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BACKGROUND AND PURPOSE: Late onset Pompe disease (LOPD) is a rare neuromuscular disorder caused by a deficit in acid alpha-glucosidase. Macroglossia and swallowing disorders have already been reported, but no study has focused yet on its frequency and functional impact on patients' daily life. METHODS: We reviewed 100 adult LOPD patients followed in 17 hospitals in France included in the French national Pompe disease registry. The Swallowing Quality of Life Questionnaire and the Sydney Swallow Questionnaire were completed by patients, and a specialist carried out a medical examination focused on swallowing and assigned a Salassa score to each patient. Respiratory and motor functions were also recorded. Subgroup analysis compared patients with and without swallowing difficulties based on Salassa score. RESULTS: Thirty-two percent of patients presented with swallowing difficulties, often mild but sometimes severe enough to require percutaneous endoscopic gastrostomy (1%). Daily dysphagia was reported for 20% of our patients and aspirations for 18%; 9.5% were unable to eat away from home. Macroglossia was described in 18% of our patients, and 11% had lingual atrophy. Only 15% of patients presenting with swallowing disorders were followed by a speech therapist. Swallowing difficulties were significantly associated with macroglossia (p = 0.015), longer duration of illness (p = 0.032), and a lower body mass index (p = 0.047). CONCLUSIONS: Swallowing difficulties in LOPD are common and have significant functional impact. Increased awareness by physicians of these symptoms with systematic examination of the tongue and questions about swallowing can lead to appropriate multidisciplinary care with a speech therapist and dietitian if needed.
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This study aims to profile biomechanical abilities during sprint front crawl by identifying technical stroke characteristics, in light of performance level. Ninety-one recreational to world-class swimmers equipped with a sacrum-worn IMU performed 25 m all-out. Intra and inter-cyclic 3D kinematical variabilities were clustered using a functional double partition model. Clusters were analysed according to (1) swimming technique using continuous visualisation and discrete features (standard deviation and jerk cost) and (2) performance regarding speed and competition calibre using respectively one-way ANOVA and Chi-squared test as well as Gamma statistics. Swimmers displayed specific technical profiles of intra-cyclic (smoothy and jerky) and inter-cyclic stroke regulation (low, moderate and high repeatability) significantly discriminated by speed (p < 0.001, η2 = 0.62) and performance calibre (p < 0.001, V = 0.53). We showed that combining high levels of both kinds of variability (jerky + low repeatability) are associated with highest speed (1.86 ± 0.12 m/s) and competition calibre (â½ = 0.75, p < 0.001). It highlights the crucial importance of variabilities combination. Technical skills might be driven by a specific alignment of stroke pattern and its associated dispersion according to the task constraints. This data-driven approach can assist eyes-based technical evaluation. Targeting the development of an explosive swimming style with a high level of body stability should be considered during training of sprinters.
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BACKGROUND & PURPOSE: In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. RESULTS: We identified 166 patients with neurological symptoms appearing in less than 1 month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50 years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1 year follow-up. One patient died, and 15% of patients relapsed. Age > 70 years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12 months. No predictors of relapse were identified. CONCLUSION: This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.
Subject(s)
Autoantibodies , Gangliosides , Miller Fisher Syndrome , Humans , Female , Male , Middle Aged , Adult , Gangliosides/immunology , Aged , Retrospective Studies , Young Adult , Adolescent , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Aged, 80 and over , Miller Fisher Syndrome/physiopathology , Miller Fisher Syndrome/blood , Miller Fisher Syndrome/diagnosis , Child , Child, Preschool , Guillain-Barre Syndrome/blood , Guillain-Barre Syndrome/physiopathology , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/immunologySubject(s)
Ileal Neoplasms , Neuroendocrine Tumors , Receptors, Somatostatin , Humans , Male , Ileal Neoplasms/diagnostic imaging , Neoplasm Metastasis , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Organometallic Compounds/therapeutic use , Radiopharmaceuticals , Receptors, Somatostatin/metabolism , Receptors, Somatostatin/antagonists & inhibitors , AgedABSTRACT
PURPOSE: To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [177Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). METHODS: This study was part of a phase I/II trial of [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients. RESULTS: In all evaluated organs, maximum [177Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57-66% within 48 h following the first treatment cycle. At the first treatment cycle, [177Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [177Lu]Lu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles. CONCLUSION: [177Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy. TRIAL REGISTRATION: NCT02592707. Registered October 30, 2015.
