Marked Clinical Improvement Research Articles

Paradoxical deterioration during treatment of tuberculous meningitis responded to infliximab but not to steroids

Paradoxical deterioration in patients with tuberculous meningitis is a significant diagnostic and treatment challenge. We present the case of a 55-year-old previously healthy male, human immunodeficiency virus (HIV)-negative, presenting with headache, fever, agitation and slurred speech, who was ultimately diagnosed with tuberculous meningoencephalitis confirmed by cerebrospinal fluid polymerase chain reaction positive for Mycobacterium tuberculosis complex. After initiation of a standard antitubercular therapy combined with glucocorticoids, the patient experienced an initial neurological improvement. However, after 3 months of therapy, he had a major stroke with neurological deterioration, clinically and radiologically attributable to a paradoxical deterioration or an immune reconstruction syndrome as described in HIV-positive patients. Due to the persistence of inflammatory symptoms and radiological evidence of worsening tuberculomas despite ongoing antituberculosis therapy, off-label use of the tumour necrosis factor (TNF) inhibitor infliximab was initiated. The patient received three doses of infliximab at 5 mg/kg at monthly intervals, which led to marked clinical and radiological improvement. Follow-up magnetic resonance imaging showed regression of lesions, and the patient was eventually discharged with a significant recovery of motor and speech functions. This case underscores the potential of TNF inhibitors in managing severe cases of paradoxical deterioration in patients with tuberculous meningitis, challenging existing treatment paradigms and suggesting a need for further research into the pathophysiology and treatment of this condition.

Hemophagocytic Lymphohistiocytosis as an Unusual Presentation in a Patient with Human Immunodeficiency Virus-associated Bone Marrow Classic Hodgkin Lymphoma: A Case Report with Literature Review

Abstract Introduction/Objective Compared to the general population, people living with human immunodeficiency virus (HIV) have a higher incidence of lymphoproliferative disorders including classic Hodgkin lymphoma (CHL). Hemophagocytic lymphohistiocytosis (HLH) triggers in HIV patients include HIV itself and HIV-associated malignancies or infections, all of which can have many overlapping symptoms, causing diagnostic challenges and delays in initiating treatments. Methods/Case Report A 56-year-old HIV-positive man presented with septic shock-like symptoms, pancytopenia, hyperferritinemia, transaminitis, elevated IL2-receptor alpha and hepatomegaly. Mild retroperitoneal lymphadenopathy found on imaging yielded non-diagnostic biopsies. A bone marrow (BM) biopsy showed no malignancy or disseminated infections and a rare hemophagocyte. Treatment for HIV-triggered HLH lead to a marked clinical improvement. Three months later he presented with worsening symptoms, negative cultures, and an EBV+ CHL on a BM biopsy. Mild increase in lymphadenopathy and multiple liver/spleen hypodensities found on imaging could not be biopsied due to rapidly deteriorating patient’s condition and death. Results (if a Case Study enter NA) NA Conclusion Per studies, HLH is more frequent in the HIV-associated lymphomas compared to the non-HIV- associated ones, usually presenting as a sepsis-like syndrome in these patients. Probability of HLH development was particularly high with BM involvement and CHL. From 2010, seven cases of HIV-associated CHL presenting with HLH were found in the literature with these findings: (n=8, including ours) sex- all males; average age- 45 years (range 28- 64); average HIV viral loads- 83,369 copies/mL (range: undetectable->300,000); average absolute CD4 count- 98 cells/microliter (range: 8-314); interval from HIV diagnosis- new to 26 years; anti-retroviral treatment- 6; symptoms- fever (all), other symptoms were variable; HLH-2004 protocol criteria- all; biopsy-proven hemophagocytes- 3; EBV+ CHL- all (6 were diagnosed on BM biopsies); outcomes- remission (2), response to treatment (4), death (2). CHL- triggered HLH in HIV patients is a complex diagnostic entity. A high index of suspicion and thorough investigations including early BM biopsies can ensure better outcomes.

