Skin Edema Research Articles

Ixazomib, Pomalidomide and Dexamethasone (IxaPD) Pan-Oral Regimen in the Treatment of Refractory and Relapsed Multiple Myeloma

Aim To analyze the efficacy and safety of Ixazomib, pomalidomide and dexamethasone (IxaPD) regimen in patients with refractory and relapsed multiple myeloma（RRMM）. Methods Clinical data of RRMM patients were collected from 5 centers in north China from Jan 2021 to Aug 2023, who were treated by IxaPD regimen for at least two courses. Response, time to next treatment and overall survival were analyzed as end points. Results A total of 34 patients were enrolled, including 21 in multicenter real-world study and 13 in investigator initiated IxaPD trial (NCT04989140) who were naïve to ixazomib or pomalidomide with previous treatment of 1 to 3 lines. There were 18 males and 16 females with the median age 65.5 (range 41-81) years old. The median duration from diagnosis to enrollment was 31 months (range 1-117), including 23/34 (67.3%) of patients were in first relapse. Thirteen in 24 (54.2%) patients had high-risk cytogenetic abnormalities. Regarding previous history, 20.6% presented renal insufficiency, 3 cases (8.8%) had extramedullary diseases, and 5 cases (14.7%) received autologous hematopoietic stem cell transplantation. After median 5 courses (range 2-24) of IxaPD chemotherapy, the overall response rate (ORR) was 64.7%, with 47.1% VGPR or better. The median time to achieve the best response was 2 months (range 1-6). After a median follow-up of 13 months (range 2-28), 52.9% of patients progressed and the median time to next treatment was 7 months (range 3-21). The mortality rate was 17.6%, and the median overall survival was not reached. In the multivariate analysis, response to first-line induction therapy significantly affected the time to next treatment(P<0.05), while age, first relapse, R-ISS stage, high-risk cytogenetics abnormalities, and renal insufficiency did not impact significantly. Neither did those factors also have significant impact on overall survival. Most of the adverse effects (AEs) were grade 1-2, mainly skin rash, peripheral neuropathy, constipation, diarrhea, edema, arthralgia, herpes zoster, and shortness of breath. Only one case of grade 3 pulmonary infection occurred. Conclusion The pan-oral IxaPD regimen showed anticipated effect and good tolerance for RRMM patients, especially appropriate for patients achieving deep response in first-line therapy. More patients are being enrolled and update data will be reported.

Abstract 15329: Echocardiographic Assessment of Cardiac Function in Preterm Miniature Pigs Supported With a Pumped Artificial Placenta

Introduction: Preterm birth is the leading cause of infant mortality and morbidity. Artificial placenta (AP) technology aims to support premature fetal piglets in an environment simulating intrauterine physiology to maintain fetal circulation and improve outcomes and survival. Hypothesis: We sought to understand the fetal cardiovascular physiology and mode of cardiac failure associated with a pumped extracorporeal membrane oxygenation circuit connected to the fetal circulation. Methods: Following umbilical cannulation, connection to a centrifugal pump and neonatal oxygenator and transition of preterm Yucatan miniature piglets to a fluid-filled biobag, echocardiographic studies measured ventricular function and fluid status including Dopplers, and strain analysis both prenatally and while maintained on the AP circuit. Results: AP fetuses (n=13; GA 102±4d; 616±139g; survival 46.4±46.8h) were tachycardic and hypertensive with supraphysiologic circuit flows initially. Strain analysis revealed significantly reduced RV strain rate within the first five hours of AP support compared to paired prenatal measurements (p=0.005) . Fetuses supported for <24h had significantly lower overall RV global longitudinal strain (p=0.001) than those surviving >24h. M-mode imaging revealed progressive cardiac hypertrophy with an increase in interventricular septum (p=0.03) and LV free (p=0.04) wall thickness from first to last measurements. Doppler measurements showed elevated peak flow velocity patterns in the MCA and reductions in MCA-PI from start to end of support (p=0.04) as well as compared to unpaired prenatal controls (p=0.03, p=0.001) . Imaging findings included ascites, skin edema, and dilated hepatic veins. Conclusions: AP fetuses exhibited signs of excessive volume and pressure loading resulting in impaired contractility, including supraphysiologic umbilical flows, reduced RV strain and strain rate, and evidence of elevated filling pressures. Myocardial hypertrophy and changes in cerebral perfusion indicated adaptation to increased afterload, potentially affecting cardiovascular and cerebrovascular development and leading to fetal deterioration. Further advancements in AP technology are necessary before clinical translation.

