High-dose Therapy Research Articles

Advanced treatment-resistant ovarian germ cell tumor (yolk sac tumor) with successful fertility realization 20 years after combined treatment: a case report

Background. Yolk sac tumors (YST) are classified as rare malignant germ cell tumors of the ovaries, most commonly found in young patients interested in preserving fertility. YST is characterized by large size, predominantly unilateral involvement, and increased production of alpha-fetoprotein, which can be used as an important diagnostic criterion for this condition. Among all germ cell tumors, YST has the least favorable prognosis. The primary goals of YST treatment are not only to improve prognosis and quality of life but also to enable the patient to fulfill her reproductive plans in the future.Description of the clinical case. We present a clinical case of an aggressive course of yolk sac tumor in the ovary of a 15-year-old girl, requiring multiple surgeries, repeated courses of high-dose drug therapy, and bone marrow transplantation.Conclusion. This is a rare case of YST with successful preservation of reproductive function due to modern medical technologies despite aggressive treatment.

Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review

Background: Spontaneous intracranial hypotension (SIH) is a rare and frequently misdiagnosed disorder characterized by a low volume of cerebrospinal fluid (CSF) caused by the leakage of CSF through the spinal dural membrane. Patients with Marfan Syndrome (MS) and other connective tissue disorders are at an increased risk for dural ectasia, which may predispose them to spontaneous CSF leaks due to the structural weakness of their dural membranes. The management of SIH in MS patients is debated. Conservative measures, an epidural blood patch (EBP), and surgical treatments are the options generally provided. Methods: Herein, we report on the case of a 52-year-old female affected by MS, genetically confirmed, with a two-month history of sudden-onset, “thunderclap” headache, worsened in an upright position and horizontal diplopia. A Computed Tomography (CT) scan of the brain showed a bilateral chronic subdural hematoma, slit ventricles, and a caudal descent of the brainstem without overt tonsillar herniation. The Magnetic Resonance Imaging (MRI) scan of the whole spine revealed dural ectasia in the lumbosacral area and presacral perineural cyst without extradural CSF collection. The case was successfully managed with bed rest and high-dose corticosteroid therapy. Then, we discuss the pertinent literature, consisting of 25 papers dealing with the treatment of SIH in patients affected by MS. Results: The literature review yielded 25 papers dealing with SIH management in patients with MS, including 28 patients overall; 21 patients underwent EBP, of whom 7 patients had multiple procedures. Overall, in 23 cases (82%), the symptoms improved. In three cases, the patients were managed conservatively with bed rest. In three of these cases, there was an improvement. In one case, the surgical fenestration of two lumbar intradural spinal meningeal cysts was performed and the patient improved after the procedure. Our patient underwent 15 days of steroid therapy (dexamethasone iv 12 mg/day for 7 days, then reduced to 4 mg/day) and intravenous hydration (Ringer lactate 1500 mL/day). In ten days, the symptoms disappeared. At the 6-month follow-up, the patient was in good clinical condition, and a CT scan showed an almost complete regression of the bilateral subdural hematoma. Conclusions: The management of SIH in MS patients is still challenging. Patients with connective tissue disorders such as MS are at an increased risk for SIH. Few studies have assessed the management of these patients and different strategies. Our case and the available literature provide further data for this type of case.

Invasive Aspergillosis with Cavernous Sinus Thrombosis Following High-Dose Corticosteroid Therapy: A Challenging Case of Rhino-Orbital-Cerebral Mycosis

