Advanced Options Research Articles

Single agent vs combination immunotherapy in advanced melanoma: a review of the evidence.

The aim of this review is to outline the current landscape of advanced melanoma treatment options, provide insights on selecting combination therapies within different clinical scenarios, capture clinical relevance of anti-programmed cell death protein 1 (PD-1) monotherapy, and explore the unmet needs with immune check-point inhibitors (ICI) in advanced melanoma. ICI based treatment consisted of single agent ICI or dual combination ICI-ICI is the standard of care of front-line treatment of metastatic or unresectable melanoma. PD-1 inhibitors (Pembrolizumab and Nivolumab) improved progression free survival (PFS) and overall survival (OS) compared to chemotherapy and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors (Ipilimumab and Tremelimumab). The dual ICI combination (Nivolumab and Ipilimumab) provided profound and durable responses better than monotherapy, and the longest overall survival ever achieved in advanced disease, including in patients with murine sarcoma viral oncogene homolog B (BRAF)-mutated disease, but at the cost of a high risk of severe toxicity. The new dual blockage of LAG-3 and PD-1 (Nivolumab-Relatlimab) emerges as a valid option with promising efficacy outcomes and a favourable toxicity profile. Mature survival data is still needed to capture the real benefit. These new plethora of options pose new challenges not only for optimal treatment sequencing strategies but especially for management of adverse effects, endorsing the need to integrate a holistic and personalized approach for patient care.

Quality of Care and Management of Atopic Dermatitis Across Different Levels of Healthcare-A Survey-Based Patient Experience.

Atopic dermatitis (AD) is a chronic and fluctuating disease. Optimal management of AD and related comorbidities requires seamless coordination across multiple layers of the healthcare system. The objective of this survey was to explore patients' experiences with current management of AD. Out of 251 responders to this anonymous survey, 76% reported to have moderate or severe AD. Sixty-nine percent with moderate and 45% with severe AD were followed up at primary care level only. Use of advanced systemic treatment options was rare, and the majority experienced itch (97%), dry skin, rash, negative impact on self-esteem and comorbidities despite ongoing treatment. Only 36% received a treatment plan, more often in secondary (78.3%) than primary care (25.0%). Forty-three percent did not know who was responsible for their follow-up and 54% felt no one was responsible. Treatment options were commonly not known or understood. The survey results demonstrate undertreatment, lack of a holistic approach for management of AD. A national pathway including clear referral criteria and timelines can streamline management of AD across multiple levels of the healthcare system.

Improved deconvolution of natural products' protein targets using diagnostic ions from chemical proteomics linkers.

Identification of interactions between proteins and natural products or similar active small molecules is crucial for understanding of their mechanism of action on a molecular level. To search elusive, often labile, and low-abundant conjugates between proteins and active compounds, chemical proteomics introduces a feasible strategy that allows to enrich and detect these conjugates. Recent advances in mass spectrometry techniques and search algorithms provide unprecedented depth of proteome coverage and the possibility to detect desired modified peptides with high sensitivity. The chemical 'linker' connecting an active compound-protein conjugate with a detection tag is the critical component of all chemical proteomic workflows. In this review, we discuss the properties and applications of different chemical proteomics linkers with special focus on their fragmentation releasing diagnostic ions and how these may improve the confidence in identified active compound-peptide conjugates. The application of advanced search options improves the identification rates and may help to identify otherwise difficult to find interactions between active compounds and proteins, which may result from unperturbed conditions, and thus are of high physiological relevance.

Refractory Crohn's Disease: Perspectives, Unmet Needs and Innovations.

Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.

