Visual and Refractive Outcomes after Phacoemulsification Cataract Surgery in Nanophthalmic Eyes.

Background/Objectives: The aim of this study was to report the visual and refractive outcomes of nanophthalmic eyes undergoing phacoemulsification at a tertiary cataract center. Methods: This is a prospective consecutive case series. Patients with an axial length of ≤20.5 mm who underwent phacoemulsification at a tertiary cataract center in Hong Kong were included. Eyes undergoing extracapsular cataract extraction or with a previous history of intraocular surgery including trabeculectomy were excluded. The outcome measures were the corrected distance visual acuity (CDVA) and refractive status at four months post-operation. Different intraocular lens formulas were used to compare the refractive outcomes. Results: Out of 22,847 cataract surgeries performed from May 2011 to March 2020, 14 eyes (0.06%) of 10 patients had axial lengths of ≤20.5 mm and underwent phacoemulsification. The mean axial length was 20.13 ± 0.44 mm. Out of these fourteen eyes, three (21%) had postoperative myopic shift with spherical equivalent refraction of more than or equal to 1D compared to the original target. Eleven eyes (79%) had postoperative refraction within 0.5D compared to the original target. Nine out of fourteen eyes (64%) had improvements in postoperative vision. There were no intraoperative complications. When comparing the Hoffer Q, Holladay 1, Holladay 2, Haigis and Hill-RBF 2.0 formulas, there was no significant difference in the absolute errors between the five formulas (p = 0.072). Conclusions: There was no significant difference in the mean absolute errors between the Hoffer Q, Holladay 1, Holladay 2, Haigis and Hill-RBF 2.0 formulas. Myopic shift was not uncommon, and more studies on intraocular lens (IOL) power calculation for short eyes are warranted.

Cultural immersion in dietetics curricula: A method for ensuring Aboriginal pedagogies are used for Aboriginal educational content.

AIMS: To describe an Aboriginal cultural immersion delivered to dietetics students at a large university in Australia and assess its effectiveness as a method to teach Aboriginal history, culture, diet, and health in dietetics. METHODS: Taking a strength-based approach, Aboriginal processes of learning were privileged, with the cultural immersion being co-designed with immersion educators, a First Nations researcher, and dietetics academic. The cultural immersion consisted of an opening ceremony and four stations of yarning, weaving, bush tucker, and artefacts/medicines. A mixed-methods approach was used, with triangulation of data from pre- and postsurveys, station mapping, and focus group interviews. Quantitative and qualitative data were simultaneously analysed from participating first-year Master of Nutrition and Dietetics students and then drawn together for an integrated understanding of the impact of the cultural immersion on student learnings. RESULTS: Fifty-three students completed pre- and postsurveys and 36 participated in focus groups. Through sharing lived experiences, learning through culture, and keeping sessions practical and Aboriginal leadership, each cultural immersion station utilised Aboriginal processes of learning that meaningfully engaged students with Aboriginal education content, appreciate holistic health and increased their general knowledge on Aboriginal history, culture, diet, and health (all p < 0.001). CONCLUSION: Cultural immersion is one teaching method to enhance student knowledges and can be a part of a programmatic and integrated approach that embeds Aboriginal content throughout the whole curriculum. It is necessary that institutions recognise the value of cultural immersions to student learnings and commit to providing ongoing support.

Looking to "Level the Field": A Qualitative Study of How Clinicians Operationalize Social Determinants in Critical Care.

