Minimal Diagnostic Criteria Research Articles

World Health Organization Classification of Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are characterized by an ineffective hematopoiesis and functional abnormalities of hematopoietic lineages. Patients with MDS present with cytopenia(s) associated with morphological dysplasia and /or increase in number of blasts, and can progress to acute myeloid leukemia. The pathogenesis of MDS is exceedingly complex and involves the hematopoietic stem cells, bone marrow microenvironment and an interaction between these two compartments. The laboratory diagnostic strategy in MDS has evolved significantly over the years from a purely morphological one based almost exclusively on peripheral blood smear and bone marrow aspirate cytology to the integrated multiparametric approach used in the 2001 and 2008 WHO classification schemes. An evolution has also occurred in the prognostic assessment and the evaluation of treatment response to include novel disease related factors as well as patient specific characteristics such as non-hematologic comorbidities. This progress in clinically relevant subclassification of MDS and inclusion of specific variables related to treatment response are particularly important considering the increasing treatment options available for MDS. This review is largely focused on the diagnostic approach to MDS including discussion of the significance of cytogenetic/genetic and immunophenotypic features. We present the overview of the minimal diagnostic criteria for diagnosing MDS and a detailed description the current World Health Organization (WHO) classification scheme.

Allergic bronchopulmonary aspergillosis without asthma complicating pulmonary tuberculosis

Allergic bronchopulmonary aspergillosis (ABPA) is typically associated with asthma. Presence of asthma is one of the minimal essential diagnostic criteria for ABPA. Rarely, ABPA has been described in association with other diseases without asthma. It has so far not been known to complicate pulmonary tuberculosis. We report one such case in a young lady where all other diagnostic criteria were fulfilled. The patient responded to corticosteroids and then had acute exacerbations of ABPA twice, each time requiring an increased dosage of corticosteroids as well as itraconazole and responded favorably.

The effect of REM sleep behaviour disorder on clinical severity in Parkinson's disease

Differently from previous studies that directly compared Parkinson's disease (PD) patients with and without rapid eye movement (REM) sleep behavioural disorder (RBD) for the stage, severity, and duration of disease, this study investigated the relationship between the duration and clinical severity of disease in PD patients with and without RBD. Materials and methods: This retrospective study consisted of 141 PD patients older than 18 years of age. The clinical diagnosis of RBD was based on the minimal diagnostic criteria of the revised 2001 International Classification of Sleep Disorders. The patients were divided into 2 subgroups, those with and without clinical RBD. The groups were then compared with each other for sex, age, the duration of disease, and the Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale scores. The correlation between the duration of disease and the clinical severity of PD was analysed in all patients. Results: There was no significant difference between the groups in terms of sex, age, disease duration, and clinical severity scores. For the RBD patients there was a weak positive correlation between the duration of PD and clinical severity scores. However, there was no such correlation in the non-RBD (NRBD) subgroup. Conclusion: Our study indicates that in PD patients with RBD compared with NRBD patients, the time taken to reach the same clinical severity scores may be shorter.

Myelodysplastic syndrome: classification and prognostic systems

Myelodysplastic syndromes (MDS) are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria forMDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO) classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

Myelodysplastic syndrome: classification and prognostic systems

Myelodysplastic syndromes (MDS) are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria forMDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO) classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

Myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic neoplasms characterized by an ineffective hematopoiesis associated with cytopenia(s), functional abnormalities of bone marrow lineages, morphologic dysplasia, and a progression to acute myeloid leukemia. The pathogenesis of MDS is exceedingly complex and involves the hematopoietic stem cells/hematopoietic precursors, bone marrow microenvironment, and complex interaction between these components. The diagnostic strategy in MDS has evolved significantly over the years from a strategy based almost exclusively on peripheral blood smear and bone marrow aspirate morphology to the integrated approach used in the 2001 and 2008 World Health Organization (WHO) classification schemes. In parallel with the diagnostic approach, evolution has occurred in the prognostic assessment and evaluation of treatment response. The prognostic assessment now includes both disease-related factors and patient-specific characteristics such as nonhematologic comorbidities. All these developments are particularly important considering the ever-increasing treatment options available for MDS. This review focuses on the diagnostic approach to MDS and highlights recent developments in the pathogenesis as well as select clinical advances. We present the overview of the minimal diagnostic criteria for a diagnosis of MDS, the WHO classification scheme, and briefly address the risk stratification.

