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Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive inherited lysosomal storage disease. With pathogenic variants of the IDS gene, the activity of iduronate-2-sulfatase (IDS) is reduced or lost, causing the inability to degrade glycosaminoglycans (GAGs) in cells and influencing cell function, eventually resulting in multisystemic manifestations, such as a coarse face, dysostosis multiplex, recurrent respiratory tract infections, and hernias. Diagnosing MPS II requires a combination of clinical manifestations, imaging examinations, urinary GAGs screening, enzyme activity, and genetic testing. Currently, symptomatic treatment is the main therapeutic approach. Owing to economic and drug availability issues, only a minority of patients opt for enzyme replacement therapy or hematopoietic stem cell transplantation. The limited awareness of the disease, the lack of widespread detection technology, and uneven economic development contribute to the high rates of misdiagnosis and missed diagnosis in China. [ABSTRACT FROM AUTHOR]

Background: Mucopolysaccharidosis (MPS) comprises a group of metabolic diseases with a disorder in the function of lysosomal enzymes that lead to the accumulation of glycosaminoglycans (mucopolysaccharides) (Kubaski et al. in Diagnostics 10:161, 2020; Hampe et al. in Cells 9:1838, 2020; Tomatsu et al. Mol Genet Metab 110(1–2):42–53, 2013). At least seven variants of this disorder have been identified to date (Muenzer et al. in Pediatrics 124(6):e1228–e1239, 2009; Muenzer et al. in Eur J Pediatr 171:181–8, 2012). this study aims to report a case of mucopolysaccharidosis in a 9-year-old child. Also, the treatments and dental observations made for the child have been described. Also, a review of past articles has been done to report the types of diseases, medical and dental considerations, etc. of this disease. Case description: the present case report describes the orofacial and systemic characteristics, diagnostic methods, and dental management of a 9-year-old boy with MPS with a one-year follow-up in association with a brief review of past articles. Conclusion: Since MPS patients have many changes in their oral and dental structures, they pose many challenges for dentists. Also, these patients need considerations in dentistry due to the involvement of different body organs. Knowing the oral-dental and systemic problems of these patients can help their dentists to provide effective and safe treatment for them. [ABSTRACT FROM AUTHOR]

In case of exocrine pancreatic insufficiency (EPI), the replacement of digestive enzymes with, for example porcine pancreatin or fungal rizoenzymes, is unavoidable under certain conditions. Current guidelines indicate that preparations from porcine pancreas have more advantageous physicochemical properties compared to those from fungi, especially at high bile salt concentrations, and that the latter can, therefore, only be used clinically to a limited extent. Since rizoenzymes are increasingly used in clinical practice, the present in vitro study investigated efficiency of enzymatic activity of rizoenzymes in comparison to pancreatin under various physiological and partly extreme environmental conditions. The lipolytic properties of two typical preparations containing digestive enzymes from porcine pancreatin and rizoenzymes were compared (same dosage of activity units) at different pH values (pH 3–9), with the addition of different bile salt concentrations (0–15 mmol/L sodium taurocholate). Lipolytic activity was measured by quantifying the fatty acids released from olive oil substrate by liquid chromatography–tandem mass spectrometry after enzymatic digestion. For both enzyme preparations, the lipolytic activity maximum was reached at pH 7 with comparable fatty acid conversion rates (57% pancreatin, 58% rizoenzymes). However, in contrast to pancreatin, rizoenzymes were already active for certain fatty acids from pH 3 to 4. At a bile salt concentration up to 10 mmol/L taurocholate, there was an increase in activity of both enzyme preparations (rizoenzymes 69% vs. pancreatin 58% enzymatic conversion). Only at rather unphysiological concentration of 15 mmol/L during EPI, there was a slight decrease in activity (to 56%) for the rizoenzymes. Rizoenzymes are an alternative therapeutic option for EPI. Relevant differences between rizoenzymes and pancreatin with regard to lipolytic activity under different physicochemical conditions could not be demonstrated in this study, whereas a potential advantage in favor of rizoenzymes activity at already low pH values was observed. [ABSTRACT FROM AUTHOR]

The article presents an update on changes to the safety labeling of drugs and therapeutic biologicals approved by the U.S. Food and Drug Administration from July to September 2024. A classwide boxed warning about serious hypersensitivity reactions was added to the labeling of several enzyme replacement therapies, such as Brineura and Cerezyme. Other products with new or revised boxed warnings include Copiktra, Estrasorb and Filspari.

Exocrine pancreatic insufficiency (EPI) is a significant complication of bariatric surgery, but its frequency and outcomes are not well-studied. If EPI is not diagnosed, it can result in nutritional deficiencies, dehydration, and acute kidney damage. Our patient, a 47-year-old woman, underwent Roux-en-Y gastric bypass (RYGB) surgery due to morbid obesity four years ago and lost contact with outpatient follow-ups. She came to us presenting chronic diarrhea and fatigue and was diagnosed with chronic pancreatic exocrine deficiency based on a low fecal elastase level. After starting her on pancreatic enzymes, her symptoms resolved. It is crucial to maintain a high degree of suspicion in order to diagnose EPI in patients who have undergone RYGB. The fecal elastase test, which is both reliable and inexpensive, is an effective diagnostic tool for EPI; prompt treatment can alleviate symptoms within days. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) affects 1% of people worldwide. Changes in the pulmonary vasculature, obstructive lesions in the pulmonary arteries, and an increase in pulmonary artery pressure are the hallmarks of PH, a progressive and deadly cardiovascular illness. These modifications result in a rise in right ventricular afterload, which frequently causes unfavorable right ventricular remodeling, right ventricular dysfunction and, in the end, mortality. One of the more severe and well-researched types of PH is pulmonary arterial hypertension (PAH), which is treatable with medication. The mechanisms involved in the regulation of pulmonary vascular tone and proliferation are the focus of PAH as well as some other forms of PH. The main characteristics of PAH (group 1) are discussed in this article, along with new and existing treatment options for the condition. [ABSTRACT FROM AUTHOR]

Despite advances in diagnosis and treatment, pulmonary hypertension has high morbidity and mortality. The presenting symptoms often are vague and may mimic other more common diseases, so patients can be misdiagnosed or missed early in the disease process. Early detection of pulmonary hypertension by primary care providers can play an important role in patient outcomes and survival. Identifying signs and symptoms, understanding the causes and classifications, and knowing the systematic approach to evaluating and diagnosing patients with suspected pulmonary hypertension are key to preventing premature patient decline. [ABSTRACT FROM AUTHOR]