Treatment outcome of pediatric rhabdomyosarcoma at national cancer institute, Egypt

Background Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in infants and children. It is the third most common solid tumor in children after neuroblastoma and Wilms tumor, making up 10–15% of all solid pediatric tumors. At National Cancer Institute (NCI), Egypt, soft tissue sarcomas represent 3.75% of total malignancies and 27.6% of these occur in the pediatric group. RMS is the most common type. Aim and objectives This work aims to study the treatment outcome, overall survival (OS), and event free survival (EFS) of pediatric RMS patients diagnosed and treated at NCI. Patients and methods This is a retrospective study that included 54 pediatric patients, newly diagnosed with RMS who were treated at the pediatric oncology department, NCI, Cairo University, Egypt during the period from January 2012 to December 2016. Results Totally 54 pediatric patients with RMS with ages ranging from 7 months to 17 years (median age 5 years) were studied. The median follow-up period ranged with a minimum 1 year for the last patient. In this study, we classify our patients into low, intermediate, and high-risk groups according to IRS and we found that 11 (20.4%) patients were eligible for the low-risk group, 27 (50%) patients were eligible for the intermediate risk group and 16 (29.6%) patients were eligible for the high-risk group. The 2-year OS for low-risk group was 90.9%, it was 52.1% for intermediate-risk group, while it was 43.8% for high-risk group (P=0.02). The 2-year EFS for low-risk group was 63.6%, it was 41.2% for intermediate-risk group, while it was 31.3% for high-risk group (P=0.203). Conclusion RMS requires combined-modality therapy. Late presentation and advanced local disease compromise treatment options and decrease OS and EFS.

Juvenile idiopathic arthritis presenting with rare extra-articular manifestations: A report of two cases

Abstract Juvenile idiopathic arthritis (JIA), a common rheumatic disease of childhood, is a consolidated term used for all chronic childhood arthritis affecting joints and extra-articular structures. Involvement of skin and internal organs such as liver, spleen, intestine, peritoneum, pleura, pericardium and myocardium will cause systemic symptoms leading to disability and mortality. Despite advanced treatment options, significant morbidity still occurs due to an unpredictable clinical course and risk of joint restriction. We describe polyarticular rheumatoid factor-negative JIA with extra-articular manifestations involving pericardium causing chronic constrictive pericarditis in a 16-year-old girl and her sibling a 13-year-old boy. The female patient developed cardiac cirrhosis, portal hypertension and oesophageal varices. Screening evaluation of this patient’s asymptomatic sibling with similar articular manifestations revealed the rare occurrence of chronic constrictive pericarditis without symptoms. Both were treated with pericardiectomy and were relieved of symptoms. Two patients of JIA from the same family presenting with constrictive pericarditis is a rare association.

Keratoconus: imaging modalities and management.

Keratoconus (KCN) is characterized by gradual thinning and steepening of the cornea, which can lead to significant vision problems owing to high astigmatism, corneal scarring, or even corneal perforation. The detection of KCN in its early stages is crucial for effective treatment. In this review, we describe current advances in the diagnosis and treatment of KCN. This narrative review focuses on recent advancements in the diagnosis and treatment of KCN, especially evolving approaches and strategies. To ensure the inclusion of the most recent literature, relevant publications discussing advanced imaging techniques and treatment options for KCN were extensively gathered from the PubMed/MEDLINE and Google Scholar databases. The following index terms and keywords were used for the online search: keratoconus, diagnosis of keratoconus, advances in the diagnosis of keratoconus, topography or tomography, anterior segment optical coherence tomography, treatment of keratoconus, advances in the treatment of keratoconus, collagen crosslinking, intrastromal ring, keratoplasty, and new techniques in keratoconus. Various screening methods such as corneal topography, tomography, anterior segment optical coherence tomography, and assessment of corneal biomechanics have been developed to identify KCN in its early stages. After diagnosis, KCN management focuses on preventing disease progression. Corneal collagen crosslinking is a minimally invasive treatment that can slow or stop the progression of the condition. Recent research has also explored the use of copper sulfate eye drops (IVMED-80) as a noninvasive treatment to prevent the progression of KCN. Current treatment options for visual improvement include scleral lenses, intracorneal ring segments, corneal allogeneic intrastromal ring segments, and deep anterior lamellar keratoplasty. Recently, novel alternative procedures, such as isolated Bowman layer transplantation, either as a corneal stromal inlay or onlay, have demonstrated encouraging outcomes. Artificial intelligence has gained acceptance for providing best practices for the diagnosis and management of KCN, and the science of its application is contentiously debated; however, it may not have been sufficiently developed. Early detection and advancements in screening methods using current imaging modalities have improved diagnosis of KCN. Improvement in the accuracy of current screening or diagnostic tests and comparison of their validities are achievable by well-designed, large-scale, prospective studies. The safety and effectiveness of emerging treatments for KCN are currently being investigated. There is an ongoing need for studies to track progress and evaluate clinicians' knowledge and practices in treating patients with KCN. Artificial intelligence capabilities in management approach considering the currently available imaging modalities and treatment options would best benefit the patient.