Subject(s)
Neuroendocrine Tumors , Humans , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/metabolism , Male , Middle Aged , Female , Aged , Adult , Radiometry , Lutetium/pharmacokinetics , Tissue Distribution , Somatostatin/analogs & derivatives , Somatostatin/pharmacokinetics , Disease Progression , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/therapeutic use , Aged, 80 and over , Octreotide/analogs & derivatives , Octreotide/pharmacokinetics , Octreotide/therapeutic use , RadioisotopesABSTRACT
Our primary aim was to compare the therapeutic index (tumor-to-bone marrow and tumor-to-kidney absorbed-dose ratios) of the new radiolabeled somatostatin receptor antagonist [177Lu]Lu-DOTA-JR11 with the established radiolabeled somatostatin receptor agonist [177Lu]Lu-DOTATOC in the same patients with progressive, standard therapy-refractory meningioma. Methods: In this prospective, single-center, open-label phase 0 study (NCT04997317), 6 consecutive patients were included: 3 men and 3 women (mean age, 63.5 y). Patients received 6.9-7.3 GBq (standard injected radioactivity) of [177Lu]Lu-DOTATOC followed by 3.3-4.9 GBq (2 GBq/m2 × body surface area) of [177Lu]Lu-DOTA-JR11 at an interval of 10 ± 1 wk. In total, 1 [177Lu]Lu-DOTATOC and 2-3 [177Lu]Lu-DOTA-JR11 treatment cycles were performed. Quantitative SPECT/CT was done at approximately 24, 48, and 168 h after injection of both radiopharmaceuticals to calculate meningioma and organ absorbed doses as well as tumor-to-organ absorbed-dose ratios (3-dimensional segmentation approach for meningioma, kidneys, liver, bone marrow, and spleen). Results: The median of the meningioma absorbed dose of 1 treatment cycle was 3.4 Gy (range, 0.8-10.2 Gy) for [177Lu]Lu-DOTATOC and 11.5 Gy (range, 4.7-22.7 Gy) for [177Lu]Lu-DOTA-JR11. The median bone marrow and kidney absorbed doses after 1 treatment cycle were 0.11 Gy (range, 0.05-0.17 Gy) and 2.7 Gy (range, 1.3-5.3 Gy) for [177Lu]Lu-DOTATOC and 0.29 Gy (range, 0.16-0.39 Gy) and 3.3 Gy (range, 1.6-5.9 Gy) for [177Lu]Lu-DOTA-JR11, resulting in a 1.4 (range, 0.9-1.9) times higher median tumor-to-bone marrow absorbed-dose ratio and a 2.9 (range, 2.0-4.8) times higher median tumor-to-kidney absorbed-dose ratio with [177Lu]Lu-DOTA-JR11. According to the Common Terminology Criteria for Adverse Events version 5.0, 2 patients developed reversible grade 2 lymphopenia after 1 cycle of [177Lu]Lu-DOTATOC. Afterward, 2 patients developed reversible grade 3 lymphopenia and 1 patient developed reversible grade 3 lymphopenia and neutropenia after 2-3 cycles of [177Lu]Lu-DOTA-JR11. No grade 4 or 5 adverse events were observed at 15 mo or more after the start of therapy. The disease control rate was 83% (95% CI, 53%-100%) at 12 mo or more after inclusion. Conclusion: Treatment with 1 cycle of [177Lu]Lu-DOTA-JR11 showed 2.2-5.7 times higher meningioma absorbed doses and a favorable therapeutic index compared with [177Lu]Lu-DOTATOC after injection of 1.4-2.1 times lower activities. The first efficacy results demonstrated a high disease control rate with an acceptable safety profile in the standard therapy for refractory meningioma patients. Therefore, larger studies with [177Lu]Lu-DOTA-JR11 are warranted in meningioma patients.