Safety of Sonazoid in Assisting High-Intensity Focused Ultrasound Ablation Therapy for Advanced Liver Malignant Lesions: A Single-Arm Clinical Study

The aim of the study described here was to evaluate the safety of Sonazoid-assisted high-intensity focused ultrasound (HIFU) in the treatment of advanced malignant liver lesions. A single-arm study was designed to enroll participants who were diagnosed with advanced primary liver cancer or liver metastases and proposed to receive Sonazoid assistance during HIFU treatment. Serological examination was conducted within 1 wk, and side effects in each patient were monitored for 1 mo. To evaluate therapeutic efficacy, the contrast-enhanced magnetic resonance imaging was performed 1 mo after treatment, and short-term follow-up was conducted a year later. A total of 17 participants (12 male, 5 female) with an average age of 58 y (range: 46-73 y) were enrolled, including 11 patients with hepatocellularcarcinoma, 2 patients with hepaticmetastasis and 4 patients with cholangiocarcinoma. The total volume of tumor mass was 111.82 (11.01-272.30) cm3. The average total ablation time for a patient was 2021 ± 1030 s, and the energy efficiency factor was 5979.7 (3108.0, 45634.5) J/cm3. Immediately after HIFU treatment, 1 patient (5.9%) achieved complete response (CR), 4 patients (23.5%) had a moderate response, 8 patients (47.1%) had partial reperfusion and 4 patients (23.5%) had stable disease (SD). The average ablation rate for all the tumors was 51.5 ± 26.7%. The level of glutamic-pyruvic transaminase (ALT) was mildly increased in 71.6% (12/17) of patients after HIFU therapy. Mean ALT values before and after treatment were 22 (14, 35) U/L and 36 (25, 41) U/L, respectively (Z=1.947, p=0.051). Mild or obvious edema in skin and subcutaneous soft tissues were observed in 76.5% of patients, but no serious side effects were found. Twelve months after treatment, the follow-up results revealed that 1 patient (5.8%) achieved a CR, 8 patients (47.1%) had SD and 8 patients (47.1%) had progressive disease. The estimated median time to progression was 11 mo after treatment, with a 95% confidence interval of 6, 11 for all involved patients. Use of Sonazoid is safe and feasible for improving HIFU ablation efficiency during the treatment of advanced malignant liver lesions. The therapeutic efficacy of Sonazoid-assisted HIFU needs to be explored in additional controlled clinical investigations.

