Diagnostic accuracy of the maximal systolic acceleration to detect peripheral arterial disease.

BACKGROUND: Diagnosing peripheral arterial disease (PAD) can be challenging owing to medial arterial calcification (MAC) in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Current bedside tests, such as the ankle-brachial index and toe-brachial index, are often insufficient. The maximal systolic acceleration (ACCmax) is a velocimetric Doppler-derived parameter and could be a new promising test in the diagnostic workup of these patients. The primary aim of this study was to evaluate the diagnostic performance of the ACCmax to detect PAD. METHODS: A retrospective cohort study was performed in a tertiary referral hospital. Patients ≥18 years old with suspected PAD who underwent ACCmax measurement(s) along with computed tomography angiography of the abdominal aorta and lower extremities (reference test) were eligible for inclusion. ACCmax measurements of the posterior tibial artery, anterior tibial artery and peroneal artery were collected. Diagnostic performance was assessed by using sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve (AUC). RESULTS: In total, 340 patients (618 limbs) were included. Approximately 40% suffered from DM and 30% had CKD. Diagnostic performance of the ACCmax to detect PAD for the posterior tibial artery showed a sensitivity of 90%, specificity of 93%, positive likelihood ratio of 12.83, and negative likelihood ratio of 0.11 (AUC, 0.953). For the anterior tibial artery, these results were 94%, 97%, 32.06, and 0.06 (same sequence as presented before) with an AUC of 0.984. The peroneal artery had a performance of 86%, 89%, 7.51, and 0.16, respectively (AUC, 0.893). Diagnostic accuracy of the ACCmax did not diminish in subgroup analysis for patients with DM or CKD. CONCLUSIONS: The ACCmax showed excellent diagnostic performance to detect PAD, independent of patients prone to medial arterial calcification.

Cost-effectiveness of one-stop-shop [18F]Fluorocholine PET/CT to localise parathyroid adenomas in patients suffering from primary hyperparathyroidism.

PURPOSE: We conducted a cost-effectiveness analysis in which we compared a preoperative [18F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in which [18F]Fluorocholine PET/CT is only recommended after negative or inconclusive [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT for patients suffering from primary hyperparathyroidism. We investigated whether the one-stop-shop strategy performs as well as current best practice but at lower costs. METHODS: We developed a cohort-level state transition model to evaluate both imaging strategies respecting an intraoperative parathyroid hormone monitored treatment setting as well as a traditional treatment setting. The model reflects patients' hospital journeys after biochemically diagnosed primary hyperparathyroidism. A cycle length of twelve months and a lifetime horizon were used. We conducted probabilistic analyses simulating 50,000 cohorts to assess joint parameter uncertainty. The incremental net monetary benefit and cost for each quality-adjusted life year were estimated. Furthermore, threshold analyses regarding the tariff of [18F]Fluorocholine PET/CT and the sensitivity of [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT were performed. RESULTS: The simulated long-term health effects and costs were similar for both imaging strategies. Accordingly, there was no incremental net monetary benefit and the one-stop-shop strategy did not result in lower costs. These results applied to both treatment settings. The threshold analysis indicated that a tariff of €885 for [18F]Fluorocholine PET/CT was required to be cost-effective compared to current best practice. CONCLUSION: Both preoperative imaging strategies can be used interchangeably. Daily clinical practice grounds such as available local resources and patient preferences should inform policy-making on whether a hospital should implement the one-stop-shop imaging strategy.

Toward Uniform Case Identification Criteria in Observational Studies on Peripheral Arterial Disease: A Scoping Review.

