Diabetes mellitus in patients with acromegaly: pathophysiology, clinical challenges and management.

Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications.

Predictors of Prolonged Length of Stay after Elective Carotid Revascularization.

OBJECTIVE: Postoperative day-one discharge is used as a quality-of-care indicator after carotid revascularization. This study identifies predictors of prolonged length of stay (pLOS), defined as a postprocedural LOS of > 1 day, after elective carotid revascularization. METHODS: Patients undergoing carotid endarterectomy (CEA), Transcarotid artery revascularization (TCAR) and Transfemoral carotid artery stenting (TFCAS) in the Vascular Quality Initiative between 2016 and 2022 were included in this analysis. Multivariable logistic regression analysis was used to identify predictors of pLOS, defined as a postprocedural LOS of > 1 day, after each procedure. RESULTS: A total of 118,625 elective cases were included. pLOS was observed in nearly 23.2% of patients undergoing carotid revascularization. Major adverse events, including neurological, cardiac, infectious, and bleeding complications, occurred in 5.2% of patients and were the most significant contributor to pLOS after the 3 procedures. Age, female sex, nonwhite race, insurance status, high comorbidity index, prior ipsilateral CEA, non-ambulatory status, symptomatic presentation, surgeries occurring on Friday and postoperative hypo- or hypertension were significantly associated with pLOS across all 3 procedures. For CEA, additional predictors included contralateral carotid artery occlusion, preoperative use of dual antiplatelets and anticoagulation, low physician volume (< 11 cases/year) and drain use. For TCAR, preoperative anticoagulation use, low physician case volume (<6 cases/year), no protamine use, and post-stent dilatation intraoperatively were associated with pLOS. One-year analysis showed a significant association between pLOS and increased mortality for all 3 procedures; CEA (HR,1.64; 95%CI, 1.49-1.82), TCAR (HR,1.56; 95%CI, 1.35-1.80), and TFCAS (HR,1.33; 95%CI,1.08-1.64) (all P<0.05). CONCLUSIONS: A postoperative LOS of more than 1 day is not uncommon after carotid revascularization. Procedure-related complications are the most common drivers of pLOS. Identifying patients are risk for pLOS highlight quality improvement strategies that can optimize short and 1-year outcomes of patients undergoing carotid revascularization.

Seven Years of The Transcarotid Artery Revascularization Surveillance Project, Comparison To Transfemoral Stenting And Endarterectomy.

OBJECTIVE: This study utilizes the latest data from the Vascular Quality Initiative (VQI), which now encompasses over 50,000 transcarotid artery revascularization (TCAR) procedures, to offer a sizeable dataset for comparing the effectiveness and safety of TCAR, transfemoral carotid artery stenting (tfCAS), and carotid endarterectomy (CEA). Given this substantial dataset, we are now able to compare outcomes overall and stratified by symptom status across revascularization techniques. METHODS: Utilizing VQI data from September 2016 to August 2023, we conducted a risk-adjusted analysis by applying inverse probability of treatment weighting to compare in-hospital outcomes between TCAR vs tfCAS, CEA vs tfCAS, and TCAR vs CEA. Our primary outcome measure was in-hospital stroke/death. Secondary outcomes included myocardial infarction and cranial nerve injury. RESULTS: A total of 50,068 patients underwent TCAR, 25,361 patients underwent tfCAS, and 122,737 patients underwent CEA. TCAR patients were older, more likely to have coronary artery disease, chronic kidney disease, and undergo coronary artery bypass grafting/percutaneous coronary intervention as well as prior contralateral CEA/CAS compared to both CEA and tfCAS. TfCAS had higher odds of stroke/death when compared with TCAR (2.9% vs 1.6%, aOR=1.84, 95% CI:1.65-2.06; P<.001) and CEA (2.9% vs 1.3%, aOR=2.21, 95% CI:2.01-2.43; P<.001). CEA had slightly lower odds of stroke/death compared with TCAR (1.3% vs 1.6%, aOR=0.83, 95% CI:0.76-0.91; P<.001). TfCAS had lower odds of cranial nerve injury compared with TCAR (0.0% vs 0.3%, aOR=0.00, 95% CI:0.00-0.00; P<.001) and CEA (0.0% vs 2.3%, aOR=0.00, 95% CI:0.0-0.0; P<.001) as well as lower odds of myocardial infarction compared with CEA (0.4% vs 0.6%, aOR=0.67, 95% CI:0.54-0.84; P<.001). CEA compared with TCAR had higher odds of myocardial infarction (0.6% vs 0.5%, aOR=1.31, 95% CI:1.13-1.54; P<.001) and cranial nerve injury (2.3% vs 0.3%, aOR=9.42, 95% CI:7.78-11.4; P<.001). CONCLUSIONS: While tfCAS may be beneficial for select patients, the lower stroke/death rates associated with CEA and TCAR are preferred. When deciding between CEA and TCAR, it's important to weigh additional procedural factors and outcomes such as myocardial infarction and cranial nerve injury, particularly when stroke/death rates are similar. Additionally, evaluating subgroups that may benefit from one procedure over another is essential for informed decision-making and enhanced patient care in the treatment of carotid stenosis.

