Partial Relief Research Articles

BlephEx-treatment for blepharitis: a prospective randomized placebo-controlled trial

Abstract Background Blepharitis is a chronic inflammatory condition of the eyelids that affects a large proportion of patients in eye care settings. First-line treatments provide only partial relief for many patients. The BlephEx™ device provides automated eyelid debridement and aims to remove pathogenic biofilms from the eyelid margin to treat blepharitis long-term. However, evidence supporting the efficacy of BlephEx™ is limited. Methods In this double-masked randomized controlled trial, 42 patients with symptomatic blepharitis refractory to treatment were assigned to the BlephEx™ treatment or sham treatment group. Outcome measures including Ocular surface disease index (OSDI), tear break-up time (TBUT), Schirmer test, and Efron grading scale scores were assessed at baseline and after 4 weeks. A crossover design in which the treatment groups were swapped after 4 weeks was used as a recruitment tool. After receiving treatment, two patients (one per group) were lost to follow-up. Results The sham group exhibited a significant decrease in the Efron Grading Scale score. No significant differences were observed in the other outcomes between the two groups. The BlephEx™ group showed slightly greater decreases in the OSDI and Efron grading scale scores and an increase in the TBUT than did the sham group, but these differences were not statistically significant. Mild discomfort was the most common side effect and occurred equally in both groups. Conclusions No significant difference in outcomes was observed between patients who underwent BlephEx™ therapy and those who received sham treatment. BlephEx™ treatment cannot be recommended for treating blepharitis. Trial registration Retrospectively registered on February 16, 2024 in the DRKS (German Clinical Trials Register under https://drks.de/search/de/trial/DRKS00033492) under the trial registration number DRKS00033492.

Economical-epidemiological analysis of the coffee trees rust pandemic.

Coffee leaf rust is a prevalent botanical disease that causes a worldwide reduction in coffee supply and its quality, leading to immense economic losses. While several pandemic intervention policies (PIPs) for tackling this rust pandemic are commercially available, they seem to provide only partial epidemiological relief for farmers. In this work, we develop a high-resolution spatiotemporal economical-epidemiological model, extending the Susceptible-Infected-Removed model, that captures the rust pandemic's spread in coffee tree farms and its associated economic impact. Through extensive simulations for the case of Colombia, a country that consists mostly of small-size coffee farms and is the second-largest coffee producer in the world, our results show that it is economically impractical to sustain any profit without directly tackling the rust pandemic. Furthermore, even in the hypothetical case where farmers perfectly know their farm's epidemiological state and the weather in advance, any rust pandemic-related efforts can only amount to a limited profit of roughly 4% on investment. In the more realistic case, any rust pandemic-related efforts are expected to result in economic losses, indicating that major disturbances in the coffee market are anticipated.

Itching for Answers: A Comprehensive Review of Cholestatic Pruritus Treatments

Cholestasis is a clinical and laboratory syndrome indicating impaired bile production or excretion. One of the hallmark symptoms of cholestasis is pruritus. Itch can be severe and debilitating for patients, impacting their quality of life similarly to pain, and, in some cases, it can be refractory. Current therapies like anion exchange resins and rifampicin, offer partial relief but with side effects. Effective, well-tolerated treatments are urgently needed. This literature review examines existing options (bile acid sequestrants, antihistamines, opioid antagonists, sertraline, and rifampicin) and explores novel therapies (monoclonal antibodies, PPAR agonists, and bile-acid-based therapies). We analyze mechanisms, limitations, and adverse effects to aid clinicians and researchers. Novel approaches include monoclonal antibodies to inhibit bile recirculation and PPAR agonists targeting pruritus signaling. Despite the limited current options, ongoing research promises better treatments for cholestatic pruritus, addressing its distressing impact. In summary, cholestasis-associated pruritus poses a significant challenge with limited treatments. Advancements in understanding its pathophysiology offer hope for more effective therapies in the future.

