The impact of telemonitoring on correct drug use, complications and quality of life among patients with multiple myeloma (ITUMM): A study protocol for an open-label, parallel-group, randomized controlled trial.

INTRODUCTION: Multiple myeloma (MM) is the second most common hematologic malignancy. MM is associated with significant morbidity due to its end-organ destruction and is a disease of the older population. Although survival rates for MM have improved over the last decade, due to an increase in treatment options, the disease remains incurable. Expensive (oral) agents are widely used in MM patients; however, tools for supporting patients in complex treatment regimens are scarce. To investigate if a tool will support MM patients and healthcare professionals, the MM e-coach was developed and tested. The aim of this study is to study the impact of telemonitoring on adherence, complications and quality of life in patients with MM (ITUMM study). METHODS: A two-arm open-label parallel-group randomized controlled trial will be conducted between March 2021 and June 2024 to compare the telemonitoring (MM e-coach) with standard MM care. This study aimed to recruit 150 patients with recently diagnosed multiple myeloma (RDMM), starting first or second line of treatment. Blinded primary outcome is adherence by pill count after start of treatment at 1-3 months. Secondary outcomes are patient reported outcomes: GFI, EQ-5D-5L, EORTC-QLQ-C30, SDM-Q-9, MARS-5, single item questions, PREMs, adverse events, OS and PFS. Patient reported outcomes were developed and integrated in the e-coach MM to regularly measure digitized outcomes of MM patients from time of RDMM until 12 months post-diagnosis. Online measurements will be performed at baseline (0), 3, 6, 9 and 12 months. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Ethics Committee of the Isala klinieken in The Netherlands (No. 201111) at 25 February 2021. Study results will be disseminated to the relevant healthcare communities by publication in peer-reviewed journals, and at scientific and clinical conferences. STUDY REGISTRATION NUMBER: ClinicalTrials.gov number: NCT05964270 and ABR number: NL75771.075.20.

Mid-term results of cemented hip arthroplasties through the direct anterior approach in the lateral decubitus position: a retrospective cohort study.

BACKGROUND: Reports show a high complication rate when starting with the Direct Anterior Approach (DAA) in a supine position for hip arthroplasty. The DAA with the patient in lateral decubitus position may avoid this problem because it supposedly provides better visibility, especially on the femoral side. However, this approach did show a rather high complication rate during the adoption of the approach at 1 year follow up in our previous report. We were interested what the overall 7 year survival estimate would be and whether improvement could be seen with growing experience. METHODS: A cohort of patients undergoing total hip arthroplasty right from the start of applying the DAA in lateral decubitus position was analysed. RESULTS: In total 175 hip prostheses (162 patients) were evaluated. The 7-year survival estimate was 95.1%, 95 CI: 91.8-98.4%. In 6 of 8 revisions there was aseptic loosening of the stem. By dividing the cohort into 3 consecutive groups in time we did not see a significantly improving revision rate. CONCLUSIONS: In our experience, the adoption of the direct anterior approach in lateral decubitus position caused a relatively low 7-year survival estimate without an apparent decrease with growing experience, however given the low number of cases further research is needed to investigate the long-term risk of adopting a new approach.

Glucose measurements with accu check inform II versus hexokinase plasma method during surgery under general anesthesia, an observational cohort study.