Simple Summary: PpIX, a metabolite of 5-aminolevulinic acid (ALA) is necessary for the synthesis of hemoglobin and cytochromes. ALA has had many clinical uses over the last 33 years. Commercial forms of ALA are used every day along with blue light, which enables the fluorescent detection (PDD) of PpIX, which is specifically accumulated in cancer cells, to find bladder cancers and brain cancers. It has been reported that 12 ALA PD, activated by red light from a laser delivered through fiber optics embedded in brain tumors, can completely clear some brain cancers and increase patient survival. The evolution of ALA PDT to ALA SDT now creates the potential for noninvasive ultrasound to activate PpIX to treat brain cancers as well as cancers almost anywhere in the body through the photodynamic effect. The selectivity of ALA for cancer cells and their accumulation of PpIX should make SDT a low risk procedure. ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and has the potential to achieve clinical success in the treatment of both intracranial and extracranial cancers. This review describes the creation and evolution of ALA PDT, from the treatment of skin cancers to PDD and PDT of malignant brain tumors and, most recently, into a noninvasive form of PDT, ALA SDT. Current clinical trials of ALA SDT for recurrent glioblastoma and high-grade gliomas in adults, and the first pediatric ALA SDT clinical trial for a lethal brainstem cancer, diffuse intrinsic pontine glioma (DIPG), are also described. [ABSTRACT FROM AUTHOR]

Current gastroscopy practices necessitate a balance between procedural efficiency and patient safety. It has been hypothesized that increasing procedure outcomes through the use of Streptomyces protease enzyme and Shutai is possible; however, precise nature of any potential adverse reactions and complications remains unknown. In Zhanjiang, China, 213 patients undergoing gastroscopy participated in this controlled trial. The subjects were allocated at random into two groups: control and treatment. The treatment group was administered topical Streptomyces protease enzyme and intravenous Shutai. Using chi‐square and t‐tests, information regarding patient demographics, adverse reactions, wound healing, procedure duration, distress levels, and satisfaction was gathered and analysed. The demographic and medical history characteristics of the groups were comparable. There was a greater prevalence of modest immediate reactions in the treatment group (p < 0.05), whereas there were no significant variations observed in delayed reactions and long‐term complications (p > 0.05). The treatment group exhibited superior efficiency metrics, including shorter durations for diagnosis, procedure completion and recuperation (p < 0.05). The treatment group exhibited significantly higher patient satisfaction scores (p < 0.05). The incorporation of Streptomyces protease enzyme and Shutai into gastroscopy procedures resulted in significantly enhanced level of procedural efficacy and patient contentment while not introducing an additional risk of long‐term complications. The increase in moderate immediate reactions that have been observed requires additional research in order to determine their clinical significance. Although these agents present a possible progression in the field of gastroscopy, their application should be tempered by the immediate adverse reactions that have been documented. [ABSTRACT FROM AUTHOR]

Introduction: Management of lysosomal storage disorders (LSDs) requires periodic visits for medical surveillance and hospitalizations. Management of LSDs may have been adversely impacted during the COVID-19 pandemic. Objective: To identify the factors impacting health care for patients with LSDs during the COVID-19 pandemic. Methods: An observational study was conducted in Mumbai comparing infusion practices and reasons for missed infusions for 15 months before March 2020 versus two phases during the pandemic (April 2020–March 2021 and April 2021–March 2022) in patients receiving intravenous enzyme replacement therapy (ERT) and on oral substrate reduction therapy (SRT). Results: Fifteen patients with LSDs were enrolled. Before the pandemic, 6/13 (46%) were receiving ERT at the study site, 4/13 (31%) at a local hospital, and 3/13 (23%) at home; two were on SRT. The median distance traveled for receiving ERT was 37 km, and 4.4 infusions/patient were missed. From April 2020 to March 2021, two more patients opted for home ERT infusions. The median distance traveled for receiving ERT was 37 km, and 11.6 infusions/patient were missed. From April 2021 to March 2022, one more patient opted for home ERT infusions. The median distance traveled for receiving ERT was 7 km, and 5.6 infusions/patient were missed. The pandemic also affected SRT compliance adversely. For all patients, the cause of disrupted treatment was travel curbs (69%) and fear of getting COVID-19 infection (38%). Conclusions: Treatment of LSDs was disrupted during the pandemic, with an increase in missed ERT infusions and SRT doses. [ABSTRACT FROM AUTHOR]

The emergence of antimicrobial resistance raises the fear of untreatable diseases. Antimicrobial resistance is a multifaceted and dynamic phenomenon that is the cumulative result of different factors. While Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile, were previously the most concerning issues in the field of public health, Gram-negative pathogens are now of prime importance. The World Health Organization's priority list of pathogens mostly includes multidrug-resistant Gram-negative organisms particularly carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and extensively drug-resistant Acinetobacter baumannii. The spread of Gram-negative bacterial resistance is a global issue, involving a variety of mechanisms. Several strategies have been proposed to control resistant Gram-negative bacteria, such as the development of antimicrobial auxiliary agents and research into chemical compounds with new modes of action. Another emerging trend is the development of naturally derived antibacterial compounds that aim for targets novel areas, including engineered bacteriophages, probiotics, metal-based antibacterial agents, odilorhabdins, quorum sensing inhibitors, and microbiome-modifying agents. This review focuses on the current status of alternative treatment regimens against multidrugresistant Gram-negative bacteria, aiming to provide a snapshot of the situation and some information on the broader context. [ABSTRACT FROM AUTHOR]

In this study, the potential of aromatic Origanum species belonging to Lamiaceae family to prevent and treat cancer was investigated. Since aromatic plants contain phytochemicals such as essential oils, phenolic acids, terpenoids, flavonoids, alkaloids, vitamins, enzymes and minerals with beneficial biological activities, they have become more interesting and important in medicine, pharmacy and industry. Publications/research between 1950 and 2022 were screened to investigate the effects of Origanum species on cancer, and the effects of their extracts and essential oils in cancer prevention and treatment. Essential phytochemicals found in plants provide efficacy in the prevention and treatment of many diseases. Besides, the essential oils found in these plant extracts are another reason that makes them important. Therefore, it is preferred in traditional medicine in the fight against many diseases as well as cancer. Essential oils of Origanum species mainly contain monoterpenes such as p-cymene, carvacrol, thymol and γ-terpinene. Since these compounds exhibit anticancer properties, Origanum species are becoming the plants of choice in the fight against cancer. In this context, Origanum majorana L. Origanum vulgare and Origanum munzurense are promising species, considering the composition of their extracts and essential oil. [ABSTRACT FROM AUTHOR]

