Prevalence and progression of arterial calcifications on computed tomography in humans with knee osteoarthritis.

OBJECTIVES: Ectopic bone deposition plays an important role in osteoarthritis (OA) and in arterial wall disease. We aimed to investigate the prevalence and progression of arterial calcifications on whole-body computed tomography (CT) in persons with knee OA. METHODS: We included 118 (36 male) participants who satisfied the clinical American College of Rheumatology classification criteria for knee OA. Baseline investigations included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kellgren-Lawrence grading. At baseline and after two years, a whole-body CT was performed using the same scanner and protocol. Calcifications were quantified in the carotid, brachiocephalic, coronary, thoracic aortic, abdominal aortic, iliac, femoropopliteal and crural arteries. Multivariable linear and logistic regression modeling was used for analyses. RESULTS: At baseline males were 66.9 ± 7.7 and females were 68.0 ± 5.6 years old. Calcifications were common, all participants except two females had some calcification, and prevalence ranged between 41.8% and 94.4% for various arterial beds. Baseline femoropopliteal calcifications were associated with a higher Kellgren-Lawrence grade (more severe knee OA). Median annual progression rate was 13.1% in males and 15.7% in females. Structural OA severity was not associated with progression, but a five points lower (worse) WOMAC was associated with 1% faster progression of arterial calcifications (p= 0.008). CONCLUSION: Around age 70 nearly all persons with knee OA have arterial calcifications, which progress substantially. For further investigation into shared causality intervention studies are needed.

Do pseudoxanthoma elasticum patients have higher prevalence of kidney stones on computed tomography compared to hospital controls?

BACKGROUND: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by diminished inorganic plasma pyrophosphate (PPi), a strong calcification inhibitor. In addition to more typical calcification of skin, retina and arterial wall a diminished plasma PPi could lead to other ectopic calcification, such as formation of kidney stones. OBJECTIVE: To compare the prevalence of kidney stones between PXE patients and hospital controls on computed tomography (CT). METHOD: Low-dose CT images of PXE patients and controls were assessed by one radiologist, who was blinded for the diagnosis PXE. The number of kidney stones, and the size of the largest stone was recorded. Odds ratios (ORs) for having kidney stone were calculated using multivariable adjusted logistic regression. RESULTS: Our study comprised 273 PXE patients and 125 controls. The mean age of PXE patients was 51.5 ± 15.9 years compared to 54.9 ± 14.2 in the control group (p = 0.04) and PXE patients more often were women (63 vs. 50%, p = 0.013). The prevalence of kidney stones on CT was similar: 6.9% in PXE patients, compared to 5.6% in controls (p = 0.6). In the multivariate analysis adjusting for age and sex, there was no significantly higher odds for PXE patients on having stones, compared to controls: OR 1.48 (95% CI 0.62-3.96). CONCLUSION: There is no significant difference in the prevalence of incidental kidney stones on CT in PXE patients versus controls.

Quantitative MRI assessment of joint effusion using T2-relaxometry at 3 Tesla: a feasibility and reproducibility study.

OBJECTIVE: T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia? MATERIALS AND METHODS: In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7 min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis. RESULTS: We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24 years; range 17-33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76-0.97; circular ROI: ICC = 0.82, 95% CI 0.66-0.91) and interobserver agreement was adequate (manual ROI: LoA = 71 ms; circular ROI: LoA = 146 ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI - 0.06-0.94; circular RO: ICC = 0.99, 95% CI 0.98-0.99) and intraobserver agreement was good (manual ROI: LoA = 63 ms; circular ROI: LoA = 41 ms). CONCLUSION: T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility.

Screening for subclinical synovial proliferation in haemophilia: A systematic review and meta-analysis comparing physical examination and ultrasound.

