Etiological Diagnosis In Patients Research Articles

A series of atypical cases of exudative retinal detachment with diagnostic dilemma presenting to a rural eye care center in South India

Abstract Introduction: Retinal detachment results due to the accumulation of fluid in the subretinal space. Retinal detachment can be rhegmatogenous, exudative, or tractional detachment. Exudative detachment occurs due to various choroidal or retinal pathologies. We report a case series of exudative retinal detachment (ERD) with atypical presentation, who were diagnosed and treated in our retina clinic. The aim of our study was to stress on the timely etiological diagnosis in patients who present with ERD in achieving a good visual recovery. We also would like to emphasize thorough systemic evaluation in the management of such cases. Materials and Methods: In this case series, patients who presented to our institution with ERD underwent a comprehensive ocular and systemic evaluation in order to determine the underlying etiology. Results: Our study showed that inflammatory causes, whether infectious or noninfectious uveitic conditions and certain systemic conditions unrelated to uveitis can also cause ERD. Conclusion: A thorough examination of both ocular and systemic condition is crucial for identifying the cause of ERD, ultimately aiding in the preservation of vision. In addition, timely recognition and management of any underlying systemic conditions by the appropriate specialist can significantly decrease the morbidity and mortality in these patients. The following core competencies are addressed in this article: Practice-based learning and improvement, Medical knowledge.

Evaluation of the diagnostic effectiveness of next generation sequencing in sepsis etiology: a systematic review and meta-analysis.

Systematic evaluation of the diagnostic value of next generation sequencing (NGS) in sepsis etiology. We conducted a systematic search on four databases (Web of Science, Cochrane, PubMed, and Embase) and compiled diagnostic experiments using NGS to evaluate sepsis etiology. Two researchers conducted research and obtained data independently. Nine documents were included comprising 747 patients, 988 blood samples, 175 bronchoalveolar lavage fluid (BALF) samples, 16 cerebrospinal fluid samples, and one urine sample. The combined sensitivity of each study was 0.89 (95% CI: 0.82-0.95). The combined specificity was 0.40 (95% CI: 0.25-0.55). The combined positive likelihood ratio was 1.51 (95% CI: 1.18-1.98). The combined negative likelihood ratio was 0.28 (95% CI: 0.11-0.48). The diagnostic odds ratio (DOR) was 6.38 (95% CI: 2.53-15.32) and the area under the curve (AUC) was 0.84, (95% CI: 0.62-0.94). Based on the data we collected, we found that compared with the blood culture technology, NGS has the advantages of high sensitivity and wide detection range, but its specificity was low. Further study is needed to confirm the value of NGS in the etiological diagnosis of patients with sepsis.

Diagnostic Utility of Cerebrospinal Fluid Biomarkers in Patients with Rapidly Progressive Dementia.

This study was undertaken to apply established and emerging cerebrospinal fluid (CSF) biomarkers to improve diagnostic accuracy in patients with rapidly progressive dementia (RPD). Overlap in clinical presentation and results of diagnostic tests confounds etiologic diagnosis in patients with RPD. Objective measures are needed to improve diagnostic accuracy and to recognize patients with potentially treatment-responsive causes of RPD. Biomarkers of Alzheimer disease neuropathology (amyloid-β 42/40 ratio, phosphorylated tau [p-tau181, p-tau231]), neuroaxonal/neuronal injury (neurofilament light chain [NfL], visinin-like protein-1 [VILIP-1], total tau), neuroinflammation (chitinase-3-like protein [YKL-40], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], glial fibrillary acidic protein [GFAP], monocyte chemoattractant protein-1 [MCP-1]), and synaptic dysfunction (synaptosomal-associated protein 25kDa, neurogranin) were measured in CSF obtained at presentation from 78 prospectively accrued patients with RPD due to neurodegenerative, vascular, and autoimmune/inflammatory diseases; 35 age- and sex-matched patients with typically progressive neurodegenerative disease; and 72 cognitively normal controls. Biomarker levels were compared across etiologic diagnoses, by potential treatment responsiveness, and between patients with typical and rapidly progressive presentations of neurodegenerative disease. Alzheimer disease biomarkers were associated with neurodegenerative causes of RPD. High NfL, sTREM2, and YKL-40 and low VILIP-1 identified patients with autoimmune/inflammatory diseases. MCP-1 levels were highest in patients with vascular causes of RPD. A multivariate model including GFAP, MCP-1, p-tau181, and sTREM2 identified the 44 patients with treatment-responsive causes of RPD with 89% accuracy. Minimal differences were observed between typical and rapidly progressive presentations of neurodegenerative disease. Selected CSF biomarkers at presentation were associated with etiologic diagnoses and treatment responsiveness in patients with heterogeneous causes of RPD. The ability of cross-sectional biomarkers to inform upon mechanisms that drive rapidly progressive neurodegenerative disease is less clear. ANN NEUROL 2024;95:299-313.

