A randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors.

BACKGROUND: Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. METHODS: In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS). RESULTS: Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event. CONCLUSION: SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.

Rare Thyroid Diseases Mimicking or Concealing Primitive Thyroid Neoplasms: A Call for a "Check and Double-Check" Clinical Mindset.

Clinical endocrinologists encounter in their practice patients with thyroid diseases on a daily basis. Still, diagnosis of rare structural thyroid disorders can be quite challenging. In some instances, they do not only impersonate but can also conceal, other conditions such as thyroid carcinomas. We describe a series of patients with structural thyroid disorders including 1) anaplastic thyroid carcinoma initially presenting with features of thyroid abscess; 2) unicentric hyaline vascular Castleman's disease of the thyroid embedded in a stroma of papillary thyroid carcinoma; and 3) primary thyroid lymphoma with a rapid and fulminant evolution. The common challenge in the diagnosis of these cases lies in both their low incidence and their complex presentation. We use the presentation of these cases to raise the attention related to their identification. We highlight the need for precision diagnosis to enable a patient-tailored management approach and improve patient outcomes.

Intratumoral administration of the immunologic adjuvant AS01B in combination with autologous CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells plus ipilimumab and intravenous nivolumab in patients with refractory advanced melanoma.

BACKGROUND: Patients with advanced melanoma who progress after treatment with immune checkpoint-inhibitors (ICI) and BRAF-/MEK-inhibitors (if BRAF V600 mutated) have no remaining effective treatment options. The presence of CD1c (BDCA-1)+ and CD141 (BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment correlates with pre-existing immune recognition and responsiveness to immune checkpoint blockade. The synthetic saponin-based immune adjuvant AS01B enhances adaptive immunity through the involvement of myDC. METHODS: In this first-in-human phase I clinical trial, patients with metastatic melanoma refractory to ICI and BRAF-/MEK inhibitors (when indicated) were recruited. Patients received an intravenous administration of low-dose nivolumab (10 mg, every 2 weeks) plus an intratumoral (IT) administration of 10 mg ipilimumab and 50 µg (0.5 mL) AS01B (every 2 weeks). All myDC, isolated from blood, were injected on day 2 into the same metastatic lesion. Tumor biopsies and blood samples were collected at baseline and repeatedly on treatment. Multiplex immunohistochemistry (mIHC) was performed on biopsy sections to characterize and quantify the IT and peritumoral immune cell composition. RESULTS: Study treatment was feasible and well tolerated without the occurrence of unexpected adverse events in all eight patients. Four patients (50%) obtained a complete response (CR) in the injected lesions. Of these, two patients obtained an overall CR, and one patient a partial response. All responses are ongoing after more than 1 year of follow-up. One additional patient had a stable disease as best response. The disease control rate was 50%. Median progression-free survival and overall survival were 24.1 and 41.9 weeks, respectively. Baseline tumor biopsies from patients who responded to treatment had features of T-cell exclusion. During treatment, there was an increased T-cell infiltration, with a reduced mean distance between T cells and tumor cells. Peripheral blood immune cell composition did not significantly change during study treatment. CONCLUSIONS: Combining an intratumoral injection of CD1c (BDCA-1)+ and CD141 (BDCA-3)+ myDC with repeated IT administration of ipilimumab and AS01B and systemic low-dose nivolumab is safe, feasible with promising early results, worthy of further clinical investigation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT03707808.

Towards validation in clinical routine: a comparative analysis of visual MTA ratings versus the automated ratio between inferior lateral ventricle and hippocampal volumes in Alzheimer's disease diagnosis.