INTRODUCTION: Current critical care practice does not integrate social determinants of health (SDOH) in systematic or standardized ways. Routine assessment of SDOH in the intensive care unit (ICU) may improve clinical decision-making, patient- and family-centered outcomes, and clinician well-being. Given the appropriateness and feasibility of SDOH assessment in the ICU is unknown, we aimed to understand how ICU clinicians think about and use SDOH. METHODS: We conducted semi-structured interviews with clinicians focused on barriers to and facilitators of assessing SDOH during critical illness and perceptions on screening for SDOH in the ICU. We used chart-stimulated recall to assist clinicians in reflecting on how SDOH applied to and was used in patients' care. After deidentifying interviews, we analyzed transcripts guided by a thematic analysis approach using a combination of inductive and deductive coding, the latter framed within the Centers for Disease Control SDOH Healthy People framework. RESULTS: We completed interviews with 30 clinicians, in a variety of professional roles. The majority of clinicians self-identified as men (17, 56.7%) of White race (25, 83.3%). Clinicians contextualize their use of SDOH within three frames of reference: 1) their own identity and experiences; 2) their relationships and communication with patients and caregivers; and 3) immediate structures of care around ICU patients including clinician advocacy, care transitions, and readmission. Clinicians identified that discussing SDOH could allow them to recognize bias faced by their patients, elucidate drivers of critical illness, and navigate communication with patients caregivers. Clinicians worried about ICU-specific factors impeding the discussion of SDOH including time contraints and acuity, high stakes and emotions, and negative anticipatory emotions. DISCUSSION: Clinicians gather SDOH during critical illness both to understand their patients' stories and provide individualized care, which may lead to better clinician satisfaction and patient- and family-centered care outcomes. Educational and operational efforts to increase SDOH assessment and use in critical care should also gather and integrate the perspectives of patients and caregivers regarding the collection and use of SDOH in the ICU.

Clinical and analytical validation of an 82-gene comprehensive genome-profiling panel for identifying and interpreting variants responsible for inherited retinal dystrophies.

Inherited retinal dystrophies comprise a clinically complex and heterogenous group of diseases characterized by visual impairment due to pathogenic variants of over 300 different genes. Accurately identifying the causative gene and associated variant is crucial for the definitive diagnosis and subsequent selection of precise treatments. Consequently, well-validated genetic tests are required in the clinical practice. Here, we report the analytical and clinical validation of a next-generation sequencing targeted gene panel, the PrismGuide IRD Panel System. This system enables comprehensive genome profiling of 82 genes related to inherited retinal dystrophies. The PrismGuide IRD Panel System demonstrated 100% (n = 43) concordance with Sanger sequencing in detecting single-nucleotide variants, small insertions, and small deletions in the target genes and also in assessing their zygosity. It also identified copy-number loss in four out of five cases. When assessing precision, we evaluated the reproducibility of variant detection with 2,160 variants in 144 replicates and found 100% agreement in terms of single-nucleotide variants (n = 1,584) and small insertions and deletions (n = 576). Furthermore, the PrismGuide IRD Panel System generated sufficient read depth for variant calls across the purine-rich and highly repetitive open-reading frame 15 region of RPGR and detected all five variants tested. These results show that the PrismGuide IRD Panel System can accurately and consistently detect single-nucleotide variants and small insertions and deletions. Thus, the PrismGuide IRD Panel System could serve as useful tool that is applicable in clinical practice for identifying the causative genes based on the detection and interpretation of variants in patients with inherited retinal dystrophies and can contribute to a precise molecular diagnosis and targeted treatments.

Toxic Epidermal Necrolysis Secondary to Iodine Versus Methimazole in a Pediatric Patient With Complex Autoimmune Disease.

We report a case of a 17-year-old girl who developed toxic epidermal necrolysis (TEN) secondary to preoperative iodine administration before thyroidectomy for Graves' disease. Past medical history was significant for COVID-19 and multisystem inflammatory syndrome in Children (MISC-C), with subsequent diagnoses of type 1 diabetes mellitus (T1DM), Addison disease, and Graves' disease. Her Graves disease was initially managed with methimazole. While there are reported cases of Stevens-Johnson syndrome (SJS) and TEN due to methimazole, the patient had discontinued methimazole over one month prior. Therefore, she likely represents the first case of TEN reported secondary to potassium iodide solution in a pediatric patient. Given the rarity of TEN in pediatric patients, our case highlights the challenges in managing complex autoimmune conditions and underscores the importance of careful medication choices in such cases.

