High-dose Therapy Research Articles

Retrobulbar Optic Neuritis after COVID-19 Infection

Purpose: To report a case of retrobulbar optic neuritis after COVID-19 infection.Case summary: A 20-year-old Korean man, without any previous relevant medical history, presented with sudden blurred vision in the left eye that began 6 days after a COVID-19 infection. At his initial visit, the best-corrected visual acuity in the left eye was counting fingers at 30 cm. The pupil showed a grade 2 relative afferent pupillary defect. The fundus exam was normal in both eyes. In the visual evoked potential (VEP) exam, the P100 amplitude of the left eye was decreased and delayed. Orbit magnetic resonance imaging showed asymmetric enlargement and mild enhancement in the left optic nerve. No other lesions were observed around the optic nerve. Steroid pulse therapy was started after a diagnosis of retrobulbar optic neuritis. After 1 month, the patient’s visual acuity had improved to 1.0 in the left eye. The relative afferent pupillary defect and visual field defect disappeared. On VEP, the P100 amplitude recovered, and the delay disappeared.Conclusions: Retrobulbar optic neuritis is a possible neuro-ophthalmological complication of COVID-19 infection. In such cases, high-dose steroid pulse therapy may be helpful, as in the treatment of other forms of optic neuritis.

Primary treatment failure in acute retinal necrosis - A comprehensive review.

Acute retinal necrosis (ARN) is a sight-threatening ophthalmic emergency that requires aggressive treatment to prevent irreversible vision loss. However, primary treatment failure (PTF), where the initial antiviral therapy is ineffective, is a common challenge in ARN management. This comprehensive review examines PTF in ARN, drawing insights from a systematic literature search spanning 1997 to 2022, which identified 35 relevant cases from 23 reports. The analysis focuses on drug resistance patterns, alternative antiviral agents, combination therapies, and emerging treatments. Potential causes of drug resistance, including host factors, viral mutations, and drug-related considerations, are elucidated. Alternative agents such as foscarnet, cidofovir, and brivudine, as well as combination approaches involving systemic and intravitreal administration, high-dose therapy, judicious use of steroids, and potential treatment-related complications, are discussed. The review also highlights emerging therapies, including vaccines, monoclonal antibodies, and natural compounds, offering insights into future directions for addressing this challenging condition.

Refractory acute retinal necrosis presenting as peripapillary choroiditis - A diagnostic and therapeutic challenge.

This report describes a challenging case of refractory acute retinal necrosis (ARN) with peripapillary choroiditis as the initial presenting sign. Imaging studies confirmed multifocal choroidal lesions and noted the novel sign of vertical hyper-reflective strips (VHRS) in the outer nuclear layer. Initial treatment with acyclovir and valacyclovir failed, and involvement of the other eye suggested a resistant variant of varicella zoster virus. High-dose oral famciclovir therapy resulted in rapid resolution of ARN in both eyes. This case highlights the rare occurrence of choroiditis, the novel finding of VHRS, and the potential utility of high-dose oral famciclovir in treating refractory ARN.

High-dose immunosuppressive therapy followed by haematopoietic stem cell transplantation as a method for the treatment of refractory forms of neuromyelitis optica spectrum disorder in children

High-dose immunosuppressive therapy followed by haematopoietic stem cell transplantation as a method for the treatment of refractory forms of neuromyelitis optica spectrum disorder in children

Monoclonal Anti-PCSK9 Antibodies: Real-World Data.

Background: Real-world data on the use of lipid-lowering therapy (LLT) in clinical practice show that about 80% of (very) high-cardiovascular (CV)-risk patients disregard the 2019 European Society of Cardiology (ESC) Guidelines' recommendations on dyslipidemias. The availability of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9mAb) should reduce this gap. Our aim was to provide data on PCSK9mAb use in clinical practice, investigating the achievement of the ESC Guidelines' recommendations in the real world. Methods: Between April 2018 and December 2022, patients who started on PCSK9mAb therapy (140 mg of evolocumab or 75 mg or 150 mg of alirocumab, subcutaneous injection every 2 weeks) were included in a prospective registry. Our cohort consisted of 256 patients: 95 (37.1%) were women (mean age: 65.43 ± 11.12 yrs), 53 (20.7%) were at high CV risk, and 203 (79.3%) were at very high CV risk. Results: After one year of PCSK9mAb treatment, nearly 60% of patients demonstrated full adherence to the ESC Guidelines' recommendations, defined as achieving at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C) levels along with reaching LDL-C target levels (≤55 and ≤70 mg/dL for very high and high risk, respectively). Concomitant high-dose statin therapy emerged as the primary predictor of LDL-C target attainment. Heterozygous familial hypercholesterolemia (HeFH), statin intolerance, and female gender were associated with a significant lower probability of achieving LDL-C target levels. Conclusions: Our analysis confirms that PCSK9mAb treatment is safe and effective, enabling 60% of our cohort to fully achieve the LDL-C guideline recommendations. The use of high-intensity statins emerged as a significant predictor of efficacy. Conversely, familial hypercholesterolemia and female gender were identified as predictors of therapeutic failure. Hence, it is crucial to address disparities in cardiovascular disease prevention between genders and to enhance strategies for managing elevated LDL-C in HeFH patients.

