Primary sensory neurons in dorsal root ganglia (DRG) have long axons and a high demand for mitochondria, and mitochondrial dysfunction has been implicated in peripheral neuropathy after diabetes and chemotherapy1,2. However, the mechanisms by which primary sensory neurons maintain their mitochondrial supply remain unclear. Satellite glial cells (SGCs) in DRG encircle sensory neurons and regulate neuronal activity and pain3. Here we show that SGCs are capable of transferring mitochondria to DRG sensory neurons in vitro, ex vivo and in vivo by the formation of tunnelling nanotubes with SGC-derived myosin 10 (MYO10). Scanning and transmission electron microscopy revealed tunnelling nanotube-like ultrastructures between SGCs and sensory neurons in mouse and human DRG. Blockade of mitochondrial transfer in naive mice leads to nerve degeneration and neuropathic pain. Single-nucleus RNA sequencing and in situ hybridization revealed that MYO10 is highly expressed in human SGCs. Furthermore, SGCs from DRG of people with diabetes exhibit reduced MYO10 expression and mitochondrial transfer to neurons. Adoptive transfer of human SGCs into the mouse DRG provides MYO10-dependent protection against peripheral neuropathy. This study uncovers a previously unrecognized role of peripheral glia and provides insights into small fibre neuropathy in diabetes, offering new therapeutic strategies for the management of neuropathic pain.
BACKGROUND:Despite the paucity of outcome data, axillary lymph node dissection (ALND) is increasingly being omitted in patients with positive sentinel lymph nodes after neoadjuvant chemotherapy, particularly in those with low-volume residual disease. We investigated oncological outcomes in patients with breast cancer and residual micrometastases in the sentinel lymph nodes treated with or without ALND. METHODS:OPBC-07/microNAC was a retrospective cohort study, using data obtained from the institutional databases of 84 cancer centres in 30 countries. Patients aged 18 years or older with clinical T1-4, N0-3 breast cancer at diagnosis treated with neoadjuvant chemotherapy followed by surgery between Jan 1, 2013, and May 31, 2023, who were found to have residual micrometastases (metastasis measuring >0·2 mm or >200 cells, not exceeding 2·0 mm in size) on frozen section or on final paraffin sections as determined by sentinel lymph node biopsy, targeted axillary dissection (sentinel lymph node biopsy with single or dual-tracer mapping plus image-guided localisation of the initially biopsy-proven and clipped node), or the marking axillary lymph nodes with radioactive iodine seeds (MARI) procedure were eligible for inclusion. The primary endpoint was the 5-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) stratified by type of axillary surgery. Given the median follow-up, here we report 3-year rates and exploratory 5-year estimates. This study was registered with ClinicalTrials.gov, NCT06529302. FINDINGS:1585 female patients with ypN1mi disease were analysed, of whom 804 (50·7%) underwent ALND and 781 (49·3%) did not. Of 1585 women, 238 (15·0%) self-identified as Asian, 65 (4·1%) as Black, 200 (12·6%) as Hispanic, 968 (61·1%) as White, and 114 (7·2%) as unknown race and ethnicity. 925 (58·4%) of 1585 women had cT2 tumours, 1054 (66·5%) were node positive, and 1267 (79·9%) received nodal radiotherapy. The median follow-up was 3·1 years (IQR 1·8-5·2). The 3-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) for the entire cohort was 2·0% (95% CI 1·3-2·9), with no statistical difference identified by extent of axillary surgery. However, patients with triple-negative disease who did not receive ALND had significantly higher rates of any axillary recurrence than women treated with ALND (8·7% [95% CI 4·4-15·0] vs 2·4% [95% CI 0·7-6·5], p=0·018). On multivariable analysis, triple-negative breast cancer (hazard ratio 3·83 [95% CI 1·72-8·52]) and omission of nodal radiotherapy (2·62 [1·19-5·73]) but not omission of ALND (0·86 [0·37-2·00]) were independently associated with an increased risk of any axillary recurrence. INTERPRETATION:Overall, these results do not support ALND for all patients with ypN1mi on sentinel lymph node biopsy treated with nodal radiotherapy; however, tumour biology should be taken into account when considering ALND omission. FUNDING:US National Institutes of Health, National Cancer Institute.
