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Assessment of Surgical Salvage Outcomes for Exposed Cranial Neuromodulating Devices.

OBJECTIVES: Implanted neuromodulating devices (NMDs) such as cochlear implants (CIs) and deep brain stimulators (DBSs) are commonly used in modern medicine. Rarely, complications arise post-operatively, including hardware exposure. Traditional teaching suggests that these devices require removal if exposed; however, surgical salvage is a high risk, high reward alternative. We review our single institution experience managing NMD exposure with surgical salvage. METHODS: Retrospective chart review was performed on individuals who had a NMD implanted and underwent an attempt at surgical salvage for exposure during the study period (January 01, 2021 through December 31, 2023). Study outcome success was defined as maintaining a functional NMD 1 year after salvage was attempted. Surgical techniques associated with successful salvage were compared. RESULTS: Nine of 729 patients (1.2%) implanted with NMDs experienced hardware exposure during this 2-year study period. Nine subjects were referred for NMD salvage; however, only 6 of 9 subjects (66.7%, CI = 3; DBS = 3) underwent NMD salvage attempts. Four of the subjects had successful salvage demonstrated successful salvage with a functioning NMD and without wound healing concerns 1 year after their salvage procedure. CONCLUSIONS: Classic teaching states that exposed NMDs require explantation. However, this approach necessarily imposes time without benefit from the NMD between explantation and reimplantation. Our experience demonstrates that surgical salvage can be a successful alternative for the majority (66.7%) of individuals.

Humans

Adductor Canal Block and Local Anesthetic Versus Local Anesthetic Alone in ACL Reconstruction: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Effective postoperative analgesia is crucial for early recovery after anterior cruciate ligament reconstruction (ACLR). Local infiltration analgesia (LIA) and adductor canal block (ACB) are common regional techniques, but their combined efficacy remains unclear. PURPOSE: To compare the effectiveness of LIA alone versus LIA combined with ACB in patients undergoing ACLR, with primary outcomes including postoperative opioid consumption and quadriceps function. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A double-blind randomized controlled trial enrolled 100 patients undergoing ACLR under general anesthesia. Patients were randomized into 2 groups: LIA + sham (saline injection) (n = 50) and LIA + ACB (n = 50). The primary outcome was postoperative opioid consumption in the first 24 hours. Secondary outcomes included visual analog scale (VAS) pain score, quadriceps function assessed by straight leg raise (SLR) at 3 hours, Quality of Recovery-15 (QoR-15) score, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1 week. Statistical analysis was performed using t tests and chi-square tests with a P value <.05 considered significant. RESULTS: There was no significant difference in 24-hour opioid consumption between the LIA + ACB and LIA-only groups (P = .109). Similarly, VAS pain scores at 24 hours postoperatively showed no significant differences between the groups (P = .0804). Early functional recovery, assessed by SLR performance at 3 hours, was equivalent between groups (P = .6711). Additionally, QoR-15 scores on postoperative day 1 and KOOS values at 1 week demonstrated no significant differences (P = .6486 and P = .9054, respectively). Intraoperative opioid consumption was not different between the groups (P = .127). CONCLUSION: These findings indicate that the addition of ACB to LIA does not yield postoperative analgesic in ACLR. Consequently, LIA alone suffices for routine ACLR, potentially enabling clinicians to optimize perioperative workflows without incurring the additional time, financial burden, and resources associated with routine ACB administration. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04721119.

Humans

Six weeks of isometric resistance training led to evidence of corticospinal but not reticulospinal adaptation in previously untrained adult males.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age ~23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10% of MVC. Loud sound (120&#xa0;dB) was used to modulate MEP area and reaction time to visual stimuli during the StartReact test. Only the intervention groups demonstrated significant improvements in MVC (27%) and RTD (60%) (both P < 0.01), along with reduced MEP area (-&#xa0;21%) and silent period duration (-&#xa0;23%) (both P < 0.01). The sustained contraction group showed reduced modulation of reaction time and increased MEP suppression due to loud sound. Short-term resistance training seemed to reduce cortical inhibition and corticospinal excitability in both training groups. The study showed conflicting changes in measures purported to evaluate reticulospinal functioning. It is recommended to examine different forms of resistance training and longer training exposure in future.

Humans

Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.

OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes. METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters. RESULTS: At least one SEP abnormality was detected in 75&#xa0;% of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p&#xa0;<&#xa0;0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p&#xa0;<&#xa0;0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities. CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction. SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.