Patient-perceived dysphagia and voice change post thyroid surgery: a telephone questionnaire.

OBJECTIVE: This study analyses the incidence of subjectively experienced dysphagia and voice change in post-thyroidectomy and parathyroidectomy patients without recurrent laryngeal nerve palsy. METHODS: A total of 400 patients were invited to participate in a telephone questionnaire based on the Dysphagia Handicap Index and Voice Handicap Index. At 6-24 months following surgery, participants were divided into: post-thyroid surgery (total, hemi-, parathyroidectomy) groups and controls (other ENT procedures). A total of 254 responses were received (127 following thyroid surgery, 127 controls). RESULTS: Twenty-two per cent of post-thyroidectomy patients had a Voice Handicap Index score of more than 3, compared to 15 per cent of parathyroid patients and 4 per cent of controls. The mean Dysphagia Handicap Index score for patients post thyroidectomy and hemi-thyroidectomy was 2.0. Parathyroidectomy patients had a mean Dysphagia Handicap Index score of 1.3, higher than controls at 1.0. CONCLUSION: Dysphagia and voice alteration are common following thyroid surgery, even in the absence of recurrent laryngeal nerve injury. Both deficits occur more frequently following thyroid surgery than parathyroid surgery.

Systems map of interventions to improve dietary intake of pre-school aged children: A scoping review.

Implementation and sustaining impact of early childhood nutrition interventions in practice remains a challenge. An understanding of the extent to which determinants across multiple levels of the food system are being addressed may improve success. This literature review aimed to synthesise the evidence on interventions targeting dietary intake and eating behaviours in preschool children using a systems approach. Eligible studies included intervention studies targeting the dietary intake of preschool children aged 2-5 years in high income countries, published in English after January 2000. Interventions were categorised to the Determinants of Nutrition and Eating (DONE) framework for children developed and evaluated by experts across multiple fields. The framework maps and ranks 411 factors driving eating behaviours and nutrition and can be used to systematically summarise determinants. DONE ranks each determinant for its perceived research priority. A total of 160 eligible studies were identified. Most interventions targeted interpersonal (n = 101, 63.1%) and individual (n = 85, 53.1%) level determinants, with fewer targeting environmental (n = 55, 34.4%) and policy level (n = 17, 10.6%) determinants. The most frequently addressed determinants were Parental Resources and Risk Factors (n = 85) and Children's Food Knowledge, Skills and Abilities (n = 67). These determinants had a Moderate research priority rating. Home Food Availability and Accessibility at the environmental level is classified as the highest research priority, however, only 15 of 160 interventions addressed this determinant. This review highlights home food availability and accessibility as potential leverage points for future interventions to improve children's dietary intake and eating behaviours.

A subpopulation of lipogenic brown adipocytes drives thermogenic memory.

Sustained responses to transient environmental stimuli are important for survival. The mechanisms underlying long-term adaptations to temporary shifts in abiotic factors remain incompletely understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which improve thermogenic responses to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis programme even after cessation of the original stimulus, which protects from subsequent exposures. Single-nucleus RNA sequencing and spatial transcriptomics reveal that this response is driven by a lipogenic subpopulation of brown adipocytes localized along the perimeter of Ucp1hi adipocytes. This lipogenic programme is associated with the production of acylcarnitines, and supplementation of acylcarnitines is sufficient to recapitulate improved secondary cold responses. Overall, our data highlight the importance of heterogenous brown adipocyte populations for 'thermogenic memory', which may have therapeutic implications for leveraging short-term thermogenesis to counteract obesity.

Assessing Patterns in Childhood Obesity Patient Education: A Quality of Online Health Information and Google Trends Analysis.