PURPOSE: Limited research exists on translation of in-vitro glucose measurement interfering compounds to the in-vivo situation. We investigated whether Point-of-Care glucose measurements by Accu Chek Inform II (ACI II) were accurate to monitor glucose concentrations during surgery with general anesthesia by comparing with the reference laboratory hexokinase plasma glucose test. METHOD: Patients undergoing surgery with general anesthesia were included. Anesthesia was maintained with either Sevoflurane or Total intravenous anesthesia (TIVA). Prior to and after induction, blood glucose was measured with ACI II and the hexokinase test. Bland-Altman analysis was performed to assess method agreement. Subgroup analyses on glucose measurement differences per type of maintenance anesthesia were performed. RESULTS: Thirty-nine patients were included, and 78 measurements were performed. All paired measurements had clinically acceptable agreement with a percentage error of 10.0% (95% CI 8.0 to 11.9). The mean difference (95% limits of agreement) between ACI II and hexokinase for all measurements was 0.0 mmol/L (-0.7 to 0.7 mmol/L). Before induction (n = 39), mean difference was -0.1 mmol/L (-0.6 to 0.4 mmol/L), and after induction (n = 39), mean difference was 0.1 mmol/L (-0.8 to 0.9 mmol/L). Further investigation showed the difference varied per test for patients receiving Sevoflurane compared to patients receiving TIVA (-0.2 ± 0.4 mmol/L vs. 0.4 ± 0.3 mmol/L, p < 0.001). Before and after induction, the difference between ACI II and hexokinase measurements increased for patients receiving Sevoflurane compared to patients receiving TIVA (0.4 ± 0.4 mmol/L vs. -0.4 ± 0.3 mmol/L, p < 0.001). CONCLUSION: The agreement between glucose measurements using ACI II and the reference laboratory hexokinase test was clinically acceptable with a percentage error of 10.0% (95% CI 8.0 to 11.9). The use of TIVA may negatively affect the measurement performance of the ACI II.

Frozen section diagnosis of borderline ovarian tumors with suspicious features of invasive cancer is a devil's dilemma for the surgeon: A systematic review and meta-analysis.

INTRODUCTION: Frozen section diagnoses of borderline ovarian tumors are not always straightforward and a borderline frozen section diagnosis with suspicious features of invasive carcinoma (reported as "at least borderline" or synonymous descriptions) presents us with the dilemma of whether or not to perform a full surgical staging procedure. By performing a systematic review and meta-analysis, the prevalence of straightforward borderline and "at least borderline" frozen section diagnoses, as well as proportion of patients with a final diagnosis of invasive carcinoma in these cases, were assessed and compared, as quantification of this dilemma may help us with the issue of this clinical decision. MATERIAL AND METHODS: PubMed, EMBASE and Cochrane library databases were searched and studies discussing "at least borderline" frozen section diagnoses were included in the review. Numbers of specific frozen section diagnoses and subsequent final histological diagnoses were extracted and pooled analysis was performed to compare the proportion of patients diagnosed with invasive carcinoma following borderline and "at least borderline" frozen section diagnoses, presented as risk ratio and risk difference with 95% confidence intervals (95% CI). RESULTS: Of 4940 screened records, eight studies were considered eligible for quantitative analysis. A total of 921 women was identified and 230 (25.0%) of these women were diagnosed with "at least borderline" ovarian tumor at the time of frozen section. Final histological diagnoses were reported in five studies, including 61 women with an "at least borderline" diagnosis and 290 women with a straightforward borderline frozen section diagnosis. Twenty-five of 61 women (41.0%) of the "at least borderline" group had invasive cancer at final diagnosis, compared with 28 of 290 women (9.7%) of the straightforward borderline frozen section group (risk difference -0.34, 95% CI -0.53 to -0.15; relative risk 0.25, 95% CI 0.13-0.50). CONCLUSIONS: Women diagnosed with "at least borderline" frozen section diagnoses were found to have a higher chance of carcinoma upon final diagnosis when compared with women with a straightforward borderline frozen section diagnosis (41.0% vs 9.7%). Especially in the serous subtype, and after preoperative consent, full staging during initial surgery might be considered in these cases to prevent a second surgical procedure.

Use of multiparametric MRI to characterize uterine fibroid tissue types.