Device regulation and surveillance in vascular care: Challenges and opportunities.

Cardiovascular devices are essential for the treatment of cardiovascular diseases including cerebrovascular, coronary, valvular, congenital, peripheral vascular and arrhythmic diseases. The regulation and surveillance of vascular devices in real-world practice, however, presents challenges during each individual product's life cycle. Four examples illustrate recent challenges and questions regarding safety, appropriate use and efficacy arising from FDA approved devices used in real-world practice. We outline potential pathways wherein providers, regulators and payors could potentially provide high-quality cardiovascular care, identify safety signals, ensure equitable device access, and study potential issues with devices in real-world practice.

Changes in acromegaly comorbidities, treatment, and outcome over three decades: a nationwide cohort study.

Objective: To study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer and mortality. Methods: Pertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990-1999, 2000-2009, and 2010-2021) based on the year of diagnosis or treatment initiation. Results: Adenoma size and insulin-like growth factor I (IGF-I) levels at diagnosis did not differ significantly between study periods. The risk of being diagnosed with diabetes, heart disease, sleep apnea, joint disease, and osteoporosis increased from the 1990s to the later decades, while the mortality risk declined to nearly half. The risk of cancer did not significantly change. Treatment changed toward the use of more medical therapy, and fewer patients underwent repeat surgeries or pituitary irradiation. A statistically significant increase in the proportion of patients achieving IGF-I normalization within 3-5 years was observed over time (69%, 83%, and 88%). The proportion of patients with three or more deficient pituitary hormones decreased significantly over time. Conclusion: Modern medical treatment regimens of acromegaly as well as increased awareness and improved diagnostics for its comorbidities have led to better disease control, fewer patients with severe hypopituitarism, and declining mortality in the Danish cohort of acromegaly patients. The risk of cancer did not increase over the study period.

Learning curve of transfemoral carotid artery stenting in the vascular quality initiative registry.

