Extension of the Human Fibrinogen Database with Detailed Clinical Information—The αC-Connector Segment

Fibrinogen, an abundant plasma glycoprotein, is involved in the final stage of blood coagulation. Decreased fibrinogen levels, which may be caused by mutations, are manifested mainly in bleeding and thrombotic disorders. Clinically relevant mutations of fibrinogen are listed in the Human Fibrinogen Database. For the αC-connector (amino acids Aα240–410, nascent chain numbering), we have extended this database, with detailed descriptions of the clinical manifestations among members of reported families. This includes the specification of bleeding and thrombotic events and results of coagulation assays. Where available, the impact of a mutation on clotting and fibrinolysis is reported. The collected data show that the Human Fibrinogen Database reports considerably fewer missense and synonymous mutations than the general COSMIC and dbSNP databases. Homozygous nonsense or frameshift mutations in the αC-connector are responsible for most clinically relevant symptoms, while heterozygous mutations are often asymptomatic. Symptomatic subjects suffer from bleeding and, less frequently, from thrombotic events. Miscarriages within the first trimester and prolonged wound healing were reported in a few subjects. All mutations inducing thrombotic phenotypes are located at the identical positions within the consensus sequence of the tandem repeats.

LIGATURE RECORD: improved capture of risk information in CAMHS PICU using a mnemonic-style documentation aid

Psychiatric risks associated with ligature-tying present significant management challenges for inpatient multidisciplinary teams (MDT). Accurate and detailed clinical information capture following incidents involving ligatures is necessary to inform future risk management. A documentation tool is presented whichhas been demonstrated to improve the accuracy of recording of clinical risk information following inpatient ligature incidents in the child and adolescent mental health service (CAMHS) psychiatric intensive care unit (PICU) setting. The LIGATURE RECORD tool provides a highly useable prompt for information capture of 14 important data elements identified as relevant to MDT risk formulation.The effectiveness of the LIGATURE RECORD tool was audited following its introduction in PICU in May 2020. Contemporaneous incident reports and progress note entries were examined with an improvement in the frequency of reporting of all 14 domains seen, with near-100% completeness where the prompt was used directly as a template. Particular improvements were seen in recordingof non-narrative elements such as circumstantial information and important negative reports. Formal and informal feedback from clinical staff indicated good usability and high rates of adoption of the tool.

The Evaluation of Risk Factors for Postoperative Infectious Complications after Percutaneous Nephrolithotomy

This study was to evaluate the risk factors of infectious complications after percutaneous nephrolithotomy (PCNL) and build a prediction tool for postoperative complications based on the risk factors. A total of 110 male (67.1%) and 54 female (32.9%) patients who underwent PCNL for renal stones between 2010 and 2014 in our institute were included. A detailed clinical information and laboratory results were obtained from patients. Systemic inflammatory response syndrome (SIRS) and postoperative fever were recorded after PCNL surgery. In all, 45 cases (27.4%) developed SIRS and fever was observed in 20 cases (12.2%). In multivariate analysis, stone size (odds ratio, OR = 1.471,p=0.009) and urine white blood cell (WBC) (OR = 1.001,p=0.007) were related to the development of SIRS. Stone size (OR = 1.644,p=0.024), urine WBC (OR = 1.001,p=0.002) and serum albumin (OR = 0.807,p=0.021) were associated with postoperative fever. We concluded that patients with larger stone size and preoperative urinary tract infection might have a higher risk of developing SIRS and fever after operation, while a high-normal level of serum albumin might be the protective factor for postoperative fever.