INTRODUCTION: Ultrasound is increasingly used as addition to physical examination for detection of subclinical joint changes in haemophilia. However, the added value of ultrasound to physical examination for detecting synovial proliferation is not fully established. AIM: To determine the diagnostic accuracy of swelling at physical examination for ultrasound-detected synovial proliferation in haemophilia. METHODS: PubMed and EMBASE were searched up to 2 August 2022. Studies reporting original data on occurrence of swelling at physical examination and synovial proliferation on ultrasound of index joints in persons with haemophilia were included. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Diagnostic accuracy parameters of swelling at physical examination for ultrasound-detected synovial proliferation were determined. Summary sensitivity and specificity were calculated using a bivariate random-effects model. RESULTS: Fifteen studies reporting on swelling at physical examination and synovial proliferation on ultrasound in 2890 joints of 627 patients were included. Prevalence of subclinical synovial proliferation ranged between 0% and 55%. Sensitivity of swelling was low [summary estimate .34; 95% confidence interval (CI) .24-.46], while specificity was high (summary estimate .97; CI .92-.99). Predictive values varied widely due to inter-study differences in prevalence of synovial proliferation. CONCLUSION: Joint swelling has low sensitivity for presence of ultrasound-detected synovial proliferation in haemophilia, suggesting underestimation of synovial proliferation by physical examination alone. Consequently, ultrasound screening may generate important information on synovial changes which would otherwise remain undetected.

Monitoring recovery of joints after bleeding: Physical examination and ultrasound are complementary.

AIM: Traditionally, recovery after a joint bleed in people with bleeding disorders is evaluated by clinical symptoms. Following a bleed, however, asymptomatic joints may still show synovial hypertrophy and effusion on ultrasound. We evaluated the duration of full recovery from a joint bleed. Additionally, we determined how recovery differed when assessed by physical examination and ultrasound. METHODS: In this retrospective cohort study, we investigated joint bleeds in elbows, knees and ankles of people with haemophilia or Von Willebrand disease who attended the Van Creveldkliniek between 2016 and 2021. Physical examination (warmth, swelling, range of motion and gait) and ultrasound (effusion and synovial hypertrophy) were performed within 7 days after the onset of the bleed, 1 week after the first examination and monthly thereafter until patients had recovered fully. Joint bleeds were treated in line with the current international treatment guidelines. RESULTS: We evaluated 30 joint bleeds in 26 patients. The median recovery time was 1 month (range 0.3-5 months). In 47% of the joint bleeds, the recovery took longer than 1 month. The moment of recovery based on physical examination and ultrasound differed in 27% of bleeds. Both persistent abnormalities at physical examination in joints with normalized ultrasounds and persistent ultrasound findings in clinically recovered joints occurred. CONCLUSION: Joint bleed recovery can take long and recovery times differed per bleed. Recovery differed when assessed by physical examination or ultrasound. Therefore, both should be used to closely monitor recovery of joint bleeds and offer personalized care.

Pre-operative synovial hyperaemia in haemophilia patients undergoing total knee replacement and the effects of genicular artery embolization: A retrospective cohort study.

AIM: Haemophilia is characterized by recurrent joint bleeding caused by a lack of clotting factor VIII or IX. Due to repeated joint bleeding, end-stage arthropathy occurs in relatively young patients. A total knee replacement (TKR) can be a solution. However, TKR may be complicated by perioperative and postoperative bleeds despite clotting factor therapy. The aim of this study was to evaluate the prevalence of pre-operative synovial hyperaemia and the effects of Genicular Artery Embolization on synovial hyperaemia and 3-month postoperative joint bleeding. METHODS: In this retrospective cohort study, all patients with haemophilia who underwent periarticular catheter angiography between 2009 and 2020 were evaluated after written informed consent. Synovial hyperaemia on angiography was scored by an interventional radiologist. RESULTS: Thirty-three angiography procedures in 24 patients were evaluated. Median age was 54.4 years (IQR 48.4-65.9). Preoperative synovial hyperaemia was observed in 21/33 joints (64%). Moderate and severe synovial hyperaemia was observed in 10/33 joints (30%). Synovial hyperaemia decreased in 13/15 (87%) joints after embolization. Three-month postoperative joint bleeding occurred in 5/32 joints: in 2/18 joints (11%) without synovial hyperaemia and in 3/14 joints (21%) with mild synovial hypertrophy. Non-embolized and embolized joints did not differ regarding 3-month postoperative bleeding (P = .425). No complications were observed after embolization. CONCLUSION: One-third of patients with haemophilia requiring a TKR had moderate or severe synovial hyperaemia which can be reduced safely by Genicular Artery Embolization prior to TKR. Three-month postoperative bleeding appears to occur independently of the presence of residual mild synovial hyperaemia.

