Minimal Diagnostic Criteria Research Articles

Exploring the Epidemiology and Clinico-Demographic Characteristics of Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis

Abstract Objective This study aimed to find the prevalence and clinico-demographic profile of cystic fibrosis (CF) children with allergic bronchopulmonary aspergillosis (ABPA). Methods A cross-sectional study was conducted at a CF clinic of a tertiary care hospital. Participants included the diagnosed cases of children with CF, of both genders, from 4 to 18 years of age. Results A total of 61 patients were enrolled. Sixteen patients (26.2%) had Aspergillus fumigatus sensitization—among these, 10 (16.4%) patients fulfilled the minimum diagnostic criteria for ABPA and 6 (9.8%) had A. fumigatus sensitization only. Two patients were below the age of 5 years, while eight patients were more than 6 years old. The female-to-male ratio was 6:4. High attenuated mucus was the specific finding in our study cohort on computed tomography (CT) chest. All patients with ABPA had significantly higher median (interquartile range [IQR]) levels of total IgE, specific IgE, and IgG for A. fumigatus, and total eosinophil count compared to patients without ABPA. There was also a significant decrease in forced exhalation volume in first second (FEV1) values (6 months apart) in ABPA patients. Conclusion Our study found that ABPA affects 16.4% of our CF population, with 20% of cases occurring in children aged 4 to 5 years. We observed a higher prevalence of ABPA in patients from rural areas. Eosinophilia and serial decline in FEV1 values were observed as potential early markers for ABPA.

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra.

Thrombotic microangiopathy (TMA) is an uncommon but serious complication that not only affects native kidneys but also transplanted kidneys. This review is specifically focused on post-transplant TMA (PT-TMA) involving kidney transplant recipients. Its reported prevalence in the latter population varies from 0.8% to 14% with adverse impacts on both graft and patient survival. It has many causes and associations, and the list of etiologic agents and associations is growing constantly. The pathogenesis is equally varied and a variety of patho genetic pathways lead to the development of microvascular injury as the final common pathway. PT-TMA is categorized in many ways in order to facilitate its management. Ironically, more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual case. Pathologically, the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the microvasculature. Early diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and pathologists. The Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first phase. Management of the condition is also challenging and still largely empirical. It varies from simple maneuvers, such as plasmapheresis, drug withdrawal or modification, or dose reduction, to lifelong complement blockade, which is very expensive. A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially effective. This review aims to increase the awareness of relevant stakeholders regarding this important, potentially treatable but under-recognized cause of kidney allograft dysfunction.

Delphi: A Democratic and Cost-Effective Method of Consensus Generation in Transplantation.

The Thrombotic Microangiopathy Banff Working Group (TMA-BWG) was formed in 2015 to survey current practices and develop minimum diagnostic criteria (MDC) for renal transplant TMA (Tx-TMA). To generate consensus among pathologists and nephrologists, the TMA BWG designed a 3-Phase study. Phase I of the study is presented here. Using the Delphi methodology, 23 panelists with >3years of diagnostic experience with Tx-TMA pathology listed their MDC suggesting light, immunofluorescence, and electron microscopy lesions, clinical and laboratory information, and differential diagnoses. Nine rounds (R) of consensus resulted in MDC validated during two Rs using online evaluation of whole slide digital images of 37 biopsies (28 TMA, 9 non-TMA). Starting with 338 criteria the process resulted in 24 criteria and 8 differential diagnoses including 18 pathologic, 2 clinical, and 4 laboratory criteria. Results show that 3/4 of the panelists agreed on the diagnosis of 3/4 of cases. The process also allowed definition refinement for 4 light and 4 electron microscopy lesions. For the first time in Banff classification, the Delphi methodology was used to generate consensus. The study shows that Delphi is a democratic and cost-effective method allowing rapid consensus generation among numerous physicians dealing with large number of criteria in transplantation.

Thrombotic Microangiopathy in the Renal Allograft: Results of the TMA Banff Working Group Consensus on Pathologic Diagnostic Criteria.

