Improving Turnaround Time of Transabdominal Pelvic Ultrasounds with Ovarian Doppler in a Pediatric Emergency Department.

Introduction: Adnexal torsion is an emergent surgical condition. Transabdominal pelvic ultrasound (US) with ovarian Doppler is used to diagnose adnexal torsion and requires a sufficient bladder volume. Reduce the turnaround time for US by 25% in girls 8-18 years of age who present to the emergency department (ED) for 24 months. Methods: Our baseline period was from January 2020 to June 2021, and the intervention period was from July 2021 to June 2023. Patients 8-18 years old who required an US in the ED were included. There are two key drivers: early identification of US readiness and expeditious bladder filling. Interventions were (1) bladder volume screening; (2) utilization of bladder volume nomogram to identify US readiness; (3) epic order panels; and (4) rapid intravenous fluid method. The primary outcome was US turnaround time. Secondary outcomes were percentage of patients requiring invasive interventions to fill the bladder and patients with an US study duration of ≤45 minutes. The percent of patients screened by bladder scan was used as a process measure. Balancing measures used episodes of fluid overload and ED length of stay. Results: Turnaround time for USs improved from 112.4 to 101.6 minutes. The percentage of patients who had successful USs without invasive bladder filling improved from 32.1% to 42.6%. Bladder volume screening using a bladder scan increased from 40.3% to 82.9%. The successful first-pass US completion rate improved from 77% to 90% consistently. Conclusions: Through quality improvement methodology, we have identified pelvic US readiness earlier, eliminated some invasive bladder-filling measures, and implemented a rapid fluid protocol. We have sustained these successful results for 2 years. This study can be generalized to any ED with similar patients.

Curvature sensing lipid dynamics in a mitochondrial inner membrane model.

Membrane curvature is essential for many cellular structures and processes, and factors such as leaflet asymmetry, lipid composition, and proteins all play important roles. Cardiolipin is the signature lipid of mitochondrial membranes and is essential for maintaining the highly curved shapes of the inner mitochondrial membrane (IMM) and the spatial arrangement of membrane proteins. In this study, we investigate the partitioning behavior of various lipids present in the IMM using coarse-grained molecular dynamics simulations. This study explores curved bilayer systems containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CDL) in binary and ternary component mixtures. Curvature properties such as mean and Gaussian curvatures, as well as the distribution of lipids into the various curved regions of the cristae models, are quantified. Overall, this work represents an advance beyond previous studies on lipid curvature sensing by simulating these systems in a geometry that has the morphological features and scales of curvature consistent with regions of the IMM. We find that CDL has a stronger preference for accumulating in regions of negative curvature than PE lipids, in agreement with previous results. Furthermore, we find lipid partitioning propensity is dominated by sensitivity to mean curvature, while there is a weaker correlation with Gaussian curvature.

Maintenance lenalidomide in newly diagnosed transplant eligible and non-eligible myeloma patients; profiling second primary malignancies in 4358 patients treated in the Myeloma XI Trial.