Frequency, Classification, and Timing of Movement Disorders in Rapidly Progressive Dementia (P14-11.004)

<h3>Objective:</h3> To compare and classify movement disorders in patients with specific causes of rapidly progressive dementia (RPD). <h3>Background:</h3> Many diseases present with RPD. The broad differential presents a unique challenge for the clinician who must rapidly organize and interpret tests to provide a timely clinical diagnosis for the patient with RPD. Movement disorders are associated with several different causes of RPD; their emergence, classification, and progression may provide clues to the specific diagnosis in patients with RPD. <h3>Design/Methods:</h3> Patients with RPD were prospectively enrolled between February 2016 and August 2022 at two tertiary care centers. Two neurologists independently determined etiologic diagnoses. A third neurologist systematically reviewed research records to identify movement disorders (e.g., parkinsonism, tremor, ataxia, myoclonus, dystonia, etc.) and classified these when present. Associations between movement disorders and specific causes of RPD were considered using Fisher’s exact test. <h3>Results:</h3> 154 patients met criteria for RPD (46.7% female). The median age-at-symptom onset was 66.0 years old (range: 18.3–84.7 years). Movement disorders were detected at presentation in 45/154 (29.2%) patients and in 73/154 (47.4%) patients at some point in the illness course. Gait disorders (n=40, 52.6%) were the most frequent movement disorder observed, followed by tremor (n=30, 40.5%), rigidity (n=24, 32.4%), ataxia (n=19, 25.7%) and myoclonus (n=19, 25.7%). Movement disorders were more commonly associated with prion disease (OR=3.65, 95% CI 1.27–11.93, p=0.008), and appeared on average 89 days after symptomatic onset. Detection of myoclonus (OR=6.80, 95%CI 2.0–22.54, p&lt;0.005) was associated with higher odds of CJD, with average time from symptom onset to myoclonus of 118 days. Bradykinesia was associated with Alzheimer disease related dementias (OR=7.38, 95%CI 1.54–46.14, p=0.004). <h3>Conclusions:</h3> Detection and classification of movement disorders may inform etiologic diagnosis in patients with RPD. <b>Disclosure:</b> Dr. Turcano has nothing to disclose. Mr. Satyadev has nothing to disclose. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Alzheimer’s Tennessee. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Charlotte County Medical Society, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Barrow Law. Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer’s Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.

The articular and the craniocervical abnormalities are of confusing age of onset in patients with Maroteaux-Lamy disease (MPS VI).