Background: Childhood obesity (CO) is rapidly increasing in prevalence and developing into a health crisis of developed nations. The condition is associated with increased risk of developing various comorbidities later in life. Current treatment algorithms primarily target family education. Thus, this study aims to understand the quality of information online regarding CO and common comorbidities, determine the readability of online information, and report patterns in public interest over time using Google Trends. Methods: Four validated quality of information tools and 6 readability tools were implemented across 36 websites derived from 4 Google searches. Pearson's correlation coefficient was used to determine the associations between Google Trends' relative search volumes (RSVs) and biennial BMI-based cumulative proportion of CO. Results: Results showed variable information quality among the websites as scores ranged from "fair" to "very poor." Using six readability formulas, no website scored at or below the sixth grade reading level recommended by the American Medical Association. Google Trends' RSVs for the term "Childhood Obesity" were repeatedly increased in the months that fall in the US academic school year (October-November and February-May), and decreased within months in the US vacation periods (December-January and June-September). Search volumes were also negatively correlated with CO and pediatric type 2 diabetes prevalence. Conclusions: In summary, while Google Trends analysis showed that schools may play a role in increasing interest and awareness online, quality of information and readability analysis displayed that the information and its accessibility are far too variable to be reliable.

Autoimmune Polyendocrinopathy in a Pediatric Patient Presenting With Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystem inflammatory syndrome (MIS) is a well-known potential sequela of COVID-19 infection. Though prevalence is higher in certain populations, this syndrome is a rare occurrence in children. Beyond MIS, there has been increasing research into COVID infection and the subsequent onset of autoimmune conditions, such as diabetes. However, evidence of a poly-endocrinopathy developing after COVID infection is lacking, and evidence within the pediatric population is virtually nonexistent. In this case, we present the evolution of an autoimmune polyglandular syndrome (APS) type 2 phenotype, consisting of type 1 diabetes, Graves' disease, and adrenal insufficiency, after diagnosis of multisystem inflammatory syndrome of children (MIS-C) in a pediatric patient.  A 15-year-old biracial female without significant past medical history tested positive for COVID-19 and two weeks later presented with respiratory symptoms and other systemic signs. She was admitted for further evaluation and was found to have elevated inflammatory markers, EKG (electrocardiogram) abnormalities, and lab evidence of organ damage. The patient was diagnosed with MIS-C, and treatment was initiated with eventual discharge. One year after this initial visit, the patient returned to the hospital due to weight loss, difficulty breathing, polyuria, polydipsia, nausea, vomiting, and fatigue. A steroid course for MIS-C treatment had been completed three months prior. Exam and lab results confirmed diabetic ketoacidosis (DKA), and the patient was diagnosed with new-onset type 1 diabetes. Further testing determined that she was glutamic acid decarboxylase 65 (GAD-65) positive. DKA was managed in the hospital, and the patient was subsequently discharged with an insulin regimen and endocrine follow-up. A couple of months later, the patient returned to the emergency department (ED) due to two weeks of dyspnea on exertion and dizziness. Since her previous admission for DKA, the patient had contracted COVID-19 again and recovered from her respiratory symptoms. Physical exam and labs were grossly unremarkable; however, the patient had EKG abnormalities and an episode of severe bradycardia, prompting hospitalization. Thyroid workup revealed thyrotoxicosis due to Graves' disease. Due to intermittent hypotension, adrenal labs were obtained. She was found to have adrenal insufficiency as well, with a positive 21-hydroxylase antibody. Throughout these hospitalizations, the patient suffered from skin and hair changes as well, ultimately requiring dermatological intervention.

A Pediatric Patient With Type 1 Diabetes Mellitus With Poor Glycemic Control, Medication-Resistant Hypertension, and New-Onset Headache Diagnosed With Adrenocorticotropic Hormone (ACTH)-Secreting Pituitary Macroadenoma.