Subject(s)
Lymphopenia , Meningeal Neoplasms , Meningioma , Neuroendocrine Tumors , Organometallic Compounds , Female , Humans , Male , Middle Aged , Meningeal Neoplasms/radiotherapy , Meningioma/radiotherapy , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/drug therapy , Octreotide/adverse effects , Organometallic Compounds/adverse effects , Prospective Studies , Radioisotopes/therapeutic use , Receptors, SomatostatinABSTRACT
Metastatic insulinoma is a rare malignant neuroendocrine tumor characterized by inappropriate insulin secretion, resulting in life-threatening hypoglycemia, which is often difficult to treat. There is currently very limited information about the efficacy of peptide receptor radionuclide therapy (PRRT) for clinical control of hypoglycemia. The aim of this long-term retrospective study was to evaluate the therapeutic efficacy of PRRT for improving hypoglycemia, to evaluate the change of medication after PRRT, and to calculate progression-free survival (PFS) and overall survival (OS). Methods: Inclusion criteria were histologically proven somatostatin receptor-positive metastatic malignant insulinoma and at least 2 cycles of [90Y]Y-DOTATOC or [177Lu]Lu-DOTATOC therapy from early 2000 to early 2022. A semiquantitative scoring system was used to quantify the severity and frequency of hypoglycemic episodes under background antihypoglycemic therapy (somatostatin analog, diazoxide, everolimus, corticosteroids): score 0, no hypoglycemic episodes; score 1, hypoglycemic events requiring additional conservative treatment with optimization of nutrition; score 2, severe hypoglycemia necessitating hospitalization and combined medication or history of hypoglycemic coma. Hypoglycemic score before and after PRRT was analyzed. Time of benefit was defined as a time range of fewer hypoglycemic episodes in the observation period than at baseline. Information on antihypoglycemic medication before and after therapy, PFS, and OS was recorded. Results: Twenty-six of 32 patients with a total of 106 [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC cycles were included. The average observation period was 21.5 mo (range, 2.3-107.4 mo). Before therapy, 81% (n = 21) of the patients had a hypoglycemia score of 2 and 19% (n = 5) had a score of 1. After PRRT, 81% of patients (n = 21) had a decreased score, and the remaining 5 patients showed a stable situation. There was temporary worsening of hypoglycemia just after injection of [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC in 19% of patients. The average time of benefit in the observation period was 17.2 mo (range, 0-70.2 mo). Antihypoglycemic medication reduction was achieved in 58% (n = 15) of patients. The median OS and PFS after the start of PRRT were 19.7 mo (95% CI, 6.5-32.9 mo) and 11.7 mo (95% CI, 4.9-18.5 mo), respectively. Conclusion: To our knowledge, our study included the largest cohort of patients with malignant insulinoma to be evaluated. Long-lasting symptom control and reduction of antihypoglycemic medications were shown in most patients after late-line PRRT.