Neurosarcoidosis presenting as transient ischemic attacks: A Case Report

Sarcoidosis is a multi-organ granulomatous disease of unknown etiology characterized by the presence of non-caseating granulomas. It has the potential to affect multiple organs including the nervous system. Neurosarcoidosis is present in around 5% of sarcoidosis patients. The clinical manifestations of neurosarcoidosis are heterogeneous, as granulomas can affect the brain, spinal cord and peripheral nervous system, separately or in different combinations. We report a case of neurosarcoidosis with pulmonary involvement in a young female patient presented with multiple episodes of transient ischemic attacks (TIAs). She was treated with boluses of cyclophosphamide followed by azathioprine which led to marked clinical and radiological improvement.

Clinical and pathological characteristics of a dog with scleromyxoedema

An 8‐year‐old male cross‐Labrador retriever was presented for a progressive appearance of folds all over the body of the dog. Scleromyxoedema was diagnosed based on clinical signs and histopathological features. Clinical signs were characterised by a papular and vesicular eruption and severe skin thickening causing exuberant folds along with concurrent severe osteoarthritis of the coxofemoral joints. Thyroid disorders were excluded and the condition was not associated with monoclonal gammopathy. Histopathological features consisted of mucin deposition, fibroblast proliferation and fibrosis. Prednisolone was prescribed to decrease mucin synthesis which allowed a marked clinical improvement. Due to the progressive inability to walk, the dog was euthanased 6 months after the first consultation.

Marked clinical improvement in a cat with a refractory non‐surgical case of dermatophytic pseudomycetoma responding to combination antifungal therapy

AbstractFeline dermatophytosis is a common dermatological manifestation that carries a good prognosis once a proper diagnosis has been achieved. In rare cases, dermatophytosis can manifest as a nodular dermatosis. This condition, known as dermatophytic pseudomycetoma, can be challenging to diagnose and treat. Surgical excision and systemic antifungal therapy are the standard treatments, which generally will carry a good prognosis for the patient. This case report describes a non‐surgical dermatophytic pseudomycetoma, which failed treatment with a singular antifungal agent, but improved when multiple antifungal medications were combined. This case highlights challenges associated with treating a cat with severe dermatophytic pseudomycetoma and concurrent feline leukaemia virus.

Beneficial therapeutic plasma exchange response in the treatment of severe relapses in patients with multiple sclerosis.

Therapeutic plasma exchange (PLEX) is effective as a second-line treatment of severe relapses of multiple sclerosis (MS) that failed to respond to standard steroid therapy. Our objective was to evaluate the effectiveness of PLEX in the severe MS relapses in a cohort of patients treated at Neurology Clinic, University Clinical Centre of Serbia, Belgrade, from 2007 until 2020. This retrospective study comprised 107 MS patients with 127 severe relapses treated with PLEX. Majority of our patients suffered from relapsing remitting MS (83.2%), 12.1% had secondary progressive MS and 4.7% had primary progressive MS. Mean age was 39.2 years (range, 19-79 years), female/male ratio 2.3:1. Pulse corticosteroid treatment was used before PLEX in 99.3% of patients. Median EDSS score at nadire during relapse was 6.0 (range 2.0-10.0). After PLEX, 73.8% relapses showed a marked clinical improvement, 7.1% showed mild improvement and in 19.0% there was no improvement. Median EDSS at discharge was 4.0 (6.0 at nadir of relapse vs. 4.0 at discharge; p<0.0001) and it was sustained at the same level, 6 month after PLEX. Multivariate regression analysis showed that higher EDSS at nadir during relapse (OR=0.63, 95% CI 0.41-0.96, p=0.039) and older age (OR=1.07, 95% CI 1.02- 1.12, p=0.010) were significantly associated with poor treatment response after 6- month follow-up. Adverse events occurred in 17.3 of procedures and they were completely resolved. Our study in a large cohort of MS patients confirmed that PLEX is effective.