The most well-known cause of hyperglycemia is diabetes mellitus, a condition that affects the body's ability to either use (type 2 diabetes mellitus - T2DM) or produce (type 1 diabetes mellitus - T1DM) insulin. Exogenous insulin is the mainstay therapy to achieve optimal glucose control in T1DM, though glucose hemostasis is affected by several factors. Following the initiation of insulin therapy, symptoms of polyuria, polydipsia, and weight loss are reversed. Diabetes mellitus is associated with several complications, including but not limited to, renal disease (hypertension, microalbuminuria), peripheral neuropathy, delayed growth, and delayed puberty. Hyperglycemia can also be caused by acute illness, surgery, trauma, infection, parenteral nutrition, obesity, or other medical conditions such as Cushing syndrome and polycystic ovarian syndrome. While refractory hyperglycemia is often attributed to poor adherence to medications, other organic etiologies should also be considered, especially in the setting of early-onset complications of diabetes mellitus. In this report, we present a case of a pediatric patient with T1DM with refractory hyperglycemia and medication-resistant hypertension who was lost to follow-up. When he returned to the endocrinology clinic, he had Cushingoid features and a headache. After multiple admissions for hypertension, the patient was discovered to have a pituitary macroadenoma. Following the removal of the adenoma, the patient's insulin requirement decreased substantially and his blood pressure returned to normal, allowing all blood pressure medications to be discontinued.

Amauroderma rugosum Extract Suppresses Inflammatory Responses in Tumor Necrosis Factor Alpha/Interferon Gamma-Induced HaCaT Keratinocytes.

Keratinocytes form the physical barrier of the skin and play an important role in the inflammatory process. Amauroderma rugosum is an edible mushroom; however, its pharmacological properties have seldom been studied. Although the anti-inflammatory effect of the organic solvent extract of Amauroderma rugosum has been previously reported, it is not known whether the aqueous extract has a similar effect. In addition, the effect of Amauorderma rugosum extract on skin has never been explored. Therefore, the objectives of the present study were to evaluate the anti-inflammatory effects of the aqueous extract of Amauroderma rugosum on HaCaT keratinocytes, to explore its mechanisms of action, and to study the possible active ingredients involved. The results showed that the aqueous extract of Amauroderm rugosum at a concentration of 1.5 mg/mL was non-toxic to HaCaT cells and inhibited the release of cytokine interleukin-1ß, and chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-stimulated HaCaT cells. Amauroderma rugosum extract reduced the intracellular levels of reactive oxygen species. In addition, Amauroderma rugosum extract reduced the total protein expression of nuclear factor-kappa B (NF-κB) and B-cells inhibitor alpha in HaCaT keratinocytes and inhibited the phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in TNF-α- and INF-γ-stimulated HaCaT keratinocytes. Chemical analysis revealed that the aqueous extract of Amauroderma rugosum contains polysaccharides, triterpenes, and phenolic compounds. Anti-inflammatory compounds, such as gallic acid, guanosine, and uridine, were also present. The anti-inflammatory effect of Amauroderma rugosum could be mimicked by a combination of gallic acid, guanosine, and uridine. In conclusion, our study suggests that the aqueous extract of Amauroderma rugosum exerts anti-inflammatory effects on keratinocytes through its antioxidant and inhibitory effects on MEK/ERK-, Akt/mTOR-, and NF-κB-dependent signaling pathways.

Protective Effects of Amauroderma rugosum on Doxorubicin-Induced Cardiotoxicity through Suppressing Oxidative Stress, Mitochondrial Dysfunction, Apoptosis, and Activating Akt/mTOR and Nrf2/HO-1 Signaling Pathways.

