Specific Clinical Presentations Research Articles

Animal Models of Coenzyme Q Deficiency: Mechanistic and Translational Learnings.

Coenzyme Q (CoQ) is a vital lipophilic molecule that is endogenously synthesized in the mitochondria of each cell. The CoQ biosynthetic pathway is complex and not completely characterized, and it involves at least thirteen catalytic and regulatory proteins. Once it is synthesized, CoQ exerts a wide variety of mitochondrial and extramitochondrial functions thank to its redox capacity and its lipophilicity. Thus, low levels of CoQ cause diseases with heterogeneous clinical symptoms, which are not always understood. The decreased levels of CoQ may be primary caused by defects in the CoQ biosynthetic pathway or secondarily associated with other diseases. In both cases, the pathomechanisms are related to the CoQ functions, although further experimental evidence is required to establish this association. The conventional treatment for CoQ deficiencies is the high doses of oral CoQ10 supplementation, but this therapy is not effective for some specific clinical presentations, especially in those involving the nervous system. To better understand the CoQ biosynthetic pathway, the biological functions linked to CoQ and the pathomechanisms of CoQ deficiencies, and to improve the therapeutic outcomes of this syndrome, a variety of animal models have been generated and characterized in the last decade. In this review, we show all the animal models available, remarking on the most important outcomes that each model has provided. Finally, we also comment some gaps and future research directions related to CoQ metabolism and how the current and novel animal models may help in the development of future research studies.

Improved diagnosis of gastrointestinal infections using a semi-automated multiplex real-time PCR for detection of enteropathogens.

Introduction. The identification of enteropathogens is critical for the clinical management of patients with suspected gastrointestinal infection. The FLOW multiplex PCR system (FMPS) is a semi-automated platform (FLOW System, Roche) for multiplex real-time PCR analysis.Hypothesis/Gap Statement. FMPS has greater sensitivity for the detection of enteric pathogens than standard methods such as culture, biochemical identification, immunochromatography or microscopic examination.Aim.The diagnostic performance of the FMPS was evaluated and compared to that of traditional microbiological procedures.Methodology. A total of 10 659 samples were collected and analysed over a period of 7 years. From 2013 to 2018 (every July to September), samples were processed using standard microbiological culture methods. In 2019, the FMPS was implemented using real-time PCR to detect the following enteropathogens: Shigella spp., Salmonella spp., Campylobacter spp., Giardia intestinalis, Entamoeba histolytica, Blastocystis hominis, Cryptosporidum spp., Dientamoeba fragilis, adenovirus, norovirus and rotavirus. Standard microbiological culture methods (2013-2018) included stool culture, microscopy and immunochromatography.Results. A total of 1078 stool samples were analysed prospectively using the FMPS from July to September (2019): bacterial, parasitic and viral pathogens were identified in 15.3, 9.71 and 5.29 % of cases, respectively. During the same period of 6 years (2013-2018), the proportion of positive identifications using standard microbiological methods from 2013 to 2018 was significantly lower. A major significant recovery improvement was observed for all bacteria species tested: Shigella spp./enteroinvasive Escherichia coli (EIEC) (P <0.05), Salmonella spp. (P <0.05) and Campylobacter spp. (P <0.05). Marked differences were also observed for the parasites G. intestinalis, Cryptosporidium spp. and D. fragilis.Conclusion. These results support the value of multiplex real-time PCR analysis for the detection of enteric pathogens in laboratory diagnosis with outstanding performance in identifying labile micro-organisms. The identification of unsuspected micro-organisms for less specific clinical presentations may also impact on clinical practice and help optimize patient management.

