Unclear Diagnoses Research Articles

Phylogenetic Position of Trichomycterus payaya and Examination of Osteological Characters Diagnosing the Neotropical Catfish Genus Ituglanis (Siluriformes: Trichomycteridae).

The Trichomycterinae is among the most diverse catfish groups in the world, with interesting ecological specializations; however, the taxonomy of Trichomycterinae is still problematic, mainly due to unclear limits and diagnoses of the eight included genera. Herein we infer the phylogenetic position and generic placement of Trichomycterus payaya, a recently described species from north-eastern Brazil, with unique morphological features among congeners. A multigene analysis including fragments of two nuclear and two mitochondrial genes (total of 2974 bp) for 53 trichomycterine taxa and three outgroups clearly supports inclusion of T. payaya in Ituglanis, a trichomycterine genus containing 29 valid species, which is corroborated by osteological characters. An examination of osteological characters used to diagnose Ituglanis in its original description indicates that a rudimentary or absent posterior cranial fontanel is synapomorphic for Ituglanis, but this is reversed in I. payaya; an anteriorly directed antero-lateral extremity of the sphenotic-prootic-pterosphenoid complex and a narrow and long lateral process of the parurohyal are synapomorphic for Ituglanis, but homoplastically occurring in other trichomycterids; and the presence of a deep medial concavity on the autopalatine is ambiguous to diagnose Ituglanis by occurring in other closely related trichomycterine taxa. Ituglanis is also distinguishable from other trichomycterines by a unique shape of the metapterygoid and by a reduced number of ribs. The analysis supports a clade, comprising I. payaya and I. paraguassuensis, that is endemic to the Chapada Diamantina, in the semiarid Caatinga of north-eastern Brazil, reinforcing the importance of this region for trichomycterid diversification. By integrating molecular analysis and comparative morphology, the present study provides a more solid basis for delimiting Ituglanis, creating a better taxonomical resolution of the Trichomycterinae, although much more research is necessary to reach a consistent generic classification for the entire subfamily.

661. Futility of Bacterial Bone Marrow Cultures: Experience over a 19 Year Period

BackgroundBone marrow biopsies are often performed on patients with unclear diagnoses and cultures may be ordered for both routine bacterial, mycobacterial and fungal pathogens. They are performed in semi-sterile conditions and involve needle penetration through the skin, posing an increased risk of skin contamination. These cultures also require a substantial amount of laboratory personnel time.MethodsCultures collected from 2001-2020 were surveyed in the lab electronic record. We assessed the culture type (fungal, bacterial, mycobacterial), and the presence of pathogens and contaminants. An organism was deemed a contaminant if it was consistent with skin flora or listed as a contaminant in the report given to the physician. Organisms for which the role in bone marrow disease is unclear were included as possible pathogens. For questionable non-contaminant organisms, clinical significance was determined based on if patient was treated for the organism. For all bone marrow cultures, growth of the same organism within 1 month of the bone marrow specimen was surveyed to determine whether the organism would have been found by alternative methods.ResultsOf 483 bacterial bone marrow cultures, there were 110 (23%) positives, of which 76 (69%) were deemed contaminants. Twenty (18%) of the 76 contaminants grew in the routine bacterial culture. However, 49 (65%) contaminants grew in the AFB culture, of which 10 also grew in the bacterial culture. For the 34 non-contaminant organisms, 26 were determined to be clinically significant. Nineteen of the 26 had a matching culture (usually blood) growing the organism within 1 month. The majority of pathogens were mycobacteria (18 of the 34). Fungal organisms represented 5 cultures and 11 were bacterial. Of the 11 bacterial organisms, 1 was a Helicobacter species (grown in special media), and 4 had a matching positive blood culture. Only 4 (1% of 483) bacterial non-contaminants grew in the routine bacterial culture. Given an unknown number of true negatives, we can only conclude a positive predictive value (PPV) of 0.16 for routine bacterial cultures. Including AFB and fungal cultures, the PPV increased to 0.30.ConclusionOur findings indicate that routine bacterial bone marrow culture is unlikely to yield a novel result and is likely a poor use of lab resources.Disclosures All Authors: No reported disclosures