Early Toxicity and Efficacy of Four Different Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Patients With Lymphoma: Impact of Drug Shortages in a Resource-Constrained Country

High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.

Delayed Post-hypoxic Leukoencephalopathy after Carbon Monoxide Intoxication Improved by High-dose Steroid Treatment

Delayed post-hypoxic leukoencephalopathy (DHPL) is a demyelinating syndrome characterized by acute onset of neuropsychiatric symptoms within days to weeks following apparent recovery from coma after a period of prolonged cerebral hypo-oxygenation. The majority of DPHL cases are associated with carbon monoxide intoxication. There is no specific treatment, and the prognosis is usually poor. However, we present a case of DHPL patient with akinetic mutism, parkinsonism, stool and urine incontinence, and severe cognitive impairment improved after treatment with high-dose steroid therapy.

Glucocorticoid modulates oxidative and thermogenic function of rat brown adipose tissue and human brown adipocytes.

Chronic and excessive glucocorticoid (GC) exposure can cause Cushing's syndrome, resulting in fat accumulation in selected body areas. Particularly in the brown adipose tissue (BAT), GC acts negatively, resulting in whitening of the tissue. We hypothesized that dysregulation of microRNAs by GC could be an additional mechanism to explain its negative actions in BAT. Male Wistar rats were divided into two groups: (1) Control sham and (2) GC group that was administered dexamethasone 6.25 mg/200 μL via osmotic pump implantation over 28 days. After this period, the animals were euthanized and BAT tissue was properly stored. Human fat cells treated with dexamethasone were used to translate the experimental results found in animals to human biology. GC-treated rat BAT presented with large lipid droplets, severely impaired thermogenic activation, and reduced glucose uptake measured by 18F-FDG PET/CT. GC exposure induced a reduction in the mitochondrial OXPHOS system and oxygen consumption. MicroRNA profiling of BAT revealed five top-regulated microRNAs and among them miR-21-5p was the most significantly upregulated in GC-treated rats compared to the control group. Although upregulation of miR-21-5p in the tissue, differentiated primary brown adipocytes from GC-treated rats had decreased miR-21-5p levels compared to the control group. To translate these results to the clinic, human brown adipocytes were treated with dexamethasone and miR-21-5p inhibitor. In human brown cells, inhibition of miR-21-5p increased brown adipocyte differentiation and prevented GC-induced glucose uptake, resulting in a lower glycolysis rate. In conclusion, high-dose GC therapy significantly impacts brown adipose tissue function, with a notable association between glucose uptake and miR-21-5p.

Clinical and preclinical insights into high-dose ambroxol therapy for Gaucher disease type 2 and 3: A comprehensive systematic review