Lumbar spondylolisthesis: STATE of the art on assessment and conservative treatment

IntroductionThere is weak relationship between the presence of lumbar spondylolisthesis [SPL] and low back pain that is not always associated with instability, either at the involved lumbar segment or at different spinal levels. Therefore patients with lumbar symptomatic SPL can be divided into stable and unstable, based on the level of mobility during flexion and extension movements as general classifications for diagnostic and therapeutic purposes. Different opinions persist about best treatment (conservative vs. surgical) and among conservative treatments, on the type, dosage, and progression of physical therapy procedures.Purpose and importance to practiceThe aim of this Masterclass is to provide clinicians evidence-based indications for assessment and conservative treatment of SPL, taking into consideration some subgroups related to specific clinical presentations.Clinical implicationsThis Masterclass addresses the different phases of the assessment of a patient with SPL, including history, imaging, physical exam, and questionnaires on disability and cognitive-behavioral components. Regarding conservative treatment, self- management approaches and graded supervised training, including therapeutic relationships, information and education, are explained. Primary therapeutic procedures for pain control, recovery of the function and the mobility through therapeutic exercise, passive mobilization and antalgic techniques are suggested. Moreover, some guidance is provided on conservative treatment in specific clinical presentations (lumbar SPL with radiating pain and/or lumbar stenosis, SPL complicated by other factors, and SPL in adolescents) and the number/duration of sessions.Future research prioritiesSome steps to improve the diagnostic-therapeutic approach in SPL are to identify the best cluster of clinical tests, define different lumbar SPL subgroups, and investigate the effects of treatments based on that classification, similarly to the approach already proposed for non-specific LBP.

Shared Molecular Mechanisms of Hypertrophic Cardiomyopathy and Its Clinical Presentations: Automated Molecular Mechanisms Extraction Approach.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a prevalence of 1 in 500 people and varying clinical presentations. Although there is much research on HCM, underlying molecular mechanisms are poorly understood, and research on the molecular mechanisms of its specific clinical presentations is scarce. Our aim was to explore the molecular mechanisms shared by HCM and its clinical presentations through the automated extraction of molecular mechanisms. Molecular mechanisms were congregated by a query of the INDRA database, which aggregates knowledge from pathway databases and combines it with molecular mechanisms extracted from abstracts and open-access full articles by multiple machine-reading systems. The molecular mechanisms were extracted from 230,072 articles on HCM and 19 HCM clinical presentations, and their intersections were found. Shared molecular mechanisms of HCM and its clinical presentations were represented as networks; the most important elements in the intersections’ networks were found, centrality scores for each element of each network calculated, networks with reduced level of noise generated, and cooperatively working elements detected in each intersection network. The identified shared molecular mechanisms represent possible mechanisms underlying different HCM clinical presentations. Applied methodology produced results consistent with the information in the scientific literature.

Laboratory Diagnosis of Porphyria.

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Colonic Volvulus and Acute Colonic Pseudo-Obstruction.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Colonic Volvulus and Acute Colonic Pseudo-Obstruction.

Clinical and molecular characterization of patients with hereditary hemorrhagic telangiectasia: Experience from an HHT Center of Excellence

In this retrospective single-center study, we evaluated whether/how pathogenic/likely pathogenic variants of three hereditary hemorrhagic telangiectasia (HHT)-associated genes (ENG, ACVRL1, and SMAD4) are associated with specific clinical presentations of HHT. We also characterized the morphological features of pulmonary arteriovenous malformations (AVMs) in patients with these variants. Pathogenic or likely pathogenic variants were detected in 64 patients. Using nonparametric statistical tests, we compared the type and prevalence of specific HHT diagnostic features associated with these three variants. Pathogenic variants in these genes resulted in gene-specific HHT clinical presentations. Epistaxis was present in 93%, 94%, and 100% of patients with ENG, ACVRL1, and SMAD4 variants, respectively (p =0.79). Pulmonary AVMs were more common in patients with the ENG variant (p =0.034) compared with other subgroups. ACVRL1 variant was associated with the lowest frequency of pulmonary AVMs (p =0.034) but the highest frequency of hepatic AVMs (p =0.015). Patients with the ACVRL1 variant did not have significantly more pancreatic AVMs compared with the other groups (p =0.72). ENG, ACVRL1, and SMAD4 pathogenic or likely pathogenic variants are associated with gene-specific HHT presentations, which is consistent with results from other HHT centers.

