Rapid identification of pathogens associated with ventilator-associated pneumonia by Nanopore sequencing.

BACKGROUND: Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens. METHODS: The endotracheal aspirate (ETA) of 83 patients with suspected VAP from Peking University Third Hospital (PUTH) was collected, saponins were used to deplete host genomes, and PCR- or non-PCR-amplified library construction methods were used and compared. Sequence was performed with MinION equipment and local data analysis methods were used for sequencing and data analysis. RESULTS: Saponin depletion effectively removed 11 of 12 human genomes, while most pathogenic bacterial genome results showed no significant difference except for S. pneumoniae. Moreover, the average sequence time decreased from 19.6 h to 3.62 h. The non-PCR amplification method and PCR amplification method for library build has a similar average sensitivity (85.8% vs. 86.35%), but the non-PCR amplification method has a better average specificity (100% VS 91.15%), and required less time. The whole method takes 5-6 h from ETA extraction to pathogen classification. After analysing the 7 pathogens enrolled in our study, the average sensitivity of metagenomic sequencing was approximately 2.4 times higher than that of clinical culture (89.15% vs. 37.77%), and the average specificity was 98.8%. CONCLUSIONS: Using saponins to remove the human genome and a non-PCR amplification method to build libraries can be used for the identification of pathogens in the ETA of VAP patients within 6 h by MinION, which provides a new approach for the rapid identification of pathogens in clinical departments.

Hepatotoxicity of FDA-approved small molecule kinase inhibitors.

Introduction: Given their importance in cellular processes and association with numerous diseases, protein kinases have emerged as promising targets for drugs. The FDA has approved greater than fifty small molecule kinase inhibitors (SMKIs) since 2001. Nevertheless, severe hepatotoxicity and related fatal cases have grown as a potential challenge in the advancement of these drugs, and the identification and diagnosis of drug-induced liver injury (DILI) are thorny problems for clinicians.Areas covered: This article summarizes the progression and analyzes the significant features in the study of SMKI hepatotoxicity, including clinical observations and investigations of the underlying mechanisms.Expert opinion: The understanding of SMKI-associated hepatotoxicity relies on the development of preclinical models and improvement of clinical assessment. With a full understanding of the role of inflammation in DILI and the mediating role of cytokines in inflammation, cytokines are promising candidates as sensitive and specific biomarkers for DILI. The emergence of three-dimensional spheroid models demonstrates potential use in providing clinically relevant data and predicting hepatotoxicity of SMKIs.

HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.

Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG(PF4-H)), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]. We observed both false positive and false negative test findings with most assays. Overall, the whole blood aggregation method provided a reasonable alternative to SRA for identifying functional HIT. STiC, AcuStar and ELISA procedures were fairly comparable in terms of screening for HIT, although STiC and AcuStar both yielded false negatives, albeit also resulting in fewer false positives than ELISA. The 4T score had less utility in our patient cohort than we were expecting, although there was an association with the likelihood of HIT. Nevertheless, we accept that our observations are based on limited test numbers. In conclusion, no single approach (clinical or laboratory) was associated with optimal sensitivity or specificity of HIT exclusion or identification, and thus, a combination of clinical evaluation and laboratory testing will best ensure the accuracy of diagnosis.

Management of Ciguatoxin Risk in Eastern Australia.

Between 2014 and 2016, five cases of ciguatera fish poisoning (CFP), involving twenty four individuals, were linked to Spanish Mackerel (Scomberomorus commerson) caught in the coastal waters of the state of New South Wales (NSW) on the east coast of Australia. Previously, documented cases of CFP in NSW were few, and primarily linked to fish imported from other regions. Since 2015, thirteen individuals were affected across four additional CFP cases in NSW, linked to fish imported from tropical locations. The apparent increase in CFP in NSW from locally sourced catch, combined with the risk of CFP from imported fish, has highlighted several considerations that should be incorporated into risk management strategies to minimize CFP exposure for seafood consumers.

Clinical and laboratory diagnosis of heparin induced thrombocytopenia: an update.