Advances in RNA therapeutics for modulation of 'undruggable' targets.

Over the past decades, drug discovery utilizing small pharmacological compounds, fragment-based therapeutics, and antibody therapy have significantly advanced treatment options for many human diseases. However, a major bottleneck has been that>70% of human proteins/genomic regions are 'undruggable' by the above-mentioned approaches. Many of these proteins constitute essential drug targets against complex multifactorial diseases like cancer, immunological disorders, and neurological diseases. Therefore, alternative approaches are required to target these proteins or genomic regions in human cells. RNA therapeutics is a promising approach for many of the traditionally 'undruggable' targets by utilizing methods such as antisense oligonucleotides, RNA interference, CRISPR/Cas-based genome editing, aptamers, and the development of mRNA therapeutics. In the following chapter, we will put emphasis on recent advancements utilizing these approaches against challenging drug targets, such as intranuclear proteins, intrinsically disordered proteins, untranslated genomic regions, and targets expressed in inaccessible tissues.

Update on non-infectious uveitis treatment: anti-TNF-alpha and beyond.

Non-infectious uveitis (NIU) encompasses a range of conditions marked by inflammation within various layers of the eye. NIU is a significant contributor to irreversible vision loss among the working-age population in developed countries. The aim of treating uveitis is to manage inflammation, prevent its recurrences and to restore or salvage vision. Presently, the standard treatment protocol for NIU involves initiating corticosteroids as the primary therapeutic agents, although more aggressive approaches and steroid sparing agent may be necessary in certain cases. These advanced treatments option include synthetic immunosuppressants like antimetabolites, calcineurin inhibitors and alkylating agents. For patients who exhibit an intolerance or resistance to corticosteroids and conventional immunosuppressive therapies, biologic agents have emerged as a promising alternative. Notably, among the biologic treatments evaluated, TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy. In this review, we delve into the latest evidence surrounding the effectiveness of biologic therapy and introduce novel therapeutic strategies targeting immune components as potential avenues for advancing treatment of NIU.

Curso de Escritura Académica. Edición, maquetación y revisión con MS Word

Second article in the series of four from the “Academic Writing Course”. This article reviews the essential functionalities of Microsoft Word. The main options are examined from the perspective of editing, formatting, and reviewing texts. The first section highlights the advanced options of Word, and then details layout options such as configuration, page orientation, line spacing, and line numbers. Next, the References menu is examined, focusing on the creation of indexes and tables of contents among other features. In the review section, comments, spell check, track changes, and split screen are highlighted. In short, this article provides a quick guide to the aspects of Word that we must master if we want to write fluently and present professional documents.

Why are genius brains of our science community not happy with research?