Structural changes after ankle joint distraction in haemophilic arthropathy: an explorative study investigating biochemical markers and 3D joint space width.

INTRODUCTION: Ankle joint distraction (AJD) is a promising treatment for patients with severe haemophilic ankle arthropathy (HAA). However, some patients showed no clinical improvement after AJD and these differences may be related to structural differences. AIM: Primarily to quantify the structural changes after AJD in patients with HAA by the use of 3D joint space width (JSW) measurements and biochemical markers and secondarily to correlate these findings with clinical pain/function. METHODS: Patients with haemophilia A/B who underwent AJD were included for this study. Bone contours on MRI (performed before and 12 and 36 months after AJD) were drawn manually and percentage change in JSW was calculated. Blood/urine (before and 6, 12, 24 and 36 months after AJD) was collected for biomarker measurement (COMP, CS846, C10C, CALC2, PRO-C2, CTX-II) and combined indexes of markers were calculated. Mixed effects models were used for analyses on group level. Structural changes were compared with clinical parameters. RESULTS: Eight patients were evaluated. On group level, percentage changes in JSW showed a slight decrease after 12 months followed by a non-statistically significant increase in JSW after 36 months compared to baseline. Biochemical marker collagen/cartilage formation also showed an initial decrease, followed by a trend towards net formation 12, 24 and 36 months after AJD. On individual patient level, no clear correlations between structural changes and clinical parameters were observed. CONCLUSION: Cartilage restoration activity on group level in patients with HAA after AJD was in concordance with clinical improvements. Correlating structural modifications with clinical parameters in the individual patient remains difficult.

Subclinical synovial proliferation in patients with severe haemophilia A: The value of ultrasound screening and biochemical markers.

AIM: Subclinical bleeding and inflammation play a role in progression of haemophilic arthropathy. Synovial proliferation is predictive of joint bleeding and its early detection may guide treatment changes and prevent arthropathy progression. This study evaluated the prevalence of active and inactive subclinical synovial proliferation and investigated potential biochemical blood/urine markers to identify patients with active subclinical synovial proliferation. METHODS: This cross-sectional study included patients with severe haemophilia A born 1970-2006 who were evaluated during routine clinic visits. Patients with (a history of) inhibitors or recent joint bleeding were excluded. Elbows, knees and ankles were examined for subclinical synovial proliferation by ultrasound and physical examination. Active synovial proliferation was distinguished from inactive synovial proliferation using predefined criteria. Blood/urine biochemical markers (serum osteopontin, sVCAM-1, Coll2-1, COMP, CS846, TIMP, and urinary CTX-II) were compared individually and as combined indexes between patients with and without active synovial proliferation. RESULTS: This cohort consisted of 79 patients with a median age of 31 years (range 16.5-50.8 years) with 62/79 (78%) of the patients using continuous prophylaxis. The annualized joint bleeding rate over the last 5 years was .6 (.2-1.1). Active (17/79, 22%) and inactive subclinical synovial proliferation (17/79, 22%) were both prevalent in this cohort. Biochemical markers were not correlated with active subclinical synovial proliferation. CONCLUSION: Subclinical synovial proliferation, both active and inactive, was prevalent in patients with severe haemophilia A with access to prophylaxis and would be overlooked without routinely performed ultrasounds. Biochemical markers were unable to identify patients with active subclinical synovial proliferation.

Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk.

OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0-12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSION: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality.

Ankle joint distraction is a promising alternative treatment for patients with severe haemophilic ankle arthropathy.