The Banff community summoned the TMA Banff Working Group to develop minimum diagnostic criteria (MDC) and recommendations for renal transplant TMA (Tx-TMA) diagnosis, which currently lacks standardized criteria. Using the Delphi method for consensus generation, 23 nephropathologists (panelists) with >3years of diagnostic experience with Tx-TMA were asked to list light, immunofluorescence, and electron microscopic, clinical and laboratory criteria and differential diagnoses for Tx-TMA. Delphi was modified to include 2 validations rounds with histological evaluation of whole slide images of 37 transplant biopsies (28 TMA and 9 non-TMA). Starting with 338 criteria in R1, MDC were narrowed down to 24 in R8 generating 18 pathological, 2 clinical, 4 laboratory criteria, and 8 differential diagnoses. The panelists reached a good level of agreement (70%) on 76% of the validated cases. For the first time in Banff classification, Delphi was used to reach consensus on MDC for Tx-TMA. Phase I of the study (pathology phase) will be used as a model for Phase II (nephrology phase) for consensus regarding clinical and laboratory criteria. Eventually in Phase III (consensus of the consensus groups) and the final MDC for Tx-TMA will be reported to the transplantation community.

Round-Robin test for the histological diagnosis of acute colonic Graft-versus-Host disease validating established histological criteria and grading systems

Histomorpholgy is one of the mainstays of acute Graft-versus-host disease (GvHD) diagnosis. However, concerns about reproducibility and the most appropriate grading system question its usefulness. Our aim was to assess histomorphological parameters and previously reported grading systems for GvHD regarding reproducibility and validity. Moreover, we propose that sum scores, derived by combining separately scored morphological parameters into a total score, might provide a simplified but equally effective means to grade GvHD. A total of 123 colon biopsies were assessed across four pathologists for intestinal GvHD using a Round-Robin test and results were correlated with clinical findings. Interobserver reproducibility was high for histological parameters that were evaluated as indicators of acute GvHD. Published grading systems were moderately reproducible (ICC 0.679–0.769) while simplified sum scores, in comparison, showed better interrater reliability (ICC 0.818–0.896). All grading systems and sum scores were associated with clinical signs of GvHD and in part with therapy response and survival. However, they were not able to stratify patients according to the clinical severity of GvHD. In a hot-spot analysis 1 crypt apoptotic body (CAB) in 10 crypts was a reasonable cut-off value for minimal diagnostic criteria of GvHD. In conclusion, histology can contribute to the diagnosis of GvHD and is reproducible. Published grading systems are able to reflect clinical findings as are simplified sum scores, which showed improved reproducibility and might be easier to handle as they are based on adding up histological parameters rather than transferring histological findings into a separate grading system. Sum scores will have to be further tested in a prospective setting.

Diabetes mellitus and optic atrophy: Study of the Wolfram syndrome

Background Wolfram syndrome (WS), also known by the acronym DIDMOAD, is a rare and progresive hereditary disease of autosomal recessive inheritance which minimum ascertainment diagnostic criteria are the occurrence together of diabetes mellitus and optic atrophy before 15 years of age. Objective To describe the clinical, biochemical and molecular profile of WS in a tertiary care hospital in Mexico. Materials and Methods We reviewed patients records who fulfill the minimum ascertainment diagnostic criteria of WS presenting between January 1987 and May 2015 in a tertiary care hospital in Mexico. Results Five patients fulfill the inclusion criteria (three male and two female). Diabetes mellitus was the first manifestation of the syndrome in all of them, with a mean age at diagnosis of 5.8 ± 2.71 years, while the WS diagnosis was established at a mean age of 15.8 ± 8.37 years. All the patients had optic atrophy and two of them presented with the complete DIDMOAD spectrum. We found new associations with autoimmune hepatitis and testicular cancer. Conclusions This study shows the variability of clinical presentation of WS, as well as two new associations.