BACKGROUND: The diagnosis of peripheral arterial disease (PAD) is commonly applied for symptoms related to atherosclerotic obstructions in the lower extremity, though its clinical manifestations range from an abnormal ankle-brachial index to critical limb ischemia. Subsequently, management and prognosis of PAD vary widely with the disease stage. A critical aspect is how this variation is addressed in administrative database-based studies that rely on diagnosis codes for case identification. The objective of this scoping review is to inventory the identification strategies used in studies on PAD that rely on administrative databases, to map the pros and cons of the International Classification of Diseases (ICD) codes applied, and to propose a first outline for a consensus framework for case identification in administrative databases. METHODS: Registry-based reports published between 2010 and 2021 were identified through a systematic PubMed search. Studies were subcategorized on the basis of the expressed study focus: claudication, critical limb ischemia, or general peripheral arterial disease, and the ICD code(s) applied for case identification mapped. RESULTS: Ninety studies were identified, of which 36 (40%) did not specify the grade of PAD studied. Forty-nine (54%) articles specified PAD grade studied. Five (6%) articles specified different PAD subgroups in methods and baseline demographics, but not in further analyses. Mapping of the ICD codes applied for case identification for studies that specified the PAD grade studied indicated a remarkable heterogeneity, overlap, and inconsistency. CONCLUSIONS: A large proportion of registry-based studies on PAD fail to define the study focus. In addition, inconsistent strategies are used for PAD case identification in studies that report a focus. These findings challenge study validity and interfere with inter-study comparison. This scoping review provides a first initiative for a consensus framework for standardized case selection in administrative studies on PAD. It is anticipated that more uniform coding will improve study validity and facilitate inter-study comparisons.

Normalization of Time-Intensity Curves for Quantification of Foot Perfusion Using Near-Infrared Fluorescence Imaging With Indocyanine Green.

PURPOSE: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is gaining popularity for the quantification of tissue perfusion, including foot perfusion in patients with lower extremity arterial disease (LEAD). However, the absolute fluorescence intensity is influenced by patient-and system-related factors limiting reliable and valid quantification. To enhance the quality of quantitative perfusion assessment using ICG NIR fluorescence imaging, normalization of the measured time-intensity curves seems useful. MATERIALS AND METHODS: In this cohort study, the effect of normalization on 2 aspects of ICG NIR fluorescence imaging in assessment of foot perfusion was measured: the repeatability and the region selection. Following intravenous administration of ICG, the NIR fluorescence intensity in both feet was recorded for 10 mins using the Quest Spectrum platform®. The effect of normalization on repeatability was measured in the nontreated foot in patients undergoing unilateral revascularization preprocedural and postprocedural (repeatability group). The effect of normalization on region selection was performed in patients without LEAD (region selection group). Absolute and normalized time-intensity curves were compared. RESULTS: Successful ICG NIR fluorescence imaging was performed in 54 patients (repeatability group, n = 38; region selection group, n = 16). For the repeatability group, normalization of the time-intensity curves displayed a comparable inflow pattern for repeated measurements. For the region selection group, the maximum fluorescence intensity (Imax) demonstrated significant differences between the 3 measured regions of the foot (P = .002). Following normalization, the time-intensity curves in both feet were comparable for all 3 regions. CONCLUSION: This study shows the effect of normalization of time-intensity curves on both the repeatability and region selection in ICG NIR fluorescence imaging. The significant difference between absolute parameters in various regions of the foot demonstrates the limitation of absolute intensity in interpreting tissue perfusion. Therefore, normalization and standardization of camera settings are essential steps toward reliable and valid quantification of tissue perfusion using ICG NIR fluorescence imaging.

Evaluation of the Angiosome Concept Using Near-Infrared Fluorescence Imaging with Indocyanine Green.

BACKGROUND: The angiosome concept is defined as the anatomical territory of a source artery within all tissue layers. When applying this theory in vascular surgery, direct revascularization (DR) is preferred to achieve increased blood flow toward the targeted angiosome of the foot in patients with lower extremity arterial disease (LEAD). This study evaluates the applicability of the angiosome concept using quantified near-infrared (NIR) fluorescence imaging with indocyanine green (ICG). METHODS: This study included patients undergoing an endovascular- or surgical revascularization of the leg between January 2019 and December 2021. Preinterventional and postinterventional ICG NIR fluorescence imaging was performed. Three angiosomes on the dorsum of the foot were determined: the posterior tibial artery (hallux), the anterior tibial artery (dorsum of the foot) and the combined angiosome (second to fifth digit). The angiosomes were classified from the electronic patient records and the degree of collateralization was classified based on preprocedural computed tomography angiography and/or X-ray angiography. Fluorescence intensity was quantified in all angiosomes. A subgroup analysis based on endovascular or surgical revascularized angiosomes, and within critical limb threatening ischemia (CLTI) patients was performed. RESULTS: ICG NIR fluorescence measurements were obtained in 52 patients (54 limbs) including a total of 157 angiosomes (121 DR and 36 indirect revascularizations [IR]). A significant improvement of all perfusion parameters in both the directly and indirectly revascularized angiosomes was found (P-values between <0.001-0.007). Within the indirectly revascularized angiosomes, 90.6% of the scored collaterals were classified as significant. When comparing the percentual change in perfusion parameters between the directly and indirectly revascularized angiosomes, no significant difference was seen in all perfusion parameters (P-values between 0.253 and 0.881). Similar results were shown in the CLTI patients subgroup analysis, displaying a significant improvement of perfusion parameters in both the direct and indirect angiosome groups (P-values between <0.001 and 0.007), and no significant difference when comparing the percentual parameter improvement between both angiosome groups (P-values between 0.134 and 0.359). Furthermore, no significant differences were observed when comparing percentual changes of perfusion parameters in directly and indirectly revascularized angiosomes for both endovascular and surgical interventions (P-values between 0.053 and 0.899). CONCLUSIONS: This study proves that both DR and IR of an angiosome leads to an improvement of perfusion. This suggests that interventional strategies should not only focus on creating in-line flow to the supplying angiosome. One can argue that the angiosome concept is not applicable in patients with LEAD.