Background: Early trials of long-term lenalidomide use reported an increased incidence of second primary malignancy (SPM), including acute myeloid leukaemia and myelodysplastic syndrome. Later, meta-analysis suggested the link to be secondary to lenalidomide in combination with melphalan. Methods: Myeloma XI is a large, phase III randomised trial in-which lenalidomide was used at induction and maintenance, in transplant eligible (TE) and non-eligible (TNE) newly diagnosed patients (NCT01554852). Here we present an analysis of SPM incidence and profile the SPM type to determine the impact of autologous stem cell transplantation (ASCT) and lenalidomide exposure in 4358 patients treated on study. Data collection took place from the start of the trial in May 2010, to May 2019, as per the protocol timeline. The Median follow-up following maintenance randomisation was 54.5 and 46.1 months for TE and TNE patients, respectively. Findings: In the TE pathway, the overall SPM incidence was 7.7% in lenalidomide maintenance patients compared to 3.2% in those being observed (p = 0.006). Although the TNE lenalidomide maintenance patients had the greatest SPM incidence (15.4%), this was not statistically significant when compared to the observed patients (10%, p = 0.10).The SPM incidence was higher in patients who received lenalidomide at induction and maintenance (double exposure), when compared to those treated with lenalidomide at one time point (single exposure). Again, this was most marked in TNE patients where the overall SPM incidence was 16.9% in double exposed patients, compared to 11.7% in single exposed patients, and 11.2% in patients who did not receive lenalidomide (p = 0.04). This is likely an effect of treatment duration, with the median number of cycles being 27 in the TNE double exposed patients, vs 6 in the single exposure patients.Haematological SPMs were uncommon, diagnosed in 50 patients (incidence 1.1%). The majority of cases were diagnosed in TE patients treated with lenalidomide maintenance (n = 25, incidence 2.8%), suggesting a possible link with melphalan. Non-melanoma skin cancer incidence was highest in patients receiving lenalidomide maintenance, particularly in TNE patients, where squamous cell carcinoma and basal cell carcinoma were diagnosed in 5.5% and 2.6% of patients, respectively. The incidence of most solid tumour types was higher in lenalidomide maintenance patients.Mortality due to progressive myeloma was reduced in patients receiving lenalidomide maintenance, noted to be 16.6% compared 22.6% in those observed in TE patients and 32.7% compared to 41.5% in TNE patients. SPM related mortality was low, 1.8% and 6.1% in TE and TNE lenalidomide maintenance patients, respectively, compared to 0.4% and 2.8% in those being observed. Interpretation: This provides reassurance that long-term lenalidomide treatment is safe and associated with improved outcomes in TE and TNE populations, although monitoring for SPM development should be incorporated into clinic review processes. Funding: Primary financial support was from Cancer Research UK [C1298/A10410].

Chemotherapy May Obviate Prophylactic Femoral Nail Surgery for Multiple Myeloma Patients With High Mirels' Score Lesions and Impending Pathological Hip Fracture.

Bone involvement presents in >80% of patients with multiple myeloma. This causes lytic lesions for which prophylactic surgery is indicated to prevent pathological fractures if the lesion is graded ≥9/12 on Mirels' score. Although successful, these surgeries have risks and extended recovery periods. We present a case indicating myeloma chemotherapy may obviate prophylactic femoral nailing for high Mirels' score lesions in the femoral head with impending pathological hip fracture. A 72-year-old woman presented in December 2017 with back pain. A plain X-ray indicated degenerative anterolisthesis in her lumbosacral spine. Serum analysis revealed abnormal protein, globulin, alkaline phosphatase, and albumin levels while protein electrophoresis and serum immunofixation revealed raised immunoglobulin A (IgA) kappa paraprotein and kappa serum free light chains, respectively. Whole-body CT scans showed widespread lytic bone lesions and bone marrow biopsy confirmed infiltration by plasma cells. She was diagnosed with International Staging System (ISS) stage 3 multiple myeloma, which was successfully treated with bortezomib, thalidomide and dexamethasone with regular bisphosphonates that year. She presented again to the hospital in June 2020 with acute back and pelvic pain; Her paraprotein and serum-free light chains had increased significantly from her previous clinic appointment, indicating serological progression. MRI showed a relapse of the myeloma deposits in her right femoral head and spine. The deposit in her femoral head was graded 10/12 on Mirels' score, which indicated prophylactic femoral nailing. Instead, the patient was treated with daratumumab, bortezomib, and dexamethasone with escalation to monthly zoledronic acid infusions, as it was thought surgery would provide limited cytoreductive effect, preventing chemotherapy for six weeks post-surgery, potentiating pathological hip fracture and disease progression at other sites. This resulted in a complete response, thus reducing the deposits such that the femoral lesion was graded <8 on Mirels' score, improved her pain, and restored her ability to traverse stairs. She remains in complete response with ongoing daratumumab and denosumab maintenance treatment as of December 2022. Chemotherapy and bisphosphonates substantially reduced the myeloma deposit in the femoral head such that indications of prophylactic surgery were eliminated according to Mirels' score recommendations. This reduced the risk of pathological hip fracture whilst eliminating surgical complications. Further research should be conducted into the safety and efficacy of this treatment regimen in patients with high Mirels' score lesions. With this knowledge, consideration can be taken as to whether prophylactic femoral nailing is necessary given strong indications.