Road to Increasing AMR: A Study on Antibiotics Prescribing Pattern

Background: Infectious diseases and the rapid emergence of multidrug-resistant pathogens continue to pose a threat to global health. The development of antimicrobial-resistant organisms is an alarming issue caused by inappropriate use of antibiotic agents. It is estimated that death from antimicrobial resistant pathogens could increase >10-fold to ~10 million deaths annually by 2050 if action is not taken. “It is essential to have reliable data on how medicines are used in order to identify areas to develop targeted interventions” (WHO 2011). Investigating antimicrobial use in hospitals is the first step in evaluating the underlying causes of AMR. In Sierra Leone, no other study related to antibiotic prescribing patterns in hospital setting has been undertaken. Objective: To investigate antibiotic prescription patterns using the WHO hospital antimicrobial use indicator tool at the Kingharman Hospital for 1 month. Methods: Data were collected from patient charts for 1 month, January 1–31, 2019. A data extraction tool was used to capture information on patient demographics, diagnosis, and antibiotics prescription details regarding dosage, duration, and frequency of administration. The tool adopted 6 selected indicators from the WHO antimicrobial use manual to measure the extent of antibiotic use in hospital and performance among prescribers. Results: Of the 189 charts reviewed, 175 included antibiotic prescriptions. The percentage of prescriptions involving antibiotics was 92.5%. The average number of drugs prescribed was 2, with an average duration of 5.2 days. Moreover, 50.5% of antibiotics prescribed were generic, and 96.6% were from the Ministry of Health and Sanitation Essential Medicine List (EML). The most commonly used antibiotics were ciprofloxacin (38.8%), followed by ceftriaxone (23.0%), amoxicillin (16.8%), metronidazole (8.5%), and others(12.7%). Typhoid accounted for 34.8% of broad-spectrum antibiotics, UTI accounted for 17.7%, malaria accounted for 12.5%, 25.5% were unspecified, and 9.5% were for unclear diagnoses. Typically, combinations of fluroquinolones and cephalosporins were used to treat typhoid and UTIs. Conclusions: This cross-sectional study represents a broad picture of antibiotic prescribing patterns at the King Harman Hospital. There was no strict adherence to the WHO recommended prescribing guidelines. These findings also indicate the degree of irrational and inappropriate prescribing of broad-spectrum antibiotics. This study highlights the need for a comprehensive assessment of antimicrobial use to gain a better understanding of national antibiotic use and to guide interventions to reducing AMR.Funding: NoneDisclosures: NoneIf I am discussing specific healthcare products or services, I will use generic names to extent possible. If I need to use trade names, I will use trade names from several companies when available, and not just trade names from any single company.DisagreeChristiana Kallon

Accessory bones of the elbow: Prevalence, localization and modified classification

Accessory bones in the region of the elbow are rare variants with high clinical significance as they may be confused with avulsion fractures. We investigated their prevalence and performed a statistical analysis to support their congenital origin. Their localization was mapped to show their exact site of occurrence. We evaluated anteroposterior and lateral X-ray images of 2413 elbows in a Central European population from which a group of accessory bony structures was selected. Their character was evaluated, and accessory bones were identified. We used logistic regression to evaluate the potential relationship between the occurrence of accessory bones, the age of patients, and the occurrence of calcar olecrani. The prevalence of accessory bones of the elbow in the sample was 0.77%. Our results did not show a statistically significant relationship with the occurrence of calcar olecrani or with the age of patients. The most common type was os subepicondylare mediale (type V) in 0.46%, which was located distal to the medial epicondyle of the humerus, followed by os subepicondylare laterale (type III; 0.21%), situated laterally to the lateral epicondyle of the humerus. In comparison with previous reports, os sesamoideum mediale (type IV) was located more distally. Our data suggest that congenital accessory bones are a rare entity. Knowledge of their exact localization should be considered during diagnosis of avulsion fractures and other unclear diagnoses including accessory bony structures in the elbow region.