Exploring the surgical personality.

Surgery is a demanding field, requiring determination and emotional stability. This review explores the surgical personality, addressing international personality differences between surgical and non-surgical specialties. Across the globe, surgically-interested individuals (i.e., medical students, residents, surgeons) generally scored higher on conscientiousness, open mindedness, and extraversion, and lower on neuroticism compared to non-surgically-interested contemporaries. Extraversion was inversely correlated to burnout in surgical residents and open mindedness to reduced competence in giving feedback. Although additional region- and/or country-specific research is warranted, being or becoming a surgeon appears to correlate to personality traits such as high conscientiousness and low neuroticism.

Exploring the Effects of Human Bone Marrow-Derived Mononuclear Cells on Angiogenesis In Vitro.

Cell therapies involving the administration of bone marrow-derived mononuclear cells (BM-MNCs) for patients with chronic limb-threatening ischemia (CLTI) have shown promise; however, their overall effectiveness lacks evidence, and the exact mechanism of action remains unclear. In this study, we examined the angiogenic effects of well-controlled human bone marrow cell isolates on endothelial cells. The responses of endothelial cell proliferation, migration, tube formation, and aortic ring sprouting were analyzed in vitro, considering both the direct and paracrine effects of BM cell isolates. Furthermore, we conducted these investigations under both normoxic and hypoxic conditions to simulate the ischemic environment. Interestingly, no significant effect on the angiogenic response of human umbilical vein endothelial cells (HUVECs) following treatment with BM-MNCs was observed. This study fails to provide significant evidence for angiogenic effects from human bone marrow cell isolates on human endothelial cells. These in vitro experiments suggest that the potential benefits of BM-MNC therapy for CLTI patients may not involve endothelial cell angiogenesis.

FDG-PET/CT in indeterminate thyroid nodules: cost-utility analysis alongside a randomised controlled trial.

PURPOSE: To evaluate cost-effectiveness of an [18F]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [18F]FDG-PET/CT avoids 40% of futile diagnostic surgeries for benign Bethesda III/IV nodules. METHODS: Lifelong societal costs and quality-adjusted life years (QALYs) were assessed for 132 patients participating in a randomised controlled multicentre trial comparing [18F]FDG-PET/CT to diagnostic surgery. The observed 1-year trial results were extrapolated using a Markov model. The probability of cost-effectiveness was estimated using cost-effectiveness acceptability curves, taking uncertainty about sampling, imputation, and parameters into account. RESULTS: The observed 1-year cost difference of [18F]FDG-PET/CT as compared to diagnostic surgery was - €1000 (95% CI: - €2100 to €0) for thyroid nodule-related care (p = 0.06). From the broader societal perspective, the 1-year difference in total societal costs was - €4500 (- €9200 to €150) (p = 0.06). Over the modelled lifelong period, the cost difference was - €9900 (- €23,100 to €3200) (p = 0.14). The difference in QALYs was 0.019 (- 0.045 to 0.083) at 1 year (p = 0.57) and 0.402 (- 0.581 to 1.385) over the lifelong period (p = 0.42). For a willingness to pay of €50,000 per QALY, an [18F]FDG-PET/CT-driven work-up was the cost-effective strategy with 84% certainty. CONCLUSION: Following the observed reduction in diagnostic surgery, an [18F]FDG-PET/CT-driven diagnostic workup reduced the 1-year thyroid nodule-related and societal costs while sustaining quality of life. It is very likely cost-effective as compared to diagnostic surgery for Bethesda III/IV nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .

A New Doppler-Derived Parameter to Quantify Internal Carotid Artery Stenosis: Maximal Systolic Acceleration.

OBJECTIVE: Doppler ultrasonography (DUS) is used as initial measurement to diagnose and classify carotid artery stenosis. Local distorting factors such as vascular calcification can influence the ability to obtain DUS measurements. The DUS derived maximal systolic acceleration (ACCmax) provides a different way to determine the degree of stenosis. While conventional DUS parameters are measured at the stenosis itself, ACCmax is measured distal to the internal carotid artery (ICA) stenosis. The value of ACCmax in ICA stenosis was investigated in this study. MATERIAL AND METHODS: All carotid artery DUS studies of a tertiary academic center were reviewed from October 2007 until December 2017. Every ICA was included once. The ACCmax was compared to conventional DUS parameters: ICA peak systolic velocity (PSV), and PSV ratio (ICA PSV/ CCA PSV). ROC-curve analysis was used to evaluate accuracy of ACCmax, ICA PSV and PSV ratio as compared to CT-angiography (CTA) derived stenosis measurement as reference test. RESULTS: The study population consisted of 947 carotid arteries and was divided into 3 groups: <50% (710/947), 50-69% (109/947), and ≥70% (128/947). Between these groups ACCmax was significantly different. Strong correlations between ACCmax and ICA PSV (R2 0.88) and PSV ratio (R2 0.87) were found. In ROC subanalysis, the ACCmax had a sensitivity of 90% and a specificity of 89% to diagnose a ≥70% ICA stenosis, and a sensitivity of 82% and a specificity of 88% to diagnose a ≥50% ICA stenosis. For diagnosing a ≥50% ICA stenosis the area under the curve (AUC) of ACCmax (0.88) was significantly lower than the AUC of PSV ratio (0.94) and ICA PSV (0.94). To diagnose a ≥70% ICA stenosis there were no significant differences in AUC between ACCmax (0.89), PSV ratio (0.93) and ICA PSV (0.94). CONCLUSIONS: ACCmax is an interesting additional DUS measurement in determining the degree of ICA stenosis. ACCmax is measured distal to the stenosis and is not hampered by local distorting factors at the site of the stenosis. ACCmax can accurately diagnose an ICA stenosis, but was somewhat inferior compared to ICA PSV and PSV ratio to diagnose a ≥50% ICA stenosis.

Assessment of Tissue Viability Following Amputation Surgery Using Near-Infrared Fluorescence Imaging With Indocyanine Green.

BACKGROUND: Patients with chronic limb threatening ischemia have a risk of undergoing a major amputation within 1 year of nearly 30% with a substantial risk of re-amputation since wound healing is often impaired. Quantitative assessment of regional tissue viability following amputation surgery can identify patients at risk for impaired wound healing. In quantification of regional tissue perfusion, near-infrared (NIR) fluorescence imaging using Indocyanine Green (ICG) seems promising. METHODS: This pilot study included adult patients undergoing lower extremity amputation surgery due to peripheral artery disease or diabetes mellitus. ICG NIR fluorescence imaging was performed within 5 days following amputation surgery using the Quest Spectrum PlatformⓇ. Following intravenous administration of ICG, the NIR fluorescence intensity of the amputation wound was recorded for 10 minutes. The NIR fluorescence intensity videos were analyzed and if a fluorescence deficit was observed, this region was marked as "low fluorescence." All other regions were marked as "normal fluorescence." RESULTS: Successful ICG NIR fluorescence imaging was performed in 10 patients undergoing a total of 15 amputations. No "low fluorescence" regions were observed in 11 out of 15 amputation wounds. In 10 out of these 11 amputations, no wound healing problems occurred during follow-up. Regions with "low fluorescence" were observed in 4 amputation wounds. Impaired wound healing corresponding to these regions was observed in all wounds and a re-amputation was necessary in 3 out of 4. When observing time-related parameters, regions with low fluorescence had a significantly longer time to maximum intensity (113 seconds vs. 32 seconds, P = 0.003) and a significantly lesser decline in outflow after five minutes (80.3% vs. 57.0%, P = 0.003). CONCLUSIONS: ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Quantitative assessment of regional perfusion remains challenging due toinfluencing factors on the NIR fluorescence intensity signal, including camera angle, camera distance and ICG dosage. This was also observed in this study, contributing to a large variety in fluorescence intensity parameters among patients. To provide surgeons with reliable NIR fluorescence cut-off values for prediction of wound healing, prospective studies on the intra-operative use of this technique are required. The potential prediction of wound healing using ICG NIR fluorescence imaging will have a huge impact on patient mortality, morbidity as well as the burden of amputation surgery on health care.