OBJECTIVE: With the recent expansion of the Centers for Medicare and Medicaid Services coverage, transfemoral carotid artery stenting (tfCAS) is expected to play a larger role in the management of carotid disease. Existing research on the tfCAS learning curve, primarily conducted over a decade ago, may not adequately describe the current effect of physician experience on outcomes. Because approximately 30% of perioperative strokes/deaths post-CAS occur after discharge, appropriate thresholds for in-hospital event rates have been suggested to be <4% for symptomatic and <2% for asymptomatic patients. This study evaluates the tfCAS learning curve using Vascular Quality Initiative (VQI) data. METHODS: We identified VQI patients who underwent tfCAS between 2005 and 2023. Each physician's procedures were chronologically grouped into 12 categories, from procedure counts 1-25 to 351+. The primary outcome was in-hospital stroke/death rate; secondary outcomes were in-hospital stroke/death/myocardial infarction (MI), 30-day mortality, in-hospital stroke/transient ischemic attack (stroke/TIA), and access site complications. The relationship between outcomes and procedure counts was analyzed using the Cochran-Armitage test and a generalized linear model with restricted cubic splines. Our results were then validated using a generalized estimating equations model to account for the variability between physicians. RESULTS: We analyzed 43,147 procedures by 2476 physicians. In symptomatic patients, there was a decrease in rates of in-hospital stroke/death (procedure counts 1-25 to 351+: 5.2%-1.7%), in-hospital stroke/death/MI (5.8%-1.7%), 30-day mortality (4.6%-2.8%), in-hospital stroke/TIA (5.0%-1.1%), and access site complications (4.1%-1.1%) as physician experience increased (all P values < .05). The in-hospital stroke/death rate remained above 4% until 235 procedures. Similarly, in asymptomatic patients, there was a decrease in rates of in-hospital stroke/death (2.1%-1.6%), in-hospital stroke/death/MI (2.6%-1.6%), 30-day mortality (1.7%-0.4%), and in-hospital stroke/TIA (2.8%-1.6%) with increasing physician experience (all P values <.05). The in-hospital stroke/death rate remained above 2% until 13 procedures. CONCLUSIONS: In-hospital stroke/death and 30-day mortality rates after tfCAS decreased with increasing physician experience, showing a lengthy learning curve consistent with previous reports. Given that physicians' early cases may not be included in the VQI, the learning curve was likely underestimated. Nevertheless, a substantially high rate of in-hospital stroke/death was found in physicians' first 25 procedures. With the recent Centers for Medicare and Medicaid Services coverage expansion for tfCAS, a significant number of physicians would enter the early stage of the learning curve, potentially leading to increased postoperative complications.

The changing landscape of acromegaly - an epidemiological perspective.

Acromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an epidemiological perspective and describe the temporal evolution of the disease pertaining to epidemiological variables, clinical presentation and mortality. We present updated epidemiological data from the population-based Danish cohort of patients with acromegaly (AcroDEN), along with meta-analyses of existing estimates from around the world.Based on this, we conclude that the incidence, prevalence and age at acromegaly diagnosis are all steadily increasing, but with considerable variation between studies. An increased number of incidental cases may contribute to the increase in incidence and age at diagnosis, respectively. The clinical features at presentation are trending toward a milder disease phenotype at diagnosis, and advances in therapeutic options have reduced the mortality of patients with acromegaly to a level similar to that of the general population. Moreover, the underlying cause of death has shifted from cardiovascular to malignant neoplastic diseases.

A registry-based study of paclitaxel drug-coated balloon angioplasty for the treatment of in-stent restenosis of the femoral-popliteal artery.

OBJECTIVE: The aim of this study was to report the results of a prospective, single-arm, registry-based study assessing the safety and performance of a paclitaxel drug-coated balloon (DCB) for the treatment of superficial femoral artery (SFA) or popliteal artery in-stent restenosis (ISR) in a United States population. METHODS: We conducted a prospective, non-randomized, multi-center, single-arm, post-market registry of the IN.PACT Admiral DCB for the treatment of ISR lesions in the SFA or popliteal artery at 43 sites within the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) Registry from December 2016 to January 2020. Clinical outcomes were assessed at 12, 24, and 36 months. The primary endpoint was target lesion revascularization at 12 months. Secondary endpoints included technical success, target vessel revascularization, major limb amputation, and all-cause mortality. Results are presented as survival probabilities based on Kaplan-Meier survival estimates. RESULTS: Patients (N = 300) were 58% male, with a mean age of 68 ± 10 years. Diabetes was present in 56%, 80% presented with claudication, and 20% with rest pain. Lesions included ISR of the SFA in 68%, SFA-popliteal in 26%, and popliteal arteries in 7%. The mean lesion length was 17.8 ± 11.8 cm. Lesions were categorized as occlusions in 43% (mean occluded length, 16 ± 10 cm). TASC type was A (17%), B (29%), C (38%), and D (15%). Technical success was 99%. Re-stenting was performed in 5% and thrombolysis in 0.6% of patients. Kaplan-Meier estimates for freedom from target lesion revascularization were 90%, 72%, and 62% at 12, 24, and 36 months. Freedom from target vessel revascularization was 88%, 68%, and 59% and freedom from major target limb amputation was 99.6%, 98.9%, and 98.9%, respectively, at 12, 24, and 36 months. Survival was 95%, 89%, and 85% at 12, 24, and 36 months. CONCLUSIONS: This post-market registry-based study shows promising results in treating femoral-popliteal ISR with paclitaxel DCB in comparison to the results of plain balloon angioplasty reported in the literature. These results demonstrate the ability of the SVS VQI to conduct post-market evaluation of peripheral devices in partnership with industry and federal regulators.