BACKGROUND: Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scaled Signal Intensity (SSI) are used to predict treatment outcome but both screening-tools appear to be suboptimal. Therefore, multiparametric and quantitative MRI was studied to evaluate various biological characteristics of UF. METHODS: 87 patients with UF underwent an MRI-examination. Differences between UF tissues and myometrium were investigated using T2-mapping, Apparent Diffusion Coefficient (ADC) maps with different b-value combinations, contrast-enhanced T1-weighted and T2-weighted imaging. Additionally, the Funaki classification and SSI were calculated. RESULTS: Significant differences between myometrium and UF tissue in T2-mapping (p = 0.001), long-TE ADC low b-values (p = 0.002), ADC all b-values (p < 0.001) and high b-values (p < 0.001) were found. Significant differences between Funaki type 3 versus type 1 and 2 were observed in SSI (p < 0.001) and T2-values (p < 0.001). Significant correlations were found between SSI and T2-mapping (p < 0.001; ρs = 0.82), ADC all b-values (p = 0.004; ρs = 0.31), ADC high b-values (p < 0.001; ρs = 0.44) and long-TE ADC low b-values (p = 0.004; ρs = 0.31). CONCLUSIONS: Quantitative MR-data allowed us to distinguish UF tissue from myometrium and to discriminate different UF tissue types and may, therefore, be a useful tool to predict treatment outcome/determine optimal treatment modality.

[Hypoxaemia during non-intubated adenotonsillectomy; more common in sitting or supine position?] / Hypoxemie bij adenotonsillectomie zonder intubatie: vaker in liggende of zittende operatiehouding?

OBJECTIVE: To investigate the incidence of hypoxaemia, bradycardia and post-operative bleeding in non-intubated Sluder method adenotonsillectomy patients in sitting versus supine position. DESIGN: Explorative study. METHOD: A retrospective database was drawn up with data from all patients on whom a Sluder method non-intubated adenotonsillectomy was performed in a Dutch district general hospital between 01 January 2012 and 01 May 2018. Depending on the preference of the surgeon and following discussion with the anaesthesiologist, the operation was performed with the patient in either a sitting or supine position. The primary outcome measure was hypoxaemia, defined as SpO2 < 85% for ≥ 60 seconds. Secondary outcome measures included bradycardia and post-operative bleeding. RESULTS: We analysed the data of 723 adenotonsillectomy patients (46% female, average age 4.5 years), of whom 193 (27%) in sitting and 530 (73%) in supine position. Hypoxaemia occurred in 13 (7%) 'sitting' cohort patients and in 13 (2%) of the supine cohort patients (p = 0.011). No perioperative complications developed as a result of the hypoxaemia. The frequency of bradycardia did not differ between the two cohorts (4 vs 2%; p = 0.442). None of the patients developed both hypoxaemia and bradycardia. In 8 (1%) patients, a secondary intervention was required due to the occurrence of post-operative haemorrhage. CONCLUSION: Patients who undergo non-intubated Sluder guillotine method adenotonsillectomy when in a sitting position are more likely to develop hypoxaemia than those who are operated on in a supine position. In order to make an informed recommendation, a randomized trial is indicated.

Magnetic resonance-high intensity focused ultrasound (MR-HIFU) therapy of symptomatic uterine fibroids with unrestrictive treatment protocols: A systematic review and meta-analysis.

PURPOSE: Reevaluation of the effectiveness of Magnetic Resonance-High Intensity Focused Ultrasound (MR-HIFU) therapy for uterine fibroids by excluding studies with restrictive treatment protocols that are no longer used. METHODS: The National Guideline Clearinghouse, Cochrane Library, TRIP, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) databases were searched from inception until the 22nd of June 2018. Keywords included "MR-HIFU", "MRgFUS", and "Leiomyoma". Only studies about MR-HIFU treatment of uterine fibroids with at least three months of clinical follow-up were evaluated for inclusion. Treatments with ultrasound-guided HIFU devices or protocols not aiming for complete ablation were eliminated. The primary outcome was the improvement in fibroid-related symptoms. Technical outcomes included screening and treatment failures, treatment time, application of bowel-interference mitigation strategies and the Non-Perfused Volume (NPV) percentage. Other secondary outcomes were the quality of life, fibroid shrinkage, safety, re-interventions, reproductive outcomes, and costs. Meta-analysis was performed using a random-effects model (DerSimonian and Laird). RESULTS: A total of 18 articles (1323 treated patients) met the inclusion criteria. All selected studies were case series except for one cross-over trial. Overall, the quality of the evidence was poor to moderate. The mean NPV% directly post-treatment was 68.1%. The use of bowel-interference mitigation strategies may lead to increased NPV%. The mean symptom reduction at 12-months was 59.9% and fibroid shrinkage was 37.7%. The number of adverse events was low (8.7%), stratification showed a difference between HIFU systems. The re-intervention percentage at 3-33.6 months follow-up ranged from 0 to 21%. Longer follow-up was associated with a higher risk at re-interventions. Reproductive outcomes and costs couldn't be analyzed. CONCLUSIONS: Treatment guidelines aiming for complete ablation enhanced the effectiveness of MR-HIFU therapy. However, controlled trials should define the role of MR-HIFU in the management of uterine fibroids.

