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This letter presents MAMMOBOT, one of the first millimetre-scale steerable soft growing robots for medical applications. MAMMOBOT aims to access the breast through the nipple and navigate the mammary ducts to detect precursors of invasive breast cancers. Addressing limitations of the state-of-the-art, MAMMOBOT maintains a hollow inner lumen throughout its soft body, enabling the passing of instruments such as miniature endoscopes, biopsy needles, and optical probes for in situ histopathology. MAMMOBOT is developed by a novel manufacturing approach entailing dual LDPE sheet adhesion with localised heat treatment. MAMMOBOT's steerability is achieved through a sub-millimetre profiled tendon-driven catheter that passes through its inner lumen. A duty cycle controller governs steering versus growing to achieve navigation in complex environments within a human-in-the-loop framework. Benchtop experimental evaluation demonstrates the robot's capabilities and agreement with a Reduced-Order Mode (ROM) of its dynamics. Finally, experimental evaluation on a bespoke breast phantom developed for the purposes of this project demonstrates the clinical relevance and potential impact of MAMMOBOT.

Introduction and Objectives: We evaluated patients who underwent treatment for prostate cancer and then subsequent robot-assisted radical cystectomy (RARC). Our objective was to understand clinical...

Several devices used to harvest stem/progenitor cells from bone marrow are available to clinicians. This study compared three devices measuring stem cell yields and correlating those yields to bone regeneration. A flexible forward aspirating system Marrow Marxman (MM), a straight needle aspirating on withdrawal system Marrow Cellutions (MC), and a straight needle aspirating on withdrawal and centrifuging the aspirate (BMAC) were compared in a side-to-side patient comparison, as well as tissue engineered bone grafts. The FlexMetric system (MM) produced greater CFU-f values compared to the straight needle (MC) Δ = 1083/ml, p 0.001 and 1225/ml, p 0.001 than the BMAC system. This increased stem/progenitor cell yield also translated into a greater radiographic bone density at 6 months Δ = 88.3 Hu, p ≤ 0.001 versus MC and Δ = 116.7, p 0.001 versus BMAC at 6 months and Δ = 72.2, p 0.001 and Δ = 93.3, p 0.001 at 9 months respectively. The increased stem/progenitor cell yield of the MM system clinically translated into greater bone regeneration as measured by bone volume p 0.014 and p 0.001 respectively, trabecular thickness p 0.007 and p 0.002 respectively, and trabecular separation p = 0.011 and p 0.001. A flexible bone marrow aspirator produces higher yields of stem/progenitor cells. Higher yields of stem/progenitor cells translate into greater bone regeneration in tissue engineering. Flexmetric technology produces better bone regeneration due to a forward aspiration concept reducing dilution from peripheral blood and its ability to target lining cells along the inner cortex. Centrifugation systems are not required in tissue engineering procedures involving stem/progenitor cells due to nonviability or functional loss from g-forces.

Primary angiitis of the central nervous system (PACNS) is a relapsing-remitting disease with a heterogeneous course. Case series have delineated the long-term disease course but not acute outcomes or their determinants. The national United States hospital burden of PACNS has not been quantified.Analysis of the United States Nationwide Readmissions Database (2016-2018) to characterize the frequency of PACNS hospitalizations, demographic features, inpatient mortality, and discharge outcomes.During the 3-year study period, unweighted 1843 (weighted 3409) patients with PACNS were admitted to the 1078 Healthcare Cost and Utilization Project HCUP participating hospitals; with weighting, this value indicates that 1136 patients were admitted each year to US hospitals, representing yearly 0.01 cases per 100 000 national hospitalizations. The majority of patients were hospitalized in metropolitan teaching hospitals (81.6%). The median age at admission was 54.9 (IQR: 44.0-66.5) years and 59.4% were women. Neurologic manifestations included ischemic stroke in 38.2%, transient ischemic attack in 20.2%, seizure disorder in 22.8%, and intracranial hemorrhage in 13.0%. Overall, 60.0% of patients were discharged home, 35.0% discharged to a rehabilitation facility or nursing home and 5.0% died before discharge. Patient features independently associated with the discharge to another facility or death included older age (odds ratio [OR], 1.03 [95% CI, [1.03-1.04]]), male sex (OR, 1.22 [1.04-1.43]), intraparenchymal hemorrhage (OR, 1.41 [1.08-1.84]), ischemic stroke (OR, 2.79 [2.38-3.28]), and seizure disorder (OR, 1.57 [1.31-1.89]).Our study showed PACNS is still a rare inflammatory disorder of the blood vessels of the central nervous system suggesting an annual hospitalization of 5.1 cases per 1,000,000 person-years in the more diverse and contemporary US population. Overall, 4 in 10 had unfavorable discharge outcome, being unable to be discharged home, and 1 in 20 died before discharge.