ACR Appropriateness Criteria® Lower Extremity Chronic Venous Disease.

Lower extremity venous insufficiency is a chronic medical condition resulting from primary valvular incompetence or, less commonly, prior deep venous thrombosis or extrinsic venous obstruction. Lower extremity chronic venous disease has a high prevalence with a related socioeconomic burden. In the United States, over 11 million males and 22 million females 40 to 80 years of age have varicose veins, with over 2 million adults having advanced chronic venous disease. The high cost to the health care system is related to the recurrent nature of venous ulcerative disease, with total treatment costs estimated >$2.5 billion per year in the United States, with at least 20,556 individuals with newly diagnosed venous ulcers yearly. Various diagnostic and treatment strategies are in place for lower extremity chronic venous disease and are discussed in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Impact of Physician Experience on Stroke or Death Rates in Transfemoral Carotid Artery Stenting: Insights from the Vascular Quality Initiative.

Objective: With the recent expansion of the Centers for Medicare and Medicaid Services (CMS) coverage, transfemoral carotid artery stenting (tfCAS) is expected to play a larger role in the management of carotid disease. Existing research on the tfCAS learning curve, primarily conducted over a decade ago, may not adequately describe the current effect of physician experience on outcomes. This study evaluates the tfCAS learning curve using VQI data. Methods: We analyzed tfCAS patient data from 2005-2023. Each physician's procedures were chronologically grouped into 12 categories, from procedure counts 1-25 to 351+. Primary outcome was in-hospital stroke/death rate; secondary outcomes were in-hospital stroke/death/MI, 30-day mortality, and in-hospital stroke/TIA. The relationship between outcomes and procedure counts was analyzed using Cochran Armitage test and a generalized linear model with restricted cubic splines, validated using generalized estimating equations. Results: We analyzed 43,147 procedures by 2,476 physicians. In symptomatic patients, there was a decrease in rates of in-hospital stroke/death (procedure counts 1-25 to 351+: 5.2% to 1.7%), in-hospital stroke/death/MI (5.8% to 1.7%), 30-day mortality (4.6% to 2.8%), in-hospital stroke/TIA (5.0% to 1.1%) (all p-values<0.05). The in-hospital stroke/death rate remained above 4% until 235 procedures. Similarly, in asymptomatic patients, there was a decrease in rates of in-hospital stroke/death (2.1% to 1.6%), in-hospital stroke/death/MI (2.6% to 1.6%), 30-day mortality (1.7% to 0.4%), and in-hospital stroke/TIA (2.8% to 1.6%) with increasing physician experience (all p-values<0.05). The in-hospital stroke/death rate remained above 2% until 13 procedures. Conclusions: In-hospital stroke/death and 30-day mortality rates post-tfCAS decreased with increasing physician experience, showing a lengthy learning curve consistent with previous reports. Given that physicians' early cases may not be included in the VQI, the learning curve was likely underestimated. With the recent CMS coverage expansion for tfCAS, a significant number of physicians would enter the early stage of the learning curve, potentially leading to increased post-operative complications.