PURPOSE: To assess the performance of the inferior lateral ventricle (ILV) to hippocampal (Hip) volume ratio on brain MRI, for Alzheimer's disease (AD) diagnostics, comparing it to individual automated ILV and hippocampal volumes, and visual medial temporal lobe atrophy (MTA) consensus ratings. METHODS: One-hundred-twelve subjects (mean age ± SD, 66.85 ± 13.64 years) with varying degrees of cognitive decline underwent MRI using a Philips Ingenia 3T. The MTA scale by Scheltens, rated on coronal 3D T1-weighted images, was determined by three experienced radiologists, blinded to diagnosis and sex. Automated volumetry was computed by icobrain dm (v. 5.10) for total, left, right hippocampal, and ILV volumes. The ILV/Hip ratio, defined as the percentage ratio between ILV and hippocampal volumes, was calculated and compared against a normative reference population (n = 1903). Inter-rater agreement, association, classification accuracy, and clinical interpretability on patient level were reported. RESULTS: Visual MTA scores showed excellent inter-rater agreement. Ordinal logistic regression and correlation analyses demonstrated robust associations between automated brain segmentations and visual MTA ratings, with the ILV/Hip ratio consistently outperforming individual hippocampal and ILV volumes. Pairwise classification accuracy showed good performance without statistically significant differences between the ILV/Hip ratio and visual MTA across disease stages, indicating potential interchangeability. Comparison to the normative population and clinical interpretability assessments showed commensurability in classifying MTA "severity" between visual MTA and ILV/Hip ratio measurements. CONCLUSION: The ILV/Hip ratio shows the highest correlation to visual MTA, in comparison to automated individual ILV and hippocampal volumes, offering standardized measures for diagnostic support in different stages of cognitive decline.

Towards Improved Identification of Vertebral Fractures in Routine Computed Tomography (CT) Scans: Development and External Validation of a Machine Learning Algorithm.

Vertebral fractures (VFs) are the hallmark of osteoporosis, being one of the most frequent types of fragility fracture and an early sign of the disease. They are associated with significant morbidity and mortality. VFs are incidentally found in one out of five imaging studies, however, more than half of the VFs are not identified nor reported in patient computed tomography (CT) scans. Our study aimed to develop a machine learning algorithm to identify VFs in abdominal/chest CT scans and evaluate its performance. We acquired two independent data sets of routine abdominal/chest CT scans of patients aged 50 years or older: a training set of 1011 scans from a non-interventional, prospective proof-of-concept study at the Universitair Ziekenhuis (UZ) Brussel and a validation set of 2000 subjects from an observational cohort study at the Hospital of Holbaek. Both data sets were externally reevaluated to identify reference standard VF readings using the Genant semiquantitative (SQ) grading. Four independent models have been trained in a cross-validation experiment using the training set and an ensemble of four models has been applied to the external validation set. The validation set contained 15.3% scans with one or more VF (SQ2-3), whereas 663 of 24,930 evaluable vertebrae (2.7%) were fractured (SQ2-3) as per reference standard readings. Comparison of the ensemble model with the reference standard readings in identifying subjects with one or more moderate or severe VF resulted in an area under the receiver operating characteristic curve (AUROC) of 0.88 (95% confidence interval [CI], 0.85-0.90), accuracy of 0.92 (95% CI, 0.91-0.93), kappa of 0.72 (95% CI, 0.67-0.76), sensitivity of 0.81 (95% CI, 0.76-0.85), and specificity of 0.95 (95% CI, 0.93-0.96). We demonstrated that a machine learning algorithm trained for VF detection achieved strong performance on an external validation set. It has the potential to support healthcare professionals with the early identification of VFs and prevention of future fragility fractures. © 2023 UCB S.A. and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

4DCT Differentiation of Parathyroid Adenoma: A Case Report.

We report the case of a 72-year-old patient presenting with recurrent primary hyperparathyroidism after total thyroidectomy and parathyroidectomy with presternal autotransplantation. Methionine-PET-CT proved false-positive and Tc-99m-tetrofosmine imaging false-negative. Using a novel multiphase-4DCT technique we identified an anterior mediastinal nodule demonstrating contrast wash-in and wash-out, suggesting parathyroid adenoma. Traditional 4DCT-protocols obtain fewer phases; therefore, this enhancement pattern might have gone unnoticed. After surgical resection the bloodwork normalized, histopathology confirmed a parathyroid adenoma. Teaching Point: Multiphase 4DCT is a potentially helpful technique for the detection of parathyroid adenomas after total thyroidectomy and parathyroidectomy.