Incidence of restless legs syndrome in two population-based cohort studies in Germany

Prospective data about the new-onset of restless legs syndrome (RLS) are lacking. Our aim was to assess the incidence rate of RLS in the general population. RLS, defined by the minimal diagnostic criteria, was assessed twice in two independently conducted prospective population-based cohort studies in Germany. The Dortmund Health Study (DHS) had a mean follow-up of 2.2 years, and included 1312 participants, and the Study of Health in Pomerania (SHIP) followed 4308 participants for, on average, 5.2 years. RLS was assessed during face-to-face interviews in both studies at baseline and at follow-up in SHIP, and with mailed questionnaires at follow-up in DHS. The age-standardized incidence rate of RLS was 22/1000 person-years (p-y) (cumulative incidence over the follow-up: 9.1%) in DHS and 9/1000 p-y (cumulative incidence: 7.0%) in SHIP. Women had a higher incidence rate than men (DHS: 27/1000 p-y vs. 17/1000 p-y, p=0.28; SHIP: 12/1000 p-y vs. 7/1000 p-y, p<0.001). There was a linear increase in RLS incidence rate with age in both studies. The persistence of RLS symptoms from baseline to follow-up was 47.4% in DHS and 41.5% in SHIP. The incidence rate of RLS is high, while the persistence of RLS over time is low, suggesting that RLS symptoms vary considerably. The increased RLS incidence rate among women and the elderly is consistent with previous prevalence data.

Flow cytometry immunophenotyping for the evaluation of bone marrow dysplasia

The pathological hallmark of myelodysplastic syndromes (MDS) is marrow dysplasia, which represents the basis of the WHO classification of these disorders. This classification provides clinicians with a useful tool for defining the different subtypes of MDS and determining individual prognosis. The WHO proposal has raised some concern regarding minimal diagnostic criteria particularly in patients with normal karyotype without robust morphological markers of dysplasia (such as ring sideroblasts or excess of blasts). Therefore, there is clearly a need to refine the accuracy to detect marrow dysplasia. Flow cytometry (FCM) immunophenotyping has been proposed as a tool to improve the evaluation of marrow dysplasia. Rationale for the application of FCM in the diagnostic work up of MDS is that immunophenotyping is an accurate method for quantitative and qualitative evaluation of hematopoietic cells and that MDS have been found to have abnormal expression of several cellular antigens. To become clinically applicable, FCM analysis should be based on parameters with sufficient specificity and sensitivity, data should be reproducible between different operators and the results should be easily understood by clinicians. In this report, we reviewed the most relevant progresses in detection of marrow dysplasia by FCM in MDS as defined by WHO criteria.

Modification of the Epworth Sleepiness Scale in Central China

PurposeThe well-known excessive daytime sleepiness (EDS) assessment, Epworth Sleepiness Scale (ESS), is not consistently qualified for patients with diverse living habits. This study is aimed to build a modified ESS (mESS) and then to verify its feasibility in the assessment of EDS for patients with suspected sleep-disordered breathing (SDB) in central China.MethodsA Ten-item Sleepiness Questionnaire (10-ISQ) was built by adding two backup items to the original ESS. Then the 10-ISQ was administered to 122 patients in central China with suspected SDB [among them, 119 cases met the minimal diagnostic criteria for obstructive sleep apnea by sleep study, e.g., apnea and hypopnea index (AHI) ≥ 5 h−1] and 117 healthy central Chinese volunteers without SDB. Multivariate exploratory techniques were used for item validation. The unreliable item in the original ESS was replaced by the eligible backup item, thus a modified ESS (mESS) was built, and then verified.ResultsItem 8 proved to be the only unreliable item in central Chinese patients, with the least factor loading on the main factor and the lowest item-total correlation both in the 10-ISQ and in the original ESS, deletion of it would increase the Cronbach’s alpha (from 0.86 to 0.87 in the 10-ISQ; from 0.83 to 0.85 in the original ESS). The mESS was subsequently built by replacing item 8 in the original ESS with item 10 in the 10-ISQ. Verification with patients’ responses revealed that the mESS was a single-factor questionnaire with good internal consistency (Cronbach’s alpha = 0.86). The sum score of the mESS not only correlated with AHI (P < 0.01) but was also able to discriminate the severity of obstructive apnea (P < 0.01). Nasal CPAP treatment for severe OSA reduced the score significantly (P < 0.001). The performance of the mESS was poor in evaluating normal subjects.ConclusionThe mESS improves the validity of ESS for our patients. Therefore, it is justified to use it instead of the original one in assessment of EDS for patients with SDB in central China.