Complex regional pain syndrome - False hopes and miscommunications.

Complex regional pain syndrome (CRPS) has been considered to be an autoimmune disease and there have been clinical trials with intravenous immunoglobulin. Often the etiology of the so-called CRPS diagnosis cannot be discerned and there are no validated instruments that provide functional metrics. The term complex regional pain syndrome (CRPS), coined in 1994 to describe patients in whom the pain is out of proportion to the injury, was actually a diagnosis proposed during the American Civil War, but was originally known as causalgia. Physicians have long observed similar sensitivity and inflammatory symptoms following periods of immobilization and disuse, which generally resolve within a few months of remobilization. Following the original description, persistent disproportionate pain would come to be known under many other names until researchers theorized that it was related to dysfunction in the sympathetic nervous system, after which it acquired the moniker, Reflex Sympathetic Dystrophy ("RSD"). In the latter quarter of the twentieth century, after researchers failed to prove the connection between the pain and the sympathetic nervous system, a small cadre of physicians-without rigorous science-invented CRPS. This new descriptor, CRPS, has become not only a diagnosis without objective data but with proposed criteria involving ambiguous signs and symptoms with low specificity. It has led to patients being treated erroneously with sympatholytic drugs, with or without pharmaceutical or surgical blockade of the sympathetic nervous system, unwarranted use of ketamine infusions, inappropriate use of narcotics and nerve stimulation. Intravenous immunoglobulin infusions have not been effective in the treatment of chronic pain. The indiscriminate use of pain medications to treat subjective symptoms of unclear diagnoses can be a risk factor for opioid and analgesic misuse or abuse.

Diagnosis and Treatment of Slipping Rib Syndrome.

(1) To investigate the clinical presentation, diagnosis, and treatment of slipping rib syndrome in athletes; (2) to investigate the hooking maneuver for diagnosis of slipping rib syndrome. Retrospective chart review of 362 athletes with rib pain. Pediatric-based sports medicine clinic between January 1, 1999, and March 1, 2014. Costochondritis, Tietze, fractures, rib tip syndrome, and unclear diagnoses were excluded. Athletes were included who had a palpable rib subluxation, mechanical rib symptom, positive hooking maneuver, or resolution of pain after the resection of a slipping rib segment. Slipping rib syndrome is associated with athletic performance. Fifty-four athletes were diagnosed with slipping rib syndrome, of which 38 (70%) were females. Mean age at presentation was 19.1 years (range 4-40 years). Mean number of previous specialist consultations per athlete was 2.3 and mean time from symptom onset to diagnosis was 15.4 months. The hooking maneuver was attempted 21 times (38.9%). Unilateral symptoms presented in 49 athletes (90.7%). The most symptomatic rib was the 10th, affecting 24 athletes (44.4%), eighth and ninth were affected in 17 athletes (31.5%) each. Most, 39 (72.2%), reported insidious onset of symptoms. Running, rowing, lacrosse, and field hockey were frequently associated activities. Twelve athletes had psychiatric diagnoses (22.2%), 10 (19.2%) were hypermobile. Sixty-six total imaging studies were performed. The most successful treatment options included: osteopathic manipulative treatment (71.4%), surgical resection (70%), and diclofenac gel (60%). Most athletes with slipping rib syndrome were active females with insidious onset of unilateral pain, a high prevalence of hypermobility and prolonged pain. The hooking maneuver was underused.

Multi-Institutional, Prospective Clinical Utility Study Evaluating the Impact of the 92-Gene Assay (CancerTYPE ID) on Final Diagnosis and Treatment Planning in Patients With Metastatic Cancer With an Unknown or Unclear Diagnosis.

