Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects.

Homozygous plakophilin-2 (PKP2) variants have been identified as a cause of a lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET) in three cases. We report three more cases from two families with homozygous pathogenic PKP2 variants and perinatal-onset, lethal DCM-ET. Identification of the genetic abnormalities played a key role in decision-making and family counselling in these cases. This case series supports the published evidence that biallelic loss of function PKP2 variants cause a lethal, perinatal-onset cardiomyopathy.

Celiac Disease, Gluten Sensitivity, and Diet Management.

PURPOSE OF REVIEW: Celiac disease is a common chronic inflammatory condition of the small bowel triggered by gluten in wheat, rye and barley in the diet. Non-celiac gluten sensitivity presents with symptoms similar to celiac disease with the ingestion of gluten or other components of wheat. In this article, we review challenges presented by a gluten free diet for the treatment of both disorders. RECENT FINDINGS: Wheat is ubiquitous in the diet and medications/products. A registered dietitian is mandatory for patient education on the gluten free diet. Naturally gluten free foods provide a healthy diet for those with celiac disease. Whole grains labelled gluten free, including oats, are encouraged in the diet as refined grains may be deficient in fiber, protein, and micronutrients, particularly folate. Gluten contamination is the most common cause of persistent symptoms in celiac disease though shared equipment of food preparation may not be as large a problem as suspected. Most with celiac disease on a gluten free diet will fully recover and gain weight that poses a problem for those overweight to start. The gluten free diet may have a negative impact on quality of life for both celiac patients and their families. Those with hypervigilance of the gluten free diet and avoidance of dining out have the lowest quality of life. The gluten free diet is currently the only effective treatment for celiac disease. A registered dietitian is needed to educate patients on the complexity of the gluten free diet with a goal of healthy eating, maintaining a healthy weight, and avoiding disordered eating or diet hypervigilance; key to a good quality of life.

Outcomes of parenteral nutrition in patients with advanced cancer and malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction (MBO) affects 3% to 15% of all cancer patients. In patients with advanced cancer and inoperable MBO, the average survival varies between four to nine weeks. Parenteral nutrition (PN) may improve survival in specific patient populations with malignant bowel obstruction. AIMS: This retrospective, single-center cohort study aimed to review individual patient outcomes on PN in the setting of advanced cancer with a diagnosis of MBO and identify clinical and laboratory markers predictive of short- and long-term survival to further highlight patients that would benefit from PN in the setting of an inoperable MBO. RESULTS: In a retrospective analysis of 68 patients receiving PN for inoperable MBO, the median survival was 142 (IQR: 63.3-239.5) days. Patients experienced a median number of two hospital readmissions (range: 0-10) and spent a median of 29 days (range: 0-105) in the hospital after starting PN. Eighteen (26.5%) patients developed a catheter-related bloodstream infection (CRBSI). A diagnosis of appendiceal cancer was identified as a predictive marker of improved survival (HR: 0.53, 95% CI: 0.29-0.92, p = 0.023). CONCLUSIONS: The use of PN in the context of end-of-life cancer care is a practice that necessitates improvement. Recognizing the outcomes and patient experiences of PN utilization is essential to physicians and patients.

Fetal hydrops caused by a novel pathogenic MECOM variant.

We report a fetus with hydrops, congenital heart disease and bilateral radioulnar synostosis caused by a novel pathogenic MECOM variant. The female fetus was referred for post-mortem examination after fetal hydrops and intrauterine death was diagnosed at 20 weeks gestation. Post-mortem examination confirmed fetal hydrops, pallor, truncus arteriosus and bilateral radioulnar synostosis. Trio whole genome sequencing analysis detected a novel de novo heterozygous pathogenic loss-of-function variant in MECOM (NM_004991), associated with a diagnosis of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia 2 (RUSAT-2). RUSAT-2 is a variable condition associated postnatally with bone marrow failure, radioulnar synostosis and congenital anomalies. RUSAT-2 is not currently associated with a prenatal phenotype or fetal demise, and was not present on diagnostic NHS prenatal gene panels at time of diagnosis. This case highlights the diagnostic value of detailed phenotyping with post-mortem examination, and of using a broad sequencing approach.

