Yield and clinical impact of image-guided bone biopsy in osteomyelitis of the appendicular skeleton: a systematic review and meta-analysis.

OBJECTIVE: To assess the yield and clinical impact of image-guided bone biopsy for osteomyelitis of the appendicular skeleton. MATERIALS AND METHODS: A literature search of several databases was conducted from inception to August 2023. Eligible studies reported patients who underwent image-guided bone biopsy for investigation of osteomyelitis of the appendicular skeleton. The pooled proportions were analyzed using a random-effects model. This review was registered in PROSPERO (CRD42023466419). RESULTS: From 370 initial studies screened, eight met the eligibility criteria, with a total of 700 patients. The pooled technical success rate was 99.6% (95% CI: 0.992, 1.001; I2 = 0%). Positive bone cultures were pooled at 31.9% (95% CI: 0.222, 0.416; I2 = 87.83%) and negative cultures at 68.1% (95% CI: 0.584, 0.778; I2 = 87.83%). Methicillin-Sensitive Staphylococcus Aureus and Methicillin-Resistant Staphylococcus Aureus yield was 24.5% (95% CI: 0.096, 0.394; I2 = 90.98%) and 7.6% (95% CI: 0.031, 0.121; I2 = 34.42%) respectively. Group A Streptococcus yield was 7.0% (95% CI: 0.014, 0.127; I2 = 70.94%). Polymicrobial culture yield was 15.7% (95% CI: 0.018, 0.297; I2 = 88.90%). Post-procedural management change rate was 36.5% (95% CI: 0.225, 0.504; I2 = 92.39%). No complications were reported across studies. CONCLUSION: For patients under investigation of osteomyelitis of the appendicular skeleton, image-guided bone biopsy demonstrates a good rate of technical success. Additional studies may provide further support for the use of image-guided bone biopsy in this population. Image-guided bone biopsy results lead to change in antibiotics therapy in a portion of patients with suspected osteomyelitis suggesting its potential utility in select patients.

Total Ankle Replacement Versus Arthrodesis for End-Stage Ankle Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF). OBJECTIVE: To determine which treatment is superior in terms of clinical scores and adverse events. DESIGN: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307). SETTING: 17 National Health Service trusts across the United Kingdom. PATIENTS: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure. INTERVENTION: Patients were randomly assigned to TAR or AF surgical treatment. MEASUREMENTS: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible. RESULTS: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was -5.6 (95% CI, -12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (-11.1 [CI, -19.3 to -2.9]). LIMITATION: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques. CONCLUSION: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research Heath Technology Assessment Programme.

Progressive vasoconstriction with sequential thermal stimulation indicates vascular dysautonomia in sickle cell disease.

Persons with sickle cell disease (SCD) exhibit subjective hypersensitivity to cold and heat perception in experimental settings, and triggers such as cold exposure are known to precipitate vaso-occlusive crises by still unclear mechanisms. Decreased microvascular blood flow (MBF) increases the likelihood of vaso-occlusion by increasing entrapment of sickled red blood cells in the microvasculature. Because those with SCD have dysautonomia, we anticipated that thermal exposure would induce autonomic hypersensitivity of their microvasculature with an increased propensity toward vasoconstriction. We exposed 17 patients with SCD and 16 control participants to a sequence of predetermined threshold temperatures for cold and heat detection and cold and heat pain via a thermode placed on the right hand. MBF was measured on the contralateral hand by photoplethysmography, and cardiac autonomic balance was assessed by determining heart rate variability. Thermal stimuli at both detection and pain thresholds caused a significant decrease in MBF in the contralateral hand within seconds of stimulus application, with patients with SCD showing significantly stronger vasoconstriction (P = .019). Furthermore, patients with SCD showed a greater progressive decrease in blood flow than did the controls, with poor recovery between episodes of thermal stimulation (P = .042). They had faster vasoconstriction than the controls (P = .033), especially with cold detection stimulus. Individuals with higher anxiety also experienced more rapid vasoconstriction (P = .007). Augmented vasoconstriction responses and progressive decreases in perfusion with repeated thermal stimulation in SCD are indicative of autonomic hypersensitivity in the microvasculature. These effects are likely to increase red cell entrapment in response to clinical triggers such as cold or stress, which have been associated with vaso-occlusive crises in SCD.

Treatment of Cheyne-Stokes Respiration in Heart Failure with Adaptive Servo-Ventilation: An Integrative Model.

The SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) multicenter trial found a small but significant increase in all-cause and cardiovascular mortality in patients assigned to adaptive servo-ventilation (ASV) versus guideline-based medical treatment. To better understand the physiological underpinnings of this clinical outcome, we employ an integrative computer model to simulate congestive heart failure with Cheyne-Stokes respiration (CHF-CSR) in subjects with a broad spectrum of underlying pathogenetic mechanisms, as well as to determine the in silico changes in cardiopulmonary and autonomic physiology resulting from ASV. Our simulation results demonstrate that while the elimination of CSR through ASV can partially restore cardiorespiratory and autonomic physiology toward normality in the vast majority of CHF phenotypes, the degree of restoration can be highly variable, depending on the combination of CHF mechanisms in play. The group with the lowest left ventricular ejection fraction (LVEF) appears to be most vulnerable to the potentially adverse effects of ASV, but the level of pulmonary capillary wedge pressure (PCWP) plays an important role in determining the nature of these effects.

Nocturnal peripheral vasoconstriction predicts the frequency of severe acute pain episodes in children with sickle cell disease.

The basic model of SCD physiology states that vaso-occlusion occurs when hemoglobin S-containing red blood cells (RBC) undergo sickling before they escape the capillary into a larger vessel. We have shown that mental stress, pain and cold, and events reported by patients to trigger SCD vaso-occlusive crisis (VOC), cause rapid and significant decrease in blood flow, reducing the likelihood that RBC could transit the microvasculature before sickling occurs. However, the critical link between decrease in microvascular blood flow and the incidence of future sickle VOC has never been established experimentally in humans. Using data from centrally adjudicated, overnight polysomnograms (PSG), previously collected in a prospective multi-center cohort sleep study, we analyzed the beat-to-beat amplitudes of vasoconstriction reported by the fingertip photoplethysmogram in 212 children and adolescents with SCD and developed an algorithm that detects vasoconstriction events and quantifies the magnitude (Mvasoc ), duration, and frequency of vasoconstriction that reflect the individual's inherent peripheral vasoreactivity. The propensity to vasoconstrict, quantified by median Mvasoc , predicted the incidence rate of post-PSG severe acute vaso-occlusive pain events (P = .006) after accounting for age and hemoglobin. Indices of sleep-disordered breathing contributed to median Mvasoc but did not predict future pain rate. Median Mvasoc was not associated with vaso-occlusive pain events that occurred prior to each PSG. These results show that SCD individuals with high inherent propensity to vasoconstrict have more frequent severe acute pain events. Our empirical findings are consistent with the fundamental SCD hypothesis that decreased microvascular flow promotes microvascular occlusion.

Loss of alpha-globin genes in human subjects is associated with improved nitric oxide-mediated vascular perfusion.

Alpha thalassemia is a hemoglobinopathy due to decreased production of the α-globin protein from loss of up to four α-globin genes, with one or two missing in the trait phenotype. Individuals with sickle cell disease who co-inherit the loss of one or two α-globin genes have been known to have reduced risk of morbid outcomes, but the underlying mechanism is unknown. While α-globin gene deletions affect sickle red cell deformability, the α-globin genes and protein are also present in the endothelial wall of human arterioles and participate in nitric oxide scavenging during vasoconstriction. Decreased production of α-globin due to α-thalassemia trait may thereby limit nitric oxide scavenging and promote vasodilation. To evaluate this potential mechanism, we performed flow-mediated dilation and microvascular post-occlusive reactive hyperemia in 27 human subjects (15 missing one or two α-globin genes and 12 healthy controls). Flow-mediated dilation was significantly higher in subjects with α-trait after controlling for age (P = .0357), but microvascular perfusion was not different between groups. As none of the subjects had anemia or hemolysis, the improvement in vascular function could be attributed to the difference in α-globin gene status. This may explain the beneficial effect of α-globin gene loss in sickle cell disease and suggests that α-globin gene status may play a role in other vascular diseases.

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups - revisiting this controversial concept after 16 years of additional evidence.

Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi-level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S') and diastole (E'), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9 years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty-eight patients (40%) were less than 21 years old at initial evaluation. Survival and Cox proportional-hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35 years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end-organ failure. On Cox proportional-hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S' results in a 91% increase, and 1 cm/s decrease in E' results in a 43% increase in mortality. While excluding cardiac parameters, higher plasma free hemoglobin was significantly associated with risk of mortality (p=.049). In conclusion, elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers.

