Citations

AbstractBackgroundAdolescent Idiopathic Scoliosis (AIS) affects 2%–4% of the general pediatric population. While surgical correction remains one of the most common orthopedic procedures performed in pediatrics, limited consensus exists on the perioperative anesthetic management.AimsTo examine the current state of anesthetic management of typical AIS spine fusions at institutions which have a dedicated pediatric orthopedic spine surgeon.MethodsA web‐based survey was sent to all members of the North American Pediatric Spine Anesthesiologists (NAPSA) Collaborative. This group included 34 anesthesiologists at 19 different institutions, each of whom has a Harms Study Group surgeon performing spine fusions at their hospital.ResultsThirty‐one of 34 (91.2%) anesthesiologists completed the survey, with a missing response rate from 0% to 16.1% depending on the question. Most anesthesia practices (77.4%; 95% confidence interval [CI], 67.7–93.4) do not have patients come for a preoperative visit prior to the day of surgery. Intravenous induction was the preferred method (74.2%; 95% CI 61.3–89.9), with the majority utilizing two peripheral IVs (93.5%; 95% CI 90.3–100) and an arterial line (100%; 95% CI 88.8–100). Paralytic administration for intubation and/or exposure was divided (51.6% rocuronium/vecuronium, 45.2% no paralytic, and 3.2% succinylcholine) amongst respondents. While tranexamic acid was consistently utilized for reducing blood loss, dosing regimens varied. When faced with neuromonitoring signal issues, 67.7% employ a formal protocol. Most anesthesiologists (93.5%; 95% CI 78.6–99.2) extubate immediately postoperatively with patients admitted to an inpatient floor bed (77.4%; 95% CI 67.7–93.3).ConclusionMost anesthesiologists (87.1%; 95% CI 80.6–99.9) report the use of some form of an anesthesia‐based protocol for AIS fusions, but our survey results show there is considerable variation in all aspects of perioperative care. Areas of agreement on management comprise the typical vascular access required, utilization of tranexamic acid, immediate extubation, and disposition to a floor bed. By recognizing the diversity of anesthetic care, we can develop areas of research and improve the perioperative management of AIS.

ObjectivesTo evaluate the effect of Alzheimer's disease (AD) ‐related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).MethodsData from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4‐R‐Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD‐positive (CBS/PSP‐AD) and AD‐negative (CBS/PSP‐noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p‐tau, t‐tau, and amyloid‐beta, and plasma ptau‐217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole‐brain gray matter volume and functional networks connectivity were compared across groups.ResultsData were analyzed from 87 CBS/PSP‐noAD and 23 CBS/PSP‐AD, 18 AD, and 30 healthy controls. CBS/PSP‐noAD showed worse performance in comparison to CBS/PSP‐AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP‐AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP‐noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP‐AD compared with CBS/PSP‐no AD and controls. The thalamic network connectivity was most affected in CBS/PSP‐noAD.InterpretationAD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co‐pathology. ANN NEUROL 2024;96:99–109

BACKGROUND Mohs micrographic surgery efficiently treats skin cancer through staged resection, but surgeons' varying resection rates may lead to higher medical costs. OBJECTIVE To evaluate the cost savings associated with a quality improvement. MATERIALS AND METHODS The authors conducted a retrospective cohort study using 100% Medicare fee-for-service claims data to identify the change of mean stages per case for head/neck (HN) and trunk/extremity (TE) lesions before and after the quality improvement intervention from 2016 to 2021. They evaluated surgeon-level change in mean stages per case between the intervention and control groups, as well as the cost savings to Medicare over the same time period. RESULTS A total of 2,014 surgeons performed Mohs procedures on HN lesions. Among outlier surgeons who were notified, 31 surgeons (94%) for HN and 24 surgeons (89%) for TE reduced their mean stages per case with a median reduction of 0.16 and 0.21 stages, respectively. Reductions were also observed among outlier surgeons who were not notified, reducing their mean stages per case by 0.1 and 0.15 stages, respectively. The associated total 5-year savings after the intervention was 92 million USD. CONCLUSION The implementation of this physician-led benchmarking model was associated with broad reductions of physician utilization and significant cost savings.