Sonographic changes in the thyroid gland after sclerotherapy with doxycycline can be mistaken for thyroid cancer.

BACKGROUND: The literature considers sclerotherapy to be a safe and effective treatment for benign thyroid cysts. No subsequent diagnostic problems have been reported as a complication. We report the occurrence of focal inflammation after said therapy, mimicking a thyroid malignancy. CASE PRESENTATION: We report a case of a young male with a solitary strongly suspicious lesion in the thyroid. The patient had undergone prior sclerotherapy of a thyroid cyst with Doxycycline. The lesion appeared to be a focal area of inflammation and thus iatrogenic in nature. Systemic use of doxycycline is known to sometimes cause a non-immune chemical thyroiditis, dubbed as black thyroid due to the intense black discoloration of the thyroid. It might be that the instillation of doxycycline was responsible for a similar, more localized area of thyroiditis. CONCLUSIONS: For the work-up of a solitary suspicious thyroid lesion, the medical history of the patient should always be considered. In case of prior ipsilateral sclerotherapy, a reactive inflammatory response may mimic thyroid malignancy. A fine needle aspiration should be performed to exclude thyroid cancer. Treatment is not necessary; the process appears to be self-limiting as evidenced in the follow-up of this case.

Lymphadenopathy after COVID-19 vaccination in patients with endocrine cancer: two case reports.

Summary: The Covid-19 vaccination has been rapidly implemented among patients with cancer. We present two cases of patients with endocrine tumours who developed lymphadenopathy following a Covid-19 vaccination. In the case of a patient with multiple endocrine neoplasia (MEN) 1 syndrome, an 18-fluorodeoxyglucose (18FDG)-PET/CT showed positive axillary lymph nodes. Further work-up with fine needle aspiration showed a reactive pattern following a Covid-19 vaccination in the ipsilateral arm shortly before the 18FDG-PET/CT. A second patient, in follow-up for thyroid cancer, developed clinical supraclavicular lymphadenopathy after a Covid-19 vaccination. Follow-up ultrasound proved the lesion to be transient. These cases demonstrate lymphadenopathy in response to a Covid-19 vaccination in two patients susceptible to endocrine tumours and metastatic disease. With growing evidence about the pattern and occurrence of lymphadenopathy after mRNA Covid-19 vaccination, recommendations for scheduling and interpretation of imaging among cancer patients should be implemented to reduce equivocal findings, overdiagnosis, and overtreatment, while maintaining a good standard of care in oncological follow-up. Learning points: Reactive lymphadenopathy is very common after an mRNA vaccination against Covid-19 and should be part of the differential diagnosis in patients with endocrine tumours who recently received a Covid-19 mRNA vaccination and present with an ipsilateral lymphadenopathy. A good vaccine history is essential in assessing the risk for lymphadenopathy and if possible, screening imaging in patients with endocrine tumours should be postponed at least 6 weeks after the previous vaccination. For now, a multidisciplinary care approach is recommended to determine the necessary steps in the diagnostic evaluation of lymphadenopathy in the proximity of a Covid-19 vaccination.

Relative Perfusion Differences between Parathyroid Adenomas and the Thyroid on Multiphase 4DCT.