The Effect of a Bacillus-Based Probiotic on Sow and Piglet Performance in Two Production Cycles.

The aim of this study was to assess the impact of Bacillus-based probiotic diets on reproduction performance, fecal scores, microflora, and economic factors in lactating sows and suckling piglets across two productive cycles. A total of 96 sows, reared in a continuous farrowing system for two full cycles, were divided into two groups: a control group and an experimental group. Sows were fed a basal diet without the probiotic or a diet supplemented with viable bacterial spores. At seven days of age, control group piglets were offered standard creep feed, whereas piglets in the experimental (probiotic) group received a diet containing the probiotic fed to their dams. Sows receiving probiotic-supplemented diets were characterized by significantly higher (p ≤ 0.05) average daily feed intake in lactation, lower (p ≤ 0.01) body weight (BW) loss during lactation, and reduced loss of backfat thickness as well as higher body condition score after lactation. Dietary probiotic supplementation increased (p ≤ 0.01) birth weight, total creep feed consumption, litter weight gain, and piglet weaning weight. The probiotic also improved (p ≤ 0.01) overall fecal scores, decreased total E. coli count on day seven and Clostridium perfringens count (trend) in sucking piglets. The total feed cost per weaned piglet was lower in the experimental (probiotic) group. Supplementing the diet with a probiotic containing Bacillus strains improved the reproductive performance of sows and the performance and health of piglets.

Ectopic Cushing's syndrome from a corticotropin-releasing hormone-secreting medullary thyroid carcinoma: a rare pitfall of inferior petrosal sinus sampling.

Summary: This case report describes a rare presentation of ectopic Cushing's syndrome (CS) due to ectopic corticotropin-releasing hormone (CRH) production from a medullary thyroid carcinoma (MTC). The patient, a 69-year-old man, presented with symptoms of muscle weakness, facial plethora, and easy bruising. An inferior petrosal sinus sampling test (IPSS) demonstrated pituitary adrenocorticotrophic hormone (ACTH) secretion, but a whole-body somatostatin receptor scintigraphy (68Ga-DOTATOC PET/CT) revealed enhanced uptake in the right thyroid lobe which, in addition to a grossly elevated serum calcitonin level, was indicative of an MTC. A 18F-DOPA PET/CT scan supported the diagnosis, and histology confirmed the presence of MTC with perinodal growth and regional lymph node metastasis. On immunohistochemical analysis, the tumor cell stained positively for calcitonin and CRH but negatively for ACTH. Distinctly elevated plasma CRH levels were documented. The patient therefore underwent thyroidectomy and bilateral adrenalectomy. This case shows that CS caused by ectopic CRH secretion may masquerade as CS due to a false positive IPSS test. It also highlights the importance of considering rare causes of CS when diagnostic test results are ambiguous. Learning points: Medullary thyroid carcinoma may secrete CRH and cause ectopic CS. Ectopic CRH secretion entails a rare pitfall of inferior petrosal sinus sampling yielding a false positive test. Plasma CRH measurements can be useful in selected cases.

Copeptin levels increase in response to both insulin-induced hypoglycemia and arginine but not to clonidine: data from GH-stimulation tests.

Background: The diagnosis of the polyuria-polydipsia syndrome is challenging. Copeptin is a robust biomarker of arginine vasopressin (AVP) secretion. Arginine, which stimulates growth hormone (GH), has been shown also to stimulate copeptin secretion via unknown mechanisms. Aim: The aim was to investigate copeptin levels in response to three different GH stimulation tests in patients suspected of GH deficiency. Methods: In this cross-sectional study, we measured plasma copeptin levels at baseline and at 60, 105, and 150 min in patients undergoing a stimulation test for growth hormone deficiency with either arginine (n = 16), clonidine (n = 8) or the insulin tolerance test (ITT) (n = 10). Results: In patients undergoing the arginine test, the mean age was 9 years, and 10 years for clonidine. The ITT was only performed in adult patients (>18 years) with a mean age of 49 years. Copeptin level increased significantly from baseline to 60 min after arginine (P <0.01) and ITT (P < 0.01). By contrast, copeptin level tended to decrease after clonidine stimulation (P = 0.14). Conclusion: These data support that infusion of arginine increases plasma copeptin levels and reveal a comparable response after an ITT. We hypothesize that the underlying mechanism is abrogation of somatostatin-induced AVP suppression.

