Citations

AbstractBackgroundThe hidradenitis suppurativa (HS) clinical response (HiSCR) has come under scrutiny as several HS clinical trials failed to meet primary endpoints with high placebo responses. This may be due to limitations of the tool and raters' ability to accurately characterize and count lesions, rather than lack of efficacy of the studied drug. Due to HS lesion complexity and potential differences in rater training, it was hypothesized that there would be discrepancies in how providers characterize and count lesions for HS clinical trials.ObjectiveTo evaluate how HS providers and patients name and count HS lesions and to identify discrepancies among providers to initiate the development of consensus‐driven guidance for HS rater training.MethodsAn online survey was distributed to the members of HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Respondents were asked to classify lesion images composed of multiple and different morphology types and answer questions regarding inclusion of associated dermatological conditions.ResultsForty‐seven HISTORIC members responded (29 providers; 18 patients). There was variability in how respondents classified HS lesions. Of 12 questions containing images, four had ≥50% of respondents choosing the same answer. With an image of a lesion composed of different morphologies, 45% of providers counted it as a single lesion and 45% counted it as multiple distinct lesions. With an image of multiple interconnected draining tunnels, 7% of providers classified it as a single draining tunnel while 79% categorized it as multiple draining tunnels with the number estimated by visual inspection. There was also variability in deciding whether lesions occurring in associated conditions should be considered separately or included in HS lesion counts. Patient responses were also variable.ConclusionsThe result of the current study reaffirms the gap in how providers characterize and count HS lesions for clinical trials and the need to develop consensus‐driven rater training related to HS outcome measures.

AbstractBackgroundWhile preclinical studies have shown that alpha‐synuclein can spread through cell‐to‐cell transmission whether it can be transmitted between humans is unknown.ObjectivesThe aim was to assess the presence of a synucleinopathy in autopsied conjugal couples.MethodsNeuropathological findings in conjugal couples were categorized as Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease with Lewy bodies (ADLB), incidental Lewy body disease (ILBD), or no Lewy bodies.ResultsNinety conjugal couples were included; the mean age of death was 88.3 years; 32 couples had no Lewy bodies; 42 couples had 1 spouse with a synucleinopathy: 10 PD, 3 DLB, 13 ADLB, and 16 ILBD; 16 couples had both spouses with a synucleinopathy: in 4 couples both spouses had PD, 1 couple had PD and DLB, 4 couples had PD and ADLB, 2 couples had PD and ILBD, 1 couple had DLB and ADLB, in 3 couples both had ADLB, and 1 couple had ADLB and ILBD. No couples had both spouses with ILBD.ConclusionsThis large series of 90 autopsied conjugal couples found 16 conjugal couples with synucleinopathies, suggesting transmission of synucleinopathy between spouses is unlikely. © 2024 International Parkinson and Movement Disorder Society.

ABSTRACT Introduction Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress tolerability of the alveolar–capillary unit. This study examined the effect of ultramarathon trail racing at different altitudes (ranging from <1000 m to between 1500 and 2700 m) on alveolar–capillary recruitment and lung diffusion. Methods Cardiac and lung function were examined before and after an ultramarathon in 67 runners (age: 41 ± 9 yr, body mass index: 23 ± 2 kg·m −2 , 10 females), and following 12–24 h of recovery in a subset ( n = 27). Cardiac biomarkers (cTnI and BNP) were assessed from whole blood, whereas lung fluid accumulation (comet tails), stroke volume (SV), and cardiac output ( Q ) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semirecumbent cycling (20, 30, and 40 W). Results Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± 0.02 vs 0.13 ± 0.03 ng·mL −1 , BNP: 20 ± 2 vs 112 ± 21 pg·mL −1 ; P < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, P < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 mL, 40 W: 93 ± 2 vs 88 ± 2 mL; P < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 L·min −1 , P < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 L·min −1 , P = 0.899). Resting DLco and Vc decreased after the race ( P < 0.01), whereas Dm was unchanged ( P = 0.465); however, during the three stages of exercise, DLco, Vc, and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL·min −1 ·mm Hg −1 , 83 ± 3 vs 73 ± 2 mL, 186 ± 6 vs 170 ± 7 mL·min −1 ·mm Hg −1 , respectively; P < 0.01). When corrected for alveolar volume and Q , DLco decreased from pre- to post-race ( P < 0.01), and changes in DLco were similar for all ultramarathon events ( P > 0.05). Conclusions Competing in an ultramarathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar–capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultramarathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures.

