Citations

Abstract Whipple disease is a rare systemic illness associated with weight loss, diarrhea, and arthralgia. Asymptomatic carriage is common, but the disease can be complicated by cardiac involvement and may result in culture-negative endocarditis. Cardiac manifestations of the disease can lead to death. This report presents the case of a 66-year-old man with Whipple disease and biventricular heart failure with cardiogenic shock. Medical therapy followed by successful replacement of the aortic and mitral valves resulted in substantial improvement.

Background: Osteochondral allograft (OCA) transplantation is an important surgical technique for full-thickness chondral defects in the knee. For patients undergoing this procedure, topography matching between the donor and recipient sites is essential to limit premature wear of the OCA. Currently, there is no standardized process of donor and recipient graft matching. Purpose: To evaluate a novel topography matching technique for distal femoral condyle OCA transplantation using 3-dimensional (3D) laser scanning to create 3D-printed patient-specific instrumentation in a human cadaveric model. Study Design: Descriptive laboratory study. Methods: Human cadaveric distal femoral condyles (n = 12) underwent 3D laser scanning. An 18-mm circular osteochondral recipient defect was virtually created on the medial femoral condyle (MFC), and the position and orientation of the best topography-matched osteochondral graft from a paired donor lateral femoral condyle (LFC) were determined using an in silico analysis algorithm minimizing articular step-off distances between the edges of the graft and recipient defect. Distances between the entire surface of the OCA graft and the underneath surface of the MFC were evaluated as surface mismatch. Donor (LFC) and recipient (MFC) 3D-printed patient-specific guides were created based on 3D reconstructions of the scanned condyles. Through use of the guides, OCAs were harvested from the LFC and transplanted to the reamed recipient defect site (MFC). The post-OCA recipient condyles were laser scanned. The 360° articular step-off and cartilage topography mismatch were measured. Results: The mean cartilage step-off and graft surface mismatch for the in silico OCA transplant were 0.073 ± 0.029 mm (range, 0.005-0.113 mm) and 0.166 ± 0.039 mm (range, 0.120-0.243 mm), respectively. Comparatively, the cadaveric specimens postimplant had significantly larger step-off differences (0.173 ± 0.085 mm; range, 0.082-0.399 mm; P = .001) but equivalent graft surface topography matching (0.181 ± 0.080 mm; range, 0.087-0.396 mm; P = .678). All 12 OCA transplants had mean circumferential step-off differences less than a clinically significant cutoff of 0.5 mm. Conclusion: These findings suggest that the use of 3D-printed patient-specific guides for OCA transplantation has the ability to reliably optimize cartilage topography matching for LFC to MFC transplantation. This study demonstrated substantially lower step-off values compared with previous orthopaedic literature when also evaluating LFC to MFC transplantation. Using this novel technique in a model performing MFC to MFC transplantation has the potential to yield further enhanced results due to improved radii of curvature matching. Clinical Relevance: Topography-matched graft implantation for focal chondral defects of the knee in patients improves surface matching and has the potential to improve long-term outcomes. Efficient selection of the allograft also allows improved availability of the limited allograft sources.

Abstract Osteoporosis and other metabolic bone diseases are prevalent in the aging population. While bone has the capacity to regenerate throughout life, bone formation rates decline with age and contribute to reduced bone density and strength. Identifying mechanisms and pathways that increase bone accrual in adults could prevent fractures and accelerate healing. G protein-gated inwardly rectifying K+ (GIRK) channels are key effectors of G protein-coupled receptor signaling. Girk3 was recently shown to regulate endochondral ossification. Here, we demonstrate that deletion of Girk3 increases bone mass after 18 weeks of age. Male 24-week-old Girk3-/- mice have greater trabecular bone mineral density and bone volume fraction than wildtype (WT) mice. Osteoblast activity is moderately increased in 24-week-old Girk3-/- mice compared to WT mice. In vitro, Girk3-/- bone marrow stromal cells (BMSCs) are more proliferative than WT BMSCs. Calvarial osteoblasts and BMSCs from Girk3-/- mice are also more osteogenic than WT cells, with altered expression of genes that regulate the wingless-related integration site (Wnt) family. Wnt inhibition via Dickkopf-1 (Dkk1) or β-catenin inhibition via XAV939 prevents enhanced mineralization, but not proliferation, in Girk3-/- BMSCs and slows these processes in WT cells. Finally, selective ablation of Girk3 from cells expressing Cre recombinase from the 2.3 kb-Col1a1 promoter, including osteoblasts and osteocytes, is sufficient to increase bone mass and bone strength in male mice at 24 weeks of age. Taken together, these data demonstrate that Girk3 regulates progenitor cell proliferation, osteoblast differentiation, and bone mass accrual in adult male mice.