Non–Specific Clinical Presentations are Not Prognostic and do not Anticipate Hospital Length of Stay or Resource Utilization

AimTo investigate whether a specific (SP) or non-specific (NSP) clinical presentation, predicts prognosis and in-hospital resource utilization in emergency medical admissions. MethodsWe studied admissions over 5 years (2015–2019) and classified the symptom presentation as SP or NSP. The predictive capacity of the NSP category was related to 30-day in-hospital mortality with a multivariable logistic regression model. Utilization of procedures/services was related to hospital length of stay (LOS) with zero truncated Poisson regression. ResultsThere were 39,776 admissions in 23,995 patients. A NSP occurred in 18.2% of our top 20 clinical presentations; the top five being shortness of breath (12.8%), ‘unwell’ (7.1%), collapse (4.1%), abdominal pain (3.6%) and headache (2.7%). Baseline demographic characteristics were similar and unrelated to type of presentation; the model adjusted mortality by SP 4.0% (95% CI: 3.8%, 4.2%) or NSP 3.9% (95% CI: 3.5%, 4.4%) was identical. LOS was a dependant quantitative function of procedures/services undertaken; for the top two presentations of shortness of breath (SP) or unwell (NSP) there was no relationship between a SP or NSP presentation and hospital utilization of procedures/services or LOS. ConclusionOur data suggest no utility for a categorisation of presentations as specific or non-specific in terms of provision of prognostic information nor as an indicator of the pattern of hospital investigation or LOS.

Acute compartment syndrome (ACS) - a case of delayed diagnosis

Acute Compartment Syndrome (ACS) is a potential limb and life-threatening complication following trauma. ACS is characterised by increased pressure within a defined fascial compartment which diminishes perfusion pressure, leading to local tissue ischaemia. Timely diagnosis of ACS is crucial to prevent serious complications or irreversible damage which may lead to amputation or death. Even though the most common aetiology for ACS is major trauma, routine examination for ACS is rarely ennforced in patients with minor trauma or soft-tissue injuries which puts patients at risk of a detrimental delay in treatment. Trauma nurses and other clinicians should therefore avoid relying solely on specific clinical presentations to detect or suspect the development of ACS. This paper will present a case of ACS with an unusual presentation, and critically evaluate the diagnostic challenges of ACS in atypical presentations.

Autism Spectrum Disorder in Early Intervention in Psychosis Services: Implementation and Findings of a 3-step Screening and Diagnostic Protocol.

Evidence indicates that autism spectrum disorder (ASD) is underidentified in populations with psychosis, but that clinical presentations of comorbid ASD and psychosis (ASD-P) and specific treatment needs that may relate to this group are not well understood. In fact, recent studies of ASD in first-episode psychosis suggest that there may be a specific clinical presentation of ASD-P. In response, the Cambridgeshire and Peterborough Early Intervention in Psychosis (EIP) service in the UK implemented and evaluated a 3-step ASD screening and diagnostic protocol, using the Autism Spectrum Disorder in Adults Screening Questionnaire (ASDASQ), case note review, and the Autism Diagnostic Observation Schedule (ADOS-2) and the Childhood Autism Spectrum Test (CAST). As a quality improvement project, the evaluation aimed to (1) establish the prevalence of patients with ASD-P, (2) describe characteristics of the clinical presentation of ASD-P and compare them to those of patients suffering from psychosis but no ASD, and (3) determine any differences in treatment between psychosis patients with and without ASD. Notably, at least 9% of the EIP service caseload met the criteria for a diagnosis of ASD-P, with half identified via the implementation of this protocol. The patients with ASD-P had specific clinical presentations and treatment needs that differed from those of patients with psychosis but no ASD. Thus, the findings from this study supported existing evidence concerning the underdetection of ASD in EIP populations. Our findings also added to emerging evidence for a clinical presentation of ASD-P with specific treatment needs. Our protocol has now been established as routine practice, and its implementation has improved the detection and treatment of patients with ASD-P within our EIP service.