Near-infrared fluorescence imaging with indocyanine green for quantification of changes in tissue perfusion following revascularization.

OBJECTIVES: Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly focus on the macrovascular level. For assessment of tissue perfusion, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) seems promising. In this prospective cohort study, ICG NIR fluorescence imaging was performed pre- and post-revascularization to assess changes in foot perfusion. METHODS: ICG NIR fluorescence imaging was performed in 36 patients with PAD pre- and post-intervention. After intravenous bolus injection of 0.1 mg/kg ICG, the camera registered the NIR fluorescence intensity over time on the dorsum of the feet for 15 min using the Quest Spectrum Platform®. Time-intensity curves were plotted for three regions of interest (ROI): (1) the dorsum of the foot, (2) the forefoot, and (3) the hallux. Time-intensity curves were normalized for maximum fluorescence intensity. Extracted parameters were the maximum slope, area under the curve (AUC) for the ingress, and the AUC for the egress. The non-treated contralateral leg was used as a control group. RESULTS: Successful revascularization was performed in 32 patients. There was a significant increase for the maximum slope and AUC egress in all three ROIs. The most significant difference was seen for the maximum slope in ROI 3 (3.7%/s to 6.6%/s, p < 0.001). In the control group, no significant differences were seen for the maximum slope and AUC egress in all ROIs. CONCLUSIONS: This study shows the potential of ICG NIR fluorescence imaging in assessing the effect of revascularization procedures on foot perfusion. Future studies should focus on the use of this technique in predicting favorable outcome of revascularization procedures.

Practice variation in the treatment of patients with renal hyperparathyroidism: a survey-based study in the Netherlands.

BACKGROUND: Renal hyperparathyroidism is a disease entity that is complex and poorly understood. Although there are guidelines regarding how to manage this patient group, evidence is scarce. Therefore, this survey-based study aims to map the physicians' attitude in terms of preference for management of renal hyperparathyroidism and the influence of patient and respondent factors. METHODS: A survey was sent to Dutch societies of nephrology, endocrinology, and surgeons with interest in endocrine surgery. The survey consisted of eight case vignettes of renal hyperparathyroidism patients who were on hemodialysis and suitable for kidney transplantation, and varied in one of three patient variables import for decision making: age (40 vs. 65 years), parathyroid hormone (40 vs. 90 pmol/L), and serum calcium level (2.25 vs. 2.8 mmol/L). For each case, respondents could choose between maintaining conservative treatment (active vitamin D metabolites), calcimimetics, or subtotal parathyroidectomy as their treatment of choice. Categorical multilevel logistic models were used to investigate the association of patient and respondent variables with treatment preference. The influence of patient variables was determined independently of each other and by means of logistic regression the probabilities of treatment choice were calculated. RESULTS: In total, 115 surveys were included in the analysis. In 6 out of 8 cases, less than two-thirds of respondents agreed on the most favoured treatment. Among patient characteristics, the main disincentive for respondents not to choose conservative therapy was an elevated serum calcium level (subtotal parathyroidectomy vs conservative OR 93.1, 95%-CI: 48.39-179.07 and calcimimetics vs conservative OR 31.2 95%-CI: 18.58-52.30). Additionally, the most significant treatment differences were found between medical specialties and the experience of the respondents, expressed as the amount of cases the physician was involved in during the past year. CONCLUSIONS: Elevated serum calcium levels were widely recognized and the prime reason for respondents to abandon conservative treatment. However, considerable disagreement in treatment preferences remained throughout the cases, demonstrating the current literature available being inconclusive in guiding physicians. Therefore, a high-quality trial comparing subtotal parathyroidectomy to medical treatment is needed to determine optimal treatment.