INTRODUCTION: Haemophilic ankle arthropathy (HAA) causes major morbidity. When conservative treatment fails, major surgical interventions are indicated. An alternative treatment to maintain joint mobility and postpone these interventions is desired. AIM: To gather prospective data on clinical/structural changes after ankle joint distraction (AJD) in HAA. METHODS: This study includes patients with severe HAA insufficiently responding to conservative treatment. AJD was performed during 8-10 weeks by use of an external frame. Questionnaires, physical examination and radiology were used to evaluate pain, function and structural changes before and 6, 12, 24 and 36 months after distraction. Mixed effect models were used for analysis. RESULTS: This study includes eight cases (21-53 years). The fixed effects estimates of the visual analogue score (0-10) improved from 7.5 at baseline to 3.4 (p = .023) 3 years after distraction. The Haemophilia Activities List (HAL, 0-100) for basic/complex lower extremities functions improved from respectively 29.6 and 31.5 to 54.3 (p = .015) and 50.7 (p = .031). Joint mobility was maintained. Magnetic resonance imaging (MRI) showed thickened cartilage and reduced bone marrow oedema and subchondral cysts. Pin tract infections (n = 6) were effectively treated and no adverse bleeding events occurred. At 3-year follow-up, in none of the patients the originally indicated arthrodesis was performed. CONCLUSION: This first prospective study showed that AJD in HAA results in decreased pain, improved function and decreased arthropathy-related MRI findings in the majority of patients for prolonged time. Although the study population is small and follow-up is relatively short, AJD may be promising to postpone invalidating interventions and might be a breakthrough treatment.

Clinical, radiological, and patient-reported outcomes 13 years after pedicle screw fixation with balloon-assisted endplate reduction and cement injection.

PURPOSE: In management of traumatic thoracolumbar burst fractures, short-segment pedicle screw fixation with balloon-assisted endplate reduction (BAER) and cement injection is a safe, feasible, and effective technique to maintain radiological alignment with minimum spinal segments involved. However, 20% of patients report daily discomfort despite good spinal alignment and fusion after this technique. This study provides clinical, radiological, and patient-reported outcomes after a minimum 13 years of follow-up. METHODS: Eighteen patients were invited at the outpatient clinic for clinical/radiological examinations. The cohort (originally 20 patients) was treated 13-14 years earlier with pedicle screw fixation, BAER, and cement injection for traumatic thoracolumbar burst fractures. Patient-reported outcome measures were obtained at time of examinations. Current data were compared with data obtained at 6 years of follow-up. RESULTS: Seventeen patients (median age 50; range 32-80) cooperated. No/minimal back pain was reported by 15 patients, and 12 patients returned to their previous heavy labor work. Median visual analog score of health (80%; 50-100%) was similar to results at 6 years (80%; 60-100% p = 0.259). An Oswestry Disability Index score of less than 20% (reflecting minimal disability) was reported by 14 patients, compared with 15 patients at 6 years of follow-up. No significant differences were found in wedge or Cobb angle between the time points. Intravertebral cement resorption was not observed. CONCLUSION: Results from this study suggest that, 13 years after pedicle screw fixation with BAER and cement injection for traumatic thoracolumbar burst fractures, functional performance, pain and radiological outcomes of the current cohort were stable or had slightly improved. These slides can be retrieved under Electronic Supplementary Material.

Criteria for Early-Phase Diffuse Idiopathic Skeletal Hyperostosis: Development and Validation.