A multiphase 4DCT technique can be useful for the detection of parathyroid adenomas. Up to 16 different phases can be obtained without significant increase of exposure dose using wide beam axial scanning. This technique also allows for the calculation of perfusion parameters in suspected lesions. We present data on 19 patients with histologically proven parathyroid adenomas. We find a strong correlation between 2 perfusion parameters when comparing parathyroid adenomas and thyroid tissue: parathyroid adenomas show a 55% increase in blood flow (BF) (p < 0.001) and a 50% increase in blood volume (BV) (p < 0.001) as compared to normal thyroid tissue. The analysis of the ROC curve for the different perfusion parameters demonstrates a significantly high area under the curve for BF and BV, confirming these two perfusion parameters to be a possible discriminating tool to discern between parathyroid adenomas and thyroid tissue. These findings can help to discern parathyroid from thyroid tissue and may aid in the detection of parathyroid adenomas.

Undetectable thyroglobulin makes 123I whole-body scan and stimulated thyroglobulin obsolete in follow-up care of differentiated thyroid cancer: a retrospective study.

BACKGROUND: Differentiated thyroid cancer (DTC) is a common malignancy with increasing incidence. Follow-up care for DTC includes thyroglobulin (Tg) measurement and ultrasound (US) of the neck, combined with 131I remnant ablation when indicated. Diagnostic precision has evolved with the introduction of the new high-sensitive Tg-assays (sensitivity ≤0.1 ng/mL). The aim of the study was to determine the prognostic utility of high-sensitive Tg and the need for other diagnostic tests in DTC. METHODS: This was a retrospective, observational study. Patients with pathologically confirmed DTC, treated with total thyroidectomy and 131I remnant ablation, who had their complete follow-up care in our institution were selected (October 2013-December 2018). Subjects with possible thyroglobulin autoantibody interference were excluded. Statistical analysis was performed using the IBM SPSS® Statistics 24 software package. RESULTS: Forty patients were eligible for analysis. A total of 24 out of the 40 patients (60%) had an undetectable high-sensitive Tg 6 months after total thyroidectomy. None of these patients had a stimulated Tg above 1 ng/mL, or remnant on the 123I Whole-Body Scan (WBS) after 1 year of follow-up. Ultrasound of the neck, performed between 6 and 12 months postoperative, was negative in 21 out of the 24 patients. CONCLUSIONS: This study shows that an undetectable high-sensitive Tg can change the management of patients with DTC and decrease the use and need of stimulated Tg and 123I WBS.

Subcutaneous emphysema of the extremities: Be wary of necrotizing fasciitis, but also consider occult rupture or perforation.

Not all causes of subcutaneous emphysema are attributable to necrotizing fasciitis. Consider other causes of subcutaneous emphysema in the differential diagnosis.

High-frequency Multiphase 4DCT for the Detection of Parathyroid Adenomas: A Pictorial Essay.

4-Dimensional computed tomography (4DCT) for the detection of (an) enlarged parathyroid(s) is a commonly performed examination in the management of primary hyperparathyroidism. In our center, we introduced a high-frequency multiphase 4DCT protocol obtaining 16 phases, including 11 different arterial phases. Exposure to this multiphase 4DCT technique is similar to that for classic helical 4DCT. In this pictorial essay we reconstructed our multiphase 4DCT series in the manner of a classic helical 4DCT and compare both techniques. We illustrate how multiphase 4DCT may aid in the detection of parathyroid adenomas. We found 17 out of 19 lesions demonstrating a type A pattern of enhancement, therefore suggesting this pattern could be more prevalent than previously thought. Some parathyroid adenomas may be mistaken for enlarged lymph nodes using classic 4DCT whereas high-frequency multiphase 4DCT can detect a temporary rise in enhancement, thus suggesting the lesions in question to be of parathyroid origin. Smaller lesions may prove more obvious as the difference in enhancement between parathyroid and thyroid can become more prominent. KEY POINT: Using high-frequency multiphase 4DCT an arterial phase with maximum enhancement of parathyroid tissue can be defined. This phase may aid in the detection of parathyroid adenomas.

Value of [11C]-Methionine PET/CT in Preoperative Localization of Parathyroid Adenomas.