FRI509 A Girl With Trisomy 21 Presents With Van Wyk-Grumbach Syndrome

Abstract Disclosure: J. Hayes dorado: None. M. Calla Ayala: None. A. Colque Arias: None. K. Lanuza Gaite: None. M. Rossell Lopez: None. D. Frias Eid: None. Van Wyc-Grumbach syndrome (VWGS) is a rare presentation of long standing prepubertal hypothyroidism characterized by bilateral multicystic enlarged ovaries, vaginal bleeding and delayed bone age. It appeared that high TSH could produce FSH and LH like activity leading to multiple ovarian cysts. A 7-year-old girl with trisomy 21, presented with vaginal bleeding for 2 days prior to admission. Physical exam revealed bradycardia (68 bbm), apathy, sluggishness, as well as dry skin and eyelid oedema. She had no breast development nor pubic hair.Causes of vaginal bleeding such as trauma, possible abuse, foreign body insertion and urethral prolapse were excluded. There was no purpura or bleeding from other sites.The abdominal sonogram revealed bilateral ovarian cystic masses (V:17.29 cm3 and 16.48 cm3, right and left, respectively). Bone age was delayed almost 3 years behind her chronological age. Laboratory tests revealed TSH 860 μIU/mL, T4 0.71 μg/dL, FSH 8.12 mIU/mL, LH < 0.1 mIU/mL, estradiol 193 pg/mL, thyroid peroxidase Abs 184 IU/mL, thyroglobulin Abs 212 IU/mL, Β-hCG < 0.1mU/mL, confirming severe hypothyroidism. The girl was diagnosed with VWGS due to unrecognized chronic lymphocytic thyroiditis and LT4 treatment (75mug/OD) was initiated. The patient responded with complete remission of symptoms and regression of the ovarian cysts one month after initiation of treatment. It is very important to think of VWGS and investigate for thyroid status during the evaluation of ovarian cysts or isolated premature menarche. Early recognition can eliminate unnecessary surgery to remove ovarian cysts, as appropriate treatment with levothyroxine leads to complete remission of symptoms. Even when the diagnosis of VWGS is confirmed, practitioners must be watchful to consider surgical intervention in the presence of uncontrolled vaginal bleeding, hemodynamic instability, or failure of regression of ovarian cysts with exogenous thyroid hormone replacement. Presentation: Friday, June 16, 2023

The Formulation and Evaluation of Deep Eutectic Vehicles for the Topical Delivery of Azelaic Acid for Acne Treatment.

The current work was aimed at the development of a topical drug delivery system for azelaic acid (AzA) for acne treatment. The systems tested for this purpose were deep eutectic systems (DESs) prepared from choline chloride (CC), malonic acid (MA), and PEG 400. Three CC to MA and eight different MA: CC: PEG400 ratios were tested. The physical appearance of the tested formulations ranged from solid and liquid to semisolid. Only those that showed liquid formulations of suitable viscosity were considered for further investigations. A eutectic mixture made from MA: CC: PEG400 1:1:6 (MCP 116) showed the best characteristics in terms of viscosity, contact angle, spreadability, partition coefficient, and in vitro diffusion. Moreover, the MCP116 showed close rheological properties to the commercially available market lead acne treatment product (Skinorin®). In addition, the formula showed synergistic antibacterial activity between the MA moiety of the DES and the AzA. In vitro diffusion studies using polyamide membranes demonstrated superior diffusion of MCP116 over the pure drug and the commercial product. No signs of skin irritation and edema were observed when MCP116 was applied to rabbit skin. Additionally, the MCP116 was found to be, physically and chemically, highly stable at 4, 25, and 40 °C for a one-month stability study.

Evaluation of early results of triamcinolone acetonide treatment in the treatment of idiopathic granulomatous mastitis introduction.

Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory breast disease with an unknown etiology. IGM patients may develop painful or painless masses, palpable lymph nodes, and skin findings that can mimic breast cancer, including retractions, skin edema, ulceration, and fistula formation. This presents a significant diagnostic challenge in clinical practice. The present study aimed to assess the early outcomes of triamcinolone acetonide treatment in patients with idiopathic granulomatous mastitis. After obtaining the necessary approvals from the ethics committee, patients who were admitted to the breast endocrine department of the general surgery clinic of our hospital between 2014 and 2022 with complaints of a mass, discharge, and fistula formation and who were histopathologically diagnosed with granulomatous mastitis after radiological examination by tru-cut biopsy were prospectively enrolled in the study. Among the 136 patients with granulomatous mastitis, the mean age was 30.09±4.14 years, the symptom duration averaged 3 weeks (range: 1-5), the follow-up period extended for 20 weeks (range: 3-72), and the mean recurrence duration was 1.08±0.28 months. Complaints included discharge (52.2%), mass (51.5%), redness (45.6%), and pain (27.2%). Masses were predominantly on the left side (61.0%) compared to the right side (38.0%). In conclusion, the heterogeneous phenotype of IGM and the lack of randomized controlled trials pose challenges. Long-acting triamcinolone acetonide proves effective in managing IGM by resolving the inflammatory process and the disease itself. Its low side effects and ease of use make it a valuable treatment modality.