Metastatic cancers of unknown primary or with unclear diagnoses pose diagnostic and management challenges, often leading to poor outcomes. Studies of the 92-gene assay have demonstrated improved diagnostic accuracy compared with standard pathology techniques and improved survival in patients treated on the basis of assay results. The current study assessed the clinical impact of the 92-gene assay on diagnostic and treatment decisions for patients with unknown or uncertain diagnoses. Patients in this prospective, multi-institutional, decision-impact study included those for whom the 92-gene assay was ordered as part of routine care. Participating physicians completed electronic case report forms that contained standardized, specialty-specific questionnaires. Data collection included patient and tumor characteristics and clinical history. The key study objective of clinical impact was calculated on the basis of changes in final diagnosis and treatment after testing. Data collection included 444 patients, 107 physicians (73 oncologists and 34 pathologists), and 28 sites. Molecular diagnoses from 22 different tumor types and subtypes across all cases were provided in 95.5% of patients with a reportable result (n = 397). Physicians reported that the 92-gene assay was used broadly for diagnostic dilemmas that ranged from single suspected tumor type (29%) to a differential diagnosis of two or more suspected tumor types (30%) or cancers of unknown primary (41%). Integration of 92-gene assay results led to a change in the recommended treatment in 47% of patients. Findings from this clinical utility study demonstrate that the 92-gene assay led to a change in treatment decisions in every other patient case. These data additionally define the role of this assay in clinical practice and strongly support the consideration of molecular tumor typing in the diagnosis and treatment planning of patients with metastatic cancer with unknown or uncertain diagnosis.

The Impact of Delay in Clostridium difficile Testing on Outcomes in Hospitalized IBD Patients With Gastrointestinal Symptoms

Introduction:Clostridium difficile infection (CDI) is common in inflammatory bowel disease (IBD) patients, and often mimics IBD exacerbations. Timely diagnosis, or exclusion of CDI after hospital presentation is critical to treatment decisions in this population. The purpose of this study was to measure the impact of delay in C. difficile cytotoxin assay (CDCA) on the length of stay (LOS), time to appropriate treatment, adverse outcomes, and CDI recurrence in IBD patients admitted with fever, diarrhea and/or abdominal pain. Methods: This is a single center, retrospective chart review of 642 patients with a diagnosis of IBD, derived from a patient database from 1/2012 to 12/2017 and included those who were admitted with fever, diarrhea and/or abdominal pain and were tested for CDI. Patients with unclear diagnoses, incomplete data, discharge prior to CDCA result or prolonged stay for unrelated reasons were excluded. Demographic, clinical, and outcomes data were collected. Depending on variable type, statistical associations and comparisons were calculated using a Pearson correlation, Chi-square, or Mann-Whitney U tests. Results: 115 admissions were included in the final analysis. Baseline characteristics are described in Table 1. Time to CDCA >48 hours and <48 hours was associated with a mean LOS of 9.06 days (CI ±1.52), and 7.16 days (CI ±1.88, p <0.001), respectively (Table 2). The premature use of non-CDI antibiotics (prior to CDCA result) was associated with mean LOS of 12.75 days (CI ±5.86) versus 7.49 days (CI ±1.17, p <0.05) in patients without premature use of non-CDI antibiotics (Table 3). Recurrent CDI, lack of remission, readmission, surgery and death trended toward association with prolonged time to CDCA but were not significant. Conclusion: Delay in CDCA in IBD patients admitted with abdominal pain, fever, and/or diarrhea is associated with prolonged hospitalization. Additionally, the premature use of non-CDI antibiotics prior to CDCA result is associated with prolonged hospitalization. Prospective data will help us clarify the impact of delay in diagnosis of CDI in acutely ill IBD patients.672_A Figure 1 No Caption available.672_B Figure 2 No Caption available.672_C Figure 3 No Caption available.