Impact of Ultra High-risk Genetics on Real-world Outcomes of Transplant-eligible Multiple Myeloma Patients.

Refined prediction of early relapse following standard-of-care (SoC) autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) could inform real-world risk-stratified post-ASCT strategies. We investigated the impact of double hit genetics (≥2 adverse markers: t(4;14), t(14;16), t(14;20), gain(1q), del(17p)) on outcome in 139 NDMM patients who underwent SoC ASCT between January 2014 and October 2019 at our center. Double hit genetics were associated with a significantly shortened progression-free survival (hazard ratio [HR] = 4.27, P < 0.001) and overall survival (HR = 4.01, P = 0.03), and characterized most early relapses. Our results support the real-world utility of extended genetic profiling for improved risk prediction in NDMM.

Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial.

Prediction of individual patient benefit from lenalidomide (Len) maintenance after autologous stem cell transplant (ASCT) remains challenging. Here, we investigated extended molecular profiling for outcome prediction in patients in the National Cancer Research Institute Myeloma XI (MyXI) trial. Patients in the MyXI trial randomized to Len maintenance or observation after ASCT were genetically profiled for t(4;14), t(14;16), t(14;20), del(1p), gain(1q), and del(17p) and co-occurrence of risk markers was computed. Progression-free survival (PFS), subsequent progression (PFS2), and overall survival (OS) were calculated from maintenance randomization, and groups were compared using Cox proportional hazards regression. Of 556 patients, 17% with double-hit multiple myeloma (MM) (≥2 risk markers), 32% with single-hit (1 risk marker), and 51% without risk markers were analyzed. Single-hit MM derived the highest PFS benefit from Len maintenance, specifically, isolated del(1p), del(17p), and t(4;14), with ∼40-fold, 10-fold, and sevenfold reduced risk of progression or death (PFS), respectively, compared with observation. This benefit translated into improved PFS2 and OS for this group of patients compared with observation; median PFS was 10.9 vs 57.3 months for observation vs Len maintenance. Patients with isolated gain(1q) derived no benefit, and double-hit MM limited benefit (regardless or risk lesions involved) from Len maintenance. Extended genetic profiling identifies patients deriving exceptional benefit from Len maintenance and should be considered for newly diagnosed patients to support management discussions along their treatment pathway. This trial was registered at www.isrctn.com/ISRCTN49407852 as # ISRCTN49407852.

MUKtwelve protocol: a phase II randomised, controlled, open, parallel group, multicentre trial of selinexor, cyclophosphamide and prednisolone (SCP) versus cyclophosphamide and prednisolone (CP) in patients with relapsed or refractory multiple myeloma.

INTRODUCTION: Multiple myeloma is a malignancy of plasma cells with around 6000 new cases per year in the UK. Cyclophosphamide plus prednisolone is considered a standard of care for disease and symptom control in the advanced relapsed or refractory myeloma setting within the UK NHS. The selective nuclear export inhibitor, selinexor, has been relatively well tolerated in previous clinical trials and offers promise when used in combination with a wide range of other anti-cancer treatments. Here, we investigate if the addition of selinexor can improve responses to cyclophosphamide plus prednisolone without adding prohibitive toxicity. METHODS AND ANALYSIS: MUKtwelve is a UK-based, randomised, controlled, open, parallel group, multicentre phase II trial designed to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisolone (SCP) in patients with relapsed or refractory multiple myeloma. A calibration arm will receive cyclophosphamide and prednisolone alone (CP). Participants who experience disease progression on the CP arm may, if eligible, receive SCP.The MUKtwelve trial results will be the first to assess clinical efficacy of selinexor with low-dose CP in relapsed/refractory multiple myeloma. It is widely accepted that the relapsing-remitting nature of the disease is accompanied by cellular changes that often result in the requirement for novel agents and drug combinations to regain disease control. Patients also often experience cumulative toxicities throughout their treatments, limiting the treatment intensity that can be given at relapse. Thus, there is a need for novel effective combination therapies with acceptable toxicity profiles. ETHICS AND DISSEMINATION: Ethics approval is obtained. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15028850.