Primary Sinonasal non-hodgkin's lymphoma: Our experiences at a tertiary care teaching hospital of Eastern India

Background: Primary sinonasal non-Hodgkin's lymphomas (NHLs) are uncommon malignancies. The lack of specific clinical presentations often causes delayed visit to the clinician and so diagnosis is done in late with advanced stage. Objective: The objective of the study was to study the primary sinonasal NHL with respect to clinical presentations, management, and outcome. Materials and Methods: This is a retrospective study conducted in a tertiary care teaching hospital from March 2010 to April 2020. The clinical data of the patients of primary sinonasal NHL were evaluated with respect to the age, sex, clinical presentations, staging, diagnosis, treatment, and outcome. Results: The mean age of the participants was 62.45 years with male-to-female ratio of 1.5:1. All the cases of sinonasal NHL involved with paranasal sinuses and nasal cavity. Nasal obstruction was the most common symptom. All were diagnosed with large B-cell lymphoma and treated with combined chemotherapy and radiation. Five patients were died during follow-up period. Conclusion: Primary sinonasal NHLs are extremely uncommon clinical entity. The diagnosis is based on the histological examination with immunohistochemical study. Early diagnosis and prompt treatment with chemo-regimen and radiotherapy are essential to achieve an optimum outcome. Early diagnosis and treatment improves the treatment outcome.

Dev Retroperitoneal Liposarkomun Yönetimi: Bir Olgu Sunumu

Retroperitoneal liposarcoma (RPLS) is a rare tumor. Early diagnosis and treatment are difficult due to absence of specific clinical presentations. We report a case of a 66-years-old woman who succesfully underwent complete surgical resection for a giant retroperitoneal liposarcoma. The complete surgical resection is the most important predictor of local recurrence and overall survival. We believe that complete surgical resection involving adjacent organs is a curative treatment to increase overall survival, especially in the presence of invasion of large tumors.

Guidelines for Speech Recording and Acoustic Analyses in Dysarthrias of Movement Disorders.

Most patients with movement disorders have speech impairments resulting from sensorimotor abnormalities that affect phonatory, articulatory, and prosodic speech subsystems. There is widespread cross-discipline use of speech recordings for diagnostic and research purposes, despite which there are no specific guidelines for a standardized method. This review aims to combine the specific clinical presentations of patients with movement disorders, existing acoustic assessment protocols, and technological advances in capturing speech to provide a basis for future research in this field and to improve the consistency of clinical assessments. We considered 3 areas: the recording environment (room, seating, background noise), the recording process (instrumentation, vocal tasks, elicitation of speech samples), and the acoustic outcome data. Four vocal tasks, namely, sustained vowel, sequential and alternating motion rates, reading passage, and monologues, are integral aspects of motor speech assessment. Fourteen acoustic vocal speech features, including their hypothesized pathomechanisms with regard to typical occurrences in hypokinetic or hyperkinetic dysarthria, are hereby recommended for quantitative exploratory analysis. Using these acoustic features and experimental speech data, we demonstrated that the hyperkinetic dysarthria group had more affected speech dimensions compared with the healthy controls than had the hypokinetic speakers. Several contrasting speech patterns between both dysarthrias were also found. This article is the first attempt to provide initial recommendations for a standardized way of recording the voice and speech of patients with hypokinetic or hyperkinetic dysarthria; thus allowing clinicians and researchers to reliably collect, acoustically analyze, and compare vocal data across different centers and patient cohorts. © 2020 International Parkinson and Movement Disorder Society.

Clinical presentations and practitioner levels appropriate for the introduction of ‘Treat and Referral’ into the Irish Emergency Medical Service: A survey of Consultants in emergency medicine.