To compare failure rates and outcomes after transosseous equivalent (TOE) double row (DR) knotted suture bridge versus knotless suture tape bridge repair techniques for rotator cuff tears.A consecutive series of 272 shoulders in 256 patients who underwent arthroscopic, double row, TOE repair for full-thickness tears of the supraspinatus tendon were reviewed. Eighty-four shoulders were repaired using knotted suture bridge (KSB) technique, and 188 shoulders were repaired using all knotless suture tape bridge (KTB) technique. Revision procedures and concomitant subscapularis tendon repairs were excluded from analysis. The minimum follow-up was 12 months. Primary outcome was failure of surgical repair, defined as either confirmed retear on MRI and/or need for revision surgery. Secondary clinical outcome measures were assessed including range of motion, strength, visual analog scale (VAS), operative time, subjective shoulder value (SSV), Patient-Reported Outcomes Measurement Information System (PROMIS) mental and physical health, American Shoulder and Elbow Surgeons Shoulder Score (ASES), Brophy shoulder activity scores, and need for manipulation under anesthesia (MUA).A total of 127 shoulders (38 KSB and 89 KTB) met inclusion criteria for the study. No significant difference in demographic variables were present between the groups at baseline. Supraspinatus tear size and average follow-up time did not differ significantly between groups. Failure rates were similar between the KSB and KTB repairs (13.1 vs 7.9%, n.s.). There was no significant difference in functional outcomes including strength, range of motion in forward flexion and external rotation, as well as patient reported outcomes including VAS, SSV, PROMIS, ASES, and Brophy scores between the groups. There was also no difference in post-operative stiffness requiring MUA.Both KSB and KTB repair techniques demonstrate low retear rates with excellent functional outcomes when compared to pre-operative examination. Both KSB and KTB techniques are viable options for achieving a successful rotator cuff repair.Level III.

The objective of this study is to illustrate the adverse events secondary to cetuximab therapy for head and neck cancer and elucidate risk factors for serious outcomes.This retrospective study was conducted using the FDA Adverse Event Reporting System (FAERS). The predictor variables were patient characteristics, country of treatment, and adverse events. The outcome variable was the rate of serious outcomes. Multivariate logistic regression was created to identify all significant risk factors of the outcome. P 0.05 was considered statistically significant.The final sample consisted of 3,086 reports of adverse events from cetuximab therapy in head and neck cancer treatment, of which 2,746 reports were considered serious (89.0%) per the FAERS criteria. Mucosal inflammation was the most common adverse event. The strongest risk factor for a serious outcome was cetuximab therapy in countries outside the US (OR 105.2, P 0.01). Polytherapy (OR 7.6, P 0.01) was also a risk factor for serious outcome.Health-care providers should be aware of potential complications following cetuximab administration, particularly when administered in countries outside the US and in conjunction with other medications.

Background: It is crucial for providers to screen high risk patients with limited data being available on young onset stroke (YOS). We aimed to determine predictors of all-cause mortality in this population using the Artificial Neural Network (ANN) model in a national cohort. Methods: We identified young adult (18-44 yrs) YOS hospitalizations from the National Inpatient Sample (2018). ANN’s predictive factors were selected for all-cause mortality. YOS admissions were randomly split between training (70%) & testing datasets (30%). Training data was used to calibrate ANN while testing data was used to evaluate accuracy of the algorithm. We compared the frequency of incorrect prediction between training and testing data and measured area under the Receiver Operating Curve (AUC) to determine ANN’s efficacy in predicting in-hospital mortality in YOS. Results: The 2018 YOS cohort consisted of 39,040 admissions with a mean age of 36 ± 6 years (50.1% male, 51.1% white, 26.2% black, 15.5% Hispanic, 3.2% Asian or Pacific islanders) patients). The all-cause-in-hospital mortality was 5.3%. Training data showed an improved lower predictions in testing model vs testing (5.0% vs 5.2% error rate) , thereby depicting better accuracy. Normalized predictors are displayed in Figure 1a. The AUC was 0.82 (Fig 1b) which shows an excellent ANN model for inpatient mortality in YOS patients. Conclusion: The ANN model successfully revealed the order of prevalent predictors for all-cause mortality that can eventually be utilized to improve survival in high-risk patients.

Background: Cancer-specific adverse events are not well defined despite chronic kidney disease (CKD) being associated with high mortality rates in cancer patients. This study explores the prevalence of major adverse cardiac and cerebrovascular events (MACCE) in cancer survivors with CKD from a national cohort. Methods: We identified cancer survivors with and without concomitant CKD along with their age, sex, race and other comorbidities who were admitted to hospitals in a National Inpatient Sample database (2018). We then identified odds of MACCE including all-cause mortality, AMI, cardiac arrest (including ventricular fibrillation) and stroke while subsequently analyzing healthcare resource utilization in patients with versus without CKD. Multivariable regression analyses were adjusted for patient and hospital level covariates and pre-existing comorbidities. A p-value Results: CKD prevalence was higher among patients with a prior history of cancer versus those without it (21.5% vs 14.6%, p[Table 1] in hospitalized cancer survivors. Said survivors with CKD were specifically noted to have higher rates of all-cause mortality (3.4% vs 2.2%, OR 1.33 [CI 1.29 -1.37]) and AMI (6.0% vs 3.3%, OR 1.54 [CI 1.50 - 1.58]) (all p Conclusion: This large retrospective analysis shows elevated burden of CKD (21.5%) amongst hospitalized cancer survivors, which is associated with not only increased rates of MACCE, all-cause mortality, AMI, cardiac arrest but also greater overall healthcare costs.

Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

The primary aim of this study was to evaluate epidemiological characteristics and prevalence of lung disease among e-cigarettes users in the United States. A population-based, cross-sectional survey was performed using the National Health and Nutrition Examination Survey (NHANES) of 2015–2018. Adults using e-cigarettes (SMQ900), traditional smoking (SMQ020: > 100 cigarettes in lifetime or SMQ040: current cigarettes use), and dual smoking (e-cigarettes and traditional smoking) were identified and compared in their sociodemographic characteristics and prevalence of lung diseases (Asthma: MCQ010 and COPD: MCQ160O). We used the chi square test (categorical variables) and Mann–Whitney test and unpaired-student t test (continuous variables). p-value

Background Osteocutaneous fibula free flap (OCFFF) donor sites are often covered with skin grafts, with an additional donor site, more postoperative care, and increased cost. The authors examine posterior tibial artery (PTA) based pedicled propeller flaps (PPF) as an alternative for OCFFF donor site coverage. Patients and methods Retrospective review of 16 consecutive patients from 30 to 79 years old, who underwent OCFFF reconstruction of head and neck defects (11 mandibular, 5 maxillary), with the closure of donor site with PPF based on a perforator from PTA. Mean donor site defect measured 12.9 × 5.1 cm, PPF was an elliptical design, and rotated 180 degrees in a propeller fashion, to cover donor site defect. Visual analog scale (VAS) was used to assess esthetic results, functional outcomes assessed using mobility and range of motion (ROM), and secondary complications including infections, hematomas, and seromas were recorded. Follow-up period was noted in months postoperatively. Other information collected included underlying head and neck pathology. Results Average dimension of PPF measured 13.9 × 4.1 cm. Successful closure of donor site defects in 14 of 16 patients, with two flaps having partial necrosis, one requiring a secondary skin graft. Follow-up was 6 to 10 months, esthetic results with mean VAS 8.8 of 10, full ROM, and mobility noted. No secondary complications were observed. The most common pathology noted was squamous cell carcinoma (6 of 16 patients). Conclusion PPFs based on the soleus branch of the PTA represent an excellent alternative to skin grafts for the closure of OCFFF donor site defects.

At Sandwell and West Birmingham Hospitals Trust, an emergency rota was put into place in anticipation of the COVID-19 pandemic. Key changes included re-deploying non-general medical (GIM) consultants on to the GIM on-call rota and re-deploying junior doctors on to medical rotas, and introducing a COVID-19 induction training programme to support these redeployments. Results from a survey showed 100% of consultants felt the rotas were resilient, with 96% of consultants stating they felt the rotas were well-staffed and 77% stating that they observed no drop in quality of care. Here we outline how these changes were made and present quantitative and qualitative feedback, with the aim of informing other trusts carrying out similar urgent reconfigurations in the future, or seeking to apply the lessons learnt to their non-emergency rotas.

Objectives To assess non-invasive imaging for detection and quantification of gland structure, inflammation and function in patients with primary Sjogren's syndrome (pSS) using PET-CT with 11C-Methionine (11C-MET; radiolabelled amino acid), and 18F-fluorodeoxyglucose (18F-FDG; glucose uptake marker), to assess protein synthesis and inflammation, respectively; multiparametric MRI evaluated salivary gland structural and physiological changes. Methods In this imaging/clinical/histology comparative study (GSK study 203818; NCT02899377) patients with pSS and age- and sex-matched healthy volunteers underwent MRI of the salivary glands and 11C-MET PET-CT. Patients also underwent 18F-FDG PET-CT and labial salivary gland biopsies. Clinical and biomarker assessments were performed. Primary endpoints were semi-quantitative parameters of 11C-MET and 18F-FDG uptake in submandibular and parotid salivary glands and quantitative MRI measures of structure and inflammation. Clinical and minor salivary gland histological parameter correlations were explored. Results Twelve patients with pSS and 13 healthy volunteers were included. Lower 11C-MET uptake in parotid, submandibular and lacrimal glands, lower submandibular gland volume, higher MRI fat fraction, and lower pure diffusion in parotid and submandibular glands were observed in patients vs healthy volunteer, consistent with reduced synthetic function. Disease duration correlated positively with fat fraction and negatively with 11C-MET and 18F-FDG uptake, consistent with impaired function, inflammation and fatty replacement over time. Lacrimal gland 11C-MET uptake positively correlated with tear flow in patients, and parotid gland 18F-FDG uptake positively correlated with salivary gland CD20+ B-cell infiltration. Conclusion Molecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.

Objective The objective of the current study was to evaluate the utility and ease of use of a novel non-invasive tablet-based application for quantification of the pivot shift (QPS) in a multicentre setting. Methods Nine senior orthopaedic surgeons were recruited from academic medical centres and enrolled a total of 90 subjects. All surgeons received video and electronic training on how to perform QPS measurement using a novel tablet-based visual tracking system. Skin markers were used for visual tracking. Each orthopaedic surgeon performed a pivot shift test and obtained a QPS measurement for 10 subjects with known anterior cruciate ligament (ACL) injuries. Anterior translation of the lateral tibial compartment during the reduction event (in millimetre) was recorded. After all subjects were evaluated, the surgeons completed a survey about the ease of use, utility and willingness to use the mobile-based application in clinical practice. All automated visual tracking used to calculate anterior translation of the lateral tibial compartment was manually evaluated to ensure accurate tracking of skin markers. Statistical comparison was made between groups using Student's t-test with significance defined as p Results The results showed that there is adequate tracking of skin markers to provide a QPS measurement across multiple academic medical centres and surgeons in only 70% of subjects. In 27 of 90 subjects, there were tracking errors which resulted in an invalid QPS measurement. Tracking errors were due to background noise, including objects in the room which were the same colour as the skin markers or use of skin preparation solution similar in colour to the skin markers. The QPS measurement was 3.2±1.8 mm, 2.4±1.3 mm in isolated ACL deficiency, and 3.2±2.0 mm with combined ACL and meniscus injury (not significant). There was significant variation among the QPS measurements of different surgeons (p=0.008). Conclusion This study showed that mobile-based QPS measurement software can be used intraoperatively to allow surgeons greater objective feedback regarding the rotatory laxity of the knee prior to and following ACL reconstruction. Software upgrades with improved real-time feedback could help prevent errors in measurement and improve utility of QPS for assessment of injury severity in subjects. Level of evidence Level III.