The Nationwide Study of Erdheim-Chester Disease in Japan

Background: Erdheim-Chester disease (ECD) is a subtype of non-Langerhans histiocytic disorder that is shown to be driven by hyperactivation of MAPK pathway (most frequently caused by BRAFV600E mutation) and characterized by generalized organ dysfunction with infiltration of CD68-positive, CD1a-negative histiocytes. However, ECD is a rare entity and therefore very little is known about epidemiology of this disorder. Methods: We underwent a postal questionnaire-based, multi-center retrospective study to clarify the clinical features of ECD patients. We first sent 3850 questionnaires to various departments including orthopedics, respiratory medicine, dermatology, hematology, and pathology to cover as many ECD patients as possible, and identified 71 ECD patients in Japan. We further collected detailed clinical information and patients' samples if available. All cases were pathologically proven and the diagnoses of ECD were self-reported by each institute. DNA was extracted from each clinical sample and Sanger sequencing or allele-specific polymerase chain reaction (PCR) for BRAFV600E mutation were underwent with specific primers. Results: Among 71 patients with ECD, detailed clinical information about 38 patients were collected. The median age was 51 years old (range: 25-76 years old) and there was a male predominance (1.9:1). Major affected lesions were the bone (84 %), central nervous system (CNS; 50 %), cardiovascular lesion (37 %), skin (37 %), retroperitoneum (37 %), endocrines (37 %), lung (24 %), and digestive organ (12 %). C-reactive protein at onset was higher than upper normal limit in 24 of 29 patients (median 23.8 mg/L). The median time from the onset to diagnosis was 17 months and median survival from initial onset was 10.9 years. In the univariate analyses, age older than 60 years old at initial onset (hazard ratio [HR], 30.2; 95% CI, 5.7-159; p < 0.001), weight loss (HR, 5.4; 95% CI, 1.4-20.8; p = 0.014), CNS involvement (HR, 25.2; 95% CI, 3.1-203; p = 0.0024), cardiovascular lesion (HR, 3.6; 95% CI, 1.2-10.8; p = 0.021) and digestive organ disease (HR, 5.6; 95% CI, 1.6-20.2; p = 0.0085) were associated with poor prognosis. Interestingly, the bone involvement was associated with better outcome (HR, 0.20; 95% CI, 0.065-0.63; p = 0.0052). Multivariate analysis revealed that older age was an independent poor prognostic factor (HR, 18.9; 95% CI, 2.12-169; p = 0.0085). In addition, patients with CNS involvement were significantly older than patients without CNS disease (median, 63.7 vs 44.0 years old; p < 0.001). We also analyzed the BRAF V600E mutation status in seven cases. Allele-specific PCR identified that three of seven patients had BRAFV600E mutation. Conclusion: Our nationwide survey revealed that older age was associated with CNS involvement and poor prognosis in ECD patients. In addition, the bone, cardiovascular, CNS and digestive organ involvement might also affect clinical outcome. It is of note that the bone lesion was associated with better survival in the univariate analysis. However, larger and prospective studies are warranted. Regional disparity such as percentage of bone lesions should be also investigated. Disclosures Ogura: Payment for lectures including service on speakers bureaus: Speakers Bureau.

Evaluation of the enterovirus laboratory surveillance system in Denmark, 2010 to 2013

The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus-transmission in a timely manner. We evaluate the national EV laboratory surveillance, to generate recommendations for system strengthening. The system was analysed for completeness of viral typing analysis and clinical information and timeliness of specimen collection, laboratory results and reporting of clinical information. Of 23,720 specimens screened, 2,202 (9.3%) were EV-positive. Submission of cerebrospinal fluid and faecal specimens from primary diagnostic laboratories was 79.5% complete (845/1,063), and varied by laboratory and patient age. EV genotypes were determined in 68.5% (979/1,430) of laboratory-confirmed cases, clinical information was available for 63.1% (903/1,430). Primary diagnostic results were available after a median of 1.4 days, typing results after 17 days, detailed clinical information after 33 days. The large number of samples typed demonstrated continued monitoring of EV-circulation in Denmark. The system could be strengthened by increasing the collection of supplementary faecal specimens, improving communication with primary diagnostic laboratories, adapting the laboratory typing methodology and collecting clinical information with electronic forms.

Transport and Use of Point-of-Care Ultrasound by a Disaster Medical Assistance Team

The role of ultrasound in disaster medicine has not been not well established. This report describes the transport and use of point-of-care ultrasound by Disaster Medical Assistance Team (DMAT) responding to a mass-casualty incident due to a cyclone. Ultrasound-competent physicians on the team were able to use portable ultrasound on cyclone casualties to exclude intra-abdominal hemorrhage, peri cardial fluid, pneumothoraces, and hemothoraces Information obtained using ultrasound made initial patient management, and subsequent decisions regarding triage for transport safer and based on more detailed clinical information.

Acute Chlormethiazole Poisoning in Patients Notified to the Poisons Unit, Guy's Hospital, 1978-1981

1 Out of 493 patients with suspected acute chlormethiazole poisoning notified to the Poisons Unit, Guy's Hospital during 1978-1981, the diagnosis was confirmed either analytically or by detailed clinical information in 108 patients, 40 of whom had ingested chlormethiazole alone. 2 The principal signs reported indicate that the clinical features of acute chlormethiazole poisoning resemble those of barbiturate poisoning, with deep coma ( n = 66), respiratory depression ( n = 26) and hypotension ( n = 17) in the severe cases. Five patients died as a result of early, profound respiratory depression. 3 In 53 survivors in whom toxicological analyses were performed, poisoning with chlormethiazole alone had a better prognosis than when ethanol or other drugs were also present, except in patients with hepatic or pulmonary disease or in the elderly. 4 These results emphasise that although patients poisoned with chlormethiazole who survive to reach hospital generally have a good prognosis, fatal respiratory complications often occur before the patient can be treated.