Chronic Endometritis: Diagnostic Considerations in Patients With Infertility

Abstract Chronic endometritis (CE) is a controversial clinical and pathological entity. Although the presence of plasma cells (PCs) is the most frequently used diagnostic criterion for CE, the minimal diagnostic criteria remain controversial and undefined. The clinical setting of CE (asymptomatic, pelvic inflammatory disease, infertility) is an important consideration regarding the clinical significance of endometrial PCs. In the setting of infertility, specifically recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL), CE may have a negative impact on endometrial receptivity, resulting in higher rates of implantation failure. The proposed pathophysiology is that a subclinical intrauterine infection alters the local inflammatory milieu resulting in a shift of the normal inflammatory cell profiles toward responses associated with implantation failure and poorer reproductive outcomes. Cure rates following antibiotic treatment are reported to be high (up to 90%). The results of meta-analyses describing the effect of CE on reproductive outcomes are mixed. There is evidence supporting CE as a treatable factor with improved reproductive outcomes following treatment and there are also results showing no differences in reproductive outcomes. Variable diagnostic criteria for CE, inclusion criteria, and treatment regimens between studies are the main limitations, hampering the ability to compare results across studies. Results regarding the optimal diagnostic criteria in the setting of RIF and RPL are also variable, with some authors recommending a cutoff of 1 or more CD138+ PCs per high-power field and some recommending a cutoff of 5 or more CD138+ PCs per high-power field. There are some studies indicating CE as a negative prognostic factor in patients with RIF and RPL, which may be reversible with antibiotic treatment. The optimal diagnostic criteria for CE in this clinical setting are undefined. For the investigation of infertility patients whom clinicians intend to treat, a descriptive diagnosis (indicating the presence/number of PCs and method of identification) is a reasonable approach. Routine use of CD138 immunohistochemistry is of limited value for the diagnosis of CE.

Diagnostic accuracy of pelvic examination in pelvic inflammatory disease: A meta-analysis.

Pelvic inflammatory disease (PID) is not a mere transient infection. PID can lead to chronic pain, ectopic pregnancy, and infertility. Although the Centers for Disease Control and Prevention have established minimum diagnostic criteria, including pelvic examination, the diagnostic value of pelvic tenderness has recently garnered controversy. Our meta-analysis aimed to confirm whether pelvic tenderness, cervical motion tenderness, and adnexal tenderness can help diagnose PID. We searched for studies reporting the diagnostic test accuracy of pelvic tenderness, cervical motion tenderness, and adnexal tenderness among female patients at risk for PID, using MEDLINE, EMBASE, CENTRAL, CINAHL, Google, and Google Scholar through May 25th, 2022. After quality assessment using QUADAS-2, we performed data synthesis using a bivariate random effect model and Bayesian hierarchical summary receiver operating characteristic model. We then conducted sensitivity analysis excluding studies with non-PID cases. The literature search produced 6769 articles. After quality assessment, 14 studies and their 2808 participants were eligible for synthesis on pelvic tenderness. Laparoscopy, either alone or in combination, was the most frequent reference standard. The main results for pelvic tenderness sensitivity and specificity were 0.81, 95% confidence interval (CI) [0.67-0.90] and 0.40, 95% CI [0.25-0.57], respectively. Sensitivity and specificity were 0.72, 95% CI [0.57-0.83] and 0.50, 95% CI [0.34-0.66], for cervical motion tenderness, and 0.87 [0.64-0.96] and 0.27, 95% CI [0.12-0.52] for adnexal tenderness, respectively. Our meta-analysis suggests that pelvic tenderness assessed by pelvic examination may be useful for PID examination with moderate-to-high sensitivity, whereas clinicians should be aware of the diagnostic significance of pelvic tenderness.