Background: Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disease caused by deficient activity of arylsulfatase A (ASA). Treatment options for patients are limited; gene therapy based on haematopoietic stem cell transplantation is the only approved treatment for some subtypes of MLD. Any therapeutic benefit of treatments must be meaningful for patients and their families. We evaluated the clinical meaningfulness of slowing the decline in gross motor function as measured by the Gross Motor Function Classification in MLD (GMFC-MLD) from the caregiver perspective via semi-structured telephone interviews with caregivers of children with late-infantile MLD. We also evaluated the perceived significance of declines in communication abilities measured by the Expressive Language Function Classification in MLD (ELFC-MLD). This work could help to inform the endpoints of a phase 2 clinical trial (NCT03771898) assessing the efficacy of intrathecal recombinant human ASA in MLD. Results: Twelve caregivers were recruited, reporting on 12 children with MLD. Children had a mean age of 6.1 years; mean age at symptom onset was 17.6 months. Most children (10/12) progressed from walking without support (categories 0–1) to a loss of locomotion (categories 5–6) in ≤ 2 years. Caregivers felt that GMFC-MLD and ELFC-MLD accurately described motor and language declines in their children, respectively. Most caregivers (10/12) reported that the idea of delaying disease progression would be meaningful. Further, a slowing of motor function decline in GMFC-MLD, from category 1 to category 3 or from category 2 to category 4 over 2 years, was seen as meaningful by all caregivers asked; however, only 3/12 caregivers reported that delayed decline would be meaningful if baseline category was ≥ 3. Caregivers also reported that delaying expressive language decline at any level that did not indicate a complete loss of expressive language (indicated by categories 1–3) would be meaningful. Conclusions: Caregivers of children with MLD felt that a delayed decline in gross motor function, as assessed by the GMFC-MLD, would be meaningful, supporting the selection of primary and secondary endpoints for the phase 2 clinical trial. Communication abilities were another area of significance for consideration in future clinical trial design. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a common leading cause of cancer related to women death worldwide. Cylindromatosis (CYLD) is known as an important tumor suppressor in various human cancers, and a deubiquitination enzyme (DUB) as well. Previously, we identified Skp2 as an E3 ligase of Aurora B ubiquitination, but the DUB of Aurora B still remains unknown. Methods: Aurora B ubiquitination site is identified through in vivo ubiquitination assay. Activity of Aurora B and CENPA was detected by immunoblotting (IB) and immunofluorescence (IF) assay. Protein-to-protein interaction was investigated by immunoprecipitation (IP). Cell chromosome dynamics was monitored by live-cell time-lapse Imaging. Cancer cell proliferation, colony formation, apoptosis, and cell invasion and migration assays were also performed. Protein level was checked by immunohistochemical (IHC) staining in clinical cervical cancer samples. Results: We identified Lysine 115 (K115) as the main Aurora B ubiquitination site for Skp2. We could also detect an interaction of Aurora B with the DUB CYLD. We found that CYLD promoted deubiquitination of Aurora B, and regulated Aurora B activity and function as well. Compared with control, we found it took more time for the cells to finish cell mitosis with CYLD over-expression. Furthermore, we found that CYLD deficiency promoted cervical cancer cell proliferation, colony formation, cell migration and invasion, and inhibited apoptosis instead, whereas it is just opposite with CYLD over-expression. In clinical cervical cancer samples, we showed a negative correlation of CYLD expression with Aurora B activation and histological cancer cell invasion. Furthermore, there was less CYLD abundance and higher Aurora B activity in advanced cancer samples compared with early stage. Conclusions: Our findings uncover CYLD as a novel potential DUB of Aurora B, which inhibits Aurora B activation and its subsequent function in cell mitosis, and also provide more evidence for its tumor suppressor function in cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This review highlights the role of phospholipase in lung cancer, a topic which should be better elucidated considering that phospholipase signaling plays a crucial role in the regulation of multiple cellular processes and its deregulation can promote lung tumorigenesis, favoring lung cancer cell proliferation, migration, and invasion. Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due to the presence of therapy-resistant cancer cells. For decades, chemotherapy and radiotherapy have dominated the treatment strategy for LC; however, relapses occur rapidly and result in poor survival. Malignant lung tumors are classified as either small- or non-small-cell lung carcinoma (SCLC and NSCLC). Despite improvements in the treatment of LC in recent decades, the benefits of surgery, radiotherapy, and chemotherapy are limited, although they have improved the prognosis of LC despite the persistent low survival rate due to distant metastasis in the late stage. The identification of novel prognostic molecular markers is crucial to understand the underlying mechanisms of LC initiation and progression. The potential role of phosphatidylinositol in tumor growth and the metastatic process has recently been suggested by some researchers. Phosphatidylinositols are lipid molecules and key players in the inositol signaling pathway that have a pivotal role in cell cycle regulation, proliferation, differentiation, membrane trafficking, and gene expression. In this review, we discuss the current understanding of phosphoinositide-specific phospholipase enzymes and their emerging roles in LC. [ABSTRACT FROM AUTHOR]

Gaucher Disease (GD) is a condition resulting from an autosomal recessive inheritance pattern, characterized by a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This leads to the accumulation of glucocerebroside and other glycolipids in multiple tissues, causing damage to various organ systems. The diagnosis of GD can be challenging due to its heterogeneity, non-specific symptoms, and variability across different geographic regions and age groups. Although GD is suspected based on symptoms or signs, the diagnosis is confirmed through the measurement of deficient b-glucocerebrosidase activity and the identification of biallelic pathogenic variants in the GBA gene. Intravenous enzyme replacement therapy (ERT) is recommended for GD patients. In this paper, we report a case of a 2-year and 8-month-old girl with massive splenomegaly and radiological finding of hepatic gaucheroma, in whom a genetic study showed homozygous mutation on the GBA gene at c.1448T>C (p.Leu483Pro) and certified the diagnosis of GD. This patient represents the youngest child reported to have gaucheroma and also the first one presenting with gaucheroma at the diagnosis and not during the follow up, highlighting that GD should be routinely included in the differential diagnosis of children presenting with splenomegaly and hepatomegaly, taking into account that the early start of ERT can change the natural history of the disease-preventing serious complications. [ABSTRACT FROM AUTHOR]

