Citations

What is the role of pcRPLND in men with retroperitoneal vital cancer after first-line chemotherapy? This question arises because of the potential predictive value of miR371 in identifying residual cancer even before pcRPLND! @cdfankhauser shared data within a multicenter cohort study redefining future practice in the miR371 era.

LINKED CONTENTThis article is linked to Almradi et al paper. To view this article, visit https://doi.org/10.1111/apt.16248

Abstract Context Levothyroxine is one of the most prescribed medications in the United States. Objective This study explores the appropriateness of levothyroxine prescriptions. Methods A retrospective multicenter study was conducted on adult patients who were prescribed levothyroxine for the first time between 2017 and 2020 at three academic centers in the United States. We classified each case of levothyroxine initiation into one of three mutually exclusive categories: appropriate (clinically supported), indeterminate (clinically unclear), or nonevidence based (NEB, not clinically supported). Results A total of 977 participants were included. The mean age was 55 years (SD 19), there was female (69%) and White race predominance (84%), and 44% had possible hypothyroid symptoms. Nearly half of the levothyroxine prescriptions were considered NEB (528, 54%), followed by appropriate (307, 31%) and indeterminate (118, 12%). The most common reason for NEB prescription was an index thyrotropin (TSH) value of less than 10 mIU/L without previous TSH or thyroxine values (131/528, 25%), for appropriate prescription, was overt hypothyroidism (163/307, 53%), and for an indeterminate prescription was a nonconfirmed subclinical hypothyroidism with TSH greater than or equal to 10 mIU/L (no confirmatory testing) (51/118, 43%). In multivariable analysis, being female (odds ratio [OR]: 1.3; 95% CI, 1.0-1.7) and prescription by a primary care provider (OR: 1.5; 95% CI, 1.2-2.0) were associated with NEB prescriptions. Conclusion There is a considerable proportion of NEB levothyroxine prescriptions. These results call for additional research to replicate these findings and to explore the perspective of those prescribing and receiving levothyroxine.

ImportanceTesting new medical devices or procedures in terms of safety, effectiveness, and durability should follow the strictest methodological rigor before implementation.ObjectivesTo review and analyze studies investigating devices and procedures used in intracranial aneurysm (IA) treatment for methods and completeness of reporting and to compare the results of studies with positive, uncertain, and negative conclusions.Data SourcesEmbase, MEDLINE, Web of Science, and The Cochrane Central Register of Clinical Trials were searched for studies on IA treatment published between January 1, 1995, and the October 1, 2022. Grey literature was retrieved from Google Scholar.Study SelectionAll studies making any kind of claims of safety, effectiveness, or durability in the field of IA treatment were included.Data Extraction and SynthesisUsing a predefined data dictionary and analysis plan, variables ranging from patient and aneurysm characteristics to the results of treatment were extracted, as were details pertaining to study methods and completeness of reporting. Extraction was performed by 10 independent reviewers. A blinded academic neuro-linguist without involvement in IA research evaluated the conclusion of each study as either positive, uncertain, or negative. The study followed Preferring Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Main Outcomes and MeasuresThe incidence of domain-specific outcomes between studies with positive, uncertain, or negative conclusions regarding safety, effectiveness, or durability were compared. The number of studies that provided a definition of safety, effectiveness, or durability and the incidence of incomplete reporting of domain-specific outcomes were evaluated.ResultsOverall, 12 954 studies were screened, and 1356 studies were included, comprising a total of 410 993 treated patients. There was no difference in the proportion of patients with poor outcome or in-hospital mortality between studies claiming a technique was safe, uncertain, or not safe. Similarly, there was no difference in the proportion of IAs completely occluded at last follow-up between studies claiming a technique was effective, uncertain, or noneffective. Less than 2% of studies provided any definition of safety, effectiveness, or durability, and only 1 of the 1356 studies provided a threshold under which the technique would be considered unsafe. Incomplete reporting was found in 546 reports (40%).Conclusions and RelevanceIn this systematic review and meta-analysis of IA treatment literature, studies claiming safety, effectiveness, or durability of IA treatment had methodological flaws and incomplete reporting of relevant outcomes supporting these claims.

SummaryBackgroundGastroparesis is defined by delayed gastric emptying with associated symptoms in the absence of mechanical obstruction.AimTo evaluate pharmacokinetics and pharmacodynamics of felcisetrag, a highly selective 5‐HT4 receptor agonist, on total gut transit in patients with documented delayed gastric emptying of solids.MethodsSingle‐centre, placebo‐controlled study of 36 participants receiving placebo, 0.1mg, 0.3mg or 1.0mg of felcisetrag I.V. infusion, daily, for 3 days. At baseline, each participant completed a 4h, 99mTc‐egg meal (300 kcal, 30% fat) gastric emptying test. Following infusion (Day 2), gastric, small bowel and colonic transit of solids were measured over 48h (same meal plus 111In‐charcoal delivered in methacrylate‐coated capsule). Samples were collected for pharmacokinetics. The primary endpoint was gastric emptying T1/2. Statistical analysis used baseline parameters as covariates (ANCOVA).ResultsPatients (22 idiopathic, 14 diabetic gastroparesis) were randomised to felcisetrag (0.1 mg, n = 10; 0.3 mg, n = 9; 1.0 mg, n = 7) or placebo (n = 10). Compared to placebo, felcisetrag significantly accelerated gastric emptying T1/2, colonic filling at 6h, and 10% small bowel transit time (overall P < 0.01; all three doses individually Bonferroni corrected P < 0.05) for all three measurements. Ascending colon emptying (T1/2) was significantly accelerated (all doses), and colonic transit at 48 hours was accelerated with 0.1 mg and 0.3 mg felcisetrag compared to placebo. Pharmacokinetic results were dose proportional. Felcisetrag was well tolerated with no clinically significant findings from clinical laboratory, vital signs or ECG.ConclusionI.V. felcisetrag significantly accelerated gastric, small bowel and colonic transit in patients with gastroparesis, and should be further evaluated for short‐term treatment of gastric and intestinal motility disorders.ClinicalTrials.gov #NCT03281577

The current study demonstrates that respiratory modulation of sympathetic nerve activity (SNA) is reduced in healthy postmenopausal (PMF) versus premenopausal females (YF). Furthermore, respiratory sympathetic modulation was negatively related to resting blood pressure in postmenopausal females, such that blood pressure was greater in individual with less modulation. Reduced respiratory sympathetic modulation may have implications for the autonomic control of blood pressure in aging postmenopausal females, by contributing to age-related sympathetic activation and reducing acute, respiratory-linked blood pressure variation.

Background: While previously used in other specialties, the preference signaling program (PSP) was implemented in the 2022 to 2023 orthopaedic surgery residency application process for the first time. The PSP allowed for 30 signaling tokens to be sent by applicants to programs of their choice to indicate particular interest in a program. It remains unknown how the PSP affects applicants and programs in the orthopaedic surgery residency match. Thus, this study's purpose was to assess the utility of preference signaling within the orthopaedic surgery residency application process in its inaugural year of use. Methods: An anonymous electronic survey was emailed to all orthopaedic surgery residency applicants who applied to the authors' institution during the 2022 to 2023 application cycle. The survey was sent after match lists were submitted and closed before the release of match results. The survey collected information regarding applicant demographics, preference signaling habits, and attitude toward preference signaling. Results: The survey was completed by 101 applicants. Applicants applied to a mean of 90 programs (range: 10-197) and received an average of 12 interview invitations (range: 0-39). Applicants almost uniformly used all 30 signals, with nearly two-thirds signaling their home programs (65%, 49/76), and nearly all applicants sending signals to programs at which they performed away rotations (95.7%, 88/92). Applicants received a mean of 9 invitations from programs they signaled, compared with 2 invitations from programs they did not signal. Applicants were significantly more likely to receive an interview invite at a program they signaled than one they did not (p < 0.01). Overall, 57% of applicants (57/101) found the PSP to be helpful, whereas 28% (28/101) found it to be unhelpful, and 16% (16/101) had a neutral opinion. Conclusions: This study reports that the PSP in the 2022 to 2023 orthopaedic surgery match was an effective method of expressing interest in a program because applicants were significantly more likely to receive interview invites to signaled programs. More than half of respondents felt PSP to be helpful; however, the effect on application numbers is still unclear. Level of Evidence: III

Although the etiology of rheumatoid arthritis (RA) is unknown, a strong genetic predisposition and the presence of preclinical antibodies before the onset of symptoms is documented. An expansion of Eggerthella lenta is associated with severe disease in RA. Here, using a humanized mouse model of collagen-induced arthritis, we determined the impact of E. lenta abundance on RA severity. Naïve mice gavaged with E. lenta produce preclinical rheumatoid factor and, when induced for arthritis, develop severe disease. The augmented antibody response was much higher in female mice, and among patients with RA, women had higher average load of E. lenta . Expansion of E. lenta increased CXCL5 and CD4 T cells, and both interleukin-17– and interferon-γ–producing B cells. Further, E. lenta gavage caused gut dysbiosis and decline in amino acids and nicotinamide adenine dinucleotide with an increase in microbe-dependent bile acids and succinyl carnitine causing systemic senescent-like inflammation.