&lt;p&gt;Objectives: Overcrowding in emergency departments (EDs) is an international issue and ambulance bypass is seen as one element of the solution to a complex problem. Irish EDs are not immune to this healthcare crisis, which, together with increased off-load delays for ambulances, is one catalyst for the introduction of Treat and Referral (paramedic non-ED disposition decision). The confidence of consultants in emergency medicine in paramedics and advanced paramedics offering Treat and Referral to patients presenting with hypoglycaemia or seizure was explored. Other specific clinical presentations were also investigated for suitability for Treat and Referral and a consensus was sought on an upper age limit for such patients. &lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;Methods: Public-sector consultants in emergency medicine in Ireland at the time of the study, were invited to complete an online survey. A 62% response was received from the targeted population.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;Results: Confidence was expressed in advanced paramedics offering Treat and Referral to patients with hypoglycaemia or seizure by the majority (78%) of respondents. However, confidence was reduced for paramedics (53%). Six of the twelve specific clinical presentations received clear support as suitable for Treat and Referral, with the remaining receiving reducing support and ‘falls in the elderly (without injury)’ was opposed. There was no consensus on an upper age limit for patients being offered Treat and Referral.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;Conclusions: Support for the highest level of EMS practitioner in Ireland, advanced paramedic, to expand their scope of practice to include Treat and Referral was identified. Clinical presentations have been identified that would be conducive to a Treat and Referral clinical care pathway. A trial implementation period may be essential to build confidence in the programme before a universal roll out.&lt;/p&gt;

Association between Clinical Presentation of Multiple Myeloma, Immunoglobulin Isotypes, and Cytogenetic Risk Groups

Introduction: In multiple myeloma (MM), chromosomal abnormalities (CAs) are valuable in risk stratifying patients and predicting disease free survival. While immunoglobulin isotypes have historically contributed to MM staging, more recently established classifications of CAs have allowed for a revised staging system that better predicts disease behavior. In this retrospective study, we hypothesized that CAs correlate with disease characteristics including immunoglobulin heavy chain isotype, degree of bone marrow infiltration (PC%), and end-organ damage. Methods: MM patients diagnosed between 2013 to 2019 were included in this retrospective chart review using electronic records from two distinct sources: (1) 442 patients from an independent pathology database and (2) a validation cohort composed of 110 patients from our institution. CAs were stratified by Mayo mSMART 2.0 criteria into standard, intermediate, and high-risk groups (Mikhael et al. Mayo Clin Proc 2013). End-organ damage was defined as the presence of lytic bone lesions, anemia, hypercalcemia, or renal failure on clinical presentation. Within each cohort, associations between categorical variables were made using the chi-squared test or Fisher's exact test, as deemed appropriate. The Mann-Whitney test was used to compare between groups for continuous variables. A result was considered statistically significant at the p&amp;lt;0.05 level of significance. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC). Results: 552 MM patients were included in the study. Multi-variate analysis revealed that del(13q14), dup(1q21), t(4;14), trisomy (11q13), del(16q23), and hypodiploidy were associated with a significantly higher PC%, whereas kappa light chain only (LCO) disease was associated with a lower PC%. Higher median PC% was found when comparing the intermediate to standard CA risk group. IgA isotype was associated with intermediate risk CAs including del(13q) and standard risk CAs including t(11;14), while IgG isotype was associated with dup(1q21), and kappa LCO disease correlated with a higher rate of higher risk CAs including deletion of p53 at 17p13 and dup(1q21). With regard to clinical presentation, lytic lesions were more frequent in patients with normal cytogenetics and trisomy 11 and less frequent in IgA isotype, whereas the presence of anemia on presentation correlated with IgA isotype. Renal failure was associated with MAF translocations including t(14;16), a high-risk CA. Conclusions: We demonstrate that a relationship exists between specific CAs, immunoglobulin isotypes, and clinical presentations in MM. Our data indicate that IgA isotype is significantly associated with intermediate-risk cytogenetics including del(13q) and anemia on presentation, and that light chain disease and renal failure correlate with high risk CAs including del(17p13). These associations between biological and clinical features further support the concept of divergent cytogenetic evolution in MM as being an underlying factor leading to distinctive disease presentations. Disclosures Braunstein: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Overview of Pathology and Laboratory Features of COVID-19