Objective: Patients with Lysosomal disorders (LSDs) are treated with regular infusions of enzyme replacement therapy (ERT). During the COVID-19 pandemic, home treatment was permitted. This study aimed at monitoring the patients' compliance with home therapy and its effects on physical, psychological, and relational issues. Moreover, we also tested the possible impact of home therapy on familial relationships and contacts with the referral hospital. Materials and Methods: Thirteen patients with Pompe disease (N = 8) and MPS (N = 5) were tested through an online questionnaire designed to assess their level of appreciation and satisfaction with home therapy and their feelings about the referral centre and psychological support provided. Results: Most of the patients (84%) stressed the positive impact of home therapy. All patients described a significant reduction in stressful conditions associated with the need to attend the hospital every week or two. Conclusions: Home ERT leads to a clear improvement in "daily life skills", as represented in our by sample by positive feelings, better emotional self-control, and an increased ability to understand the feelings of relatives. Our data underline the paramount positive effect home ERT has on both patients and their families. [ABSTRACT FROM AUTHOR]

Adagrasib (MRTX849) is a KRASG12C inhibitor with favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration. As of September 1, 2022, a total of 853 patients with KRASG12C-mutated solid tumors, including patients with CNS metastases, had received adagrasib (monotherapy or in combination). Adagrasib-related treatment-related adverse events (TRAEs) are generally mild to moderate in severity, start early in treatment, resolve quickly with appropriate intervention, and result in a low rate of treatment discontinuation. Common TRAEs seen in clinical trials included gastrointestinal-related toxicities (diarrhea, nausea, and vomiting); hepatic toxicities (increased alanine aminotransferase/aspartate aminotransferase) and fatigue, which can be managed through dose modifications, dietary modifications, concomitant medications (such as anti-diarrheals and anti-emetics/anti-nauseants) and the monitoring of liver enzymes and electrolytes. To manage common TRAEs effectively, it is imperative that clinicians are informed, and patients are fully counseled on management recommendations at treatment initiation. In this review, we provide practical guidance on the management of adagrasib TRAEs and discuss some best practices for patient and caregiver counseling to facilitate optimal outcomes for patients. Safety and tolerability data from the phase II cohort of the KRYSTAL-1 study will be reviewed and presented with practical management recommendations based on our experience as clinical investigators. [ABSTRACT FROM AUTHOR]

Background: Pompe disease (PD) is a lysosomal glycogen storage disorder caused by a deficiency in acid α-glucosidase (GAA) activity. Various organs, including the skeletal muscle, cardiac muscle, and liver, are commonly involved. Early initiation of enzyme replacement therapy (ERT) with recombinant human α-glucosidase (rhGAA) can improve the outcome. However, some patients experience a poor clinical course despite ERT because of the emergence of anti-rhGAA antibodies that neutralize rhGAA. Treatment against anti-rhGAA antibodies is challenging. Case–diagnosis/treatment: A 14-year-old boy with late-onset PD was referred to our hospital with proteinuria detected by school urinalysis screening. He was diagnosed with PD at the age of 4 years based on muscle biopsy and decreased GAA activity. Treatment with rhGAA was initiated, but anaphylaxis occurred frequently. Anti-rhGAA antibodies were detected and immune tolerance therapy was therefore given, but his antibody titer remained high. Kidney biopsy revealed stage II membranous nephropathy. Immunohistochemistry staining revealed anti-rhGAA antibody/rhGAA immune complexes along the glomerular capillary loop. Aggressive immunotherapy combined with bortezomib and rituximab was then initiated. Serum levels of anti-rhGAA antibodies decreased significantly and his proteinuria finally resolved. Conclusions: There have been few reports of membranous nephropathy associated with ERT for PD. We clarified the cause in the current patient. Bortezomib and rituximab effectively suppressed anti-rhGAA antibody production resulting in the resolution of proteinuria and maintenance of ERT efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal carcinomas (PDACs) are difficult to diagnose at an early stage and carry a poor overall prognosis for patients. Many patients with PDACs have serious nutritional deficiencies relating to their cancer. Typically, the pancreas produces enzymes resulting in food digestion. However, patients with pancreatic cancer often have a limited ability to digest their food due to decreased enzyme function, known as pancreatic enzyme insufficiency (PEI). These patients then become malnourished, which lowers their quality of life and reduces their survival. Unfortunately, PEI in PDACs is sometimes missed by healthcare providers. This paper reviews past studies describing malnutrition in PDAC, focusing on PEI and its treatment. It focuses on guidelines and recommendations for the appropriate treatment of PEI. We also review knowledge gaps of healthcare professionals regarding PEI to enhance treatment uptake and improve future patients' quality of life. Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients. [ABSTRACT FROM AUTHOR]

The article focuses on Pompe disease, a hereditary disorder caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase.

BACKGROUND: Cervical cancer is a common leading cause of cancer related to women death worldwide. Cylindromatosis (CYLD) is known as an important tumor suppressor in various human cancers, and a deubiquitination enzyme (DUB) as well. Previously, we identified Skp2 as an E3 ligase of Aurora B ubiquitination, but the DUB of Aurora B still remains unknown. METHODS: Aurora B ubiquitination site is identified through in vivo ubiquitination assay. Activity of Aurora B and CENPA was detected by immunoblotting (IB) and immunofluorescence (IF) assay. Protein-to-protein interaction was investigated by immunoprecipitation (IP). Cell chromosome dynamics was monitored by live-cell time-lapse Imaging. Cancer cell proliferation, colony formation, apoptosis, and cell invasion and migration assays were also performed. Protein level was checked by immunohistochemical (IHC) staining in clinical cervical cancer samples. RESULTS: We identified Lysine 115 (K115) as the main Aurora B ubiquitination site for Skp2. We could also detect an interaction of Aurora B with the DUB CYLD. We found that CYLD promoted deubiquitination of Aurora B, and regulated Aurora B activity and function as well. Compared with control, we found it took more time for the cells to finish cell mitosis with CYLD over-expression. Furthermore, we found that CYLD deficiency promoted cervical cancer cell proliferation, colony formation, cell migration and invasion, and inhibited apoptosis instead, whereas it is just opposite with CYLD over-expression. In clinical cervical cancer samples, we showed a negative correlation of CYLD expression with Aurora B activation and histological cancer cell invasion. Furthermore, there was less CYLD abundance and higher Aurora B activity in advanced cancer samples compared with early stage. CONCLUSIONS: Our findings uncover CYLD as a novel potential DUB of Aurora B, which inhibits Aurora B activation and its subsequent function in cell mitosis, and also provide more evidence for its tumor suppressor function in cervical cancer. [ABSTRACT FROM AUTHOR]