Moebius sequence and autism spectrum disorders—Less frequently associated than formerly thought

Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. It is questionable, whether there is a strong association of the sequence with autism spectrum disorders (ASDs) as suggested in some earlier case reports and studies. Twenty-two participants with Möbius sequence aged 6–16 years followed a request of the German Moebius foundation to participate in a nationwide study. All patients had a physical examination and intelligence testing. Primary caregivers were asked to complete two screening measures of ASD (Behaviour and Communication Questionnaire, VSK; Marburger Asperger's Syndrome Rating Scale, MBAS). For those who reached the cut-off for ASD and/or showed behavioural aspects indicative of ASDs during IQ testing and/or physical examination, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and Kinder-DIPS) were administered. Minimal diagnostic criteria for Möbius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Three boys (one of them mentally retarded) out of 22 participants (12 males and 10 females) were found suspicious of ASD by screening, but none of them fulfilled diagnostic criteria of ASD on a clinical consensus conference. Therefore, ASDs seem to be not as frequent as reported in previous studies on patients with Möbius sequence.

Prevalence, comorbidities and risk factors of restless legs syndrome in the Korean elderly population – results from the Korean Longitudinal Study on Health and Aging

The aim of this study was to determine the prevalence, neuropsychiatric comorbidities, iron metabolism and potential risk factors of restless legs syndrome (RLS) in the elderly Korean population. As a community-based epidemiological study, a simple random sample of 1118 was drawn from a roster of 61 730 adult individuals aged 65 years and older and 714 participated. The diagnosis of RLS was established in face-to-face interviews using the four minimal diagnostic criteria for RLS recommended by National Institute of Health. Depressive symptoms, nocturnal sleep disturbances, daytime sleepiness and quality of life were evaluated. Laboratory tests of iron metabolism, markers of inflammation, renal and endocrine function, hormones and vitamins were performed. A total of 59 patients (42 women and 17 men) were diagnosed as RLS with a prevalence of 8.3% (95% confidence interval: 6.2-10.3%), with an almost twofold higher prevalence in women (10.2%) than in men (5.7%). Depression was more prevalent among the subjects with RLS than without RLS and poor nocturnal sleep and quality of life were also observed in subjects with RLS. Daytime sleepiness was observed in 32.8% of subjects with RLS. No significant differences were found in iron metabolism or other risk factors between the subjects with and without RLS. The prevalence of RLS in the Korean elderly population was comparable with that in the Caucasian population. RLS had undesirable effects on mood, sleep quality and general wellbeing of elderly individuals.

HOXA1 mutations are not a common cause of Möbius syndrome

The HOXA1-related syndromes result from autosomal-recessive truncating mutations in the homeobox transcription factor, HOXA1. Limited horizontal gaze and sensorineural deafness are the most common features; affected individuals can also have facial weakness, mental retardation, autism, motor disabilities, central hypoventilation, carotid artery, and/or conotruncal heart defects. Möbius syndrome is also phenotypically heterogeneous, with minimal diagnostic criteria of nonprogressive facial weakness and impaired ocular abduction; mental retardation, autism, motor disabilities, additional eye movements restrictions, hearing loss, hypoventilation, and craniofacial, lingual, and limb abnormalities also occur. We asked, given the phenotypic overlap between these syndromes and the variable expressivity of both disorders, whether individuals with Möbius syndrome might harbor mutations in HOXA1. Our results suggest that HOXA1 mutations are not a common cause of sporadic Möbius syndrome in the general population.

Myelodysplastic syndrome: classification and prognostic systems

Myelodysplastic syndromes (MDS) are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria for MDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO) classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

Obesity, obstructive sleep apnoea, and diabetes mellitus: anaesthetic implications

Obesity is an epidemic in much of the Western World. The extent of this problem, combined with the increasing preference for ambulatory surgical procedures, has produced a difficult situation for many anaesthesiologists. Even the simplest anaesthetic procedures can become very complicated and potentially difficult in this population. Although there are numerous complications associated with obesity, perhaps obstructive sleep apnoea (OSA) and diabetes mellitus are among the more significant. Patients with OSA are often not ideal candidates for certain day-case procedures, but many outpatient procedures can be performed on patients with OSA as long as attention is paid to anaesthetic technique. Diabetic patients are prone to numerous complications in the perioperative period, including cardiac problems, but with careful management, they are able to undergo day-case surgical procedures safely.