Gastric-Type Enteric Duplication Cyst Communicating with an Accessory Pancreatic Duct.

Enteric duplication cysts are rare congenital anomalies defined by the location along the gastrointestinal tract from which they communicate as well as the epithelial lining they contain. Enteric duplication cysts in communication with the pancreas are an even rarer subset that are often difficult to diagnose due to nonspecific presenting symptoms. In a pediatric patient with a history of recurrent pancreatitis episodes, a pancreatic duplication should be on the differential. High clinical suspicion and specific imaging characteristics can aid in the diagnosis. The management of pancreatic duplication cysts requires surgical excision or drainage procedures to alleviate symptoms and prevent associated complications such as recurrent pancreatitis, bleeding, bowel obstruction, or malignancy. Here we present a case of a gastric duplication cyst in communication with an accessory pancreatic lobe with special focus on the preoperative workup, intraoperative findings, and histopathologic examination. [Pediatr Ann. 2022;51(8):e324-e327.].

Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial.

INTRODUCTION: Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life. METHODS AND ANALYSIS: Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North East-Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN17973108, NCT03720041.

Accuracy of Chest Computed Tomography in Distinguishing Cystic Pleuropulmonary Blastoma From Benign Congenital Lung Malformations in Children.

Importance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear. Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children. Design, Setting, and Participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed from January 18 to September 6, 2020. Preoperative CT scans were interpreted independently by 9 experienced pediatric radiologists in a blinded fashion and analyzed from January 24, 2019, to September 6, 2020. Main Outcomes and Measures: Accuracy, sensitivity, and specificity of CT in correctly identifying children with malignant tumors. Results: Among 477 CT scans identified (282 boys [59%]; median age at CT, 3.6 months [IQR, 1.2-7.2 months]; median age at resection, 6.9 months [IQR, 4.2-12.8 months]), 40 cases were extensively reviewed; 9 cases (23%) had pathologically confirmed cystic PPB. The median age at CT was 7.3 months (IQR, 2.9-22.4 months), and median age at resection was 8.7 months (IQR, 5.0-24.4 months). The sensitivity of CT for detecting PPB was 58%, and the specificity was 83%. High suspicion for malignancy correlated with PPB pathology (odds ratio, 13.5; 95% CI, 2.7-67.3; P = .002). There was poor interrater reliability (κ = 0.36 [range, 0.06-0.64]; P < .001) and no significant difference in specific imaging characteristics between PPB and benign cystic lesions. The overall accuracy rate for distinguishing benign vs malignant lesions was 81%. Conclusions and Relevance: This study suggests that chest CT, the current criterion standard imaging modality to assess the lung parenchyma, may not accurately and reliably distinguish PPB from benign congenital lung malformations in children. In any cystic lung lesion without a prenatal diagnosis, operative management to confirm pathologic diagnosis is warranted.

Autologous Blood Injection With Dry-Needling vs Dry-Needling Alone Treatment for Chronic Plantar Fasciitis: A Randomized Controlled Trial.