Exploring the Neuropharmacological Terrain of Depression and Anxiety: Mechanisms, Therapies, and Future Avenues

Depression and anxiety are prevalent mental health illnesses that have significant worldwide consequences, impacting millions of individuals who experience chronic feelings of melancholy, excessive worry, and significant limitations in their everyday activities. Major Depressive Disorder (MDD) and several anxiety disorders, such as Generalized Anxiety Disorder (GAD), panic disorder, and social anxiety disorder, are defined by severe symptoms that make their treatment more difficult, especially when these illnesses happen at the same time. Gaining a comprehensive understanding of the neuropharmacological mechanisms that are responsible for these illnesses is of utmost importance in order to facilitate the development of treatments that are very effective. The existing therapy approaches, such as Selective Serotonin Reuptake Inhibitors (SSRIs) and newer antidepressants, provide partial relief but do not work for everyone. This suggests that further research is necessary to explore the underlying neurological causes of these illnesses. Recent developments in the field of neuropharmacology have provided insights into the significance of imbalances in neurotransmitters, specifically serotonin, norepinephrine, and dopamine, in the underlying mechanisms of mood disorders. Disruption of the Hypothalamic-Pituitary-Adrenal (HPA) axis and neuroinflammation are also major factors in the development of these illnesses. This review offers a thorough examination of these pathways, emphasizing the functions of neurotransmitter systems, neurostimulation treatments, and developing pharmaceutical medicines. This study investigates the possibility of new neuropharmacological targets, including NMDA receptor antagonists, AMPA receptor modulators, and neurosteroids, to enhance the effectiveness of treatment. In addition, it discusses non-pharmacological methods such as Cognitive Behavioral Therapy (CBT), physical activity, and mindfulness, highlighting their neuropharmacological foundations and advantages.This review is to provide an in-depth investigation of the current understanding and approaches to addressing depression and anxiety by including latest research findings. The text discusses crucial therapeutic approaches and presents potential areas of future study that could improve treatment results for these prevalent mental health illnesses.

Advances in Understanding and Managing Alzheimer's Disease: From Pathophysiology to Innovative Therapeutic Strategies.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by the presence of amyloid-β (Aβ) plaques and tau-containing neurofibrillary tangles, leading to cognitive and physical decline. Representing the majority of dementia cases, AD poses a significant burden on healthcare systems globally, with onset typically occurring after the age of 65. While most cases are sporadic, about 10% exhibit autosomal forms associated with specific gene mutations. Neurofibrillary tangles and Aβ plaques formed by misfolded tau proteins and Aβ peptides contribute to neuronal damage and cognitive impairment. Currently, approved drugs, such as acetylcholinesterase inhibitors and N-methyl D-aspartate receptor agonists, offer only partial symptomatic relief without altering disease progression. A promising development is using lecanemab, a humanized IgG1 monoclonal antibody, as an immune therapeutic approach. Lecanemab demonstrates selectivity for polymorphic Aβ variants and binds to large soluble Aβ aggregates, providing a potential avenue for targeted treatment. This shift in understanding the role of the adaptive immune response in AD pathogenesis opens new possibilities for therapeutic interventions aiming to address the disease's intricate mechanisms. This review aims to summarize recent advancements in understanding Alzheimer's disease pathophysiology and innovative therapeutic approaches, providing valuable insights for both researchers and clinicians.

The PATCH trial: 5% lidocaine-medicated plaster for trigeminal neuralgia-Results of a multicentric, enriched enrollment, randomized withdrawal, double-blind, vehicle-controlled, parallel-group study.

To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.

Spontaneous Intracranial Hypotension: Role of Computed Tomography-guided Cervical Epidural Blood Patch.

Lumbar epidural blood patch (EBP) is not successful in all cases of cerebrospinal fluid (CSF) leak, particularly in the cervicothoracic region. The present study is a retrospective analysis of a cohort of patients who had undergone computed tomography (CT)-guided cervical EBP for spontaneous intracranial hypotension (SIH) due to CSF leak in the cervical region. We retrospectively collected data from March 2009 to 2020. Our inclusion criteria were (1) clinical syndrome associated with CSF leak, (2) headache coming on shortly after assuming the erect position and relief achieved by lying down, (3) CT myelography evidence of CSF leak in the cervical region, and (4) patient not responding to conservative management for 7 days. Exclusion criteria were patients with bleeding diathesis and infection. There were six females and four males. Ages ranged from 32 to 57, with an average of 42 years. On presentation, all patients underwent contrast-enhanced magnetic resonance imaging (MRI) and CT myelography. Cervical EBP was done under CT scan guidance. Assessment of headache was done on a 10-point numerical rating scale (NRS) before and after the procedure. Results are categorized into complete relief, partial relief, and no relief categories. Nine out of 10 patients were completely recovered. One patient was partially recovered. The average NRS scale was 9.6 before treatment, which became 0.4 after EBP. No neurological or vascular complications were seen. Computed tomography-guided cervical EBP is an optimum and effective way of treating SIH due to a leak in the cervical region. It has a higher success rate than lumbar EBP. However, prospective randomized controlled trials of cervical vs lumbar EBP will further validate our observation.