Invasive aspergillosis is a rare but severe fungal infection primarily affecting immunocompromised individuals. The Coronavirus Disease-2019 (COVID-19) pandemic has introduced new complexities in managing aspergillosis due to the widespread use of corticosteroids for treating COVID-19-related respiratory distress, which can increase susceptibility to fungal infections. Here, we present a challenging case of progressive cerebral aspergillosis complicated by cavernous sinus thrombosis (CST) in a 67-year-old male with a history of COVID-19. The patient, initially misdiagnosed with temporal arteritis, received pulse corticosteroid therapy twice before presenting with persistent left-sided headaches and vision loss. Cranial imaging revealed findings consistent with fungal sinusitis, Tolosa–Hunt syndrome, and orbital pseudotumor, which progressed despite initial antifungal therapy. Subsequent magnetic resonance imaging indicated an invasive mass extending into the left cavernous sinus and other intracranial structures, raising suspicion of aspergillosis. A transsphenoidal biopsy confirmed Aspergillus infection, leading to voriconazole therapy. Despite aggressive treatment, follow-up imaging revealed significant progression, with extension to the right frontal region and left cavernous sinus. The patient then developed visual impairment in the right eye and was diagnosed with CST secondary to fungal sinusitis. Management included a combination of systemic antifungals and antibiotics; however, the patient declined surgical intervention. This case underscores the diagnostic challenges and rapid progression associated with cerebral aspergillosis in post-COVID-19 patients treated with corticosteroids. This report highlights the need for heightened clinical suspicion and prompt, targeted interventions in similar cases to improve patient outcomes. Further research is required to understand the optimal management of invasive fungal infections.

Mutations in human cytymegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) UL97 gene lead to increase in viremia duration and poor antiviral response in recipients of allogeneic hematopoietic stem cells.

Human cytomegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) (HCMV) is one of the most commonly detected viruses in recipients of allogeneic hematopoietic stem cell (allo-HSCT) transplants. However, the emergence of resistance to antiviral drugs such as ganciclovir (GCV) poses a challenge in managing these patients. This study aims to investigate the prevalence and impact of mutations in the HCMV UL97 gene associated with resistance to GCV on the course of infection among allo-HSCT patients. The study examined the association between UL97 mutations and the clinical course of HCMV infection in allo-HSCT patients. Genetic sequencing was performed to identify mutations, and their impact on viral replication and resistance to GCV was assessed. Six mutations were identified (D490A, T502A, C592G, C592F, E596G, C603W). C592G, C592F, E596G, and C603W are associated with resistance to antiviral drugs, while D490A and T502A described for the first time. When comparing patients with wild-type and those carrying the mutant variant, several parameters of peripheral blood were significantly lower in the former group. The median time to peak viral load following allo-HSCT, duration of viremia, and rate of virological response to high-dose therapy also differed significantly between the two groups. It was shown that approximately one third (4 out of 14) of allogeneic stem cell transplant recipients had mutations associated with resistance to GCV. Patients carrying the mutant variant of HCMV had longer viremia and took longer to achieve a negative virological test result after starting high-dose therapy. Performing genotyping may help make more evidence-based therapeutic decisions.

Resting state functional magnetic resonance imaging in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hemopoietic stem cell transplantation

BACKGROUND: Multiple sclerosis is a chronic autoimmune disease characterized by multifocal foci of demyelination in the central nervous system, usually affecting people of working age. The disease causes damage to the blood-brain barrier, the development of multifocal inflammation, destruction of the myelin sheath of axons and various degrees of damage. It is clinically manifested by restriction of motor activity, visual acuity, as well as other symptoms leading to loss of performance and disability of the patient. AIM: determination of changes in the functional connectivity of brain neural networks in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation by performing functional magnetic resonance imaging at rest. MATERIALS AND METHODS: The data of functional magnetic resonance imaging of patients with multiple sclerosis were analyzed in dynamics before and after the use of high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation. The study involved 25 patients with a verified diagnosis of multiple sclerosis. Each underwent complex magnetic resonance imaging at two time points (before and after high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation) with a difference of 12 months, which included structural magnetic resonance imaging - in order to exclude the presence of pathological foci in the brain (in addition to foci of multiple sclerosis) and functional magnetic resonance imaging.-resonance imaging at rest — to assess functional connectivity. Also, according to the method generally accepted in classical neurology, a clinical neurological examination was performed. RESULTS: At the stage of comparing data on the two groups obtained using functional magnetic resonance imaging at rest, changes in functional activity were detected in various parts of the brain, presumably responsible for clinical differences in the studied groups. CONCLUSION: Currently, the links between brain structures and morphological changes that cause cognitive impairment in multiple sclerosis are being studied. To predict the progression of the disease, the development of biomarkers, including those based on functional magnetic resonance imaging, is required. Evaluating changes in the functional connectivity of brain neural networks can help personalize therapeutic and rehabilitation approaches.