There are multiple imaging modalities in primary hyperparathyroidism. Ultrasound examination and subtraction scintigraphy are usually the first-line imaging techniques. When these results are negative or inconsistent, additional [11C]-methionine PET/CT (MET-PET/CT) or 4-dimensional computed tomography can be performed. ​This study aims to evaluate MET-PET/CT in comparison with other imaging techniques in primary hyperparathyroidism. This is a retrospective cohort study. Eighty-four patients with primary hyperparathyroidism, who underwent parathyroid surgery, were included. ​Imaging results have been correlated to the perioperative drop in parathyroid hormone level and to the pathological analysis. ​Descriptive statistics are used, supplemented with 95% Clopper-Pearson confidence intervals for sensitivity and specificity and a sub-analysis with the McNemar test on paired data only. The per-lesion sensitivity of MET-PET/CT seems higher than that of [99mTc]-sestamibi or [99mTc]-tetrofosmin and [99mTc]-pertechnetate subtraction scintigraphy. The McNemar test, on paired data only, shows significantly higher sensitivity of MET-PET/CT compared to ultrasound (p=0.039) and significantly higher specificity of ultrasound compared to subtraction scintigraphy (p=0.035).​ MET-PET/CT after inconclusive or negative ultrasound and/or subtraction scintigraphy has an additional value in 70% of the cases.​ Preoperative parathyroid hormone levels were higher in patients in whom MET-PET/CT correctly predicted the pathological parathyroid glands, compared to those where MET-PET/CT missed at least one adenoma. The same trend was seen for 4-dimensional computed tomography. In conclusion, MET-PET/CT seems a valuable imaging modality in primary hyperparathyroidism, at least as second line imaging approach, with a higher per-lesion sensitivity than ultrasound in such setting. Especially when ultrasound and/or subtraction scintigraphy are inconclusive or negative, MET-PET/CT directs the surgeon to the correct localization of the parathyroid adenoma.

4DCT Scanning Technique for Primary Hyperparathyroidism: A Scoping Review.

OBJECTIVE: 4DCT for the detection of (an) enlarged parathyroid(s) is a commonly performed examination in the management of primary hyperparathyroidism. Protocols are often institution-specific; this review aims to summarize the different protocols and explore the reported sensitivity and specificity of different 4DCT protocols as well as the associated dose. MATERIALS AND METHODS: A literature study was independently conducted by two radiologists from April 2020 until May 2020 using the Medical Literature Analysis and Retrieval System Online (MEDLINE) database. Articles were screened and assessed for eligibility. From eligible studies, data were extracted to summarize different parameters of the scanning protocol and observed diagnostic attributes. RESULTS: A total of 51 articles were included and 56 scanning protocols were identified. Most protocols use three (n = 25) or four different phases (n = 23). Almost all authors include noncontrast enhanced imaging and an arterial phase. Arterial images are usually obtained 25-30 s after administration of contrast, and less agreement exists concerning the timing of the venous phase(s). A mean contrast bolus of 100 mL is administered at 3-4 mL/s. Bolus tracking is not often used (n = 3). A wide range of effective doses are reported, up to 28 mSv. A mean sensitivity of 81.5% and a mean specificity of 86% are reported. CONCLUSION: Many different 4DCT scanning protocols for the detection of parathyroid adenomas exist in the literature. The number of phases does not appear to affect sensitivity or specificity. A triphasic approach, however, seems preferable, as three patterns of enhancement of parathyroid adenomas are described. Bolus tracking could help to reduce the variability of enhancement. Sensitivity and specificity also do not appear to be affected by other scan parameters like tube voltage or tube current. To keep the effective dose within limits, scanning at a lower fixed tube current seems preferable. Lowering tube voltage from 120 kV to 100 kV may yield similar image contrast but would also help lower the dose.

Detection of parathyroid adenomas with multiphase 4DCT: towards a true four-dimensional technique.