RationaleGaucher disease (GD), an autosomal recessive lysosomal storage disease, results from GBA1 variants causing glucocerebrosidase (GCase) deficiency. While enzyme replacement therapy (ERT) helps with systemic symptoms, neurological complications in GD2 and GD3 persist due to the blood-brain-barrier (BBB) limiting ERT efficacy. Ambroxol, a BBB-permeable chaperone, enhances GCase activity. Our review explores high-dose ambroxol's therapeutic potential, both preclinical and clinical, in GD2 and GD3. MethodsPubMed was searched for studies published before March 2023, including clinical, animal, and in vitro studies focusing on the effect of high-dose ambroxol in GD2 and GD3. A narrative synthesis was performed. ResultsNine in vitro, three animal, and eight clinical studies were included, demonstrating varied responses to ambroxol across diverse outcome measures. In vitro and animal studies demonstrated reduced endoplasmatic reticulum stress due to the relocation of GCase from the ER to the lysosomes. In vitro cell lines exhibited varying degrees of increased GCase activity. Clinical trials observed reduced lyso-GL1 levels in plasma (41–89%) and cerebrospinal fluid (CSF) (26–97%), alongside increased GCase activity in GD3 patients. Ambroxol exhibited varying effects on neurological outcomes and development. No severe adverse events were reported. ConclusionHigh-dose ambroxol shows promise in managing neurological manifestations in GD3, albeit with uncertainties resulting from genetic heterogeneity and variable response. Further clinical trials, are essential for elucidating dosage-response relationships and refining treatment outcomes and strategies for neuronopathic GD.

Impact of pharmacist-led interventions in a multidisciplinary consultation meeting for bone and joint infection

IntroductionManagement of bone and joint infections (BJI) requires prolonged and high-dose antibiotic therapy to achieve target concentrations in bone tissue. However, these therapies often lead to adverse effects in patients who are frequently fragile, with multiple comorbidities and associated medications. The decision to treat these complex cases is made during a multidisciplinary team meeting at the reference centre for complex osteoarticular infections (CRIOAC). Material and MethodsElaborated by a pharmacist during CRIOAC meetings, a single-centre before-and-after comparative study of drug-related issues observed during pharmaceutical interventions (PIs), was conducted. For each patient included, a retrospective case was added. PIs were independently evaluated by a committee of infectiologists and pharmacists to assess their criticality. ResultsSixty patients were included in the intervention group, with 59 controls. The population was homogeneous, with a median age of 65 years. Most BJI cases were complex (65.5 %), primarily involving prosthetic joint infections. Staphylococcus species were the predominant pathogens. Antibiotic therapy adapted to antibiograms was orally relayed for 74 % of patients, with 5.9 % requiring re-hospitalization due to adverse effects. Sixty-two PIs were performed, representing an average of 1.8 PIs per meeting or 34.4 % of patients. Dosage adjustment accounted for 42 % of PIs, drug interactions for 46 %, and treatment availability in community pharmacies for 8 %.Regarding criticality, three PIs were classified as vital, 22 as major, 22 as moderate, and 15 as minor in both groups, with the same distribution between the intervention and control groups. ConclusionThis study demonstrates that by collaborating with surgeons and infectiologists, pharmacists participating in CRIOAC meetings can strongly help to prevent drug-related problems in patients with BJIs.

Significance of androgen-deprivation therapy for intermediate- and high-risk prostate cancer treated with high-dose radiotherapy: A literature review.

The real-world benefits of adding androgen-deprivation therapy (ADT) and its optimal duration when combined with current standard high-dose radiation therapy (RT) remain unknown. We aimed to assess the efficacy of and toxicities associated with ADT in the setting of combination with high-dose RT for intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). This article is a modified and detailed version of the commentary on Clinical Question 8 described in the Japanese Clinical Practice Guidelines for Prostate Cancer (ver. 2023). A qualitative systematic review was performed according to the Minds Guide. All relevant published studies between September 2010 and August 2020, which assessed the outcomes of IR or HR PCa treated with high-dose RT, were screened using two databases (PubMed and ICHUSHI). A total of 41 studies were included in this systematic review, mostly consisting of retrospective studies (N = 34). The evidence basically supports the benefit of adding ADT to high-dose RT to improve tumor control. Regarding IR populations, many studies suggested the existence of a subgroup for which adding ADT had no impact on either overall survival or the BF-free duration. On the other hand, regarding HR populations, several studies suggested the positive impact of adding ADT for ≥1 year on overall survival. Adding ADT increases not only the risk of sexual dysfunction but also that of cardiovascular toxicities or bone fracture. Although the benefit of adding ADT was basically suggested for both IR and HR populations, further investigations are warranted to identify subgroups of patients for whom ADT has no benefit, as well as the appropriate duration of ADT for those who do derive benefit.

The Effect of Age on High-Dose Therapy with Autologous Stem Cell Support in Multiple Myeloma: A Single-Center Experience.