Monitoring of three-phase variations in the mortality of COVID-19 pandemic using control charts: where does Pakistan stand?

BACKGROUND: At the end of December 2019, the world in general and Wuhan, the industrial hub of China, in particular, experienced the COVID-19 pandemic. Massive increment of cases and deaths occurred in China and 209 countries in Europe, America, Australia, Asia and Pakistan. Pakistan was first hit by COVID-19 when a case was reported in Karachi on 26 February 2020. Several methods were presented to model the death rate due to the COVID-19 pandemic and to forecast the pinnacle of reported deaths. Still, these methods were not used in identifying the first day when Pakistan enters or exits the early exponential growth phase. OBJECTIVE: The present study intends to monitor variations in deaths and identify the growth phases such as pre-growth, growth, and post-growth phases in Pakistan due to the COVID-19 pandemic. METHODS: New approaches are needed that display the death patterns and signal an alarming situation so that corrective actions can be taken before the condition worsens. To meet this purpose, secondary data on daily reported deaths due to the COVID-19 pandemic have been considered, and the $c$ and exponentially weighted moving average (EWMA) control charts are used To meet this purpose, secondary data on daily reported deaths in Pakistan due to the COVID-19 pandemic have been considered. The $ c$ and exponentially weighted moving average (EWMA) control charts have been used for monitoring variations. RESULTS: The chart shows that Pakistan switches from the pre-growth to the growth phase on 31 March 2020. The EWMA chart demonstrates that Pakistan remains in the growth phase from 31 March 2020 to 17 August 2020, with some indications signaling a decrease in deaths. It is found that Pakistan moved to a post-growth phase for a brief period from 27 July 2020 to 28 July 2020. Pakistan switches to re-growth phase with an alarm on 31/7/2020, right after the short-term post-growth phase. The number of deaths starts decreasing in August in that Pakistan may approach the post-growth phase shortly. CONCLUSION: This amalgamation of control charts illustrates a systematic implementation of the charts for government leaders and forefront medical teams to facilitate the rapid detection of daily reported deaths due to COVID-19. Besides government and public health officials, it is also the public's responsibility to follow the enforced standard operating procedures as a temporary remedy of this pandemic in ensuring public safety while awaiting a suitable vaccine to be discovered.

Dermatofibrosarcoma protuberans: the diagnosis of high-grade fibrosarcomatous transformation.

OBJECTIVES: Dermatofibrosarcoma protuberans (DFSP) is an intermediate-grade tumour which may undergo fibrosarcomatous transformation to a high-grade sarcoma (DFSP-FST). DFSP-FST requires wide local resection, and therefore, pre-operative identification is important. The aims of this study are to see if DFSP and DFSP-FST can be differentiated based on MRI appearances, and to determine the ability of ultrasound-guided core needle biopsy (US-CNB) to identify DFSP-FST. MATERIALS AND METHODS: Retrospective review of patients with a histological diagnosis of DFSP with/without transformation to DFSP-FST. Patient age, gender, lesion location and maximal size were recorded, as were several MRI features. MRI studies were reviewed independently by 2 musculoskeletal radiologists and the assessed features were then compared with final surgical resection histology. Histological results of US-CNB were also compared with final surgical pathology. RESULTS: A total of 42 patients were included, 26 males and 16 females with a mean age of 41.3 years (range 3-78 years). The upper limb was involved in 12 cases, the lower limb in 17 and the trunk in 13. Final surgical histological diagnosis was DFSP in 21 (50%) cases and DFSP-FST in 21 (50%) cases. Mean tumour dimension for DFSP was 32 mm and DFSP-FST 68 mm (p < 0.001). MRI features indicative of DFSP-FST included multi-lobular morphology (p = 0.03), T2W hypointensity compared with fat (p = 0.03), internal flow voids (p = 0.03) and peri-tumoral oedema (p < 0.001). Only 3 cases of DFSP-FST were correctly diagnosed on US-CNB. CONCLUSIONS: Various MRI findings can suggest a diagnosis of DFSP-FST, but US-CNB is unreliable at identifying high-grade fibrosarcomatous transformation.

The incidence and diagnostic relevance of pathological fracture in conventional central chondrosarcoma.