Polydopamine-loaded prunetin nanomaterials activate DRD2 to reduce UV-induced inflammation by stabilizing and promoting Nrf2 nuclear translocation.

Skin damage caused by exposure to ultraviolet (UV) light has been well documented clinically and histologically. Dopamine receptor D2 (DRD2) possesses various biological functions. However, no study has reported the possible association of DRD2 with UV-induced skin damage. We established DRD2 conditional knockout and UV damage models in this work. The results showed that DRD2 played an important role in the treatment of UV-induced skin damage. The findings of the molecular mechanism study revealed that the internalization of DRD2 after activation can stabilize nuclear factor erythroid 2-related factor 2 (Nrf2). However, the entry of Nrf2 into the nucleus did not increase. We prepared and characterized hyaluronic acid (HA)-coated mesoporous polydopamine (MPDA) nanoparticles (H@P@M). HA facilitated skin epidermal penetration of the nanoparticles to reach the site of inflammation smoothly. Meanwhile, MPDA activated DRD2 internalization to stabilize Nrf2. The release of prunetin inhibited the interaction of Kelch-like ECH-associated protein 1 with Nrf2 and promoted the nuclear translocation of Nrf2. In summary, this study unveiled that in skin inflammation, H@P@M activated and internalized DRD2, which subsequently formed a protein complex with arrestin beta 1-ubiquitin specific protease 8 (USP8)-Nrf2. Deubiquitination was performed to stabilize Nrf2 while promoting the nuclear translocation of Nrf2 to exert anti-inflammatory and antioxidant functions. STATEMENT OF SIGNIFICANCE: Skin is the body's largest physical barrier, always protecting the body from the interference of the external environment. However, excessive exposure to ultraviolet rays in the sun can cause skin inflammation, leading to skin erythema, itching, edema and pain, which can be troublesome in our daily lives. The complex mechanism of skin inflammation caused by ultraviolet radiation has not been fully clarified. In this study, the role of DRD2 in UV-induced skin inflammation was explored, and nano-composite particles HA@Prunetin@MPDA, which act on multiple targets in the anti-inflammatory pathway of DRD2, were developed to maximize the effect of the drug. It provides a new way to treat skin inflammation caused by UV.

P22 Will the real scleroderma please stand up?: a case of a rare scleroderma mimic in ED

P22 Will the real scleroderma please stand up?: a case of a rare scleroderma mimic in ED

Effects of Orbicularis Oculi Flap Suspension on Transcutaneous Lower Blepharoplasty.

The purpose of this study was to analyze the clinical effects of orbicularis oculi muscle suspension in conjunction with transcutaneous blepharoplasty in patients 60 years of age or older. A retrospective study was conducted on patients aged 60 or older who underwent orbicularis oculi flap suspension in conjunction with transcutaneous blepharoplasty to treat lower lid festoons, lower lid fat prolapse, and lid laxity at Korea University Guro Hospital. The outcomes were surgical success rate, recurrence rate, postoperative complications, and patient satisfaction. In total, 39 patients (18 males and 21 females) were included, with an average age of 67.5 years (60-86y) and a follow-up period of 145.7 days (95-195d). In all patients, eyelid laxity was effectively corrected, and there was no recurrence of eyelid laxity after surgery. Three patients suffered postoperative complications, transient skin edema in 2 patients, and transient ectropion in 1 patient. Subjective satisfaction score following surgery was high, with an average score of 2.56 out of 3 points. Orbicularis oculi flap suspension with transcutaneous blepharoplasty can shorten operation time due to surgical ease. It also has the advantage of not involving conjunctival-related complications such as conjunctival edema since it does not pass through the conjunctiva. Finally, it can successfully treat lid laxity and could be used in lower blepharoplasty procedures.