Type 2 Diabetes Mellitus (T2DM) is a pandemic that affects millions of patients worldwide. Diabetes affects multiple organ systems leading to comorbidities including hypertension. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) recently have been approved for the treatment of T2DM and heart failure with reduced and preserved ejection fraction. Retrospective analyses of clinical trials have noted SGLT2 inhibitors to have a promising effect on blood pressure. Moreover, the observed blood pressure reduction is not just an acute effect of treatment initiation but has been shown to have a long-term impact on both systolic and diastolic blood pressure. The mechanism of action leading to the blood pressure reduction is still unclear; however, proposed mechanisms are related to the natriuretic effect, modification of the renin-angiotensin-aldosterone system, and/or the reduction in the sympathetic nervous system, SGLT2i should be considered as second-line medication in those patients with diabetes or heart disease and concomitant hypertension. This article reviews the pharmacology, side effect profile, and clinical trials surrounding the use of SGLT2i for the treatment of hypertension.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches associated with segmental vasoconstriction of cerebral arteries, which may result in intracranial hemorrhage (ICH). There is a lack of contemporary data available regarding the ICH burden in RCVS cohort. Our aim of the study is to assess the ICH burden, associated risk factors, and discharge outcome of ICH in patients with RCVS.All patients diagnosed with RCVS in the 2016 Nationwide Readmission Database were identified using ICD-10 code after excluding patients with the concurrent diagnosis of primary angiitis. ICH was defined as both intraparenchymal (IPH), subarachnoid hemorrhage (SAH), and subdural hematoma (SDH). Categorical and continuous variables were assessed by the Rao-Scott Chi-square test and the Wilcoxon signed-rank sum test respectively. We used a multivariable survey-weighted logistic model to determine the association between ICH and RCVS patient-level characteristics.A total of 799 patients were identified with RCVS. Total hospitalization of ICH was 43.4% [(95% CI 36.4-50.4%); (n = 346)] including SAH 35.9% [(95% CI 29.7-42.1%); (n = 287)], IPH 13.1% [(95% CI 9.5-16.7%); (n = 105)] and SDH 3.6% [(95% CI 1.5-5.6%); (n = 28)]. Patients with hemorrhagic RCVS (H-RCVS) had a mean age (years ± SE) of 47.4 ± 1.1 vs. 45.5 ± 1.2 years in R-RCVS (p = 0.247); and were predominantly female (84.0% vs. 68.8%; p = 0.001); with longer inpatient stays (10.9 vs. 6.8 days; p = 0.016); and a higher inpatient cost ($44,300 vs. $21,350; p 0.001). On multivariable analyses, higher odds of ICH were female sex 2.57 (95% CI 1.45-4.55; p = 0.001), middle age-group (45-64 years) 1.87 (CI: 1.11-3.15; p = 0.018) and older age group ( 64 years) 3.72 (CI: 1.15-12.03; p = 0.029). About 67.0% of all H-RCVS patients were discharged home, with no observed inpatient mortality.Intracerebral hemorrhage is the most common vascular complication in hospitalized RCVS patients, resulting in longer hospitalizations with more invasive procedures and higher healthcare expenditure. However, overall outcomes are excellent regardless of types of ICH, with no inpatient mortality observed in patients with hemorrhagic RCVS. Female sex and middle to older age-group are associated with higher odds of ICH.

Purpose Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [89Zr]Zr(oxinate)4 utilizing clinical PET/CT and PET/MRI. Methods Jurkat T cells were labeled with varying concentrations of [89Zr]Zr(oxinate)4 to generate different cell-specific activities (0.43–31.91 kBq/106 cells). Different concentrations of labeled cell suspensions (104, 105, and 106 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm3 cubic wells as a gel matrix. Plates were imaged on clinical PET/CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection. Results Using this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 104, when the specific activity was 27.8 kBq/106 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 104 cells could be detected on images with a specific activity of 15.4 kBq/106 cells. Conclusion The results show the feasibility of detecting [89Zr]Zr(oxinate)4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require detection of low cell numbers while minimizing radiation dose per cell.

Purpose\ud\udEarly and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, 18F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of 18F-fluciclovine on management of men with BCR of prostate cancer.\udMethods and Materials\ud\udMen with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) according to standardized procedures. Clinicians documented management plans before and after scanning, recording changes to treatment modality as major and changes within a modality as other. The primary outcome measure was record of a revised management plan postscan. Secondary endpoints were evaluation of optimal prostate specific antigen (PSA) threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine-involvement, and safety.\udResults\ud\ud18F-Fluciclovine was well tolerated in the 104 scanned patients (median PSA = 0.79 ng/mL). Lesions were detected in 58 out of 104 (56%) patients. Detection was broadly proportional to PSA level; ≤1 ng/mL, 1 out of 3 of scans were positive, and 93% scans were positive at PSA >2.0 ng/mL. Sixty-six (64%) patients had a postscan management change (80% after a positive result). Major changes (43 out of 66; 65%) were salvage or systemic therapy to watchful waiting (16 out of 66; 24%); salvage therapy to systemic therapy (16 out of 66; 24%); and alternative changes to treatment modality (11 out of 66, 17%). The remaining 23 out of 66 (35%) management changes were modifications of the prescan plan: most (22 out of 66; 33%) were adjustments to planned brachytherapy/radiation therapy to include a 18F-fluciclovine-guided boost. Where 18F-fluciclovine guided salvage therapy, the PSA response rate was higher than when 18F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]).\udConclusions\ud\ud18F-Fluciclovine PET/CT located recurrence in the majority of men with BCR, frequently resulting in major management plan changes. Incorporating 18F-fluciclovine PET/CT into treatment planning may optimize targeting of recurrence sites and avoid futile salvage therapy.