An efficient and successful outcome after haematopoietic stem cell transplantation in a patient with an LPS-responsive beige-like anchor gene mutation.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Case Report: Opposite Tumoral and Hormonal Responses to Low-dose Pasireotide in Cushing’s Disease

Background:: Pasireotide is a multireceptor somatostatin analogue approved for the treatment of patients with Cushing's disease (CD) who are ineligible or poor candidates for pituitary surgery. Here we present a patient with severe recurrent CD who was treated with pasiretide and showed opposite results between hormonal levels and pituitary tumour size. Case Presentation:: A 54-year-old woman was diagnosed with CD, a first surgical transsphenoidal procedure was performed at the time of diagnosis, and the disease recurred seven years later. She underwent a second transsphenoidal surgery, but despite apparent complete removal of the adenoma, the hypercortisolism worsened. Magnetic resonance imaging showed a tiny remnant of the adenoma adjacent to the cavernous sinus, and ketoconazole was started at a dose of 800 mg/day. Due to the persistence of pathological urinary free cortisol levels, 600 μg bid pasireotide was added. The combination therapy induced first normalisation of urinary free cortisol and later hypoadrenalism, so that ketoconazole was discontinued and pasireotide was maintained. A marked clinical improvement was achieved with pasireotide. Adrenal insufficiency persisted despite progressive tapering of the pasireotide dose to 150 mg once daily. Pituitary magnetic resonance imaging performed at 12 and 24 months during low-dose pasireotide treatment showed a few millimetres increase of the remnant. Conclusions:: This report suggests that CD Pas induces an opposite effect between hormonal profile and increase of pituitary tumor size. This peculiar phenomenon may be a consequence of the unusually low doses of pasireotide needed to control hormonal hypersecretion.

ACAD9 treatment with bezafibrate and nicotinamide riboside temporarily stabilizes cardiomyopathy and lactic acidosis

Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy. Treatment with high dose bezafibrate and nicotinamide riboside resulted in marked clinical improvement including reduced lactate and NT-pro-brain type natriuretic peptide levels, with stabilized echocardiographic measures. After a long stable period, the child succumbed from cardiac failure with infection at 10.5 months. Therapy was well tolerated. Peak bezafibrate levels exceeded its EC50. The clinical improvement with this treatment illustrates its potential, but weak PPAR agonist activity of bezafibrate limited its efficacy.

Failed bioprosthetic tricuspid valve replacement treated with transcatheter valve for valve repair

Tricuspid bioprosthetic valve failure may lead to right-sided heart failure and is traditionally managed with surgical valve replacement. However, the substantial mortality risk associated with reoperation for failed tricuspid bioprosthesis prompts the need for less invasive alternatives. Transcatheter valve-in-valve (TViV) implantation presents a promising minimally invasive option for patients with failing bioprosthetic valves. This case involves a 32-year-old man with a history of recurrent failed bioprosthetic tricuspid valves who underwent successful percutaneous TViV implantation using a 29 mm Edwards Sapien S3 valve, resulting in marked clinical and hemodynamic improvement. This case contributes essential insights to the limited literature on TViV in the tricuspid position, particularly in patients with complex surgical histories. The high procedural success rate and substantial improvement in valve function underscore the potential of TViV as an effective alternative to surgical replacement for failed tricuspid bioprosthetic valves. Keywords: Transcatheter tricuspid valve replacement; tricuspid valve-in-valve; bioprosthetic tricuspid valve; tricuspid valve stenosis

Impressive Response to TANDEM Peptide Receptor Radionuclide Therapy with 177Lu/225AcDOTA-LM3 Somatostatin Receptor Antagonist in a Patient with Therapy-Refractory, Rapidly Progressive Neuroendocrine Neoplasm of the Pancreas.

The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [68Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [177Lu]LuDOTA-LM3 and [225Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest-abdomen-pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity.

Indomethacin-Responsive Headache Disorders.

This article describes the clinical features and treatment of the indomethacin-responsive headache disorders paroxysmal hemicrania and hemicrania continua. Both paroxysmal hemicrania and hemicrania continua are treated with indomethacin at the lowest clinically useful dose. It has recently become clear that some patients with either condition may respond to treatment with noninvasive vagus nerve stimulation, which can be both indomethacin sparing and, in some cases, headache controlling. Given the lifelong nature of both paroxysmal hemicrania and hemicrania continua, brain imaging with MRI is recommended when the conditions are identified, specifically including pituitary views. Paroxysmal hemicrania and hemicrania continua are indomethacin-responsive headache disorders that offer a rewarding and unique opportunity to provide marked clinical improvement when recognized and treated appropriately. These disorders share the final common pathway of the trigeminal-autonomic reflex, with head pain and cranial autonomic features, and are differentiated pathophysiologically by the pattern of brain involvement, which can be seen using functional imaging. They have distinct differential diagnoses to which the clinician needs to remain alert.