Heparin remains a commonly used anticoagulant in prophylaxis and treatment of venous and arterial thrombosis, in addition to ensuring patency of artificial blood circuits such as cardiopulmonary bypass (CPB). Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy that results from production of polyclonal antibodies to heparin in complex, usually with platelet factor 4 (PF4). In a proportion of patients, this causes platelet activation and thrombin generation, which may result in thrombosis. However, identification of patients with HIT can be complicated as thrombocytopenia is common in hospitalised patients receiving heparin, and is usually due to other causes. Clinical assessment of the likelihood of HIT is paramount in order to make appropriate decisions regarding laboratory investigations and ongoing anticoagulation, especially given clinically expressed pro-thrombotic states. However, clinical assessment, on its own, cannot guarantee diagnosis or exclusion of HIT, and therefore is facilitated by laboratory testing, although unfortunately, this is frequently limited by local availability of assays and delay in availability of results. Nevertheless, there are an increasing number of available laboratory tests that can be used to identify antibodies causing HIT, including both immunological and functional assays. This narrative review will discuss the existing tools for clinical assessment in addition to evaluating the advantages and disadvantages of the available laboratory assays for HIT.

Opportunity of forensic medical identification for simple traumatic subarachnoid hemorrhage / 复旦学报（医学版）

Objective To investigate the identification time and attention issue for simple traumatic subarachnoid hemorrhage (STSAH).Methods A total of 51 cases of STSAH from Center of Forensic Science,Siping Policy Security Bureau during 2014 to 2016 were analyzed retrospectively.Statistical methods used for sex,age,bleeding site,injury style and treatment outcome in forensic medical identification.Results In 46 cases of STSAH,high-density shadow in bleeding site narrowed gradually with regular change by CT scan,meanwhile clinical features disappeared gradually after longer treatment and was given the recognition in clinical identification.In addition,5 cases of STSAH had no obvious change 14 days after the injury confirmed by repeated CT,which were not given the recognition by forensic medical identification.Conclusions Early evaluation of injury degree in STSAH cases was carefully made to ensure the reliability of forensic medical identification;meantime false positive results could be avoided by follow-up CT scan.

A Decision Tree to Identify Children Affected by Prenatal Alcohol Exposure.

OBJECTIVE: To develop and validate a hierarchical decision tree model that combines neurobehavioral and physical measures to identify children affected by prenatal alcohol exposure even when facial dysmorphology is not present. STUDY DESIGN: Data were collected as part of a multisite study across the US. The model was developed after we evaluated more than 1000 neurobehavioral and dysmorphology variables collected from 434 children (8-16 years of age) with prenatal alcohol exposure, with and without fetal alcohol syndrome, and nonexposed control subjects, with and without other clinically-relevant behavioral or cognitive concerns. The model subsequently was validated in an independent sample of 454 children in 2 age ranges (5-7 years or 10-16 years). In all analyses, the discriminatory ability of each model step was tested with logistic regression. Classification accuracies and positive and negative predictive values were calculated. RESULTS: The model consisted of variables from 4 measures (2 parent questionnaires, an IQ score, and a physical examination). Overall accuracy rates for both the development and validation samples met or exceeded our goal of 80% overall accuracy. CONCLUSIONS: The decision tree model distinguished children affected by prenatal alcohol exposure from nonexposed control subjects, including those with other behavioral concerns or conditions. Improving identification of this population will streamline access to clinical services, including multidisciplinary evaluation and treatment.

Clinical Identification of the Vertebral Level at Which the Lumbar Sympathetic Ganglia Aggregate.

BACKGROUND: The location and the number of lumbar sympathetic ganglia (LSG) vary between individuals. The aim of this study was to determine the appropriate level for a lumbar sympathetic ganglion block (LSGB), corresponding to the level at which the LSG principally aggregate. METHODS: Seventy-four consecutive subjects, including 31 women and 31 men, underwent LSGB either on the left (n = 31) or the right side (n = 43). The primary site of needle entry was randomly selected at the L3 or L4 vertebra. A total of less than 1 ml of radio opaque dye with 4% lidocaine was injected, taking caution not to traverse beyond the level of one vertebral body. The procedure was considered responsive when the skin temperature increased by more than 1℃ within 5 minutes. RESULTS: The median responsive level was significantly different between the left (lower third of the L4 body) and right (lower margin of the L3 body) sides (P = 0.021). However, there was no significant difference in the values between men and women. The overall median responsive level was the upper third of the L4 body. The mean responsive level did not correlate with height or BMI. There were no complications on short-term follow-up. CONCLUSIONS: Selection of the primary target in the left lower third of the L4 vertebral body and the right lower margin of the L3 vertebral body may reduce the number of needle insertions and the volume of agents used in conventional or neurolytic LSGB and radiofrequency thermocoagulation.