Aim: To analyse the functional outcome of Medial malleoli after Internal Fixation of medial malleolar fracture with fully threaded 4 mm cancellous cannulated screws. Introduction: Ankle fractures are one of the commonest fractures encountered by an orthopaedic surgeon with the majority being treated with open reduction and tension band wiring but it has a midterm and long term complications like hardware prominence, low-grade infection and hardware removal. Purpose of this study on medial malleolus fracture is to evaluate functional outcome after open reduction and fully threaded 4 mm cancellous cannulated screw fixation which has a very low complication rate. Materials and Method: This is a prospective study done in c u shah medical college and hospital Surendranagar. In the present study 30 cases of bimalleolar ankle fracture.Common Mechanism of Injury was Road traffic accidents and fall from height. the diagnosis was confirmed by Anteroposterior, lateral and Mortise radiograph. Classifications used are Lauge-Hanse Classification and DenisWeber Classification. Fully threaded 4 mm Cannulated cancellous screw was used for medial malleolus fixation.The anatomical plate used for fibula fixation. Post-op protocol: Postoperatively limb were immobilized in a plaster splint for 6 weeks and limb were elevated. Results: According to Baird and Jackson scoring system out of 30 cases, 56.67% were excellent and 26.67% were good, 13.34% were fair and 3.32% were poor. Conclusion: Open reduction and tension band wiring fixation of medial malleolus has biomechanically proved stable fixation but it has a midterm and long term complications like hardware prominence, low-grade infection and hardware removal. The current study has studied that open reduction and fully threaded 4 mm cancellous cannulated screw in medial malleolus fracture have a comparable functional outcome with a low complication rate.

Fetal hepatomegaly is associated with significant fetal morbidity and mortality. However, hepatomegaly might be overlooked when numerous other fetal anomalies are present, or it might not be noticed when it is an isolated entity. As the largest solid organ in the abdomen, the liver can be seen well with US or MRI, and the normal imaging characteristics are well described. The length of the fetal liver, which can be used to identify hepatomegaly, can be determined by measuring the liver from the diaphragm to the tip of the right lobe in the sagittal plane. Fetal hepatomegaly is seen with infection, transient abnormal myelopoiesis, liver storage and deposition diseases, some syndromes, large liver tumors, biliary atresia, and anemia. Some of these diagnoses are treatable during the fetal period. Attention to the associated findings and specific hepatic and nonhepatic imaging characteristics can help facilitate more accurate diagnoses and appropriate patient counseling.©RSNA, 2020.

Everyday use of denture cleansers to prevent microbial colonization on dentures can affect the properties of the denture base material. Limited literature is available on the effects of denture cleanser on reinforced resins. This study aimed to evaluate and compare the effect of denture cleanser on the flexural and impact strength of conventional and reinforced heat cure acrylic resins. Materials and Methods: Rectangular shaped specimens were prepared for flexural and impact strength as per ISO 1567. The denture base resins used included conventional, high impact, nylon fiber reinforced and glass fiber reinforced heat cure acrylic resins. They were further categorized into subgroups A and B depending on immersion in distilled water or denture cleanser (3.8% sodium perborate based). The flexural strength and impact strength of specimens were measured. The study design is a observational case-control study. SPSS version 25 statistical analysis software was used, and the STROBE statement checklist was followed. Results: The mean flexural strength was highest for glass fiber reinforced heat cure resin followed by conventional heat cure resin, high impact heat cure resin and nylon reinforced heat cure resin, respectively. The mean impact strength was highest for high impact heat cure resin followed by glass fiber reinforced heat cure resin, conventional heat cure resin, and nylon fiber-reinforced resin respectively.Conclusion: All the denture base resins tested exhibited a decrease in flexural and impact strength following use of a denture cleanser.

Background: Post renal transplant UTI is very common, increasing the morbidity and mortality with high chances of graft failure. Majority of centres use prophylactic antibioitcs like TMP-SMX after renal transplantation within first 6 months. Aims and Objectives: To understand the incidence of UTI and it's risk factors, to compare the effectiveness of using individual commode in decreasing incidence of post transplant UTI with historical cohort of renal transplant recipients. Materials and Methods: 25 patients were recruited from April 01, 2017, to June 01, 2017. They were encouraged to bring along a portable commode to use it during their stay as well as at home after discharge and followed for 1 month for presence of urinary tract infection. Results: 6 patients had culture proven UTI(24%) in historical cohort while no patient had UTI in study group using commode(0%). Conclusion: Individualizing personal waste disposal techniques using disposable bedside commode is an effective and economical strategy.

