Nevin Manimala

Ann Biomed Eng. 2021 Feb 26. doi: 10.1007/s10439-021-02747-6. Online ahead of print.

ABSTRACT

Although critical for understanding and simulating pelvic floor muscle function and pathophysiology, the fascicle arrangements of the coccygeus and levator ani remain mostly undetermined. We performed close-range photogrammetry on cadaveric pelvic floor muscles to robustly quantify surface fascicle orientations. The pelvic floor muscles of 5 female cadavers were exposed through anatomic dissections, removed en bloc, and photographed from every required angle. Overlapping images were mapped onto in silico geometries and muscle fascicles were traced manually. Tangent vectors were calculated along each trace; interpolated to define continuous, 3D vector fields; and projected onto axial and sagittal planes to calculate angles with respect to the pubococcygeal line. Contralateral and ipsilateral pelvic floor muscles were compared within each donor (Kuiper’s tests) and using mean values from all donors (William-Watsons tests). Contralateral muscles and all but one ipsilateral muscle pair differed significantly within each donor (p < 0.001). When mean values were considered collectively, no contralateral or ipsilateral statistical differences were found but all muscles compared differed by more than 10° on average. Close-range photogrammetry and subsequent analyses robustly quantified surface fascicle orientations of the pelvic floor muscles. The continuous, 3D vector fields provide data necessary for improving simulations of the female pelvic floor muscles.

PMID:33638030 | DOI:10.1007/s10439-021-02747-6

Eur Heart J Cardiovasc Imaging. 2021 Feb 26:jeab023. doi: 10.1093/ehjci/jeab023. Online ahead of print.

ABSTRACT

AIMS: The concept of proportionate/disproportionate functional mitral regurgitation (FMR) has been limited by the lack of a simple way to assess it and by the paucity of data showing its prognostic superiority. The aim of this study was to evaluate the prognostic value of an individualized method of assessing FMR proportionality.

METHODS AND RESULTS: We retrospectively identified 572 patients with at least mild FMR and reduced left ventricular ejection fraction (<50%) under medical therapy. To determine FMR proportionality status, we used an approach where a simple equation determined the individualized theoretical regurgitant volume (or effective regurgitant orifice area) threshold associated with haemodynamically significant FMR. Then, we compared the measured with the theoretical value to categorize the population into non-severe, proportionate, and disproportionate FMR. The primary endpoint was all-cause mortality. During a median follow-up of 3.8 years (interquartile range: 1.8-6.2), 254 patients died. The unadjusted mortality incidence per 100 persons-year rose as the degree of FMR disproportionality worsened. On multivariable analysis, disproportionate FMR remained independently associated with all-cause mortality [adjusted hazard ratio: 1.785; 95% confidence interval (CI): 1.249-2.550; P = 0.001]. The FMR proportionality concept showed greater discriminative power (C-statistic 0.639; 95% CI: 0.597-0.680) than the American (C-statistic 0.583; 95% CI: 0.546-0.621; P for comparison <0.001) and European guidelines (C-statistic 0.584; 95% CI: 0.547-0.620; P for comparison <0.001). When added to any of the before-mentioned guidelines, FMR proportionality also improved risk stratification by reclassifying patients into lower and higher risk subsets.

CONCLUSION: Disproportionate FMR is independently associated with all-cause mortality and improves the risk stratification of current guidelines.

PMID:33637993 | DOI:10.1093/ehjci/jeab023

Eye (Lond). 2021 Feb 26. doi: 10.1038/s41433-021-01468-3. Online ahead of print.

ABSTRACT

BACKGROUND: It has been suggested that ocular antihypertensives are associated with an increased risk of nasolacrimal duct obstruction. This study aims to assess the effect of topical antihypertensive treatment on surgical outcomes for patients undergoing Dacryocystorhinostomy (DCR) with intubation.

METHODS: Single centre, retrospective analysis of 170 operations carried out on 144 patients between January 2014 and January 2019. Statistical analysis of DCR failure rates comparing patients on topical ocular antihypertensive treatment and those not on any topical ocular antihypertensive treatment was carried out following medical case record analysis.

RESULTS: 6.9% of patients undergoing DCR surgery were on topical antihypertensive treatment. The overall failure rate for all DCR operations during this time period was 11.2%. There was a statistically significant higher rate of primary DCR failure in patients on antihypertensive treatment (p = 0.02), with the endonasal DCRs worse affected (p = 0.01). The most commonly used topical treatments were carbonic anhydrase inhibitors (CAI, 81.8%), followed by beta-blockers (72.7%). All patients who had failure of primary DCR were using topical beta-blockers and CAI at the time of surgery and post-operatively. There was no statistically significant association between failure rates and the use of preserved or unpreserved drops (p = 1.0) CONCLUSIONS: Topical ocular antihypertensive treatment may lead to a higher failure rate for DCR surgery due to the provocation of an inflammatory cicatricial response. Beta-blockers and CAIs appear to have the strongest association. Considering a primary external approach in this group as well as switching the class of topical antihypertensive treatment pre-operatively could perhaps improve DCR outcomes.