Marked Improvement of Nightmare Disorder and Backaches Following Treatment with Amphetamine Salts

Rationale: A relative deficiency of dopamine in various tissues leading to increased tissue permeability allowing infiltration of irritants to cause inflammation with subsequent pain, or disrupt normal function of organs, may be the etiologic factor in a wide variety of medical conditions. Evidence to support this hypothesis has been shown by quick improvement of symptomatology after treatment with dopaminergic drugs especially dextroamphetamine sulfate, but also cabergoline, for both corporeal conditions and psychological ones. Objective: To determine not only if treatment with dextroamphetamine may ameliorate backaches (which has been previously reported) but also improve chronic nightmare syndrome which has never been previously reported. Findings: A total daily dosage of 18.8mg of dextroamphetamine sulfate was not only able to immediately completely relieve the backache, but while taking it he did not have one nightmare during three months of treatment. Previously he never had one week for 30 years without at least 1-3 nightmares. Conclusion: Sometimes one case report provides more valid conclusions of the efficacy of a given drug than a randomized controlled study. The standard medication used for chronic nightmares is prazosin which may not be very effective in ameliorating chronic nightmares. The dramatic complete improvement of chronic nightmare syndrome, though it was only one patient, is sufficient for a treating physician to try dextroamphetamine therapy for prazosin failures or for patients who only had partial relief from prazosin and/or side effects, to try amphetamine therapy. Certainly, it would make sense to try dextroamphetamine for chronic nightmares if the patient also has other manifestations of the increased cellular permeability disorder.

Near total head resection of pancreas in patients with chronic pancreatitis - Outcome of a novel surgical technique

BackgroundChronic pancreatitis (CP) is characterized by debilitating pain which affects patients' quality of life. Early surgical intervention has been shown to mitigate pain and prevent a decline in quality of life. The present study evaluated the impact of bile duct and duodenum preserving pancreatic head resection (BDPPHR), an innovative technique, on pain relief, functional outcomes, postoperative morbidity, and mortality in patients with CP. MethodsBetween March 2019 and July 2022, a total of 37 patients underwent bile duct and duodenum preserving pancreatic head resection (BDPPHR) for pain relief in patients with CP. Post-operative outcomes were assessed by Izbicki pain score, exocrine insufficiency, endocrine insufficiency, and return to work. The safety of the surgical procedure was determined by evaluation of postoperative morbidity and mortality as per Clavien-Dindo scores. ResultsBDPPHR showed a significant reduction in Izbicki pain scores with 30 (81 %) patients experiencing complete or partial pain relief up to 18 months of follow up. 32(86 %) patients ceased narcotic use by the end of the 18-month follow-up period. 33 (89 %) patients were able to resume regular work at the end of 18 months. There were no significant alterations in both exocrine and endocrine statuses post-surgery. The median duration of hospital stay was 4.5 days (3-11). Major complications occurred in 2 (5 %) patients. There was no post-operative mortality. ConclusionBDPPHR is a novel and safe technique of near total head resection which results in very good pain relief in 81 % of patients.