Injuries of the posterior cruciate ligament (PCL) are, compared to other knee injuries, quite rare. They account for around 3% of all acute traumatic knee injuries. The underlying mechanism leading to a PCL injury is a posterior directed force onto the anterior proximal tibia causing posterior tibial translation. This occurs normally during high-velocity collisions as a “dashboard” injury as well as in competitive athletic sports such as football. Similar to the anterior cruciate ligament (ACL), the PCL consist of two bundles (anterolateral and posteromedial) and is designed to prevent posterior translation of the tibia. The tension on the PCL differs according to the flexion angle of the knee. The diagnosis of PCL injuries is based on a careful clinical examination and radiological analysis. The radiological analysis consists of several X-rays with and without force loaded to the anterior proximal tibia, as well as an MRI which is considered the gold standard. CT scans can be performed to analyze for possible bony injuries. The treatment options include nonoperative treatment for isolated, partial PCL injuries and operative reconstruction for high-grade isolated PCL injuries or multiligamentous knee injuries. The surgical approach can be either open or arthroscopic, and similar to ACL reconstruction, a single or double bundle approach can be performed. Regarding the literature, there is no clear evidence for either double or single bundle reconstruction. Various PCL reconstruction techniques exist, including transtibial tunnel or a tibial-inlay technique. Common complications in PCL reconstruction include persistent posterior laxity and injury to the popliteal artery, the neurovascular structures, and meniscal roots during tunnel reaming. The postoperative treatment protocol includes restriction to 90° of flexion for the first 2 weeks with weight bearing as tolerated and the knee locked in extension, followed by free range of motion in a brace with weight bearing as tolerated. Physical therapy should focus on quadriceps muscle strengthening. Return to sports following PCL reconstruction should be delayed until 9–12 months from surgery.

Introduction: Compared to men, women have an increased risk of having a stroke, cardiovascular disease, and death. It requires continuous anticoagulation use based on CHA 2 DS 2 -VASc scores for stroke prevention. The Watchman device is indicated for patients with non-valvular AF at high risk of stroke who have contraindications to long-term anticoagulation use. We sought to determine the periprocedural outcome difference based on gender in the patients undergoing watchman device implantation. Methods: National Inpatient Sample databases from 2016 to 2018 were utilized using Stata 16.0. NIS databases are the ICD-10-CM code-based largest publicly available all-payer inpatient database. Patients with atrial fibrillation who underwent the watchman procedure were identified; later divided and compared based on gender. Multivariate logistic regression, linear regression, and student t-t-tests were used for analysis. Data were further analyzed after greedy propensity matching for accuracy. Results: Out of 33,825 patients who had the procedure, 14,105 (41.8%) were female, and 19,690 (58.2%) were male. The mean age for women and men were 76.5±7.5 and 75.6±8.1 respectively. Co-morbidities such as DM, CAD, CKD, PVD, and history of CABG were more in men, whereas anemia and pulmonary hypertension were more in women. Mortalities in women were 30 whereas it was 26 in men. There was no difference in mortality on multivariate logistic regression analysis. Complications such as pericardial drain and major bleeding requiring blood transfusion were higher in women. There was no difference in pericardial complications, ischemic stroke, hemorrhagic stroke, and AKI. The overall mean LOS and cost per hospitalization were higher in women. Conclusions: Patients undergoing watchman procedure showed no difference in periprocedural mortality between men and women; however, women had high events of pericardial drainage and major bleeding requiring blood transfusion.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an appealing alternative to transvenous ICD systems. However, data on indications for S-ICD explantations are sparse. The objective of this study was to assess the incidence and indications for S-ICD explantation at a large tertiary referral center. We conducted a retrospective study of all S-ICD explantations performed from 2014-2020. Data on demographics, comorbidities, implantation characteristics, and indications for explantation were collected. A total of 64 patients underwent S-ICD explantation during the study period. During that time, there were 410 S-ICD implantations at our institution, of which 53 (12.9%) were explanted with a mean duration from implant to explant of 19.7 ± 20.1 months. The mean age of the patients at explantation was 44.8 ± 15.3 years, and 42% (n = 27) were women. The indication for S-ICD implantation was primary prevention in 58% and secondary prevention in 42% of patients, respectively. The most common reason for explantation was infection (32.8%), followed by abnormal sensing (25%) and the need for pacing (18.8%). Those who underwent S-ICD explantation for pacing indications were significantly older (55.7 ± 13.6 vs. 42.3 ± 14.6 years

While tumors of the nervous system (NS) are rare, they contribute to significant morbidity and mortality. Despite advances in imaging technology, initial diagnosis and characterization of treatment response remains problematic for devastating tumors such as glioblastoma (GBM). A liquid biopsy can provide a minimally-invasive and serial source of biomarkers to supplement current diagnostic methods. Here, we utilize a unique characteristic of NS tumors including GBM and schwannoma/neurofibroma – the overexpression of the a2 variant of the IL-13 receptor which is not detectable in normal tissue. Previously, we have shown that IL13Ra2 is elevated in the plasma of some GBM patients above baseline levels. We hypothesize that the presence of circulating IL13Ra2 not only predicts the level of this receptor in the tumor tissue, but also has clinical prognostic value. Here, we used ELISA to measure the plasma levels of IL13Ra2 in the GBM (n=77) and schwannoma/neurofibroma (n=15) patients and correlated these levels to tumor levels, diagnosis, and clinical characteristics. We have demonstrated that elevated levels of plasma IL13Ra2 correlated with tumor presence compared to non-tumor controls for both GBM and schwannoma/neurofibroma patients, indicating this biomarker’s diagnostic utility. Further, for both GBM and schwannoma/neurofibroma patients the plasma concentration of IL13Ra2 is correlated to its tumor concentration, indicating that sampling patient plasma could provide insight into the tumor’s composition. Finally, elevated levels of IL13Ra2 protein in the tumor and plasma of GBM patients predicted longer patient survival. These exciting findings lay the groundwork for a plasma-based NS tumor liquid biopsy.