Clinical characteristics of infants hospitalized with early congenital syphilitic nephropathy: a single-center retrospective cross-sectional study in China

BackgroundEarly studies claimed that early congenital syphilitic (CS) nephropathy was rare, and systematic studies about this disease are absent, which may lead to poor awareness of early CS nephropathy in clinicians and result in misdiagnosis and poor patient prognosis. The present study systematically and comprehensively analyzes the clinical characteristics of infants with early CS nephropathy hospitalized in Beijing Ditan Hospital, an infectious disease hospital in China in order to improve the understanding and management of this disorder.MethodsData of the children with early CS from July 1, 2008, to December 31, 2021, were collected from the electronic medical record system of the hospital. Each patient’s demographic characteristics, clinical history, mother’s history of syphilitic infection, and laboratory values were extracted. The patients were enrolled to either the nephropathy group or the non-nephropathy group depending on diagnosis. Descriptive statistics was used to report basic demographics, clinical and laboratory test values, and variables were compared between the two groups by nonparametric tests, t test or χ2 tests.ResultsOf the 122 children with early CS enrolled, 24(19.7%) were diagnosed with early CS nephropathy. All of the children with CS nephropathy were young infants < 6 months old. A majority of them showed typical congenital syphilitic skin lesions, but a quarter of them did not have skin lesions. Compared with non-nephropathic children with early CS, those with nephropathy had higher frequency of hepatosplenomegaly, fever, edema, gastrointestinal (GI) symptoms, and anemia, as well as decreased C3 levels. Urinalysis results showed hematuria in all patients with early CS nephropathy, with proteinuria and renal function impairment in 91.7% and 12.5% of the patients, respectively. Nephritic-type nephrotic syndrome and glomerulonephritis were diagnosed in 45.8% and 54.2% of these patients, respectively. All infants with CS nephropathy were cured or improved after appropriate treatments.ConclusionInfants with early CS nephropathy often presented with nephritic-type nephrotic syndrome or glomerulonephritis, and the typical skin lesions, fever, hepatosplenomegaly, and edema, etc., were its common clinical presentations, and these characteristics could help with the diagnosis. But for infants with nephropathy who did not have typical clinical presentations, CS should also be screened as an important etiology to avoid misdiagnosis.

A MANAGEMENT OF VICHARCHIKA WITH ARKAHARIDRA OIL- A CASE REPORT

Vicharchika is one of the most common skin diseases. Vicharchika can be co-related with eczema, which is a form of dermatitis or inflammation of the upper layers of the skin. The term eczema is broadly applied to a range of persistent or recurring skin rashes characterized by redness, skin edema, itching, and dryness, with possible crusting, flaking, blistering, cracking, oozing, or bleeding. Areas of temporary skin discoloration are sometimes characterized as healed lesions, though scarring is rare. Long-standing eczema is often dry and is characterized by thickened, scaling skin with hyper pigmentation and visible crisscross markings (lichenification). No satisfactory treatment is available in contemporary medical practice except antihistamines and topical steroids. A patient approached OPD with chief complaints of edema, blackish skin lesions, with intense itching at the dorsum of both ears. A remarkable improvement in the condition was observed with the local application of Arkaharidra taila in a span of 2 weeks

Evidence for developmental vascular-associated necroptosis and its contribution to venous-lymphatic endothelial differentiation.

During development, apoptosis removes redundant cells and ensures proper organ morphogenesis. Necrosis is long known as an adult-bound inflammatory and pathologic cell death. Whether there exists physiological necrosis during early development has been speculated but yet clearly demonstrated. Here, we report evidence of necroptosis, a type of programmed necrosis, specifically in perivascular cells of cerebral cortex and skin at the early stage of development. Phosphorylated Mixed Lineage Kinase Domain-Like protein (MLKL), a key molecule in executing necroptosis, co-expressed with blood endothelial marker CD31 and venous-lymphatic progenitor marker Sox18. Depletion of Mlkl did not affect the formation of blood vessel network but increased the differentiation of venous-lymphatic lineage cells in postnatal cerebral cortex and skin. Consistently, significant enhancement of cerebrospinal fluid diffusion and lymphatic drainage was found in brain and skin of Mlkl-deficient mice. Under hypobaric hypoxia induced cerebral edema and inflammation induced skin edema, Mlkl mutation significantly attenuated brain-blood-barrier damage and edema formation. Our data, for the first time, demonstrated the presence of physiological vascular-associated necroptosis and its potential involvement in the development of venous-lymphatic vessels.