Pain prevalence and pain relief in end-of-life care – a national registry study

BackgroundDespite pain control being a top priority in end-of-life care, pain continues to be a troublesome symptom and comprehensive data on pain prevalence and pain relief in patients with different diagnoses are scarce.MethodsThe Swedish Register of Palliative Care (SRPC) was used to retrieve data from 2011 to 2022 about pain during the last week of life. Data were collected regarding occurrence of pain, whether pain was relieved and occurrence of severe pain, to examine if pain differed between patients with cancer, heart failure, chronic obstructive pulmonary disease (COPD) and dementia. Binary logistic regression models adjusted for sex and age were used.ResultsA total of 315 000 patients were included in the study. Pain during the last week of life was more commonly seen in cancer (81%) than in dementia (69%), heart failure (68%) or COPD (57%), also when controlled for age and sex, p < 0.001. Severe forms of pain were registered in 35% in patients with cancer, and in 17–21% in non-cancer patients. Complete pain relief (regardless of pain intensity) was achieved in 73–87% of those who experienced pain, depending on diagnosis. The proportion of patients with complete or partial pain relief was 99.8% for the whole group.ConclusionsThe occurrence of pain, including severe pain, was less common in patients with heart failure, COPD or dementia, compared to patients with cancer. Compared with cancer, pain was more often fully relieved for patients with dementia, but less often in heart failure and COPD. As severe pain was seen in about a third of the cancer patients, the study still underlines the need for better pain management in the imminently dying.Trial registrationNo trial registration was made as all patients were deceased and all data were retrieved from The Swedish Register of Palliative Care database.

Measurement of microclimates in a warming world: problems and solutions.

As the world warms, it will be tempting to relate the biological responses of terrestrial animals to air temperature. But air temperature typically plays a lesser role in the heat exchange of those animals than does radiant heat. Under radiant load, animals can gain heat even when body surface temperature exceeds air temperature. However, animals can buffer the impacts of radiant heat exposure: burrows and other refuges may block solar radiant heat fully, but trees and agricultural shelters provide only partial relief. For animals that can do so effectively, evaporative cooling will be used to dissipate body heat. Evaporative cooling is dependent directly on the water vapour pressure difference between the body surface and immediate surroundings, but only indirectly on relative humidity. High relative humidity at high air temperature implies a high water vapour pressure, but evaporation into air with 100% relative humidity is not impossible. Evaporation is enhanced by wind, but the wind speed reported by meteorological services is not that experienced by animals; instead, the wind, air temperature, humidity and radiation experienced is that of the animal's microclimate. In this Commentary, we discuss how microclimate should be quantified to ensure accurate assessment of an animal's thermal environment. We propose that the microclimate metric of dry heat load to which the biological responses of animals should be related is black-globe temperature measured on or near the animal, and not air temperature. Finally, when analysing those responses, the metric of humidity should be water vapour pressure, not relative humidity.

Effects of different intrusion patterns during anterior teeth retraction using clear aligners in extraction cases: an iterative finite element analysis.

Overtreatment design of clear aligner treatment (CAT) in extraction cases is currently primarily based on the clinical experience of orthodontists and is not supported by robust evidence on the underlying biomechanics. This study aimed to investigate the biomechanical effects of overtreatment strategies involving different maxillary anterior teeth intrusion patterns during anterior teeth retraction by CAT in extraction cases. A finite element model of the maxillary dentition with the first premolar extracted was constructed. A loading method of clear aligners (CAs) based on the initial state field was proposed. The iterative method was used to simulate the long-term orthodontic tooth movement under the mechanical load exerted by the CAs. Three groups of CAs were utilized for anterior teeth retraction (G0: control group; G1: incisors intrusion group; G2: anterior teeth intrusion group). Tooth displacement and occlusal plane rotation tendency were analyzed. In G0, CAT caused lingual tipping and extrusion of the incisors, distal tipping and extrusion of the canines, mesial tipping, and intrusion of the posterior teeth. In G1, the incisors showed minimal extrusion, whereas the canines showed increased extrusion and distal tipping tendency. G2 showed the smallest degree of posterior occlusal plane angle rotation, while the inclination tendency of the canines and second premolars decreased. 1. In CAT, tooth displacement tendency may change with increased wear time. 2. During anterior teeth retraction, the incisor intrusion pattern can provide effective vertical control for the lateral incisors but has little effect on the central incisors. Anterior teeth intrusion patterns can alleviate the inclination of canines and second premolars, resulting in partial relief of the roller-coaster effect.