OBJECTIVE: To determine the incidence and diagnostic relevance of pathological fracture in patients with conventional central chondrosarcoma (CC-CS). MATERIALS AND METHODS: Retrospective review of patients with CC-CS diagnosed between January 2007 and December 2019. Data collected included age, sex, skeletal location and the presence of pathological fracture at presentation. Histological tumour grade based on surgical resection or needle biopsy was classified as atypical cartilaginous tumour (ACT)/grade 1 CS (ACT/Gd1 CS), high-grade CS (HG-CS) and dedifferentiated CS (DD-CS). The presence of pathological fracture was correlated with age, skeletal location and tumour grade. RESULTS: Three hundred seventeen patients were included (177 males and 140 females with mean age 55.8 years, range 9-91 years). Mean age of patients without pathological fracture was 54.4 years and those with pathological fracture 62.9 years (p = 0.002). The major long bones were involved in 171 cases, the flat bones in 112 cases, the mobile spine in 7 cases and the small bones of the hands and feet in 27 cases. There were 81 ACT/Gd 1 CS, 168 HGCS and 68 DD-CS. Pathological fracture was evident at presentation in 51 (16.1%) cases, the commonest bones involved being the femur (n = 21; 41.2%), humerus (n = 10; 19.6%) and acetabulum (n = 7; 13.7%). Pathological facture occurred in 7 cases of ACT/Gd 1 CS (13.7%), 23 cases of HGCS (45.1%) and 21 cases of DD-CS (41.2%) (p = 0.001). Following multivariate analysis, both older age and histological grade were independently significant factors. CONCLUSIONS: Pathological fracture was seen in 16.1% of patients with CC-CS. Pathological fractures in the femur, humerus and acetabulum very likely indicate higher tumour grade.

Introducing image-guided synovial aspiration and biopsy in assessing peri-prosthetic joint infection: an early single-centre experience.

AIM: Synovial sampling can be used in the diagnosis of peri-prosthetic joint infection (PJI). The purpose of this study was to establish the role of simultaneous image-guided synovial aspiration and biopsy (SAB) during an initial 2-year experience at our institution. METHODS: Retrospective review of consecutive SABs performed during 2014-2016 at a tertiary referral musculoskeletal centre. Radiological SAB microbiology culture results were compared with intra-operative surgical samples or multidisciplinary team (MDT) meeting outcome at 1-year follow-up if surgery was not undertaken. Sensitivity, specificity and accuracy of synovial aspiration (SA), synovial biopsy (SB) and simultaneous SAB were calculated. RESULTS: 103 patients (46 male, 57 female) totalling 111 procedures were analysed with mean age 65 years (range 31-83). Image-guided synovial procedures were performed on 52 (46.9%) hip and 59 (53.1%) knee joint prostheses. The mean combined sensitivity, specificity and accuracy for the entire cohort was 72.6%, 96.9% and 90%, respectively. When only SB was obtained, diagnostic accuracy (92.5%) was similar to SA alone (94.1%). In total, there were 21 (18.9%) true-positive, 80 (72.1%) true-negative, 2 (1.8%) false-positive and 8 (7.2%) false-negative cases (PPV 91.3% and NPV 90.9%). No post-procedural complications were recorded at 1-year follow-up. CONCLUSION: Percutaneous image-guided SAB is a valuable technique in assessing suspected PJI, with most samples indicative of infective status and causative organisms when validated against intra-operative results and specialist MDT evaluation. Image-guided SB is a safe and useful additional procedure following failed SA with equivalent levels of diagnostic accuracy.

MRI-histopathological correlation in paediatric conventional central chondrosarcoma: a report of 17 cases.

OBJECTIVE: To describe the MRI features of paediatric conventional central chondrosarcoma (CC-CS) and correlate with histological grade. MATERIALS AND METHODS: A retrospective review of children/adolescents with histologically confirmed CC-CS. Data collected included age, sex, skeletal location, and histology from needle biopsy or resection, which was classified as atypical cartilaginous tumours/grade 1 CS (ACT/Gd 1 CS), high-grade chondrosarcoma (HGCS), and dedifferentiated chondrosarcoma (DD-CS). MRI studies were reviewed independently by 2 radiologists blinded to the histology grade, who graded the tumours as ACT/Gd 1 CS, HGCS, and DD-CS based on MRI features. RESULTS: The study included 7 males and 10 females with mean age 13.9 years (range 6-18 years). Tumours were located in the femur (n = 6), humerus (n = 3), tibia, ilium, scapula, and ulna (n = 1 each), and the small bones of the hands or feet (n = 4). Final histology grade was ACT/Gd 1 CS in 15 cases and HGCS in 2 (both grade 1 CS with focal transition to grade 2), 15 based on surgical specimens, 1 based on open biopsy, and 1 on needle biopsy alone. Predicted MRI grade for the 2 readers was ACT/Gd 1 CS in 11 cases each and HGCS in 6 cases each, indicating a mismatch between predicted MRI grade and histological grade in 8 (47%) cases (4 cases with one reader mismatch and 4 cases with both). CONCLUSIONS: MRI findings in paediatric CC-CS may be misleading, showing features suggestive of HGCS 7 of 17 (41.2%) of cases. This should be taken into consideration when planning surgical treatment.