Background: This retrospective one-center study demonstrates the complications related to high-dose therapy with autologous stem cell support (HDT) and the survival of multiple myeloma (MM) patients according to age groups. Methods: We categorized the patients into two groups: those who were ≤65 years old (group 1) (N = 115) and those who were >65 years old (group 2) (N = 26). The mean duration of follow-up was 48 (1-125) months. Results: In group 2 patients, the use of a reduced dosage of melphalan (12 [46%] versus 30 [26%]) was more frequent in comparison to group 1 (p = 0.046). There was a statistically significant difference between the two groups regarding the neutrophil engraftment days (p = 0.001) and the median progression-free survival (PFS) (p = 0.02). The PFS was 44 months for group 1 and 30 months for group 2. There was no statistically significant difference between the groups in relation to the median duration of hospitalization, presence of bacteremia, intravenous antibiotic administration, and overall survival (OS). Conclusions: The study's results indicate that HDT is a reliable method of treatment for older patients with MM, provided that they obtain a suitable conditioning regimen and, furthermore, these patients achieved a comparable OS rate to that of younger patients.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Bacteriophage therapy and infective endocarditis - is itrealistic?

Infective endocarditis (IE) is a severe infection of the inner heart. Even with current standard treatment, the mean in-hospital mortality is as high as 15-20%, and 1-year mortality is up to 40% for left-sided IE. Importantly, IE mortality rates have not changed substantially over the past 30 years, and the incidence of IE is rising. The treatment is challenging due to the bacterial biofilm mode of growth inside the heart valve vegetations, resulting in antibiotic tolerance. Achieving sufficient antibiotic anti-biofilm concentrations in the biofilms of the heart valve vegetations is problematic, even with high-dose and long-term antibiotic therapy. The increasing prevalence of IE caused by antibiotic-resistant bacteria adds to the challenge. Therefore, adjunctive antibiotic-potentiating drug candidates and strategies are increasingly being investigated. Bacteriophage therapy is a reemerging antibacterial treatment strategy for difficult-to-treat infections, mainly biofilm-associated and caused by multidrug-resistant bacteria. However, significant knowledge gaps regarding the safety and efficacy of phage therapy impede more widespread implementation in clinical practice. Hopefully, future preclinical and clinical testing will reveal whether it is a viable treatment. The objective of the present review is to assess whether bacteriophage therapy is a realistic treatment for IE.

EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN ALONE ON CORONARY ARTERY LESION REDUCTION IN KAWASAKI DISEASE.

Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance. The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups. This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction. URL: http://www.clinicaltrials.gov ; identifier: NCT02951234. This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments. Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.

Research perspective in the clinical management of Kawasaki disease.

This study examines research perspective in the clinical diagnosis, treatment, and prevention of cardiovascular complications in Kawasaki Disease (KD). Starting with an overview of the disease, it introduces KD's clinical manifestations, etiology, epidemiological features, and its impact on the cardiovascular system. Subsequently, the study discusses in detail the diagnostic methods, pathological mechanisms, and treatment strategies for KD, including foundational and emerging approaches such as high-dose intravenous immunoglobulin and aspirin therapy, biologic therapy, and corticosteroid pulse therapy. Additionally, it outlines strategies for preventing cardiovascular complications, including early risk assessment and long-term management. The study also explores the intersection of the COVID-19 pandemic with an increase in KD-like symptoms, emphasizing the need for further studies on the association between SARS-CoV-2 and KD. Lastly, it explores future research directions to enhance understanding of KD and improve patient outcomes and quality of life. This study provides valuable insights into the comprehensive treatment and management of KD and highlights avenues for future research.

Mixed Autoimmune Hemolytic Anemia - A Rare Case Report

Abstract Mixed autoimmune hemolytic anemia (MAIHA) is a rare clinical condition where both warm and cold antibodies cause red cell destruction, leading to anemia. MAIHA can present as a blood group discrepancy or crossmatch incompatibility, which can be very challenging for transfusion medicine services to diagnose and issuing of best-matched blood. Therefore, a comprehensive immunohematology workup, including a monospecific direct antiglobulin test, and indirect antiglobulin test is performed to determine the thermal amplitude and titer of autoantibodies. It is important to be aware of this phenomenon because, like warm AIHA and MAIHA should be treated immediately, with steroids. We hereby report a case of a 14-year-old girl presenting with a history of generalized weakness and dizziness; preliminary investigations revealed anemia, increased reticulocyte count, and antinuclear antibodies positive. Hence, further diagnosis of MAIHA associated with systemic lupus erythematosus was made. A high-dose steroid therapy was given to the patient, and significant improvement was seen clinically.