Abstract Patient-specific targeting of the Ventral intermediate nucleus (Vim) of the thalamus can be achieved with MR connectivity. Nevertheless, there are several drawbacks to using tractography-based targeting methods to visualise distinct thalamic nuclei (e.g., subjective region of interest selection, and thresholding of resulting tracts and clusters). Fractional anisotropy (FA) mapping, another product of diffusion MRI (dMRI), does not rely on tractography, and could thus be clinically more viable for discerning thalamic anatomy for stereotactic surgery. The aim of this study is to develop and present a hybrid, high-resolution, and high-fidelity imaging modality that combines contrast from FA maps as well as anatomical T1 sequences (FAT1 imaging); and to evaluate FAT1 based Vim-target definition. Imaging and outcome data of 35 consecutive refractory tremor patients who had undergone 43 connectivity guided deep brain stimulation (DBS) and/or radiofrequency thermocoagulation (RF-T) between 2013 and 2021 were included. First, the pre-operatively acquired dMRI and MPRAGE sequences were used to create FAT1 maps in retrospect. Then, an FAT1 based Vim-target was planned by an experienced functional neurosurgeon who was blinded for patient outcome. Finally, to investigate FAT1 based targeting, a post-hoc analysis was carried out of the degree of overlap between the newly created FAT1 based Vim-target, and the volume of tissue activation (VTA, in case of DBS) or lesion volume (in case of RF-T). This degree of overlap was compared between favourable and unfavourable outcome groups: outcomes were measured by experts blinded for imaging data at the last follow-up using a Clinical Global Impression-Improvement score (CGI-I), where a CGI-I score of 1-2 (i.e., FTMTRS improvement of ≥50%) was considered favourable. In 36 of the 43 (84%) performed surgeries (24 DBS and 19 RF-T), FAT1 based Vim-targeting was possible. For the group showing favourable outcome (71% of the patients at a median follow-up of 13 months), the mean amount of overlap between the FAT1 based Vim-target and the VTA or lesion was 42% (±13), versus 17% (±15) for patients with an unfavourable outcome (MD 25%, 95% CI 14–35, p < 0.0001). Retrospective use of FAT1 based Vim-targeting as a tool to predict outcome had a sensitivity of 90%, specificity of 80%, positive predictive value of 90%, and negative predictive value of 80%. In conclusion, FAT1 imaging is a new, high-resolution, and high-fidelity modality that combines diffusion and anatomical MRI. It provides a fast and efficacious way of targeting the ventral intermediate nucleus of the thalamus. In this study, FAT1 based targeting was highly accurate in predicting outcomes after deep brain stimulation and radiofrequency thalamotomy.

Background: While posterior medial meniscus root (PMMR) techniques have evolved, there remains a need to both optimize repair strength and improve resistance to cyclic loading. Hypothesis: Adjustable tensioning would lead to higher initial repair strength and reduce displacement with cyclic loading compared with previously described transtibial pull-out repair (TPOR) fixation techniques. Study Design: Controlled laboratory study. Methods: A total of 56 porcine medial menisci were used. Eight intact specimens served as a control for the native meniscus. For the others, PMMR tears were created and repaired with 6 different TPOR techniques (8 in each group). Fixed PMMR repairs were executed using 4 different suture techniques (two No. 2 cinch sutures, two cinch tapes, two No. 2 simple sutures, and two No. 2 sutures in a Mason-Allen configuration) all tied over a cortical button. Adjustable PMMR repairs using Mason-Allen sutures were fixed with an adjustable soft tissue anchor fixation tensioned at either 80 N or 120 N. The initial force, stiffness, and relief displacement of the repairs were measured after fixation. Repair constructs were then cyclically loaded, with cyclic displacement and stiffness measured after 1000 cycles. Finally, the specimens were pulled to failure. Results: The PMMR repaired with the 2 cinch sutures fixed technique afforded the lowest ( P < .001) initial repair load, stiffness, and relief displacement. The adjustable PMMR repairs achieved a higher initial repair load ( P < .001) and relief displacement ( P < .001) than all fixed repairs. The 2 cinch sutures fixed technique showed an overall higher cyclic displacement ( P < .028) and was completely loose compared with the native meniscus functional zone. Repairs with adjustable intratunnel fixation showed displacement with cyclic loading similar to the native meniscus. With cyclic loading, the Mason-Allen adjustable repair with 120 N of tension showed less displacement ( P < .016) than all fixed repairs and a stiffness comparable to the fixed Mason-Allen repair. The fixed Mason-Allen technique demonstrated a higher ultimate load ( P < .007) than the adjustable Mason-Allen techniques. All repairs were less stiff, with lower ultimate failure loads, than the native meniscus root attachment ( P < .0001). Conclusion: Adjustable TPOR led to considerably higher initial repair load and relief displacement than other conventional fixed repairs and restricted cyclic displacement to match the native meniscus function. However, the ultimate failure load of the adjustable devices was lower than that of a Mason-Allen construct tied over a cortical button. All repair techniques had a significantly lower load to failure than the native meniscus root. Clinical Relevance: Knotless adjustable PMMR repair based on soft anchor fixation results in higher tissue compression and less displacement, but the overall clinical significance on healing rates remains unclear.

Abstract Background Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies. Objectives To explore the effects of spesolimab treatment in patients with HS. Methods This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS for ≥ 1 year before enrolment. Patients were randomized (2 : 1) to receive a loading dose of 3600-mg intravenous spesolimab (1200 mg at weeks 0, 1 and 2) or matching placebo, followed by maintenance with either 1200-mg subcutaneous spesolimab every 2 weeks from weeks 4 to 10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at week 12. Secondary endpoints were the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of 0, absolute change from baseline in the revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥ 1 flare (all at week 12) and patient-reported outcomes. Results In this completed trial, randomized patients (n = 52) received spesolimab (n = 35) or placebo (n = 17). The difference vs. placebo in least squares mean is reported. At week 12, the percentage change in total AN count was similar between treatment arms: –4.1% [95% confidence interval (CI) –31.7 to 23.4]. There was greater numerical improvement in the spesolimab arm, as measured by IHS4 (13.9, 95% CI –25.6 to –2.3); percentage change from baseline in dT count (–96.6%, 95% CI –154.5 to –38.8); and the proportion of patients achieving a dT count of 0 (18.3%, 95% CI –7.9 to 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 vs. placebo. Spesolimab demonstrated a favourable safety profile, similar to that observed in trials in other diseases. Conclusions This exploratory PoCC study supports the development of spesolimab as a new therapeutic option in HS.

Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle–dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways. We also identified a distinct signature of upregulated and downregulated genes common to all the diseases investigated when compared with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies.