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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in death within 2–5 years of diagnosis. Respiratory failure is the most common cause of death in ALS. Mutations in the transactive response DNA binding protein 43 (TDP-43) encoded by the TARDBP gene are associated with abnormal cellular aggregates in neurons of patients with both familial and sporadic ALS. The role of these abnormal aggregates on breathing is unclear. Since respiratory failure is a major cause of death in ALS, we sought to determine the role of TDP-43 mutations on the respiratory motor unit in the Prp-hTDP43A315T mouse model – a model that expresses human TDP-43 containing the A315T mutation. We assessed breathing using whole-body plethysmography, and investigated neuropathology in hypoglossal and phrenic respiratory motor units. Postmortem studies included quantification of hypoglossal and putative phrenic motor neurons, activated microglia and astrocytes in respiratory control centers, and assessment of hypoglossal and phrenic nerves of TDP43A315T mice. The male TDP43A315T mice display an early onset of rapid progression of disease, and premature death (less than 15 weeks) compared to control mice and compared to female TDP43A315T mice who die between 20 and 35 weeks of age. The TDP43A315T mice have progressive and profound breathing deficits at baseline and during a respiratory challenge. Histologically, hypoglossal and putative phrenic motor neurons of TDP43A315T mice are decreased and have increased microglial and astrocyte activation, indicating pronounced neurodegeneration and neuroinflammation. Further, there is axonopathy and demyelination in the hypoglossal and phrenic nerve of TDP43A315T mice. Thus, the TDP-43A315T mice have significant respiratory pathology and neuropathology, which makes them a useful translatable model for the study of novel therapies on breathing in ALS. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does pulmonary vein isolation have a placebo effect in treatment of atrial fibrillation? Findings: In this double-blind randomized trial of 126 patients with symptomatic atrial fibrillation, pulmonary vein isolation resulted in a significant and clinically important decrease in atrial fibrillation burden, with substantial improvements in symptoms and quality of life, compared with a sham procedure. Meaning: Pulmonary vein isolation significantly reduced atrial fibrillation burden compared with a sham control, providing evidence that the benefit of pulmonary vein isolation in symptomatic atrial fibrillation is not because of a placebo effect. Importance: There are concerns that pulmonary vein isolation for atrial fibrillation may have a profound placebo effect, but no double-blind randomized clinical trials have been conducted. Objective: To determine whether pulmonary vein isolation is more effective than a sham procedure for improving outcomes in atrial fibrillation. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 2 tertiary centers in the UK between January 2020 and March 2024 among patients with symptomatic paroxysmal or persistent atrial fibrillation. Major exclusion criteria included long-standing persistent atrial fibrillation, prior left atrium ablation, other arrhythmias requiring ablative therapy, a left atrium of 5.5 cm or larger, and ejection fraction of less than 35%. Intervention: Participants were randomly assigned to receive pulmonary vein isolation with cryoablation (n = 64) or a sham procedure with phrenic nerve pacing (n = 62). Main Outcomes and Measures: The primary end point was atrial fibrillation burden at 6 months, excluding a 3-month blanking period. Secondary outcomes included quality-of-life measures, time to events, and safety. Atrial fibrillation burden was measured by an implantable loop recorder. Results: A total of 126 participants were randomized (mean age, 66.8 years; 89 men [70.63%]; 20.63% with paroxysmal atrial fibrillation). The absolute mean atrial fibrillation burden change from baseline to 6 months was 60.31% in the ablation group and 35.0% in the sham group (geometric mean difference, 0.25; 95% CI, 0.15-0.42; P <.001). The estimated difference in the overall Atrial Fibrillation Effect on Quality of Life score at 6 months, favoring catheter ablation, was 18.39 points (95% CI, 11.48-25.30 points). The Short Form 36 general health score also improved substantially more with ablation, with an estimated difference of 9.27 points at 6 months (95% CI, 3.78-14.76 points). Conclusions and Relevance: Pulmonary vein isolation resulted in a statistically significant and clinically important decrease in atrial fibrillation burden at 6 months, with substantial improvements in symptoms and quality of life, compared with a sham procedure. Trial Registration: ClinicalTrials.gov Identifier: NCT04272762 This randomized clinical trial assesses the effect of pulmonary vein isolation vs a sham procedure on atrial fibrillation burden at 6 months in patients with symptomatic paroxysmal or persistent atrial fibrillation. [ABSTRACT FROM AUTHOR]

Introduction: Pulsed‐field ablation (PFA) is a novel nonthermal energy that shows unique features that can be of use beyond pulmonary vein ablation, like tissue selectivity or proximity rather than contact dependency. Methods and Results: We report three cases of right focal atrial tachycardias arising from the superior cavoatrial junction and the crista terminalis, in close relationship with the phrenic nerve, effectively ablated using a commercially available PFA catheter designed for pulmonary vein isolation without collateral damage. Conclusion: PFA can be useful for treating right atrial tachycardias involving sites near the phrenic nerve, avoiding the need for complex nerve‐sparing strategies. [ABSTRACT FROM AUTHOR]

Objective To explore the effects of mechanical ventilation and mechanical ventilation combined with phrenic nerve electrical stimulation on the morphology of the phrenic nerve-diaphragm neuromuscular junction in rats. Methods The rats were divided into a control group (CON group, n = 6); an 18-hour mechanical ventilation group (MV group, n = 6); an 18-hour ventilation combined with sham electrical stimulation group (S-MS group, n = 6); and an 18-hour ventilation combined with electrical stimulation group (MS group, n = 6), in which the diaphragm contraction force was detected through the biological signal acquisition system, the stimulation frequency-contraction curve was fitted, and the muscle fatigue index was calculated. The muscle fiber crosssectional area (CSA) of the diaphragm specimen was observed through HE staining; the endplate membrane area of the neuromuscular junction (NMJ) was observed through immunohistochemistry (IHC) staining of the diaphragm combined with laser confocal technology. Results As compared with the CON group, the contractility of isolated diaphragm muscles in the MV group and S-MS group decreased; the fatigue resistance of isolated diaphragm, as compared with the CON group (0.686 8 ± 0.049 42), decreased in the MV group (0.360 3 ± 0.066 89) and the S-MS group (0.367 9 ± 0.034 94), with a greater decline in the MS group (0.536 2 ± 0.054 38); as compared with the CON group [674.3(523.9, 863.6)], diaphragm CSA was reduced in the MV group [374.5(293.3, 522.7)] and S-MS group [392.8(309.5, 542.6)], with a relatively lower reduction in the MS group [592.7(425.1, 820.0)]; as compared with the CON group [393.7(293.5, 471.3)], the diaphragm endplate membrane area decreased in the MV group [289.7(227.0, 354.2)] and S-MS group [243.1(190.8, 331.7)], with a lower degree of reduction in the MS group [331.0(262.8, 413.7). Conclusions Mechanical ventilation causes diaphragm dysfunction in rats and decreases the endplate membrane area of the diaphragm NMJ. Bilateral phrenic nerve electrical stimulation for 10 min/h can improve diaphragm dysfunction and changes in the endplate membrane area of the diaphragm NMJ caused by mechanical ventilation. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The coeliac plexus is often approached due to the diagnosis and treatment of the intractable pain associated with cancerous or non‐cancerous pathology of the pancreas or neighbouring organs. Various methods of coeliac plexus blocks are used and the variations in its structure are causes of the failures of such procedures.Twenty human cadavers (17 male, 3 females, age range 30–86 years, without any abdominal pathology) were dissected in the supine position. The abdominal autonomics was studied bilaterally after the incision of the abdominal wall the peritoneal sac was cut and the abdominal organs were removed. The coeliac plexus becomes visible after removing the hepatogastric and hepatoduodenal ligaments and pulling the stomach to the left and the pancreas downward.The largest coeliac ganglion was 45 mm on the right and 25 mm on the left. The average distance of the ganglia from the coeliac trunks was 6–9 mm from the right and left. The size of coeliac ganglia varies from 5 to 45 mm and their number from 2 to 12. Ganglia can be diffusely or concentrically organized. The coeliac plexus almost always receives the branches from the greater splanchnic and vagus nerves. Sometimes the contributions from the lesser splanchnic nerve, phrenic nerve, and accessory phrenic nerve (60%) were observed. Very rarely are missing both phrenic nerves.Sympathectomy (splanchnicectomy), as well as the coeliac blocks (under US, CT control, or laparotomic) aimed at pain relief usually by pancreatic cancer, should consider these possible variabilities. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions The effectiveness and safety of 50 W, high‐power, short‐duration (HPSD) ablation in superior vena cava isolation (SVCI) for patients with atrial fibrillation (AF) have been reported. However, the acute outcomes of SVCI combined with 90 W/4 s, very high‐power, short‐duration (vHPSD) ablation remain unknown. In this study, we aimed to investigate a novel approach that combines 50 W‐HPSD and 90 W/4 s‐vHPSD ablation in SVCI and to elucidate the characteristics, outcomes, and safety of this approach by comparing SVCI with conventional ablation index (AI)‐guided middle‐power, middle‐duration (MPMD) ablation.Overall, 126 patients who underwent AF ablation with SVCI using the QDOT MICROTM catheter were retrospectively reviewed; one group underwent SVCI with a combined approach of HPSD and vHPSD ablation (50 W/90 W group, n = 73) and another group underwent AI‐guided MPMD ablation (30–40 W group, n = 53). This study compared the procedural details, radiofrequency (RF) ablation profiles, and complications. The RF settings used in the 50 W/90 W group were 50 W/7 s for the lateral segment close to the phrenic nerve and 90 W/4 s for the nonlateral segment.The 50 W/90 W group required a significantly shorter procedural time (3.2 vs. 5.9 min, p < .001), shorter RF duration (42.0 vs. 162.0 s, p < .001), and lower RF energy (2834 vs. 5480 J, p < .001) than the 30–40 W group. Procedural success, first‐pass SVCI, number of RF applications, and SVC reconnection after isoproterenol loading were comparable between the groups. The maximum tip‐electrode temperature of the multi‐thermocouple system was significantly higher in the 50 W/90 W group than in the 30–40 W group (50.0°C vs. 47.0°C, p < .001). No complications, such as phrenic nerve injury or bleeding requiring transfusion, were observed in either group.The combined approach of 50 W/7 s‐HPSD and 90 W/4 s‐vHPSD ablation resulted in successful and safe SVCI with shorter procedural time, shorter RF duration, and lower RF energy. [ABSTRACT FROM AUTHOR]

Background: Superior vena cava (SVC) is atrial fibrillation (AF)’s most common non-pulmonary vein (PV) foci. Studies reported conflictory results when SVC isolation (SVCi) was combined with PVi and long-term outcomes were lacking. Therefore, we aimed to evaluate the long-term efficacy and safety of empirical SVCi as an adjunct to cryoballoonbased PV isolation (PVi) in persistent AF ablation. Methods: A total of 40 consecutive persistent AF patients (60.6 ± 8.2 years, 52.5% females) who underwent SVCi in addition to PVi compared with a propensity score matched cohort of 40 persistent AF patients (58.6 ± 8.7 years, 50% female) in whom PVionly was performed. Second-generation cryoballoon (CB2) was used in all procedures. Atrial tachyarrhythmia (ATa) recurrence was defined as the detection of AF, atrial flutter, or atrial tachycardia (≥30 s) after a 3-month blanking period. Results: Pulmonary veins and SVC were successfully isolated in all patients. At a mean of 46.7 ± 7.8 months follow-up, 22 (55%) patients in the PVi-only group, and 27 (67.5%) patients in the PVi+SVCi group were free of ATa after the index procedure (P = .359). Phrenic nerve injury (PNI) was detected in 2 (5%) patients in the PVi-only group (during right PVi) and 2 (5%) patients in the PVi+SVCi group (during SVCi) (P = 1.00). Cox regression analysis revealed that early recurrence was the only predictor of recurrence (hazard ratio 4.88, 95% confidence interval 1.59-14.96; P = .005). Conclusion: Long-term results of our small sample-sized study revealed that CB-based PVi+SVCi was associated with outcomes similar to the PVi-only strategy in patients with persistent AF. Although complication rates were similar between the groups, close follow-up of diaphragmatic movement is crucial to prevent PNI during SVCi. [ABSTRACT FROM AUTHOR]

Purpose: The hemiclamshell (HCS) approach provides a comprehensive view of the anterior mediastinum, whereas the transmanubrial osteomuscular sparing approach (TMA) allows sufficient exposure of the cervico-thoracic transition. We assessed the effectiveness and the outcomes of the combined HCS plus TMA approach to resect thoracic malignant tumors. Methods: We reviewed five patients with thoracic malignant tumors invading the thoracic outlet who underwent surgery using an HCS and TMA approach between 2018 and 2021. Results: The preoperative diagnosis was myxofibrosarcoma, lung cancer, thymic cancer, thymoma, and neurofibromatosis type1 in one patient each, respectively. Cardiovascular reconstruction was done on the aortic arch in two patients, on the descending aorta in one, and on the superior vena cava in one, combined with resection of the vagus nerve in three patients, of the phrenic nerve in two, and of vertebra in one, with overlap in some cases. The TMA was added because all patients required dissection of the periphery of the subclavian artery, and two had tumor extension to the neck. Macroscopic complete resection was achieved in four patients. There was no postoperative mortality. Conclusion: The combination of the HCS and TMA approaches at the same operation provides a comprehensive view of the mediastinum, lung, and cervico-thoracic transition and allows safe access to the thoracic great vessels and subclavian vessels. [ABSTRACT FROM AUTHOR]

Electromagnetic stimulation of the phrenic nerve induces diaphragm contractions, but no coils for clinical use have been available. We recently demonstrated the feasibility of ventilation using bilateral transcutaneous noninvasive electromagnetic phrenic nerve stimulation (NEPNS) before surgery in lung-healthy patients with healthy weight in a dose-dependent manner. Is NEPNS feasible in critically ill patients in an ICU setting? This feasibility nonrandomized controlled study aimed to enroll patients within 36 h of intubation who were expected to remain ventilated for ≥ 72 h. The intervention group received 15-min bilateral transcutaneous NEPNS bid, whereas the control group received standard care. If sufficient, NEPNS was used without pressure support to ventilate the patient; pressure support was added if necessary to ventilate the patient adequately. The primary outcome was feasibility, measured as time to find the optimal stimulation position. Further end points were sessions performed according to the protocol or allowing a next-day catch-up session and tidal volume achieved with stimulation reaching only 3 to 6 mL/kg ideal body weight (IBW). A secondary end point was expiratory diaphragm thickness measured with ultrasound from days 1 to 10 (or extubation). The revised European Union regulation mandated reapproval of medical devices, prematurely halting the study. Eleven patients (five in the intervention group, six in the control group) were enrolled. The median time to find an adequate stimulation position was 23 s (interquartile range, 12-62 s). The intervention bid was executed in 87% of patients, and 92% of patients including a next-day catch-up session. Ventilation with 3 to 6 mL/kg IBW was achieved in 732 of 1,701 stimulations (43.0%) with stimulation only and in 2,511 of 4,036 stimulations (62.2%) with additional pressure support. A decrease in diaphragm thickness was prevented by bilateral NEPNS (P =.034) until day 10. Bilateral transcutaneous NEPNS was feasible in the ICU setting with the potential benefit of preventing diaphragm atrophy during mechanical ventilation. NEPNS ventilation effectiveness needs further assessment. ClinicalTrials.gov ; No.: NCT05238753 ; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

To investigate the efficacy of ultrasound-guided interscalene brachial plexus block in the treatment of shoulder pain following hepatectomy. Design: A randomized controlled trial. Methods: We conducted a single-center, randomized controlled trial. Forty-four patients with shoulder pain scores of at least 5 were randomly assigned to two groups: the treatment group, which received 0.5% ropivacaine (5mL) combined with dexamethasone (5 mg) (n=22), and the control group, which received normal saline (5mL) (n=22). The intervention was performed in the postanesthesia care unit after shoulder pain was identified by using the visual analogue scale. The shoulder pain was re-evaluated 15 minutes after intervention. The incidence of effective pain relief, defined as at least 75% reduction in pain intensity, was the primary outcome. Secondary outcomes included shoulder pain intensity within 2 days after surgery, the timing of the first rescue analgesia, total additional analgesic use, arterial oxygen saturation, intervention-related adverse reactions, and patient satisfaction regarding shoulder pain. Results: The incidence of effective pain relief was significantly higher in the treatment group compared to the control group (15 (68.2%) vs 2 (9.1%), P< 0.001). The interscalene brachial plexus block not only prolonged the time to first analgesic request (P < 0.001), but also reduced the number of analgesic requests (P < 0.001). In the comparison between groups, arterial oxygen saturation was lower in the control group than that in the treatment group, attributed to the use of sufentanil for remedial analgesia (92.4% vs 94.5%, P=0.014). Conclusion: Interscalene brachial plexus block can effectively relieve post-hepatectomy shoulder pain without clinically significant hypoxemia. [ABSTRACT FROM AUTHOR]

Background: Diaphragmatic myoclonus is a rare motor disorder that affects muscle tone. It is characterized by involuntary movements of the abdominal wall and rhythmic, repetitive contractions of the accessory or respiratory muscles, all of which are innervated by the cervical nerve roots. Case description: We reviewed the case of a 57-year-old male patient who underwent surgery for a left cerebellar hemorrhage. He exhibited persistent myoclonus in the palate, jaw, and thoracoabdominal region. Following treatment, there was a significant reduction in flutter amplitude in these areas. Conclusion: The clinical rarity and variability of presentations often make diagnosis challenging and delayed. It is believed that this condition stems from abnormal excitation within the central nervous system or neural pathways that involve the phrenic nerve. Another potential mechanism is the direct irritation of the diaphragm. Ultrasound, chest fluoroscopy, and electromyography (EMG) can support the diagnosis. Various pharmacological and surgical treatments have been tried, yet specific treatment guidelines are still lacking. [ABSTRACT FROM AUTHOR]

Background: In the United States in 2017, there were an estimated 903,745 hospitalizations involving mechanical ventilation (MV). Complications from ventilation can result in longer hospital stays, increased risk of disability, and increased healthcare costs. It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or reverse diaphragm dysfunction, resulting in faster weaning. Methods: The ReInvigorate Trial is a prospective, multicenter, randomized, controlled clinical trial evaluating the safety and efficacy of Stimdia's pdSTIM System for facilitating weaning from MV. The pdSTIM system employs percutaneously placed multipolar electrodes to stimulate the cervical phrenic nerves and activate contraction of the diaphragm bilaterally. Patients who were on mechanical ventilation for at least 96 h and who failed at least one weaning attempt were considered for enrollment in the study. The primary efficacy endpoint was the time to successful liberation from mechanical ventilation (treatment vs. control). Secondary endpoints will include the rapid shallow breathing index and other physiological and system characteristics. Safety will be summarized for both primary and additional analyses. All endpoints will be evaluated at 30 days or at the time of removal of mechanical ventilation, whichever is first. Discussion: This pivotal study is being conducted under an investigational device exception with the U.S. Food and Drug Administration. The technology being studied could provide a first-of-kind therapy for difficult-to-wean patients on mechanical ventilation in an intensive care unit setting. Trial registration: Clinicaltrials.gov, NCT05998018, registered August 2023. [ABSTRACT FROM AUTHOR]

Abstract Background In the United States in 2017, there were an estimated 903,745 hospitalizations involving mechanical ventilation (MV). Complications from ventilation can result in longer hospital stays, increased risk of disability, and increased healthcare costs. It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or reverse diaphragm dysfunction, resulting in faster weaning. Methods The ReInvigorate Trial is a prospective, multicenter, randomized, controlled clinical trial evaluating the safety and efficacy of Stimdia’s pdSTIM System for facilitating weaning from MV. The pdSTIM system employs percutaneously placed multipolar electrodes to stimulate the cervical phrenic nerves and activate contraction of the diaphragm bilaterally. Patients who were on mechanical ventilation for at least 96 h and who failed at least one weaning attempt were considered for enrollment in the study. The primary efficacy endpoint was the time to successful liberation from mechanical ventilation (treatment vs. control). Secondary endpoints will include the rapid shallow breathing index and other physiological and system characteristics. Safety will be summarized for both primary and additional analyses. All endpoints will be evaluated at 30 days or at the time of removal of mechanical ventilation, whichever is first. Discussion This pivotal study is being conducted under an investigational device exception with the U.S. Food and Drug Administration. The technology being studied could provide a first-of-kind therapy for difficult-to-wean patients on mechanical ventilation in an intensive care unit setting. Trial registration Clinicaltrials.gov, NCT05998018 , registered August 2023.

Background: Protein kinase A (PKA) enhances neurotransmission at the neuromuscular junction (NMJ), which is retrogradely regulated by nerve-induced muscle contraction to promote Acetylcholine (ACh) release through the phosphorylation of molecules involved in synaptic vesicle exocytosis (SNAP-25 and Synapsin-1). However, the molecular mechanism of the retrograde regulation of PKA subunits and its targets by BDNF/TrkB pathway and muscarinic signalling has not been demonstrated until now. At the NMJ, retrograde control is mainly associated with BDNF/TrkB signalling as muscle contraction enhances BDNF levels and controls specific kinases involved in the neurotransmission. Neurotransmission at the NMJ is also highly modulated by muscarinic receptors M1 and M2 (mAChRs), which are related to PKA and TrkB signallings. Here, we investigated the hypothesis that TrkB, in cooperation with mAChRs, regulates the activity-dependent dynamics of PKA subunits to phosphorylate SNAP-25 and Synapsin-1. Methods: To explore this, we stimulated the rat phrenic nerve at 1Hz (30 minutes), with or without subsequent contraction (abolished by µ-conotoxin GIIIB). Pharmacological treatments were conducted with the anti-TrkB antibody clone 47/TrkB for TrkB inhibition and exogenous h-BDNF; muscarinic inhibition with Pirenzepine-dihydrochloride and Methoctramine-tetrahydrochloride for M1 and M2 mAChRs, respectively. Diaphragm protein levels and phosphorylation' changes were detected by Western blotting. Location of the target proteins was demonstrated using immunohistochemistry. Results: While TrkB does not directly impact the levels of PKA catalytic subunits Cα and Cβ, it regulates PKA regulatory subunits RIα and RIIβ, facilitating the phosphorylation of critical exocytotic targets such as SNAP-25 and Synapsin-1. Furthermore, the muscarinic receptors pathway maintains a delicate balance in this regulatory process. These findings explain the dynamic interplay of PKA subunits influenced by BDNF/TrkB signalling, M1 and M2 mAChRs pathways, that are differently regulated by pre- and postsynaptic activity, demonstrating the specific roles of the BDNF/TrkB and muscarinic receptors pathway in retrograde regulation. Conclusion: This complex molecular interplay has the relevance of interrelating two fundamental pathways in PKA-synaptic modulation: one retrograde (neurotrophic) and the other autocrine (muscarinic). This deepens the fundamental understanding of neuromuscular physiology of neurotransmission that gives plasticity to synapses and holds the potential for identifying therapeutic strategies in conditions characterized by impaired neuromuscular communication. [ABSTRACT FROM AUTHOR]

Mutual interactions between the diaphragm and lung transplantation (LTx) are known to exist. Before LTx, many factors can exert notable impact on the diaphragmatic function, such as the underlying respiratory disease, the comorbidities, and the chronic treatments of the patient. In the post-LTx setting, even the surgical procedure itself can cause a stressful trauma to the diaphragm, potentially leading to morphological and functional alterations. Conversely, the diaphragm can significantly influence various aspects of the LTx process, ranging from graft-to-chest cavity size matching to the long-term postoperative respiratory performance of the recipient. Despite this, there are still no standard criteria for evaluating, defining, and managing diaphragmatic dysfunction in the context of LTx to date. This deficiency hampers the accurate assessment of those factors which affect the diaphragm and its reciprocal influence on LTx outcomes. The objective of this narrative review is to delve into the complex role the diaphragm plays in the different stages of LTx and into the modifications of this muscle following surgery. [ABSTRACT FROM AUTHOR]

Phrenic nerve stimulation is currently being investigated for the prevention of diaphragm atrophy in patients with mechanically supported breathing. Patients receiving breathing support from mechanical ventilation are at risk of mismatches between respiratory demand and ventilator support. Our objectives were to determine if a novel phrenic nerve stimulation device provided stimulation during inspiration as intended and did not exacerbate any potential discordances. A benchtop electromechanical simulation model was developed to validate phrenic nerve stimulation with simulated breathing. The phrenic nerve stimulation device was evaluated with a mechanical ventilator attached to a breathing simulator. The trigger ratio and time lag between phrenic nerve stimulation and mechanical ventilation was measured for multiple disease and ventilator parameters. For the 1:1 breath trigger ratio test, 99.79% of intended stimulation breaths received stimulation at the correct time. For the 1:4 breath trigger ratio test, 99.72% of intended stimulation breaths received stimulation at the correct time. For trigger lag times for the inspiratory and expiratory phases, the mean inspiratory lag was 36.10 ± 10.50 ms and 16.61 ± 3.61 ms, respectively. The following discordance scenarios were evaluated in conjunction with simulated phrenic nerve stimulation: asynchrony-false trigger, dyssynchronyearly trigger, dyssynchrony-late trigger, dyssynchrony-early cycling, dyssynchrony-late cycling. Testing demonstrated none of these discordances were exacerbated by the simulated phrenic nerve stimulation. The novel phrenic nerve stimulation device delivered electrical stimulation therapy as intended and did not exacerbate any simulated discordances. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion The QDOT MICROTM Ablation Catheter is a next‐generation ablation catheter that allows for high‐power ablation up to 90 watts.We aimed to assess AE associated with the QDOT MICROTM catheter using the MAUDE database. A MAUDE database search was conducted on May 25, 2024, to capture all AEs (since FDA approval) associated with this ablation catheter.A total of 302 AEs from November 23, 2022, to April 30, 2024, were reported including 148 (49%) catheter‐related issues and 154 (51%) clinical complications. Among the catheter‐related issues, physical catheter damage (74.3%, n = 110) was most common, followed by communication or display issue (10.8%, n = 16), irrigation issue (9.5%, n = 14), signal issue or artifact (3.4%, n = 5), and inaccurate temperature measurement (2.0%, n = 3). Regarding clinical complications, the most common AE was pericardial effusion (43.5%, n = 67), followed by char formation (11.7%, n = 18), catheter thrombosis (7.1%, n = 11), stroke (7.1%, n = 11), pericarditis (7.1%, n = 11), esophageal complications (6.5%, n = 10), phrenic nerve palsy (3.9%, n = 6), cardiac arrest (3.9%, n = 6), significant AV block (3.9%, n = 6), pulmonary vein stenosis (3.2%, n = 5), coronary artery spasm (1.3%, n = 2), and pulmonary embolism (0.6%, n = 1). There were 11 deaths (five related to esophageal complications, five related to cardiac arrest, and one related to pericardial effusion with cardiac tamponade).As high‐power ablation strategy with novel ablation catheters is becoming more widely utilized, operators must be aware of potential catheter‐related issues and clinical complications that may arise. More data are needed to further evaluate risks of these complications to improve the catheter's safety and efficacy. [ABSTRACT FROM AUTHOR]

Respiratory dysfunction is an important hallmark of amyotrophic lateral sclerosis (ALS). Elevation of creatine kinase (CK) has been reported in 23–75% of ALS patients, but the underlying mechanisms remain unknown. This work aims to enlighten the role of CK as a prognostic factor of respiratory dysfunction in ALS. A retrospective analysis of demographic and clinical variables, CK, functional decline per month (ΔFS), forced vital capacity (%FVC), and mean amplitude of the phrenic nerve compound motor action potential (pCMAP) in 319 ALS patients was conducted. These measurements were evaluated at study entry, and patients were followed from the moment of first observation until death or last follow-up visit. High CK values were defined as above the 90th percentile (CK ≥ P90) adjusted to sex. We analyzed survival and time to non-invasive ventilation (NIV) as proxies for respiratory impairment. Linear regression analysis revealed that high CK was associated with male sex (p < 0.001), spinal onset (p = 0.018), and FVC ≥ 80% (p = 0.038). CK was 23.4% higher in spinal-onset ALS patients (p < 0.001). High CK levels were not linked with an increased risk of death (p = 0.334) in Cox multivariate regression analysis. CK ≥ P90 (HR = 1.001, p = 0.038), shorter disease duration (HR = 0.937, p < 0.001), lower pCMAP (HR = 0.082, p < 0.001), and higher ΔFS (HR = 1.968, p < 0.001) were risk factors for respiratory failure. The association between high CK levels and poorer respiratory outcomes could derive from cellular metabolic stress or a specific phenotype associated with faster respiratory decline. Our study suggests that CK measurement at diagnosis should be more extensively investigated as a possible marker of poor respiratory outcome in future studies, including a larger population of patients. [ABSTRACT FROM AUTHOR]

Neck pain is a leading cause of disability worldwide. Visceral referred pain is a common form of disease-induced pain, with visceral nociception being referred to somatic tissues. The aim of this case report was to evaluate the immediate and long term effects of a novel osteopathic visceral technique (OVT) on pain and cervical range of motion (CROM) in a patient with nonspecific neck pain (NS-NP). A case of a 47-year-old female suffering with NS-NP for four months. The patient had sought physiotherapy treatment several times, and occasionally used anti-inflammatory medication to relieve symptoms. The patient presented muscle cervical tenderness and hyperalgesia over the spinous processes of C3–C4 spinal segments with limited CROM. A novel osteopathic visceral manipulation (OVM) technique was applied in the epigastric region targeting the pancreas. Immediately after the treatment, the patient reported reduction in pain evaluated with the numerical evaluation scale (NRS), and a clinically significant increase in pressure pain threshold (PPT) in C3 spinous process. Improvement in CROM was also observed. The post-treatment improvements have been maintained at 1-month of follow-up assessment. A single OVT was effective in reducing cervical pain and increasing CROM in a patient with NS-NP caused by a viscerosomatic reflex. The results of this case study provides preliminary evidence that OVM can produce hypoalgesia in somatic tissues with segmentally related innervation. This finding encourages future research to gain a better understanding of the mechanisms of regional inhibitory interdependence involving the viscerosomatic reflexes of OVM. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Point‐of‐care ultrasound of the diaphragm is highly sensitive and specific in the detection of neuromuscular diaphragmatic dysfunction. In some patients with neuromuscular diaphragmatic dysfunction, paradoxical thinning of the diaphragm during inspiration is observed on ultrasound; however, its frequency, electrodiagnostic associations, and prognostic significance remain uncertain.Medical records of patients presenting to two electrodiagnostic laboratories (Mayo Clinic, Rochester, Minnesota and University of Alberta, Edmonton, Alberta) from January 1, 2022 to December 31, 2022, for evaluation of suspected neuromuscular respiratory failure, were reviewed.214 patients were referred and 19 patients excluded due to incomplete information. Of 195 patients (384 hemidiaphragms), 104 had phrenic neuropathy, 12 had myopathy, and 79 had no evidence of neuromuscular disease affecting the diaphragm. Paradoxical thinning occurred in 31 (27%) patients with neuromuscular diaphragmatic dysfunction and was unilateral in 30, the majority (83%) having normal contralateral ultrasound. Phrenic nerve conduction studies and diaphragm electromyography results did not distinguish patients with paradoxical thinning versus without. Most patients (71%) with paradoxical thinning required non‐invasive ventilation (NIV), including 16 with unilateral paradoxical thinning. Paradoxical thinning and BMI ≥30 kg/m2 were risk factors for requiring NIV in multivariable logistic regression analysis, with odds ratios of 2.887 (95% CI:1.166, 7.151) and 2.561 (95% CI: 1.186, 5.532), respectively.Paradoxical thinning of the diaphragm occurs in patients with prominent neuromuscular diaphragmatic dysfunction, most commonly from phrenic neuropathy, and is a significant risk factor for requiring NIV. Unilateral paradoxical thinning is sufficient for needing NIV. BMI ≥30 kg/m2 additionally increases risk of requiring NIV in patients with neuromuscular diaphragmatic dysfunction. [ABSTRACT FROM AUTHOR]

The phrenic nerve innervates the respiratory diaphragm, the primary muscle active during ventilation. The canonical path of the phrenic nerve originates from the cervical spine at C3–C5 spinal nerves and travels inferiorly through the neck and thoracic cavity to reach the diaphragm. During a cadaver dissection, a variation of the phrenic nerve was discovered in a 93-year-old male specimen. A traditional origin of the phrenic nerve was noted; however, the nerve branched into medial and lateral components at the level of the superior trunk of the brachial plexus. The branches reconnected at the apex of the aortic arch and continued inferiorly to innervate the ipsilateral diaphragm. This case study describes a rare type of branching of the phrenic nerve and explores its potential impact on clinical procedures. [ABSTRACT FROM AUTHOR]

Prolonged inhibition of respiratory neural activity elicits a long-lasting increase in phrenic nerve amplitude once respiratory neural activity is restored. Such long-lasting facilitation represents a form of respiratory motor plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although facilitation also occurs in inspiratory intercostal nerve activity after diminished respiratory neural activity (iIMF), it is of shorter duration. Atypical PKC activity in the cervical spinal cord is necessary for iPMF and iIMF, but the site and specific isoform of the relevant atypical PKC are unknown. Here, we used RNA interference to test the hypothesis that the zeta atypical PKC isoform (PKCζ) within phrenic motor neurons is necessary for iPMF but PKCζ within intercostal motor neurons is unnecessary for transient iIMF. Intrapleural injections of siRNAs targeting PKCζ (siPKCζ) to knock down PKCζ mRNA within phrenic and intercostal motor neurons were made in rats. Control rats received a nontargeting siRNA (NTsi) or an active siRNA pool targeting a novel PKC isoform, PKCθ (siPKCθ), which is required for other forms of respiratory motor plasticity. Phrenic nerve burst amplitude and external intercostal (T2) electromyographic (EMG) activity were measured in anesthetized and mechanically ventilated rats exposed to 30 min of respiratory neural inactivity (i.e., neural apnea) created by modest hypocapnia (20 min) or a similar recording duration without neural apnea (time control). Phrenic burst amplitude was increased in rats treated with NTsi (68 ± 10% baseline) and siPKCθ (57 ± 8% baseline) 60 min after neural apnea vs. time control rats (−3 ± 3% baseline), demonstrating iPMF. In contrast, intrapleural siPKCζ virtually abolished iPMF (5 ± 4% baseline). iIMF was transient in all groups exposed to neural apnea; however, intrapleural siPKCζ attenuated iIMF 5 min after neural apnea (50 ± 21% baseline) vs. NTsi (97 ± 22% baseline) and siPKCθ (103 ± 20% baseline). Neural inactivity elevated the phrenic, but not intercostal, responses to hypercapnia, an effect that was blocked by siPKCζ. We conclude that PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient iIMF. NEW & NOTEWORTHY: We report important new findings concerning the mechanisms regulating a form of spinal neuroplasticity elicited by prolonged inhibition of respiratory neural activity, inactivity-induced phrenic motor facilitation (iPMF). We demonstrate that the atypical PKC isoform PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient inspiratory intercostal facilitation. Our findings are novel and advance our understanding of mechanisms contributing to phrenic motor plasticity. [ABSTRACT FROM AUTHOR]

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation—a cornerstone of AF treatment—rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Forced inspiration during mechanical ventilation risks self‐inflicted lung injury. However, controlling it with sedation or paralysis may cause polyneuropathy and myopathy. We tested bilateral phrenic nerve paralysis with local anesthetic in a patient, showing reduced inspiratory force. This offers an alternative to drug‐induced muscle paralysis. Mechanical ventilation, although a life‐saving measure, can also pose a risk of causing lung injury known as "ventilator‐induced lung injury" or VILI. Patients undergoing mechanical ventilation sometimes exhibit heightened inspiratory efforts, wherein the negative pressure generated by the respiratory muscles adds to the positive pressure generated by the ventilator. This combination of high pressures can lead to a syndrome similar to VILI, referred to as "patient self‐inflicted lung injury" or P‐SILI. Prevention of P‐SILI requires the administration of deep sedation and muscle paralysis to the patients, but both these measures can have undesired effects on their health. In this case report, we demonstrate the effect of a bilateral phrenic nerve block aiming to reduce excessive inspiratory respiratory efforts in a patient suffering from COVID‐19 pneumonitis. [ABSTRACT FROM AUTHOR]

Purpose: The available data on the treatment strategy of pulsed field ablation (PFA) for patients with atrial fibrillation (AF) is limited. This study aims to provide a comparative analysis of the efficacy, safety, and procedural efficiency between PFA and cryoballoon ablation (CBA) for AF. Methods: We conducted a comprehensive search of the EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov databases to identify trials comparing PFA with CBA for AF from their inception until December 2023. The odds ratio (OR) and mean difference (MD), along with a 95% confidence interval (CI), were utilized as measures of treatment effect. Results: The analysis included 15 eligible trials with a total enrollment of 1880 patients. No significant differences were found in recurrent atrial arrhythmia (OR 0.83, 95% CI 0.64, 1.07) or periprocedural complications (OR 0.78, 95% CI 0.46, 1.30) between the two ablation techniques examined in this study. However, the PFA technique demonstrated a significantly shorter procedure time (MD ‐7.17, 95% CI ‐13.60, ‐0.73), but a longer fluoroscopy time (MD 2.53, 95% CI 0.87, 4.19). Similarly, PFA was found to be significantly associated with a decreased incidence of phrenic nerve palsy (OR 0.20, 95% CI 0.07, 0.59), but an increased incidence of cardiac tamponade (OR 4.07, 95% CI 1.15, 14.39). Moreover, there was a significantly higher release of troponin with PFA compared to CBA (MD 470.28, 95% CI 18.89, 921.67), while the increase in S100 protein and heart rate was significantly lower with PFA than with CBA (MD ‐64.41, 95% CI ‐105.46, ‐17.36), (MD ‐8.76, 95% CI ‐15.12, ‐2.40). Conclusion: The utilization of PFA provides a safer, time‐saving, and tissue‐specific procedure compared to CBA, while maintaining comparable success rates. This has the potential to enhance procedural efficiency and optimize resource utilization in clinical practice. These findings underscore the feasibility and promise of PFA as an alternative technique for PVI in patients with AF. [ABSTRACT FROM AUTHOR]

The description of anastomosis of the phrenic nerve has been little studied and even controversial at present. Classical authors such as Testut have briefly described this anastomosis. 13 anatomical preparations formalized at 10% were used, identifying 26 phrenic nerves from their location in the neck and being dissected to their terminal distribution in the diaphragm muscle. A distribution of the phrenic nerve was observed in 3 terminal branches, anterior, lateral and posterior. These branches penetrate the muscle and run initially between the muscle fibers and then on the underside of the muscle and the fascia. In monitoring the anterior branch of the phrenic nerve, it was found that it divided into several branches. 2 constantly stood out, one anterior towards the sternum and another medial that borders the pericardium, which was of interest to us. In 38% of the cases, anastomoses were found between the right and left phrenic nerves, located mainly anterior to the pericardium, which would indicate a justification for reinnervation due to damage to the phrenic. This anatomical description is of utmost importance in cases of bilateral injury to the phrenic nerve and explains the recovery of the denervated diaphragm. [ABSTRACT FROM AUTHOR]

The number of motor neurons (MNs) declines precipitously during the final trimester before birth. Thereafter, the number of MNs remains relatively stable, with their connections to skeletal muscle dependent on neurotrophins, including brain-derived neurotrophic factor (BDNF) signaling through its high-affinity full-length tropomyosin-related kinase receptor subtype B (TrkB.FL) receptor. As a genetic knockout of BDNF leads to extensive MN loss and postnatal death within 1–2 days after birth, we tested the hypothesis that postnatal inhibition of BDNF/TrkB.FL signaling is important for postnatal phrenic MN (PhMN) survival. In the present study, we used a 1NMPP1-sensitive TrkBF616A mutant mouse to evaluate the effects of inhibition of TrkB kinase activity on phrenic MN (PhMN) numbers and diaphragm muscle (DIAm) fiber cross-sectional area (CSA). Pups were exposed to 1NMPP1 or vehicle (DMSO) from birth to 21 days old (weaning) via the mother's ingestion in the drinking water. Following weaning, the right phrenic nerve was exposed in the neck and the proximal end dipped in a rhodamine solution to retrogradely label PhMNs. After 24 h, the cervical spinal cord and DIAm were excised. Labeled PhMNs were imaged using confocal microscopy, whereas DIAm strips were frozen at ∼1.5× resting length, cryosectioned, and stained with hematoxylin and eosin to assess CSA. We observed an ∼34% reduction in PhMN numbers and increased primary dendrite numbers in 1NMPP1-treated TrkBF616A mice. The distribution of PhMN size (somal surface area) DIAm fiber cross-sectional areas did not differ. We conclude that survival of PhMNs during early postnatal development is sensitive to BDNF/TrkB.FL signaling. NEW & NOTEWORTHY: During early postnatal development, BDNF/TrkB signaling promotes PhMN survival. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact PhMN size. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact the number or CSA of DIAm fibers. [ABSTRACT FROM AUTHOR]

Aims Pulmonary vein isolation (PVI) represents the gold standard in the treatment of atrial fibrillation (AF) and the use of single-shot techniques, such as cryoballoon ablation (CBA) and pulsed field ablation (PFA) using a pentaspline catheter, has gained prominence. Recent studies hypothesize that PFA might be superior to CBA, although procedural efficacy and safety data are inconsistent. A meta-analysis was conducted to compare both energy sources for the treatment of AF. Methods and results A structured systematic database search and meta-analysis were performed on studies investigating outcomes, periprocedural complications, and/or procedural parameters of AF patients treated by either CBA or PFA. Eleven studies reporting data from 3805 patients were included. Pulmonary vein isolation by PFA was associated with a significantly lower recurrence of atrial fibrillation/atrial tachycardia [odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.54–0.98, I2 = 20%] and fewer periprocedural complications (OR = 0.62, 95% CI = 0.40–0.96, I2 = 6%) compared to CBA. The lower complication rate following PFA was mainly driven by fewer phrenic nerve injuries (OR = 0.19, 95% CI = 0.08–0.43, I2 = 0%). However, there were more cases of cardiac tamponades after PFA (OR = 2.56, 95% CI = 1.01–6.49, I2 = 0%). Additionally, using PFA for PVI was associated with shorter total procedure times [mean difference (MD) = −9.68, 95% CI = −14.92 to −4.43 min, I2 = 92%] and lower radiation exposure (MD = −148.07, 95% CI = −276.50 to −19.64 µGy·mI2 = 7%). Conclusion Our results suggest that PFA for PVI, compared to CBA, enables shorter procedure times with lower arrhythmia recurrence and a reduced risk of periprocedural complications. Randomized controlled trials need to confirm our findings. [ABSTRACT FROM AUTHOR]

Stimulated contraction of the diaphragm by non-invasive electrical stimulation of the phrenic nerve is demonstrated. A specialized device including a programmable current source and an electrode system has been developed to generate the stimulating signal. We report here a study on the effectiveness of stimulation on the contractile activity of the diaphragm by assessment of transdiaphragmatic pressure. [ABSTRACT FROM AUTHOR]

The article focuses on the establishment of a new subspecialty in pulmonary medicine dedicated to addressing chronic respiratory failure. It highlights the need for standardized criteria, education, and training programs to meet the growing demand for expertise in this area. It discusses the challenges and gaps in current clinical practice and proposes interdisciplinary collaboration and policy changes to improve patient care.

Background Left ventricular (LV) summit arrhythmias account for up to 14% of LV arrhythmias. The ablation of LV summit arrhythmias is challenging, as testified by the fact that radiofrequency (RF) catheter ablation failure is frequent. Retrograde coronary venous ethanol infusion has been proposed as an alternative approach for the ablation of LV summit arrhythmias. Case summary A 47-year-old man with Lamin A/C cardiomyopathy was referred for the ablation of a pleiomorphic ventricular tachycardia (VT) storm, with dominant morphology compatible with LV summit origin. He first received a combined endo- and epicardial RF ablation with the elimination of three clinically relevant VTs. However, the dominant VT could not be ablated due to the proximity of the coronary vasculature and phrenic nerve and remained inducible. Accordingly, an urgent rescue redo procedure consisting of retrograde coronary venous ethanol ablation was performed. Based on the best pace-match and precocity, the first septal, retro-pulmonary branch and the first diagonal branch were infused with ethanol with immediate cessation of the tachycardia and non-inducibility. Anti-arrhythmic drugs were withdrawn, while guideline-directed medical therapy for heart failure was continued. No complications occurred. After 3 months, the patient remained free from any arrhythmias. Discussion Ablation of LV summit arrhythmias is challenging, especially in the context of an electrical storm or in patients with structural heart disease. In such a situation, rescue ablation with retrograde coronary venous ethanol infusion represents an attractive alternative ablation modality. [ABSTRACT FROM AUTHOR]

The article discusses a rare case of diaphragmatic spasms caused by a glomangioma. The patient developed scalp swelling seven months after a hair transplant, which was attributed to an infection from the hair transplantation procedure. The article recommends that patients with allogenic cranioplasty flaps, like the one in this case, should be warned about the possibility of infection spreading to the underlying implant before undergoing hair transplantation. The article also mentions the use of prophylactic antibiotics and staphylococcal decolonization regimen as preventive measures. Additionally, the article briefly mentions other studies on glomangiomas in different parts of the body. Another article in the same journal discusses a novel and simple method called no-laboratory epidermal cell paste (NLEP) for the treatment of stable vitiligo. The NLEP technique does not require specialized laboratory equipment, is less time-consuming, and more cost-effective compared to other cellular graft methods. The article provides details of three patients who underwent the NLEP procedure and achieved repigmentation with minimal adverse effects. [Extracted from the article]

This article provides an overview of phrenic neuropathy, a condition that affects the phrenic nerve responsible for controlling the diaphragm. The study examines a diverse group of patients with phrenic neuropathy and explores different causes and recovery patterns. The findings suggest that recovery can take more than a year and vary depending on the underlying cause. The article also mentions three related articles that discuss the use of ultrasonography in diagnosing neuralgic amyotrophy and present a case series and literature review on idiopathic phrenic neuropathies. These articles may be useful for library patrons researching these specific medical conditions. [Extracted from the article]

This document discusses the management of intractable hiccups using phrenic nerve cryoablation. Intractable hiccups can have significant effects on patients, particularly those with cancer or who have undergone surgery. Traditional methods of managing intractable hiccups include physical maneuvers and medications, but when these fail, other interventions such as phrenic nerve block or radioablation can be used. Cryotherapy has emerged as a potential treatment for intractable hiccups. The document presents a case study of an 87-year-old male with chronic hiccups who underwent phrenic nerve cryoneurolysis and experienced relief from his symptoms. The effectiveness of cryoneurolysis in treating intractable hiccups is discussed, along with its potential advantages over radiofrequency ablation. The document concludes by suggesting that cryoneurolysis may be a viable treatment option for intractable hiccups and similar conditions. [Extracted from the article]

Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here, we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation in mice during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.

Background: A frequent complication of Fontan operations is unilateral diaphragmatic paresis, which leads to hemodynamic deterioration of the Fontan circulation. A potential new therapeutic option is the unilateral diaphragmatic pacemaker. In this study, we investigated the most effective stimulation location for a potential fully implantable system in a porcine model. Methods: Five pigs (20.8 ± 0.95 kg) underwent implantation of a customized cuff electrode placed around the right phrenic nerve. A bipolar myocardial pacing electrode was sutured adjacent to the motor point and peripherally at the costophrenic angle (peripheral diaphragmatic muscle). The electrodes were stimulated 30 times per minute with a pulse duration of 200 µs and a stimulation time of 300 ms. Current intensity was the only variable changed during the experiment. Results: Effective stimulation occurred at 0.26 ± 0.024 mA at the phrenic nerve and 7 ± 1.22 mA at the motor point, a significant difference in amperage (p = 0.005). Even with a maximum stimulation of 10 mA at the peripheral diaphragm muscle, however, no effective stimulation was observed. Conclusion: The phrenic nerve seems to be the best location for direct stimulation by a unilateral thoracic diaphragm pacemaker in terms of the required amperage level in a porcine model. [ABSTRACT FROM AUTHOR]

Background: Diaphragmatic paralysis due to phrenic nerve injury is a rare but potentially serious complication following congenital cardiac surgery, with reported incidences ranging from 0.28 to 5.6%. Early plication has been recommended for children diagnosed with diaphragmatic paralysis, especially those requiring prolonged respiratory support after cardiopulmonary bypass. It is important to note that late plication may jeopardize the results of successful surgical plication due to diaphragm atrophy. Results: This retrospective study was performed between May 2020 and June 2023. Patients who could not be weaned from the ventilator and underwent diaphragmatic plication in symptomatic patients after phrenic nerve injury were included in the study. During the study period, 22 (3.5%) of 624 pediatric patients operated for congenital heart disease required diaphragm plication. The mean age of the patients ranged from 1 month to 13 years with a mean of 23.88 ± 37.99 months. Fourteen (63.6%) of the patients were female, and 8 (36.4%) were male. Two of the patients (9%) were exited due to ventilator-associated pneumonia and sepsis. Conclusions: In conclusion, diaphragmatic paralysis after congenital heart surgery is a rare but important complication that can lead to serious respiratory and cardiac problems. Diaphragmatic plication has been shown to be an effective intervention for pediatric patients with the potential to improve pulmonary function, reduce dyspnea, and minimize complications associated with diaphragmatic paralysis. Careful consideration of patient selection, timing, and potential complications is crucial in optimizing the outcomes of this surgical intervention. [ABSTRACT FROM AUTHOR]

Background and Aims: The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in shoulder surgery. The current study was conducted to evaluate the same. Material and Methods: Patients scheduled for shoulder surgery under general anesthesia (GA) received ultrasound-guided UT-ESPB. The outcomes measured were diaphragmatic movements, block characteristics, and quality of recovery at 24 h. Results: A total of 43 patients were recruited. The incidence of phrenic nerve palsy was 0%. The sensory level achieved by the maximum number of patients at the end of 30 min was C7-T5 level, and none had a motor block. Forty-two percent of patients did not require rescue analgesia till 24 h postoperative. In the rest of the patients, the mean (SD) duration of analgesia was 724.2 ± 486.80 min, and the mean postoperative requirement of fentanyl was 98.80 ± 47.02 µg. The median pain score (NRS) during rest and movement is 2 to 3 and 3 to 4, respectively. The median quality of recovery score at the end of 24 h after the block was 14 (15-14). Conclusion: The upper thoracic ESPB resulted in a sensory loss from C7-T5 dermatomes without any weakness of the diaphragm and upper limb. However, the block was moderately effective in terms of the total duration of analgesia, postoperative pain scores, analgesic requirement, and quality of recovery in patients undergoing proximal shoulder surgeries under GA. Further studies are required to establish its role due to its poor correlation with sensory spread. [ABSTRACT FROM AUTHOR]

The post–COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%–10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints. We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n = 30) and compared them with subjects fully recovered from acute COVID-19 (n = 14) and with individuals never infected (n = 16). We evaluated the structure and function of the vagus nerve and respiratory muscles. Participants were mostly women (24 of 30, 80%), and the median age was 44 years (interquartile range [IQR] 35–51 years). Their most prevalent symptoms were cognitive dysfunction 25 of 30 (83%), dyspnea 24 of 30 (80%), and tachycardia 24 of 30 (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (cross-sectional area [CSA] [mean ± standard deviation]: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2; p 0.08), reduced esophageal-gastric-intestinal peristalsis (34% vs. 0% vs. 21%; p 0.02), gastroesophageal reflux (34% vs. 19% vs. 7%; p 0.13), and hiatal hernia (25% vs. 0% vs. 7%; p 0.05). Subjects with PCC showed flattening hemidiaphragms (47% vs. 6% vs. 14%; p 0.007), and reductions in maximum inspiratory pressure (62% vs. 6% vs. 17%; p ≤ 0.001), indicating respiratory muscle weakness. The latter findings suggest additional involvement of the phrenic nerve. Vagus and phrenic nerve dysfunction contribute to the complex and multifactorial pathophysiology of PCC. [ABSTRACT FROM AUTHOR]

Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia (AIH) is a valuable model for studying obstructive sleep apnea (OSA) pathophysiology, and stimulation of breathing during AIH is known to elicit long-term changes in respiratory and sympathetic functions. The aim of this study was to record the renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA) during the AIH protocol in rats exposed to monoanesthesia with sevoflurane or isoflurane. Adult male Sprague-Dawley rats (n = 24; weight: 280–360 g) were selected and randomly divided into three groups: two experimental groups (sevoflurane group, n = 6; isoflurane group, n = 6) and a control group (urethane group, n = 12). The AIH protocol was identical in all studied groups and consisted in delivering five 3 min-long hypoxic episodes (fraction of inspired oxygen, FiO2 = 0.09), separated by 3 min recovery intervals at FiO2 = 0.5. Volatile anesthetics, isoflurane and sevoflurane, blunted the RSNA response to AIH in comparison to urethane anesthesia. Additionally, the PNA response to acute intermittent hypoxia was preserved, indicating that the respiratory system might be more robust than the sympathetic system response during exposure to acute intermittent hypoxia. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation often necessitates catheter ablation when antiarrhythmic drug therapy fails. Single-shot technologies using thermal energy, such as cryoballoon ablation, are commonly used, but pulsed field ablation (PFA), an innovative non-thermal ablation technique, is a potential alternative. This retrospective observational study aimed to compare the safety and efficacy of cryoballoon ablation and PFA in patients undergoing their first pulmonary vein isolation (PVI) procedure for atrial fibrillation treatment. Methods: We utilised real-world data from patients who underwent PVI using cryoballoon ablation or PFA. The primary outcome encompassed procedural complications, including phrenic nerve palsy, cardiac tamponade, thromboembolic complications, bleeding complications and mortality. Secondary outcomes were procedural characteristics including procedure duration, length of hospital admission, and re-do ablation rates within 6 months. Results: A total of 1714 procedures were analysed: 1241 in the cryoballoon group and 473 in the PFA group. Gender distribution (p = 0.03) and estimated glomerular filtration rate (p = 0.01) differed significantly. With regard to the primary outcome, the cryoballoon group demonstrated a higher incidence of phrenic nerve palsy compared with the PFA group (15 vs 0; p = 0.02). The procedure duration was shorter in the PFA group, even after adjusting for baseline characteristics (95.0 vs 74.0 min; p < 0.001). After adjustment for baseline characteristics, admission duration differed between the groups as well (p = 0.04). Conclusion: The study results supported the safety and efficacy of PFA over cryoballoon ablation for PVI, highlighting advantages such as shorter procedure duration and absence of phrenic nerve palsy. [ABSTRACT FROM AUTHOR]

Background: Ventilator‐induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non‐invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter‐individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time‐consuming calibration processes to achieve reliable stimulation. Methods: We applied non‐invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed‐loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. Results: Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38–59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra‐subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. Conclusion: We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed‐loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator‐induced diaphragm dysfunction. [ABSTRACT FROM AUTHOR]

Background Endovascular thoracic aortic treatment frequently requires extending the proximal landing zone up into the aortic arch with consecutive covering of the left subclavian artery orifice. Our aim was to report on our outcome of left subclavian artery revascularization using carotid-subclavian bypass via lateral access to the subclavian artery. Methods Patients' charts in our aortic center were screened for all those who had undergone carotid-subclavian bypass during endovascular thoracic aortic repair procedures. We analyzed perioperative complications such as cervical plexus nerve or phrenic nerve injury, bleeding, and primary and follow-up graft patency. Results Between 2001 and 2020, 118 patients underwent carotid-subclavian bypass implantation. Postoperative complications included left-sided stroke in 3% and axillary, phrenic, and recurrent laryngeal nerve palsy in 3, 2, and 3%, respectively. Carotid-subclavian bypass–related death rate was 0%. Bypass patency was 92 ± 7% at 5 years. We documented nine (8%) bypass late occlusions with one left upper extremity ischemia and one late stroke due to an embolized thrombus formed at the bypass anastomosis. All others were asymptomatic. Conclusion Carotid-subclavian bypass surgery is associated with very low risk of death, stroke, or any nerve palsy. Lateral access to the left subclavian artery reduces the risk of phrenic nerve injury. [ABSTRACT FROM AUTHOR]

Results obtained from studies of the development of a device for non-invasive electrical stimulation of the phrenic nerve are presented. A block diagram of the device and schematics of key functional blocks are presented and the design of the device and the original software for its operation are described. [ABSTRACT FROM AUTHOR]

Background: Sepsis has a high mortality rate due to multiple organ failure. However, the influence of peripheral inflammation on brainstem autonomic and respiratory circuits in sepsis is poorly understood. Our working hypothesis is that peripheral inflammation affects central autonomic circuits and consequently contributes to multiorgan failure in sepsis. Methods: In an Escherichia coli (E. coli)–fibrin clot model of peritonitis, we first recorded ventilatory patterns using plethysmography before and 24 h after fibrin clot implantation. To assess whether peritonitis was associated with brainstem neuro-inflammation, we measured cytokine and chemokine levels in Luminex assays. To determine the effect of E. coli peritonitis on brainstem function, we assessed sympatho-respiratory nerve activities at baseline and during brief (20 s) hypoxemic ischemia challenges using in situ-perfused brainstem preparations (PBPs) from sham or infected rats. PBPs lack peripheral organs and blood, but generate vascular tone and in vivo rhythmic activities in thoracic sympathetic (tSNA), phrenic and vagal nerves. Results: Respiratory frequency was greater (p < 0.001) at 24 h post-infection with E. coli than in the sham control. However, breath-by-breath variability and total protein in the BALF did not differ. IL-1β (p < 0.05), IL-6 (p < 0.05) and IL-17 (p < 0.04) concentrations were greater in the brainstem of infected rats. In the PBP, integrated tSNA (p < 0.05) and perfusion pressure were greater (p < 0.001), indicating a neural-mediated pathophysiological high sympathetic drive. Moreover, respiratory frequency was greater (p < 0.001) in PBPs from infected rats than from sham rats. Normalized phase durations of inspiration and expiration were greater (p < 0.009, p < 0.015, respectively), but the post-inspiratory phase (p < 0.007) and the breath-by-breath variability (p < 0.001) were less compared to sham PBPs. Hypoxemic ischemia triggered a biphasic response, respiratory augmentation followed by depression. PBPs from infected rats had weaker respiratory augmentation (p < 0.001) and depression (p < 0.001) than PBPs from sham rats. In contrast, tSNA in E. coli-treated PBPs was enhanced throughout the entire response to hypoxemic ischemia (p < 0.01), consistent with sympathetic hyperactivity. Conclusion: We show that peripheral sepsis caused brainstem inflammation and impaired sympatho-respiratory motor control in a single day after infection. We conclude that central sympathetic hyperactivity may impact vital organ systems in sepsis. [ABSTRACT FROM AUTHOR]

Background and purpose: In amyotrophic lateral sclerosis (ALS), phrenic nerve (PN) atrophy has been found, whereas there is controversy regarding vagus nerve (VN) atrophy. Here, we aimed to find out whether PN atrophy is related to respiratory function and 12‐month survival. Moreover, we investigated the relevance of VN and spinal accessory nerve (AN) atrophy in ALS. Methods: This prospective observational monocentric study included 80 adult participants (40 ALS patients, 40 age‐ and sex‐matched controls). The cross‐sectional area (CSA) of bilateral cervical VN, AN, and PN was measured on high‐resolution ultrasonography. Clinical assessments included the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS‐R), the Non‐Motor Symptoms Questionnaire, and handheld spirometry of forced vital capacity (FVC). One‐year survival was documented. Results: The CSA of each nerve, VN, AN, and PN, was smaller in ALS patients compared to controls. VN atrophy was unrelated to nonmotor symptom scores. PN CSA correlated with the respiratory subscore of the ALSFRS‐R (Spearman test, r = 0.59, p < 0.001), the supine FVC (r = 0.71, p < 0.001), and the relative change of sitting–supine FVC (r = −0.64, p = 0.001). Respiratory impairment was predicted by bilateral mean PN CSA (p = 0.046, optimum cutoff value of ≤0.37 mm2, sensitivity = 92%, specificity = 56%) and by the sum of PN and AN CSA (p = 0.036). The combination of ALSFRS‐R score with PN and AN CSA measures predicted 1‐year survival with similar accuracy as the combination of ALSFRS‐R score and FVC. Conclusions: Ultrasonography detects degeneration of cranial nerve motor fibers. PN and AN calibers are tightly related to respiratory function and 1‐year survival in ALS. [ABSTRACT FROM AUTHOR]

Repeated hypoxic episodes can produce a sustained (>60 min) increase in neural drive to the diaphragm. The requirement of repeated hypoxic episodes (vs. a single episode) to produce phrenic motor facilitation (pMF) can be removed by allosteric modulation of a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors using ampakines. We hypothesized that the ampakinehypoxia interaction resulting in pMF requires that ampakine dosing precedes the onset of hypoxia. Phrenic nerve recordings were made from urethane-anesthetized, mechanically ventilated, and vagotomized adult male Sprague-Dawley rats during isocapnic conditions. Ampakine CX717 (15 mg/kg iv) was given immediately before (n = 8), during (n = 8), or immediately after (n = 8) a 5-min hypoxic episode (arterial oxygen partial pressure 40-45 mmHg). Ampakine before hypoxia (Aprior) resulted in a sustained increase in inspiratory phrenic burst amplitude (i.e., pMF) reaching þ70 ± 21% above baseline (BL) after 60 min. This was considerably greater than corresponding values in the groups receiving ampakine during hypoxia (þ28 ± 47% above BL, P = 0.005 vs. Aprior) or after hypoxia (þ23 ± 40% above BL, P = 0.005 vs. Aprior). Phrenic inspiratory burst rate, heart rate, and systolic, diastolic, and mean arterial pressure (mmHg) were similar across the three treatment groups (all P > 0.3, treatment effect). We conclude that the presentation order of ampakine and hypoxia impacts the magnitude of pMF, with ampakine pretreatment evoking the strongest response. Ampakine pretreatment may have value in the context of hypoxia-based neurorehabilitation strategies. [ABSTRACT FROM AUTHOR]