BACKGROUND: The third identified severe respiratory disease in the past two decades and the first to result in a pandemic is the coronavirus disease 2019 (COVID-19) specifically caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).&#x0D; AIM: The aim of this study was to provide an overview of the basic pathology and diagnostic laboratory features of COVID-19.&#x0D; METHODS: This review involved search of literatures on PubMed, Science alert, Medline, and Advanced Google search using the keywords “SARS-CoV2,” “Coronavirus” along with “pathology of COVID-19” and “diagnosis of COVID-19” with related articles pooled, relevant information extracted, and properly referenced.&#x0D; RESULTS: The recommended method of diagnosis is by nucleic acid testing of the viral ribonucleic acid in which real-time reverse-transcription polymerase chain reaction followed by nucleic acid sequencing when required is performed while some serologic techniques developed include enzyme-linked immunosorbent assay, immunochromatographic lateral flow assay, neutralization bioassay, and specific chemosensors to detect the immunoglobulin M and immunoglobulin G antibodies produced, although sole use of serologic tests is highly discouraged by monitoring agencies. The hematological features display leukocytosis with lymphocytopenia, eosinopenia, reduced procalcitonin along with increased D-dimer, C-reactive protein, serum amyloid A, fibrin, fibrin degradation products, and some inflammatory markers such as interleukin (IL)-2, IL-6, IL-7, IL-10, granulocyte colony-stimulating factor, MCP10, interferon gamma-induced protein 10, and tumor necrosis factor-α. The pathologic presentations include pleurisy, lung consolidation, pulmonary edema and pericarditis along with other features of acute respiratory syndrome, myocardial injury, and acute kidney injury.&#x0D; CONCLUSION: There are highly efficacious and reliable methods of diagnosis of COVID-19 which also determine the stage and severity of the condition, and these methods are performed in line with specific clinical presentations. However, more studies are required to identify the capabilities, characteristics, and tendencies of this novel virus.

Management of Zygomatic Arch Fractures by Intraoral Open Reduction and Transbuccal Fixation: A Technical Note.

Fractures of the zygomatic arch are common due to its anatomical prominence. The post-traumatic restoration of the arch form is important to maintain the midfacial symmetry and anteroposterior projection of the face. Open reduction and internal fixation (ORIF) of fractured arch is indicated in specific clinical presentations. The traditional methods of ORIF of zygomatic arch fractures require cutaneous incisions, which are associated with complications such as scarring and facial nerve injury. This article presents a simple technique of "intraoral reduction and transbuccal fixation" of the arch that negates the problems associated with the conventional approaches to ORIF.

Abstract P6-08-19: Germline mutation prevalence among US and non-US Hispanic patients undergoing genetic testing for breast and ovarian cancer predisposition

Abstract Background: A variety of studies have examined the prevalence of germline mutations in patients undergoing genetic testing for a wide variety of breast cancer predisposition genes. Many of these studies have focused on patients of Northern European descent, leaving variant prevalence and clinical presentations of patients from underrepresented, and often underserved, populations much less well understood. Our study aimed to examine the prevalence of germline mutations among referred patients from Mexico, Central and South America, as well as a comparative population of Hispanic patients from the United States. Methods: We analyzed a de-identified laboratory-based cohort of patients who had received physician-ordered germline multigene panel test results between December 2014 and June 2019. Inclusion criteria for this study were a personal or family history of breast or ovarian cancer, and either (a) an ordering physician based in Mexico, Central America, or South America, or (b) a Hispanic self-reported ethnicity and a US based ordering physician. For this analysis, Mexican patients were combined with Central Americans. Panel size was per physician discretion, and most (&amp;gt;70%) physicians chose large (at least 20 gene) panels of high- and moderate-risk genes including BRCA1, BRCA2, PALB2, CHEK2, ATM, and TP53, among others. Full gene sequencing and deletion/duplication analysis were performed as described previously [PMID: 26207792] and variants were classified using a framework based on the ACMG/AMP guidelines for variant interpretation [PMID: 28492532]. Results: Of the 25,249 participants who met criteria, 18,513 were self-identified Hispanic-Amercians and 6,736 were non-US participants. Of the non-US group, 6,398 were from South America (including 1200 from Chile and 3781 from Brazil) while 273 were from Mexico and 65 from Central America. Pathogenic or Likely Pathogenic variants were uncovered in 14.4% of all participants, with 1864 findings (representing 7.4% of participants) in BRCA1 or BRCA2, and 1769 (7.0% of participants) in other cancer risk genes. Stratified by location, mutation positive rates were highest among Central (26.9%) and South Americans (19.2%), and lowest among the US Hispanics (12.5%). Based on NCCN guidelines, many of these findings would warrant consideration of a change in care for the patient and/or reflex testing of family members. Conclusions: Cancer patients in Mexico, Central, and South America may have less access to germline genetic testing than patients in (for example) the United States, although our study suggests that Latin American patients and their families can benefit from genetic testing at least at the same rate as Hispanic patients in the US. The higher positive rate among Central and South Americans in this study compared to Hispanic-Americans may be due to referral patterns and cost impact, although this question requires further study. The relative VUS rates between populations, mutation rates for specific clinical presentations, and relevant psychosocial issues also need further study to help maximize the utility of germline genetic testing in Latin America. Citation Format: Stephen E Lincoln, Daniel Pineda-Alvarez, Scott T Michalski, Shan Yang, Edward D Esplin. Germline mutation prevalence among US and non-US Hispanic patients undergoing genetic testing for breast and ovarian cancer predisposition [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-19.