BACKGROUND: IPAA has become the criterion standard for treating ulcerative colitis, familial adenomatous polyposis, and selected cases of Crohn’s colitis. Robotic surgery promises improved postoperative outcomes and decreased length of stay. However, few studies have evaluated the benefits of robotic IPAA compared to laparoscopy. OBJECTIVE: To compare short-term 30-day postoperative outcomes of robotic versus laparoscopic proctectomy with IPAA and diverting loop ileostomy. DESIGN: Retrospective observational study from a single, high-volume center. SETTINGS: Mayo Clinic, Rochester, Minnesota (tertiary referral center for IBD). PATIENTS: All adult patients undergoing minimally invasive proctectomy with IPAA and diverting loop ileostomy between January 2015 and April 2023. MAIN OUTCOME MEASURES: Thirty-day complications, hospital length of stay, estimated blood loss, conversion rate, 30-day readmission, and 30-day reoperation. RESULTS: Two hundred seventeen patients were included in the study; 107 underwent robotic proctectomy with IPAA and diverting loop ileostomy, whereas 110 had laparoscopic proctectomy with IPAA and diverting loop ileostomy. Operating time was significantly longer in the robotic group (263 ± 38 vs 228 ± 75 minutes, p < 0.0001). The robotic group also had lower estimated blood loss (81.5 ± 77.7 vs 126.8 ± 111.0 mL, p = 0.0006) as well as fewer conversions (0% vs 8.2%, p = 0.003). Patients in the robotic group received more intraoperative fluids (3099 ± 1140 vs 2472 ± 996 mL, p = 0.0001). However, there was no difference in length of stay, 30-day morbidity, 30-day readmission, 30-day reoperation, rate of diverting loop ileostomy closure at 3 months, and surgical IPAA complication rate after ileostomy closure. LIMITATIONS: Retrospective design, single-center study, potential bias because of the novelty of the robotic approach, and lack of long-term and quality-of-life outcomes. CONCLUSIONS: Robotic proctectomy with IPAA and diverting loop ileostomy may offer advantages in terms of estimated blood loss and conversion rate while maintaining the benefits of minimally invasive surgery. Further research is needed to evaluate long-term outcomes. See Video Abstract. NAVEGANDO EL PROGRESO: EXPERIENCIA DE OCHO AÑOS EN UN SOLO CENTRO CON PROCTECTOMÍA MÍNIMAMENTE INVASIVA Y ANASTOMOSIS ANAL-BOLSA ILEAL ANTECEDENTES: La anastomosis anal-bolsa ileal (IPAA) se ha convertido en el estándar de oro para el tratamiento de la colitis ulcerosa, la poliposis adenomatosa familiar y casos seleccionados de colitis de Crohn. La cirugía robótica promete mejores resultados posoperatorios y una menor duración de la estancia hospitalaria. Sin embargo, pocos estudios han evaluado los beneficios de la IPAA robótica en comparación con la laparoscopia. OBJETIVO: Comparar los resultados postoperatorios a corto plazo a 30 días de la proctectomía robótica versus laparoscópica con IPAA e ileostomía en asa de derivación. DISEÑO: Estudio observacional retrospectivo de un único centro de gran volumen. AJUSTES: Mayo Clinic, Rochester, Minnesota (centro terciario de referencia para EII). PACIENTES: Todos los pacientes adultos sometidos a proctectomía mínimamente invasiva con IPAA y DLI entre Enero de 2015 y Abril de 2023. PRINCIPALES MEDIDAS DE RESULTADOS: Complicaciones a los 30 días, duración de la estancia hospitalaria, pérdida de sangre estimada, tasa de conversión, reingreso a los 30 días y reoperación a los 30 días. RESULTADOS: Se incluyeron en el estudio 217 pacientes; 107 se sometieron a proctectomía robótica con IPAA y DLI, mientras que 110 se sometieron a proctectomía laparoscópica con IPAA y DLI. El tiempo operatorio fue significativamente mayor en el grupo robótico (263 ± 38 minutos versus 228 ± 75 minutos, p < 0,0001); la pérdida de sangre estimada (EBL) fue menor en el grupo robótico (81,5 ± 77,7 ml versus 126,8 ± 111,0 ml, p = 0,0006), así como el número de conversiones (0% versus 8,2%, p = 0,003). Los pacientes del grupo robótico recibieron más líquidos intraoperatorios (3099 ± 1140 ml versus 2472 ± 996 ml, p = 0,0001). Sin embargo, no hubo diferencias en la duración de la estancia hospitalaria, la morbilidad a los 30 días, el reingreso a los 30 días, la reoperación a los 30 días, la tasa de cierre del DLI a los tres meses y la tasa de complicaciones quirúrgicas de la IPAA después del cierre de la ileostomía. LIMITACIONES: Diseño retrospectivo, estudio unicéntrico, posible sesgo debido a la novedad del enfoque robótico, falta de resultados a largo plazo y de calidad de vida. CONCLUSIONES: La proctectomía robótica con IPAA y DLI puede ofrecer ventajas en términos de EBL y tasa de conversión, manteniendo al mismo tiempo los beneficios de la cirugía mínimamente invasiva. Se necesita más investigación para evaluar los resultados a largo plazo. (Traducción—Dr. Yesenia Rojas-Khalil)