Ag-Pt@BSA bimetallic nanoparticles for breast cancer radiation treatment dose augmentation

Cancer has traditionally been treated with surgery and chemotherapy. Radiation therapy (RT) is a branch of oncology based on radiation therapy that can be used alone or in combination with surgery and chemotherapy to achieve local control of breast cancer. Radiosensitizers make tumor cells more responsive and sensitive to ionizing radiation, consequently facilitating production of free radicals and hastening DNA damages. Stages I to III of breast cancer is managed with curative intent with multimodality treatment including radiotherapy. The current cancer therapies in particular radiotherapy have a high risk of serious side effects to the healthy tissues and do not guarantee remission. In response to this challenge, the present study developed bovine serum albumin capped platinum and silver nanoparticles (Ag-Pt@BSA NPs), a bimetallic radiosensitizer, which is a remedy to the aforementioned issue. This research makes use of a nanoplatform that contains two high-Z nanoparticles— Pt and Ag. A variety of methods were used to fully characterize the developed Ag-Pt@BSA NPs. Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), UV–Vis, X-ray diffractometery (XRD) and energy-dispersive X-ray spectroscopy (EDS) techniques were used to investigate the physical and chemical features of designed bimetallic nanoradiosensitizer. The Ag-Pt@BSA naoradiosensitizer was proven to have successfully prepared by FTIR, XRD and EDX. According to the DLS result, the hydrodynamic size of the NPs is 35.42 nm, and the average diameter in the TEM image is around 7.8 ± 2.6 nm. The initial hydrodynamic size Ag-Pt@BSA was around 35 nm and within the storage time its size remained below 40 nm which indicating the unique colloidal stability of fabricated nanoradiosensitizers. The zeta potential of Ag-Pt@BSA radio-enhancement was determined to be approximately −17.9 mV, providing additional support for the nanoparticles’ colloidal stability. The results showed that the utilization of Ag-Pt@BSA NPs in conjunction with X-ray irradiation could substantially enhance the effectiveness of cancer therapy. This is supported by research, examining a series of in vitro tests including reactive oxygen species generation (ROS), cell viability, apoptosis and colony formation assay. Furthermore, the dosage-dependent radiosensitizing ability of the Ag-Pt@BSA NPs was also observed in the apoptosis and MTT assay against 4 T1 cells by increasing the localized radiation dosage. Ag-Pt@BSA NPs could be a potential radio-enhancer agent against breast cancers and, by extension, other cancers, since it multiplies the therapeutic effect of low-dose radiation while reducing the damage to normal tissues compared to high-dose radiation therapy. Increasing the concentration of Ag-Pt@BSA NPs and the dosage of X-ray irradiation boosted the radiosensitizing capacity in a dose-dependent way.

Successful Electroconvulsive Therapy in a Patient With Catatonia and Maternal Duplication 15q11-13 Syndrome.

The 15q11-q13 chromosomal region contains genes encoding for GABA-A receptor subunits and is a known region of epigenetic modification associated with the development of neurodevelopmental disorders. The presence of at least one additional copy of the maternal 15q11-q13 results in a syndrome (maternal dup15q) characterized by intellectual disability, autism spectrum disorder, mood disorders, and epilepsy. Catatonia is a serious syndrome of behavioral and motor dysfunction, which occurs across a variety of psychiatric, neurologic, and general medical conditions, which has successfully been treated with benzodiazepines and electroconvulsive therapy. In this case report, we describe the treatment course of a patient with established maternal dup 15q with comorbid intellectual disability, autism spectrum disorder, bipolar mood disorder, and juvenile epilepsy who developed hypokinetic catatonia refractory to high-dose benzodiazepine therapy. In contrast with benzodiazepine treatment, electroconvulsive therapy resulted in rapid improvement in catatonic symptoms and return to premorbid baseline. This case suggests that electroconvulsive therapy can be safely delivered for some patients with maternal dup 15q and may be rapidly effective when benzodiazepine treatment results in inadequate symptom improvement.

High-Dose Epidermal Radionuclide Therapy with 188Re (Rhenium) Resin in a Patient with Multiple Actinic Keratoses

High-Dose Epidermal Radionuclide Therapy with 188Re (Rhenium) Resin in a Patient with Multiple Actinic Keratoses