ABSTRACT
Introduction: Prostate-specific membrane antigen (PSMA) is present in high amounts in salivary glands, but it is unclear whether labeled binders of PSMA are excreted in the saliva. Methods: Ten patients with prostate cancer underwent whole-body [18F]DCFPyL PET/CT (NCT03181867), and saliva samples were collected between 0-120 minutes post-injection. [18F]DCFPyL salivary excretion was measured over 120 minutes and expressed as %ID/g. Protein-associated binding was estimated by the percentage of [18F]DCFPyL versus parent radiotracer. Results: All PET scans of 10 patients (69 ± 8 years) with histologically confirmed prostate cancer (PSA= 2.4 ± 2.4, and Gleason Grade = 6-9) showed high uptake of [18F]-DCFPyL in salivary glands while 8 patients demonstrated high uptake in the saliva at 45 minutes. The intact [18F]-DCFPyL (98%) was also confirmed in the saliva samples at 120 min with increasing salivary radioactivity between 30-120 min. Conclusion: Systemically injected [18F]DCFPyL shows salivary gland uptake, an increasing amount of which is secreted in saliva over time and is not maximized by 120 minutes post-injection. Although probably insignificant for diagnostic studies, patients undergoing PSMA-targeted therapies should be aware of radioactivity in saliva.
ABSTRACT
INTRODUCTION: Cannabis may provide inflammatory bowel disease (IBD) patients with an alternative to opioids for pain. METHODS: We conducted a difference-in-difference analysis using MarketScan. Changes over time in rates of opioid prescribing were compared in states with legalized cannabis to those without. RESULTS: We identified 6,240 patients with IBD in states with legalized cannabis and 79,272 patients with IBD in states without legalized cannabis. The rate of opioid prescribing decreased over time in both groups and were not significantly different (attributed differential = 0.34, confidence interval -13.02 to 13.70, P = 0.96). DISCUSSION: Opioid prescribing decreased from 2009 to 2016 among patients with IBD in both states with legalized and state without legalized cannabis, similar to what has been observed nationally across a variety of diseases. Cannabis legalization was not associated with a lower rate of opioid prescribing for patients with IBD.
ABSTRACT
INTRODUCTION: Insurer-mandated barriers to timely initiation of advanced therapies used to treat inflammatory bowel disease (IBD) have been shown to worsen clinical outcomes and increase healthcare utilization, yet rarely alter the medication ultimately prescribed. METHODS: We conducted a survey within the IBD Partners longitudinal cohort to evaluate the frequency and patient-reported impacts of medication utilization barriers on insurance satisfaction and clinical outcomes. Barriers included medication denials, prior authorizations, and forced medication switches. Variables associated with insurance satisfaction, measured on a 1-7 Likert scale, were identified. The association between insurance-related barriers and downstream clinical outcomes (surgery, corticosteroid requirement, and disease activity) were evaluated. RESULTS: Two thousand seventeen patients (age 45 [interquartile range 34-58] years, 73% female) were included. Seventy-two percent experienced an insurer-mandated barrier, most commonly prior authorizations (51%). Fifteen percent were denied an IBD medication by their insurer, 22% experienced an insurance-related gap in therapy, and 8% were forced by their insurer to switch from an effective medication. Insurance satisfaction was negatively associated with medication denials, prior authorization-related delays, gaps in therapy, and high-deductible health plan coverage. In the year following the initial survey, several insurance barriers were linked to negative downstream clinical outcomes, including prior authorizations associated with corticosteroid rescue (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.25-4.00), forced medication switches associated with continued disease activity (OR 3.28, 95% CI 1.56-6.89), and medication denials associated with IBD-related surgery (OR 8.92, 95% CI 1.97-40.39). DISCUSSION: These data illustrate the frequency and negative impacts of insurer-mandated medication barriers on patients with IBD, including decreased insurance satisfaction and negative downstream clinical outcomes.
ABSTRACT
BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.