Identifying Factors Influencing Decision Making in Patients Diagnosed with Carotid Body Tumors: An Exploratory Study.

BACKGROUND: Carotid body tumors (CBTs) are rare highly vascularized and slow enlarging tumors arising from the paraganglionic tissue at the carotid bifurcation. Main treatment options for CBTs are surgical resection or "wait and scan" strategy. The choice for either strategy may be equally good medically in many patients. A structured "shared decision making" (SDM) might be helpful for guiding patients. OBJECTIVES: To develop an SDM strategy for the surgical treatment, we aim to (1) identify considerations and factors involved in the decision making of patients with CBTs and (2) evaluate the current practice in our clinic and explore the opinions of patients on their treatment. METHODS: This exploratory study was conducted in patients of the Leiden University Medical Centre (LUMC), The Netherlands. Patients who met the inclusion criteria were invited for a semi-structured interview. All conversations were fully audiotaped and transcripted. RESULTS: Fifteen patients were included and interviewed. Ten of these patients underwent previously surgical resection of at least one tumor. Five patients underwent the wait and scan policy. The most important factors influencing decision making in CBT treatment are family, fears, co-consultants, and doctor-patient relationship. CONCLUSIONS: This study has identified the factors influencing decision making in CBT and should be considered during consultations. The decision for surgery or not was mainly influenced by physician preferences and family members' prior experiences.

Outcomes of parathyroidectomy versus calcimimetics for secondary hyperparathyroidism and kidney transplantation: a propensity-matched analysis.

PURPOSE: Calcimimetics are currently indicated for severe secondary hyperparathyroidism (SHPT). However, the role of parathyroidectomy (PTX) for these patients is still under debate, and its impact on subsequent kidney transplantation (KTX) is unclear. In this study, we compare the outcomes of kidney transplantation after PTX or medical treatment. METHODS: Patients who underwent KTX and had SHPT were analyzed retrospectively. Two groups were selected (patients who had either PTX or calcimimetics prior to KTX) using a propensity score for sex, age, donor type, and parathyroid hormone levels (PTH) during dialysis. The primary outcome was graft failure, and secondary outcomes were surgical KTX complications, survival, serum PTH, serum calcium, and serum phosphate levels post-KTX. RESULTS: Matching succeeded for 92 patients. After PTX, PTH was significantly lower on the day of KTX as well as at 1 and 3 years post-KTX (14.00 pmol/L (3.80-34.00) vs. 71.30 pmol/L (30.70-108.30), p < 0.01, 10.10 pmol/L (2.00-21.00) vs. 32.35 pmol/L (21.58-51.76), p < 0.01 and 13.00 pmol/L (6.00-16.60) vs. 19.25 pmol/L (13.03-31.88), p = 0.027, respectively). No significant differences in post-KTX calcium and phosphate levels were noted between groups. Severe KTX complications were more common in the calcimimetics group (56.5% vs. 30.4%, p = 0.047). There were no differences in 10-year graft failure and overall survival. CONCLUSION: PTX resulted in lower PTH after KTX in comparison to patients who received calcimimetics. Severe complications were more common after calcimimetics, but graft failure and overall survival were similar.

Timing of Parathyroidectomy Does Not Influence Renal Function After Kidney Transplantation.

BACKGROUND: Parathyroidectomy (PTx) is the treatment of choice for end-stage renal disease (ESRD) patients with therapy-resistant hyperparathyroidism (HPT). The optimal timing of PTx for ESRD-related HPT-before or after kidney transplantation (KTx)-is subject of debate. METHODS: Patients with ESRD-related HPT who underwent both PTx and KTx between 1994 and 2015 were included in a multicenter retrospective study in four university hospitals. Two groups were formed according to treatment sequence: PTx before KTx (PTxKTx) and PTx after KTx (KTxPTx). Primary endpoint was renal function (eGFR, CKD-EPI) between both groups at several time points post-transplantation. Correlation between the timing of PTx and KTx and the course of eGFR was assessed using generalized estimating equations (GEE). RESULTS: The PTxKTx group consisted of 102 (55.1%) and the KTxPTx group of 83 (44.9%) patients. Recipient age, donor type, PTx type, and pre-KTx PTH levels were significantly different between groups. At 5 years after transplantation, eGFR was similar in the PTxKTx group (eGFR 44.5 ± 4.0 ml/min/1.73 m2) and KTxPTx group (40.0 ± 6.4 ml/min/1.73 m2, p = 0.43). The unadjusted GEE model showed that timing of PTx was not correlated with graft function over time (mean difference -1.0 ml/min/1.73 m2, 95% confidence interval -8.4 to 6.4, p = 0.79). Adjustment for potential confounders including recipient age and sex, various donor characteristics, PTx type, and PTH levels did not materially influence the results. CONCLUSIONS: In this multicenter cohort study, timing of PTx before or after KTx does not independently impact graft function over time.