Subject(s)
Hypoglycemia , Insulinoma , Neuroendocrine Tumors , Organometallic Compounds , Pancreatic Neoplasms , Humans , Retrospective Studies , Insulinoma/radiotherapy , Treatment Outcome , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/drug therapy , Octreotide/adverse effects , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/drug therapy , Radioisotopes , Hypoglycemia/chemically induced , Hypoglycemia/drug therapy , Receptors, Peptide/chemistry , Hypoglycemic Agents , Organometallic Compounds/therapeutic useABSTRACT
INTRODUCTION: Sentinel lymph node biopsy for oral and oropharyngeal squamous cell carcinoma is a well-established staging method. One variation is to inject a radioactive tracer near the primary tumor of the patient. After a few minutes, audio feedback from an external hand-held [Formula: see text]-detection probe can monitor the uptake into the lymphatic system. Such probes place a high cognitive load on the surgeon during the biopsy, as they require the simultaneous use of both hands and the skills necessary to correlate the audio signal with the location of tracer accumulation in the lymph nodes. Therefore, an augmented reality (AR) approach to directly visualize and thus discriminate nearby lymph nodes would greatly reduce the surgeons' cognitive load. MATERIALS AND METHODS: We present a proof of concept of an AR approach for sentinel lymph node biopsy by ex vivo experiments. The 3D position of the radioactive [Formula: see text]-sources is reconstructed from a single [Formula: see text]-image, acquired by a stationary table-attached multi-pinhole [Formula: see text]-detector. The position of the sources is then visualized using Microsoft's HoloLens. We further investigate the performance of our SLNF algorithm for a single source, two sources, and two sources with a hot background. RESULTS: In our ex vivo experiments, a single [Formula: see text]-source and its AR representation show good correlation with known locations, with a maximum error of 4.47 mm. The SLNF algorithm performs well when only one source is reconstructed, with a maximum error of 7.77 mm. For the more challenging case to reconstruct two sources, the errors vary between 2.23 mm and 75.92 mm. CONCLUSION: This proof of concept shows promising results in reconstructing and displaying one [Formula: see text]-source. Two simultaneously recorded sources are more challenging and require further algorithmic optimization.
Subject(s)
Augmented Reality , Sentinel Lymph Node Biopsy , Humans , Sentinel Lymph Node Biopsy/methods , Lymph Nodes/pathology , Neoplasm StagingABSTRACT
PURPOSE: To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy. METHODS: Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021-01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan-Meier methodology (log-rank test). RESULTS: Between 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4-26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09-0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07-0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16-0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01-0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02-0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively). CONCLUSION: Six weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.
Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant , Urea/analogs & derivatives , Male , Humans , Prostatic Neoplasms, Castration-Resistant/diagnostic imaging , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Switzerland , Single Photon Emission Computed Tomography Computed Tomography , Treatment Outcome , Heterocyclic Compounds, 1-Ring/therapeutic use , Lutetium/therapeutic use , Dipeptides/therapeutic use , Retrospective StudiesABSTRACT
INTRODUCTION: Fatty-acid oxidation disorders (FAODs) are recessive genetic diseases. MATERIALS AND METHODS: We report here clinical and paraclinical data from a retrospective study of 44 adults with muscular FAODs from six French reference centers for neuromuscular or metabolic diseases. RESULTS: The study cohort consisted of 44 adult patients: 14 with carnitine palmitoyl transferase 2 deficiency (32%), nine with multiple acyl-CoA deficiency (20%), 13 with very long-chain acyl-CoA dehydrogenase deficiency (30%), three with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (7%), and five with short-chain acyl-CoA dehydrogenase deficiency (11%). Disease onset occurred during childhood in the majority of patients (59%), with a mean age at onset of 15 years (range = 0.5-35) and a mean of 12.6 years (range = 0-58) from disease onset to diagnosis. The principal symptoms were acute muscle manifestations (rhabdomyolysis, exercise intolerance, myalgia), sometimes associated with permanent muscle weakness. Episodes of rhabdomyolysis were frequent (84%), with a mean creatinine kinase level of 68,958 U/L (range = 660-300,000). General metabolic complications were observed in 58% of patients, respiratory manifestations in 18% of cases, and cardiological manifestations in 9% of cases. Fasting acylcarnitine profile was used to orient genetic explorations in 65% of cases. After a mean follow-up of 10 years, 33% of patients were asymptomatic and 56% continued to display symptoms after exercise. The frequency of rhabdomyolysis decreased after diagnosis in 64% of cases. CONCLUSION: A standardized register would complete this cohort description of muscular forms of FAODs with exhaustive data, making it possible to assess the efficacy of therapeutic protocols in real-life conditions and during the long-term follow-up of patients.