Comparing a Tailored Self-Help Mobile App With a Standard Self-Monitoring App for the Treatment of Eating Disorder Symptoms: Randomized Controlled Trial.

BackgroundEating disorders severely impact psychological, physical, and social functioning, and yet, the majority of individuals with eating disorders do not receive treatment. Mobile health apps have the potential to decrease access barriers to care and reach individuals who have been underserved by traditional treatment modalities.ObjectiveThe objective of this study was to evaluate the effectiveness of a tailored, fully automated self-help version of Recovery Record, an app developed for eating disorders management. We examined differences in eating disorder symptom change in app users that were randomized to receive either a standard, cognitive behavioral therapy–based version of the app or a tailored version that included algorithmically determined clinical content aligned with baseline and evolving user eating disorder symptom profiles.MethodsParticipants were people with eating disorder symptoms who did not have access to traditional treatment options and were recruited via the open-access Recovery Record app to participate in this randomized controlled trial. We examined both continuous and categorical clinical improvement outcomes (measured with the self-report Eating Disorder Examination Questionnaire [EDE-Q]) in both intervention groups.ResultsBetween December 2016 and August 2018, 3294 Recovery Record app users were recruited into the study, out of which 959 were considered engaged, completed follow-up assessments, and were included in the analyses. Both study groups achieved significant overall outcome improvement, with 61.6% (180/292) of the tailored group and 55.4% (158/285) of the standard group achieving a clinically meaningful change in the EDE-Q, on average. There were no statistically significant differences between randomized groups for continuous outcomes, but a pattern of improvement being greater in the tailored group was evident. The rate of remission on the EDE-Q at 8 weeks was significantly greater in the group receiving the tailored version (d=0.22; P≤.001).ConclusionsThis is the first report to compare the relative efficacy of two versions of a mobile app for eating disorders. The data suggest that underserved individuals with eating disorder symptoms may benefit clinically from a self-help app and that personalizing app content to specific clinical presentations may be more effective in promoting symptomatic remission on the EDE-Q than content that offers a generic approach.Trial RegistrationClinicalTrials.gov NCT02503098; https://clinicaltrials.gov/ct2/show/NCT02503098.

Editors' note: Unintended consequences of Mayo paraneoplastic evaluations

In the article “Unintended consequences of Mayo paraneoplastic evaluations,” Ebright et al. retrospectively identified 500 consecutive patients with Mayo paraneoplastic antibody testing and used chart abstraction to decide whether positive antibody results (17.4% of the sample) were true or false positives. Cases were classified as true positives if no other explanation was found, and the patient's presentation was known to be associated with the antibody, or improved clinically with treatment, or was associated with a new malignancy being identified. They concluded that 71.3% of the positive tests were false positives, with this being more common with clinical presentations that were not well established as paraneoplastic, and suggested the construction of panels targeted to specific clinical presentations while ensuring that tests are ordered in the appropriate context. In the article “Unintended consequences of Mayo paraneoplastic evaluations,” Ebright et al. retrospectively identified 500 consecutive patients with Mayo paraneoplastic antibody testing and used chart abstraction to decide whether positive antibody results (17.4% of the sample) were true or false positives.