BACKGROUND: Four-dimensional computed tomography (4DCT) is a commonly performed examination in the management of primary hyperparathyroidism, combining three-dimensional imaging with enhancement over time as the fourth dimension. We propose a novel technique consisting of 16 different contrast phases instead of three or four different phases. The main aim of this study was to ascertain whether this protocol allows the detection of parathyroid adenomas within dose limits. Our secondary aim was to examine the enhancement of parathyroid lesions over time. METHODS: For this prospective study, we included 15 patients with primary hyperparathyroidism and a positive ultrasound prior to surgery. We performed 4DCT with 16 different phases: an unenhanced phase followed by 11 consecutive arterial phases and 4 venous phases. Continuous axial scanning centered on the thyroid was performed over a fixed 8 cm or 16 cm coverage volume after the start of contrast administration. RESULTS: In all patients, an enlarged parathyroid lesion was demonstrated, and the mean lesion size was 13.6 mm. The mean peak arterial enhancement for parathyroid lesions was 384 Hounsfield units (HU) compared to 333 HU for the normal thyroid. No significant difference could be found. The time to peak (TTP) was significantly earlier for parathyroid adenomas than for normal thyroid tissue: 30.8 s versus 32.3 s (p value 0.008). The mean slope of increase (MSI) of the enhancement curve was significantly steeper than that of normal thyroid tissue: 29.8% versus 22.2% (p value 0.012). The mean dose length product was 890.7 mGy cm with a calculated effective dose of 6.7 mSv. CONCLUSION: Our 4DCT protocol may allow better visualization of the pattern of enhancement of parathyroid lesions, as enhancement over time curves can be drawn. In this way, wash-in and wash-out of contrast in suspected lesions can be readily demonstrated. Motion artifacts are less problematic as multiple phases are available. Exposure to our proposed 4DCT technique is comparable to that for classic helical 4DCT. Careful selection of parameters (lowering kV and SNR) can help to further reduce the dose.

Immune checkpoint inhibitor therapy for ACTH-secreting pituitary carcinoma: a new emerging treatment?

BACKGROUND: Pituitary carcinomas are rare but aggressive and require maximally coordinated multimodal therapies. For refractory tumors, unresponsive to temozolomide (TMZ), therapeutic options are limited. Immune checkpoint inhibitors (ICI) may be considered for treatment as illustrated in the present case report. CASE: We report a patient with ACTH-secreting pituitary carcinoma, progressive after multiple lines of therapy including chemotherapy with TMZ, who demonstrated disease stabilization by a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) ICI therapy. DISCUSSION: Management of pituitary carcinoma beyond TMZ remains ill-defined and relies on case reports. TMZ creates, due to hypermutation, more immunogenic tumors and subsequently potential candidates for ICI therapy. This case report adds support to the possible role of ICI in the treatment of pituitary carcinoma. CONCLUSION: ICI therapy could be a promising treatment option for pituitary carcinoma, considering the mechanisms of TMZ-induced hypermutation with increased immunogenicity, pituitary expression of CTLA-4 and PD-L1, and the frequent occurrence of hypophysitis as a side effect of ICI therapy.

Ingestion of gelatinous candy, mimicking acute gastric bleeding.

A detailed medical history is vital in the correct interpretation of medical images: Peer-to-peer feedback and a thorough medical history can help avoid diagnostic pitfalls and unnecessary therapy.

Intrathyroidal parathyroid carcinoma presenting as an asymptomatic hypercalcemia: a case report.