Medicine is an ever-changing science and mandates ongoing research. Medical colleges are engines for research all over the world. The increase in longevity across the world is the result of improvements over the years in diagnosis and treatment options of various diseases. This has been possible only due to continuous progress and innovations in medical research globally. Research secures better growth progression. The field of medical research is currently at cross-roads and is being intensively scrutinized for validity and reproducibility. It describes an area of knowledge that can be explained in terms of scientific observation. Research is the greatest cumulative venture and gives rise to explanations and answers to everyday life .It gives solutions to the great mysteries of the universe. Research inspires curiosity and an attitude of discovery. It offers perspective, encourages the integration of subjects, and ,ideas ,and promotes truth-seeking. Researchers are the people who tear down myths and solve the mysteries that stand in the way of the development of society. Clinical research aims at taking their expertise to the next level. The high advanced diagnosis and treatment options of various diseases increase in longevity. This has been possible only due to continuous progress and innovations in medical research, improving the quality of health care.

Reducing the hospitalization epidemic of chronic heart failure by disease management programs.

Chronic heart failure is the most common cause of hospitalization in Europe and rates are steadily increasing due to aging of the population. Hospitalization identifies a fundamental change in the natural history of heart failure (HF) increasing the risk of re-hospitalization and mortality. Heart failure management programs improve the quality of care for HF patients and reduce hospitalization burden. The goals of the heart failure management programs include optimization of drug therapy, patient education, early recognition of signs of decompensation, and management of comorbidities. Randomized clinical trials evidenced that system of care for heart failure patients improved adherence to treatment and reduced unplanned re-admissions to hospital. Multidisciplinary programs and home-visiting have shown improved efficacy with reductions in HF and all-cause hospitalizations and mortality. Community HF clinics should take care of the management of stable patients in strict contact with primary care, while hospital out-patients clinics should care of patients with severe disease or persistent clinical instability, candidates to advanced treatment options. In any case a holistic, patient-centered approach is suggested, to optimize care considering the needs of the individual patient. Telemonitoring is a new opportunity for HF patients, because it allows the continuity of care at home. All heart failure patients should require follow-up in a specific management program, but most of date come from clinical trials that included high-risk patients. While clinical trials have a specified duration (from months to some years), lifelong follow-up is recommended with differentiated approaches according to the patient's need.

Biomass-derived Activated Carbon with Nickel Ferrite Nanocomposite for Broadband Microwave Absorption

This study presents a novel approach using a composite material consisting of Biomass-derived Activated Carbon and Nickel Ferrite Nanocomposite as an advanced option for achieving effective microwave absorption over a wide range of frequencies. The use of biomass, which is a sustainable and easily accessible resource, serves as the fundamental basis for this methodology. This approach effectively tackles the need for enhanced electromagnetic interference shielding in communication and radar systems by integrating activated carbon generated from biomass with nickel ferrite nanoparticles. Traditional approaches often encounter challenges related to the limited absorption of bandwidth and environmental considerations. The utilization of Biomass-derived Activated Carbon for Broadband Microwave Absorption (BMAC-BMA) presents a significant advancement, characterized by a noteworthy Absorption Coefficient of 14.25 Np/m, Return Loss of -20.37 dB, specific surface area of 580.25 m²/g, pore size distribution of 2.8 nm, Saturation Magnetization of 1.35 A/m and Reflection Coefficient of 0.1. These characteristic holds promise for driving breakthroughs in technology and communication systems. This study demonstrates the significant impact of using sustainable biomass resources in producing advanced materials for various applications.