CT radiation dose reduction in patients with total hip arthroplasties using model-based iterative reconstruction and orthopaedic metal artefact reduction.

OBJECTIVE: To evaluate the impact of radiation dose reduction on image quality in patients with metal-on-metal total hip arthroplasties (THAs) using model-based iterative reconstruction (MBIR) combined with orthopaedic metal artefact reduction (O-MAR). MATERIALS AND METHODS: Patients with metal-on-metal THAs received a pelvic CT with a full (FD) and a reduced radiation dose (RD) with -20%, -40%, -57%, or -80% CT radiation dose respectively, when assigned to group 1, 2, 3, or 4 respectively. FD acquisitions were reconstructed with iterative reconstruction, iDose4. RD acquisitions were additionally reconstructed with iterative model-based reconstruction (IMR) levels 1-3 with different levels of noise suppression. CT numbers, noise and contrast-to-noise ratios were measured in muscle, fat and bladder. Subjective image quality was evaluated on seven aspects including artefacts, osseous structures, prosthetic components and soft tissues. RESULTS: Seventy-six patients were randomly assigned to one of the four groups. While reducing radiation dose by 20%, 40%, 57%, or 80% in combination with IMR, CT numbers remained constant. Compared with iDose4, the noise decreased (p < 0.001) and contrast-to-noise ratios increased (p < 0.001) with IMR. O-MAR improved CT number accuracy in the bladder and reduced noise in the bladder, muscle and fat (p < 0.01). Subjective image quality was rated lower on RD IMR images than FD iDose4 images on all seven aspects (p < 0.05) and was not related to the applied radiation dose reduction. CONCLUSION: In RD IMR with O-MAR images, CT numbers remained constant, noise decreased and contrast-to-noise ratios between muscle and fat increased compared with FD iDose4 with O-MAR images in patients with metal-on-metal THAs. Subjective image quality reduced, regardless of the degree of radiation dose reduction.

Radioactive seed localization is the preferred technique in nonpalpable breast cancer compared with wire-guided localization and radioguided occult lesion localization.

OBJECTIVES: Three commonly used techniques for localization of nonpalpable breast cancer are radioactive seed localization (RSL), wire-guided localization (WGL) and radioguided occult lesion localization (ROLL). In this study, we analysed the surgical margins of these three techniques. METHODS: Women diagnosed with nonpalpable breast cancer undergoing breast-conserving surgery with one of the above-mentioned techniques were retrospectively included. The primary outcome parameter was tumour-free margin rate. Secondary outcomes were re-excision rate, recurrence of disease and volume of removed tissue. RESULTS: In total, 272 women were included in whom RSL (n=69), WGL (n=76) or ROLL (n=137) was performed. RSL showed a higher tumour-free margin rate [64 (92.8%)] compared with WGL [51 (67.1%)] and ROLL [113 (82.5%)] (P=0.001). In our multivariable analysis, RSL showed a higher tumour-free margin rate as well compared with WGL (P=0.036) and ROLL (P=0.049). Also, fewer re-excisions were encountered using RSL [5 (7.2%)] compared with WGL [13 (17.1%)] and ROLL [15 (10.9%)] (P=0.171). In 11 patients (WGL n=2, ROLL n=9), recurrence of disease occurred, despite a radical excision. The mean resection volumes were comparable within the three groups. CONCLUSION: RSL results in a higher tumour-free margin rate in nonpalpable breast tumours compared with WGL and ROLL. Therefore, we prefer using RSL in nonpalpable breast tumours.