Deemed one of the most problematic neurodegenerative diseases in the elderly population, Parkinson's disease remains incurable to date. Ongoing diagnostic studies, however, have revealed that a large number of small molecule drugs that trigger the BMP2-Smad signaling pathway with an osteogenic nature may be effective in Parkinson's disease treatment. Although BMP2 and Smad1, 3, and 5 biomolecules promote neurite outgrowth and neuroprotection in dopaminergic cells as well, small molecules are quicker at crossing the BBB and reaching the damaged dopaminergic neurons located in the substantia nigra due to a molecular weight less than 500 Da. It is worth noting that osteogenic small molecules that inhibit Smurf1 phosphorylation do not offer therapeutic opportunities for Parkinson's disease; whereas, osteogenic small molecules that trigger Smad1, 3, and 5 phosphorylation may have strong therapeutic implications in Parkinson's disease by increasing the survival rate of dopaminergic cells and neuritogenesis. Notably, from a different perspective, it might be said that osteogenic small molecules can possibly put forth therapeutic options for Parkinson's disease by improving neuritogenesis and cell survival. [ABSTRACT FROM AUTHOR]

Fabry disease (FD) is a rare, lysosomal storage disorder characterized by multi-organ accumulation of predominantly globotriaosylceramide (GL3) and its metabolite. Resulting renal, cardiac, and cerebrovascular complications are crucial causes of morbidity and mortality in FD. Enzyme replacement therapy (ERT) shows promising outcomes for these patients, provided that therapy is initiated early. Thus, precise and early diagnosis of the disease is a pivotal factor determining the corollary of the disease. We report two cases of young adult males who presented to the nephrology department with proteinuria. A kidney biopsy was performed in both cases, which was suggestive of FD. The final conclusive diagnosis of FD was provided by electron microscopy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 9-year-old boy with Hunter's syndrome, characterized by rare genetic mutations and distinct clinical features. Topics discussed include the clinical presentation of skin pebbling, radiographic findings indicative of dysostosis multiplex, and the identification of a unique missense mutation in the Iduronate-2-sulfatase (IDS) gene.

Objective: The objective of this paper is to assess the economic profile of enzyme replacement therapy (ERT) to symptomatic patients with Pompe, Fabry, Gaucher disease and Lysosomal acid lipase (LAL) deficiency. Methods: A systematic search was performed to retrieve and critically assess economic evaluations of enzyme replacement therapy. Publications were screened according to predefined criteria and evaluated according to the Quality of Economic Studies. Data were narratively synthesized. Results: The Incremental Cost-Effectiveness Ratio greatly exceeded willingness to pay thresholds. The cost of the medication dominated the sensitivity analysis. For Infantile-onset Pompe's disease, the incremental cost-effectiveness ratio (ICER) was estimated at €1.043.868 per Quality-adjusted life year (QALY) based on the dose of alglucosidase 40 mg/kg/ week, and €286.114 per QALY for 20 mg of alglucosidase/kg/2 weeks. For adults patients presenting with Pompe disease the reported was ICER € 1.8 million/ QALY. In the case of Fabry disease, the ICER per QALY amounts to 6.1 million Euros/QALY. Respectively for Gaucher's disease, the ICER /QALY was estimated at € 884,994 per QALY. Finally, for patients presenting LAL deficiency NCPE perpetuated an ICER of €2,701,000/QALY. Discussion: ERT comprise a promising treatment modality for orphan diseases; nevertheless, it is interlaced with a substantial economic burden. Moreover, the available data on the cost-effectiveness ratio are scarce. For certain diseases, such as Fabry, a thorough selection of patients could exert a beneficial effect on the reported ICER. Steep price reductions are imperative for these products, in the conventional reimbursement pathway or a new assessment framework should be elaborated, which in principle, should target uncertainty. [ABSTRACT FROM AUTHOR]

The article presents a summary of best available evidence on the experiences of patients with lysosomal storage disorders (LSD) receiving enzyme replacement therapy (ERT), along with the experiences of their family members. Topics include several types, organs affected and causes of LSDs, symptoms prevented by ERT and how this therapy is administered, and some of the experiences of LSD patients under ERT such as anxiety and psychological burden.

Pompe disease (PD) is an inherited metabolic disorder caused by a deficiency of acid α-glucosidase (GAA), leading to lysosomal accumulation of glycogen, mainly in skeletal and cardiac muscles as well as the nervous system. Patients with PD develop cellular dysfunction and muscle damage. PD can be classified into two classic forms, namely infantile-onset PD (IOPD) and late-onset PD (LOPD). Delayed treatment, particularly in IOPD, would result in significant organ damage and early death. Nonetheless, early diagnosis and timely treatment are often hampered by the rarity of PD and its wide variety of, but overlapping, symptoms. This article reviews the common clinical presentations of PD and outlines the essentials of PD management. In particular, the implications of newborn screening (NBS) and clinical performance of enzyme replacement therapy (ERT) are highlighted. [ABSTRACT FROM AUTHOR]

Exebacase, an antistaphylococcal lysin produced from a bacteriophage-encoded gene, is a promising adjunctive therapy for severe methicillin-resistant Staphylococcus aureus infections. We describe the first infant to receive exebacase, dosing, and pharmacokinetics. Exebacase may be safe and efficacious in children; however, further clinical trials are needed to optimize dosing. [ABSTRACT FROM AUTHOR]