Maroteaux-Lamy disease (MPS Type VI) is an autosomal recessive lysosomal storage disorder. Skeletal abnormalities are vast. Early recognition may facilitate timely diagnosis and intervention, leading to improved patient outcomes. The most challenging is when patients manifest a constellation of craniocervical and articular deformities with variable age of onset. We collected 15 patients with MPS VI (aged from 6 years-58 years). From within our practice in Pediatric Orthopedics, we present patients with MPS type VI who were found to manifest a diverse and confusing clinical presentation of hip deformities and cervical cord compression. Stem cell transplants were proposed as treatment tool and enzyme replacement therapy has been instituted in some patients. The spectrum of the clinical involvement in our group of patients was supported firstly via the clinical phenotype followed by assessment of the biochemical defect, which has been detected through the deficiency of N-acetylgalactosamine-4-sulfatase (arylsulphatase B) leading to increased excretion of dermatan sulphate. Secondly, through the molecular genetic results, which showed homozygous or compound heterozygous mutation in the ARSB gene on chromosome 5q14. Hip replacements and decompression operations have been performed to restore function and to alleviate pain in the former and life saving procedure in the latter. The efforts in searching for the etiological diagnosis in patients with skeletal dysplasia/MPSs has not been rewarding as many had anticipated. This emerged from several facts such as improper clinical documentation, missing diagnostic pointers in radiographic interpretations, limited knowledge in skeletal dysplasia and its variants, and the reliance on underpowered studies. Physicians and radiologists are required to appreciate and assess the diverse phenotypic and the radiographic variability of MPS VI. The importance of considering MPS in the differential diagnosis of other forms skeletal dysplasia is mandatory. Finally, we stress that the value of early diagnosis is to overcome dreadful complications.

Identification of specific causes of myelopathy in a large cohort of patients initially diagnosed with transverse myelitis

Background and objectivesIdentifying the etiologic diagnosis in patients presenting with myelopathy is essential in order to guide appropriate treatment and follow-up. We set out to examine the etiologic diagnosis after comprehensive clinical evaluation and diagnostic work-up in a large cohort of patients referred to our specialized myelopathy clinic, and to explore the demographic profiles and symptomatic evolution of specific etiologic diagnoses. MethodsIn this retrospective study of patients referred to the Johns Hopkins Myelitis and Myelopathy Center between 2006 and 2021 for evaluation of “transverse myelitis”,the final etiologic diagnosis determined after comprehensive evaluation in each patient was reviewed and validated. Demographic characteristics and temporal profile of symptom evolution were recorded. ResultsOf 1193 included patients, 772 (65%) were determined to have an inflammatory myelopathy and 421 (35%) were determined to have a non-inflammatory myelopathy. Multiple sclerosis/clinically isolated syndrome (n = 221, 29%) and idiopathic myelitis (n = 149, 19%) were the most frequent inflammatory diagnoses, while spinal cord infarction (n = 197, 47%) and structural causes of myelopathy (n = 108, 26%) were the most frequent non-inflammatory diagnoses. Compared to patients with inflammatory myelopathies, patients with non-inflammatory myelopathies were more likely to be older, male and experience chronic symptom evolution (p < 0.001 for all). Hyperacute symptom evolution was most frequent in patients with spinal cord infarction (74%), while chronic symptom evolution was most frequent in patients with structural causes of myelopathy (81%), arteriovenous fistula or arteriovenous malformation (81%), myelopathy associated with rheumatologic disorder (71%), and sarcoidosis-associated myelopathy (61%). ConclusionsPatients initially diagnosed with “transverse myelitis” are eventually found to have a more specific inflammatory or even non-inflammatory cause, potentially resulting in inappropriate treatment and follow-up. Demographic characteristics and temporal profile of symptom evolution may help inform a differential diagnosis in these patients. Etiological diagnosis of myelopathies would provide better therapeutic decisions.

Comparison of the Multiplex Real Time Polymerase Chain Reaction Method Directly from Whole Blood and from Blood Culture Bottle with the Conventional Method for the Etiological Diagnosis in Patients with Pre-Diagnosis of Sepsis