Efficacy of a Novel Melatonin-Loaded Gelatin Sponge in Palatal Wound Healing

ObjectivesThe aim of this research was to assess both clinically and histologically the effect of a topically applied melatonin-loaded gelatin sponge on palatal wound healing after graft harvesting. MethodsTwenty-six patients for whom free palatal graft procurement was indicated were divided equally into 2 groups. In the test group, the donor site was covered by a melatonin-loaded gelatin sponge, and in the control group the site was covered by a placebo-loaded gelatin sponge. Wound healing was evaluated on the day of surgery and at 7 and 14 days postsurgery using photo-digital planimetry. Histologic specimens were taken to verify healing type and rate. Pain was assessed via Visual Analogue Scale (VAS) for 7 days from the day of the surgery. ResultsAt the 7-day interval, photo-digital planimetry showed a significant decrease in the traced raw area (P = .04) in the test group compared with the control group and a significant increase in the mean area of immature epithelia (P = .04). At the 14-day interval, there was no statistically significant difference in any area of interest. Histologically, the application of melatonin was associated with accelerated healing and superior maturation at all follow-up time points. No significant differences were noted in VAS scores between the 2 groups. ConclusionsMelatonin-treated tissue showed marked clinical improvement in the first week postsurgery, indicating an increased rate of healing. Similarly, histologic analysis revealed significant maturation at both time intervals. A melatonin-loaded gelatin sponge is a novel palatal wound dressing that can be used to improve wound healing outcomes and reduce patient morbidity.

Abstract 6663: Innovative CPMV immunotherapy: A canine model for poor-prognosis breast cancer treatment

Abstract Cowpea Mosaic Virus (CPMV) is a plant comovirus non-infectious to humans or animals. In mice models, intratumor immunotherapy (ITI) with CPMV devoid of nucleic acids (empty CPMV, eCPMV) and full CPMV results in a highly potent, systemic, antitumor immune response, with full CPMV being much more effective. Dogs with spontaneous mammary (breast) cancer (MC) serve as a valuable model for studying breast cancer (BC), bridging the gap between studies in rodents and human clinical trials. Canine MC develops in the presence of an intact immune system and has a unique advantage of shorter endpoint periods compared to women BC clinical trials. New immunotherapeutic approaches are necessary for poor-prognosis BC, such as triple-negative BC, metastatic BC, and the very aggressive and lethal inflammatory BC (IBC). Previous studies by our group using eCPMV ITI in dogs with MC revealed a substantial reduction in tumor size in both injected and non-injected tumors (abscopal effect), extended survival, and improved quality of life without any adverse effects or toxicity. In this clinical trial, we employed full CPMV nanoparticles ITI in dogs with poor-prognosis (inoperable) MC, comparing them with untreated controls. Regular tumor volume assessments and clinical evaluations have been conducted. Histopathology and immunohistochemistry of immune cell populations were performed to study tumor microenvironment (TME) modifications. Thus far, 5 dogs have been treated: four cases of inflammatory mammary cancer (IMC) and one case of metastatic MC. After at least two weekly CPMV ITI sessions, a significant reduction in tumor volumes was observed. In IMC cases, marked clinical improvement of typical signs (warmth, edema, erythema, and cutaneous pain) was observed in 3 out of 4 cases, and tumor reduction was so remarkable in one dog that surgery was recommended and successfully carried out. In IMC CPMV ITI cases, the survival of 2 dogs exceeded historical IMC records; the dog with metastatic MC maintains stable disease after one year, which is also superior to controls. TME studies showed that eCPMV immunotherapy significantly increased intratumor inflammatory infiltrates, neutrophils, T lymphocytes, and macrophages. Additionally, Treg cells (FOXP3+)/T lymphocytes (CD3+) ratio was significantly reduced. Our results demonstrate that immunotherapy with eCPMV induces a potent immunostimulatory effect on dogs with poor-prognosis MC by recruiting and activating neutrophils as the main drivers of the inflammatory response. This process reduces the immunosuppressive action of regulatory T lymphocytes and produces a breakdown of tumor immune suppression. These findings underscore the therapeutic potential of CPMV nanoparticles ITI in the management of canine IMC and metastatic MC. From a translational point of view, this study lays the groundwork for advancing the treatment of human breast cancer. Citation Format: Guillermo Valdivia, Dolores Pérez-Alenza, Lucía Barreno, Ángela Alonso-Diez, Jessica Fernanda Affonso de Oliveira, María Suárez-Redondo, Steven F. Fiering, Nicole F. Steinmetz, Laura Peña. Innovative CPMV immunotherapy: A canine model for poor-prognosis breast cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6663.