Vericiguat (Verquvo®) is the first oral soluble guanylate cyclase (sGC) stimulator to be approved for the treatment of adults with symptomatic, chronic heart failure with reduced ejection fraction (HFrEF). In the phase III VICTORIA trial, vericiguat added to standard of care (SOC) was associated with a significantly lower risk of the primary composite endpoint of death from cardiovascular (CV) causes or first hospitalization from heart failure (HHF) than placebo added to SOC in adults with chronic HFrEF. The risk of all-cause mortality or first HHF (secondary composite endpoint) and the total number of HHF were also statistically significantly reduced by vericiguat therapy. Vericiguat showed no benefit with respect to the primary endpoint in a subgroup of patients with grossly elevated N-terminal pro-brain natriuretic peptide levels. Vericiguat was generally well tolerated; the most common treatment-related adverse event (AE) was hypotension. AEs of special interest included symptomatic hypotension and syncope, which occurred with low incidences that were similar between treatment groups. Thus, vericiguat is an effective and generally well-tolerated treatment option in patients with symptomatic, chronic HFrEF who have experienced a recent worsening event, expanding the options currently available for chronic HFrEF management. Plain Language Summary: Approximately half of patients with heart failure develop chronic heart failure with reduced ejection fraction (HFrEF). Despite using various standard treatments that are available, some patients with symptomatic, chronic HFrEF still develop worsening heart failure. Soluble guanylate cyclase (sGC) stimulators are an emerging treatment option for heart failure management. They work by stimulating sGC activity (which is reduced in patients with heart failure), with potential benefits for myocardial and vascular function. Vericiguat (Verquvo®) is the first oral sGC stimulator to be approved for the treatment of adults with symptomatic, chronic HFrEF. When added to standard treatment(s) for chronic HFrEF, vericiguat reduced the combined risk of death from cardiovascular causes or first hospitalization for heart failure. This was primarily driven by a reduction in hospitalizations for heart failure (rather than in mortality). Vericiguat was generally well tolerated in these patients, and the incidences of adverse events of special interest such as symptomatic low blood pressure and fainting were low and similar between vericiguat and placebo recipients. Thus, vericiguat is an effective and well-tolerated treatment option in patients with symptomatic, chronic HFrEF who have experienced a recent worsening event. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by multiple motor and non-motor symptoms. Mutations in the glucocerebrosidase (GBA) gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), which hydrolyzes glucosylceramide (GlcCer) to glucose and ceramide, are the most important and common genetic PD risk factors discovered to date. Homozygous GBA mutations result in the most common lysosomal storage disorder, Gaucher's disease (GD), which is classified according to the presence (neuronopathic types, type 2 and 3 GD) or absence (non-neuronopathic type, type 1 GD) of neurological symptoms. The clinical manifestations of PD in patients with GBA mutations are indistinguishable from those of sporadic PD at the individual level. However, accumulating data have indicated that GBA -associated PD patients exhibit a younger age of onset and a greater risk for cognitive impairment and psychiatric symptoms. The mechanisms underlying the increased risk of developing PD in GBA mutant carriers are currently unclear. Contributors to GBA -PD pathogenesis may include mitochondrial dysfunction, autophagy-lysosomal dysfunction, altered lipid homeostasis and enhanced α-synuclein aggregation. Therapeutic strategies for PD and GD targeting mutant GCase mainly include enzyme replacement, substrate reduction, gene and pharmacological small-molecule chaperones. Emerging clinical, genetic and pathogenic studies on GBA mutations and PD are making significant contributions to our understanding of PD-associated pathogenetic pathways, and further elucidating the interactions between GCase activity and neurodegeneration may improve therapeutic approaches for slowing PD progression. [ABSTRACT FROM AUTHOR]

Aim: The coronavirus disease-2019 (COVID-19) pandemic has caused a worldwide public health emergency, especially affecting people with chronic illnesses including lysosomal storage disorders (LSDs). The unfavorable conditions due to COVID-19 have mostly affected people with chronic conditions, in terms of disease vulnerability and access to health-care. In the present study, we aimed to assess the problems the patients with LSDs on enzyme replacement therapy (ERT) have encountered during the pandemic, and their level of anxiety. Parental evaluation has also been made for pediatric patients. Materials and Methods: A total of 19 participants were recruited. A semi-structured interview was structured to evaluate the effects of the COVID-19 pandemic on ERT. The Turkish version of "Hospital Anxiety and Depression scale" (HADS) for adult patients and parents were used to evaluate anxiety. Patients between ages 8-17 completed the child version of the Revised Child Anxiety and Depression scale (RCADS). Results: The study was completed by 19 patients, and 13 parents. Five patients (26%) admitted temporary disruption of treatment, of which the most common reason was the fear of getting infected. Eighty-nine percent of all participants were willing to receive treatment at home. Only one adult patient revealed to feel anxiety (16%). While among parents evaluated with HADS, 7/13 had scores that indicated depression and anxiety, 3/4 pediatric patients had RCADS scores indicative of anxiety and depression. Conclusion: The problems LSD patients have been facing during the pandemic, should be identified along with their attitudes regarding ERT in order to maintain the sustainability of their treatment. The psychological health of these patients should also be identified and supported, to provide optimal care to patients. [ABSTRACT FROM AUTHOR]

Pancreatic enzyme replacement therapy (PERT) and fat predigestion are key in ensuring the optimal growth of patients with cystic fibrosis. Our study attempted to highlight differences between fat predigestion and conventional PERT on body composition of young pigs with exocrine pancreatic insufficiency (EPI). EPI and healthy pigs were fed with high-fat diet for six weeks. During the last two weeks of the study, all pigs received additional nocturnal alimentation with Peptamen AF (PAF) and were divided into three groups: H—healthy pigs receiving PAF; P—EPI pigs receiving PAF+PERT; and L—EPI pigs receiving PAF predigested with an immobilized microbial lipase. Additional nocturnal alimentation increased the body weight gain of EPI pigs with better efficacy in P pigs. Humerus length and area in pigs in groups L and P were lower than that observed in pigs in group H (p value 0.005-0.088). However, bone mineral density and strength were significantly higher in P and L as compared to that of H pigs (p value 0.0026-0.0739). The gut structure was improved in P pigs. The levels of neurospecific proteins measured in the brain were mainly affected in P and less in L pigs as compared to H pigs. The beneficial effects of the nocturnal feeding with the semielemental diet in the prevention of EPI pigs' growth/development retardation are differently modified by PERT or fat predigestion in terms of growth, bone properties, neurospecific protein distribution, and gut structure. [ABSTRACT FROM AUTHOR]

Dermatitis as an initial manifestation of cystic fibrosis (CF) is unusual. The eruption is usually first noted in the perineum anywhere from several days to few months after birth. It subsequently spreads to the extremities and trunk. We report a 2-month-old male baby who presented with failure to thrive, hypoproteinemia, anemia, and a cutaneous eruption resembling acrodermatitis enteropathica. Oral zinc supplementation resulted in temporary resolution of the dermatitis. A further workup revealed the diagnosis of CF. The rash was responsive to nutritional and pancreatic enzyme supplementation. [ABSTRACT FROM AUTHOR]