Prenatal diagnosis of CLCN4-related neurodevelopmental disorder in fetuses with congenital brain anomalies.

We report two male fetuses born to a healthy unrelated couple, with agenesis of the corpus callosum identified on detailed 20-week ultrasound scans and confirmed by in-utero MRI. Whole-genome sequencing identified a likely pathogenic missense variant in the CLCN4 gene, establishing this as the causative gene in the family. Pathogenic variants in the CLCN4 gene cause a neurodevelopmental disorder (also called Raynaud-Claes syndrome) inherited in an X-linked pattern. The disorder is characterised by developmental delay, intellectual disability, autism spectrum disorder, epilepsy, mental health conditions, and significant feeding difficulties, predominantly, but not exclusively, affecting males. This is the first report of a prenatal phenotype associated with variants in the CLCN4 gene. The diagnosis of the CLCN4-related neurodevelopmental disorder in this family allowed accurate genetic counseling and discussion of reproductive choices. This leaves uncertainty about the possibility of a postnatal neurodevelopmental phenotype in heterozygous females, which we discuss.

Parenteral fish oil lipid emulsion use in adults: a case series and review from an intestinal failure referral center.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) is a complication of long-term PN use, attributed to the use of ω-6 injectable lipid emulsions (ILE). Fish oil (FO) ILE have been successful in reversing liver injury in neonates. Evidence for pure FO ILE use in adult patients is limited. METHODS: Case series of the use of FO lipid emulsions in adults with IFALD from the University of Chicago PN registry. Analysis of medical charts and PN formulations was performed. RESULTS: Three cases of IFALD treated with FO ILE were identified. The first case was a 30-year-old man with short bowel syndrome (SBS), hyperbilirubinemia, and biopsy-proven IFALD. Following a change from a soy lipid emulsion to FO lipid emulsion, his liver tests rapidly improved and remained stable over 202 weeks of use. The second case was a 76-year-old woman with intestinal failure (IF) due to a frozen bowel. A change from a soy ILE to a composite lipid and later to a pure FO ILE did not result in improvement in her liver tests. The third case was a 28-year-old man with SBS and biopsy-proven IFALD. Change to a composite ILE and subsequently FO lipid emulsion resulted in a gradual improvement in liver tests. No clinical essential fatty acid (EFA) deficiencies were identified during treatment. CONCLUSION: FO ILE may be effective in the treatment of adult patients with cholestatic IFALD. Use is safe with no EFA deficiencies detected in up to 4 years of use.

Navigating nutrition and hydration care in the adult patient with short bowel syndrome.

Attending diligently to the nutrition and hydration needs of patients with short bowel syndrome (SBS) is a key tenet of their care, both postoperatively and in the years that follow. For, without each, patients are left to themselves to navigate the nutrition consequences of SBS, including malnutrition, nutrient deficiencies, renal compromise, osteoporosis, fatigue, depression, and impaired quality of life. The intent of this review is to discuss the initial nutrition assessment, oral diet, hydration, and home nutrition support for the patient with SBS.

Plating and Stripping Calcium Metal in Potassium Hexafluorophosphate Electrolyte toward a Stable Hybrid Solid Electrolyte Interphase.