Childhood asthma complications, management, and environmental triggers

Childhood asthma, which is a chronic respiratory condition, presents challenges in terms of its complications, management, and identification of environmental triggers. This review of existing literature explores the complexities surrounding asthma. It delves into complications, strategies for managing the condition, and the crucial role that environmental factors play in worsening it. Uncontrolled asthma in children has far-reaching consequences as it affects lung function, physical activity levels, and overall quality of life. Early recognition and addressing of these complications are essential to minimize long-term effects. The management of childhood asthma has evolved to focus on treatment plans, with corticosteroids being a key component. For cases, advanced therapeutic options like biologics are available. Indoor and outdoor environmental triggers have an impact on asthma exacerbations, making targeted preventive measures necessary. Education plays a role by providing caregivers and children with asthma action plans as well as proper inhaler technique guidance. Regular follow-up visits ensure assessment and adjustment of treatment plans while fostering a relationship between healthcare providers and families. Comprehensive care for childhood asthma involves an approach that includes pediatricians, pulmonologists, allergists, and respiratory therapists. The triad of interventions, environmental modifications, and educational strategies forms an encompassing framework for the management of asthma. This review highlights how crucial it is to tackle childhood asthma issues. By doing so, we can improve outcomes. Promote the overall well-being of children who are affected by this condition.

Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer.

Gall bladder cancer (GBC) is becoming a very devastating form of hepatobiliary cancer in India. Every year new cases of GBC are quite high in India. Despite recent advanced multimodality treatment options, the survival of GBC patients is very low. If the disease is diagnosed at the advanced stage (with local nodal metastasis or distant metastasis) or surgical resection is inoperable, the prognosis of those patients is very poor. So, perspectives of targeted therapy are being taken. Targeted therapy includes hormone therapy, proteasome inhibitors, signal transduction and apoptosis inhibitors, angiogenesis inhibitors, and immunotherapeutic agents. One such signal transduction inhibitor is the specific short interfering RNA (siRNA) or short hairpin RNA (shRNA). For developing siRNA-mediated therapy shRNA, although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells, many more clinical trials are required. To date, many such genes have been identified. This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.

BASIL: A toolbox for perfusion quantification using arterial spin labelling

Abstract Arterial Spin Labelling (ASL) MRI is now an established non-invasive method to quantify cerebral blood flow and is increasingly being used in a variety of neuroimaging applications. With standard ASL acquisition protocols widely available, there is a growing interest in advanced options that offer added quantitative precision and information about haemodynamics beyond perfusion. In this article, we introduce the BASIL toolbox, a research tool for the analysis of ASL data included within the FMRIB Software Library (FSL), and explain its operation in a variety of typical use cases. BASIL is not offered as a clinical tool, and nor is this work intended to guide the clinical application of ASL. Built around a Bayesian model-based inference algorithm, the toolbox is designed to quantify perfusion and other haemodynamic measures, such as arterial transit times, from a variety of possible ASL input data, particularly exploiting the information available in more advanced multi-delay acquisitions. At its simplest, the BASIL toolbox offers a graphical user interface that provides the analysis options needed by most users; through command line tools, it offers more bespoke options for users needing customised analyses. As part of FSL, the toolbox exploits a range of complementary neuroimaging analysis tools so that ASL data can be easily integrated into neuroimaging studies and used alongside other modalities.

Abstract B011: GDF-15 is a biomarker of aggressiveness in epithelioid hemangioendothelioma and is down-regulated by sirolimus through ATF4 suppression