A modified intensive, comprehensive aphasia program (mICAP) has better reported outcomes than usual care: a randomized controlled trial

ABSTRACT Background Intensive Comprehensive Aphasia Programs (ICAPs) are a new model of service delivery that show promising pre-post outcomes but have yet to be compared with usual care. Aim To compare the clinical effectiveness of a modified Intensive Comprehensive Aphasia Program (mICAP) to usual care in a parallel two arm study utilizing stratified block randomisation. Methods & Procedures Participants were a referred sample with post stroke aphasia from ten local speech pathology departments. Assessments were completed prior to, immediately after, and follow up at 3 months after the mICAP. While 269 participants with aphasia were approached for the study, only 52 were eligible to be randomised with 113 participants approached not meeting selection criteria and 99 of eligible participants declining to participate. Block randomization was based on matched moderate/mild versus severe aphasia pairs. Three of the 26 mICAP participants withdrew. In the experimental arm of the mICAP (the LIFT program), participants with aphasia and their family attended goal directed tailored therapy three times weekly for 8 weeks. Therapy included 14 hours each of impairment therapy, functional communication therapy, and computer therapy and 7 hours of group therapy and a challenge task. The main outcome measures were the self-reported Assessment for Living with Aphasia (ALA) and Content Information Units (#CIU’s) in connected speech. Outcomes & Results Linear Mixed Modelling was completed on the remaining 42 participants’ data and found a significant benefit for the mICAP on the ALA Total score (p= .014; 95% CI= −21.48- −2.57) ALA Aphasia domain (p = .027; 95% CI= −3.23 - −0.203), ALA Environment domain (p = .017; 95% CI= −4.70 - −0.493) immediately post intervention with maintenance of effects for the ALA Aphasia domain in the follow up period (p = .014; 95% CI= −3.64 - −0.438). Family members in the mICAP reported significant reduction in caregiving burden in the follow up period (p= .017; CI= −14.12 - −1.52.). There were no significant differences on the other main outcome measure of Content Information Units (95% CI= −34.94 – 55.15). Conclusions For those suitable and interested, the mICAP was more beneficial than usual care for participants with aphasia and their family members. However, lack of significant differences in discourse and other language functions, suggests that individual elements of mICAPs and their evaluation require review. Based on these results, the LIFT program has been refined to become the Comprehensive High-dose Aphasia Therapy (CHAT) program.

Case report: Rapid clinical improvement of anti-HMGCR immune-mediated necrotizing myopathy treated with efgartigimod

Immune-mediated necrotizing myopathy (IMNM) with anti-HMGCR antibody positivity is characterized by proximal extremity weakness, increased creatine kinase, and extensive muscle edema. There is an urgent need to find more appropriate treatment options for anti-HMGCR IMNM patients who do not respond well to conventional therapy in the acute phase. With the advent of targeted biologics, new treatment options are available. We report on a 66-year-old anti-HMGCR IMNM patient who initially presented with a 1-month history of progressive proximal extremity weakness and dysphagia with markedly elevated creatine kinase. The patient did not respond to conventional high-dose glucocorticoid and intravenous immunoglobulin therapy, and his symptoms rapidly deteriorated over the 2 weeks after this treatment, with worsening limb weakness that prevented walking, marked proximal muscle atrophy, and weight loss. After one cycle (four infusions) of efgartigimod, the patient’s symptoms improved markedly and he has since (for several months) remained in a good clinical state.

Clinical Impact of High-dose Esomeprazole-amoxicillin Dual Therapy as Rescue Treatment for Helicobacter pylori Infection: A Prospective, Multicenter, Randomized Trial.