The Vascular Quality Initiative assessment of the Bard Lifestent for the treatment of popliteal artery occlusive disease.

OBJECTIVE: The Bard LifeStent self-expanding stent is approved for the treatment of occlusive disease involving the superficial femoral artery and proximal popliteal artery. We conducted a post-market trial of treatment of the popliteal artery above and below the knee (P1, P2, and P3 segments) within the Society for Vascular Surgery Vascular Quality Initiative (VQI) Peripheral Vascular Intervention registry. METHODS: A single-arm, prospective trial was conducted at 29 VQI sites in the United States, enrolling 74 patients from November 2016 to May 2019. The primary safety outcome was freedom from major adverse events including device-/procedure-related mortality and major amputation at 1 year. The primary efficacy outcomes were freedom from target vessel revascularization and freedom from target lesion revascularization at 1 year. Secondary outcomes included lesion success; procedural success; primary, primary-assisted, and secondary patency; and sustained clinical (improvement in Rutherford class) and hemodynamic success (increase in ankle brachial index >0.10). Outcomes were assessed by Kaplan-Meier analysis. Arteriogram of patients undergoing target lesion revascularization were assessed for stent fracture by a core laboratory. RESULTS: The mean age was 71 years, with 63.5% male and 55% with diabetes. The indication was claudication 28% and chronic limb-threatening ischemia in 72%. The superficial femoral artery-popliteal artery was stented in 38% and the popliteal artery alone in 62%. The majority of stents were placed in the P1 + P2 (39%) or P1 + P2 + P3 (37%) segments of the popliteal artery. The composite primary endpoint of freedom from major adverse events was 82% and 74% at 1 and 2 years, respectively. Freedom from mortality was 100% and 97%, and freedom from major amputation was 100% and 90% at 1 and 12 months, with all deaths and major amputations occurring in patients with chronic limb-threatening ischemia. freedom from target lesion revascularization was 86%, and freedom from target vessel revascularization was 84% at 12 months. At discharge, lesion treatment success was 99%, and procedural success was 82%. Primary patency was 80% and 72%, primary-assisted patency was 80% and 72%, and secondary patency was 89% and 82% at 12 and 24 months. Sustained clinical success was 98% and 95%, and sustained hemodynamic success was 100% and 79% at 12 and 24 months. CONCLUSIONS: In this multi-center, registry-based, single-arm prospective study the Bard LifeStent self-expanding stent demonstrated favorable performance in the challenging anatomy of the P2 and P3 popliteal segment. Post-market studies for label expansion of peripheral vascular intervention devices can be successfully conducted within the Society for Vascular Surgery VQI registry.

Key Device Attributes for Injectable Somatostatin Receptor Ligand Therapy in Acromegaly and Neuroendocrine Tumours.

INTRODUCTION: People living with acromegaly and neuroendocrine tumours (NETs) may be treated with injectable somatostatin receptor ligands (SRLs), administered by either a caregiver or as self-injection via a proprietary or generic device. Injection device attributes that contribute to ease of use and storage, minimise preparation requirements, and reduce injection pain are associated with improved adherence and more favourable therapeutic outcomes. The aim of this study was to assess current opinion surrounding favourable SRL device attributes for people living with acromegaly and NETs as well as that of their caregivers. METHODS: Participants (healthcare professionals [HCPs] and patients/non-HCP caregivers) from 11 countries were invited to answer survey questions related to their demographic, experience, and preferences as they relate to the real-world use of injectable SRL devices. Questions were developed based on review of available literature and meetings with a Scientific Committee. RESULTS: Device attributes preferred by the patient/non-HCP caregiver group (n = 211) included confidence that the correct drug amount is delivered (76%), quick administration with minimal pain/discomfort (68%), and device safety (needle-safety and low risk of contamination; 53%). Device attributes preferred by HCPs (n = 52) were quick administration with minimal pain/discomfort (69%), correct use is easy to learn, confidence in handling the device (63%), and confidence that the correct drug amount is delivered (62%). CONCLUSION: The results identified key features of injection devices for SRL therapy which merit consideration for optimal management and underscore the importance of patient partnership in treatment decisions.