Arnica Ointment 10% Does Not Improve Upper Blepharoplasty Outcome: A Randomized, Placebo-Controlled Trial.

BACKGROUND: It has been suggested that arnica can reduce postoperative edema and ecchymosis associated with cosmetic surgical procedures and improve outcome. Despite a high incidence of arnica use among upper blepharoplasty patients, evidence to support its treatment effect is lacking. The authors performed a randomized, double-blind, placebo-controlled trial to investigate the efficacy of arnica ointment after upper blepharoplasty. METHODS: One hundred thirty-six bilateral upper blepharoplasty patients were randomized between arnica ointment 10% and placebo ointment. In both study arms, one periorbital area was designated as the treatment side (either arnica or placebo ointment), and the contralateral side served as an untreated (no ointment) internal control. As the primary endpoint, the overall periorbital appearance as based on light photography and judged by a medical and nonmedical panel, was assessed after 3 days, 7 days, and 6 weeks. Secondary endpoints were swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome. RESULTS: There was no significant difference between arnica and placebo in overall judgment of periorbital appearance 3 days, 7 days, and 6 weeks after surgery. Furthermore, swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome did not differ between arnica and placebo. Postoperative outcome in untreated eyelids was not different from eyelids treated with either arnica or placebo on any of the studied outcome measures. CONCLUSION: The authors' study demonstrates that topical arnica ointment after upper blepharoplasty does not improve postoperative outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

CT-based quantification of bone stock in large head metal-on-metal unilateral total hip replacements.

PURPOSE: To explore ipsilateral and contralateral acetabular roof bone stock density in unilateral large head MoM THA whether there is a significant lower acetabular bone stock in the hip with a metal-on-metal (MoM) total hip replacement compared to the contralateral side. Second part of this study is to examine if there are any associates with regard to potential bone stock density difference. MATERIALS & METHODS: A database of 317 patients with unilateral metal-on-metal (MoM) total hip replacements was set up retrospectively for this study. On computed tomography scans, conducted after a relative short in situ time period averaging 2.8 years, regions-of-interests were drawn in the trabecular bone of the acetabulum to measure average Hounsfield Units (HU). HU differences were calculated and tested by Wilcoxon signed-rank test. Univariate analysis was conducted to examine associates of potential bone loss. RESULTS: In a population of 317 patients (156 male, 161 female) with an average age of 61.9 ± 7.8, the median HU on the side of the MoM replacement was 123.3 (7.6-375.4). On the contralateral side, median HU was 144.7 (-0.4 to 332.8). The median HU difference was 21.4 after a mean post-operative in situ time of 2.8 years. The Wilcoxon signed-rank test proved a significant difference (p<0.001). Univariate analyses show that the in situ time of the MoM THA has a significant correlation with the bone density difference. CONCLUSION: Results show a significant lower bone density at the acetabular roof at the side of the prosthesis compared with the contralateral side after short in situ time of the MoM THA in patients with unilateral MoM total hip replacements. In our patient population, the in situ time showed a significant association with the acetabular bone density difference. As acetabular roof bone stock measurements are feasible and show temporal decline this could become an important parameter to be used in orthopedic decision making for revision surgery.

Development and first validation of a simplified CT-based classification system of soft tissue changes in large-head metal-on-metal total hip replacement: intra- and interrater reliability and association with revision rates in a uniform cohort of 664 arthroplasties.