Subject(s)
Mitochondrial Diseases , Muscular Diseases , Rhabdomyolysis , Adult , Humans , Infant , Child, Preschool , Child , Adolescent , Young Adult , Retrospective Studies , Muscular Diseases/complications , Mitochondrial Diseases/complications , PrognosisABSTRACT
This study aims to identify stroke regulation profiles and tipping-points in stroke regulation timing during international open water races according to performance level. Twelve elite or world-class swimmers were analysed during 18 international races. Stroke rate and jerk cost were computed cycle-to-cycle using an Inertial Measurement Unit and regulations profiles fitted using polynomials. We performed two-ways mixed-ANOVA to compare stroke kinematics among race segments and performance groups (G1 -fastest- to G3 -slowest-). Swimmers displayed specific regulation profiles (i.e., J-shape with end-spurt, J-shape without end-spurt and reverse L-shape for stroke rate and U-shape, reverse J-shape and reverse L-shape for jerk cost, for respectively G1, G2 and G3) with significant effect of race segment on stroke kinematics for G1 and G2. We highlighted tipping-points in stroke regulations profiles (TP1 and TP2) at respectively 30% and 75% of the race with greater magnitude in G1 than G2. TP1 reflects the end of a stroke economy period (0-30%) and TP2 the end of a progressive increase in stroke kinematics (30-75%) towards end-spurt (75-100%). Open water races follow a high-grading dynamics requiring biomechanical regulations along the race. Targeting stroke rate reserve and management of stroke smoothness should be considered during training of open water swimmers.
Subject(s)
Athletic Performance , Humans , Athletic Performance/physiology , Swimming/physiology , Biomechanical Phenomena , Algorithms , Water , Competitive Behavior/physiologyABSTRACT
PURPOSE: We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [177Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity. METHODS: This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [177Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.5 GBq/300 µg). Part B, which included 25 patients who received one to five cycles of [177Lu]Lu-satoreotide tetraxetan, evaluated different administered activities (4.5 or 6.0 GBq/cycle) and peptide amounts (300, 700, or 1300 µg/cycle), limited to a cumulative absorbed radiation dose of 23 Gy to the kidneys and 1.5 Gy to the bone marrow. RESULTS: Median cumulative administered activity of [177Lu]Lu-satoreotide tetraxetan was 13.0 GBq over three cycles (13.1 GBq in part A and 12.9 GBq in part B). Overall, 17 (42.5%) patients experienced grade ≥ 3 treatmentrelated adverse events; the most common were lymphopenia, thrombocytopenia, and neutropenia. No grade 3/4 nephrotoxicity was observed. Two patients developed myeloid neoplasms considered treatment related by the investigator. Disease control rate for part A and part B was 94.7% (95% confidence interval [CI]: 82.3-99.4), and overall response rate was 21.1% (95% CI: 9.6-37.3). CONCLUSION: [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three cycles, has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs. A 5-year long-term follow-up study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02592707. Registered October 30, 2015.
Subject(s)
Neuroendocrine Tumors , Organometallic Compounds , Humans , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/drug therapy , Receptors, Somatostatin , Octreotide/adverse effects , Follow-Up Studies , Organometallic Compounds/adverse effectsABSTRACT
The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the available options is of the utmost importance. While international guidelines list relevant pivotal trials and give recommendations for a variety of clinical scenarios, there is much room for interpretation, and several important questions remain highly debated. The goal of developing a national consensus on the use of these novel diagnostic and therapeutic strategies in order to improve disease management and eventually patient outcomes has prompted a Swiss consensus meeting. Experts from several specialties, including urology, medical oncology, radiation oncology, pathology and nuclear medicine, discussed and voted on questions of the current most important areas of uncertainty, including the staging and treatment of high-risk localized disease, treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and use of new options to treat metastatic castration-resistant prostate cancer (mCRPC).