Background Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the formation of new bone along the anterolateral spinal column at four adjacent vertebral bodies. Purpose To propose and validate criteria for the early phase of DISH by using CT data from two large-scale retrospective cohorts, each with 5-year follow-up. Materials and Methods For this retrospective study, CT data at baseline and follow-up in 1367 patients (cohort I) from 2004 to 2011 were evaluated by two observers to define no DISH, early-stage DISH, and definite DISH on the basis of interval development of consecutive complete or incomplete bone bridges. An independent group of 2267 participants from the COPDGene cohort from 2008 to 2016 was used to validate the early DISH criteria (cohort II). The sensitivity and specificity of early DISH criteria were based on findings in the last CT study as the reference standard by using a nested case-control design. κ Values were calculated between seven readers and with a 3-month interval for one reader. Results Cohort I consisted of 100% men, with a mean age of 60.0 years ± 5.6 (standard deviation) and a mean time between baseline and follow-up CT of 5.0 years ± 1.1. Cohort II consisted of 51% men, with a mean age of 59.9 years ± 8.6 and a mean time between baseline and follow-up CT of 5.4 years ± 0.5. In the derivation cohort, 55 patients comprised the early DISH group. Early DISH was defined as the presence of a spinal segment with a complete bone bridge with an adjacent segment of at least a near-complete bone bridge and another adjacent segment with at least the presence of newly formed bone or when three or more adjacent segments were recorded as showing a near-complete bone bridge. In the validation cohort, sensitivity for early DISH (vs no DISH) was 96% (99 of 103 participants; 95% confidence interval [CI]: 90%, 99%). The corresponding specificity was 83% (1695 of 2034 participants; 95% CI: 82%, 85%). The Fleiss κ for interrater reliability was 0.78 (95% CI: 0.77, 0.78), and the κ for intrarater reliability was 0.89 (95% CI: 0.82, 0.96). Conclusion Early diffuse idiopathic skeletal hyperostosis (DISH) criteria had high sensitivity and specificity for predicting the development of DISH. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Block in this issue.

Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study.

Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds were matched for age, sex and Factor VIII level or von Willebrand Factor activity in a nested case-control study within the Willebrand in the Netherlands study. Assessments included the Hemophilia Joint Health Score (0-124), Pettersson score (0-13 per joint X-ray), Hemophilia Activity List score (0-100), joint pain (Visual Analog Scale 0-10), and the Impact on Participation and Autonomy questionnaire (0-20). Arthropathy was defined as a Hemophilia Joint Health Score of 10 or higher, or a Pettersson score over 3 of at least one joint. We included 48 patients with verified joint bleeds (cases) and 48 controls: 60% males, mean age 46 years (range 18-80), median von Willebrand Factor activity 5 versus 8 IU/dL and Factor VIII 24 versus 36 IU/dL. Arthropathy occurred in 40% of the cases versus 10% of the controls (P<0.01). The cases reported more functional limitations compared to the controls (median Hemophilia Activity List score: 88 vs. 100, P<0.01). Arthropathy was related to joint pain and less social participation (Visual Analog Scale>3: 13 of 19 vs. 3 of 28, P<0.01, and median score on the participation questionnaire 6.1 vs. 0.9, P<0.01). In conclusion, arthropathy occurs in 40% of VWD patients after joint bleeds and is associated with pain, radiological abnormalities, functional limitations, and less social participation (Dutch trial register: NTR4548).

Scoring haemophilic arthropathy on X-rays: improving inter- and intra-observer reliability and agreement using a consensus atlas.

OBJECTIVES: The radiological Pettersson score (PS) is widely applied for classification of arthropathy to evaluate costly haemophilia treatment. This study aims to assess and improve inter- and intra-observer reliability and agreement of the PS. METHODS: Two series of X-rays (bilateral elbows, knees, and ankles) of 10 haemophilia patients (120 joints) with haemophilic arthropathy were scored by three observers according to the PS (maximum score 13/joint). Subsequently, (dis-)agreement in scoring was discussed until consensus. Example images were collected in an atlas. Thereafter, second series of 120 joints were scored using the atlas. One observer rescored the second series after three months. Reliability was assessed by intraclass correlation coefficients (ICC), agreement by limits of agreement (LoA). RESULTS: Median Pettersson score at joint level (PSjoint) of affected joints was 6 (interquartile range 3-9). Using the consensus atlas, inter-observer reliability of the PSjoint improved significantly from 0.94 (95 % confidence interval (CI) 0.91-0.96) to 0.97 (CI 0.96-0.98). LoA improved from ±1.7 to ±1.1 for the PSjoint. Therefore, true differences in arthropathy were differences in the PSjoint of >2 points. Intra-observer reliability of the PSjoint was 0.98 (CI 0.97-0.98), intra-observer LoA were ±0.9 points. CONCLUSIONS: Reliability and agreement of the PS improved by using a consensus atlas. KEY POINTS: • Reliability of the Pettersson score significantly improved using the consensus atlas. • The presented consensus atlas improved the agreement among observers. • The consensus atlas could be recommended to obtain a reproducible Pettersson score.