Subject(s)
Artificial Intelligence , Colonic Polyps , Colonoscopy , Diagnosis, Computer-Assisted , Sensitivity and Specificity , Humans , Colonic Polyps/pathology , Prospective Studies , Female , Male , Middle Aged , Aged , Adenoma/pathology , Adenoma/diagnosis , Colorectal Neoplasms/pathology , Clinical Competence , AdultABSTRACT
OBJECTIVES: Increased fetal lung heterogeneity has been associated with term fetal lungs in singleton gestations. The objective of this study was to determine if fetal lung heterogeneity index (HI) differs between twin and singleton fetuses in the late second and third trimesters. METHODS: Prospective cohort study of women with singleton and twin gestations with medically-indicated ultrasound examinations at 24 weeks of gestation onward. Grayscale transverse fetal lung images were obtained at the level of the four-chamber heart. A region of interest was selected in each fetal lung image. Fetal lung HI was determined with MATLAB software using a dithering technique with ultrasound image pixels transformed into a binary map form from which a dynamic range value was determined. HI averages and standard deviations were generated for twin and singleton fetuses from 24 weeks gestation onward. Two sample t-tests were used to compare the mean HI at each gestational week between singleton and twin fetuses. RESULTS: In total, 388 singleton and 478 twin images were analyzed. From 35 through 38 weeks of gestation a statistically significant divergence in mean HI was observed with higher means in singleton compared to twin fetuses. At 24 weeks of gestation there was a significantly higher HI in twin fetuses compared to singletons. No differences in fetal lung HI were observed between 25 and 34 weeks gestational age. CONCLUSIONS: Differences in fetal lung HI were observed when comparing twin and singleton fetuses. Further investigation is required to determine the potential clinical significance of these findings.
Subject(s)
Lung , Pregnancy, Twin , Ultrasonography, Prenatal , Humans , Female , Pregnancy , Ultrasonography, Prenatal/methods , Lung/diagnostic imaging , Lung/embryology , Prospective Studies , Adult , Pregnancy Trimester, Third , Gestational Age , Pregnancy Trimester, SecondABSTRACT
Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-producing tumors that express somatostatin receptors (SSTR) that can be treated with lutetium-177 DOTATATE (Lu-177-TRT); however, treatment can be associated with life-threatening cardiovascular events. A patient case with management strategies for high-risk PPGL patients receiving Lu-177-TRT is described. The 78-year-old patient with metastatic paraganglioma was enrolled and treated under NCT03206060. Deemed to be at high risk, the patient was preemptively admitted to the intensive care unit (ICU) with central line access placed. Due to comorbidities, a reduced dose of 100 mCi x 4 cycles was used for this patient. Vital signs, blood work, and serum catecholamine levels were obtained at various time points. Despite reduced dosing, the patient still developed a severe hypertensive reaction with systolic blood pressure of 240â mmHg within minutes of Lu-177-TRT infusion, which was controlled with an intravenous nicardipine drip. The patient remained in the ICU for 24â hours post Lu-177-TRT before moving to an inpatient ward for an additional 24â hours. All subsequent infusions were performed using reduced doses with elective ICU admissions and were well-tolerated. Despite the increased risk, metastatic PPGL patients can be safely treated with proper staff training, monitoring, and preparation for intravenous medications, especially nicardipine.
ABSTRACT
OBJECTIVE: To compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases. MATERIALS AND METHODS: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRIspine), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRIWB), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CTWB). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported. RESULTS: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [18F]FDG (72.0%, 275/382, p < 0.001), MRIspine (80.6%, 308/382, p < 0.001), MRIWB (55.3%, 136/246, p < 0.001), and CTWB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [68Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [18F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRIspine (97.6%, 40/41, p = 1.00), MRIWB (95.7%, 22/23, p = 1.00), and CTWB (81.8%, 27/33, p = 0.03). CONCLUSIONS: [68Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate. CLINICAL RELEVANCE STATEMENT: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [18F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001). KEY POINTS: ⢠Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. ⢠[68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [18]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. ⢠[68Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma.
ABSTRACT
Our objective was to determine if placental lake presence or size is associated with adverse pregnancy outcomes. This was a retrospective cohort of patients who had fetal anatomy ultrasounds at 18-22 weeks and delivered between 2018 and 2022. Placental lakes were classified as small (>2.0 to 3.9 cm) or large (≥4 cm). Multiple gestations, placenta previas, and placenta accretas were excluded. Outcomes included low birthweight, cesarean delivery, primary cesarean for non-reassuring fetal heart tracing, fetal growth restriction, preterm birth, and severe preeclampsia. A total of 1052 patients were included; 294 had placental lakes (204 small, 90 large). No differences in pregnancy outcomes were observed.