Humans

King's Mill anterior-posterior and transverse versus paracervical block in operative outpatient hysteroscopy: a randomised trial.

BACKGROUND: Pain control during operative outpatient hysteroscopy remains a clinical challenge, with the paracervical block (PCB) showing inconsistent efficacy. The King's Mill Anterior-Posterior and Transverse (KAPT) block targets the Lee-Frankenhauser plexus within the uterosacral ligament complex, where the highest density of uterine and cervical sensory fibres lies. We compared the KAPT block with the PCB in operative outpatient hysteroscopy. METHODS: Single-centre, participant- and outcome assessor-blinded randomised controlled trial in a UK district general hospital. Forty-eight women undergoing operative outpatient hysteroscopy were randomised 1:1 to the KAPT block or the PCB, each delivered with 10&#x2009;ml of prilocaine. Pain was measured on a 10-point Visual Analogue Scale (VAS) during the procedure and 10&#x2009;minutes post-procedure (co-primary endpoints), and during cervical dilatation (exploratory). Analyses used the Mann-Whitney U test on an intention-to-treat basis, with Hodges-Lehmann median differences, percentile bootstrap 95% confidence intervals, and a hierarchical fixed-sequence testing strategy. RESULTS: Median intra-procedural VAS was 1 (IQR 0 to 3) with the KAPT block versus 2 (IQR 1 to 6) with the PCB (Hodges-Lehmann median difference -1.00, 95% CI -3.00 to 0.00; p&#x2009;=&#x2009;0.040). At 10&#x2009;minutes post-procedure, median VAS was 0 (IQR 0 to 1.25) versus 2 (IQR 0 to 3.25) (median difference -1.00, 95% CI -2.00 to 0.00; p&#x2009;=&#x2009;0.011). Both co-primary endpoints reached significance under hierarchical testing. Cervical dilatation pain did not differ significantly (p&#x2009;=&#x2009;0.146). Satisfaction was 100% in both arms; willingness to recommend was 100% (KAPT) versus 95.8% (PCB). No serious adverse events occurred. CONCLUSIONS: The KAPT block was associated with lower intra-procedural and post-procedural pain than the PCB, with effect sizes consistent with a clinically meaningful difference. These findings support the KAPT block as a superior, anatomically targeted alternative to the PCB and justify evaluation in a larger multicentre trial.Trial registration: ISRCTN15619382.

Humans

Predicting training outcomes for developmental dyslexia from EEG data.

Developmental dyslexia (DD) is characterised by lower-than-average reading abilities and is diagnosed in approximately 10% of individuals. The societal barriers may limit professional fulfilment and psychological wellbeing of individuals with DD, calling for the development of effective interventions to counteract them. As DD is associated with challenges in both phonological and visuo-attentional domains, different longitudinal training approaches were developed to strengthen them. However, they require a considerable amount of personal, social and economic resources and the outcomes may vary depending on individual differences in behavioural and neurophysiological functionality. Hence, predicting training outcomes might help in developing personalised treatment protocols and optimising the use of resources. In the present work we applied machine learning to resting-state EEG to predict longitudinal training outcomes in adults with DD enrolled in a randomized clinical trial. In particular, one group received a visuo-attentional training combined with transcranial alternating current stimulation (tACS), another group received visuo-attentional training with sham/placebo stimulation, and the third group received a phonological training with sham/placebo stimulation. The improvement in text reading speed was associated with spectral power in low-beta and individual frequencies in the alpha (IAF) and beta (IBF) bands, while the improvement in pseudoword reading was associated with IBF. The findings highlight the potential of capturing neural markers of treatment responsiveness in DD. Future studies should focus on the generalisability of predictive models to real-world settings, while investigating whether specific EEG markers predict responsiveness to distinct remediation protocols, thus supporting the development of personalised interventions.

Humans

Dexamethasone as an adjuvant to continuous erector spinae plane block for postoperative analgesia after video-assisted thoracoscopic surgery for pulmonary nodule surgery: a randomized controlled trial.