Clinical outcomes for doxorubicin (Dox) are limited by its cardiotoxicity but a combination of Dox and agents with cardioprotective activities is an effective strategy to improve its therapeutic outcome. Natural products provide abundant resources to search for novel cardioprotective agents. Ganoderma lucidum (GL) is the most well-known edible mushroom within the Ganodermataceae family. It is commonly used in traditional Chinese medicine or as a healthcare product. Amauroderma rugosum (AR) is another genus of mushroom from the Ganodermataceae family, but its pharmacological activity and medicinal value have rarely been reported. In the present study, the cardioprotective effects of the AR water extract against Dox-induced cardiotoxicity were studied in vitro and in vivo. Results showed that both the AR and GL extracts could potentiate the anticancer effect of Dox. The AR extract significantly decreased the oxidative stress, mitochondrial dysfunction, and apoptosis seen in Dox-treated H9c2 rat cardiomyocytes. However, knockdown of Nrf2 by siRNA abolished the protective effects of AR in these cells. In addition, Dox upregulated the expression of proapoptotic proteins and downregulated the Akt/mTOR and Nrf2/HO-1 signaling pathways, and these effects could be reversed by the AR extract. Consistently, the AR extract significantly prolonged survival time, reversed weight loss, and reduced cardiac dysfunction in Dox-treated mice. In addition, oxidative stress and apoptosis were suppressed, while Nrf2 and HO-1 expressions were elevated in the heart tissues of Dox-treated mice after treatment with the AR extract. However, the GL extract had less cardioprotective effect against Dox in both the cell and animal models. In conclusion, the AR water extract demonstrated a remarkable cardioprotective effect against Dox-induced cardiotoxicity. One of the possible mechanisms for this effect was the upregulation of the mTOR/Akt and Nrf2/HO-1-dependent pathways, which may reduce oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis. These findings suggested that AR may be beneficial for the heart, especially in patients receiving Dox-based chemotherapy.

Mindfulness Practices for Children and Adolescents Receiving Cancer Therapies.

Background: Mindfulness is our innate capacity to pay full, conscious, and compassionate attention to something in the moment. It is also a skill that can be strengthened by mental practice. More recently, mindfulness-based interventions (MBIs) are identified within clinical practice guidelines as an intervention in the treatment of certain symptoms for children with cancer. However, there is little guidance available on the practice of using MBIs in the pediatric oncology population. The aim of this paper is to provide an overview of mindfulness, highlights symptoms where mindfulness practices may be of benefit, identifies trauma-sensitive considerations, and provides examples of MBIs that may be considered in the context of pediatric oncology. Methods: Collaboration of expert opinion, which included The Mindfulness Project Team, has enabled this collective informative paper. Results: Mindfulness has been recommended to help with the symptom of fatigue in children with cancer. Emotional symptoms such as anxiety, sadness, and anger may also benefit from the use of MBIs. Ideal MBIs for this population may include mindful movement, mindfulness of the senses, mindfulness of breath, mindfulness of emotions, and the body scan. These approaches can easily be adapted according to the age of the child. Many approaches have been administered with minimal training, with very few requiring a facilitator. However, hospitals have started to incorporate mindfulness experts within their care provision. Conclusion: Future research should continue to investigate the use of MBI programs for children with cancer.

Severe Hypertriglyceridemia-Induced Necrotizing Pancreatitis Associated With Ketogenic Diet in a Well-Controlled Patient With Type 2 Diabetes Mellitus.

The ketogenic diet (keto diet) has become an increasingly popular approach for both weight loss and as an alternative diet for type 2 diabetes mellitus (T2DM). Owing to the nature of the keto diet, patients are at risk of developing hypertriglyceridemia (HTG) due to the high amount of triglycerides consumed by individuals during the initiation of this diet. Acute pancreatitis can result from HTG. We present a case of a 19-year-old African American male with well-controlled T2DM and no history of HTG who developed severe necrotizing HTG-induced pancreatitis after an unsupervised three-month trial of the keto diet.

Development of a Data Visualization Tool for Occupational Exposure to Chemicals of Concern for Breast Cancer Among California Working Women, 2010-2014.