Cancer is the dangerous disease which caused millions of deaths in worldwide. Enzyme prodrug therapy uses enzymes artificially introduced into the body to convert pro-drugs which have poor biological activity to the active form in the desired location within the body. The use of enzyme pro-drug therapy has gained attention as it has the ability to improve the efficacy and safety of cancer treatment. Chemotherapy for cancer patients has limited success including some drawbacks like systemic toxicity, insufficient drug concentration in tumors. To overcome these drawbacks and improve the cancer treatment the enzyme pro-drug therapy is selected. Enzyme prodrug therapy uses enzymes artificially introduced into the body to convert pro-drugs which have poor biological activity to the active form in the desired location within the body. The selective activation of pro-drugs in tumor tissues by exogenous enzymes for cancer therapy was accomplished by several ways including gene-directed enzyme pro-drug therapy(GDEPT), virus-directed enzyme pro-drug therapy(VDEPT), antibody-directed enzyme pro-drug therapy(ADEPT). Most of these therapies are based on antibody dependent cellular cyto-toxicity, targeted delivery of cytotoxic drugs/tumor site specific activation of prodrugs. This review aims at providing an overview regarding four major systems of GDEPT, ADEPT, VDEPT. Later this review focuses on the bystander effect and combination therapy associated with gene therapy. [ABSTRACT FROM AUTHOR]

Background: Medication use is important to collect accurately in medically complex patients in both clinical and research settings. Aim: We assessed patient‐level agreement for medication use between self‐reported survey and electronic health record (EHR) for children with cystic fibrosis (CF). Methods: Our retrospective cross‐sectional study focused on children with CF ages 6‐20 years from Seattle Children's Hospital in Washington state, USA (N = 85). A self‐ or parent‐reported survey included questions on current use of specific medications and antibiotic use in the past 2 months. We compared survey data with data abstracted from the individual's EHR and derived Cohen's Kappa statistics to estimate the level of agreement between the two methods. Results: Self‐reported medication use was generally higher in the survey than in the EHR. The level of agreement ranged from slight for probiotics (74.1% agreement; 95% confidence interval [CI]: 64.6%‐83.6%; kappa: 0.07), pancreatic enzymes (80% agreement; 95% CI: 71.3%‐88.7%; kappa: 0.12), and vitamin D (55.3% agreement; 95% CI: 44.5%‐66.1%; kappa: 0.20) to moderate for chronic azithromycin (80% agreement; 95% CI: 7.13%‐88.7%; kappa: 0.50), proton pump inhibitors (76.5% agreement; 95% CI: 67.3%‐85.7%; kappa: 0.46), and oral antibiotics (70.6% agreement; 95% CI: 60.7%‐80.5%; kappa: 0.42). Conclusion: There is considerable heterogeneity in level of agreement in medication use between self‐reported survey and EHR data for children with CF. Standardized approaches are needed to improve the accuracy of medication data collected in clinical practice and research. [ABSTRACT FROM AUTHOR]

Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step‐up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non‐opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner. [ABSTRACT FROM AUTHOR]

Inherited metabolic disorders are a large group of rare disorders affecting normal biochemical pathways. Many metabolic disorders can present with symptoms affecting the eye, and eye disorders can evolve later in the natural history of an already diagnosed metabolic disorder. The ophthalmic involvement can be very varied affecting any part of the eye, including abnormalities of cornea, lens dislocation and cataracts, retina and the distal optic pathway, and extraocular muscles. Awareness of inherited metabolic disorders is important to facilitate early diagnosis and in some cases instigate early treatment if a patient presents with eye involvement suggestive of a metabolic disorder. Ophthalmological interventions are also an important component of the multisystem holistic approach to treating patients with metabolic disorders. [ABSTRACT FROM AUTHOR]

Purpose. Mucopolysaccharidoses (MPS) are group of inherited lysosomal storage diseases caused by mutations of enzymes involved in catalyzing different glycosaminoglycans (GAGs). MPS I and MPS II exhibit both somatic and neurological symptoms with a relatively high disease incidence. Hematopoietic stem cell therapy (HSCT) and intravenous enzyme replacement therapy (ERT) have had a significant impact on the treatment and comprehension of disease. This review is aimed at providing a comprehensive evaluation of the pros and cons of HSCT and ERT, as well as an up-to-date knowledge of new drugs under development. In addition, multiple disease management strategies for the uncontrollable manifestations of MPS I and MPS II to improve patients' quality of life are presented. Findings. Natural history of MPS I and MPS II shows that somatic and neurological symptoms occur earlier in severe forms of MPS I than in MPS II. ERT increases life expectancy and alleviates some of the somatic symptoms, but musculoskeletal, ophthalmological, and central nervous system (CNS) manifestations are not controlled. Additionally, life-long treatment burdens and immunogenicity restriction are unintended consequences of ERT application. HSCT, another treatment method, is effective in controlling the CNS symptoms and hence has been adopted as the standard treatment for severe types of MPS I. However, it is ineffective in MPS II, which can be explained by the relatively late diagnosis. In addition, several factors such as transplant age limits or graft-versus-host disease in HSCT have limited its application for patients. Novel therapies, including BBB-penetrable-ERT, gene therapy, and substrate reduction therapy, are under development to control currently unmanageable manifestations. BBB-penetrable-ERT is being studied comprehensively in the hopes of being used in the near future as a method to effectively control CNS symptoms. Gene therapy has the potential to "cure" the disease with a one-time treatment rather than just alleviate symptoms, which makes it an attractive treatment strategy. Several clinical studies on gene therapy reveal that delivering genes directly into the brain achieves better results than intravenous administration in patients with neurological symptoms. Considering new drugs are still in clinical stage, disease management with close monitoring and supportive/palliative therapy is of great importance for the time being. Proper rehabilitation therapy, including physical and occupational therapy, surgical intervention, or medications, can benefit patients with uncontrolled musculoskeletal, respiratory, ophthalmological, and neurological manifestations. [ABSTRACT FROM AUTHOR]

Various amyloidogenic proteins have been suggested to be involved in the onset and progression of neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Particularly, the aggregation of misfolded amyloid-β and hyperphosphorylated tau and α-synuclein are linked to the pathogenesis of AD and PD, respectively. In order to care the diseases, multiple small molecules have been developed to regulate the aggregation pathways of these amyloid proteins. In addition to controlling the aggregation of amyloidogenic proteins, maintaining the levels of the proteins in the brain by amyloid degrading enzymes (ADE; neprilysin (NEP), insulin-degrading enzyme (IDE), asparagine endopeptidase (AEP), and ADAM10) is also essential to cure AD and PD. Therefore, numerous biological molecules and chemical agents have been investigated as either inducer or inhibitor against the levels and activities of ADE. Although the side effect of enhancing the activity of ADE could occur, the removal of amyloidogenic proteins could result in a relatively good strategy to treat AD and PD. Furthermore, since the causes of ND are diverse, various multifunctional (multitarget) chemical agents have been designed to control the actions of multiple risk factors of ND, including amyloidogenic proteins, metal ions, and reactive oxygen species. Many of them, however, were invented without considerations of regulating ADE levels and actions. Incorporation of previously created molecules with the chemical agents handling ADE could be a promising way to treat AD and PD. This review introduces the ADE and molecules capable of modulating the activity and expression of ADE. [ABSTRACT FROM AUTHOR]