Non-specific complaints at emergency department presentation result in unclear diagnoses and lengthened hospitalization: a prospective observational study

BackgroundUp to 20% of patients admitted to an emergency department present with non-specific complaints. Retrospective studies suggest an increased risk of misdiagnosis and hospital admission for these patients, but prospective comparisons of the outcomes of emergency patients with non-specific complaints versus specific complaints are lacking.MethodsAll consecutive patients ≥18 years of age admitted to any internal medicine ward at Bern University Hospital via the emergency department from August 15th 2015 to December 7th 2015 were prospectively included and followed up upon. Patients with non-specific complaints were compared against those with specific complaints regarding the quality of their emergency department diagnosis, length of hospital stay and in-hospital mortality.ResultsSeven hundred and-eleven patients, 165 (23.21%) with non-specific complaints and 546 with specific complaints, were included in this study. No differences between patient groups regarding age, gender or initial severity of the medical problem (deducted from triage category and treatment in a resuscitation bay) were found. Patients with non-specific complaints received more unspecific diagnoses (30.3% vs. 23.1%, p = 0.001, OR = 1.82 [95% CI 1.159–2.899]), were hospitalized significantly longer (Median = 6.51 (IQR = 5.85) vs. 5.22 (5.83) days, p = 0.025, d = 0.2) but did not have a higher mortality than patients with specific complaints (7.3% vs. 3.7%, p = 0.087, OR 1.922 [95% CI 0.909–4.065]).ConclusionsNon-specific complaints in patients admitted to an emergency department result in low-quality diagnoses and lengthened hospitalization, despite the patients being comparable to patients with specific complaints at admission.

Utilizing Peptide Ligand GPCRs to Image and Treat Pancreatic Cancer.

It is estimated that early detection of pancreatic ductal adenocarcinoma (PDAC) could increase long-term patient survival by as much as 30% to 40% (Seufferlein, T. et al., Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 74–75). There is an unmet need for reagents that can reliably identify early cancerous or precancerous lesions through various imaging modalities or could be employed to deliver anticancer treatments specifically to tumor cells. However, to date, many PDAC tumor-targeting strategies lack selectivity and are unable to discriminate between tumor and nontumor cells, causing off-target effects or unclear diagnoses. Although a variety of approaches have been taken to identify tumor-targeting reagents that can effectively direct therapeutics or imaging agents to cancer cells (Liu, D. et al., J. Controlled Release 2015, 219, 632–643), translating these reagents into clinical practice has been limited, and it remains an area open to new methodologies and reagents (O’Connor, J.P. et al., Nat. Rev. Clin. Oncol. 2017, 14, 169–186). G protein–coupled receptors (GPCRs), which are key target proteins for drug discovery and comprise a large proportion of currently marketed therapeutics, hold significant promise for tumor imaging and targeted treatment, particularly for pancreatic cancer.

Diagnosis of the cause of chronic dyspnoea in primary and tertiary care: characterizing diagnostic confidence.

Chronic dyspnoea (breathlessness) in adults is a common symptom, the exact cause of which may be difficult to diagnose on initial presentation. We characterised the diagnostic complexity of chronic dyspnoea in primary care and tertiary care. This retrospective observational study screened consecutive referral letters of all adult patients referred to cardiology or respiratory clinics at a tertiary referral hospital, during May to June 2015. For patients referred due to chronic dyspnoea, data were analysed from the initial referral letter and subsequent specialist clinic letters for the 6-month time period after referral. Of 1,370 patient referrals, 122 patients (mean age 63 y, 55% female) were referred due to chronic dyspnoea. One hundred and five patients (86%) were referred from primary care and 17 (14%) from other hospital clinics. Sixty-one percent were referred with an evident diagnosis (referrer was confident of the initial diagnosis), whereas 39% had non-evident or unclear diagnoses. By 6 months after referral, a definitive final diagnosis had been determined by the specialist clinics in 62% of patients. The majority of patients had been referred appropriately to a cardiology or respiratory clinic, based on the final diagnosis. However, only 26% of diagnoses were fully concordant between the initial referrer diagnosis and the final specialist clinic diagnosis, with 26% being partially concordant and 48% non-concordant. Diagnostic certainty of the referrer was associated with concordance of diagnosis between the referrer and specialist clinic (P<0.001). In adult patients referred due to chronic dyspnoea to hospital specialist clinics, there is considerable diagnostic uncertainty about its aetiology, for both referring doctors and specialist clinics. These results demonstrate the current difficulty in diagnosing the cause of chronic dyspnoea in adults, and highlight the need for evidence-based diagnostic pathways.