Clinical characteristics and whole exome sequencing results of patients with Möbius syndrome

Objective: To analyze the clinical characteristics of patients with Möbius syndrome (MBS) and to explore likely pathogenic genes. Methods: Cross-sectional study. The study enrolled 18 sporadic MBS patients who visited the Eye Center of Beijing Tongren Hospital Affiliated to Capital Medical University from July 2018 to December 2021. All patients completed the general information questionnaire and underwent detailed ophthalmic examinations and general physical examinations. Seventeen patients received MRI examination of cranial nerves and the orbit. The peripheral venous blood of all patients and their nuclear family members was collected, the genomic DNA was extracted, and the pathogenic gene variations that may lead to MBS were identified by whole exome sequencing and bioinformatics analysis. Results: Among the 18 patients, there were 8 males and 10 females, and the age was (4.5±4.0) years (range, 8 months to 17 years). All patients showed congenital, bilateral or unilateral abduction deficit and facial weakness, which met the minimum diagnostic criteria of MBS. Among them, bilateral abduction deficit (16/18) and bilateral facial weakness (15/18) were more common. Nine patients were orthotopic in primary position, eight presented with esotropia, and one showed hypotropia. All patients had ametropia, of which 4 patients were diagnosed as amblyopia. Fifteen patients were also accompanied by other multiple congenital malformations, mainly characterized by abnormal development of glossopharynx (14/18) and limbs (5/18), and 7 patients were also accompanied by motor retardation. In addition, 9 patients had intrauterine exposure to adverse factors. Among the 17 patients who underwent MRI, 15 patients had bilateral hypoplasia of the abducens nerve, two had unilateral hypoplasia of the abducens nerve, 14 showed bilateral hypoplasia of the facial nerve, and three showed hypoplasia of the left facial nerve. Besides, some patients were also accompanied by hypoplasia of other cranial nerves, mainly the glossopharyngeal nerve and the hypoglossal nerve. No definite pathogenic variations were found by whole exome sequencing and bioinformatics analysis. Conclusions: The main clinical features of MBS were congenital abduction deficit and facial weakness, with complicated manifestations and variable severity. MRI showed absence or thinning of the abducens nerve and the facial nerve. The results of MRI can be used as a supplement to the diagnostic criteria of MBS. The mutation detection rate of MBS was low, and half of patients had exposure to adverse factors during pregnancy, suggesting that there was a multifactorial pathogenic mechanism in MBS.

The association between restless leg syndrome and anxiety in Parkinson’s disease: a case-control study

ABSTRACT Objective To shed light on the association between restless leg syndrome (RLS) and anxiety in Parkinson’s disease (PD) population. Methods This was a case-control study including 129 PD participants with and without anxiety who presented to the Aerospace Center Hospital in Beijing, China. Anxiety was evaluated by using the Beck Anxiety Index score. RLS was assessed using the minimal diagnostic criteria of the International Restless Legs Study Group and RLS symptom frequency and treatment. We then examined the relationship between RLS and anxiety by logistic regression models and subgroup as well as interaction analyses. Results The proportion of RLS in PD with anxiety was significantly higher in the PD without anxiety (p < 0.001). The multivariate logistic regression models indicated that PD participants with RLS had a 5.98-fold higher risk of anxiety in PD than those without RLS (OR, 6.98; 95% CI, 2.77–17.59). Subgroup analyses indicated that PD with RLS tended to be associated with a greater risk of anxiety in all stratified subgroups (adjusted ORs >1). Furthermore, the interaction analyses revealed no interactive role in the association between RLS and anxiety. Conclusions The present case-control study suggests that RLS is an independent risk factor for anxiety in PD patients. Early attention and targeted treatment for RLS may be necessary for mood management in PD. Larger prospective cohort studies are wanted to validate these findings.

Investigation of Genetic Causes in a Developmental Disorder: Oculoauriculovertebral Spectrum.