Subject(s)
Prostatic Neoplasms , Male , Humans , Consensus , Switzerland , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Interdisciplinary Studies , Medical OncologyABSTRACT
OBJECTIVES: Based on previous studies, single-photon emission computed tomography/computed tomography (SPECT/CT) has been proven more accurate and reproducible than planar lung perfusion scintigraphy to assess lobar perfusion. However, the impact of 3D-quantitated SPECT/CT on intended management in functionally marginal candidates for pulmonary resection is unknown. The evaluation of this impact was the main aim of this study. METHODS: Consecutive candidates for lung resection underwent preoperative evaluation according to ERS/ESTS Algorithm and underwent preoperative lung perfusion imaging. The lobar contribution to the total lung perfusion was estimated using established planar scintigraphic methods and 3-dimensional quantitative SPECT/CT method (CT Pulmo3D and xSPECT-Quant, Siemens). The difference in estimated lobar perfusion with resulting changes in predicted postoperative (ppo) lung function and extent of lung resection were analyzed to reveal possible changes in operability. In-hospital outcome was assessed. RESULTS: One hundred twenty patients (46 females) were enrolled. The mean age (±SD) of patients was 68 ± 9 years, target lesions were in upper lobes in 57.7% and in lower lobes in 33.5%. The median FEV1 (forced expiratory volume in 1 second) was 70.5% (IQR 52-84) and median DLCO (diffusion capacity of lung for carbon monoxide) was 56.6% [47.1-67.4]. The planar posterior oblique method, compared to 3D-quantitated SPECT/CT, underestimated the perfusion of upper lobes by a median difference of 5% (right [2-9], left [2.5-8]; P = <.0001), while it overestimated the perfusion of lower lobes (left by 4% [2-7], right by 6% [2-9]; P = <.0001). In contrast to planar scintigraphy-based evaluation, 4 patients (3.3%), all with upper lobe lesions, were classified as inoperable when 3D-quantitated SPECT/CT was used for calculation of the ppo lung function. CONCLUSIONS: In selected patients with upper lobe lesions, 3D-quantitated SPECT/CT would have changed the treatment strategy from operable to inoperable. Importantly, postoperative mortality in this particular subgroup was disproportionally high. 3D-quantitated SPECT/CT shall be further evaluated as it might improve preoperative risk stratification in functionally marginal candidates.
Subject(s)
Lung Neoplasms , Female , Humans , Middle Aged , Aged , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Single Photon Emission Computed Tomography Computed Tomography/methods , Lung/diagnostic imaging , Lung/surgery , Radionuclide Imaging , Pneumonectomy , Perfusion , Tomography, Emission-Computed, Single-PhotonABSTRACT
BACKGROUND: Recreational use of nitrous oxide (N2 O) has dramatically increased in recent years, resulting in numerous cases of acute sensorimotor tetraparesis secondary to nitrous oxide-induced neuropathy (N2 On). Challenging clinical features can mimic Guillain-Barré syndrome (GBS), the main differential diagnosis upon admission. The most sensitive biomarkers for distinguishing between these two conditions remain to be determined. METHODS: Fifty-eight N2 On patients from three referral centers were retrospectively included over a 2-year period and compared to GBS patients hospitalized during the same timeframe (47 patients). Collected demographic, clinical, biological, and electrophysiological data were compared between the two groups. RESULTS: The typical N2 On clinical pattern included distal sensorimotor deficit in lower limbs with absent reflexes, proprioceptive ataxia, and no cranial involvement (56.7% of our cohort). Misleading GBS-like presentations were found in 14 N2 On patients (24.1%), and 13 patients (22.4%) did not report N2 O use during initial interview. Only half the N2 On patients presented with reduced vitamin B12 serum levels upon admission. A slightly increased cut-off (<200 pmol/L) demonstrated 85.1% sensitivity and 84.5% specificity in distinguishing N2 On from GBS. Only 6.9% of N2 On patients met the criteria for primary demyelination (p < 0.01), with only one presenting conduction blocks. A diagnostic algorithm combining these two biomarkers successfully classified all GBS-like N2 On patients. CONCLUSIONS: Vitamin B12 serum level < 200 pmol/L cut-off and conduction blocks in initial electrophysiological study are the two most sensitive biomarkers for rapidly distinguishing N2 On from GBS patients. These two parameters are particularly useful in clinically atypical N2 On with GBS-like presentation.