The lesser of two evils: a qualitative study of quetiapine prescribing by family physicians.

Quetiapine is an antipsychotic that is widely prescribed off-label by family physicians despite evidence that safer alternatives exist. The aim of this research was to explore, in-depth, family physicians' reasons for this behaviour. We conducted qualitative interviews with 15 urban family physicians in Alberta between October 2015 and April 2016. Participants were purposively selected based on sex, years of experience and practice type. Interviews explored participants' experiences prescribing quetiapine. Interviews were recorded, transcribed verbatim and coded with the use of thematic analysis. A wish to support day-to-day function of patients with complex psychosocial needs without causing benzodiazepine addiction motivated participants to prescribe quetiapine. The indications were varied and included incomplete symptom resolution, unclear or multiple mental health diagnoses, and complicated psychosocial problems. Family physicians benchmarked their prescribing against peers and were reluctant to stop medication started by colleagues. Limited knowledge of quetiapine's adverse effects led prescribers to choose low dosages. Quetiapine helped family physicians treat patients with complex mental health problems without prescribing benzodiazepines, but awareness of quetiapine's adverse effects was poor. Education about quetiapine should combine psychopharmacology with multidisciplinary educational initiatives that focus on symptom resolution, comorbidity and nondrug options to promote more appropriate prescribing.

Up to 89% of neonates received antibiotics in cross-sectional Indian study including those with no infections and unclear diagnoses.

There is a global lack of data on antibiotic prescribing for neonates. This study compared antibiotic prescribing practices in the neonatal intensive care units (NICUs) of two private-sector, tertiary-level hospitals. A three-year, cross-sectional study was conducted from 2008 to 2011 in the NICUs of a teaching and nonteaching hospital in the Ujjain district of India. The data were analysed using methods recommended by the World Health Organization. Of the 1789 inpatients, 89% (1399/1572) in the nonteaching hospital and 71% (154/217) in the teaching hospital were prescribed antibiotics and 123 patients died. All the antibiotics were prescribed empirically and cephalosporins and aminoglycosides were the most commonly prescribed subclasses. Fixed-dose combinations of cephalosporins were commonly prescribed in the nonteaching hospital. Neonatal sepsis was the most common diagnosis, in more than 30% of patients, and more than 93% neonates with sepsis were prescribed antibiotics. In addition, 40% of neonates in the nonteaching hospital were admitted for observation and were frequently prescribed antibiotics. These two Indian NICUs prescribed antibiotics for noninfectious or unclear diagnoses in addition to prescribing combinations of broad-spectrum antibiotics. Such practices increase the global risk of treatment failure, neonatal mortality rates and antibiotic resistance.