This study aimed to compare the effectiveness and safety of high-dose dual therapy (HDDT) using esomeprazole and amoxicillin to furazolidone-based quadruple therapy (FBQT) in treating nonresponsive patients with Helicobacter pylori (H. pylori) infection. A total of 209 patients with H. pylori infection, who had previously received ineffective treatment and visited an outpatient clinic, were randomly assigned to either the HDDT or FBQT groups. All patients underwent a 14-day treatment regimen, and the success rates of H. pylori eradication and safety of the treatment regimens were assessed 4 weeks posttreatment. Following the 14-day treatment period, the intention-to-treat (ITT) analysis revealed eradication rates of 93.6% for HDDT and 86.9% for FBQT. In the per-protocol (PP) analysis, eradication rates were 94.5% for HDDT and 88.7% for FBQT. No significant difference in eradication rates was observed between the two groups. HDDT exhibited significantly lower rates of adverse reactions (9.1% in ITT and 9.2% in PP) compared with FBQT (58.6% in ITT and 59.8% in PP). Multivariate analysis identified interval time, alkaline phosphatase, and serum creatinine level as factors influencing the eradication rate. The area under the receiver operating curve of the interval time between the FBQT group and the HDDT group and the success of H. pylori eradication were 0.622 and 0.578, respectively. The optimal salvage treatment intervals were determined as 6 months for FBQT and 1 year for HDDT. HDDT using high-dose esomeprazole and amoxicillin demonstrated efficacy in treating H. pylori infection, with the added benefits of reduced side effects and improved medication compliance compared with FBQT. HDDT can be considered a rescue treatment option when other methods fail, with treatment intervals optimized accordingly.

Long-term effect of postoperative radioactive iodine therapy on parathyroid function in patients with differentiated thyroid cancer.

The study aimed to assess the impact of postoperative radioactive iodine (RAI) therapy on parathyroid function in patients who underwent total or subtotal thyroidectomy for differentiated thyroid cancer (DTC). Data from 150 patients treated with RAI for DTC and 76 patients with low-risk DTC not receiving RAI were retrospectively analyzed. Clinical characteristics, preoperative and 1-month postoperative biochemical parameters, and adjusted calcium, phosphorus, parathyroid hormone (PTH), and 25-hydroxyvitamin D3 (25-OH-D) levels at 3months, 1year, 3years, and 5years post-RAI (or in the low-risk group) were recorded. A total of 226 DTC patients were included in the study (80.5% female, mean age 42.7 ± 13.2years). Total thyroidectomy was performed in 97.3% (n = 220) of patients, with central lymph node dissection (CLND) in 41.6% (n = 94). No significant preoperative differences in PTH, aCa, P, Mg, or 25-hydroxyvitamin D3 levels were observed. However, patients receiving ≥ 3.7GBq (or 100mCi) RAI (n = 70) had lower calcium and PTH levels at the end of the first year following RAI treatment (p = 0.048, p = 0.032). The non-RAI group showed significantly higher calcium levels at one month postoperatively (p = 0.031) and lower rates of CLND and neck dissection. No significant differences in biochemical parameters were found at the five-year follow-up, except for one patient who developed normocalcemic hyperparathyroidism after RAI. High-dose RAI therapy may lead to transient decreases in calcium and PTH levels in the early post-treatment period. However, long-term parathyroid function appears to remain unaffected in DTC patients, regardless of the RAI dose administered. Nonetheless, close monitoring of calcium and PTH levels is recommended, particularly in the early post-treatment period, to promptly manage any potential transient hypoparathyroidism.

Analysis of the quality of life in patients with multiple sclerosis within 3 years after high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation

Introduction. To date, data have been accumulated indicating the high effectiveness of the HDIT-AHSCT and the possibility of preserving and improving the quality of life of patients after its application.The objective was to analyze the dynamics of quality of life using standardized assessment tools in patients with MS for 3 years after the use of HDIT-AHSCT, who participated in the program of clinical approbation of the method.Methods and materials. The single-center observational study included 21 patients (10 women, 11 men) with a reliable diagnosis of MS, who underwent HDIT-AHSCT at the Pavlov First Saint Petersburg State Medical Universityin accordance with the protocol of clinical approbation. Distribution by type of MS course: remitting (RMS) 16 (76.2 %), secondary progressive (SPMS) 4 (19 %), primary progressive (PPMS) 1 patient (4.8 %). The assessment of quality of life (SF-36, FAMS, CSP-MS42, HADS) and severity of disability (EDSS) in all patients was performed before, 12 and 36 months after HDIT-AHSCT.Results. Three years after the HDIT-AHSCT, a significant decrease in weakness, feelings of constant fatigue and rapid fatigue during exertion was recorded. The level of anxiety decreased in more than 50 % of patients. A direct relationship between the dynamics of clinical characteristics and the data of the scales of the SF-36 questionnaire was revealed; at the same time, after 36 months, an improvement in all parameters of the scale was noted.Conclusion. The assessment of the indicators of the quality of life questionnaires allows us to confirm the effectiveness and significance of therapy not only from the point of view of objective clinical and radiation parameters necessary for the evidence base of the treatment method, but also from the patient’s position, which in conditions of a chronic progressive process is an integral factor for the appointment of therapeutic intervention.