In this study, it was aimed to evaluate the use of multiplex real time polymerase chain reaction (RtPCR) method, directly from whole blood and blood culture bottles of intensive care unit patients with a pre-diagnosis of sepsis for the determination of the causative agent by comparing it with the conventional method. The study was carried out prospectively between November 2019 and August 2020. Ninety patients hospitalized with a pre-diagnosis of sepsis were included in the study. Samples were collected simultaneously with aseptic technique as whole blood and at least two sets of blood cultures. Blood culture bottles were monitored by the BACT/ALERT 3D (bioMerieux, France) instrument. Blood culture bottles were studied both by Sepsis Pathogens Panel Kit v1 (Anatolia, Turkey) using the multiplex Rt-PCR and with the conventional culture methods. The duration of detection and reporting of the multiplex Rt-PCR methods were compared with the conventional method. In this study, a total of 90 whole blood samples and 280 blood culture bottles were collected from the patients. It was found that 73 (81%) patients had already been administered antibiotic treatment at the time of blood sampling. Conventional blood culture was accepted as the gold standard in the diagnosis of sepsis. Rt-PCR performed from blood culture bottles was found to have a sensitivity of 89.58%; specificity of 57.14%; positive predictive value of 70.49%; negative predictive value of 82.76% and accuracy of 74.44% (p= 0.019). On the basis of the bacterial species, the sensitivity of the Rt-PCR method was determined to be between 66.7-100% and the specificity was between 86.6-100%. The Rt-PCR performed from whole blood, was found to have a sensitivity of 11.67% and a specificity of 96.67%; positive predictive value of 87.50%; negative predictive value of 35.37% and accuracy of 40% (p= 1.684). In this study, the duration of reporting of blood culture results was in average 116:50 hours, that of PCR from blood culture bottles was 80:57 hours, and that of PCR from whole blood samples was 15:38 hours (p<0.001). It was determined that the PCR from whole blood shortened the reporting time by an average of 101:12 hours (approximately four days), and that the PCR from blood culture bottles shortened the reporting time by an average of 35:53 hours (1.5 days) compared to the conventional method. In this study, the results determined by the Sepsis Pathogens Panel Kit v1 (Anatolia, Turkey) performed from blood culture bottles were superior compared to the conventional method. It has been determined that improvement is required for the usage of the sepsis kit directly from whole blood. On the other hand, considering the species detected by the blood culture method and not by the assay, the species range detected by the multiplex assay panel needs to be improved.

Application of Metagenomic Next-Generation Sequencing in the Etiological Diagnosis of Infective Endocarditis During the Perioperative Period of Cardiac Surgery: A Prospective Cohort Study

ObjectiveThe present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE).MethodsFrom May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS.ResultsIn the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS further improved the diagnostic accuracy (sensitivity 89.9%, specificity 72.7%, AUC 0.813). Preoperative white blood cell (P = 0.029) and neutrophils (P = 0.046) were identified as independent factors affecting the detection rate of mNGS. In the mNGS-positive group, 95 strains of pathogens were found and 10 cases were identified with mixed infection. There were 72 gram-positive bacteria and 14 gram-negative bacteria. mNGS positive group displayed higher species richness than mNGS negative group with enrichment of Streptococcus sanguis, Streptococcus buccalis, and Streptococcus griseus. Proteobacteria and Actinomycetes were enriched in mNGS negative group. Notably, six patients showed disconcordant results between culture and mNGS. Rothia aeria was identified in the blood culture, valve culture, and valve mNGS in one patient. Bartonella Quintana and Coxiella burnetii, which were fastidious intracellular bacteria, were found in two blood and valve culture-negative cases.ConclusionsmNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.

Oculomasticatory Myorhythmia, an Underrecognized Yet Key Finding for the Topographic and Etiological Diagnosis in Patients with Rhombencephalitis. Videographic Record of a Case.

Oculomasticatory Myorhythmia, an Underrecognized Yet Key Finding for the Topographic and Etiological Diagnosis in Patients with Rhombencephalitis. Videographic Record of a Case.

The articular and the craniocervical abnormalities are of confusing age of onset in patients with Maroteaux-Lamy disease (MPS VI).