BACKGROUND: While dexamethasone is proven to enhance single-shot erector spinae plane block (ESPB), its role as an adjuvant in continuous ESPB catheters is unclear. This randomised controlled trial evaluated whether adding dexamethasone to ropivacaine improves analgesia after video-assisted thoracoscopic surgery (VATS). METHODS: 85 patients undergoing VATS with continuous ESPB were randomised to receive postoperative infusion of either 0.2% ropivacaine(C-ESPB group) or ropivacaine with 10&#x2009;mg dexamethasone(D&#x2009;+&#x2009;C-ESPB group). The primary outcome was resting pain visual analog scale (VAS)at 12&#x2009;h postoperatively, while secondary outcomes included QoR-15 scores, tramadol consumption, time to first analgesic requirement, postoperative adverse events, 3-month incidence of chronic pain, catheter-related complications, pain intensity at other times, and hospital stay. RESULTS: The D&#x2009;+&#x2009;C-ESPB group had significantly lower resting pain at 12&#x2009;h [2.56 (1.03) vs 3.24 (1.21), mean difference -0.680, p&#x2009;=&#x2009;0.006]; and lower coughing pain at 12&#x2009;h [4.60 (1.48) vs 5.69 (1.35), mean difference 1.086, p&#x2009;<&#x2009;0.001], with analgesic superiority sustained through 72&#x2009;h. Quality of Recovery-15 scores were higher at 12&#x2009;h [124.70 (12.48) vs 117.26 (12.24); mean difference -7.436, p&#x2009;=&#x2009;0.007] and 48&#x2009;h [141.60 (5.51) vs 138.98 (6.64); mean difference -2.628, p&#x2009;=&#x2009;0.050]; Total tramadol consumption over 72&#x2009;h was markedly reduce [0 (0,100) vs 100 (75,100), z&#xa0;=&#xa0;-3.807, p&#x2009;<&#x2009;0.001], and hospital stay was shorter [Mean (SD) 6.09 (1.34)&#xa0;d vs 6.93 (1.55)d, p&#x2009;<&#x2009;0.001]. The intervention did not, however, alter the 3-month incidence of chronic postsurgical pain (31% vs 34%, p&#x2009;=&#x2009;0.756). CONCLUSION: Dexamethasone significantly enhances the analgesic efficacy of continuous ESPB, improving early pain control, recovery quality, and opioid-sparing after VATS, but does not reduce the incidence of chronic persistent surgical pain.

Humans

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (&#x223c;19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (&#x223c;6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans

Clinical effectiveness of transversus abdominis plane block versus local anaesthesia wound infiltration for postoperative pain relief after laparoscopic appendicectomy in children: A multicentre, double-blind, randomised, controlled phase III trial.

BACKGROUND: Postoperative pain relief after laparoscopic appendicectomy in children provided by transversus abdominis plane (TAP) block and local anaesthesia wound infiltration (LAWI) of trocar insertion sites has never been compared. OBJECTIVE: To investigate whether TAP block could decrease postoperative opioid requirements after laparoscopic appendicectomy in children compared with LAWI. DESIGN: Multicentre, double-blind, phase III randomised trial. SETTING: Two tertiary paediatric surgery centres. PATIENTS: Children aged 3 to 15&#x200a;years admitted for laparoscopic appendicectomy. MAIN OUTCOME MEASURES: The primary outcome was the total dose of nalbuphine delivered within 24&#x200a;h after surgery. Secondary outcomes were the Face Legs Activity Cry Consolability (FLACC) scale values at 1, 2, 6, 12 and 24&#x200a;h, the time from levobupivacaine injection to the first dose of nalbuphine, and the time from the end of surgery to the first mobilisation. Patients received either ultrasound-guided TAP block (TAP group) or LAWI of trocar insertion sites (infiltration group) with 0.6&#x200a;ml&#x200a;kg -1 of levobupivacaine 2.5&#x200a;mg&#x200a;ml -1 , combined with standardised systemic multimodal analgesia including paracetamol, ketoprofen, phloroglucinol and nalbuphine. RESULTS: Forty-six and 50 patients were analysed in the TAP and infiltration groups, respectively [age: 10 [7 to 12] versus 10 [8 to 12] years; females: 16 (35%) versus 25 (50%); duration of surgery: 71 [64 to 90] versus 69 [56 to 89] min]. The primary outcome (total nalbuphine dose) was 0.2 [0.0 to 0.2] and 0.2 [0.0 to 0.2] mg&#x200a;kg -1 in the TAP and infiltration groups, respectively ( P &#x200a;=&#x200a;0.95). FLACC scale values did not significantly differ between the two groups ( P &#x200a;=&#x200a;0.78). Time to the first dose of nalbuphine or to first mobilisation was not significantly different between groups ( P value for log-rank test&#x200a;=&#x200a;0.095 and 0.18, respectively). CONCLUSION: TAP block does not appear to provide a greater opioid-sparing effect than LAWI of trocar insertion sites after laparoscopic appendicectomy in children, when combined with systemic multimodal analgesia including nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04969133.