The importance of MRI review following the diagnosis of atypical cartilaginous tumour using image-guided needle biopsy.

OBJECTIVE: To evaluate the role of pre-biopsy MRI for management planning in patients with atypical cartilaginous tumours (ACT) diagnosed on image-guided core needle biopsy (IGCNB). MATERIALS AND METHODS: Retrospective review of patients diagnosed with ACT of the appendicular skeleton based on IGCNB who subsequently underwent surgical curettage or resection. Data collected included age, sex, skeletal location and surgical histology classified as ACT, high-grade chondrosarcoma (HG-CS) and dedifferentiated chondrosarcoma (DD-CS). Pre-biopsy MRI studies were reviewed independently by 2 radiologists blinded to surgical histology results and graded as ACT, HG-CS and DD-CS based on MRI features. RESULTS: The study included 24 males and 28 females (mean age 42.1 years; range 9-76 years). One patient had 2 lesions treated, making a total of 53 lesions. Tumours were located in the femur in 21 cases, humerus in 17, tibia in 9, radius in 4 and ulna and fibula in 1 each. Surgical histology was ACT in 41 cases, HG-CS in 10 and DD-CS in 2, indicating mismatch between IGCNB and surgical histology in 12/53 cases (22.6%). Predicted MRI grade for the 2 readers was ACT in 39 cases each, HG-CS in 13 and 14 cases and DD-CS in 1 and 0 cases. Sensitivity, specificity and accuracy of MRI for predicting HG-CS/DD-CS were 91%, 93% and 92%, respectively. Inter-observer correlation was very good (kappa = 0.94). DISCUSSION: Review of MRI findings in patients with ACT diagnosed on IGCNB is vital for identifying patients with a HG-CS/DD-CS and is recommended when planning surgical management or considering repeat IGCNB.

High Breath-by-Breath Variability Is Associated With Extubation Failure in Children.

OBJECTIVES: Extubation failure is multifactorial, and most tools to assess extubation readiness only evaluate snapshots of patient physiology. Understanding variability in respiratory variables may provide additional information to inform extubation readiness assessments. DESIGN: Secondary analysis of prospectively collected physiologic data of children just prior to extubation during a spontaneous breathing trial. Physiologic data were cleaned to provide 40 consecutive breaths and calculate variability terms, coefficient of variation and autocorrelation, in commonly used respiratory variables (i.e., tidal volume, minute ventilation, and respiratory rate). Other clinical variables included diagnostic and demographic data, median values of respiratory variables during spontaneous breathing trials, and the change in airway pressure during an occlusion maneuver to measure respiratory muscle strength (maximal change in airway pressure generated during airway occlusion [PiMax]). Multivariable models evaluated independent associations with reintubation and prolonged use of noninvasive respiratory support after extubation. SETTING: Acute care, children's hospital. PATIENTS: Children were included from the pediatric and cardiothoracic ICUs who were greater than 37 weeks gestational age up to and including 18 years who were intubated greater than or equal to 12 hours with planned extubation. We excluded children who had a contraindication to an esophageal catheter or respiratory inductance plethysmography bands. INTERVENTIONS: Noninterventional study. MEASUREMENTS AND MAIN RESULTS: A total of 371 children were included, 32 of them were reintubated. Many variability terms were associated with reintubation, including coefficient of variation and autocorrelation of the respiratory rate. After controlling for confounding variables such as age and neurologic diagnosis, both coefficient of variation of respiratory rate(p < 0.001) and low PiMax (p = 0.002) retained an independent association with reintubation. Children with either low PiMax or high coefficient of variation of respiratory rate had a nearly three-fold higher risk of extubation failure, and when these children developed postextubation upper airway obstruction, reintubation rates were greater than 30%. CONCLUSIONS: High respiratory variability during spontaneous breathing trials is independently associated with extubation failure in children, with very high rates of extubation failure when these children develop postextubation upper airway obstruction.

