygos vein. The time course of migration, access route of the catheters, outcome, and depth of placement in the superior vena cava were evaluated. RESULTS: All of these catheters were placed from the left; six through the subclavian vein, four as PICC lines, and one from the left internal jugular vein. Seven of the catheters were originally positioned in the superior vena cava. Four of the catheters were originally positioned in the azygos vein and were repositioned into the superior vena cava at the time of placement. The time to migration ranged from 2 to 126 days, average 43 days. In three cases, the migration was not reported at the first opportunity, resulting in a delay in diagnosis ranging from 10 to 27 days. All but one of the catheters extended at least 3.5 cm (range 1.8-7 cm) below the top of the right mainstem bronchus when in the superior vena cava. CONCLUSION: Risk factors for migration into the azygos vein include placement from a left-sided approach and original positioning in the azygos vein with correction at placement. The depth of placement in the superior vena cava was not a protective factor. It is important to recognize migration because of the elevated risk of complications when central lines are placed in the azygos vein.