Clinical Identification of the Vertebral Level at Which the Lumbar Sympathetic Ganglia Aggregate

BACKGROUND: The location and the number of lumbar sympathetic ganglia (LSG) vary between individuals. The aim of this study was to determine the appropriate level for a lumbar sympathetic ganglion block (LSGB), corresponding to the level at which the LSG principally aggregate. METHODS: Seventy-four consecutive subjects, including 31 women and 31 men, underwent LSGB either on the left (n = 31) or the right side (n = 43). The primary site of needle entry was randomly selected at the L3 or L4 vertebra. A total of less than 1 ml of radio opaque dye with 4% lidocaine was injected, taking caution not to traverse beyond the level of one vertebral body. The procedure was considered responsive when the skin temperature increased by more than 1℃ within 5 minutes. RESULTS: The median responsive level was significantly different between the left (lower third of the L4 body) and right (lower margin of the L3 body) sides (P = 0.021). However, there was no significant difference in the values between men and women. The overall median responsive level was the upper third of the L4 body. The mean responsive level did not correlate with height or BMI. There were no complications on short-term follow-up. CONCLUSIONS: Selection of the primary target in the left lower third of the L4 vertebral body and the right lower margin of the L3 vertebral body may reduce the number of needle insertions and the volume of agents used in conventional or neurolytic LSGB and radiofrequency thermocoagulation.

Put a face to a name: a randomized controlled trial evaluating the impact of providing clinician photographs on inpatients' recall.

BACKGROUND: Inpatients are visited by many health care providers daily; many cannot remember the name of even one member of their clinical care team. We provided inpatients with photographs of their clinicians and evaluated the impact on patient recall and communication with their health care providers. METHODS: A concealed allocation, randomized controlled trial (ClinicalTrials.gov NCT01658644) was conducted between September 2012 and April 2013 in the general internal medicine wards of a large teaching hospital in Toronto, Canada. Consenting patients were randomized into 3 groups: the control group received the current standard of care; the second group received handouts with the names and roles of their clinical care team; and the third group received handouts with the names, roles, and photographs of their clinical care team. Before discharge, patients completed a survey on their ability to recall their clinicians and were asked to rate the quality of communication with their care team. RESULTS: Of the 186 patients (mean age 61 years, female = 44%) who completed surveys (control n = 60; names n = 65; photos n = 61), those receiving photos in the handout correctly identified significantly more clinicians by photograph (P = .001) and recalled more names (P = .002) than patients assigned to the control group. Regarding the perceived quality of communication, the results did not show differences between the control and intervention groups. CONCLUSION: In this era of patient-centered care, providing patients with more information about who is directly involved with their health care appears to be warranted.

Anomalies and specific functions in the clinical identification of defense mechanisms.

Standard teaching about defense mechanisms generally focuses on definitions, which do not readily aid the clinician in identifying defenses whenever individuals use them. This report demonstrates a process by which the clinician can identify when a defense is used, which ones are likely being used, and with what aim. Clinicians first notice that a defense may be operating whenever the other individual presents with anomalies in the expression of affect, behavior, speech, or its content. Some of these anomalies are described. Next, to identify the specific defense or general level of defensive functioning used, the clinician must identify the specific function of the defense in context using a process of guided clinical inference. This report examines 2 verbatim examples from recorded interviews of one case to demonstrate this process. The examples present a microcosm of clinical concerns that have a surprising relationship to the individual's course and prognosis.

Clinical and pathological features of nonfunctional pituitary adenomas: Analysis of 220 cases / 中华内分泌代谢杂志

A retrospective analysis was carried out in 220 cases of nonfunctional pituitary adenoma (NFA).The diagnosis was based on negative immunohistochemical staining,no elevation of plasma hormone level,and no symptom caused by increased hormone level.Incidence of NFA was the highest(33.13％) among the pituitary tumors.It was more common in males than in females (132 ∶ 88).The highest prevalence resided in the elder group.N FA often caused pituitary apoplexy,and mainly presented as compression symptoms including visual field abnormalities (85.00％),headache (80％),hypopsia (68.66％),and other symptoms of hypopituitarism (44.04％).Imaging features showed tumor size usually within 2-4 cm (71.82％),and aggregated degree Ⅲ or Ⅳ (83.64％).