Consensus minimum core data elements adapted to peripheral vascular intervention in the drug-eluting era: Consensus report from the Registry Assessment of Peripheral Interventional Devices (RAPID) Pathways "LEAN" working group.

Registry Assessment of Peripheral Interventional Devices (RAPID) initiated the Pathways Program to provide a transparent, collaborative forum in which to pursue insights into multiple unresolved questions on benefit-risk of paclitaxel-coated devices, including understanding the basis of the mortality signal, without a demonstrable potential biological mechanism, and whether the late mortality signal could be artifact intrinsic to multiple independent prospective randomized data sources that did not prespecify death as a long-term end point. In response to the directive, the LEAN-Case Report Form working group focused on enhancements to the RAPID Phase I Minimum Core Data set through the addition of key clinical modifiers that would be more strongly linked to longer-term mortality outcomes after peripheral arterial disease intervention in the drug-eluting device era, with the goal to have future mortality signals more accurately examined.

Feeding Bacillus-based probiotics to gestating and lactating sows is an efficient method for improving immunity, gut functional status and biofilm formation by probiotic bacteria in piglets at weaning.

The effects of dietary probiotic supplementation with viable Bacillus subtilis and Bacillus amyloliquefaciens spores on sow performance, immunity, gut functional status and biofilm formation by probiotic bacteria in piglets at weaning were investigated. Ninety-six sows reared in a continuous farrowing system for one full cycle were fed gestation diets during the first 90 d of pregnancy and lactation diets until the end of lactation. The sows were fed a basal diet without probiotics (control; n = 48) or a diet supplemented with viable spores (1.1 × 109 CFU/kg of feed) (probiotic; n = 48). At 7 d of age, sucking piglets (n = 12/group) were provided prestarter creep feed until weaning at 28 d of age. The piglets in the probiotic group were supplemented with the same probiotic and dosage as their dams. Blood and colostrum collected from sows and ileal tissues collected from piglets on the day of weaning were used for analyses. Probiotics increased the weight of piglets (P = 0.077), improved the weaning weight (P = 0.039) and increased both the total creep feed consumption (P = 0.027) and litter gain (P = 0.011). Probiotics also improved the faecal score in the second (P = 0.013) week of life. The immunoglobulin G (IgG) concentrations in sow blood at farrowing and the IgM concentrations in piglet blood at weaning were higher in the probiotic group than in the control group (P = 0.046). The piglets from the probiotic-treated sows showed a higher IgM concentration in the ileal mucosa (P = 0.050) and a lower IgG concentration in the ileal mucosa (P = 0.021) compared with the piglets from control sows. The probiotic-treated piglets had a thicker ileal mucosa (P = 0.012) due to the presence of longer villi and larger Peyer's patches (P < 0.001). B. subtilis and B. amyloliquefaciens were detected in the probiotic-treated piglets but not the control piglets; these bacteria were present in the digesta and villus structures and formed structures resembling biofilms. Overall, Bacillus-based probiotic supplementation improves the health indices of sows and their piglets.

Regional variation in patient selection, practice patterns, and outcomes based on techniques for carotid artery revascularization in the Vascular Quality Initiative.

OBJECTIVE: Significant regional variation is known with multiple surgical procedures. This study describes regional variation in carotid revascularization within the Vascular Quality Initiative (VQI). METHODS: Data from the VQI carotid endarterectomy (CEA) and carotid artery stenting (CAS) databases from 2016 to 2021 were used. Nineteen geographic VQI regions were divided into three tertiles based on the average annual volume of carotid procedures performed per region (low-volume: 956 cases [range, 144-1382]; medium-volume: 1533 cases [range, 1432-1589]; and high-volume: 1845 cases [range, 1642-2059]). Patients' characteristics, indications for carotid revascularization, practice patterns, and outcomes (perioperative and 1-year stroke/death) of different revascularization techniques were compared between these regional groups. Regression models that adjust for known risk factors and allow for random effects at the center level were used. RESULTS: CEA was the most common revascularization procedure (>60%) across all regional groups. Significant regional variation was observed in the practice of CEA such as variability in the use of shunting, drain placement, stump pressure and electroencephalogram monitoring, intraoperative protamine, and patch angioplasty. For transfemoral CAS, high-volume regions had a higher proportion of asymptomatic patients with <80% stenosis (30.5% vs 27.8%) in addition to higher use of local/regional anesthesia (80.4% vs 76.2%), protamine (16.1% vs 11.8%), and completion angiography (81.6% vs 77.6%) during transfemoral carotid artery stenting (TF-CAS) compared with low-volume regions. For transcarotid artery revascularization (TCAR), high-volume regions were less likely to intervene on asymptomatic patients with <80% stenosis (32.2% vs 35.8%) than low-volume regions. They also had a higher proportion of urgent/emergent procedures (13.6% vs 10.4%) and were more likely to use general anesthesia (92.0% vs 82.1%), completion angiography (67.3% vs 63.0%), and poststent ballooning (48.4% vs 36.8%). For each carotid revascularization technique, no significant differences were noted in perioperative and 1-year outcomes between low-, medium-, and high-volume regions. Finally, there were no significant differences in outcomes between TCAR and CEA across the different regional groups. In all regional groups, TCAR was associated with a 40% reduction in perioperative and 1-year stroke/death compared with TF-CAS. CONCLUSIONS: Despite significant variation in clinical practices for the management of carotid disease, no regional variation exists in the overall outcomes of carotid interventions. TCAR and CEA continue to show superior outcomes to TF-CAS across all VQI regional groups.

Whole-Body and Forearm Muscle Protein Metabolism in Patients With Acromegaly Before and After Treatment.

BACKGROUND: Active acromegaly is characterized by increased lean body mass, but the mechanisms underlying the protein anabolic effect are unclear. AIM: To study if active acromegaly induces reversible changes in whole-body and skeletal muscle protein kinetics. PATIENTS AND METHODS: Eighteen patients with acromegaly were investigated before and 47 ± 10 weeks after disease control by surgery (n = 8) and/or medical treatment (n = 10). Labeled phenylalanine and tyrosine tracers were employed to assess whole-body and regional forearm muscle protein kinetics. Intramyocellular protein signaling was assessed in skeletal muscle biopsies, and whole-body dual-energy X-ray absorptiometry scan and indirect calorimetry assessed lean body mass (LBM) and resting energy expenditure, respectively. RESULTS: Disease control induced a 7% decrease in lean body mass (P < .000) and a 14% decrease in LBM-adjusted energy expenditure. Whole-body phenylalanine breakdown decreased after disease control (P = .005) accompanied by a decrease in the degradation of phenylalanine to tyrosine (P = .005) and a decrease in whole-body phenylalanine synthesis (P = .030). Skeletal muscle protein synthesis tended to decrease after disease control (P = .122), whereas the muscle protein breakdown (P = .437) and muscle protein loss were unaltered (P = .371). Unc-51 like autophagy activating kinase 1 phosphorylation, an activator of protein breakdown, increased after disease control (P = .042). CONCLUSIONS: Active acromegaly represents a reversible high flux state in which both whole-body protein breakdown and synthesis are increased, whereas forearm muscle protein kinetics are unaltered. Future studies are needed to decipher the link between protein kinetics and the structure and function of the associated growth hormone-induced increase in lean body mass.