Maroteaux-Lamy disease (MPS Type VI) is an autosomal recessive lysosomal storage disorder. Skeletal abnormalities are vast. Early recognition may facilitate timely diagnosis and intervention, leading to improved patient outcomes. The most challenging is when patients manifest a constellation of craniocervical and articular deformities with variable age of onset. We collected 15 patients with MPS VI (aged from 6 years-58 years). From within our practice in Pediatric Orthopedics, we present patients with MPS type VI who were found to manifest a diverse and confusing clinical presentations of hip deformities and cervical cord compression. Stem cell transplants were proposed as treatment tool and enzyme replacement therapy has been instituted in some patients. The spectrum of the clinical involvement in our group of patients was supported firstly via the clinical phenotype followed by assessment of the biochemical defect , which has been detected through the deficiency of N-acetylgalactosamine-4-sulfatase (arylsulphatase B) leading to increased excretion of dermatan sulphate. Secondly, through the molecular genetic results, which showed homozygous or compound heterozygous mutation in the ARSB gene on chromosome 5q14. Hip replacements and decompression operations have been performed to restore function and to alleviate pain in the former and life saving procedure in the latter. The efforts in searching for the etiological diagnosis in patients with skeletal dysplasia/MPSs has not been rewarding as many had anticipated. This emerged from several facts such as improper clinical documentation, missing diagnostic pointers in radiographic interpretations, limited knowledge in skeletal dysplasia and its variants, and the reliance on underpowered studies. Physicians and radiologists are required to appreciate and assess the diverse phenotypic and the radiographic variability of MPS VI. The importance of considering MPS in the differential diagnosis of other forms skeletal dysplasia is mandatory. Finally, we stress that the value of early diagnosis is to overcome dreadful complications.

“Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy” with a novel mutation

“Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy” is a newly described disorder related to homozygous mutations in TRAPPC6B gene. Although nonspecific, the features of this disorder appear to have a characteristic course of postnatal progressive microcephaly that should raise the suspicion of this disorder. To the best of our knowledge, only eight cases were published in the literature. Here, we report a new case with a novel mutation and compare the clinical findings to the published cases. This case was not picked up by whole-exome sequencing but rather by whole-genome sequencing, emphasizing the importance of pursuing an etiological diagnosis in patients with otherwise unexplained progressive neurological disorders.

Neumonía grave en la comunidad: ¿cuándo pensar en SAMR-AC?

Introducción: Aunque la incidencia de neumonía adquirida en la comunidad (NAC) por Staphylococcus aureus meticilino-resistente adquirido en la comunidad (SAMR-AC) es inferior al 10%, por su elevada mortalidad debe considerarse en los pacientes graves.&#x0D; Objetivo: Identificar factores de riesgo asociados con SAMR-AC en pacientes con NAC grave.&#x0D; Material y métodos: Estudio observacional, retrospectivo, que analizó pacientes con NAC con diagnóstico etiológico ingresados en terapia intensiva en un hospital público entre 2006 y 2017.&#x0D; Resultados: Se incluyeron 250 episodios de NAC, 53 por SAMR-AC y 197 por otros agentes. Los pacientes con SAMR fueron más jóvenes (35,6±13,4 vs 43,1±12,4, p&lt;0,001) y mostraron mayores tasas de infecciones de piel y estructuras relacionadas (IPER) (58,4% vs 2,0%, p&lt;0,001), empiema (15,9% vs 5,0%, p=0,006), compromiso radiológico bilateral (81,1% vs 36,0%, p&lt;0,001), promedio de score APACHE II basal (16,7±3,8 vs 13,2±4,3, p&lt;0,001) y requerimiento de ventilación mecánica (VM) (33,9 vs 17,6 p=0,009). La tasa de mortalidad fue significativamente mayor para los pacientes con SAMR-AC (35,8% vs 11,1%, p&lt;0,001). Las variables que se asociaron con SAMR-AC fueron IPER (OR 67,99, IC 5% 21,94-210,65), compromiso radiológico bilateral (OR 7,63, IC 95% 3,67-16,11), score APACHE II ≥ 15 (OR 4,37, IC 95% 2,08-9,16), edad ≤ 35 años (OR 3,60, IC 95% 1,77-7,29), empiema (OR 3,32, IC 95% 1,24-8,10) y VM (OR 2,85, IC 95% 1,36-5,86).&#x0D; Conclusión: En pacientes con NAC grave, la presencia de IPER, compromiso radiológico bilateral, score APACHE II ≥ 15, edad ≤ 35 años, empiema y VM se asociaron significativamente con mayor probabilidad de infección por SAMR-AC.