Objectives: Irreparable rotator cuff tears can be challenging to manage in younger patients who are not well indicated for reverse total shoulder replacement. Treatment options in this patient population include both marginal convergence (MC) and superior capsular reconstruction (SCR). While both treatment options have demonstrated good short term outcomes, they have vastly different associated costs and operative times. Thus, the purpose of this study was to compare range of motion (ROM), patient reported outcomes, and re-operation rates following MC and SCR. We hypothesized that SCR would outperform MC regarding functional and subjective outcomes. Methods: A retrospective review was conducted on 44 patients from two surgeons with irreparable rotator cuff tears that underwent either MC (28 patients, 28 shoulders) or SCR (16 patients, 16 shoulders) from 2014-2019 at a single academic center. Patient inclusion criteria were the following: failed conservative or prior surgical management, no or mild glenohumeral arthritis, Goutallier grade 3 or 4 fatty infiltration of the involved muscles, Hamada grade 1 or 2 rotator cuff arthropathy, intact or repairable subscapularis tear and minimum of 1 year follow-up. Visual Analogue Scale (VAS) for pain, active forward flexion (FF) and external rotation (ER) range of motion, reoperation rate, and rate of conversion to reverse total shoulder arthroplasty were evaluated. For statistical analysis, t-tests were used to determine differences in functional outcomes and VAS, while Chi-Squared tests were used to determine differences in the rate of re-operation and conversion to arthroplasty (*p < 0.05). Results: The mean age at the time of surgery for the MC and SCR groups was 64.4 and 58.5 years, respectively, with an average follow-up of 31.5 months for the MC group and 17.8 months for the SCR group. There were no significant differences in the mean age at the time of surgery, gender, body mass index, pre-operative FF and ER, and pre-operative VAS between the groups. The MC group did not have a significant improvement FF with a mean pre-operative FF of 144.4°(range: 30-170°) and post-operative FF of 150.5°(range: 90-180). The same was true for the SCR group, with a mean pre-operative FF 127.5°(range: 40-170°) and post-operative FF of 146.3°(range: 40-170). There was also no significant improvement in ER post-operatively in either group. Both the MC and SCR group had significant improvements in VAS for pain from an average of 7.3 (range: 1-10) pre-operatively to 2.5 (range: 0-10) post-operative for the MC group (p < 0.01) and from 7.3 (range: 3-10) pre-operatively to 1 (range: 0-4) post-operative for the SCR group (p < 0.01). There were no significant differences in the post-operative FF or ER, change in FF or ER, post-operative VAS, or change in VAS between the two treatment groups. The rate of conversion to arthroplasty was not significantly different between the groups at 3.6% for the MC group and 12.5% for the SCR group. Additionally, the overall reoperation rate was not significantly different between the MR and SCR groups at 10.7% and 12.5%, respectively. Conclusions: There were no significant differences between the MC and SCR treatment groups. While both MC and SCR were effective in improving VAS for pain, neither treatment consistently resulted in significant improvement in ROM. Further studies with long term outcomes are needed to determine if there are certain indications for which one treatment results in better outcomes.

Objectives: While rotator cuff tears often require repair of the supraspinatus, patients can also have a concurrent tear of the subscapularis requiring repair. Previous smaller studies have shown good clinical outcomes following the repair of the subscapularis and rotator cuff during the same procedure.1 The purpose of this study was to compare clinical outcome measures between patients who had isolated supraspinatus repairs versus those who had a supraspinatus tear with a concurrent subscapularis repair. Methods: A retrospective review of 166 patients who underwent arthroscopic supraspinatus repair with or without a concurrent subscapularis repair between 2013-2018 with a minimum of one-year follow up was performed. Patients were separated into two groups based on their treatment: 100 had an isolated supraspinatus repair (SP) and 66 had both a supraspinatus and subscapularis repair (SB). The primary outcome was revision rotator cuff repair. Secondary outcomes were objective measures such as range of motion (ROM) and strength testing, including flexion (FF), external rotation (ER), and internal rotation (IR), as well as patient-reported outcome measures (PROs) including visual analog pain scale (VAS) and subjective shoulder value (SSV). Outcomes were compared using the Mann- Whitney Test and Fisher’s Exact Test with pResults: There was no significant difference in the rate of revision surgery required following isolated supraspinatus repair versus those with a subscapularis repair. Additionally, there were no significant differences between groups for all PROs, all ROM parameters, and all strength parameters (all p > 0.05) (Table 1). Conclusions: The data from this study demonstrated that patients who require a subscapularis repair at the time of their rotator cuff repair can expect similar short term outcomes to those patients who only required repair of their supraspinatus.

Introduction: The temporal bone is a complex anatomic structure that contains the organs of hearing and balance and has direct contact with brainstem, cerebellum and temporal lobe of brain. Radiographic assessment of temporal bone is difficult owing to complicated anatomical structure of middle and inner ear. High resolution computed tomography (HRCT) - a modification of routine CT produces images with higher contrast and a better spatial resolution. HRCT has the advantage of topographic visualization, devoid of artifacts from superimposition of structures. It provides information not only about bony outline but also soft tissue changes making it possible for the accurate assessment of pathology prior to surgical exploration regarding location, extent and complication of the disease. Material and methods: This was a cross sectional study of 50 patients who were clinically suspected of having symptoms related to the temporal bone like hearing loss, otorrhea, otalgia, tinnitus, vertigo, ear bleed, cranial nerve palsies, fever, ataxia etc were referred and subjected to HRCT of the temporal bone at Geetanjali Medical College and Hospital (Udaipur) between Nov 2017 and June 2019. Results: CSOM and Cholesteatoma were the most common diseases found by HRCT and Intra-op/Follow-up scan followed by Fractures, acoustic neuroma, Glomus tympanicum and Atretic EAC. Almost all the lesions were correctly detected by HRCT when confirmed with Intra-op/follow up findings. Conclusion: HRCT can very accurately detect Temporal bone pathology. Keywords: HRCT, CSOM, CT