The use of calcium (Ca) metal anodes in batteries is currently challenged by the development of a suitable solid electrolyte interface (SEI) that enables effective Ca2+ ion transport. Native calcium electrolytes produce a passivation layer on the surface of the calcium electrodes during cycling, causing a decrease in capacity during cycling and the need for large overpotentials. The use of a hybrid SEI is a strategy to mitigate the uncontrolled production of a passivation layer and reduce the overpotentials needed for the plating and stripping of calcium. Here, we report the development of a hybrid potassium (K)/Ca SEI layer investigated in symmetric Ca//Ca cell configurations. Using KPF6 salt in a ternary mixture of carbonate solvent (EC/EMC/DMC), Ca//Ca cells can be cycled up to 200 h at a capacity of 0.15 mAh/cm2 with a current density of 0.025 mA/cm2. The symmetrical cells consistently cycle at overpotentials of 1.8 V. Ex-situ X-ray diffraction (XRD) of cycled electrodes reveals plating and stripping of both calcium and potassium. Energy dispersive X-ray (EDX) maps confirm the plating of calcium and potassium during galvanostatic cycling. Scanning electron microscopy (SEM) cross-sectional views of the calcium electrodes reveal a continuous SEI layer formed over the calcium metal. XRD analysis reveals the SEI layer consists of K-based inorganics along with the identification of permanent and transient phases. FTIR outlines the parallel plating of both calcium and potassium at both regions of redox activity. Raman spectroscopy of the electrolyte reveals compositional changes over the course of cycling that promote increased plating and stripping. The results indicate that potassium electrolytes are a possible route for tuning the SEI to enable reversible calcium electrochemical cycling.

Exploring Calcium Manganese Oxide as a Promising Cathode Material for Calcium-Ion Batteries.

The dependence on lithium for the energy needs of the world, coupled with its scarcity, has prompted the exploration of postlithium alternatives. Calcium-ion batteries are one such possible alternative owing to their high energy density, similar reduction potential, and naturally higher abundance. A critical gap in calcium-ion batteries is the lack of suitable cathodes for intercalating calcium at high voltages and capacities while also maintaining structural stability. Transition metal oxide postspinels have been identified as having crystal structures that can provide low migration barriers, high voltages, and facile transport pathways for calcium ions and thus can serve as cathodes for calcium-ion batteries. However, experimental validation of transition metal oxide postspinel compounds for calcium ion conduction remains unexplored. In this work, calcium manganese oxide (CaMn2O4) in the postspinel phase is explored as an intercalation cathode for calcium-ion batteries. CaMn2O4 is first synthesized via solid-state synthesis, and the phase is verified with X-ray diffraction (XRD). The redox activity of the cathode is investigated with cyclic voltammetry (CV) and galvanostatic (GS) cycling, identifying oxidation potentials at 0.2 and 0.5 V and a broad insertion potential at -1.5 V. CaMn2O4 can cycle at a capacity of 52 mAh/g at a rate of C/33, and calcium cycling is verified with energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) and modeled with density functional theory (DFT) simulations. The results from the investigation concluded that CaMn2O4 is a promising cathode for calcium-ion batteries.

Outcomes of parenteral nutrition in patients with advanced cancer and malignant bowel obstruction.

Background: Malignant bowel obstruction (MBO) affects 3-15% of all cancer patients. In patients with advanced cancer and inoperable MBO, the average survival varies between four to nine weeks. Parenteral nutrition (PN) may improve survival in specific patient populations with malignant bowel obstruction. Aims: This retrospective, single-center cohort study aimed to review individual patient outcomes on PN in the setting of advanced cancer with a diagnosis of MBO and identify clinical and laboratory markers predictive of short- and long-term survival to further highlight patients that would benefit from PN in the setting of an inoperable MBO. Results: In a retrospective analysis of 68 patients receiving PN for inoperable MBO, the median survival was 142 (IQR: 63.3-239.5) days. Patients experienced a median number of two hospital readmissions (range: 0-10) and spent a median of 29 days (range: 0-105) in the hospital after starting PN. Eighteen (26.5%) patients developed a catheter-related bloodstream infection (CRBSI). A diagnosis of appendiceal cancer was identified as a predictive marker of improved survival (HR: 0.53, 95% CI: 0.29-0.92, p = 0.023). Conclusions: The use of PN in the context of end-of-life cancer care is a practice that necessitates improvement. Recognizing the outcomes and patient experiences of PN utilization is essential to physicians and patients.

A multidisciplinary team evaluation of management guidelines for adult short bowel syndrome.