CD38 Expression On CD34+ Cells as a Single Flow Cytometric Parameter to Distinguish Myelodysplastic Syndromes (MDS) From Non-Clonal Cytopenias.

Abstract 2783Poster Board II-759Myelodysplastic syndromes are a heterogeneous group of bone marrow (BM) disorders characterised by clonal proliferation. The diagnosis of MDS can be challenging, especially in cases with minimal dysplastic changes by morphology and without characteristic karyotypic abnormalities. Recent investigations show that multi parameter analysis of BM samples of MDS patients by flow cytometry (FCM) might be of value in the diagnosis of MDS and for discriminating MDS from other disease entities. Detection of immunophenotypic abnormalities in the immature and the maturing myelomonocytic compartment is even included as a co-criterion in the minimal diagnostic criteria for MDS (Valent et al., Leuk Res 2009,31:727–36). Integration of FCM as a diagnostic tool in MDS requires a simple method with high sensitivity and specificity with low inter laboratory variation. Recently, reduced CD38 expression was demonstrated to discriminate between MDS and other disease entities (Goardon et al., Haematologica 2009, 94:1160–63).To validate the value of CD38 in the diagnosis of MDS, we analysed BM samples of 27 MDS patients (refractory anemia n=4; refractory anemia with multi lineage dysplasia n=15; refractory anemia with excess blasts [RAEB]-1 n=4 and RAEB-2 n=4), age-matched healthy volunteers (n=16) and pathologic controls (n=39). The pathologic control group consisted of aplastic anemia (n=3), iron deficiency (n=6), Multiple Myeloma (n=8), B-cell non-Hodgkin lymphoma (n=6) and autoimmune thrombocytopenia (n=3) patients. We found that CD38 RMFI on CD34+ cells was significantly decreased in MDS with less than 5% blasts (mean±SD: 216.5±95.4) as compared to pathologic controls (mean±SD: 377.2±246.1, P=0.01) and healthy volunteers (mean±SD: 322.8±138.1, P=0.02). In RAEB-1/-2, CD38 RMFI (mean±SD: 111.3±74.9, P=0.001) was even more decreased in comparison with both pathologic controls and healthy volunteers. Expression of CD38 on CD34+ cells is heterogeneous and the most immature cells or hematopoietic stem cells are considered to be negative for CD38 expression. By using the median fluorescence intensity (RMedFI), the skewed distribution of CD38 expression on CD34+ cells is taken into account. In our cohort, RMedFI is significantly decreased in MDS with <5% blasts (mean±SD: 368.1±210.3, P=0.03) and MDS RAEB -1/-2 (mean±SD: 139.7±108.5, P<0.001) as compared to pathologic controls (mean±SD: 521.6±314.2). However, no significant differences were observed between RMedFI of CD38 of MDS with less than 5% blasts and healthy volunteers. In conclusion, we show that CD38 expression is reduced in CD34+ cells of MDS patients and might be of value in the diagnosis of MDS. However, there is considerable overlap in CD38 expression between the MDS with less than 5% blasts group and pathologic controls group and healthy volunteers group. Differentiation of MDS from other disease entities by FCM is based on an accumulation of aberrancies rather than a single aberrancy which might reflect the degree of deviation from normal. The number of aberrancies in the myelomonocytic and blast compartment can be translated by a flow cytometric scoring system into a flow score (Wells et al., Blood, 2003,102:394–403, van de Loosdrecht et al., Blood, 2008,111:1067–77). A flow score above 3 is suggestive for MDS. The clinical impact of CD38 expression as a single flow cytometric parameter or as part of a multi parameter analysis requires validation with emphasis on inconclusive cases such as idiopathic cytopenia of unknown significance and idiopathic dysplasia of unknown significance. Flow cytometry in MDS is highly promising and prospective studies are warranted. Disclosures:No relevant conflicts of interest to declare.

Delusional infestation.