No role for standard imaging workup of patients with clinically evident necrotizing soft tissue infections: a national retrospective multicenter cohort study.

PURPOSE: To assess the diagnostic contribution of different imaging studies to diagnose necrotizing soft tissue infections (NSTIs) and the time to surgery in relation to imaging with the hypothesis that imaging studies may lead to significant delays without being able to sufficiently dismiss or confirm the diagnosis since a NSTI is a surgical diagnosis. METHODS: A retrospective multicenter cohort study of all NSTI patients between 2010 and 2020 was conducted. The primary outcome was the number of cases in which imaging contributed to or led to change in treatment. The secondary outcomes were time to treatment determined by the time from presentation to surgery and patient outcomes (amputation, intensive care unit (ICU) admission, length of ICU stay, hospital stay, and mortality). RESULTS: A total of 181 eligible NSTI patients were included. The overall mortality was 21% (n = 38). Ninety-eight patients (53%) received imaging in the diagnostic workup. In patients with a clinical suspicion of a NSTI, 81% (n = 85) went directly to the operating room and 19% (n = 20) underwent imaging before surgery; imaging was contributing in only 15% (n = 3) by ruling out or determining underlying causes. In patients without a clinical suspicion of a NSTI, the diagnosis of NSTI was considered in 35% and only after imaging was obtained. CONCLUSION: In patients with clinically evident NSTIs, there is no role for standard imaging workup unless it is used to examine underlying diseases (e.g., diverticulitis, pancreatitis). In atypical presenting NSTIs, CT or MRI scans provided the most useful information. To prevent unnecessary imaging and radiation and not delay treatment, the decision to perform imaging studies in patients with a clinical suspicion of a NSTI must be made extremely careful.

Arthropathy on X-rays in 363 persons with hemophilia: long-term development, and impact of birth cohort and inhibitor status.

Background: Arthropathy following repeated bleeding is common in persons with hemophilia. Since the introduction of prophylaxis, treatment has intensified and joint health has improved. However, data on the long-term development of arthropathy are still scant. Objectives: To evaluate long-term arthropathy development since the introduction of prophylaxis according to birth cohort, hemophilia severity, and inhibitor status. Methods: This single-center historic cohort study included persons with severe and moderate hemophilia A and hemophilia B born between 1935 and 2005. Arthropathy on X-rays was evaluated using the Pettersson score. Patient and joint characteristics were studied per birth cohort (<1970, 1970-1980, 1981-1990, and >1990) and compared according to hemophilia severity. The distribution of affected joints and cumulative incidence of arthropathy were analyzed. The association of Pettersson score with birth cohort and inhibitor characteristics was explored using multivariable regression analyses adjusted for age at evaluation. Results: In total, 1064 X-rays of 363 patients were analyzed. Of persons with severe hemophilia (n = 317, 87.3%), 244 (77.0%) developed arthropathy. Prophylaxis was started at younger ages over time, from a median of 18 to 2.1 years, and concomitantly, arthropathy decreased in consecutive birth cohorts. Ankles were most commonly affected in 188 of 258 (72.9%) patients. Persons with moderate hemophilia (n = 46, 12.7%) had a lower risk of arthropathy (27/46 [58.7%]), but a reduction over time was less pronounced. In the multivariable analyses, birth cohort and age at evaluation were predictors for the development of arthropathy, while inhibitor status showed no association. Conclusion: The development and severity of arthropathy have decreased over the past decades. However, patients have remained at risk for developing arthropathy, especially in their ankles.

Ultrasound in addition to clinical assessment of acute musculoskeletal complaints in bleeding disorders: impact on patient management.