BACKGROUND & AIMS: An international, multidisciplinary management working group (MWG) convened to review clinically useful short bowel syndrome (SBS) literature and identify gaps and inconsistencies in the management of adults with SBS. METHODS: Using nominal group technique for literature review, key publications were identified, discussed, and ranked by importance related to management of SBS. Gaps in management recommendations for SBS were identified upon critical review of the selected publications. RESULTS: Five guidelines, seven review articles, one series of six articles, and one single center series were selected and prioritized for their importance to SBS management. Evaluation of the articles by the MWG identified ten gaps and opportunities to standardize and improve SBS management. CONCLUSION: The main practice areas in need of more definitive guidelines are the management of high stool output and strategies to improve absorption of medications, nutrients, and fluids. An understanding of current real-world clinical practices related to these gaps could allow for development of best practice standards and improve patient-focused care.

Real-World Management of High Stool Output in Patients with Short Bowel Syndrome: An International Multicenter Survey.

BACKGROUND: International practice guidelines for high-stool-output (HSO) management in short bowel syndrome (SBS) are available, but data on implementation are lacking. This study describes the approach used to manage HSO in SBS patients across different global regions. METHODS: This is an international multicenter study evaluating medical management of HSO in SBS patients using a questionnaire survey. Thirty-three intestinal-failure centers were invited to complete the survey as one multidisciplinary team. RESULTS: Survey response rate was 91%. Dietary recommendations varied based on anatomy and geographic region. For patients without colon-in-continuity (CiC), clinical practices were generally consistent with ESPEN guidelines, including separation of fluid from solid food (90%), a high-sodium diet (90%), and a low-simple-sugar diet (75%). For CiC patients, practices less closely followed guidelines, such as a low-fat diet (35%) or a high-sodium diet (50%). First-line antimotility and antisecretory medications were loperamide and proton-pump inhibitors. Other therapeutic agents (e.g., pancreatic enzymes and bile acid binders) were utilized in real-world practices, and usage varied based on intestinal anatomy. CONCLUSION: Expert centers largely followed published HSO-management guidelines for SBS patients without CiC, but clinical practices deviated substantially for CiC patients. Determining the reasons for this discrepancy might inform future development of practice guidelines.

Characteristics of adult intestinal failure centers: An international multicenter survey.

BACKGROUND: Current guidelines recommend that patients with chronic intestinal failure (CIF) should be managed by a multidisciplinary team (MDT). However, the characteristics of real-world IF centers and the patients they care for are lacking. The study aims to describe IF center characteristics as well as characteristics of patients with CIF across different global regions. METHODS: This is an international multicenter study of adult IF centers using a survey. The questionnaire survey included questions regarding program and patient characteristics. Thirty-three investigational centers were invited to participate. Each center was asked to answer the survey questions as one MDT. RESULTS: The survey center response rate was 91%. The median number of patients with CIF per center was 128 (range, 30-380). The most common disciplines reported were gastroenterologist (93%), dietitian (90%), nurse (83%), and advanced practitioner (nurse practitioner and physician assistant, 77%). There were centers that did not have a pharmacist, surgeon, psychologist, and social worker (30%, 37%, 60%, and 70%, respectively). The median full-time equivalents (FTEs) per 100 patients were 1.1 for nurses, 1 for dietitians, 1 for advanced practitioners, and 0.9 for gastroenterologists. Short bowel syndrome was the most common cause of CIF (50%) followed by intestinal dysmotility (20%). CONCLUSION: The majority of centers were managing around 100 patients with CIF. Despite the widespread use of the MDT, there are some variances in team characteristics. Gastroenterologists were the most common physicians supporting MDTs. In IF centers, one FTE of each core discipline was supported to manage 100 patients with CIF.

The prenatal exome - a door to prenatal diagnostics?