BACKGROUND: Autologous blood injection (ABI) for patients with chronic plantar fasciitis has been promoted as an approach to improve outcomes over standard dry-needling approaches. The purpose of this trial was to investigate if there are improved outcomes following an ultrasonography-guided ABI compared to dry needling alone for patients with chronic plantar fasciitis. METHODS: A double-blinded (participant-blinded and observer-blinded) RCT within a single clinic enrolled 90 patients with symptoms of plantar fasciitis that had failed to improve with a minimum of 3 months of rehabilitation. The mean age was 49.5±8.9 years, 67% were female, and the mean symptom duration was 40.0±28.2 months (range: 8 months-10 years). Participants were randomized to receive ABI or an identical dry-needle fenestration-procedure without coadministration of autologous blood. All participants received identical structured rehabilitation and were followed up at 2, 6, 12, and 26 weeks. Outcome measures included local foot pain, validated foot patient-reported outcome measures (Foot Function Index-revised, Manchester-Oxford Foot Questionnaire, Foot and Ankle Ability Measure), measures of general function and "ability" (EuroQol [EQ]-5D-5L, Oswestry Disability Index), specific measures of activity (International Physical Activity Questionnaire), sleep (Pittsburgh Sleep Quality Index), and mood (Hospital Anxiety and Depression Scale). RESULTS: There were no significant between-group differences seen at any time-point studied. There were a number of statistically significant within-group improvements for local foot pain and function in both groups comparing baseline/follow-up data. Overall, levels of pain improved by 25% by 6 weeks and by 50% at 6 months. There were improvements in some generalized function markers. Activity rates did not change, demonstrating that improvements in pain did not necessarily influence physical activity. CONCLUSION: Coadministration of 3 mL of autologous blood had no additional effect compared to a dry-needling procedure alone for patients with chronic plantar fasciitis. LEVEL OF EVIDENCE: Level I, double-blinded randomized controlled trial.

Autologous stem cell transplantation is safe and effective for fit older myeloma patients: exploratory results from the Myeloma XI trial.

Autologous stem cell transplant (ASCT) remains standard of care for consolidation after induction therapy for eligible newly diagnosed myeloma patients. In recent clinical trials comparing ASCT to delayed ASCT, patients aged over 65 were excluded. In real-world practice stem cell transplants are not restricted to those aged under 65 and clinicians decide on transplant eligibility based on patient fitness rather than a strict age cut off. Data from the UK NCRI Myeloma XI trial, a large phase III randomised controlled trial with pathways for transplant-eligible (TE) and ineligible (TNE) patients, was used in an exploratory analysis to examine the efficacy and toxicity of ASCT in older patients including analysis using an agematched population to compare outcomes for patients receiving similar induction therapy with or without ASCT. Older patients within the TE pathway were less likely to undergo stem cell harvest at the end of induction than younger patients and of those patients undergoing ASCT there was a reduction in PFS associated with increasing age. ASCT in older patients was well tolerated with no difference in morbidity or mortality between patients aged.

Three Sessions of Radial Extracorporeal Shockwave Therapy Gives No Additional Benefit Over "Minimal-Dose" Radial Extracorporeal Shockwave Therapy for Patients With Chronic Greater Trochanteric Pain Syndrome: A Double-Blinded, Randomized, Controlled Trial.

OBJECTIVE: To investigate the outcomes following 3 weekly sessions of radial extracorporeal shockwave therapy (rESWT) in patients with chronic greater trochanteric pain syndrome (GTPS) presenting to an NHS Sports Medicine Clinic in the United Kingdom. DESIGN: Double-blinded randomized controlled trial. SETTING: A single NHS Sports Medicine Clinic, in the United Kingdom. PATIENTS: One hundred twenty patients in an NHS Sports Medicine clinic presenting with symptoms of GTPS who had failed to improve with a minimum of 3 months of rehabilitation were enrolled in the study and randomized equally to the intervention and treatment groups. Mean age was 60.6 ± 11.5 years; 82% were female, and the mean duration of symptoms was 45.4 ± 33.4 months (range, 6 months to 30 years). INTERVENTIONS: Participants were randomized to receive either 3 sessions of ESWT at either the "recommended"/"maximally comfortably tolerated" dose or at "minimal dose." All patients received a structured home exercise program involving flexibility, strength, and balance exercises. MAIN OUTCOME MEASURES: Follow-up was at 6 weeks, 3 months, and 6 months. Outcome measures included local hip pain, validated hip PROMs (Oxford hip score, non-arthritic hip score, Victorian Institute of Sport assessment questionnaire), and wider measures of function including sleep (Pittsburgh sleep quality index) and mood (hospital anxiety and depression scale). RESULTS: Results were available for 98% of patients at the 6-month period. There were statistically significant within-group improvements in pain, local function, and sleep seen in both groups. However, fewer benefits were seen in other outcome measures, including activity or mood. CONCLUSION: There were no time × group interaction effects seen between the groups at any time point, indicating that in the 3 sessions, the "recommended-dose" rESWT had no measurable benefit compared with "minimal dose" rESWT in this group of patients with GTPS. The underlying reason remains unclear; it may be that rESWT is ineffective in the treatment of patients with chronic GTPS, that "minimal dose" rESWT is sufficient for a therapeutic effect, or that a greater number of treatment sessions are required for maximal benefit. These issues need to be considered in further research.