Derivative chromosomes involving 5p large rearranged segments went unnoticed with the use of conventional cytogenetics

BackgroundIn countries where comparative genomic hybridization arrays (aCGH) and next generation sequencing are not widely available due to accessibility and economic constraints, conventional 400–500-band karyotyping is the first-line choice for the etiological diagnosis of patients with congenital malformations and intellectual disability. Conventional karyotype analysis can rule out chromosomal alterations greater than 10 Mb. However, some large structural abnormalities, such as derivative chromosomes, may go undetected when the analysis is performed at less than a 550-band resolution and the size and banding pattern of the interchanged segments are similar. Derivatives frequently originate from inter-chromosomal exchanges and sometimes are inherited from a parent who carries a reciprocal translocation.Case presentationWe present two cases with derivative chromosomes involving a 9.1 Mb 5p deletion/14.8 Mb 10p duplication in the first patient and a 19.9 Mb 5p deletion/ 18.5 Mb 9p duplication in the second patient. These long chromosomal imbalances were ascertained by aCGH but not by conventional cytogenetics. Both patients presented with a deletion of the Cri du chat syndrome region and a duplication of another genomic region. Each patient had a unique clinical picture, and although they presented some features of Cri du chat syndrome, the phenotype did not conclusively point towards this diagnosis, although a chromosomopathy was suspected.ConclusionsThese cases highlight the fundamental role of the clinical suspicion in guiding the approach for the etiological diagnosis of patients. Molecular cytogenetics techniques, such as aCGH, should be considered when the clinician suspects the presence of a chromosomal imbalance in spite of a normal karyotype.

Etiologic Diagnosis by DXA in Diabetes Mellitus

A 45-years-old female patient with uncontrolled diabetes mellitus and severe hyper tryglyceridemia has presented to endocrinology OPD. Pioglitazones were started as a part of her treatment. Patient complained of progressive weight gain and fat accumulation in the lower limbs due to which she has difficulty in walking. In subsequent visit, body composition analysis was ordered which revealed acquired partial lipodystrophy. Compensatory lipohypertrophy in lower body was noted. Change in treatment along with low calorie diet helped in controlling her blood sugar. This case emphasizes the importance of BCA with DXA in arriving at etiological diagnosis in patients with suspected lipodystrophies.

The application of Critical Care Chest Ultrasonic Evaluation-plus Protocol in the etiological diagnosis of dyspnea and/or hemodynamic instability caused by abdominal abnormality

Objective: To investigate the application of Critical Care Chest Ultrasonic Examination (CCUE)-plus (CCUE-plus) in the etiological diagnosis in patients with dyspnea and/or hemodynamic instability caused by abdominal abnormalities. Methods: Patients who suffered from dyspnea and/or hemodynamic instability in the Department of Critical Care Medicine, Xiangya Hospital, Central South University from September 2013 to September 2016 were recruited in this study. A total of 255 consecutive patients completed CCUE within 2hrs of admission. If the diaphragm could not be seen in the routine phrenic points according to Bedside Lung Ultrasound Evaluation (BLUE) protocol, it would be found along midaxillary line and defined m-point. The 59 patients with altered diaphragmatic position (m-point was more than 2 cm higher than phrenic point) received sequential abdominal ultrasonography. The latter ultrasonographic findings were compared with CT results. Results: There were 42(71.19%) cases with positive findings of abdominal ultrasonography, including 18 cases of seroperitoneum, 16 cases of intestinal obstruction and 8 cases combined. Compared with 56 patients who applied with CT exam, the abdominal ultrasonography revealed a sensitivity of 76.7% and a specificity of 100.0% to diagnose seroperitoneum (AUC(ROC) 0.917); whereas the sensitivity was 75.0% and the specificity was 90.9% (AUC(ROC) 0.778) to diagnose intestinal obstruction. Moreover, there were 44(74.58%) patients with normal left ventricular systolic function; more than three quarters (46/59, 77.97%) patients had pulmonary consolidation. Conclusion: In patients with dyspnea and/or hemodynamic instability caused by abdominal abnormalities and altered diaphragmatic position in BLUE protocol, CCUE-plus protocol has a high positive predictive value of more than 90% in abdominal abnormality. The findings of abdominal ultrasonography may change therapeutic target from cardio-pulmonary optimization to relief of intestinal obstruction or drainage of seroperitoneum.