Introduction: Prenatal exome sequencing (ES) allows parents the opportunity to obtain arapid molecular diagnosis of monogenic etiology when their fetus is found to have structural anomalies detected on prenatal ultrasound. Such information can improve antenatal and neonatal counseling, decision-making and management, and expand reproductive options in subsequent pregnancies.Areas covered: This review appraises the evidence, from acomprehensive search of bibliographic databases, for the introduction of ES into the fetal medicine care pathway when investigating congenital malformations. The perspectives of clinical geneticists, clinical scientists, fetal medicine specialists, and patients are explored in relation to the novel investigation and the benefits and challenges of its use in ongoing pregnancies with particular reference to UK medical practice.Expert opinion: ES provides agenetic diagnosis for more than 1 in 10 fetuses with structural differences on ultrasound and normal conventional tests (karyotype or chromosomal microarray) in carefully selected cases. The diagnostic rate increases for certain phenotypes and can range between 6% and 80% where conventional cytogenetics have not detected adiagnosis. Expert oversight is required to ensure that patients receive high-quality, evidence-based care and accurate counseling, supported by amultidisciplinary team familiar with the test and its implications.

Long-Term Outcomes With Teduglutide From a Single Center.

BACKGROUND: The aim of this study was to quantify the long-term clinical outcomes for individuals receiving teduglutide for short-bowel syndrome (SBS). METHODS: A single-center, retrospective study was performed for individuals commencing use of teduglutide between March 2013 and May 2019. RESULTS: Eighteen patients were included in the final analysis, among which the median duration of teduglutide administration was 3.2 (range, 0.6-6.2) years. Twelve of 16 (75%) patients at 12 months, 10 of 13 (76.9%) at 24 months, 7 of 10 (70%) at 36 months, and 3 of 3 (100%) at 60 months had a response to teduglutide therapy, defined as a >20% reduction in parenteral support (PS) requirement. Among responders at 12, 24, and 36 months, the presence of a colon-in-continuity, an ileocecal valve, a response at 3 months, the length of small bowel, nor the baseline volume affected response to therapy (P > .05 for all comparisons). Five (28%) patients were able to achieve freedom from PS, among which all had a history of Crohn's disease with loss of the ileocecal valve and among which 3 had a colon-in-continuity. Four of the 5 patients discontinued PS by 6 months of teduglutide therapy. CONCLUSIONS: In a real-world experience, teduglutide therapy results in rapid and sustained reductions in PS. Larger postmarketing studies will be required to reliably predict response to treatment and the factors associated with enteral autonomy.

The Impact of a Non-profit Market on Food Store Choice and Shopping Experience: A Community Case Study.

Research evaluating the impact of new food stores in "food deserts" have reported limited impact on eating and health outcomes of residents who live nearby. Few studies have reported on shoppers' food store choices and experiences in these new stores. This study focused on residents' experience with a new non-profit food market in Chester, PA and analyzes spatial patterns regarding who did and did not choose to shop at the new store. Phone surveys (n = 135) and in-person interviews (n = 13) were conducted with the primary food shopper for households living in Chester 1-2 years, respectively, after the opening of a store. Participants who shopped at the new market reported positive experiences in regard to convenience, customer service, food quality, and prices and believed that the new market had a positive impact on the community. But most participants had not shopped at the new market, citing many of the same factors in their decision to shop at supermarkets outside the city. Our findings underscore the need to combine new food retail strategies with community engagement and other interventions, such as in-store promotions and health education programs, to maximize the number of people who shop at new food outlets designed to improve access to healthful foods.

An overview of short bowel syndrome management: adherence, adaptation, and practical recommendations.

Short bowel syndrome (SBS) refers to the clinical consequences resulting from loss of small bowel absorptive surface area due to surgical resection or bypass. The syndrome is characterized by maldigestion, malabsorption, and malnutrition. Survival of patients with SBS is dependent on adaptation in the remaining bowel and a combination of pharmacologic and nutrition therapies. Individual plans of care are developed based on the length and sites of remaining bowel, the degree of intestinal adaptation, and the patient's ability to adhere to the medication and dietary regimens. Antisecretory and antidiarrheal medications are prescribed to slow intestinal transit times and optimize fluid and nutrient absorption. Based on postsurgical anatomy, enteral feedings, parenteral infusions, complex diet plans, and vitamin and mineral supplementation are used in various combinations to nourish patients with SBS. In the acute care setting, registered dietitians (RDs) assist with infusion therapy, diet education, and discharge planning. Long-term, as the small intestine adapts, RDs revise the nutrition care plan and monitor for nutrient deficiencies, metabolic bone disease, and anemia. The frequent monitoring and revision of care plans, plus the appreciable benefits from proper medical nutrition therapy, make this patient population extremely challenging and rewarding for RDs to manage. This article provides a brief, case study-based overview of the medical and nutrition management of SBS.