OBJECTIVE: After implantation of a metal-on-metal total hip arthroplasty (MoM THA), a large incidence of pseudotumor formation has been described recently. Several centers have invited patients for follow-up in order to screen for pseudotumor formation. The spectrum of abnormalities found by CT in MoM THA patients can be unfamiliar to radiologists and orthopedic surgeons. Previously, a CT five-point grading scale has been published. In this paper, a simplification into a three-point classification system gives insight in the morphological distinction of abnormalities of the postoperative hip capsule in MoM implants in relation to the decision for revision. The reliability of this simplified classification regarding intra- and interrater reliability and its association with revision rate is investigated and discussed. MATERIALS AND METHODS: All patients who underwent MoM THA in our hospital were invited for screening. Various clinical measures and CT scan were obtained in a cross-sectional fashion. A decision on revision surgery was made shortly after screening. CT scans were read in 582 patients, of which 82 patients were treated bilaterally. CT scans were independently single read by two board-certified radiologists and classified into categories I-V. In a second meeting, consensus was obtained. Categories were subsequently rubricated in class A (categories I and II), B (category III), and C (categories IV and V). Intra- and inter-radiologist agreement on MoM pathology was assessed by means of the weighted Cohen's kappa. Categorical data were presented as n (%), and tested by means of Fisher's exact test. Continuous data were presented as median (min-max) and tested by means of Mann-Whitney U test (two group comparison) or Kruskal-Wallis test (three group comparison). Logistic regression analysis was performed in order to study independence of CT class for association with revision surgery. Univariate statistically significant variables were entered in a multiple model. All statistical analysis was performed two-tailed using alpha 5% as the significance level. RESULTS: In total, 664 scores from 664 MoM hips obtained by two observers were available for analyses. Interobserver reliability for the non-simplified version (I-V) was κw = 0.71 (95% CI: 0.62-0.79), which indicates good agreement between the two musculoskeletal radiologists. Intra- and interobserver reliability for the simplified version (A-C) were respectively κw 0.78 (95% CI: 0.68-0.87), and κw = 0.71 (95% CI: 0.65-0.76). This indicates good agreement within and between the two observers. The simplified A-C version is significantly associated with revision exclusively due to MoM pathology, in both patients with unilateral MoM THA (p < 0.001) and patients with bilateral MoM THA (p < 0.044). The simplified A-C version is associated with several clinical measures. In patients with unilateral MoM THA, with or without contralateral THA, in situ time (p < 0.008), cobalt and chromium (p < 0.001) were statistically significant. In patients with bilateral MoM, cobalt (p < 0.001) and chromium (p < 0.027) were statistically significant. Revision is significantly associated with cup size (p < 0.001), anteversion of the cup (p < 0.004), serum ion levels of cobalt and chromium (p < 0.001) and the adapted classification system (p < 0.001). In univariate logistic regression analysis on revision, cup, anteversion of the cup, cobalt-chromium ion serum levels, and the simplified (A-C) CT category system were statistically significant. The simplified (A-C) CT category system was an independent associate of revision, in several multiple logistic regression models. CONCLUSIONS: The presented simplified CT grading system (A-C) in its first clinical validation on 48- and 64-multislice systems is reliable, showing good intra- and interrater reliability and is independently associated with revision surgery.

Assessment of the variations in fat content in normal liver using a fast MR imaging method in comparison with results obtained by spectroscopic imaging.

A recently published Dixon-based MRI method for quantifying liver fat content using dual-echo breath-hold gradient echo imaging was validated by phantom experiments and compared with results of biopsy in two patients (Radiology 2005;237:1048-1055). We applied this method in ten healthy volunteers and compared the outcomes with the results of MR spectroscopy (MRS), the gold standard in quantifying liver fat content. Novel was the use of spectroscopic imaging yielding the variations in fat content across the liver rather than a single value obtained by single voxel MRS. Compared with the results of MRS, liver fat content according to MRI was too high in nine subjects (range 3.3-10.7% vs. 0.9-7.7%) and correct in one (21.1 vs. 21.3%). Furthermore, in one of the ten subjects the MRI fat content according to the Dixon-based MRI method was incorrect due to a (100-x) versus x percent lipid content mix-up. The second problem was fixed by a minor adjustment of the MRI algorithm. Despite systematic overestimation of liver fat contents by MRI, Spearman's correlation between the adjusted MRI liver fat contents with MRS was high (r = 0.927, P < 0.001). Even after correction of the algorithm, the problem remaining with the Dixon-based MRI method for the assessment of liver fat content,is that, at the lower end range, liver fat content is systematically overestimated by 4%.