Subject(s)
Guillain-Barre Syndrome , Humans , Guillain-Barre Syndrome/chemically induced , Guillain-Barre Syndrome/diagnosis , Retrospective Studies , Nitrous Oxide/adverse effects , Biomarkers , Vitamin B 12ABSTRACT
BACKGROUND: Guillain-Barre syndrome (GBS) is an acute inflammatory polyradiculoneuropathy rarely observed during pregnancy. METHODS: In this retrospective study, we analyzed the characteristics of pregnant women with GBS (pGBS) diagnosed in French University Hospitals in the 2002-2022 period and compared them with a reference group of same-age non-pregnant women with GBS (npGBS) identified in the same institutions & timeframe. RESULTS: We identified 16 pGBS cases. Median age was 31 years (28-36), and GBS developed in the 1st, 2nd, and 3rd trimester in 31%, 31% and 38% of cases respectively. A previous infection was identified in six cases (37%), GBS was demyelinating in nine cases (56%), and four patients (25%) needed respiratory assistance. Fifteen patients (94%) were treated with intravenous immunoglobulins, and neurological recovery was complete in all cases (100%). Unscheduled caesarean section was needed in five cases (31%), and two fetuses (12.5%) died because of cytomegalovirus (CMV) infection (1 case) and HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome (1 case). In comparison with a reference group of 18 npGBS women with a median age of 30 years (27-33), pGBS patients more frequently had CMV infection (31% vs 11%), had a prolonged delay between GBS onset and hospital admission (delay > 7 days: 57% vs 12%), more often needed ICU admission (56% vs 33%) and respiratory assistance (25% vs 11%), and more often presented with treatment-related fluctuations (37% vs 0%). CONCLUSIONS: This study shows GBS during pregnancy is a severe maternal condition with significant fetal mortality.
Subject(s)
Cytomegalovirus Infections , Guillain-Barre Syndrome , Humans , Female , Pregnancy , Adult , Guillain-Barre Syndrome/complications , Guillain-Barre Syndrome/therapy , Guillain-Barre Syndrome/diagnosis , Retrospective Studies , Cesarean Section , FetusABSTRACT
INTRODUCTION/AIMS: Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most common form of Guillain-Barré syndrome (GBS) in Western countries. However, electrophysiological descriptions of changes in abnormalities suggestive of demyelination after an AIDP episode are rare. We aimed to describe the clinical and electrophysiological features of AIDP patients after the acute episode, to investigate changes in abnormalities suggestive of demyelination and to compare with electrophysiological features of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We reviewed the clinical and electrophysiological characteristics of 61 patients followed at regular intervals after the AIDP episode. RESULTS: We detected early electrophysiological abnormalities from the first nerve conduction studies (NCS) performed before 3 wk. Abnormalities suggestive of demyelination worsened on subsequent examinations. This worsening continued after more than 3 mo of follow-up for some parameters. We also found the persistence of abnormalities suggestive of demyelination for long periods after the acute episode, beyond 18 mo of follow-up, despite clinical improvement in most patients. DISCUSSION: In AIDP, NCS findings continue to worsen several weeks or even months after the onset of symptoms, and "CIDP-like" abnormalities suggestive of demyelination may persist for a long period of time, in contrast to the existing literature and the usually favorable clinical course. Thus, the discovery of conduction abnormalities on NCS performed long after an AIDP should always be interpreted according to the clinical context and not systematically lead to a diagnosis of CIDP.