Embryonic and fetal tiny pericardial fluid collections at less than 12 weeks of gestation.

To describe embryonic and fetal tiny pericardial fluid collections (PFCs) using transvaginal sonography and HDlive Silhouette at less than 12 weeks of gestation. During an 8-month period from November 2021 to June 2022, one-hundred and thirty transvaginal scans were performed for first-trimester dating, and eleven tiny PFCs of the embryo or fetus were identified at 8+4 - 11+3 weeks of gestation (three at 8, six at 9, and two at 11 weeks). HDlive Silhouette features of PFC were evaluated. Their clinical characteristics and outcomes were also investigated. The incidence of tiny PFCs was 8.5 % at less than 12 weeks of gestation. The mean gestational age at the initial examination was 9.5 weeks (SD: ± 0.9). The mean crown-rump length was 25.0 mm (SD: ± 8.5). The mean PFC dimension was 0.8 mm (range: 0.5-1.3, SD: ± 0.2). Pleural effusion was associated with 3 out of 11 PFCs (27.2 %). Ascites was noted in 2 cases (18.2 %). Skin edema was identified in only in 1 case (0.09 %). There was no arrhythmia. Tiny PFC could also be depicted using HDlive Silhouette. First-trimester fetal ultrasound scans at 11 - 13+6 weeks showed no abnormal findings. PFCs resolved until 13 weeks of gestation (Mean: 12 weeks, SD: ± 1.2). All PFC pregnancies resulted in healthy neonates. The incidence of tiny PFCs was relatively high in early pregnancy. HDlive Silhouette can depict tiny PFCs of the embryo. Tiny PFCs in early gestation are transient, benign findings in utero.

Manifestaciones dermatológicas en una lactante con síndrome de kwashiorkor: Claves para el diagnóstico y tratamiento oportuno

Kwashiorkor syndrome is characterized by protein malnutrition and edema, risk factors are recent weaning, infections, and diets based on corn and rice. This malnutrition can lead to skin manifestations such as thin, dry skin, hyperpigmentation, confluent areas of scaling, dry, hypopigmented, and detachable hair, as well as erosive dermatitis, predominantly in skin folds. The diagnosis is based on a nutritional evaluation exam, physical examination and laboratory finding, the treatment is based on early nutritional rehabilitation. Clinical case: 8-month-old female infant who attended the Instituto Nacional de Pediatría, presenting a scaling dermatosis of 1 months of evolution that was treated with topical ketoconazole. The mother reported exclusive feeding with corn gruel due to the diagnosis of “lactose allergy” and commented not enough resources to buy hydrolyzed formula. The patient presented a disseminated dermatosis to all- body segments, characterized by well-defined, irregularly shaped, hyperpigmented plaques with scaling in thick sheets in the perioral region and extremities, as well as areas of eroded skin and paleness and edema of extremities. Laboratory tests were taken, where anemia (Hb 11.2 g/dl) and hypoalbuminemia (3.3 g/dl) were documented, the diagnosis of Kwashiorkor syndrome was integrated. The clinical and laboratory findings were reported to the Gastroenterology and Nutrition service, who performed a nutritional assessment, and began nutritional treatment, emollients and general skin care were documented; twenty days later, the dermatosis and edema had subsided. Keywords: Malnutrition; dermatoses; edema; feeding; desquamation.