Urinary Symptoms Change and Quality of Life After Robotic Radical Prostatectomy: A Secondary Analysis of a Randomized Controlled Trial

ObjectiveTo present the patient-reported QoL outcomes from a prospective, randomized controlled trial comparing the use of pelvic floor muscle training (PFMT) and duloxetine after robot-assisted radical prostatectomy (RARP). MethodsWe identified 213 men with organ-confined disease having post-RARP urinary incontinence who were randomly assigned to received PFMT, duloxetine, combined PFMT-duloxetine and pelvic floor muscle home exercises. Urinary symptoms burden was measured by marked clinical important difference improvement (MCID) defined by using the International Prostate Symptom Score(IPSS) difference of -8 points(ΔIPSS ≤ -8). QoL was assessed according to Visual Analog Scale(VAS), King’s Health Questionnaire(KQH), and International Index of Erectile Function(IIEF-5). Multivariable regression analyses aimed to predict MCID, burden of urinary symptoms (IPSS ≥8), and patients reporting to be satisfied (IPSS QoL ≤2) or comfortable (VAS ≤1) post-RARP. ResultsModerate to severe urinary symptoms decreased from 48% pre-operatively to 40%, 34% and 23% at 3mo, 6mo and 12mo post-RARP. After surgery, MCID improvement was observed in 19% of patients, and deterioration in 3.3%. Large prostate was the only factor associated to MCID (OR 1.03 [95%CI 1.01-1.05], p=0.005). At 6mo, patients reached the same degree of preoperative satisfaction. NVB preservation was the only predictor of being comfortable regarding urinary symptoms postoperatively (OR12.8 [CI95% 1.47-111.7],P=0.02 at 3mo) and was also associated to higher median postoperative IIEF-5. ConclusionDespite UI following RARP, patients with larger prostates experience a reduction of lower urinary tract symptoms (LUTS) within a year, which subsequently elevates QoL. Furthermore, nerve-sparing surgery augments erectile function and urinary outcomes, shaping postoperative QoL.

Case report: successful treatment of primary intradural extramedullary extraskeletal Ewing sarcoma in adult patient with intralesional surgery, chemotherapy, and proton beam therapy of the cerebrospinal axis

Ewing sarcoma is a rare malignant neoplasm that primarily affects bone in children. Extraskeletal location is less common, while intradural extramedullary Ewing sarcoma (IEES) in adults is a casuistic phenomenon. Due to its rarity, a standardized treatment strategy for IEES has not been established. The clinical use of proton beam therapy (PBT) for craniospinal irradiation (CSI) in the treatment of IEES has not been reported in the literature. A 41-year-old previously healthy man presented with disabling gluteal and lower extremity pain, decreased sensation, and progressive paraparesis without sphincter dysfunction. Imaging showed intradural extramedullary spinal lesions. The patient underwent urgent surgery. Histology and immunohistochemistry suggested a poorly differentiated neuroendocrine tumor. Negative chromogranin staining and a high Ki67 index prompted further investigation. Next-generation sequencing later confirmed an EWSR1/FLI1 translocation, leading to the diagnosis of extraskeletal Ewing sarcoma. The patient received standardized chemotherapy with marked clinical improvement. PBT CSI was initiated but was interrupted due to COVID-19 and other complications. At 20 months follow-up, no recurrence was observed, and the patient reported an active life. Despite intra-spinal spread and multiple complications, intensive chemotherapy combined with PBT CSI led to a favorable outcome. CSI rather than focal radiotherapy should be considered for patients with IEES limited to the cerebrospinal axis. PBT may be used as an alternative to photon radiotherapy to better spare organs at risk.