Mental stress causes vasoconstriction in subjects with sickle cell disease and in normal controls.

Vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD) and occurs when deoxygenated sickled red blood cells occlude the microvasculature. Any stimulus, such as mental stress, which decreases microvascular blood flow will increase the likelihood of red cell entrapment resulting in local vaso-occlusion and progression to VOC. Neurally mediated vasoconstriction might be the physiological link between crisis triggers and vaso-occlusion. In this study, we determined the effect of mental stress on microvascular blood flow and autonomic nervous system reactivity. Sickle cell patients and controls performed mentally stressful tasks, including a memory task, conflict test and pain anticipation test. Blood flow was measured using photoplethysmography, autonomic reactivity was derived from electrocardiography and perceived stress was measured by the State-Trait Anxiety Inventory questionnaire. Stress tasks induced a significant decrease in microvascular blood flow, parasympathetic withdrawal and sympathetic activation in all subjects. Of the various tests, pain anticipation caused the highest degree of vasoconstriction. The magnitude of vasoconstriction, sympathetic activation and perceived stress was greater during the Stroop conflict test than during the N-back memory test, indicating the relationship between magnitude of experimental stress and degree of regional vasoconstriction. Baseline anxiety had a significant effect on the vasoconstrictive response in sickle cell subjects but not in controls. In conclusion, mental stress caused vasoconstriction and autonomic nervous system reactivity in all subjects. Although the pattern of responses was not significantly different between the two groups, the consequences of vasoconstriction can be quite significant in SCD because of the resultant entrapment of sickle cells in the microvasculature. This suggests that mental stress can precipitate a VOC in SCD by causing neural-mediated vasoconstriction.

Pilot study to differentiate lipoma from atypical lipomatous tumour/well-differentiated liposarcoma using MR radiomics-based texture analysis.

AIMS: This pilot study aims to determine if tumour heterogeneity assessed using magnetic resonance imaging (MRI) radiomics-based texture analysis (TA) can differentiate between lipoma and atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL). MATERIALS AND METHODS: Thirty consecutive ALT/WDLs and 30 lipomas were included in the study, cases diagnosed both histologically and with murine double minute 2 (MDM2) gene amplification by fluorescence in situ hybridisation (FISH) in excision specimens. Multiple patient, MRI and MRTA factors were assessed. Heterogeneity was evaluated using a filtration-histogram technique-based textural analysis on single axial proton density (PD) and coronal T1-W images of the most homogenously fatty component of the lesion. RESULTS: Thirty-three percent of the diagnoses of ALT/WDL vs lipoma were confirmed using FISH MDM2 analysis. ALT/WDLs were statistically different from lipomas in location (site in the body and depth from skin surface) and fat content, with p values of 0.021, 0.001, and 0.021 respectively. Nine of 36 (25%) texture parameters had significant differences between ALT/WDLs and lipomas on axial PD MRTA, with the most significant results at medium and coarse texture scales particularly mean intensity (p = 0.003) at SSF = 6, and kurtosis (p = 0.012) at SSF = 5. A cut-off value of < 304 for coarse-filtered texture on axial PD MRI identified ALT from lipoma with a sensitivity and specificity of 70% (AUC = 0.73, p = 0.003). CONCLUSIONS: Texture heterogeneity quantified at fine, medium, and coarse texture scales are significant differentiators of lipoma and ALT/WDL with the difference particularly marked in medium and coarse texture scales for two MR TA parameters: mean and kurtosis.

The differentiation between aneurysmal bone cyst and telangiectatic osteosarcoma: a clinical, radiographic and MRI study.