Background: The subcutaneous implantable-cardioverter defibrillator (S-ICD) is an appealing alternative to transvenous ICD systems. However, data on indications for S-ICD explantations are sparse. Objectives: To assess incidence and indications for S-ICD explantation at a large tertiary referral center. Methods: We conducted a retrospective study of all S-ICD explantations performed from 2014 to 2020. Data on demographics, comorbidities, implantation characteristics, and indications for explantation, were collected. Results: A total of 64 patients underwent S-ICD explantation during the study period. During that time, there were 410 S-ICD implantations at our institution of which 53 (12.9%) were explanted with a mean duration from implant to explant of 19.7±20.1 months. The mean age of the patients at explantation was 44.8±15.3 years, and 42% (n=27) were female. The indication for S-ICD implantation was primary prevention in 58% and secondary prevention in 42% of the patients. The most common reason for explantation was infection (32.8%) followed by abnormal sensing (25%) and need for pacing (18.8%). Those who underwent S-ICD explantation for pacing indications were significantly older (55.7±13.6 vs 42.3± 14.6 years, p = 0.005) with a wider QRS duration (111±19 ms vs 98±19 ms, p = 0.03) at device implantation compared to patients who underwent explantation for other indications. Conclusion: Incidence of S-ICD explantation in a large tertiary practice was 12.9%. While infection was the indication for a third of the explantations, a significant number were due to sensing abnormalities and need for pacing. These data may have implications for patient selection for S-ICD implantation.

Aim Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC. Methods Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI Results Data on 35 patients (18 F: 17 M; median age 54 [range: 18-86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3-15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age (p Conclusion The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient's hormonal status on the manifestation of sarcopenia should be further defined.

BackgroundTranscription factor(TF) interactions are known to regulate target gene(TG) expression in eukaryotes via TF regulatory modules(TRMs). Such interactions can be formed due to co-localizing TFs binding proximally to each other in the DNA sequence or over long distances between distally binding TFs via chromatin looping. While the former type of interaction has been characterized extensively, long distance TF interactions are still largely understudied. Furthermore, most prior approaches have focused on characterizing physical TF interactions without accounting for their effects on TG expression regulation. Understanding TRM based TG expression regulation could aid in understanding diseases caused by disruptions to these mechanisms. In this paper, we present a novel neural network based TRM detection approach that consists of using multi-omics TF based regulatory mechanism information to generate features for building non-linear multilayer perceptron TG expression prediction models in the GM12878 immortalized lymphoblastoid cells.ResultsWe estimated main effects of 149 individual TFs and interaction effects of 48 distinct combinations of TFs forming TRMs based on their influence on TG expression. We identified several well-known and discovered multiple previously uncharacterized TF interactions within our detected set of TRMs. We further characterized the pairwise TRMs using long distance chromatin looping and motif co-occurrence data. We found that nearly all the TFs constituting TRMs detected by our approach interacted via chromatin looping, and that these TFs further interacted with promoters to influence TG expression through one of four possible regulatory configurations.ConclusionHere, we have provided a framework for detecting TRMs using neural network models containing multi-omics TF based regulatory features. We have also described these TRMs based on their regulatory potential along with presenting evidence for the possibility of TF interactions forming the TRMs occurring via chromatin looping.

A large proportion of non-coding variants are present within binding sites of transcription factors(TFs), which play a significant role in gene regulation. Thus, deriving the impact of non-coding variants on TF binding is the first step towards unravelling their regulatory roles within their associated disease traits. Most of the modern algorithms used for this purpose are based on convolutional neural network(CNN) architectures. However, these models are incapable of capturing the positional effect of different sub-sequences within the TF binding sites on the binding affinity. In this paper, we utilize the attentive gated neural network(AGNet) architecture to build a set of TF-AGNet models for predicting in vivo TF binding intensities in the GM12878 lymphoblastoid cells. These models have novel layers capable of deriving the impact of relative positions of different DNA sub-sequences, within a binding site, on TF binding affinity, and of extracting the most relevant prediction features. We show that the TF-AGNet models are able to outperform conventional CNNs for predicting continuous values of TF binding affinity. We also train additional TF-AGNet models for 20 TFs using data from 4 other cell-lines to assess the generalizability of their prediction accuracy. Lastly, we show that the TF-AGNet based models more accurately classify non-coding variants that significantly affect TF binding compared to models based on 7 variant annotation tools. This accuracy can be leveraged to derive gene regulatory roles of millions of non-coding variants across the genome to further examine their mechanistic associations with complex disease traits.

We report the case of a 66-year-old previously healthy man presenting with blood and mucus in his urine. Cystoscopy revealed a mass in the prostatic urethra, and endoscopic biopsy showed adenocarcinoma in situ with mucinous features. Endorectal multiparametric prostate MRI demonstrated a 1.9 cm T2 hyperintense mass in the peripheral zone of the left prostatic apex with extension into the urethral lumen. No diffusion restriction or early enhancement was seen in the mass. Radical prostatectomy was performed, and final pathology demonstrated a mucin-producing urothelial adenocarcinoma arising from the prostatic urethra. The peripheral zone T2 hyperintense abnormality correlated with abundant pools of mucin extending into the prostatic stroma and surrounded by neoplastic prostatic glandular cells. We conclude prostatic urethral mucinous urothelial carcinoma should be included in the differential diagnosis for T2 hyperintense prostatic masses.