Peripheral sterile corneal infiltrate after cross linking in keratoconus: A case report

Aims/Purpose: The aim of our work is to describe the clinical aspect of sterile corneal infiltrates after cross linking and to evaluate the risk factors involved in their occurrence.Methods: We report the case of a young girl, followed for bilateral keratoconus having made a cross linking which was complicated by sterile catarrhal infiltrates.Results: This is a 15 years old girl, followed for allergic conjunctivitis with notion of self‐medication. The ophthalmological examination on admission found a visual acuity with correction counting fingers at 1 metre in oculus uterque (OU), some conjunctival papillae, minimal blepharitis, clear cornea, cortico‐nuclear cataract ocular tone was 10 mmHg in OU, normal fundus in OU. A corneal topography was performed showing signs of bilateral keratoconus classified as stage III according to the Krumeich classification. An emergency cross linking was indicated in OU starting with the OL, the patient was put on a topical antibiotic treatment, artificial tears with a daily control. At 4 days post‐op, the cornea had completely re‐epithelialized with the presence of a slight central haze and the appearance of 2 inferior stromal opacities of 1 mm/1 mm associated with a crescent infiltrate and 2 similar superior stromal opacities taking the fluorescent in front of the free edge. A corneal swab was taken for bacteriological, mycological and parasitological study and came back negative. The patient was initially put on ceftazidime and vancomycin based eye drops with a blepharitis treatment based on azyter collyrium lavage and artificial tear. The examination 48 h later showed persistence of stromal opacities without taking fluo. A local corticosteroid therapy was started with strict monitoring. The evolution was marked by an almost total regression of the stromal opacities and a disappearance of the central haze. The diagnosis of sterile infiltrate was made in view of the marked clinical improvement under local corticosteroid therapy and the absence of germs in the corneal sample.Conclusions: Evaluation of risk factors showed that epithelial injury may be the common pathway in pathogenesis, as no sterile infiltrate in Epi‐on CXL occurred, and postoperative NSAIDs use increased the risk of developing sterile infiltrates approximately fourfold.

Belantamab Mafodotin in Relapse/Refractory AL Amyloidosis- Real-Life Multi-Center Experience