P105: Patient outcome feedback in emergency medicine

Introduction: Emergency medicine (EM) is characterized by one time patient encounters where the end diagnosis is often unknown. Seeking patient outcome feedback, (POF) which is defined as following a patient’s clinical course once they leave your care, is crucial as it can highlight a discord between an intended verses actual result, thus spurring clinical change. This study seeks to determine whether EM staff and residents currently seek POF, the types of patients followed and the barriers faced. Methods: An online survey was administered to all EM staff and residents (CCFP-EM and FRCP) working at a tertiary academic hospital to determine their current practices and attitudes towards POF. Results: A total of 72 responses were received, of which 41 were residents and 31 were staff, for an overall response rate of 95%. If feedback was sought, the most commonly used tools were looking up imaging results (52%) and talking to EM colleagues (42%). The patients most frequently followed were those with a poor outcome during their ED admission, sick patients with unclear final diagnosis or unplanned returns within 48 hours (55%, 58%, 34% respectively). However, up to 30% of respondents never or rarely sought out POF even in these situations (16%, 19% and 30% respectively). Patients least commonly followed were those where the diagnosis was more certain. Respondents identified many barriers, primarily being time (83%), not being notified about bouncebacks (79%) and remembering which patients to follow (70%). Barriers were amplified for residents as they had a harder time accessing or automatically receiving POF. The most useful tools not currently available, would be being able to easily create electronic tracking lists, being automatically sent discrepant imaging reports and automatic notification of patients who return to the ED within 48hrs. Also, automatic follow up information on patients who experienced a negative outcome or on sick patients with unclear diagnosis is desired. Conclusion: POF is a useful and crucial practice for clinical care, but is currently not often performed. The most commonly used tools are those that are easiest to access, and POF was mainly performed on patients with either negative results or unclear diagnoses. Thus, identifying the types of patients deemed most relevant for receiving POF and addressing the major barriers faced by clinicians can help improve the frequency with which POF is sought, potentially improving patient care.

Genetic and Neuroimaging Features of Personality Disorders: State of the Art.

Personality disorders often act as a common denominator for many psychiatric problems, and studies on personality disorders contribute to the etiopathology, diagnosis, and treatment of many mental disorders. In recent years, increasing evidence from various studies has shown distinctive features of personality disorders, and that from genetic and neuroimaging studies has been especially valuable. Genetic studies primarily target the genes encoding neurotransmitters and enzymes in the serotoninergic and dopaminergic systems, and neuroimaging studies mainly focus on the frontal and temporal lobes as well as the limbic-paralimbic system in patients with personality disorders. Although some studies have suffered due to unclear diagnoses of personality disorders and some have included few patients for a given personality disorder, great opportunities remain for investigators to launch new ideas and technologies in the field.

Clinical Impact of a Second FDG-PET in Atypical/Unclear Dementia Syndromes.

Diagnosis of atypical/unclear dementia is often difficult and this delays treatment initiation. Several authors have shown that beyond standard dementia workup, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) reduces the number of unclear diagnoses, leads to earlier treatment, and has a beneficial impact on families. However, it is not uncommon that the FDG-PET findings are equivocal in this setting. For those cases, a repeat FDG-PET may clarify the diagnosis and prevent treatment delay. We retrospectively assessed the clinical impact of a repeat FDG-PET in 59 patients with atypical/unclear dementia syndromes and inconclusive initial FDG-PET. Changes in primary diagnosis, diagnostic confidence, and management following the second FDG-PET were examined. Conducting a second FDG-PET reduced the number of unclear diagnoses from 80% to 34% , led to diagnostic change in 24% of cases, and treatment modification in 22% of patients. Overall, the clinical impact was higher when initial diagnostic confidence was low and the second FDG-PET repeated ≥12 months after the first one. In tertiary care memory clinic settings, when diagnostic incertitude persists despite extensive evaluation and an equivocal FDG-PET, repeating the FDG-PET 12 months later can greatly clarify the diagnosis and improve management.

Molecular profiling with the 92-gene assay and decision-impact on cancer treatment: Interim results from a prospective, multidisciplinary study.