Background: Ultrasound is increasingly used for musculoskeletal assessment in hemophilia care. Objectives: To evaluate the impact of point-of-care ultrasound added to clinical assessment for diagnosis and treatment of acute musculoskeletal episodes in a heterogeneous cohort of children and adults with hemophilia and von Willebrand disease (VWD). Methods: This prospective cross-sectional study consecutively included children and adults with hemophilia or VWD who visited the outpatient clinic with acute musculoskeletal complaints between March 2020 and May 2023. For all episodes, initial diagnosis and treatment determined by clinical assessment were recorded on a case report form. Subsequently, a physiotherapist (M.A.T. and J.B.) with knowledge of the clinical diagnosis performed point-of-care ultrasound. After ultrasound, updated diagnosis and treatment were recorded. Diagnosis and treatment before and after ultrasound were compared, and proportions of change with 95% CIs were determined. Results: We evaluated 77 episodes in 67 patients (median age, 24 years; IQR, 13-42 years). Before ultrasound, 37 joint bleeds, 13 muscle bleeds, and 27 other diagnoses were diagnosed. After ultrasound, 33 joint bleeds, 11 muscle bleeds, and 33 other diagnoses were confirmed. The diagnosis changed in 28 of 77 episodes (36%; 95% CI, 26%-48%). Nine joint bleeds and 2 muscle bleeds were missed by clinical assessment. Ultrasound findings changed treatment strategy in 30 of 77 episodes (39%; 95% CI, 28%-51%). Conclusion: Ultrasound in addition to clinical assessment of acute musculoskeletal complaints in people with hemophilia and VWD has an impact on diagnosis (36%) and treatment (39%), which supports the use of ultrasound in acute musculoskeletal complaints in hemophilia and VWD.

The prevalence of vertebral fractures in diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis: A systematic review and meta-analysis.

Background: Subjects with ankylosing spinal disorders, including diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) are more prone to vertebral fractures and frequently present with neurological deficit compared to the patients without an ankylosed spine. Moreover, prevalent vertebral fractures are an important predictor for subsequent fracture risk. However, the pooled fracture prevalence for DISH is unknown and less recent for AS. We aimed to systematically investigate the prevalence and risk of vertebral fractures in DISH and AS populations. Methods: Publications in Medline and EMBASE were searched from January 1980 until July 2023 for cohort studies reporting vertebral fractures in AS and DISH. Data on prevalence were pooled with random effects modeling after double arcsine transformation. Heterogeneity was assessed with I2 statistics and we performed subgroup analysis and meta-regression to explore sources of heterogeneity. Results: We included 7 studies on DISH (n = 1,193, total fractures = 231) with a pooled vertebral fracture prevalence of 22.6% (95%CI: 13.4%-33.4%). For AS, 26 studies were included (n = 2,875, total fractures = 460) with a pooled vertebral fracture prevalence of 15.2% (95%CI: 11.6%-19.1%). In general, fracture prevalence for AS remained similar for several study-level and clinically relevant characteristics, including study design, diagnostic criteria, spine level, and patient characteristics in subgroup analysis. AS publications from 2010 to 2020 showed higher fracture prevalence compared to 1990 to 2010 (18.6% vs. 11.6%). Fractures in DISH were most common at the thoracolumbar junction, whereas for AS, the most common location was the mid-thoracic spine. Conclusions: Vertebral fractures are prevalent in AS and DISH populations. Differences in fracture distribution along the spinal axis exist between the 2 disorders. Additional longitudinal studies are needed for incident fracture assessment in patients with ankylosing spinal disorders.

Towards Personalized Treatment in Haemophilia: The Role of Genetic Factors in Iron and Heme Control to Identify Patients at Risk for Haemophilic Arthropathy.

The treatment landscape for haemophilia is changing rapidly, creating opportunities for personalized treatment. As major morbidity is still caused by haemophilic arthropathy, understanding the factors affecting joint damage and joint damage progression might lead to more individualized treatment regimens. We investigated the association of HFE mutations or HMOX1 polymorphisms affecting iron/heme handling with radiographic joint damage in 252 haemophilia patients (severe and moderate). Although iron levels and transferrin saturation were significantly increased in the 95 patients with an HFE mutation, neither carrying this mutation nor the HMOX1 polymorphism was associated with radiographic joint damage, and the same was true after adjustment for well-known factors associated with arthropathy. In conclusion, this study does not support the hypothesis that HFE mutations or HMOX1 polymorphisms can be used to predict the development of haemophilic arthropathy.