BACKGROUND: Ulcerative colitis, total colectomy, and tofacitinib have all been associated with an increased risk of venous thromboembolism. OBJECTIVE: To determine whether preoperative tofacitinib exposure increases venous thromboembolism or other postoperative complications among patients with ulcerative colitis undergoing subtotal colectomy, total colectomy, or total proctocolectomy. DESIGN: Retrospective, case-controlled study at a single institution. SETTINGS: A tertiary referral center. PATIENTS: Adult patients with ulcerative colitis undergoing subtotal colectomy, total colectomy, or total proctocolectomy after 2018 who were taking tofacitinib within 30 days of surgery (n = 56) were compared to age- and sex-matched patients with ulcerative colitis undergoing the same surgeries but who were not exposed to tofacitinib (n = 56). MAIN OUTCOME MEASURE: The primary outcome was differences in the incidence of venous thromboembolism within 90 days of surgery based on tofacitinib exposure. Secondary outcomes were 90-day postoperative complications. RESULTS: Groups were well matched for age (non-tofacitinib: mean 35.2 years [SD 12.0], tofacitinib: 35.9 [SD 12.1], p = 0.36) and sex (41% women in each group, p = 1.00). Medical characteristics were similar between groups except for biological medication exposure 30 days before surgery (non-tofacitinib: 66%, tofacitinib: 36%, p = 0.004). Surgical characteristics did not differ between groups. Most patients were discharged on extended venous thromboembolism prophylaxis (non-tofacitinib: 80% and tofacitinib: 77%). Adjusted for biological exposure, there were no statistically significant differences in venous thromboembolism (non-tofacitinib exposed: 14%, tofacitinib exposed: 4%, p = 0.09) or other postoperative outcomes. LIMITATION: Retrospective, single institutional study. CONCLUSIONS: Among patients with ulcerative colitis undergoing total colectomy or proctocolectomy, exposure to tofacitinib was not associated with an increased risk of venous thromboembolism or other postoperative complications. See Video Abstract . LA EXPOSICIÓN A TOFACITINIB NO AUMENTA LAS COMPLICACIONES POSOPERATORIAS ENTRE PACIENTES CON COLITIS ULCEROSA SOMETIDOS A COLECTOMÍA TOTAL: UN ESTUDIO RETROSPECTIVO DE CASOS Y CONTROLES ANTECEDENTES: La colitis ulcerosa, la colectomía total y el tofacitinib han sido asociados con un mayor riesgo de tromboembolismo venoso. OBJETIVO: Determinar si la exposición preoperatoria a tofacitinib aumenta la tromboembolia venosa u otras complicaciones posoperatorias entre pacientes con colitis ulcerosa sometidos a colectomía subtotal, colectomía total o proctocolectomía total. DISEÑO: Estudio retrospectivo de casos y controles en una sola institución. AJUSTES: Un centro de referencia terciario. PACIENTES: Los pacientes adultos con colitis ulcerosa sometidos a colectomía subtotal, colectomía total o proctocolectomía total después del año 2018 que se encontraron consumiendo tofacitinib dentro de los 30 días posteriores a la cirugía (n = 56) fueron comparados con pacientes con colitis ulcerosa de la misma edad y sexo sometidos a las mismas cirugías pero que no estuvieron expuestos a tofacitinib (n = 56). MEDIDA DE RESULTADO PRINCIPAL: El resultado primario fueron las diferencias en las incidencias de tromboembolismo venoso dentro de los 90 días posteriores a la cirugía según la exposición a tofacitinib. Los resultados secundarios fueron las complicaciones posoperatorias a los 90 días. RESULTADOS: Los grupos se encontraban bien emparejados por edad (sin tofacitinib: media 35,2 años [DE 12,0], tofacitinib: 35,9 [DE 12,1], p = 0,36) y sexo (41% mujeres en cada grupo, p = 1,00). Las características médicas fueron similares entre los grupos, excepto por la exposición a medicamentos biológicos 30 días antes de la cirugía (sin tofacitinib: 66 %, tofacitinib: 36 %, p = 0,004). Las características quirúrgicas no difirieron entre los grupos. La mayoría de los pacientes fueron dados de alta con profilaxis extendida para tromboembolismo venoso (sin tofacitinib: 80% y tofacitinib: 77%). Ajustado a la exposición biológica, no hubo diferencias estadísticamente significativas en el tromboembolismo venoso (no expuestos a tofacitinib: 14%, expuestos a tofacitinib: 4%, p = 0,09) u otros resultados posoperatorios. LIMITACIÓN: Estudio institucional único, retrospectivo. CONCLUSIÓN: Entre los pacientes con colitis ulcerosa sometidos a colectomía total o proctocolectomía, la exposición a tofacitinib no se asoció con un mayor riesgo de tromboembolismo venoso u otras complicaciones posoperatorias. (Traducción—Dr Osvaldo Gauto )