Purpose To investigate the feasibility and accuracy of 3‐dimensional (3D) iPhone scans using commercially available applications compared with computed tomography (CT) for mapping chondral surface topography of the knee. Methods Ten cadaveric dysplastic trochleae, 16 patellae, and 24 distal femoral condyles (DFCs) underwent CT scans and 3D scans using 3 separate optical scanning applications on an iPhone X. The 3D surface models were compared by measuring surface‐to‐surface least distance distribution of overlapped models using a validated 3D‐3D registration volume merge method. The absolute least mean square distances for the iPhone‐generated models from each scanning application were calculated in comparison to CT models using a point‐to‐surface distance algorithm allowing regional “inside/outside” measurement of the absolute distance between models. Results Only 1 of the 3 scanning applications created models usable for quantitative analysis. Overall, there was a median absolute least mean square distance between the usable model and CT‐generated models of 0.18 mm. The trochlea group had a significantly lower median absolute least mean square distance compared with the DFC group (0.14 mm [interquartile range, 0.13‐0.17] vs 0.19 mm [0.17‐0.25], P = .002). iPhone models were smaller compared with CT models (negative signed distances) for all trochleae, 83% of DFCs, and 69% of patellae. Conclusions In this study, we found minimal differences between a 3D iPhone scanning application and conventional CT scanning when analyzing surface topography. Clinical Relevance Emerging 3D iPhone scanning technology can create accurate, inexpensive, real‐time 3D models of the intended target. Surface topography evaluation may be useful in graft selection during surgical procedures such as osteochondral allograft transplantation.

Abstract Introduction/Aims Biomarkers have shown promise in amyotrophic lateral sclerosis (ALS) research, but the quest for reliable biomarkers remains active. This study evaluates the effect of debamestrocel on cerebrospinal fluid (CSF) biomarkers, an exploratory endpoint. Methods A total of 196 participants randomly received debamestrocel or placebo. Seven CSF samples were to be collected from all participants. Forty‐five biomarkers were analyzed in the overall study and by two subgroups characterized by the ALS Functional Rating Scale‐Revised (ALSFRS‐R). A prespecified model was employed to predict clinical outcomes leveraging biomarkers and disease characteristics. Causal inference was used to analyze relationships between neurofilament light chain (NfL) and ALSFRS‐R. Results We observed significant changes with debamestrocel in 64% of the biomarkers studied, spanning pathways implicated in ALS pathology (63% neuroinflammation, 50% neurodegeneration, and 89% neuroprotection). Biomarker changes with debamestrocel show biological activity in trial participants, including those with advanced ALS. CSF biomarkers were predictive of clinical outcomes in debamestrocel‐treated participants (baseline NfL, baseline latency‐associated peptide/transforming growth factor beta1 [LAP/TGFβ1], change galectin‐1, all p < .01), with baseline NfL and LAP/TGFβ1 remaining ( p < .05) when disease characteristics ( p < .005) were incorporated. Change from baseline to the last measurement showed debamestrocel‐driven reductions in NfL were associated with less decline in ALSFRS‐R. Debamestrocel significantly reduced NfL from baseline compared with placebo (11% vs. 1.6%, p = .037). Discussion Following debamestrocel treatment, many biomarkers showed increases (anti‐inflammatory/neuroprotective) or decreases (inflammatory/neurodegenerative) suggesting a possible treatment effect. Neuroinflammatory and neuroprotective biomarkers were predictive of clinical response, suggesting a potential multimodal mechanism of action. These results offer preliminary insights that need to be confirmed.