High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation in crohn disease: literature review

The literature review presents the current status of the method of high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation in the treatment of Crohn’s disease.In recent decades, there has been an increase in Crohn’s disease. The frequency of CD the response rate to biopreparations ranges from 20 to 50%, up to 80% of patients need surgical treatment. Due to the insufficient effectiveness of therapy, an active research is underway for new therapeutic opportunities, one of which is the method of HDIT-AHSCT. In the Russian Federation, there are data on the use of mesenchymal stem cells for the treatment of CD, there are no studies on the use of HDIT-AHSCT in IBD. According to the EBMT register in the period from 1994 to 2023. more than 4000 HDIT-AHSCT were performed in patients with autoimmune diseases, the proportion of CD was 6.13% of all protocols. The HDIT-AHSCT procedure consists of the following stages: mobilization of autologous HSCs, apheresis and cryopreservation of HSCs, immunoablative conditioning and infusion of HSCs. Most of the publications on the use of HDIT-AHSCT in CD were not universal in the selection and management of patients. Currently, there is the only one completed RCT on the use of HDIT-AHSCT in CD, the results of which have not received a definite outcome. However, for a cohort of patients with refractory CD, it is necessary to consider the possibility of using this method. The review presents the indications and selection criteria for the HDIT-AHSCT protocol. Further studies of the HDIT-AHSCT in CD will help expand the therapeutic opportunities of treating patients with refractory CD to standard and biological therapy.

Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS

IntroductionHigh-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the...

Successful Adjunctive Treatment of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) with High-Dose Intravenous Immunoglobulin Therapy (IVIG).

Purpose: The management of bilateral diffuse uveal melanocytic proliferation is controversial, with most earlier reports advocating for plasmapheresis. Here, we report a case of bilateral diffuse uveal melanocytic proliferation secondary to gastric adenocarcinoma that was successfully treated with adjunctive intravenous immunoglobulin, using a loading dose followed by a treat-and-extend strategy. Methods: Clinical case report with 3 years of follow-up including serial ophthalmologic examinations. Functional assessments included visual acuity and subjective visual complaints. Periodic anatomic assessments were performed including serial optical coherence tomography, ultra-widefield fundus imaging, multimodal angiography, and ophthalmic ultrasound. Results: A 75-year-old man presented with a 6-month history of blurry vision and difficulty with dark and light adaptation in both eyes. A diagnosis of bilateral diffuse uveal melanocytic proliferation was established based on clinical findings and subsequent discovery of an underlying gastric malignancy; the diagnosis of a paraneoplastic syndrome was further substantiated by documentation of cancer-associated antiretinal antibodies and serum reactivity against human retina by immunohistochemistry. Treatment with high-dose (2 g/kg) intravenous immunoglobulin was initiated with biweekly, followed by monthly, then q2-3 monthly dosing intervals. Meanwhile, the patient received surgical resection and systemic chemotherapy resulting in complete radiographic remission of the primary cancer. Over the course of 3 years, the patient has demonstrated clinically significant improvements in visual acuity and subjective visual function. Rapid and sustained anatomic improvements were observed in serous retinopathy and choroidal thickness. Conclusion: Intravenous immunoglobulin may be a viable adjunctive treatment option for some patients with bilateral diffuse uveal melanocytic proliferation.