Complementary advantages of microsurgical treatment for vertebral artery dolicoarteriopathies: Mitigating symptoms of restless leg syndrome in refractory vertebrobasilar insufficiency

Objective: This retrospective study examines the impact of microsurgical treatment on vertebral artery (VA) dolicoarteriopathies and associated restless leg syndrome (RLS) in patients with refractory vertebrobasilar insufficiency (VBI). Patients and Methods: We analyzed 78 patients with grade 2 and 3 kinks, and found out that the targeted microsurgical interventions, primarily designed to address VBI, improved secondary RLS symptoms in 12 patients. Procedures included arteriolysis and, depending on severity, grafting. Statistical analysis was conducted using Stata 16 (StataCorp LP, Texas, USA). Results: In twelve patients aged 55 to 72 years with refractory VBI and drug-resistant RLS, micro-neurosurgical correction of V1 segment dolicoarteriopathy, abnormal elongation and kinks in the artery, demonstrated promising outcomes. Postoperatively, 83.33% (10 patients) reported complete resolution of RLS symptoms, and 16.66% (2 patients) experienced partial symptom relief (p&amp;lt;0.05). Overall, 86.8% of various VBI-related symptoms were significantly improved or resolved (p&amp;lt;0.05). The microsurgical technique, avoiding traditional flow-arresting procedures, proved to be highly effective in this preliminary study with no mortality and minimal temporary complications, underscoring its potential treatment avenue for such complex neurovascular conditions. Conclusion: This study illuminates the relationship between VBI and RLS, proposing a potential vascular etiology for RLS, and highlights the need for a broader diagnostic approach for patients with refractory VBI.

Exploring precision treatments in immune‐mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery

AbstractImmune‐mediated inflammatory diseases (IMIDs) impose an immeasurable burden on individuals and society. While the conventional use of immunosuppressants and disease‐modifying drugs has provided partial relief and control, their inevitable side effects and limited efficacy cast a shadow over finding a cure. Promising nucleic acid drugs have shown the potential to exert precise effects at the molecular level, with different classes of nucleic acids having regulatory functions through varying mechanisms. For the better delivery of nucleic acids, safe and effective viral vectors and non‐viral delivery systems (including liposomes, polymers, etc.) have been intensively explored. Herein, after describing a range of nucleic acid categories and vectors, we focus on the application of therapeutic nucleic acid delivery in various IMIDs, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis, asthma, ankylosing spondylitis, systemic lupus erythematosus, and uveitis. Molecules implicated in inflammation and immune dysregulation are abnormally expressed in a series of IMIDs, and their meticulous modulation through nucleic acid therapy results in varying degrees of remission and improvement of these diseases. By synthesizing findings centered on specific molecular targets, this review delivers a systematic elucidation and perspective towards advancing and utilization of nucleic acid therapeutics for managing IMIDs.

A CASE OF RIGHT HEART FAILURE: WHEN IT IS NOT PULMONARY EMBOLISM

Abstract A 66–year–old patient, showing exertional dyspnea and atypical chest pain, came to our attention with instrumental findings at echocardiogram of right ventricular failure and was hospitalized due to worsening signs and symptoms of right heart failure. Signs of right ventricular strain and the McGinn–White sign (S1Q3T3 pattern) were seen on the ECG, leading to the suspicion of pulmonary thromboembolism (PE). Pulmonary CT angiography confirmed bilateral PE involving the main pulmonary artery. Oral anticoagulant therapy was initiated with initial partial benefit and relief of symptoms. However, after four weeks, the patient was readmitted for severe heart failure and signs of low cardiac output. Echocardiography showed the presence of a conspicuous, mobile, isoechoic mass occupying most of the main pulmonary artery, suggesting thrombosis. The patient underwent urgent surgical thromboendoarterectomy extended to the third segmental left branches and to the second segmental right branches of the pulmonary artery; a severe pulmonary valve regurgitation was observed and therefore the valve was replaced with a Edwards–Magna pericardial bioprosthetic valve. ECMO (Extracorporeal Membrane Oxygenation) was initiated due to haemodinac instability. In the postoperative period, the severe heart failure worsened, unresponsive to pharmacological treatments and mechanical support, leading to the patient passing away in the following days. Unexpectedly, histological analysis of the surgical specimen revealed neoplastic cells with vascular/endothelial differentiation; fluorescence in situ hybridization (FISH) detected the MDM2 gene (cfr.23–F–00275), involved in the p53 protein regulation mechanisms, which is consistent with a diagnosis of angiosarcoma. Pulmonary–artery angiosarcomas are extremely rare (few anecdotical cases are described in literature) and resemble the CT–signs and clinical features of PE, seriously delaying the diagnosis. They are usually associated with a worse prognosis than PE, one and a half months survival time when inoperable. Radical surgery, associated with thirty six and a half months survival time, is often unfeasible because of locally advanced disease or metastatic disease already present at diagnosis. The main differences with PE are the more proximal and almost–occluding involvement of the pulmonary artery, the absence of peripheral vein thrombosis and the absence of response to anticoagulant therapy.