PMID:33637965 | DOI:10.1038/s41433-021-01468-3

Br Dent J. 2021 Feb;230(4):229-235. doi: 10.1038/s41415-021-2662-3. Epub 2021 Feb 26.

ABSTRACT

Objective To compare the clinical effectiveness and cost benefit of different frequencies of scale and polish (S&P) treatments in combination with different types of oral hygiene advice (OHA).Design Multi-centre, multi-level cluster randomised factorial open trial with blinded outcome evaluation. UK dental practices were cluster randomised to deliver OHA as usual or personalised. In a separate randomisation, patients were allocated to receive S&P 6-monthly, 12-monthly or never.Setting UK primary dental care.Participants Practices providing NHS care and adults who had received regular dental check-ups.Main outcome measures The percent of sites with bleeding on probing, patient confidence in self-care, incremental net benefits (INB) over three years.Results Sixty-three practices and 1,877 adult patients were randomised and 1,327 analysed (clinical outcome). There was no statistically significant or clinically important difference in gingival bleeding between the three S&P groups (for example, six-monthly versus none: difference 0.87% sites, 95% CI: 1.6 to 3.3, p = 0.48) or between personalised or usual OHA groups (difference -2.5% sites, -95%CI: -8.3 to 3.3, p = 0.39), or oral hygiene self-efficacy (cognitive impact) between either group (for example, six-monthly versus none: difference -0.028, 95% CI -0.119 to 0.063, p = 0.543). The general population place a high value on, and are willing to pay for, S&P services. However, from a dental health perspective, none of the interventions were cost-effective.Conclusion Results suggest S&P treatments and delivering brief personalised OHA provide no clinical benefit and are therefore an inefficient approach to improving dental health (38% of sites were bleeding whatever intervention was received). However, the general population value both interventions.

PMID:33637926 | DOI:10.1038/s41415-021-2662-3

Mod Pathol. 2021 Feb 26. doi: 10.1038/s41379-021-00735-8. Online ahead of print.

ABSTRACT

Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited data on the factor(s) at a cellular level that drive progression from type I to type III. In this study, we evaluated the expression of p53 and its prognostic implications. A total of 143 PPB cases were included in the study with the following distribution in PPB types: Ir (14%), I (23%), II (32%), and III (31%). P53 expression by immunohistochemistry (IHC) was recorded as four groups: 0%, 1-25%, 26-75%, and 76-100%. All type I PPBs showed 0-25% p53 expression compared to the higher p53 expression (>25%) in type III PPB (p < 0.0001), to support the argument that p53 has a role in tumor progression. In addition, type Ir with the architectural hallmarks of type I PPB, but lacking the primitive cell population, has negligible p53 expression. High p53 expression (staining observed in >25% of the tumor cells) was significantly associated with age over 1 year (p = 0.0033), neoadjuvant therapy (p = 0.0009), positive resection margin (p = 0.0008) and anaplasia (p < 0.0001). P53 expression was significantly associated with recurrence-free survival (p < 0.0001) and overall survival (p = 0.0350), with higher p53 expression associated with worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphologic types compared to p53 expression groups (p = 0.647). TP53 sequence was performed in 16 cases; the most common variant identified was a missense variant (12 cases), and in one case a frameshift truncating variant was noted. Based on these findings, we recommend performing p53 IHC in all newly diagnosed cases of types II and III PPB to further aid in risk stratification.

PMID:33637876 | DOI:10.1038/s41379-021-00735-8

Physiol Meas. 2021 Feb 26. doi: 10.1088/1361-6579/abea25. Online ahead of print.

ABSTRACT

OBJECTIVE: Heart rate (HR) monitoring provides a convenient and inexpensive way to predict energy expenditure (EE) during physical activity. However, there is a lot of variation among individuals in the EE-HR relationship, which should be taken into account in predictions. The objective is to develop a model that allows the prediction of EE based on HR as accurately as possible and allows an improvement of the prediction using calibration measurements from the target individual.

APPROACH: We propose a nonlinear (logistic) mixed model for EE and HR measurements and an approach to calibrate the model for a new person who does not belong to the data set used to estimate the model. The calibration utilizes the estimated model parameters and calibration measurements of HR and EE from the person in question. We compare the results of the logistic mixed model with a simpler linear mixed model for which the calibration is easier to perform.

MAIN RESULTS: We show that the calibration is beneficial already with only one pair of measurements on HR and EE. That is an important benefit over an individual-level model fitting which requires a larger number of measurements. Moreover, we present an algorithm for calculating the confidence and prediction intervals of the calibrated predictions. The analysis was based on up to eleven pairs of EE and HR measurements from each of 54 individuals of a heterogeneous group of people, who performed a maximal treadmill test.