249 Background: Metastatic lesions with unknown (CUP), unclear, or differential diagnoses pose significant challenges, particularly when presenting in the GI tract, leading to suboptimal treatment and outcomes. In clinical studies, molecular classification with the 92-gene assay demonstrated improved diagnostic accuracy compared to standard pathology techniques and improved survival in patients treated based on assay results. The current study assessed the utility of the 92-gene assay in diagnoses and treatment decision-making in clinical practice. Methods: Cases in which the 92-gene assay was ordered as part of routine clinical care were submitted into a study database via web-based, standardized, discipline-specific questionnaires. Utilization and impact of the assay were characterized for medical oncologists and pathologists. Physician-reported results from medical oncologists are included in this interim analysis of 134 cases. Results: Results from this registry-based reporting study showed that molecular profiling impacted treatment decisions in 53% of cases. Significantly, 46% of these cases reported a change in treatment regimen associated with integration of 92-gene assay results. Clinical scope included 18 tumor types with 52% having a molecular diagnosis of GI origin. The top 3 diagnoses were pancreaticobiliary, intestine, and gastroesophageal adenocarcinoma. The pre-assay working diagnosis was unknown in 41%, a differential diagnosis in 26%, and a single suspected site in 33% of cases. Conclusions: Findings from this study demonstrate that use of the 92-gene assay impacted treatment decisions and selection in a significant proportion of patients, and further define its role in clinical practice in the diagnosis and treatment planning of diagnostically-challenging metastatic cancer. [Table: see text]

Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1.

We describe two brothers who presented at birth with bone growth abnormalities, followed by development of increasingly severe intellectual and physical disability, growth restriction, epilepsy, and cerebellar and brain stem atrophy, but normal ocular phenotypes. Case 1 died at 19 years of age due to chronic respiratory illnesses without a unifying diagnosis. The brother remains alive but severely disabled at 19 years of age. Whole exome sequencing identified compound heterozygous stop mutations in the peroxisome biogenesis factor 7 gene in both individuals. Mutations in this gene cause rhizomelic chondrodysplasia punctata, type 1 (RCDP1). One mutation, p.Arg232∗, has only been documented once before in a Japanese family, which is of interest given these two boys are of European descent. The other mutation, p.Leu292∗, is found in approximately 50% of RCDP1 patients. These are the first cases of RCDP1 that describe the coinheritance of the p.Arg232∗ and p.Leu292∗ mutations and demonstrate the utility of WES in cases with unclear diagnoses.

Gamma knife surgery for pineal region tumors: an alternative strategy for negative pathology

Pineal region tumors (PRTs) are uncommon, and treatments vary among neoplasm types. The authors report their experience with gamma knife surgery (GKS) as an initial treatment in a series of PRT patients with unclear pathological diagnoses. Seventeen PRT patients with negative pathology who underwent GKS were retrospectively studied. Nine patients had further whole-brain and spinal cord radiotherapy and chemotherapy 6-9 months after GKS. Sixteen of 17 cases were followed up over a mean of 33.3 months. The total response rate was 75%, and the control rate was 81.3%. No obvious neurological deficits or complications were attributable to GKS. The findings indicate that GKS may be an alternative strategy in selected PRT patients who have negative pathological diagnoses, and that good outcomes and quality of life can be obtained with few complications.

NHETS - Necropsy Heart Transplantation Study.

BackgroundDiscrepancies between pre and post-mortem diagnoses are reported in the literature, ranging from 4.1 to 49.8 % in cases referred for necropsy, with important impact on patient treatment.ObjectiveTo analyze patients who died after cardiac transplantation and to compare the pre- and post-mortem diagnoses.MethodsPerform a review of medical records and analyze clinical data, comorbidities, immunosuppression regimen, laboratory tests, clinical cause of death and cause of death at the necropsy. Then, the clinical and necroscopic causes of death of each patient were compared.Results48 deaths undergoing necropsy were analyzed during 2000-2010; 29 (60.4 %) had concordant clinical and necroscopic diagnoses, 16 (33.3%) had discordant diagnoses and three (6.3%) had unclear diagnoses. Among the discordant ones, 15 (31.3%) had possible impact on survival and one (2.1%) had no impact on survival. The main clinical misdiagnosis was infection, with five cases (26.7 % of discordant), followed by hyperacute rejection, with four cases (20 % of the discordant ones), and pulmonary thromboembolism, with three cases (13.3% of discordant ones).ConclusionDiscrepancies between clinical diagnosis and necroscopic findings are commonly found in cardiac transplantation. New strategies to improve clinical diagnosis should be made, considering the results of the necropsy, to improve the treatment of heart failure by heart transplantation.