Comparison of Safety and Efficacy of Two Different Chemotherapy Dosing Schedules Used in Concurrent Chemoradiation of Head and Neck Cancer: A Retrospective Experience from a Tertiary Cancer Care Institute of Eastern India

Introduction: Concurrent chemoradiation has shown improvements in local control and survival in various multi-institutional trials and been the standard of care for locally advanced head and neck cancers. Platinum-based chemotherapy has shown the maximum benefit without any significant difference between mono- or polychemotherapy. Despite a general consensus that platinum-containing regimens are optimal, the actual dose schedule remained open questions. Our study aimed to assess the efficacy and toxicity of concurrent weekly cisplatin with radical radiotherapy and compare two different chemotherapy dosing schedules of concurrent chemoradiation in head and neck cancer. Materials and methods: The records of 62 eligible patients of locally advanced (T3-4a, N1-2) squamous cell carcinoma of oropharynx, hypopharynx and larynx registered between 2016 to 2020 at a regional cancer centre in India were analysed from the hospital database after approval of the Institutional Ethical Committee and informed consent taken from all the eligible patients.One group of patients (Group A) received Concurrent Chemo-radiation with injection Cisplatin 40 mg/m2 weekly with Radiotherapy to a dose of 66 Gy delivered in 33 fractions for six &amp; half weeks and the patients of the other group (Group B) received injection Cisplatin 100 mg/m2 in three weekly schedule on Days 1, Day 22 &amp; Day 43 along with the same radiation schedule. Results: There was no significant difference in the baseline characteristics between the two groups (p value≥0.05). Though the complete response occurred more in 3 weekly group compared to weekly cisplatin group at follow up of 6 weeks (67.7% vs 61.3%), 6 months (80.6% vs. 67.7%) and 12 months from the completion of CCRT (78.9% vs 65%), it was not statistically significant (p value≥0.05). No statistically significant differences were found in terms of both the acute toxicities (anaemia, leukopenia, mucositis, dermatitis, UGI toxicities, dysphagia) and late toxicities (laryngeal edema, dryness of mouth and edema of skin of neck) when weekly concurrent chemoradiotherapy was compared to three weekly chemoradiotherapy (p value ≥ 0.05).Conclusion: Weekly chemotherapy regimen can be delivered safely on a day care basis and can be helpful in a set up with limited logistics and considerable patient burden.&#x0D;

The Significance of Skin Oedema in Locally Advanced Breast Cancer and Its Response to Neoadjuvant Chemotherapy

The Significance of Skin Oedema in Locally Advanced Breast Cancer and Its Response to Neoadjuvant Chemotherapy

Organization of medical care for patients with HAE and experience in treating patients with lanadelumab

Background. Hereditary angioedema is a rare autosomal dominant disease that can cause edema of skin and mucous membranes, including life-threatening localization, in pathogenesis of which plasma kallikrein is also important. The main therapy aim is to achieve complete control over symptoms and improve quality of life. The first available specialized drug for long-term prophylaxis is lanadelumab blocking plasma kallikrein.&#x0D; Aim. The aim is to show principles of medical care for patients with HAE in Sverdlovsk region and to determine lanadelumab efficacy in patients with HAE in real clinical practice.&#x0D; Materials and methods. We conducted a single-center prospective non-interventional study. There are 22 patients with HAE in register of primary immunodeficiencies in Sverdlovsk region. The analysis of patients' therapy was performed. Lanadelumab efficacy was studied in 5 patients received drug for at least 4 months. The validated questionnaires AAS, AECT, AE-QoL were used to assess lanadelumab efficacy.&#x0D; Results: Educational program for practitioners and implemented diagnostic algorithm led to increase HAE detection: the number of HAE patients doubled over past 3.5 years (11 patients in 2019, 22 patients in 2023). School for patients education was organized. Lanadelumab has been introduced into clinical practice since December 2021. All patients included in lanadelumab efficacy study were female. According to AAS28 scale, patients had high disease activity before and there was an almost 10-fold decrease in disease activity in 4 month of lanadelumab therapy. A positive effect was observed after the first month of treatment with lanadelumab. HAE activity decreased to 0 after 4 months of therapy. The average score on AEST scale was 5.40 2.41, which indicated an uncontrolled course of HAE. By the 4th month of therapy, control was achieved - 13.60 2.61 points on AEST scale. Quality of life on AE-Qol scale improved from 81% to 38% by the 4th month of therapy (p=0.050).&#x0D; Conclusion: Current system of medical care for patients with HAE in Sverdlovsk Region makes it possible to improve HAE detection and provide patients with special pharmacotherapy betimes. Lanadelumab significantly reduces HAE activity, allows to achieve controlled course and high quality of life in real clinical practice.