Update on Clinically Relevant Genetic Testing in Pediatric Dermatology.

Clinical genetic testing enables the detection of specific gene mutations and variants that predispose individuals and their family members to disease. In recent years, tremendous strides have been made in the variety of clinically useful tests. Targeted testing for specific mutations that cause well-known syndromes enables the efficient diagnosis of genetic diseases with cutaneous manifestations. Testing for specific genes, however, may not always reveal a diagnosis. Expanded options are available. This review outlines the major types of available technology with a focus on those tests most useful for pediatric dermatologists.

Quality Improvement Project to Improve the Timeliness of Care for Children With Testicular Torsion in the Emergency Department.

Introduction: Testicular torsion (TT) is a urologic emergency that requires timely diagnosis and surgery. We noted variation in the door-to-detorsion times for patients with TT at our institution and our orchiectomy rate was 25.8%. We aimed to decrease the mean door-to-detorsion time from 124.6 to 114.6 minutes or less over 12 months. Methods: A multidisciplinary team of pediatric emergency medicine, radiology, urology physicians, and nurses, was formed. Our key drivers were use of Testicular Workup for Ischemia and Suspected Torsion (TWIST) score, prompt urology consultation, and efficient transfer from emergency department (ED) to operating room. Our process measures were TWIST score documentation rate and early urology consultation rate, outcome measures were door-to-detorsion time and orchiectomy rate, and balancing measure was ultrasound utilization rate. Early urology consultation occurred when the ED provider documented telephone communication with urology, immediately after placing a testicular doppler ultrasound (TDUS) order and before TDUS result. Results: Over 2 years, 45 cases of TT were diagnosed. TWIST score documentation was implemented and was sustained at 78%. This improved early urology consultations from 40% to 60%. The mean door-to-detorsion time improved from 124.6 to 114.2 minutes. There was no reduction in the orchiectomy rate or TDUS utilization rate. Conclusions: A quality improvement project to improve the timeliness of care for children with TT resulted in expedited ED care but did not impact the orchiectomy rate.

Prospective Evaluation of Whole-Body MRI versus FDG PET/CT for Lesion Detection in Participants with Myeloma.

Purpose To compare disease detection of myeloma using contemporary whole-body (WB) MRI and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT protocols and to correlate imaging with laboratory estimates of disease burden, including molecular characteristics. Materials and Methods In this observational, prospective study, participants were recruited from November 2015 to March 2018 who had a diagnosis of myeloma, who were planned to undergo chemotherapy and autologous stem cell transplantation, and who underwent baseline WB-MRI and FDG PET/CT (ClinicalTrials.gov identifier NCT02403102). Baseline clinical data, including genetics, were collected. Paired methods were used to compare burden and patterns of disease. Results Sixty participants (mean age, 60 years ± 9 [standard deviation]; 35 men) underwent baseline WB-MRI and FDG PET/CT. WB-MRI showed significantly higher detection for focal lesions at all anatomic sites (except ribs, scapulae, and clavicles) and for diffuse disease at all sites. Two participants presented with two or more focal lesions smaller than 5 mm only at WB-MRI but not FDG PET/CT. Participants with diffuse disease at MRI had higher plasma cell infiltration (percentage of nucleated cells: median, 60% [interquartile range {IQR}, 50%-61%] vs 15% [IQR, 4%-50%]; P = .03) and paraprotein levels (median, 32.0 g/L [IQR, 24.0-48.0 g/L] vs 20.0 g/L [IQR, 12.0-22.6 g/L]; P = .02) compared with those without diffuse disease. All genetically high-risk tumors showed diffuse infiltration at WB-MRI. Conclusion WB-MRI helped detect a higher number of myeloma lesions than FDG PET/CT, and diffuse disease detected at WB-MRI correlated with laboratory measures of disease burden and molecular markers of risk. Keywords: MR-Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Hematologic Diseases, Oncology Clinical trial registration no. NCT02403102. Supplemental material is available for this article. © RSNA, 2021.