Gastric point-of-care ultrasound (POCUS) may offer clinical value in assessing aspiration risk among medically complex patients undergoing regional anesthesia and pain procedures. While the American Society of Anesthesiologists (ASA) preoperative fasting guidelines primarily apply to healthy individuals, medically complex populations often present with differing gastric emptying and aspiration risk. This narrative review, conducted by the American Society of Regional Anesthesia and Pain Medicine (ASRA-PM), adhered to PRISMA guidelines and was registered with PROSPERO. It focused on seven medically complex patient groups: those who are pregnant, obese, diabetic, have gastroesophageal reflux disease (GERD), are receiving emergency care, are enterally fed, or are taking GLP-1 receptor agonists (GLP-1RA). Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). Practice recommendations were developed using an iterative expert consensus process, with final recommendations based on evidence strength, clinical relevance, and expert agreement. Findings support the use of gastric POCUS in patients in active labor, those undergoing urgent cesarean sections, and those with diabetes. Conditional support is given for obesity, emergency care, enteral feeding, and GLP-1RA use. Routine use is not recommended in non-laboring pregnancies, elective cesarean delivery, or GERD. While gastric POCUS may aid with aspiration risk evaluation, its use should complement clinical judgment. Implementation may be limited by practical and training constraints, requiring individualized decision-making. These recommendations serve as a foundation for future research and potential clinical guideline development. PROSPERO registration number: CRD42023445927.
BACKGROUND AND AIMS:Radial access site for percutaneous coronary intervention (PCI) is recommended by clinical practice guidelines because of superior outcomes compared with femoral access site. Historically, the adoption of radial access site in the USA has lagged behind much of the rest of the world, but contemporary data on access site selection across the spectrum of clinical presentations and its association with outcomes are lacking. METHODS:A retrospective cohort study from the National Cardiovascular Data Registry's CathPCI Registry was conducted including PCIs performed between 1 January 2013 and 30 June 2022. The comparative safety of radial vs femoral access site for PCI was evaluated with instrumental variable analysis, a technique that can be used to support causal inference, exploiting operator variation in access site preferences as the instrumental variable. RESULTS:Overall, 6 658 479 PCI procedures were performed during the study period, of which 40.4% (n = 2 690 355) were performed via radial access site, increasing from 20.3% in 2013 to 57.5% in 2022. This increase was seen in all geographic regions and across the full spectrum of presentations, with the largest relative increase seen in patients with ST-elevation myocardial infarction. Overall, 2 420 805 PCIs met inclusion criteria for the comparative safety analysis. In instrumental variable analyses, radial access site was associated with lower in-hospital mortality [absolute risk difference (ARD) -.15%, 95% confidence interval (CI) -.20 to -.10], major access site bleeding (ARD -.64%, 95% CI -.68 to -.60), and other major vascular complications (ARD -.21%, 95% CI -.23 to -.18) but a higher risk of ischaemic stroke (ARD .05%, 95% CI .03-.08). There was no association with the falsification endpoint of gastrointestinal or genitourinary bleeding (ARD .00%, 95% CI -.03-.03). CONCLUSIONS:Over the past decade, use of radial access site for PCI has increased 2.8-fold in the USA and now represents the dominant form of access site across all procedural indications. Based on instrumental variable analyses, PCI with radial access site had lower rates of in-hospital mortality, major access site bleeding, and other major vascular complications compared with femoral access site but a slightly higher risk of ischaemic stroke in contemporary practice.
Renal replacement therapy (RRT) is frequently used in critically ill patients with acute kidney injury (AKI). Here, we provide guidelines for the management of RRT in critically ill patients on the intensive care unit (ICU). We convened a systemic literature research and a Delphi process with a bi-national multidisciplinary consensus panel including 22 clinicians of 12 different German-speaking societies (Germany and Austria) with expertise in RRT. This structured guideline process was the basis for the evidence-based statements and recommendations. We identified seven clinical areas needing guidance: (1) start, (2) modality (diffusion and convection), (3) continuous/ intermittent, (4) anticoagulation, (5) dose (6) pharmacotherapy, (7) stopping criteria. The consensus produced 73 statements and recommendations regarding key clinical areas, the most important 47 statements and recommendations are summarized in this overview. This evidence-based bi-national guideline should provide physicians with guidance for delivering best practice to critically ill patients with a dialysis-dependent AKI.