Pancreatic exocrine insufficiency (PEI) is associated with significant gastrointestinal symptoms, but is readily treated by pancreatic enzyme replacement therapy (PERT). We reviewed our current practice and examined the factors that predict repeating a positive faecal elastase-1 (FE1; <200 µg/g), the repeat FE1 being normal, initiation of PERT and clinical response to treatment. A single-centre retrospective cohort study was conducted. Outpatients with FE1 <200 μg/g between 2012 and 2018 were included. Logistic regression was used to explore the associations with each outcome, with statistical adjustment for confounders. Two-hundred and ten patients were included; 28.1% of patients had their FE1 repeated, 47.5% of whom had a normal repeat result. Patients with initial FE1 <15 µg/g were unlikely to be reclassified on repeat testing. Patients with a confirmatory low FE1, abnormal pancreatic imaging or abnormal nutrition blood tests were more likely to be started on PERT (all p<0.05). Patients with abnormal pancreatic imaging were 10 times more likely to respond to PERT (odds ratio 10.70; 95% confidence interval 1.62-70.70; p=0.01). Augmenting clinical judgement with pancreatic imaging and repeat FE1 testing could improve the rate of PERT prescription and inform the approach to non-response, particularly in cases where there is diagnostic doubt. [ABSTRACT FROM AUTHOR]

Background/Aim: The aim of this study was to establish a patient-derived orthotopic xenograft (PDOX) mouse model of liver metastasis of triple-negative breast cancer (TNBC) and examine the efficacy of oral recombinant methioninase (o-rMETase) on the liver metastasis. Materials and Methods: TNBC from a patient was implanted in the left hepatic lobe of nude mice to simulate liver metastasis in a PDOX model. Ten days later, all mice underwent laparotomy to measure tumor size and were randomized to three groups: control; o-rMETase 100 U once daily (qd); and o-rMETase 200 U qd. After 9 days of treatment, all mice were sacrificed. Results: At the end of the treatment period for the liver metastasis, the size of liver metastases was 372.6 mm3 in the control group; 160.0 mm3 in the o-rMETase 100 U group; and 245.3 mm3 in the orMETase 200 U group. All mice had ascites and 12 out of 14 mice in all groups had mesenteric lymph-node metastasis, as re-metastasis. The mean body-condition score was 1.5 in the control group; 2.4 in the o-rMETase 100 U group; and 2.6 in the o-rMETase 200 U group (control group vs. o-rMETase 200 U group, p<0.05). Conclusion: The TNBC liver metastasis was highly aggressive resulting in re-metastasis and ascites. o-rMETase tended to inhibit the liver metastasis and significantly improved the mouse bodycondition score. This new PDOX model of TNBC liver metastasis will be useful for identifying effective agents for this recalcitrant disease. [ABSTRACT FROM AUTHOR]

In this article, Margaret Gettis and Betsy Anne Dye describe how they partnered to align the care provided to cystic fibrosis (CF) patients during hospitalization with the evidence-based care practices of their organization's outpatient center. It mentions that chronic illnesses like CF are long in duration and slowly progress throughout a person's life; and treatment plans for patients with CF should ensure the patient's continuing capability to self-manage the condition.

The clinical effectiveness and scar quality of the randomized controlled trial comparing enzyme alginogel with silver sulfadiazine (SSD) for treatment of partial thickness burns were previously reported. Enzyme alginogel did not lead to faster wound healing (primary outcome) or less scar formation. In the current study, the health‐related quality of life (HRQoL), costs, and cost‐effectiveness of enzyme alginogel compared with SSD in the treatment of partial thickness burns were studied. HRQoL was evaluated using the Burn Specific Health Scale‐Brief (BSHS‐B) and the EQ‐5D‐5L questionnaire 1 week before discharge and at 3, 6, and 12 months postburn. Costs were studied from a societal perspective (health care and nonhealth‐care costs) for a follow‐up period of 1 year. A cost‐effectiveness analysis was performed using cost‐effectiveness acceptability curves and comparing differences in societal costs and Quality Adjusted Life Years (QALYs) at 1 year postburn. Forty‐one patients were analyzed in the enzyme alginogel group and 48 patients in the SSD group. None of the domains of BSHS‐B showed a statistically significant difference between the treatment groups. Also, no statistically significant difference in QALYs was found between enzyme alginogel and SSD (difference −0.03; 95% confidence interval [CI], −0.09 to 0.03; P =.30). From both the health care and the societal perspective, the difference in costs between enzyme alginogel and SSD was not statistically significant: the difference in health‐care costs was €3210 (95% CI, €‐1247 to €7667; P =.47) and in societal costs was €3377 (95% CI €‐6229 to €12 982; P =.49). The nonsignificant differences in costs and quality‐adjusted life‐years in favor of SSD resulted in a low probability (<25%) that enzyme alginogel is cost‐effective compared to SSD. In conclusion, there were no significant differences in quality of life between both treatment groups. Enzyme alginogel is unlikely to be cost‐effective compared with SSD in the treatment of partial thickness burns. [ABSTRACT FROM AUTHOR]

Inborn errors of metabolism (IEMs) or metabolic disorders are complex conditions involving abnormalities in biochemical and metabolic pathways necessary for healthy human existence. They are often caused by partial or total deficiency of key enzymes and these conditions usually present in infancy or early childhood. Some may not be identified until adolescence or even during the adult years. This discussion reviews some of the IEMs that can become evident in the adolescent years, such as adrenoleukodystrophy, glycogen storage diseases, lysosomal storage diseases, urea cycle disorders, and others. Management focuses on symptomatic treatment and when available as well as affordable, enzyme replacement therapies. Gene therapy and stem cell transplantation are options under current research in addition to finding more replacement enzymes. [ABSTRACT FROM AUTHOR]

Exocrine pancreatic insufficiency (EPI) prevents the pancreas from making enough of the exocrine pancreatic enzymes that help the body digest food. EPI can be challenging to recognize and diagnose because many of its signs and symptoms overlap with other gastrointestinal disorders. This article offers practical advice to nurses for patient assessment and nursing interventions. [ABSTRACT FROM AUTHOR]