No Clinical Benefit of Intramuscular Delivery of Bone Marrow-derived Mononuclear Cells in Nonreconstructable Peripheral Arterial Disease: Results of a Phase-III Randomized-controlled Trial.

BACKGROUND AND AIMS: Prospects for no-option, end-stage peripheral artery disease (PAD) patients remain poor. Although results from open and semiblinded studies fuel hope for cell-based strategies in no-option patients, so far conclusions from the available placebo-controlled studies are not supportive. With the intention to end the remaining controversy with regard to cell therapy for PAD we conducted a confirmatory, double-blinded randomized placebo-controlled phase 3 trial. STUDY DESIGN: This randomized controlled trial was registered (NCT00539266). Inclusion criteria included stable or progressive disabling PAD, no imminent need for amputation, absent accepted options for revascularization. Diabetic disease was an exclusion criterion. Bone marrow (500-700 mL) was harvested and bone marrow-derived mononuclear cells were concentrated to 40 mL. Concentrated cells or placebo (diluted blood) were intramuscularly injected at 40 locations of the calf muscle. RESULTS: Fifty-four patients (mean (sd) age 58.2 (14.2) yrs, 58% males) were randomized. Twenty-eight patients received BM-MNCs, 26 placebo. Baseline criteria were similar in the 2 groups. No significant differences were observed for the primary (number of amputations, (pain free) walking distance) and secondary outcome parameters (ankle brachial index, pain scores, quality of life (SF-36)). DISCUSSION: This fully blinded replication trial of autologous BM-MNC fails to confirm a benefit for cell therapy in no-option PAD patients, consequently BM-MNC therapy should not be offered as a clinical treatment. Apparent contrasting conclusions from open and controlled studies underscore the importance of a controlled trial design in evaluating cell-based interventions in PAD.

Safety and efficacy of subtotal or total parathyroidectomy for patients with secondary or tertiary hyperparathyroidism in four academic centers in the Netherlands.

PURPOSE: Hyperparathyroidism (HPT) is a common abnormality in patients with end-stage renal disease (ESRD). Since the introduction of cinacalcet in 2004, a shift from surgery toward predominantly medical treatment has occurred. Surgery is thought to be associated with more complications than oral medication. The aim of this retrospective study was to evaluate 30-day outcomes and effectiveness of parathyroidectomy (PTx) in ESRD patients in the Netherlands. METHODS: A national database containing data from four academic medical centers in the Netherlands of patients with ESRD-related HPT, who had undergone PTx and kidney transplantation between 1994 and 2015, was established. Primary endpoints were 30-day mortality and complication rate. Secondary endpoints were biochemical measurements. RESULTS: We identified 187 HPT patients undergoing PTx, with a median age of 46 years. Median preoperative PTH level was 866 pg/mL (interquartile range [IQR] 407-1547 pg/mL). At 3 months, the median PTH drop from baseline was 93% (IQR, 71-98%) to a median of 61 pg/mL (IQR, 23-148 pg/mL, p < 0.001). Over the 25-year inclusion period, 13 patients (7.0%) required re-exploration for persistent or recurrent disease. Thirty-day mortality and complication rate were 0.0% and 7.9% respectively. Median serum calcium levels improved significantly postoperatively from 2.6 (2.4-2.8) mmol/L to 2.3 (2.1-2.5) mmol/L (p < 0.001). CONCLUSIONS: PTx is a safe and effective procedure in the frail ESRD population. These data show that there should be no reluctance for surgical intervention and when indicated, nephrologists can safely refer these patients for PTx.