This papers aims at familiarizing psychiatric and nonpsychiatric readers with delusional infestation (DI), also known as delusional parasitosis. It is characterized by the fixed belief of being infested with pathogens against all medical evidence. DI is no single disorder but can occur as a delusional disorder of the somatic type (primary DI) or secondary to numerous other conditions. A set of minimal diagnostic criteria and a classification are provided. Patients with DI pose a truly interdisciplinary problem to the medical system. They avoid psychiatrists and consult dermatologists, microbiologists, or general practitioners but often lose faith in professional medicine. Epidemiology and history suggest that the imaginary pathogens change constantly, while the delusional theme "infestation" is stable and ubiquitous. Patients with self-diagnosed "Morgellons disease" can be seen as a variation of this delusional theme. For clinicians, clinical pathways for efficient diagnostics and etiology-specific treatment are provided. Specialized outpatient clinics in dermatology with a liaison psychiatrist are theoretically best placed to provide care. The most intricate problem is to engage patients in psychiatric therapy. In primary DI, antipsychotics are the treatment of choice, according to limited but sufficient evidence. Pimozide is no longer the treatment of choice for reasons of drug safety. Future research should focus on pathophysiology and the neural basis of DI, as well as on conclusive clinical trials, which are widely lacking. Innovative approaches will be needed, since otherwise patients are unlikely to adhere to any study protocol.

Apparent third patient with cutaneous mastocytosis, microcephaly, conductive hearing loss, and microtia

Mastocytosis refers to a heterogeneous group of rare disorders characterized by an abnormal accumulation of mast cells in one or more organ systems. Cutaneous mastocytosis (CM) is the most frequent form in children and is characterized by hyperpigmented macules or papules symmetrically distributed over the trunk, and less so over the limbs, neck, and scalp. Two published articles have reported on unrelated girls presenting with mastocytosis, microcephaly, hearing loss, and hypotonia. Based on the original observation, this disorder was defined as CM with short stature, conductive hearing loss, and microtia (OMIM 248910). Here we report on a girl with similar manifestations who corroborates the existence of this rare disorder. CM, microcephaly, microtia, and/or hearing loss are the minimal diagnostic criteria. All the known patients were sporadic, but parental consanguinity in the first case argues for a possible autosomal-recessive inheritance.

Factors related to clinically probable REM sleep behavior disorder in Parkinson disease

Rapid eye movement sleep behavior disorder (RBD) is commonly accompanied in Parkinson disease (PD). However, the underlying mechanism linking RBD to PD remains unclear. We interviewed and examined 447 consecutive patients with PD to investigate factors associated with the presence of RBD in PD patients. Using the minimal diagnostic criteria for parasomnias provided in the International Classification of Sleep Disorders-Revised (ICSD-R), 164 patients (36.5%) were diagnosed with clinically probable RBD (cpRBD). PD patients with cpRBD were older, had a longer duration of PD, a more severe level of disability, a longer duration of antiparkinsonian medication, and a lower proportion of their Unified Parkinson Disease Rating Scale (UPDRS) scores accounted for by tremor than those without RBD. Multivariate and univariate logistic regression analyses revealed that patient age, PD symptom duration (and, accordingly, more severe motor disability), tremor score, and proportion of the UPDRS score accounted for by tremor were significant factors associated with the presence of RBD in PD patients. The results of the present study support previous observations that PD with RBD may result from a different underlying pattern of neurodegeneration than PD without RBD.

Liver biopsy in alcoholic and non-alcoholic steatohepatitis patients

Alcoholic liver disease and non-alcoholic liver disease share a similar histological spectrum that starts with 'simple' steatosis, and may be accompanied by inflammation. Alcoholic steatohepatitis and non-alcoholic steatohepatitis (NASH) are progressive forms of alcoholic liver disease and non-alcoholic liver disease, respectively, and can evolve into cirrhosis. The currently accepted minimum diagnostic criteria for steatohepatitis include steatosis, lobular inflammation and hepatocellular injury, but not fibrosis. Steatosis involving more than 5% of hepatocytes is required for the diagnosis of non-alcoholic fatty liver disease, but is not necessary for the diagnosis of alcoholic liver disease. Lobular inflammation is usually mild and frequently consists of a mixed, acute and chronic, inflammatory cell infiltrate composed of neutrophils and mononuclear cells. The presence of large numbers of neutrophils favors an alcoholic etiology. Hepatocellular injury in fatty liver disease usually occurs in the form of ballooning, but it can also present as apoptotic (acidophilic) bodies and lytic necrosis. The characteristic pattern of fibrosis in non-cirrhotic steatohepatitis is pericellular/perisinusoidal and is the result of deposition of collagen in the space of Disse. In both alcoholic steatohepatitis and NASH, sinusoidal collagen formation is the result of hepatic stellate cell activation that, in NASH, has been correlated with the grade of steatosis and fibrosis.

De Novo Mutations in POLG Presenting with Acute Liver Failure or Encephalopathy

De Novo Mutations in <i>POLG</i> Presenting with Acute Liver Failure or Encephalopathy