Abstract Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma marked by two fusions - TAZ-CAMTA1 (~90%) and YAP-TFE3 (~10%) - that lead to Hippo-pathway activation. EHE clinical behavior ranges from indolent disease to highly aggressive presentation, but no biomarkers are known to predict the clinical outcome at disease onset. Conventional chemotherapy has limited effectiveness in advanced EHE patients and new treatment options are needed, as well as novel biomarkers of aggressiveness. We exploited i) two independent patient series to identify circulating biomarkers of EHE aggressiveness; ii) an EHE patient-derived xenograft (PDX) model and the derived cell line to investigate the effectiveness of sirolimus, one of the antitumor agents considered more effective in EHE. Methods: Two independent patient series were exploited to test the association between Growth/differentiation factor 15 (GDF-15) serum levels and EHE aggressiveness. A PDX model was generated from a patient with advanced EHE and showed consistency with the original tumor in terms of histomorphology, presence of the TAZ-CAMTA1 fusion and transcriptomic profile. This model - the only human EHE model available worldwide - has been used to generate a corresponding cell line. GDF-15 release from EHE cells and PDX was quantified by ELISA. Drugs cytotoxicity on EHE cells was assessed through cell counting and TUNEL assay. Western blotting was used to investigate sirolimus effects on EHE cells. Results: Analyses of blood samples from two independent patient series showed a statistically significant correlation between GDF-15 levels and EHE aggressiveness. ELISA on the blood of EHE-carrying mice and EHE cell culture medium revealed that GDF-15 is released by tumor cells. Sirolimus induced a significantly higher tumor growth inhibition (80%) compared to doxorubicin, whose activity was almost negligible in the EHE PDX. Also in EHE cells, sirolimus showed a lower IC50 (0.01µM versus 0.1µM) and a greater apoptotic response (TUNEL-positive cells: 20% vs 10%) than doxorubicin. Interestingly, sirolimus reduced GDF-15 expression/release in both in vivo and in vitro EHE models by reducing the expression of the GDF-15 transcription factor ATF4, as a consequence of the drug-induced inhibition of phosphorylation/activation of 4E-BP1, which is involved in the regulation of ATF4 translation. Conclusions: Results from this study indicate that: i) GDF-15 is a novel biomarker of EHE aggressiveness; ii) sirolimus is more effective than doxorubicin in our experimental model, supporting the suitability of the model for comparative studies on the activity of anticancer drugs for EHE treatment. Moreover, the notion that sirolimus inhibits the release of GDF-15 from EHE would suggest the relevance of this cytokine as a biomarker for monitoring sirolimus activity in patients. Further investigations are ongoing to clarify the role of GDF-15 in EHE progression. Citation Format: Alessia Beretta, Valentina Zuco, Silvia Martini, Anna Maria Frezza, Sandro Pasquali, Silvia Stacchiotti, Nadia Zaffaroni. GDF-15 is a biomarker of aggressiveness in epithelioid hemangioendothelioma and is down-regulated by sirolimus through ATF4 suppression [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B011.

Genetic, Hematological, and Endocrine Involvement in a Patient with Pearson Syndrome: Clinical Management and Discussion

Background: Pearson syndrome (PS) is a rare mitochondrial DNA deletion disorder characterized by pancytopenia and exocrine pancreas dysfunction. Currently, there are less than 150 cases ever reported. The mutations are predominately de novo with only a handful of instances of mother to child inheritance documented. Mortality is typically in early childhood or those making it past oftentimes developing chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS). While no curative treatment exists today, our goal is to document the clinical phenotype of a patient with PS to allow for a greater understanding and management for future patients. Diagnosis: We present the case of a child with PS and associated findings of resolved pancytopenia, ringed sideroblasts, failure to thrive, and renal tubular acidosis. Born premature at 32 weeks and anemic at birth, he required PRBC transfusions twice during his one-month NICU admission. At 2 months old, he was vomiting and appeared pale in which he was admitted and had a hemoglobin of 3.5 g/dL. Found then to have pancytopenia, a bone marrow aspiration and biopsy was performed showing ringed sideroblasts, hypocellularity at 60%, 5-8% blasts, moderate dyserythropoiesis, and dysmyelopoiesis. Phenotypically, he was also referred to genetics for facial dysmorphism with a flat nasal bridge, thin philtrum, and small ears. Upon further genetic testing, he had an 80% Heteroplasmic 5kb deletion including m.8483_13459 encompassing the following genes: MT-ATP8, MT-ATP6, MT-CO3, MT-TG, MT-ND3, MT-TR, MT-ND4L, MT-ND4, MT-TH, MT-TS2, MT-TL2, MT-ND, consistent with PS. Since diagnosis, he has been admitted on several occasions for emesis and metabolic acidosis. Management: Patient has been following up with genetics, hematology, endocrinology, cardiology, gastroenterology, neurology, and nephrology. He had been receiving granulocyte colony-stimulating factor (G-CSF) until the age of 1 and more than 20 transfusions up until 1.5 years old with the pancytopenia having since resolved. Most recent values show a hemoglobin of 13.9 g/dL, WBC 5,600/mcL, and platelets still low at 86,000/mcL. He has been evaluated for short stature with height and weight both below the 1st percentile and IGF-1 low at 25 leading to considerations for a G-tube and/or GH supplementation. He continues to receive physical therapy for low muscle mass. He is currently taking sodium bicarbonate, magnesium bicarbonate, and levocarnitine due to deficiencies, pancrelipase for exocrine pancreatic insufficiency, and leucovorin for anemia. He is also seeing dermatology for a hemangioma, facial telangiectasias on the forehead and cheeks, as well as skin photosensitivity and hypopigmentation of the arms and legs. Discussion/Conclusion: With PS being discovered less than 50 years ago, more research still needs to be done to better understand clinical phenotype and treatment management. Resolved pancytopenia, ringed sideroblasts, failure to thrive, and renal tubular acidosis have all been seen in the literature and in our patient. Other areas however are still being assessed. While failure to thrive has been reported, the efficacy of growth hormone supplementation has not been adequately described. With regards to skin findings, hypopigmentation has been reported in the literature in reference to various mitochondrial diseases, however there are limited findings in specific with reference to PS. Furthermore, it would be beneficial to see whether others with PS have any of the same facial dysmorphisms to aid in future diagnosis. Gene therapies and other therapeutics are newly emerging for mitochondrial diseases and it is our hope that PS will have more advanced treatment options in the future.