INTRODUCTION: A 26-year-old female presented with severe hypercalcemia. She was asymptomatic. Blood analysis revealed high serum calcium (13 mg/dL = 3.25 mmol/L) and elevated intact parathyroid hormone (iPTH) levels (267.5 ng/L). RESULTS: Ultrasonography showed a mixed solid-cystic nodule of 30 mm in the left thyroid lower lobe and a nodular lesion of 14 mm posterior of the thyroid upper pole suggestive for parathyroid adenoma. Sestamibi scan and magnetic resonance imaging (MRI) revealed hyperfunctioning parathyroid tissue posterior of the left thyroid upper lobe. During surgery, a 15 mm nodule in the usual location of the left superior parathyroid was resected. Intraoperative frozen section revealed normal parathyroid tissue and intraoperative PTH levels did not decrease. Left thyroidectomy was performed due to the large solid-cystic nodule. Intraoperative PTH levels normalized 10 min later. Pathologic examination revealed a 28 mm nodule in the lower thyroid pole compatible with a parathyroid carcinoma (PC). Due to positive margins, a completion thyroidectomy was performed. 5-year follow-up showed no recurrence. CONCLUSIONS: PC is a rare entity comprising 0.5-2% of patients with primary hyperparathyroidism. Even more unusual is an intrathyroidal parathyroid gland (0.2%). Only a dozen cases of intrathyroidal PC have been reported. Our case is the second patient reported to be asymptomatic.

Exercise in knee osteoarthritis: do treatment outcomes relate to bone marrow lesions? A randomized trial.

PURPOSE: Exercise is effective for reducing knee osteoarthritis (OA) pain but effect sizes vary widely. Moreover, not all knee OA patients perceive beneficial effects. Tailoring specific exercises to subgroups of knee OA patients may increase effectivity. Bone marrow lesions (BMLs) have been suggested as a criterion to define such subgroups. This study aimed to investigate whether BMLs' presence/absence is related to treatment outcomes in a group of knee OA patients who exercised for 18 weeks. METHODS: Subjects with symptomatic knee OA started a strength or walking exercise program. BMLs' presence at baseline was assessed. Pain was assessed before and after the intervention with the intermittent and constant osteoarthritis pain (ICOAP) questionnaire. Also the global perceived effect (GPE) on the patient's complaints was rated. RESULTS: Thirty-five patients (strength (N = 17) and walking (N = 18)) were analyzed for BMLs. BMLs were present in 25 (71%) knees. Five (14%) patients dropped out and 19 (54%) improved (GPE ≥5). All dropouts had BMLs, but no difference was seen between dropouts and retainers (p > 0.05). Pain scores did not differ between intervention groups (p > 0.05) or between patients with BMLs and without BMLs (p > 0.05). CONCLUSIONS: Pain scores and GPE was not different between knee OA patients with and without baseline BMLs in this sample. Implications for Rehabilitation Both walking and strengthening exercises are effective means of improving pain in patients with knee osteoarthritis. In a relatively small sample, this study shows that the presence or absence of subchondral bone marrow lesions, as seen on magnetic resonance images, is not related to treatment outcomes.

[A patient with high creatinine levels but no renal failure: reversed autodialysis in a patient with a ruptured bladder]. / Een patiënt met hoog creatinine maar zonder nierfalen: omgekeerde auto-dialyse bij een patiënt met een blaasruptuur.

BACKGROUND: In case of a ruptured bladder with urine leakage into the peritoneal cavity 'reversed autodialysis' can occur, in which urea and creatinine diffuse back into the bloodstream via the peritoneum. This causes clinical signs of pseudorenal failure, with raised concentrations of creatinine and urea. The urea/creatinine ratio does not change. CASE DESCRIPTION: A 34-year-old female patient experienced increasing abdominal pain 3 days after laparoscopic myomectomy. Acute renal failure was suspected because of increased serum concentrations of creatinine and urea, but no cause could be found. There was a build-up of fluid in the abdominal cavity, which proved to be urine originating from an iatrogenic rupture of the bladder. Serum levels normalised following repair of the rupture. CONCLUSION: If serum creatinine levels rise rapidly following abdominal surgery or blunt abdominal trauma the bladder should be examined for possible perforation, particularly if the abdominal dimension increases. A ruptured bladder leading to pseudorenal failure is an indication for rapid surgical intervention.