Intellectual Disability & Rare Disorders: A Diagnostic Challenge.

Rare disorders constitute a large and heterogeneous group of diagnoses of which many cause chronic disabilities with significant impact on the lives of affected individuals and their families as well as on the health-care system. Each individual disorder is rare, but when considered as a group, rare disorders are common with a total prevalence of approximately 6-8%. The clinical presentation of these disorders includes a broad diversity of symptoms and signs, often involving the nervous system and resulting in symptoms such as intellectual disability, neuropsychiatric disorders, epilepsy and motor dysfunction. The methods for establishing an etiological diagnosis in patients with rare disorders have improved dramatically during recent years. With the introduction of genomic screening methods, it has been shown that the cause is genetic in the majority of the patients and many will receive an etiological diagnosis in a clinical setting. However, there are a lot of challenges in diagnosing these disorders and despite recent years' advances, a large number of patients with rare disorders still go without an etiological diagnosis. In this chapter we will review the etiology of rare disorders with focus on intellectual disability and what has been learned from massive parallel sequencing studies in deciphering the genetic basis. Furthermore, we will discuss challenges in the etiological diagnostics of these disorders including issues that regard interpretation of the numerous genetic variants detected by genomic screening methods and challenges in the translation of massive parallel sequencing technologies into clinical practice.

Clinicopathological profile of spectrum of thrombocytopenic cases – a cross sectional study

Background: Thrombocytopenia is a common finding in many hospitalized patients and its etiology is diverse. Aim: This study aimed to do a detailed clinicopathological correlation of various cases of thrombocytopenia in adults by elucidating the various etiological factors, severity of thrombocytopenia, various mode of clinical presentation and the proportion of patients presenting with bleeding manifestations. Materials and Methods: This is a cross sectional study done for a period of 2 months. The relevant clinical and investigatory findings all patients with a platelet count of less than 1,50,000 were collected from the patients’ medical records. Results: A total of 120 patients were included out of which 71 (59.2%) males and 49 (40.8%) females and most of the study population belonged to 20-60 age group. The platelet count was <50,000 - 24(20%), 50,000 – 1,00,000 – 65 (54.2%), 1,00,000 to 1,50,000 - 31(25.8%). The etiological diagnosis of patients were Dengue - 26 (21.67%), Malaria – 8(6.7%), Enteric fever – 7 (5.9%), Septicemia – 6(5%), Chronic liver disease – 20 (16.7%), Chronic kidney disease – 4 (3.4%), Diabetes – 9 (7.7%), Malignancy – 2 (1.67%), Coronary artery disease – 4 (3.4%), Pregnancy – 6 (5%) Hematological disorders – 22 (18.4%) and miscellaneous – 6 (5%). 54 (45%) presented with fever and 16 (13.3%) with bleeding manifestations. Conclusion: Infectious diseases was the most common cause of thrombocytopenia. Chronic liver disease was the commonest non infectious cause followed by diabetes. Most presented with fever followed by bleeding manifestations. Early recognition and continuous monitoring of patients with thrombocytopenia can avoid bleeding manifestations including fatal intra cranial haemorrhage.