The initial high-dose versus maintenance-dose anticoagulation therapy with direct oral anticoagulants for cancer-associated venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background/Introduction Initial high-dose anticoagulation therapy with rivaroxaban and apixaban has been a standard treatment for venous thromboembolism (VTE), although there could be concerns of an increased risk of bleeding events especially among high bleeding-risk patients including those with active cancer. Purpose The present study aimed to evaluate the clinical outcome of initial high-dose anticoagulation therapy comparing to maintenance-dose anticoagulation therapy in patients with cancer-associated VTE using propensity score-matching analysis. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Among 1507 patients with cancer-associated VTE, we evaluated 180-day clinical outcomes before discontinuation of anticoagulation therapy using a 1:1 propensity score-matching model with 21 risk-adjusting variables Results After the propensity score-matching, we enrolled 324 patients with initial high-dose anticoagulation therapy and 324 patients with initial maintenance dose anticoagulation therapy. Of patients with initial high-dose anticoagulation therapy, rivaroxaban and apixaban were administered in 198 and 126 patients, respectively. Of those with initial maintenance-dose anticoagulation therapy, rivaroxaban, apixaban, and edoxaban were administered in 34, 46 and 244 patients, respectively. The median durations of initial high-dose anticoagulation therapy were 18 [IQR: 15-21] days for rivaroxaban and 7 [IQR: 7-7] days for apixaban. In the current study population, the mean age was 67±12 years, 346 were women, and the mean body weight was 58±12 kg. There was no significant difference in the distribution of gastrointestinal cancer such as stomach and colorectal cancer between the 2 groups (4.6% vs. 4.9%, P=1.0, 8.3% vs. 11.4%, P=0.22). The cumulative 180-day incidence of discontinuation of anticoagulation was not significantly different between the 2 groups (27.8% vs. 30.5%, P=0.50). There were no significant differences in the cumulative 180-day incidences of recurrent VTE (3.1% vs. 1.0%, P=0.08), nor major bleeding (8.1% vs. 7.0%, P=0.66), nor all-cause death (25.1% vs. 21.6%, P=0.33) between the 2 groups. There were also no significant differences in the cumulative 180-day incidences of all clinically relevant bleeding (14.9% vs. 13.3%, P=0.72), gastrointestinal bleeding (8.4% vs. 5.4%, P=0.15), nor major gastrointestinal bleeding (5.4% vs. 2.7%, P=0.10). Conclusions There was no signal of an increased risk of recurrent VTE in the initial maintenance-dose anticoagulation therapy. Considering a numerically slightly higher incidence of gastrointestinal bleeding in the initial high-dose anticoagulation therapy for cancer-associated VTE, the initial maintenance-dose anticoagulation therapy could be a potential treatment option for selected patients including patients at a high risk of gastrointestinal bleeding.Study flow chartResults

Ischemic Stroke Unveiling Takayasu Arteritis Complicated by Coronary Arteritis: A Case Study

Context: We present the case of a 38-year-old woman admitted for ischemic stroke. Etiological evaluation revealed halo signs on transesophageal echocardiography (TEE), suggestive of Takayasu arteritis. Case Presentation: During hospitalization, the patient developed chest pain, elevated troponin levels (300 ng/L), left ventricular hypokinesia on echocardiography, and T-wave inversions on electrocardiogram (ECG), indicating coronary arteritis. High-dose corticosteroid therapy led to rapid improvement in inflammatory markers. The diagnosis of Takayasu arteritis was confirmed based on the American College of Rheumatology (ACR) criteria. This case highlights the variable clinical presentation of Takayasu arteritis, including coronary involvement, and underscores the effectiveness of corticosteroid therapy in controlling inflammation. Conclusion: Takayasu arteritis, though rare, can manifest with ischemic stroke and coronary arteritis. Prompt recognition and corticosteroid treatment are essential in managing this potentially life-threatening condition.