SIGNIFICANCE: The proposed method allows accurate energy expenditure predictions based on only a few calibration measurements from a new individual without access to the original dataset, thus making the approach viable for example on wearable computers.

PMID:33636716 | DOI:10.1088/1361-6579/abea25

J Neurosurg. 2021 Feb 26:1-6. doi: 10.3171/2020.9.JNS202781. Online ahead of print.

ABSTRACT

OBJECTIVE: Middle meningeal artery (MMA) embolization is a promising treatment strategy for chronic subdural hematomas (cSDHs). However, studies comparing MMA embolization and conventional therapy (surgical intervention and conservative management) are limited. The authors aimed to compare MMA embolization versus conventional therapy for cSDHs using a propensity-adjusted analysis.

METHODS: A retrospective study of all patients with cSDH who presented to a large tertiary center over a 2-year period was performed. MMA embolization was compared with surgical intervention and conservative management. Neurological outcome was assessed using the modified Rankin Scale (mRS). A propensity-adjusted analysis compared MMA embolization versus surgery and conservative management for all individual cSDHs. Primary outcomes included change in hematoma diameter, treatment failure, and complete resolution at last follow-up.

RESULTS: A total of 231 patients with cSDH met the inclusion criteria. Of these, 35 (15%) were treated using MMA embolization, and 196 (85%) were treated with conventional treatment. On the latest follow-up, there were no statistically significant differences between groups in the percentage of patients with worsening mRS scores. Of the 323 total cSDHs found in 231 patients, 41 (13%) were treated with MMA embolization, 159 (49%) were treated conservatively, and 123 (38%) were treated with surgical evacuation. After propensity adjustment, both surgery (OR 12, 95% CI 1.5-90; p = 0.02) and conservative therapy (OR 13, 95% CI 1.7-99; p = 0.01) were predictors of treatment failure and incomplete resolution on follow-up imaging (OR 6.1, 95% CI 2.8-13; p < 0.001 and OR 5.4, 95% CI 2.5-12; p < 0.001, respectively) when compared with MMA embolization. Additionally, MMA embolization was associated with a significant decrease in cSDH diameter on follow-up relative to conservative management (mean -8.3 mm, 95% CI -10.4 to -6.3 mm, p < 0.001).

CONCLUSIONS: This propensity-adjusted analysis suggests that MMA embolization for cSDH is associated with a greater extent of hematoma volume reduction with fewer treatment failures than conventional therapy.

PMID:33636706 | DOI:10.3171/2020.9.JNS202781

J Neurosurg. 2021 Feb 26:1-5. doi: 10.3171/2020.8.JNS20386. Online ahead of print.

ABSTRACT

OBJECTIVE: Endovascular thrombectomy (EVT) and tissue plasminogen activator (tPA) are effective ischemic stroke treatments in the initial treatment window. In the extended treatment window, these treatments may offer benefit, but CT and MR perfusion may be necessary to determine patient eligibility. Many hospitals do not have access to advanced imaging tools or EVT capability, and further patient care would require transfer to a facility with these capabilities. To assist transfer decisions, the authors developed risk indices that could identify patients eligible for extended-window EVT or tPA.

METHODS: The authors retrospectively identified stroke patients who had concurrent CTA and perfusion and evaluated three potential outcomes that would suggest a benefit from patient transfer. The first outcome was large-vessel occlusion (LVO) and target mismatch (TM) in patients 5-23 hours from last known normal (LKN). The second outcome was TM in patients 5-15 hours from LKN with known LVO. The third outcome was TM in patients 4.5-12 hours from LKN. The authors created multivariable models using backward stepping with an α-error criterion of 0.05 and assessed them using C statistics.

RESULTS: The final predictors included the National Institutes of Health Stroke Scale (NIHSS), the Alberta Stroke Program Early CT Score (ASPECTS), and age. The prediction of the first outcome had a C statistic of 0.71 (n = 145), the second outcome had a C statistic of 0.85 (n = 56), and the third outcome had a C statistic of 0.86 (n = 54). With 1 point given for each predictor at different cutoffs, a score of 3 points had probabilities of true positive of 80%, 90%, and 94% for the first, second, and third outcomes, respectively.

CONCLUSIONS: Despite the limited sample size, compared with perfusion-based examinations, the clinical variables identified in this study accurately predicted which stroke patients would have salvageable penumbra (C statistic 71%-86%) in a range of clinical scenarios and treatment cutoffs. This prediction improved (C statistic 85%-86%) when utilized in patients with confirmed LVO or a less stringent tissue mismatch (TM < 1.2) cutoff. Larger patient registries should be used to validate and improve the predictive ability of these models.