Prospective evaluation of yield of endoscopic ultrasonography in the etiological diagnosis of "idiopathic" acute pancreatitis

Abstract Background: Etiology of acute pancreatitis (AP) remains idiopathic in 30% of patients. Endoscopic ultrasound (EUS) has been shown to increase the diagnostic yield in patients with idiopathic AP (IAP). Aim: The aim of this study was to evaluate the role of EUS in achieving etiological diagnosis in patients with IAP. Materials and Methods: Consecutive 192 patients with IAP were evaluated prospectively with EUS over a period of 2 years. Patients who had no etiological diagnosis for AP after detailed history, clinical examination, laboratory investigations, and magnetic resonance cholangiopancreatography were included in the study. Results: The mean age of patients was 34.6 ± 12 and male:female ratio was 2.1:1. Of these, 135 patients had gallbladder intact (Group A) and 57 patients had undergone cholecystectomy (Group B). In Group A, EUS identified a possible cause in 79 (58.5%) patients; microlithiasis (n = 48), chronic pancreatitis (CP) (n = 23), common bile duct (CBD) and gallbladder stone (n = 3), pancreatic divisum (n = 3), small pancreatic tumor (n = 1), and anomalous pancreaticobiliary junction (n = 1). In Group B, EUS yielded diagnosis in 28 (49.1%) patients; CP (n = 22), ascariasis (n = 3), CBD stone (n = 2), and pancreatic divisum (n = 1). Overall EUS helped in achieving etiological diagnosis in 107 (55.1%) of patients with IAP. The presence of intact gallbladder showed a tendency for increased diagnostic yield (P = 0.06). Conclusion: EUS is a useful modality to establish the diagnosis in IAP and this technique should be incorporated in the evaluation of IAP.

Effects of critical ultrasonic management of Peking Union Medical College Hospital on the etiological diagnosis of patients with acute respiratory failure

To evaluate the diagnostic value and potential therapeutic impact of Peking Union Medical College Hospital critical ultrasonic management (PCUM) in the early management of critically ill patients with acute respiratory failure (ARF). Patients admitted into the ICU of Peking Union Medical College Hospital for ARF were consecutively recruited over a 18-month period. Patients were randomly divided into conventional group and PCUM group (critical care ultrasonic examination was added in addition to conventional examinations). The two groups were compared with respect to time to preliminary diagnosis, time to final diagnosis, diagnostic accuracy, time to treatment response, time to other examination. A total of 187 patients were included in this study. The two groups showed no significant differences in general clinical information or final diagnosis (P > 0.05). The PCUM group had a shorter time to preliminary diagnosis, time to final diagnosis, time to treatment response, time to X-ray/CT examination, and a higher diagnostic accuracy than the conventional group (P < 0.001). PCUM had high sensitivity and specificity for the diagnosis of acute respiratory distress syndrome (ARDS) (sensitivity 92.0%, specificity 98.5%), acute pulmonary edema (sensitivity 94.7%, specificity 96.1%), pulmonary consolidation (sensitivity 85.7%, specificity 98.6%), COPD/asthma (sensitivity 84.2%, specificity 98.7%). The PCUM is seem to be an attractive complementary diagnostic tool and able to contribute to an early therapeutic decision for the patients with ARF.

Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly.

BackgroundClinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid in identifying a specific cause in some cases, the majority of patients remain undiagnosed.Here, we investigated the utility of whole-exome sequencing as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with varied intellectual disability and microcephaly.MethodsWhole-exome sequencing was performed in 38 patients, including three sib-pairs, in addition to or in parallel with genetic analyses that were performed during the diagnostic work-up of the study participants.ResultsIn ten out of these 35 families (29 %), we found mutations in genes already known to be related to a disorder in which microcephaly is a main feature. Two unrelated patients had mutations in the ASPM gene. In seven other patients we found mutations in RAB3GAP1, RNASEH2B, KIF11, ERCC8, CASK, DYRK1A and BRCA2. In one of the sib-pairs, mutations were found in the RTTN gene. Mutations were present in seven out of our ten families with an established etiological diagnosis with recessive inheritance.ConclusionsWe demonstrate that whole-exome sequencing is a powerful tool for the diagnostic evaluation of patients with highly heterogeneous neurodevelopmental disorders such as intellectual disability with microcephaly. Our results confirm that autosomal recessive disorders are highly prevalent among patients with microcephaly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0167-8) contains supplementary material, which is available to authorized users.