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The discovery of a novel pyrrolo[2,3-b]pyridine as a selective CDK8 inhibitor offers a new approach against psoriasis

Currently, the drugs used in clinical to treat psoriasis mainly broadly suppress cellular immunity. However, these drugs can only provide temporary and partial symptom relief, they do not cure the condition and may lead to recurrence or even serious toxic side effects. In this study, we describe the discovery of a novel potent CDK8 inhibitor as a treatment for psoriasis. Through structure-based design, compound 46 was identified as the most promising candidate, exhibiting a strong inhibitory effect on CDK8 (IC50 value of 57 nM) along with favourable inhibition against NF-κB. Additionally, it demonstrated a positive effect in an in vitro psoriasis model induced by TNF-α. Furthermore, this compound enhanced the thermal stability of CDK8 and exerted evident effects on the biological function of CDK8, and it had favourable selectivity across the CDK family and tyrosine kinase. This compound showed no obvious inhibitory effect on CYP450 enzyme. Further studies confirmed that compound 46 exhibited therapeutic effect on IMQ-induced psoriasis, alleviated the inflammatory response in mice, and enhanced the expression of Foxp3 and IL-10 in the dorsal skin in vivo. This discovery provides a new strategy for developing selective CDK8 inhibitors with anti-inflammatory activity for the treatment of psoriasis.

Endoscopically assisted transaxillary release of the scalene muscles for thoracic outlet syndromes: a comparison with or without first rib resection.

There are several surgical techniques for thoracic outlet syndrome (TOS). However, there have been no reports of endoscopically assisted transaxillary release of the anterior and middle scalene muscles (EATRS), leaving the first rib intact for TOS. We hypothesized that EATRS would achieve a good Quick Disability of the Arm, Shoulder and Hand score. This study aims to present our experience with a new technique for TOS using endoscopy. We chose two surgeries depending on the patient's TOS condition. If the costoclavicular space was under 12mm, we selected endoscopically assisted transaxillary first rib resection (EAFRR). If the costoclavicular space was over 12mm, we selected EATRS. Between January 2021 and December 2022, 31 consecutive surgeries for TOS were performed in our institution. Twenty-five patients underwent EAFRR, and six (19%) underwent EATRS. Since July 2022, EAFRR has been performed under differential lung ventilation. Complete and almost complete relief was achieved in 24 patients (77%), and partial relief was conducted in seven patients (23%) at a mean of 19.7months after surgery. The symptoms improved in all cases. Intraoperative pneumothorax did not occur, and no other complications were observed. Both EAFRR and EATRS were effective and safe surgeries for TOS. Operative time was significantly shorter in EATRS than in EAFRR. We first report EATRS surgery for TOS. EATRS is indicated for patients whose costoclavicular space is preserved before surgery. Good surgical results were obtained after surgery for this indication.

Abstract PO1-15-09: Vitamin A Metabolism Induces Ferroptosis to Enhance Immune Therapy Efficacy in HR+/HER2- Breast Cancer