Management of Toxicities of BTK Inhibitors in B-Cell Malignancies

Brüton’s tyrosine kinase (BTK) inhibitors have significantly advanced treatment options for patients with B-cell malignancies; however, side effects with these agents are not uncommon, and a multidisciplinary approach is necessary for monitoring and managing adverse events such as bleeding, hypertension, and atrial fibrillation. In the treatment of patients on BTK inhibitors, maintaining communication between patients and all providers is essential, particularly concerning the use of any concurrent medications or supplements, as is educating patients on identifying early risk factors and reporting any signs or symptoms of toxicities. Ongoing clinical studies with both covalent and noncovalent BTK inhibitors are expected to further increase the understanding of these toxicities while improving the efficacy and safety of this class of medications.

Stormwater Treatment Using Natural and Engineered Options in an Urban Growth Area: A Case Study in the West of Melbourne

The expected increase in urbanization and population in coming years is going to increase the impervious land area, leading to substantial increases in stormwater runoff and hydrological challenges, and presents significant challenges for urban potable water supply. These are worldwide challenges that can potentially be ameliorated by harvesting stormwater for potable use or for other uses that can reduce the pressure on potable water supply. This study sought to assist the local water authority in planning for future potable water supply through a review of the scientific literature to determine the likely chemical and microbial characteristics of stormwater, the treatment train (TT) requirements, and the likely costs of treatment to achieve potable standards for the high-growth metropolitan region of Melbourne, Australia. Literature stormwater quality statistical data and treatment process performance data were used to model the expected product water microbial and chemical quality after treatment using a number of advanced TT options. The results of the modelling were compared with literature microbial log reduction targets (LRTs) for the potable use of stormwater and with the Australian Drinking Water Guidelines (ADWG). It was found that a reverse osmosis (RO)-based TT with microfiltration pre-treatment and post-RO advanced oxidation and chlorination in storage reservoirs is a conservative stormwater potable use treatment option. A less conservative and less expensive ozone-and-biologically active filtration (O3/BAF)-based TT option is also proposed if RO concentrate disposal is deemed to be too challenging. These results could be useful in climate change adaptation involving the evaluation of options for the mitigation of future population-growth- and climate-change-driven water supply challenges, as well as urbanization-driven stormwater hydrology and receiving water pollution challenges.