We identified the occupations that employ California women and a list of chemicals of concern for breast cancer. We evaluated the likelihood of on-the-job exposure to the categories of chemicals by occupation among formally and informally employed women. We selected 145 occupations representing more than 6.6 million women (85% of California working women), along with an additional sixteen occupations for informal workers only. We organized 1012 chemicals (including mammary gland carcinogens, developmental toxicants, and endocrine-disrupting chemicals) into twenty-five categories. More than 80 percent of occupations investigated had possible or probable exposure to at least one category of chemicals. This is the first categorization of occupational exposure to chemicals of concern for breast cancer among California working women. Our investigation revealed significant data gaps, which could be improved by policy changes resulting in enhanced collection of data on occupation and chemical exposure.

Infant With Severe Penoscrotal Hypospadias: A Complex Case of Genital Ambiguity and Mistaken Identity.

Individuals with an incongruence of their chromosomal sex and genital appearance are classified as having a disorder of sexual development (DSD), and they often present with ambiguous genitalia. The diagnosis and management of DSD patients are usually challenging and require a multidisciplinary approach. Gender assignment should not be based solely on physical exam and imaging but also on the genotype and hormonal function of the gonads. We present an infant born with ambiguous genitalia; the parents were told they were having a male infant during the prenatal ultrasound but at birth, the infant was found to have female-appearing external genitalia with no palpable gonads. MRI of the abdomen was inconclusive, but further workup, including karyotype, hormonal function, and intraoperative evaluation, was consistent with a male infant. He was, therefore, subsequently assigned to the male sex.

Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female.

Congenital sucrase isomaltase deficiency (CSID) is an autosomal recessive disorder which leads to chronic intestinal malabsorption of nutrients from ingested starch and sucrose. Symptoms usually present after consumption of fruits, juices, grains, and starches, leading to failure to thrive and malnutrition. Diagnosis is suspected on detailed patient history and confirmed by a disaccharidase assay using small intestinal biopsies or sucrose hydrogen breath test. Treatment of CSID consists of limiting sucrose in diet and replacement therapy with sacrosidase. Due to its nonspecific symptoms, CSID may be undiagnosed in many patients for several years. We present a case of a 50-year-old woman with persistent symptoms of bloating in spite of extensive evaluation and treatment.

Clinical significance of TP53, BIRC3, ATM and MAPK-ERK genes in chronic lymphocytic leukaemia: data from the randomised UK LRF CLL4 trial.

Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with chemotherapy trials representing an invaluable resource to explore disease-related/genetic features contributing to long-term outcomes. In 499 LRF CLL4 cases, a trial with >12 years follow-up, we employed targeted resequencing of 22 genes, identifying 623 mutations. After background mutation rate correction, 11/22 genes were recurrently mutated at frequencies between 3.6% (NFKBIE) and 24% (SF3B1). Mutations beyond Sanger resolution (<12% VAF) were observed in all genes, with KRAS mutations principally composed of these low VAF variants. Firstly, employing orthogonal approaches to confirm <12% VAF TP53 mutations, we assessed the clinical impact of TP53 clonal architecture. Whilst ≥ 12% VAF TP53mut cases were associated with reduced PFS and OS, we could not demonstrate a difference between <12% VAF TP53 mutations and either wild type or ≥12% VAF TP53mut cases. Secondly, we identified biallelic BIRC3 lesions (mutation and deletion) as an independent marker of inferior PFS and OS. Finally, we observed that mutated MAPK-ERK genes were independent markers of poor OS in multivariate survival analysis. In conclusion, our study supports using targeted resequencing of expanded gene panels to elucidate the prognostic impact of gene mutations.

Measuring the Transition Readiness of Adolescents With Type 1 Diabetes Using the Transition Readiness Assessment Questionnaire.

IN BRIEF This study aimed to assess readiness to transition from pediatric to adult health care in adolescents with type 1 diabetes using the Transition Readiness Assessment Questionnaire (TRAQ). TRAQ is a non-disease-specific self-report measure that assesses self-management and advocacy skills of youth with special health care needs. This study provides guidance on assessing transition readiness scores of adolescents with diabetes and identifying when health care providers should intervene.