Abstract Background: Immune checkpoint blockade (ICB) has substantially improved patient overall and progression-free survival in triple-negative breast cancer (TNBC), but its efficacy remains to be elucidated in the hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, which is characterized by generally impotent lymphocytic infiltration. In the I-SPY2 trial (NCT01042379), pembrolizumab- or durvalumab-containing neoadjuvant therapy increased the pathologic complete response of HR+/HER2- patients. However, pembrolizumab-containing therapy failed to improve the survival of metastatic HR+/HER2- breast cancer patients (NCT03051659). These inconsistent results underscored the necessity of the investigation of predictive biomarkers to pinpoint potential ICB responders in HR+/HER2- breast cancer. Method: In this study, we collected pretreatment tumor samples from 16 patients in two respective clinical trials (NCT: 04215003 and 04355858) and profiled droplet-based single-cell sequencing, bulk RNA-Seq. Patients were treated with camrelizumab (PD-1 inhibitor)-containing therapy, and five of them achieved partial relief after an 8-week course. We also leveraged the bulk RNA-Seq data from the I-SPY2 trial and Fudan University Shanghai Cancer Center (FUSCC) TNBC ICB trials (NCT04418154 and NCT04613674) for external validation. Another FUSCC transcriptome dataset consisting of 933 treatment-naïve HR+/HER2- or TNBC breast cancer patients was used to detect the abundance of cell types. In vitro and in vivo experiments were used to explore mechanisms of anti-tumor immune response. Results: Based on the single-cell sequencing results, we comprehensively delineated the microenvironmental landscape of HR+/HER2- breast cancer. We discovered responders of immunotherapy showed a higher presence of CXCL9/10+ M1-like macrophages and exhibited enrichment of tumor cells with ferroptosis. We further identified the upregulation of vitamin A metabolism and the vitamin A metabolic gene CRABP1 in tumor cells with ferroptosis. We verified the vitamin A metabolism could induce ferroptosis in HR+/HER2- breast cancers rather than TNBC by CRABP1-ERK axis, which could further recruit CXCL9/10+ M1-like macrophages and promote anti-tumor immune response in HR+/HER2- breast cancer. Combining anti-PD1 with enhancing vitamin A metabolism via retinoid acid possessed greater therapeutic efficacy than monotherapy in HR+/HER2- breast cancers. Finally, we developed an immune therapy response score and validated its reliability in predicting the immunotherapy efficacy for HR+/HER2-breast cancers through both internal and external cohorts. Conclusion: Our study represents the earliest efforts to decipher the microenvironmental landscape and the mechanisms underlying the response to ICB in HR+/HER2- breast cancer at single-cell resolution. We unraveled a HR+/HER2- breast cancer-specific Vitamin A-ferroptosis axis that mediated immunotherapy response and constructed a robust immunotherapy efficacy prediction score based on this Vitamin A-ferroptosis axis. Citation Format: Yi-Fan Zhou, Hu-Yun-Long Zhang, Xi Jin, Yi-Zhou Jiang, Zhi-Ming Shao. Vitamin A Metabolism Induces Ferroptosis to Enhance Immune Therapy Efficacy in HR+/HER2- Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-09.

Surgical Treatment of Breast Lymphedema: A Distinct Pathology With Unique Challenges.

Supermicrosurgical advances such as lymphovenous bypass (LVB) have enabled effective physiologic treatment of lymphedema affecting the extremities. Reports of surgical treatment for breast lymphedema (BL) are sparse, consisting of case reports and almost exclusively LVB. We report our experience with BL, including a case of mastectomy and breast reconstruction with abdominal free flap and inguinal vascularized lymph node transfer (VLNT) for BL. We compare our series with the surgical literature to discern unique characteristics and treatment limitations inherent to this disease. A database was prospectively maintained from September 2020 to May 2023 including all patients diagnosed with BL who were referred to our institution. Breast lymphedema was diagnosed using clinical criteria, and relevant patient data were recorded. Patients interested in surgical management underwent indocyanine green lymphography to determine candidacy for LVB or other interventions. All patients, including those surgically managed, were treated with complex decongestive therapy. Nine patients with BL were included. Eight had undergone breast-conserving therapy for breast cancer with whole breast irradiation. One patient was treated for Hodgkin lymphoma with axillary lymphadenectomy and axillary radiation. Indocyanine green lymphography was performed in 6 patients, of which 4 patients had diffuse dermal backflow. Two patients had lymphatic targets suitable for LVB, including the patient without breast irradiation. Three patients were managed surgically. One patient without bypass targets underwent breast reduction with partial symptomatic relief, later followed by a mastectomy with abdominal free flap reconstruction and VLNT. Two patients with suitable bypass targets underwent LVB, with resolution of breast swelling and subjective symptoms. The diffuse lymphatic obliteration due to radiation field effect in BL results in a distinct pathophysiology compared with extremity lymphedema. Although published reports of surgical BL treatment almost exclusively describe LVB, other surgical options may be more frequently required. Ablative strategies such as mastectomy and regenerative techniques such as VLNT should be considered potential first-line treatment options for these patients.