OBJECTIVES: Aneurysmal bone cyst (ABC) and telangiectatic osteosarcoma (TOS) share several clinical and imaging features, including young presentation, long bone involvement, lytic appearance on radiography and fluid-fluid levels on MRI. Therefore, they may be difficult to differentiate. The aim of this study is to identify clinical, radiological and MRI features which aid differentiation of the two lesions. MATERIALS AND METHODS: Retrospective review of all histologically confirmed ABC and TOS over an 11-year period. Data recorded include age at presentation, sex, skeletal location and various radiographic and MRI features. RESULTS: This retrospective study included 183 patients, 92 males and 91 females. Mean age at presentation of 18.4 years (range 1-70 years); 152 cases of ABC and 31 TOS. No significant difference between age and sex. TOS was significantly less likely to involve the axial skeleton; no difference related to location within the bone. Radiographic findings significantly favouring ABC included a less aggressive pattern of bone destruction, a purely lytic appearance, an expanded but intact cortex, no periosteal response and no soft tissue mass. MRI features significantly favouring ABC included smaller tumour size (maximum mean dimension 46 mm compared to 95 mm for TOS), absence of soft tissue mass, > 2/3 of the lesion filled with fluid levels and thin septal enhancement following contrast. CONCLUSIONS: Several radiographic and MRI features aid in the differentiation between ABC and TOS. Lesions with a geographic Type 1A or IB pattern of bone destruction which are completely filled with FFLs on MRI can confidently be diagnosed as ABC.

The radiological diagnosis of extra-articular posteromedial talocalcaneal coalition.

OBJECTIVES: Extra-articular posteromedial talocalcaneal coalition (EA-PM TCC) accounts for approximately one-third of TCC, but its radiographic features are not well-described. The current study aims to compare the radiographic features of EA-PM TCC with normal ankles and with the commoner forms of TCC. MATERIALS AND METHODS: A retrospective review of cases of TCC over 12 years for whom radiographs, CT, and/or MRI study were available. Radiographs were assessed by 2 radiologists for the presence of the C-sign, talar beak, dysmorphic sustentaculum, absent middle facet, and prominence of the posterior subtalar joint. TCC was classified by a third radiologist based on CT/MRI findings into 3 groups: no TCC, EA-PM TCC, and other TCCs. The radiographic findings for the 3 groups were compared. RESULTS: The study included 50 patients, 28 males and 22 females with a mean age of 21.1 years (range 8-70 years). In 15 patients, both ankles had been imaged, resulting in a total of 65 cases. In 17 ankles, no TCC was identified, while 15 ankles were classified as EA-PM TCC and 33 as having other types of TCC. There were no statistically significant differentiating radiological features between the groups with no TCC and EA-PM TCC apart from prominence of the posterior subtalar joint, while only the C-sign allowed identification of patients with other types of TCC. CONCLUSIONS: The study suggests that EA-PM TCC cannot be diagnosed based on the classical indirect radiological signs of TCC, but can be identified by prominence of the posterior subtalar joint.

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

STUDY OBJECTIVES: Current evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects. METHODS: Twenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures. RESULTS: Baseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose. CONCLUSIONS: These findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present.

Sickle cell microvascular paradox-oxygen supply-demand mismatch.

We have previously demonstrated that sickle cell disease (SCD) patients maintain normal global systemic and cerebral oxygen delivery by increasing cardiac output. However, ischemic end-organ injury remains common suggesting that tissue oxygen delivery may be impaired by microvascular dysregulation or damage. To test this hypothesis, we performed fingertip laser Doppler flowmetry measurements at the base of the nailbed and regional oxygen saturation (rSO2 ) on the dorsal surface of the same hand. This was done during flow mediated dilation (FMD) studies in 26 chronically transfused SCD, 75 non-transfused SCD, and 18 control subjects. Chronically transfused SCD patients were studied prior to and following a single transfusion and there was no acute change in rSO2 or perfusion. Laser Doppler estimates of resting perfusion were 76% higher in non-transfused and 110% higher in transfused SCD patients, compared to control subjects. In contrast, rSO2 was 12 saturation points lower in non-transfused SCD patients, but normal in the transfused SCD patients. During cuff occlusion, rSO2 declined at the same rate in all subjects suggesting similar intrinsic oxygen consumption rates. Upon cuff release, laser doppler post occlusive hyperemia was blunted in SCD patients in proportion to their resting perfusion values. Transfusion therapy did not improve the hyperemia response. FMD was impaired in SCD subjects but partially ameliorated in transfused SCD subjects. Taken together, non-transfused SCD subjects demonstrate impaired conduit artery FMD, impaired microcirculatory post-occlusive hyperemia, and resting hypoxia in the hand despite compensated oxygen delivery, suggesting impaired oxygen supply-demand matching. Transfusion improves FMD and oxygen supply-demand matching but not microcirculation hyperemic response.