Risk of recurrent ischaemic events in ACS patients with baseline LDL-C below guideline-recommended thresholds: insights from the prospective SPUM-ACS study

Abstract Introduction The 2023 European Society of Cardiology (ESC) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with acute coronary syndromes (ACS), adding ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to achieve recommended target goals (LDL-C<55 mg/dL). Purpose This population-based, real-world study aimed to examine cardiovascular (CV) events in ACS patients with baseline LDL-C levels below current guideline thresholds. Methods ACS patients admitted to four Swiss University Hospitals and enrolled in the multicenter SPUM registry (NCT 01000701) between 2009 and 2017 were followed prospectively until 1 year. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE); i.e., non-fatal stroke, myocardial infarction (MI), and death) at 1 year. Multivariable-adjusted Cox proportional hazard regression models were fit to estimate ischaemic risk among those with LDL-C<55 mg/dL. Results Out of 4’787 ACS patients, 226 patients (4.7%) had baseline LDL-C<55 mg/dL. These patients were older (69.7±11.3 vs 63.4±12.4, p<0.001), more frequently male (20.8%vs 15.9%, p<0.001), had more often traditional CV risk factors (all p<0.001) and were more likely to have a complex history of CV disease, such as previous MI (37.2% vs 10.9%, p<0.001), prior percutaneous (47.8% vs 13.2%, p<0.001) or surgical (15.0% vs 3.5%, p<0.001) coronary revascularization. Inflammatory biomarkers were also higher (hs-CRP, 30.1±63.6 vs 10.7±25.8 mg/L), with most patients being on high-dose statin therapy (82.4% vs 38.7%, p<0.001). At 1 year, patients with LDL-C<55 mg/dL had a higher rate of MACCE (16.4% vs 7.0%, p<0.001), with individual components of the primary endpoint occurring more frequently among these patients (all p<0.001), except for a numerical increase in CE (2.7% vs 1.7%, p=n.s.), as shown in the figure (Panel A). The enhanced MACCE risk persisted after adjustment for potential differences in baseline characteristics, with a 51% (adj. HR 1.51, CI95% 1.05-2.17, p=0.026) increase in MACCE (Panel B). Diabetes, low eGFR and high hs-CRP levels remained independent predictors of MACCE in patients with low baseline LDL-C (all p<0.001). Conclusions Our real-world data confirm that even ACS-patients reaching currently recommended LDL-C thresholds have a substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to further reduce CV risk.Event-risk according to baseline LDL-C

The high-dose statin treatment reduces neutrophil extracellular traps formation in patients with coronary artery disease

Abstract Background Neutrophil extracellular traps formation (NETosis) is currently considered as an important mediator in atherosclerosis and atherothrombosis. However, the impact of high-dose statin treatment, as potent cholesterol-lowering agents with pleiotropic effects, on NETosis in coronary artery disease (CAD) has been poorly described. Purpose We sought to assess whether in CAD patients the recommended statin treatment intensification is associated with changes in NETs-related markers and if such changes can alter fibrin clot properties. Methods 130 patients with advanced CAD, who did not achieve the target low-density lipoprotein cholesterol (LDL-C) were included. Before and at least 6 months after initiation of high-dose statin therapy (rosuvastatin 40 mg/d or atorvastatin 80 mg/d) citrullinated histone H3 (H3cit), myeloperoxidase (MPO) and neutrophil elastase (NE) as markers associated with NETosis were assessed in relation to C-reactive protein (CRP), thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. Results At baseline, NETosis did not differ depending on gender and cardiovascular risk factors but H3cit correlated with MPO (R=0.543, P<0.001) and CRP (R=0.540, P<0.001). All NETosis markers were inversely correlated with Ks. Median LDL-C reduction by 25% (P<0.001) on high-dose statin treatment was independent from H3cit reduction by 30.4%, MPO by 28.1%, and NE by 25.5% (in all P<0.001, Figure 1). The ΔH3cit and ΔMPO, but not ΔNE were associated with ΔCRP (R=0.855, P<0.001; R=0.250, P=0.004, respectively), Δthrombin activatable fibrinolysis inhibitor (TAFI) (R=0.385, P<0.001; R=0.245, P=0.005), and inversely with ΔKs (R=-0.315, P<0.001; R=-0.395, P=0.001). In multivariable analysis the H3cit decrease was independently associated with ΔCRP (β=0.771, P<0.001), ΔTAFI (β=0.125, P=0.013) and Δfibrinogen (β=0.106, P=0.034) but not with ΔLDL-C. Conclusions As has been shown for the first time high-dose statin treatment reduces levels of NETs-related markers, regardless of lipid-lowering effect in CAD patients.