Communication outcomes for groups of children using cochlear implants enrolled in auditory-verbal, aural-oral, and bilingual-bicultural early intervention programs.

OBJECTIVE: The relative impact of early intervention approach on speech perception and language skills was examined in these 3 well-matched groups of children using cochlear implants. STUDY DESIGN: Eight children from an auditory verbal intervention program were identified. From a pediatric database, researchers blind to the outcome data, identified 23 children from auditory oral programs and 8 children from bilingual-bicultural programs with the same inclusion criteria and equivalent demographic factors. PATIENTS: All child participants were male, had congenital profound hearing loss (pure tone average >80 dBHL), no additional disabilities, were within the normal IQ range, were monolingual English speakers, had no unusual findings on computed tomography/magnetic resonance imaging, and received hearing aids and cochlear implants at a similar age and before 4 years of age. MAIN OUTCOME MEASURES: Open-set speech perception (consonant-nucleus-consonant [CNC] words and Bamford-Kowal-Bench [BKB] sentences) and the Peabody Picture Vocabulary Test (PPVT) were administered. RESULTS: The mean age at cochlear implant was 1.7 years (range, 0.8-3.9; SD, 0.7), mean test age was 5.4 years (range, 2.5-10.1; SD, 1.7), and mean device experience was 3.7 years (range, 0.7-7.9; SD, 1.8). Results indicate mean CNC scores of 60%, 43%, and 24% and BKB scores of 77%, 77%, and 56% for the auditory-verbal (AV), aural-oral (AO), and bilingual-bicultural (BB) groups, respectively. The mean PPVT delay was 13, 19, and 26 months for AV, AO, and BB groups, respectively. CONCLUSION: Despite equivalent child demographic characteristics at the outset of this study, by 3 years postimplant, there were significant differences in AV, AO, and BB groups. Results support consistent emphasis on oral/aural input to achieve optimum spoken communication outcomes for children using cochlear implants.

Hearing impairment in otitis media with effusion: a cross-sectional study based in Pokhara, Nepal.

OBJECTIVE: Otitis media with effusion (OME) is a major cause of childhood hearing impairment (HI) in the developing world, but its prevalence has never been quantified in Nepal. This study therefore set out to determine the proportion of cases of OME complicated by HI and to identify associated factors. METHODS: This was a cross-sectional prevalence survey carried out in rural, urban and Tibetan schools in and around Pokhara, Nepal. HI was the primary outcome, and was defined as a middle-frequency pure tone average >25 dB on audiological testing. The study population was defined as children aged four years and older, attending primary school and with a diagnosis of OME. RESULTS: One hundred and eleven schoolchildren with a combined total of 172 ears affected by OME underwent audiometric assessment. HI was most prevalent in the rural Nepali population; 27% (95%CIs 18-38%) had HI, with a mean hearing loss of 22 dB (15-25 dB). In the Tibetan population, 16% (8-29%) had HI, with a mean loss of 17 dB (12-22 dB). The urban Nepali population had the least HI; 4% (1-13%) were affected, with a mean loss of 16 dB (15-19 dB). The difference in prevalence between the urban and rural Nepali populations was statistically significant (p>0.05). Logistic regression analysis did not identify any associated factors. CONCLUSIONS: HI is a common complication of OME in Nepal. There is hitherto-unreported variation between populations in the number of cases of OME complicated by HI. This study identified higher rates of morbidity amongst rural populations but was unable to identify associated factors.