Introduction: Bortezomib and daratumumab revolutionized the therapy for AL amyloidosis (AL). However, relapsed/refractory AL resistant to both drugs is an unmet clinical need, with limited options due to the frailty of these patients and paucity of prospective data. The safety profile and efficacy of belantamab mafodotin (BLM) in multiple myeloma (MM) are well known. In contrast, published data for AL are currently limited to case series of 6 (Zhang, Ann Hematol. 2022) and 12 patients only (Khwaga, Blood Cancer J. 2022). Here, we report a multicenter real-world data on 12 AL patients treated with BLM and compare these to the prior reports. Methods: We retrospectively identified all AL amyloidosis patients who received BLM outside a clinical trial, between Feb 2020-Sep 2022. The diagnosis, staging, hematologic and organ responses and progression of AL were evaluated according to consensus criteria. Event-free survival (EFS) was defined as the time from the first day of BLM administration to hematologic progression or therapy change for inadequate response or death. Results: Twelve AL patients from 5 centers in Israel and Italy were included. The median age at BLM initiation was 66 y (range 54-70). The most common FISH aberrations were 1q gain in 8 patients (67%) and t(11;14) in 5 (42%). All patients except one had cardiac involvement (92%) and 9 (75%) had renal involvement. The median number of prior lines of therapy was 3 (range 2-9). All patients previously received bortezomib, an alkylator and daratumumab, 11 (92%) received lenalidomide, 10 (83%) received pomalidomide and 9 (75%) underwent prior autologous transplant. Seven patients (58%) had Eastern cooperative oncology group performance status (ECOG-PS) of at least 2 at BLM initiation and half of the patients had AL Mayo stage of at least 3a. Most patients (10/12) received BLM as a single agent at 2.5mg/kg q3 weeks. The overall hematological response rate (ORR) to BLM was 75% (9/12), including 5 patients with complete response, 3 with very good partial response, and 1 with partial response (Figure 1). Detailed biomarker-based evaluation of organ responses was missing in many patients, yet, of 4 evaluable patients, 3 cardiac responses were observed. An additional patient had marked clinical improvement of heart failure. Four renal responses (out of 5 evaluable patients) and 2 hepatic responses (out of 2 evaluable) were also observed. With a median follow-up of 13.0 months (m) from initiation of BLM therapy (range 1.1-33.8m), the median EFS was 22.3m and the median OS was 28.8m. At data cutoff 6/12 (50%) were still on therapy, 9/12 patients (75%) were alive, all 3 deaths were due to heart disease. Seven patients (58%) had at least one grade 3 toxicity, included mostly infections/corneal toxicity. Apart from one event of grade 3 thrombocytopenia, there were no grade ≥3 hematological toxicities. No grade 4/5 toxicities were observed. Most patients (10/12, 83%) had corneal toxicity (6 patients- grade 1-2; 4 patients- grade 3), and dose reductions/delays were frequent (4/12 and 6/12, respectively). However, 7/10 patients with corneal toxicity improved overtime, no permanent visual disabilities were observed and only one patient stopped BLM due to keratopathy. Discussion: While BLM provides an ORR of 30-45% in triple-refractory MM patients, it might have a greater efficacy in AL patients. The ORR in our heavily pre-treated AL patients, as well as in other studies (2 small, retrospective + preliminary results of the EMN27 prospective study (Kastritis, EHA conference 2023) approached 60-83%, and the EFS was also encouraging. This difference may be attributed to the lower burden of disease in AL compared to MM. Alternatively, AL plasma cells may be more sensitive to BLM, in a mechanism that still merits further exploration. Corneal toxicity was similar to what was seen in MM, and overall manageable. Hematological toxicity was significantly milder than that observed in MM, probably related to the better marrow reserve in AL. Conclusions: BLM, being an off-the shelf immune therapy, with acceptable toxicity even in frail patients, can be a valuable option in AL, with a high ORR, and a signal for durable responses and high-quality organ responses in these patients.

Shenshu Dingchuan Decoction Enhances Clinical Benefits of Budesonide/Formoterol in Chronic Bronchial Asthma Patients

We have evaluated the clinical benefits of Shenshu Dingchuan decoction in chronic bronchial asthma patients treated with budesonide or formoterol. To this end, chronic bronchial asthma patients were divided into two groups and treated with budesonide or formoterol alone (the control group) or budesonide or formoterol plus Shenshu Dingchuan decoction (the treatment group). Shenshu Dingchuan decoction combined with budesonide formoterol decreased traditional Chinese medicine syndrome scores, elevated forced expiratory volume in one second, forced vital capacity, and forced expiratory volume in one second/forced vital capacity levels, decreased fractional exhaust nitric oxide and total immunoglobulin E levels, and the elevated total effective rate after treatment. In conclusion, these observed changes reflect a marked clinical improvement in lung function.

High-resolution MR neurography follow-up of SARS-CoV-2 vaccination-associated neuralgic amyotrophy.

Little is known about the value of high-resolution follow-up imaging in patients with neuralgic amyotrophy (NA) and the question of the best treatment algorithm remains unclear. Three patients (one female, two male) with the clinical presentation of SARS-CoV-2-vaccination-associated NA underwent initial magnetic resonance neurography (MRN) imaging and follow-up examinations. All patients showed a marked clinical improvement, independent of treatment, including an almost full recovery of motor function over the course of 8-12 months which was accurately mirrored by imaging findings on MRN. MRN imaging is a valuable tool for monitoring the further clinical course of patients suffering from vaccination-associated NA.