Advantages of single high-dose radiation therapy compared with conventional fractionated radiation therapy in overcoming radioresistance

Background Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms. Methods Radioresistant cell lines were previously established by exposing SK-BR-3 and MCF-7 cells to 48 Gy and 70 Gy of radiation, respectively, in multiple fractions. We compared the effects of 2 Gy × 5 and 7 Gy × 1 fractions on these cells using clonogenic survival assays and western blot analysis. In vivo antitumor effects were assessed in SR tumor-bearing BALB/c mice irradiated with either 2 Gy × 5 or 7 Gy × 1 fractions. Results 7 Gy x1 was more efficient at killing radioresistant breast cancer cells than 2 Gy x5. Furthermore, the 7 Gy x1 fraction produced higher levels of reactive oxygen species (ROS) and decreased the expression of radioresistance factors such as p-STAT3, ACSL4, FOXM1, RAD51, Bcl-xL, and survivin. Consistent with the in vitro studies, the 7 Gy × 1 fraction also showed superior antitumor effects in SR tumor-bearing BALB/c mice. Conclusions Single high-dose RT offers superior advantages over conventional fractionated RT in regard to overcoming radioresistance, supporting its potential as a promising treatment for recurrent tumors.

Multicenter randomized phase III study of high-dose therapy with autologous stem cell transplantation versus observation for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy (JCOG2210, TRANSFER study).

Patients with peripheral T-cell lymphoma demonstrated a poor prognosis after obtaining a complete response with induction treatment compared to those with B-cell lymphoma. Once it relapsed, curative treatment is frequently limited to invasive treatments with significant treatment-related mortality, including allogeneic stem cell transplantation. The limitations of these treatment choices indicate the necessity for developing optimal consolidation therapies to prevent relapse. This multicenter randomized phase III trial aims to confirm the superiority of the high-dose therapy with autologous stem cell transplantation over observation alone in terms of progression-free survival for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy. A total of 140 patients from 52 hospitals will be enrolled in Japan over 5.5years. This trial is registered in the Japan Registry of Clinical Trials as jRCTs031240169 (https://jrct.niph.go.jp/latest-detail/jRCTs031240169).

Treatment of mildandmoderateforms of ulcerativecolitis: the possibilities of mesalazine

The article indicates the specific niche and principles for choosing mesalazine formulations, and the selection of a dose for the treatment of mild to moderate extensive (left-sided and total) ulcerative colitis (UC). It doesn’t consider any approaches to the treatment of more severe UC or distal UC (proctitis). The current concepts on the use of 5-aminosalicylic acid (5-ASA) formulations to induce and maintain remission in mild to moderate active UC are discussed. The principles for drug administration and a comparative analysis of domestic and international mesalazine dosing recommendations are provided. The guidelines place special emphasis on the importance of high-dose mesalazine therapy (≥4 g/day), which allows to achieve the targets set by the Treat-to-target (T2T) strategy and to reach the clinical and endoscopic remission. The evidence from meta-analyses and comparative studies demonstrating the same efficacy of different forms of mesalazine in the treatment of UC are presented. Attention is drawn to the choice of the optimal drug with enteric coating that consists of two types of Eudragit (Eudragit L and Eudragit S) in contrast to mesalazine formulations with one and the same type of coating (only L or only S). The double Eudragit (L + S) pH-dependent coating of mesalazine tablets dissolves in the terminal ileum, cecum and partially in the right half of the colon at pH 6–7.5, while formulations coated with only L or S dissolve at a narrower pH range. The clinical efficacy of mesalazine directly depends on its intraluminal concentration that is determined by the amount of the released drug according to the pH level in the intestinal lumen. The double Eudragit coating allows to cover the entire pH range in the ileum and colon. The paper presents evidence from the domestic clinical practice that confirms the Cochrane meta-analysis statements on the comparable efficacy of different mesalazine formulations concerning the targets to reach remission and reduce the level of fecal calprotectin. In addition, a high incidence of clinical remissions (more than 80% at 48 weeks of treatment) on double coated (L + S) mesalazine is demonstrated.