Humans

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n&#x2009;=&#x2009;73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5&#x2009;&#xb1;&#x2009;3.7 before treatment to 8.2&#x2009;&#xb1;&#x2009;4.1 after treatment (t&#x2009;=&#x2009;15.900, p&#x2009;<&#x2009;0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3&#x2009;&#xb1;&#x2009;2.9 before treatment to 8.0&#x2009;&#xb1;&#x2009;3.8 after treatment (t&#x2009;=&#x2009;17.232, p&#x2009;<&#x2009;0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7&#x2009;&#xb1;&#x2009;6.8 to 14.0&#x2009;&#xb1;&#x2009;5.0 (t&#x2009;=&#x2009;6.363, p&#x2009;<&#x2009;0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans

Effects of cinnamon supplementation combined with exercise training on anthropometric indices and reproductive hormones in overweight and obese women.

BACKGROUND: The prevalence of obesity and increased fat in the chest and abdomen in women and hormonal changes, can affect female fertility. The present study aims to investigate the effect of exercise training combined with cinnamon supplementation on chest and abdominal circumference, as well as sex hormones, in overweight and obese women. METHODS: Twenty-six inactive overweight and obese women were randomly allocated to an exercise (E; n = 13) and exercise plus cinnamon supplementation (E+S; n = 13) group. Both groups completed a 4-week exercise program three times weekly, while the E+S group additionally received cinnamon supplementation three times weekly. Chest and abdominal circumferences and serum concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed before and after the intervention. RESULTS: Significant pre-to-post reductions in chest and abdominal circumference were observed in both groups (all p &#x2264; 0.005). Estradiol, progesterone, and FSH concentrations increased, whereas LH concentrations decreased significantly in both groups (all p &#x2264; 0.005). However, between-group comparisons revealed a significant difference only for chest circumference (p = 0.003), with no significant group differences in abdominal circumference or any reproductive hormone concentration (all p > 0.05). CONCLUSION: Both groups showed favorable changes in anthropometric and reproductive hormone measures following the 4-week study period. However, the significant between-group difference was limited to chest circumference, providing no clear evidence that cinnamon supplementation conferred additional benefits for abdominal circumference or reproductive hormone profiles beyond those observed with exercise. These findings highlight the potential relevance of exercise-based interventions while warranting confirmation in larger, adequately powered trials.

Humans

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20&#xa0;min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20&#xa0;min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

Humans

Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications.

OBJECTIVE: This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia. METHODS: 101 patients with baseline hemoglobin <12.0&#x2009;g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3&#x2009;months post-enrollment and maintained ESA/danazol &#x2265;3&#x2009;months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0&#x2009;g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (&#x2265;50% reduction from baseline) and symptom response (&#x2265;6.5-point improvement in FACT-Lym score). RESULTS: Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3&#x2009;months, n&#x2009;=&#x2009;1242). Mean total daily ruxolitinib dose remained >25&#x2009;mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N&#x2009;=&#x2009;2233). Outcomes were similar between the hemoglobin <12.0&#x2009;g/dL analysis population and patients with baseline hemoglobin <10.0&#x2009;g/dL (n&#x2009;=&#x2009;52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease. DISCUSSION: This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia. CONCLUSION: Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

Humans

Efficacy of targeted neuromodulation treatments: a clinical report.

BACKGROUND: Peripheral neuropathy is a debilitating condition characterized by chronic pain, numbness, tingling, burning, and tightness/swelling. Conventional therapies often focus on symptom management, and some patients experience chronic and refractory symptoms. RESEARCH DESIGN AND METHODS: This retrospective clinical analysis evaluated the clinical outcomes of neuromodulation neuropathy treatment using the NeuroGen-Series device in patients with diabetic peripheral neuropathy (DPN) or idiopathic peripheral neuropathy (IPN). 9,805 unique patients who underwent 133,741 treatments between 18 August 2017, and 23 July 2024, were analyzed. Patients were divided into treatment completers (&#x2265;24 sessions) and noncompleters (<24 sessions). Paired t-tests confirmed statistically significant reductions in pre- and post-treatment symptom scores (p&#x2009;<&#x2009;0.001). RESULTS: Among completers, symptom severity decreased by an average of 46.2%. Tingling and pain showed the greatest improvement, while tightness/swelling and numbness showed the least reduction. 64% of patients reported improvement after one session, and 84% reported improvement after 24 sessions. Nonresponders accounted for 5.8% of patients overall. Younger patients and those with higher initial symptom severity were more likely to discontinue treatment. CONCLUSIONS: Overall, neuromodulation treatment resulted in statistically significant reductions in symptom severity, though nonresponders and high attrition rate highlight the need for individualized treatment strategies and further investigation.