PMID:33636705 | DOI:10.3171/2020.8.JNS20386

J Neurosurg. 2021 Feb 26:1-10. doi: 10.3171/2020.9.JNS201980. Online ahead of print.

ABSTRACT

OBJECTIVE: Primary central nervous system lymphoma (PCNSL) is a rare CNS tumor with a poor prognosis. It is usually diagnosed by needle biopsy and treated mainly with high-dose chemotherapy. Resection is currently not considered a standard treatment option. A possible prolonged survival after resection of PCNSL lesions in selected patients has been suggested, but selection criteria for surgery, especially for solitary lesions, have never been established.

METHODS: The authors retrospectively searched their patient database for records of adult patients (≥ 18 years) who were diagnosed and treated for a solitary PCNSL between 2005 and 2019. Patients were divided into groups according to whether they underwent resection or needle biopsy. Statistical analyses were performed in an attempt to identify variables affecting outcome and possible survival advantage and to characterize subgroups of patients who would benefit from resection of their tumor compared with undergoing biopsy only.

RESULTS: A total of 113 patients with a solitary lesion of PCNSL were identified; 36 patients underwent resection, and 77 had a diagnostic stereotactic biopsy only. The statically significant preoperative risk factors included age ≥ 70 years (adjusted HR 9.61, 95% CI 2.42-38.11; p = 0.001), deep-seated lesions (adjusted HR 3.33, 95% CI 1.13-9.84; p = 0.030), and occipital location (adjusted HR 4.26, 95% CI 1.08-16.78; p = 0.039). Having a postoperative Karnofsky Performance Scale (KPS) score < 80 (adjusted HR 3.21, 95% CI 1.05-9.77; p = 0.040) and surgical site infection (adjusted HR 4.27, 95% CI 1.18-15.47; p = 0.027) were significant postoperative risk factors after the adjustment and selection by means of other possible risk factors. In a subgroup analysis, patients younger than 70 years who underwent resection had a nonsignificant trend toward longer survival than those who underwent needle biopsy (median survival 35.0 months vs 15.2 months, p = 0.149). However, patients with a superficial tumor who underwent resection had significantly longer survival times than those who underwent needle biopsy (median survival 34.3 months vs 8.9 months, p = 0.014). Patients younger than 70 years who had a superficial tumor and underwent resection had significantly prolonged survival, with a median survival of 35.0 months compared with 8.9 months in patients from the same group who underwent needle biopsy (p = 0.007).

CONCLUSIONS: Specific subgroups of patients with a solitary PCNSL lesion might gain a survival benefit from resection compared with undergoing only a diagnostic biopsy.

PMID:33636699 | DOI:10.3171/2020.9.JNS201980

J Mech Behav Biomed Mater. 2021 Feb 13;117:104377. doi: 10.1016/j.jmbbm.2021.104377. Online ahead of print.

ABSTRACT

Osteogenesis imperfecta (OI), a brittle bone disease, is known to result in severe bone fragility. However, its ultrastructural origins are still poorly understood. In this study, we hypothesized that deficient intrafibrillar mineralization is a key contributor to the OI induced bone brittleness. To test this hypothesis, we explored the mechanical and ultrastructural changes in OI bone using the osteogenesis imperfecta murine (oim) model. Synchrotron X-ray scattering experiments indicated that oim bone had much less intrafibrillar mineralization than wild type bone, thus verifying that the loss of mineral crystals indeed primarily occurred in the intrafibrillar space of oim bone. It was also found that the mineral crystals were organized from preferentially in longitudinal axis in wild type bone to more randomly in oim bone. Moreover, it revealed that the deformation of mineral crystals was more coordinated with collagen fibrils in wild type than in oim bone, suggesting that the load transfer deteriorated between the two phases in oim bone. The micropillar test revealed that the compression work to fracture of oim bone (8.2 ± 0.9 MJ/m³) was significantly smaller (p < 0.05) than that of wild type bone (13.9 ± 2.7 MJ/m³), while the bone strength was not statistically different (p > 0.05) between the two genotype groups. In contrast, the uniaxial tensile test showed that the ultimate strength of wild type bone (50 ± 4.5 MPa) was significantly greater (p < 0.05) than that of oim bone (38 ± 5.3 MPa). Furthermore, the nanoscratch test showed that the toughness of oim bone was much less than that of wild type bone (6.6 ± 2.2 GJ/m³ vs. 12.6 ± 1.4 GJ/m³). Finally, in silico simulations using a finite element model of sub-lamellar bone confirmed the links between the reduced intrafibrillar mineralization and the observed changes in the mechanical behavior of OI bone. Taken together, these results provide important mechanistic insights into the underlying cause of poor mechanical quality of OI bone, thus pave the way toward future treatments of this brittle bone disease.

PMID:33636677 | DOI:10.1016/j.jmbbm.2021.104377