Oculoauriculovertebral spectrum (OAVS) is a genetically and clinically heterogeneous disorder that occurs due to a developmental field defect of the first and second pharyngeal arches. Even though recent whole exome sequencing studies (WES) have led to identification of several genes associated with this spectrum in a subset of individuals, complete pathogenesis of OAVS remains unsolved. In this study, molecular genetic etiology of OAVS was systematically investigated. A cohort of 23 Turkish patients with OAVS, referred to Hacettepe University Hospital, Department of Pediatric Genetics from 2008 to 2018, was included in this study. Minimal diagnostic criteria for OAVS were considered as unilateral microtia or hemifacial microsomia with preauricular skin tag. The cohort was clinically reevaluated for craniofacial and extracranial findings. Molecular etiology was investigated using candidate gene sequencing following copy number variant (CNV) analysis. WES was also performed for 2 of the selected patients. Patients in the study cohort presented similar demographic and phenotypic characteristics to previously described patients in the literature except for a higher frequency of bilaterality, cardiac findings, and intellectual disability/developmental delay. CNV analysis revealed a possible genetic etiology for 3 patients (13%). Additional WES in 1 of the 2 patients uncovered a novel heterozygous nonsense variant in Elongation factor Tu GTP-binding domain-containing 2 (EFTUD2) causing mandibulofacial dysostosis with microcephaly (MFDM), which clinically overlaps with OAVS. Detailed clinical evaluation for any patient with OAVS is recommended due to a high rate of accompanying systemic findings. We further expand the existing genetic heterogeneity of OAVS by identifying several CNVs and a phenotypically overlapping disorder, MFDM.

A Questionnaire-Based Study on Clinical REM Sleep Behavior Disorder and Subtypes in Multiple System Atrophy

Objectives: Studies documenting the association between rapid eye movement sleep behavior disorder (RBD) and subtypes of multiple system atrophy (MSA) are rare. In this study, we investigated the presence of clinical RBD in MSA patients and compared the prevalence and severity of RBD in patients with MSA-P and MSA-C subtypes. Methods: We evaluated 54 consecutive patients presenting with MSA and hospitalized in the neurology ward of Beijing Hospital from February 2012 to June 2020. The healthy control (HC) group consisted of 100 healthy individuals who came to our hospital for physical examination. The clinical diagnosis of RBD was based on the minimal diagnostic criteria of International Classification of Sleep Disorders, revised. The severity of clinical RBD was rated on a digital scale from 0 to 3. The patients were divided into 2 subgroups: MSA-P and MSA-C. The MSA and HC groups were compared in terms of frequency of clinical RBD. The MSA-P and MSA-C subgroups were compared with each other for age, sex, onset age, disease duration, and features of clinical RBD. The correlation between severity of clinical RBD and clinical characteristics of MSA was analyzed in the patient groups. Results: The frequency of clinical RBD in MSA and HC groups was 70.4% (38/54) and 5% (5/100), respectively. The difference between 2 groups was significant (χ² = 74.453, p = 0.000). Among the patients, 57.4% (31/54) had the MSA-P subtype. There were no significant differences between MSA-P and MSA-C subtypes in the prevalence (χ² = 1.734, p = 0.188) and severity (χ² = 1.776, p = 0.412) of clinical RBD. The onset of clinical RBD during the premotor period was not different between the subtypes of MSA, either in patients’ number of preceding the onset of motor symptoms (χ² = 0.581, p = 0.446) or the preceding time (Z = −0.550, p = 0.582). For the MSA-C patients, there was a negative correlation between the score of severity of the RBD scale and RBD preceding motor symptoms (r = −0.482, p = 0.020). Conclusion: In our study, the prevalence of clinical RBD is unrelated to the subtypes of MSA. The onset of clinical RBD during the premotor period was not different between subtypes of MSA. However, we found that the severity of RBD occurring before the motor symptoms was more than that occurring after the motor symptoms in MSA-C patients. Our results showed that MSA-P and MSA-C patients may have a probable indicator for the similar pathologic mechanism of the disease and its sleep problems.

Expansion of the CCDC22 associated Ritscher-Schinzel/3C syndrome and review of the literature: Should the minimal diagnostic criteria be revised?