Humans

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4&#xa0;days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9&#xa0;&#xb1;&#xa0;12.7; active/sham 50/54). The model yielded a Time &#xd7; Novelty Seeking interaction (&#x3b2;&#xa0;=&#xa0;-1.70, p&#xa0;=&#xa0;0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p&#xa0;=&#xa0;0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85&#xa0;years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (&#x2265;30&#xa0;mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans

The effect of olfactory training and odor exposure on visual selective attention.

Olfactory training (OT) is a well-established, non-invasive intervention that improves olfactory function by repeated, structured exposure to odorants. Beyond sensory outcomes, it also influences multiple aspects of cognition. Yet, its influence on attention, a fundamental process underlying many cognitive domains, remains unclear. This study examined the impact of a 12-week OT program on visual selective attentional performance and the effect of on-task odor exposure. Ninety-four healthy participants were initially included, and randomized into OT or placebo groups. Participants completed the d2 Test of Attention simultaneously with and without odor exposure in a randomized sequence at baseline, post-training, and a follow-up four weeks after stopping the training. The d2 test measures commission errors, omission errors, and concentration performance. Ninety-three participants (OT=51, placebo=42) completed baseline measurement, 74 (OT=39, placebo=35) returned for post-training session, and 57 participants (OT=29, placebo=28) returned for the follow-up appointment. Results showed that OT did not significantly improve d2 test performance. In the primary model, on-task PEA exposure reduced commission errors compared to the odorless condition, suggesting a possible transient effect of olfactory input on the inhibitory control in the context of the d2 attentional test. This effect, however, was no longer significant once the follow-up data were included and should be regarded as preliminary. Overall, these findings raise the possibility of a distinction between relatively long-term OT and short-term odor exposure: while OT did not improve visual selective attention, brief on-task odor exposure may transiently enhance inhibitory control during attentional tasks, a possibility that remains to be confirmed.

Humans

Gonadal function and fertility outcomes after orchiopexy versus orchiectomy for testicular torsion: A systematic review and meta-analysis.

PURPOSE: To review the early and late changes in hormonal profiles, semen parameters, and clinical outcomes in patients treated with orchiopexy versus orchiectomy for testicular torsion. METHODS: A systematic search was conducted across MEDLINE, Scopus, Web of Science, Cochrane Library, and other databases, following PRISMA guidelines. PRIMARY OUTCOMES: FSH, LH, testosterone, inhibin-B, and semen parameters. Quality was assessed using the Newcastle-Ottawa Scale. Certainty of evidence was evaluated using the GRADE framework. Statistical analysis was performed using the random-effects model. RESULTS: Eleven studies involving 538 participants (197 orchiectomy, 341 orchiopexy) were included. Orchiectomy was associated with a significant increase in FSH (SMD: 1.63, P < 0.0001) and LH (SMD: 1.31, P < 0.0001) compared to orchiopexy. However, testosterone (MD: 0.31 ng/mL; P = 0.4) and inhibin-B (SMD: -0.14; P = 0.87) levels were comparable between groups. Regarding semen parameters, orchiectomy resulted in a significant reduction in sperm concentration (MD: -18 million/mL, P = 0.01). No significant differences were found in sperm count (MD: 13.9 million; P = 0.43), normal morphology (MD: 4.97%; P = 0.12), or total motility (MD: 4.05%; P = 0.49). The pooled rate for ipsilateral atrophy following orchiopexy was 38%, which likely depends on ischemia duration. CONCLUSION: Surgical choice in testicular torsion does not significantly affect the overall hormonal balance or most semen parameters due to compensatory mechanisms of the hypothalamic-pituitary-gonadal axis. Clinical decisions should consider individual case factors, as we lack reliable data on subsequent paternity rates.

Male