Study Design. Retrospective review of prospectively collected data. Objective. The aim of this study was to investigate what factors predict delayed improvement after surgical treatment of low-grade spondylolisthesis. Summary of Background Data. Lumbar surgery leads to clinical improvement in the majority of patients with low-grade spondylolisthesis. Most patients improve rapidly after surgery, but some patients demonstrate a delayed clinical course. Methods. The Quality and Outcomes Database (QOD) was queried for grade 1 spondylolisthesis patients who underwent surgery who had patient-reported outcome measures (PROMs) collected at baseline, 3, 6, and 12 months, including back and leg pain Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and EuroQol-5D (EQ-5D). Patients were stratified as “early responders” reaching MCID at 3 months and maintaining improvement through 12 months and “delayed responders” not reaching MCID at 3 months but ultimately reaching MCID at 12 months. These two groups were compared with respect to factors which predicted delayed improvement. Results. Of 608 patients enrolled, 436 (72%) met inclusion criteria for this study. Overall, 317 patients (72.7%) reached MCID for ODI at 12 months following surgery. Of these patients, 249 (78.5%) exhibited a rapid clinical improvement trajectory and had achieved ODI MCID threshold by the 3-month postoperative follow-up. Sixty-eight patients (21.4%) showed a delayed trajectory, and had not achieved ODI MCID threshold at 3 months, but did ultimately reach MCID at 12-month follow-up. Factors associated with delayed improvement included impaired preoperative ambulatory status, better baseline back and leg pain scores, and worse 3-month leg pain scores ( P <0.01). Conclusions. The majority of patients undergoing surgery for low-grade spondylolisthesis reach ODI MCID threshold rapidly, within the first 3 months after surgery. Factors associated with a delayed clinical course include impaired preoperative ambulation status, relatively better preoperative back and leg pain, and persistent leg pain at 3 months.

Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in patients with cirrhosis awaiting LT. This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score. Among the 317 patients in this study, 170 had an AKI response (53.6%), and 147 had no response (46.4%). Compared to nonresponders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted subhazard ratio for mortality 0.34, p=0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p<0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted subhazard ratio 0.55, p=0.005); 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in nonresponders occurred during hospitalization, with the remainder occurring postdischarge at a median of 58 days. In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.

AbstractMulti‐energy computed tomography (MECT) offers the opportunity for advanced visualization, detection, and quantification of select elements (e.g., iodine) or materials (e.g., fat) beyond the capability of standard single‐energy computed tomography (CT). However, the use of MECT requires careful consideration as substantially different hardware and software approaches have been used by manufacturers, including different sets of user‐selected or hidden parameters that affect the performance and radiation dose of MECT. Another important consideration when designing MECT protocols is appreciation of the specific tasks being performed; for instance, differentiating between two different materials or quantifying a specific element. For a given task, it is imperative to consider both the radiation dose and task‐specific image quality requirements. Development of a quality control (QC) program is essential to ensure the accuracy and reproducibility of these MECT applications. Although standard QC procedures have been well established for conventional single‐energy CT, the substantial differences between single‐energy CT and MECT in terms of system implementations, imaging protocols, and clinical tasks warrant QC tests specific to MECT. This task group was therefore charged with developing a systematic QC program designed to meet the needs of MECT applications. In this report, we review the various MECT approaches that are commercially available, including information about hardware implementation, MECT image types, image reconstruction, and postprocessing techniques that are unique to MECT. We address the requirements for MECT phantoms, review representative commercial MECT phantoms, and offer guidance regarding homemade MECT phantoms. We discuss the development of MECT protocols, which must be designed carefully with proper consideration of MECT technology, imaging task, and radiation dose. We then outline specific recommended QC tests in terms of general image quality, radiation dose, differentiation and quantification tasks, and diagnostic and therapeutic applications.

Importance Plasma biomarkers show promise for identifying Alzheimer disease (AD) neuropathology and neurodegeneration, but additional examination among diverse populations and throughout the life course is needed. Objective To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults. Design, Setting, and Participants In 1525 participants from the US-based Atherosclerosis Risk in Communities (ARIC) study, plasma biomarkers were measured using stored specimens collected in midlife (1993-1995, mean age 58.3 years) and late life (2011-2013, mean age 76.0 years; followed up to 2016-2019, mean age 80.7 years). Midlife risk factors (hypertension, diabetes, lipids, coronary heart disease, cigarette use, and physical activity) were assessed for their associations with change in plasma biomarkers over time. The associations of biomarkers with incident all-cause dementia were evaluated in a subpopulation (n = 1339) who were dementia-free in 2011-2013 and had biomarker measurements in 1993-1995 and 2011-2013. Exposure Plasma biomarkers of amyloid-β 42 to amyloid-β 40 (Aβ42:Aβ40) ratio, phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured using the Quanterix Simoa platform. Main Outcomes and Measures Incident all-cause dementia was ascertained from January 1, 2012, through December 31, 2019, from neuropsychological assessments, semiannual participant or informant contact, and medical record surveillance. Results Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black. A total of 252 participants (16.5%) developed dementia. Decreasing Aβ42:Aβ40 ratio and increasing p-tau181, NfL, and GFAP were observed from midlife to late life, with more rapid biomarker changes among participants carrying the apolipoprotein E epsilon 4 ( APOE ε4) allele. Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP. Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aβ42:Aβ40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25). All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14). Conclusions and Relevance Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors. AD-specific biomarkers’ association with dementia starts in midlife whereas late-life measures of AD, neuronal injury, and astrogliosis biomarkers are all associated with dementia.

AbstractThe present study investigated the impact of central α2‐adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2‐adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg−1; maintenance infusion of 0.1–0.5 µg kg h−1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats−1, P = 0.003) most strongly for medium‐sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats−1; P < 0.001). Dexmedetomidine progressively de‐recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de‐recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats−1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ –0.09 ± 0.07 to Δ –0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium‐sized APs (normalized cluster 2: –6.0 ± 5 to –1.6 ± 2 % mmHg−1; P = 0.008). These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. imageKey points Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α2‐adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.