Subject(s)
Pregnancy Outcome , Ultrasonography, Prenatal , Humans , Female , Pregnancy , Retrospective Studies , Adult , Placenta/diagnostic imaging , Placenta/anatomy & histology , Pregnancy Trimester, Second , Cesarean SectionABSTRACT
Paragangliomas can metastasize, posing potential challenges both in symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma-targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. Perspectives in radiotherapies of paraganglioma patients are outlined since they hold promising approaches in the near future that can improve patient outcomes.
Subject(s)
Paraganglioma , Humans , Paraganglioma/radiotherapy , Paraganglioma/pathology , Radiopharmaceuticals/therapeutic use , 3-Iodobenzylguanidine/therapeutic use , Octreotide/analogs & derivatives , Octreotide/therapeutic use , Organometallic Compounds/therapeutic use , Adrenal Gland Neoplasms/radiotherapyABSTRACT
OBJECTIVES: Pediatric patients diagnosed with inflammatory bowel disease (IBD) are at risk of suboptimal peak bone mass attainment. This study aimed to understand rates of bone health screening adherence, describe factors associated with dual-energy X-ray absorptiometry (DXA) acquisition, and identify factors associated with abnormal DXA. METHODS: We performed a retrospective cohort study of pediatric IBD patients over a 10-year time frame. We included IBD patients (2-20 years of age) enrolled in ImproveCareNow and excluded patients with primary metabolic bone disease. Time-to-event methods and multivariable logistic regression were employed to identify factors associated with DXA acquisition and abnormal DXA. RESULTS: In 676 patients, 464 (68.63%) pediatric patients with IBD had a risk factor for low bone mineral density (BMD); 137 (29.53%) underwent an initial DXA scan. Quiescent disease was significantly associated with a reduced likelihood of DXA (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97), while weight z-score <-2 was significantly associated with DXA performance (HR: 2.07; 95% CI: 1.08-3.98). Abnormal DXA results (BMD z-score ≤-1) occurred in 59 (35.54%) individuals. After adjusting for visit diagnosis, delayed puberty, severe disease course, 6 months or greater of steroid exposure, and history of fracture, BMI z-score <-1 (odds ratio: 5.45; 95% CI: 2.41-12.33) was associated with abnormal DXA. CONCLUSIONS: DXA screening occurred in less than one-third of eligible pediatric IBD patients. Compliance was more common in patients with a weight z-score <-2 and less common in those with quiescent disease. BMI strongly predicted abnormal DXA results when adjusting for risk factors for abnormal BMD.
Subject(s)
Bone Diseases, Metabolic , Inflammatory Bowel Diseases , Humans , Child , Absorptiometry, Photon/adverse effects , Absorptiometry, Photon/methods , Bone Density , Retrospective Studies , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/diagnostic imaging , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/diagnosisABSTRACT
INTRODUCTION AND IMPORTANCE: Sclerosing epitheloid fibrosarcoma is a rare variant of low grade sarcoma with specific histologic and immunohistochemical features, and often associated with a poor prognosis. CLINICAL PRESENTATION: We report a case of a 35-year old male who presented with 2 year history of lower back pain, radiating to both lower limbs, weakness to both lower limbs and weight loss more than 5kgs in the past 6 months, no past history of trauma, drenching night sweats, no TB contact history, no incontinence and no any comorbidities. He reported no history of alcohol intake or cigarette smoking, no history of exposure to radiations or similar presentation to his family and no features suggestive of metastasis. On examination - he had maximum midline tenderness L3-S1, no gibbous, upper limbs neurologically intact and power 3/5 to both lower limbs, sensation intact. Computed tomography scan and magnetic resonance imaging revealed an ill-defined osteolytic mass spanning L3 to L5, vertebral plana of L4 and involvement of the left paraspinal muscles. The tumor extended to the extradural space and was also abutting on the distal great vessels. Our intervention entailed laminectomy, tumor debulking and posterior instrumental fusion of the spine. Histopathology findings were in keeping with an invasive sclerosing epitheloid fibrosarcoma. He had adjuvant chemotherapy with good outcome. DISCUSSION: This case was unique due to its lumbar column location, abutting the distal vessels and despite its low grade, it illustrates the malignant potential which responded well to adjuvant chemotherapy. CONCLUSION: Invasive SEF is an aggressive tumor that requires early diagnosis. Multi-modal treatment with surgical resection, adjuvant chemotherapy can improve patient survival and quality of life.
ABSTRACT
Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context.
Subject(s)
COVID-19 , Depression , Adult , Humans , Female , Depression/diagnosis , Depression/epidemiology , Depression/psychology , COVID-19/epidemiology , Pandemics , Switzerland/epidemiology , AnxietyABSTRACT
BACKGROUND: Regional anesthesia techniques are increasingly used in high-income countries (HICs) for both surgical anesthesia and postoperative analgesia. However, regional anesthesia has not been utilized to the same degree in low- to middle-income countries (LMICs) due to a lack of resources and trained personnel. This study evaluates patient satisfaction with, and outcomes of, ultrasound-guided regional anesthesia for extremity surgery at Kilimanjaro Christian Medical Center (KCMC) in the Northeastern zone of Tanzania. METHODS: Study patients were ≥18 years of age; American Society of Anesthesiologists (ASA) physical status I, II, or III; and underwent extremity surgery under peripheral nerve block with ultrasound guidance at KCMC. After placement, blocks were assessed for effectiveness intraoperatively, as demonstrated by the need for supplemental analgesic or sedative medication or conversion to a general anesthetic. Postoperatively, patients were assessed for satisfaction with their nerve block and pain at 12 and 24 hours. Adverse events related to regional anesthesia were assessed immediately, 45 minutes after block placement, and at 12 and 24 hours postoperatively. The primary outcome was patient satisfaction at 12 hours. Secondary outcomes were block success rate and analgesia at 12 and 24 hours postoperatively. RESULTS: A convenience sample of 170 patients was included in the study, of whom 156 (95% confidence interval [CI], 87-95) were either satisfied or very satisfied with their block. Block placement was highly successful with only 8 of 170 participants (95% CI, 2.4-8.3), requiring conversion to a general anesthetic. Analgesia continued in the postoperative period, with 164 of 170 (95% CI, 93-98) patients and 145 of 170 (95% CI, 80-90) patients reporting acceptable analgesia at 12 and 24 hours, respectively. No major adverse events, such as local anesthetic toxicity, infection, bleeding, nerve injury, or pneumothorax, were observed. CONCLUSIONS: Our study found that ultrasound-guided regional anesthesia in a resource-constrained setting was effective for extremity surgery and resulted in high patient satisfaction. No complications occurred. The use of ultrasound-guided regional anesthesia shows promise for the safe and effective care of patients undergoing extremity surgery in LMICs.
Subject(s)
Anesthesia, Conduction , Anesthetics, General , Humans , Patient Satisfaction , Cross-Sectional Studies , Tanzania , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Pain, Postoperative/drug therapy , Anesthesia, Conduction/adverse effects , Ultrasonography, Interventional/methods , Anesthetics, General/therapeutic useABSTRACT
Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.
Subject(s)
Adrenal Gland Neoplasms , Paraganglioma , Pheochromocytoma , Adult , Humans , Child , Pheochromocytoma/genetics , Pheochromocytoma/therapy , Pheochromocytoma/diagnosis , Paraganglioma/genetics , Paraganglioma/therapy , Germ-Line Mutation/genetics , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/therapy , Adrenal Gland Neoplasms/diagnosis , Succinate Dehydrogenase/geneticsABSTRACT
BACKGROUND: Imaging evaluation of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains challenging. Myocardial strain assessment by echocardiography is an increasingly utilized technique for detecting subclinical left ventricular (LV) and right ventricular (RV) dysfunction. We aimed to evaluate the diagnostic and prognostic utility of LV and RV strain in ARVC. METHODS: Patients with suspected ARVC (n = 109) from a multicenter registry were clinically phenotyped using the 2010 ARVC Revised Task Force Criteria and underwent baseline strain echocardiography. Diagnostic performance of LV and RV strain was evaluated using the area under the receiver operating characteristic curve analysis against the 2010 ARVC Revised Task Force Criteria, and the prognostic value was assessed using the Kaplan-Meier analysis. RESULTS: Mean age was 45.3±14.7 years, and 48% of patients were female. Estimation of RV strain was feasible in 99/109 (91%), and LV strain was feasible in 85/109 (78%) patients. ARVC prevalence by 2010 ARVC Revised Task Force Criteria is 91/109 (83%) and 83/99 (84%) in those with RV strain measurements. RV global longitudinal strain and RV free wall strain had diagnostic area under the receiver operating characteristic curve of 0.76 and 0.77, respectively (both P<0.001; difference NS). Abnormal RV global longitudinal strain phenotype (RV global longitudinal strain > -17.9%) and RV free wall strain phenotype (RV free wall strain > -21.2%) were identified in 41/69 (59%) and 56/69 (81%) of subjects, respectively, who were not identified by conventional echocardiographic criteria but still met the overall 2010 ARVC Revised Task Force Criteria for ARVC. LV global longitudinal strain did not add diagnostic value but was prognostic for composite end points of death, heart transplantation, or ventricular arrhythmia (log-rank P=0.04). CONCLUSIONS: In a prospective, multicenter registry of ARVC, RV strain assessment added diagnostic value to current echocardiographic criteria by identifying patients who are missed by current echocardiographic criteria yet still fulfill the diagnosis of ARVC. LV strain, by contrast, did not add incremental diagnostic value but was prognostic for identification of high-risk patients.
Subject(s)
Arrhythmogenic Right Ventricular Dysplasia , Ventricular Dysfunction, Right , Humans , Female , Adult , Middle Aged , Male , Arrhythmogenic Right Ventricular Dysplasia/diagnostic imaging , Arrhythmogenic Right Ventricular Dysplasia/genetics , Prospective Studies , Ventricular Function, Right , Myocardium , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology , RegistriesABSTRACT
Purpose: While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated. Methods: The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed. Results: Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours. Conclusions: [177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.
Subject(s)
Adrenal Gland Neoplasms , Pheochromocytoma , Humans , Male , Female , Adult , Middle Aged , Aged , Pheochromocytoma/radiotherapy , Retrospective Studies , Prolactin , Hydrocortisone , Adrenocorticotropic Hormone , Follicle Stimulating Hormone , Catecholamines , ThyrotropinABSTRACT
Alzheimer Disease (AD) constitutes a major global healthcare problem. Standard AD pharmacotherapies offer only modest transient cognitive and behavioral benefits. Aducanumab, an amyloid monoclonal antibody, was the first disease modifying agent to be approved for AD treatment. However, concerns about its efficacy and side effects led regulatory institutions around the world to restrict its use. Lecanemab was the second amyloid antibody to receive accelerated approval for use in early AD. This review and consensus statement was prepared by the Saudi Chapter of Cognitive and Behavioral Neurology to review the current developments in AD immunotherapies from a Saudi perspective. We outline recommendations with regards to offering aducanumab and other future immunotherapies to Saudi AD patients. We describe resources, infrastructure, research, and clinical practice changes that must be attained to transform the patient journey and clinical pathways of AD in Saudi Arabia to enable offering AD immunotherapies in Saudi Arabia.
Subject(s)
Alzheimer Disease , Neurology , Humans , Alzheimer Disease/therapy , Saudi Arabia , Immunotherapy , CognitionABSTRACT
BACKGROUND: Recent studies have suggested that sleeve gastrectomy (SG) is associated with the development of Barrett esophagus (BE) even in the absence of gastroesophageal reflux disease (GERD) symptoms. OBJECTIVE: The aim of this study was to assess the rates of upper endoscopy and incidence of new BE diagnoses in patients undergoing SG. SETTING: This was a claims-data study of patients who underwent SG between 2012 and 2017 while enrolled in a U.S. statewide database. METHODS: Diagnostic claims data were used to identify pre- and postoperative rates of upper endoscopy, GERD, reflux esophagitis, and BE. Time-to-event analysis using a Kaplan-Meier approach was performed to estimate the cumulative postoperative incidence of these conditions. RESULTS: We identified 5562 patients who underwent SG between 2012 and 2017. Of these, 1972 patients (35.5%) had at least 1 diagnostic record of upper endoscopy. The preoperative incidences of a diagnosis of GERD, esophagitis, and BE were 54.9%, 14.6%, and .9%, respectively. The predicted postoperative incidences of GERD, esophagitis, and BE, respectively, were 18%, 25.4%, and 1.6% at 2 years and 32.1%, 85.0%, and 6.4% at 5 years. CONCLUSIONS: In this large statewide database, rates of esophagogastroduodenoscopy remained low after SG, but the incidence of a new postoperative esophagitis or BE diagnosis in patients who underwent esophagogastroduodenoscopy was higher than in the general population. Patients undergoing SG may have a disproportionately high risk of developing reflux complications including BE after surgery.