The Ritscher-Schinzel syndrome (RTSCS) is a rare condition with craniofacial, cardiac and fossa posterior abnormalities. RTSCS is subdivided into Ritscher-Schinzel syndrome 1 (RTSCS1) caused by pathogenic variants in coiled-coil domain-containing protein 22 (CCDC22), and Ritscher-Schinzel syndrome 2 (RTSCS2) caused by pathogenic variants in WASH complex subunit 5 (WASHC5). CCDC22 is inherited in an X-linked recessive manner while WASHC5 is inherited in an autosomal recessive manner. Only 17 individuals with a molecular diagnosis are reported. In the past, the diagnosis of RTSCS was solely based on the clinical findings, and minimal diagnostic criteria has been proposed for the syndrome: Cardiac malformations (other than isolated patent ductus arteriosis), fossa posterior malformations, and certain dysmorphic features. However, those criteria are not present in all patients. We aim to further delineate the spectrum of CDCC22 associated RTSCS and present a novel patient with epileptic encephalopathy due to a presumed disease causing CCDC22 missense variant inherited from a healthy mother and grandmother. An affected maternal uncle had passed away at the age of 12 months and was thus unavailable for genetic testing. The proband and the maternal uncle had the typical facial dysmorphism associated with RTSCS, and they closely resembled previously published RTSCS2 patients with a molecular diagnosis. This suggests that RTSCS1 and RTSCS2 patients have a similar facial gestalt. We also review the literature on RTSCS, we explore potential differences and similarities between CCDC22 and W ASHC5 associated RTSCS and discuss the minimal diagnostic criteria.

Breast Cancer Diagnostics, Therapy, and Outcomes in Sub-Saharan Africa: A Population-Based Registry Study.

Breast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival. Random samples of patients with BC (≥40 patients per registry), diagnosed from 2009 through 2015, were drawn from 11 urban population-based cancer registries from 10 countries (Benin, Congo, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mozambique, Namibia, Uganda, and Zimbabwe). Active methods were used to update the therapy and outcome data of diagnosed patients ("traced patients"). Excess hazards of death by therapy use were modeled in a relative survival context. A total of 809 patients were included. Additional information was traced for 517 patients (63.8%), and this proportion varied by registry. One in 5 traced patients met the minimum diagnostic criteria (cancer stage and hormone receptor status known) for use of the NCCN Harmonized Guidelines. The hormone receptor status was unknown for 72.5% of patients. Of the traced patients with stage I-III BC (n=320), 50.9% received inadequate or no cancer-directed therapy. Access to therapy differed by registry area. Initiation of adequate therapy and early-stage diagnosis were the most important determinants of survival. Downstaging BC and improving access to diagnostics and care are necessary steps to increase guideline adherence and improve survival for women in SSA. It will also be important to strengthen health systems and facilities for data management in SSA to facilitate patient follow-up and disease surveillance.

Research Priorities in Pediatric Asthma: Results of a Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in Real Life (PeARL) Think Tank

Pediatric asthma remains a public health challenge with enormous impact worldwide. The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities. We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared. A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations. Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider.

Brain phenotyping in Moebius syndrome and other congenital facial weakness disorders by diffusion MRI morphometry.