Sex Differences in Multiple Myeloma Biology but not Clinical Outcomes: Results from 3894 Patients in the Myeloma XI Trial.

BACKGROUND: Sex differences in the incidence and outcomes of several cancers are well established. Multiple myeloma (MM) is a malignant plasma cell dyscrasia accounting for 2% of all new cancer cases in the UK. There is a clear sex disparity in MM incidence, with 57% of cases in males and 43% in females. The mechanisms behind this are not well understood and the impact of sex on patient outcomes has not been thoroughly explored. PATIENTS AND METHODS: We investigated the association of sex with baseline disease characteristics and outcome in 3894 patients recruited to the phase III UK NCRI Myeloma XI trial, in which treatment exposure to lenalidomide predominated. RESULTS: Females were significantly more likely to have the molecular lesions t(14;16) and del(17p) and were more likely to meet the cytogenetic classification of high-risk (HiR) or ultra-high-risk disease (UHiR). There was no difference in progression-free survival (PFS) or overall survival (OS) between the sexes in the overall population. CONCLUSION: Our data suggest that the genetic lesions involved in the initiation and progression of MM may be different between the sexes. Although females were more likely to have the poor prognosis lesions t(14;16) and del(17p), and were more likely to be assessed as having HiR or UHiR disease, this was not associated with reduced PFS or OS. In female patients the trial treatment may have been able to overcome some of the adverse effects of high-risk cytogenetic lesions. MicroAbstract Multiple myeloma (MM) is more common in males compared to females but the reasons behind this are not well understood and the impact of sex on patient outcomes is unclear. This study demonstrates fundamental differences in genetic lesions underlying the biology of MM between males and females. However, we found that progression-free survival and overall survival were the same in both sexes.

Pleuropulmonary Blastoma in Pediatric Lung Lesions.

BACKGROUND: Pediatric lung lesions are a group of mostly benign pulmonary anomalies with a broad spectrum of clinical disease and histopathology. Our objective was to evaluate the characteristics of children undergoing resection of a primary lung lesion and to identify preoperative risk factors for malignancy. METHODS: A retrospective cohort study was conducted by using an operative database of 521 primary lung lesions managed at 11 children's hospitals in the United States. Multivariable logistic regression was used to examine the relationship between preoperative characteristics and risk of malignancy, including pleuropulmonary blastoma (PPB). RESULTS: None of the 344 prenatally diagnosed lesions had malignant pathology (P < .0001). Among 177 children without a history of prenatal detection, 15 (8.7%) were classified as having a malignant tumor (type 1 PPB, n = 11; other PPB, n = 3; adenocarcinoma, n = 1) at a median age of 20.7 months (interquartile range, 7.9-58.1). Malignancy was associated with the DICER1 mutation in 8 (57%) PPB cases. No malignant lesion had a systemic feeding vessel (P = .0427). The sensitivity of preoperative chest computed tomography (CT) for detecting malignant pathology was 33.3% (95% confidence interval [CI]: 15.2-58.3). Multivariable logistic regression revealed that increased suspicion of malignancy by CT and bilateral disease were significant predictors of malignant pathology (odds ratios of 42.15 [95% CI, 7.43-340.3; P < .0001] and 42.03 [95% CI, 3.51-995.6; P = .0041], respectively). CONCLUSIONS: In pediatric lung masses initially diagnosed after birth, the risk of PPB approached 10%. These results strongly caution against routine nonoperative management in this patient population. DICER1 testing may be helpful given the poor sensitivity of CT for identifying malignant pathology.