1024-P: Management Algorithm of Patients with Concomitant Diabetes Mellitus and Chronic Venous Insufficiency

Introduction: Diabetes mellitus (DM) and Chronic Venous Insufficiency (CVI) are significant burden in patient daily life. While the two diseases share common risk factors and pathophysiology, they are often assessed and managed as separate conditions. Aim: To develop recommendations for the identification and treatment of patients with concomitant DM and CVI. Methods: Using a modified Delphi method, a panel of experts developed 38 statements and 2 multiple choice questions. These were used to form an online survey which was disseminated through vascular and diabetes specialists across Europe, Central America, South America, and Middle East. Respondents indicated their level of agreement with each statement. The threshold for consensus was set as ≥75% of agreement. Results: A total of 238 responses were received. Most of the statements (27/38) reached &amp;gt;90% agreement, 9/38 attained between 75-90% agreement, and 2 failed to meet the threshold. The awareness around the impact of the two diseases was high and a gap was highlighted in the identification of patients suffering from concomitant DM and CVI. Seventy-seven (77%) respondents consider overweight (BMI &amp;gt;30) and leg oedema as signs for assessment of the presence of DM and diabetic microvascular complications (DmVC) in patients with CVI, while 63% agreed that three parameters (skin changes, leg burden and oedema) would be required to trigger investigation for coexistent CVI in patients with DM. Treatment of patients with DmVC and CVI should be accomplished with a combination approach, including lifestyle change, non-medical and pharmacological treatments. Venoactive drugs indicated in both DmVC and CVI were recognized as treatment option in this patient population. Conclusion: These results raised the need to consider DM and CVI as a combined therapy area. As outcome, an algorithm is proposed to help the identification of at-risk patients and to provide recommendation on the management of patients with concomitant diseases. Disclosure G.Gastaldi: Advisory Panel; Ascensia Diabetes Care, Insulet Corporation, Novo Nordisk, Lilly, Other Relationship; Abbott Diabetes, AlfaSigma, Research Support; Ypsomed AG, Speaker's Bureau; Dexcom, Inc., Medtronic, Roche Diabetes Care. A.K.Bozkurt: Advisory Panel; OM PHARMA. M.Van rijn: None. E.Bouskela: None. F.Glauser: Consultant; Servier Laboratories. E.Rabe: Consultant; Sigvaris Int., EUROCOM, Mylan, Speaker's Bureau; OM Pharma. A.Mansilha: None. H.Haller: None. J.Rosas-saucedo: None. Funding OM Pharma Ltd.

Basophil Characteristics as a Marker of the Pathogenesis of Chronic Spontaneous Urticaria in Relation to the Coagulation and Complement Systems.

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch and pruritus anywhere on the body for more than 6 weeks. Although basophil- and mast cell-released inflammatory mediators, such as histamine, play important roles in the pathogenesis of CSU, the detailed underlying mechanism is not clear. Since several auto-antibodies, IgGs which recognize IgE or the high-affinity IgE receptor (FcεRI) and IgEs against other self-antigens, are detected in CSU patients, they are considered to activate both mast cells in the skin and basophils circulating in the blood. In addition, we and other groups demonstrated that the coagulation and complement system also contribute to the development of urticaria. Here, we summarized the behaviors, markers and targets of basophils in relation to the coagulation-complement system, and for the treatment of CSU.

"They are closely interconnected, complement each other and pass into each other, there are no clear boundaries between them". Case report

Hereditary angioedema is a rare (1:50,000) hereditary chronic disease from the group of primary immunodeficiencies, which manifests in the form of recurrent skin and mucous membrane edema of the respiratory tract and gastrointestinal tract.Pathogenesis of this disease are associated with an increased risk of a number of cardiovascular pathologies, which is associated with the complexity of management and choosing optimal treatment methods. This case report demonstrates the complexity of managing a patient with hereditary angioedema, multifocal atherosclerosis, severe aortic stenosis, and gastric neuroendocrine cancer.