In this study, we used a novel imaging technique, DTI (diffusion tensor imaging)-driven tensor-based morphometry, to investigate brain anatomy in subjects diagnosed with Moebius syndrome (n = 21), other congenital facial weakness disorders (n = 9) and healthy controls (n = 15). First, we selected a subgroup of subjects who satisfied the minimum diagnostic criteria for Moebius syndrome with only mild additional neurological findings. Compared to controls, in this cohort, we found a small region of highly significant volumetric reduction in the paramedian pontine reticular formation and the medial longitudinal fasciculus, important structures for the initiation and coordination of conjugate horizontal gaze. Subsequently, we tested if volume measurements from this region could help differentiate individual subjects of the different cohorts that were included in our study. We found that this region allowed discriminating Moebius syndrome subjects from congenital facial weakness disorders and healthy controls with high sensitivity (94%) and specificity (89%). Interestingly, this region was normal in congenital facial weakness subjects with oculomotor deficits of myopathic origin, who would have been classified as Moebius on the basis of purely clinical diagnostic criteria, indicating a potential role for diffusion MRI morphometry for differential diagnosis in this condition. When the entire Moebius syndrome cohort was compared to healthy controls, in addition to this 'landmark' region, other areas of significantly reduced volume in the brainstem emerged, including the location of the nuclei and fibres of cranial nerve VI (abducens nerve), and fibres of cranial nerve VII (facial nerve), and a more rostral portion of the medial longitudinal fasciculus. The high sensitivity and specificity of DTI-driven tensor-based morphometry in reliably detecting very small areas of volumetric abnormality found in this study suggest broader applications of this analysis in personalized medicine to detect hypoplasia or atrophy of small pathways and/or brainstem nuclei in other neurological disorders.

Convergence of psychiatric symptoms and restless legs syndrome: A cross-sectional study in an elderly French population

ObjectiveThe objective was to evaluate the association between restless legs syndrome (RLS) with generalized anxiety disorder (GAD), major depression disorder (MDD), dysthymia, and GAD-depression comorbidity. Secondary aims were to examine the association between RLS with the cognitive-affective and somatic-vegetative disturbances experienced as part of depression and GAD. MethodsThis was a cross-sectional study of 1493 elderly participants (median age 80.6 years, 64% women) from Dijon, France. Probable RLS was assessed using the minimal diagnostic criteria of the International Restless Legs Study Group and RLS symptom frequency and treatment. Participants underwent structured interviews for MDD, dysthymia, and GAD. Participants also completed the Center for Epidemiological Studies-Depression scale (CES-D). The association between RLS and psychiatric disorders, their criterion symptoms, or symptom factors was examined using logistic regression. ResultsThe point prevalence of probable RLS in this sample was 8.2%. Probable RLS was associated with isolated GAD (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.01–4.68) and comorbid GAD-any depression disorder (OR 3.26, 95% CI 1.14–9.29), but not MDD or dysthymia. Probable RLS was also associated with the GAD criterion worry most days and feeling tense, and the CES-D factors representing depressed affect, somatic symptoms, and positive affect. ConclusionsProbable RLS was associated with GAD-depression comorbidity as well as isolated GAD. The findings challenge previous reports linking RLS solely with MDD, suggesting the association is partly driven by GAD-depression comorbidity.

UNCOMMON FORM OF ECTODERMAL DYSPLASIA: TRICHO-DENTO-OSSEOUS SYNDROME

<h3>Background</h3> Tricho-dento-osseous syndrome (TDOS) is an autosomal dominant genetic disorder, which is characterized by inherited defects in tissues that arise from epithelial–mesenchymal interaction. The minimal diagnostic criteria for TDOS include enamel hypoplasia, posterior taurodonts, autosomal dominant inheritance pattern, tightly curly hair at birth, and/or radiographic evidence of bone sclerosis. Some authors have questioned whether amelogenesis imperfecta of the hypomaturation–hypoplasia type with taurodontism (AIHHT) and TDOS are distinct conditions or denote a spectrum of the same disease. <h3>Objective(s)</h3> The aim of this study was to increase awareness of TDOS. <h3>Results</h3> A 25-year-old female patient was seeking restorative treatment for the yellowish-brown discoloration of her teeth. Clinical evaluation revealed that she had multiple missing teeth, discolored teeth, frontal bossing, and a concave profile. She was otherwise healthy and not taking any medications. Her medical history indicated a previous diagnosis of ectodermal dysplasia (ED). Panoramic radiography and cone beam computed tomography (CBCT) revealed multiple missing and impacted teeth, as well as retained primary teeth. Reduction in enamel thickness on deciduous and permanent teeth was observed, in addition to taurodont appearance of second permanent molars. Generalized homogeneous ground-glass trabecular pattern in the maxilla and the mandible with a square shape of mandible was noted. <h3>Discussion/Conclusions</h3> In this report, we describe an unusual phenotype of ED, which represents a group of inherited conditions in which 2 or more ectodermally derived anatomic structures fail to develop. TDOS is an uncommon form of ED. The dental findings are clinically similar between TDOS and AIHHT; however, patients with AIHHT lack changes in their hair and bone. In cases where hair, bone, and nail changes are not significant, genetic analysis may help in differential diagnosis. TDOS is genetically linked to markers on chromosome 17 q21.

The distinct roles of OSA and depression severity in day- and night-time symptomatology in OSA patients: a pilot study.

Obstructive sleep apnoea (OSA) is a common sleep disorder and is associated with a number of comorbid conditions, including the frequent occurrence of depression. Notably, there is a considerate overlap in day- as well as night-time symptomatology in depression and OSA. In light of this, we aimed to disentangle the distinct effects of OSA and depression severity on day- and night-time symptomatology. This pilot study (N = 320) utilized a retrospective chart review design and included both males and females who met the minimum diagnostic criteria for OSA. Daytime symptoms (sleepiness and fatigue) were assessed via questionnaires, while night-time symptoms were measured via polysomnography. Main findings include the following: (a) no association between OSA and depression severity, (b) depression severity significantly predicted increased sleepiness and fatigue (c) OSA severity significantly predicted increased stage 2 non-rapid eye movement sleep percentage, (d) OSA significantly predicted decreased stage 3 non-rapid eye movement sleep percentage and rapid eye movement sleep percentage. Overall, depression severity exerts the strongest influence on daytime symptomatology, while OSA severity exerts the strongest influence on night-time symptomatology. Moreover, with the exception of sleepiness, no overlap between day- and night-time findings was detected. OSA and depression, although comorbid, possibly constitute distinct disease processes in this population group. Consequently, solely devising treatment targeting a reduction in apnoea-hypopnoea index might not be sufficient in alleviating debilitating daytime symptoms in treatment-seeking individuals.

Defining the Minimum Acceptable Diagnostic Accuracy of Noninvasive Fibrosis Testing in Cirrhosis: A Decision Analytic Modeling Study.

No studies explore the clinical consequences of using noninvasive tests (NITs) compared to liver biopsy (LB) in diagnosing cirrhosis. Our aim was to combine two decision analytic models to determine the minimum diagnostic accuracy criteria for NITs to diagnose cirrhosis with equivalence to LB in terms of mortality. We further evaluated selected existing NITs used alone and sequentially. A decision tree was constructed with associated 2-year mortality incorporating an LB or NIT strategy to diagnose cirrhosis in a hypothetical cohort of 1,000 asymptomatic patients. Cirrhosis prevalence was modeled at 5%, 20%, and 50%. Decision curve analyses were performed, expressing the net benefit of tests over a range of threshold probabilities (Pt ). The NIT deriving from the two models that could diagnose cirrhosis with at least equal mortality to LB was termed "mNIT." Existing NITs were then compared using both decision models. The combined mNIT minimum sensitivity and specificity to diagnose cirrhosis with equivalence to LB at 5%, 20% and 50% cirrhosis prevalence were; 89% and 88%, 94% and 85%, and 94% and 87%, respectively at Pt =0.20. Sequential NITs performed better than single NITs at any prevalence. Combining both decision models, FibroTest plus vibration-controlled transient elastography (VCTE) and VCTE alone were the only existing NITs that were better than or equal to LB at diagnosing cirrhosis at 5% prevalence. At 20% and 50% prevalence, only FibroTest high specificity cutoff plus VCTE was equivalent to or better than LB. Conclusion: Decision analytic models were used to determine the minimum acceptable diagnostic accuracy of NITs for diagnosing cirrhosis; we recommend that such models should be used as the standard in evaluating the diagnostic performance of NITs.