Design of a compact off-axis four-mirror objective system for a thermal camera.

The optical design of a compact off-axis four-mirror objective system (OFOS) of a thermal camera for a syndromic surveillance system that captures bioclinical signals, like temperature, directly related to the physical symptoms of the COVID-19 disease through thermal images is presented. The OFOS design works on wavelengths of 7.5-14 µm, with an f-number of 4, and a field of view (FOV) of 24×4 deg.

Children with Kawasaki disease or Kawasaki-like syndrome (MIS-C/PIMS) at the time of COVID-19: are they all the same? Case series and literature review.

Since the coronavirus disease 2019 (COVID-19) outbreak started, children have been considered marginally involved compared to adults, with a quite significant percentage of asymptomatic carriers. Very recently, an overwhelming inflammatory activation, which shares clinical similarities with Kawasaki disease (KD), has been described in children exposed to COVID-19. We report three KD-like cases that occurred during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a highly affected area of Northern Italy. The clinical presentation was characterized by the presence of unremitting fever, diarrhea and elevated inflammatory markers. Case #1 and Case #2 occurred one week apart and shared other clinical features: laboratory tests confirmed COVID-19 exposure and high inflammatory activation with myocardial involvement. Case #3 followed a more typical pattern for KD. Interestingly, this patient showed lower levels of procalcitonin, C-reactive protein, D-dimers, and ferritin compared to the other two cases, whereas platelet count was higher. We hypothesize that SARS-CoV-2 might act in children as a trigger, either inducing a classical KD phenotype or causing a systemic inflammatory response leading to a severe KD-like phenotype, eventually characterized by myocardial impairment. We think that bringing these cases and their differences to the attention of the rheumatology community during the COVID-19 pandemic will be beneficial in order to highlight the importance of early diagnosis and to increase awareness of this new phenomenon.

Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis.

OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.

Travel time to health facilities in areas of outbreak potential: maps for guiding local preparedness and response.

BACKGROUND: Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. METHODS AND FINDINGS: We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. CONCLUSIONS: These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country's preparedness plans.

Takotsubo syndrome in a teen health centre.

BACKGROUND: Takotsubo syndrome is also referred to as stress cardiomyopathy and typically occurs in females aged 55 years and older. This demographic represents a significant part of the healthcare workforce and they have over recent decades experienced increasing levels of violence from patients and clients. AIMS: Our study describes a Takotsubo syndrome that occurred following an incident of physical and verbal aggression at work in a teen health centre. CASE REPORT: We report the case of a 56-year-old female community educator who suffered chest pain 48 h after suffering an aggressive incident at work. She had no history of cardiovascular disease. During hospitalization she was investigated with an electrocardiogram, echocardiography, coronary angiography, left ventriculography and a cardiac magnetic resonance imaging. Examinations confirmed the diagnosis of Takotsubo cardiomyopathy. This was deemed to be a work-related accident. With the help of her occupational physician, the patient was able to return to work with work adjustments. CONCLUSIONS: Increasing levels of violent behaviours towards staff in the health care sector underscores the need for measures in the workplace to help prevent precipitation of this syndrome in workers.

Gold as a modifier of metal nanoparticles: effect on structure and catalysis.

Bimetallic gold based catalysts have been prepared using a sol immobilisation technique. Despite a very similar metal dispersion, different structures are revealed depending on the second metal, with alloyed systems being preferred in the case of Pd, Pt and Cu, and core-shell in the case of Ru. A positive synergistic effect between the metals has been revealed only in the cases of Pd and Cu in the oxidation of benzyl alcohol. AuPd/C has been also studied in the hydrogenation of benzaldehyde where the bimetallic catalyst revealed a different selectivity compared to the monometallic counterpart.

Estimating gestational age at birth from fundal height and additional anthropometrics: a prospective cohort study.

OBJECTIVE: Accurate assessment of gestational age (GA) is critical to paediatric care, but is limited in developing countries without access to ultrasound. Our objectives were to assess the accuracy of prediction of GA at birth and preterm birth classification using routinely collected anthropometry measures. DESIGN: Prospective cohort study. SETTING: United States. POPULATION OR SAMPLE: A total of 2334 non-obese and 468 obese pregnant women. METHODS: Enrolment GA was determined based on last menstrual period, confirmed by first-trimester ultrasound. Maternal anthropometry and fundal height (FH) were measured by a standardised protocol at study visits; FH alone was additionally abstracted from medical charts. Neonatal anthropometry measurements were obtained at birth. To estimate GA at delivery, we developed three predictor models using longitudinal FH alone and with maternal and neonatal anthropometry. For all predictors, we repeatedly sampled observations to construct training (60%) and test (40%) sets. Linear mixed models incorporated longitudinal maternal anthropometry and a shared parameter model incorporated neonatal anthropometry. We assessed models' accuracy under varied scenarios. MAIN OUTCOME MEASURES: Estimated GA at delivery. RESULTS: Prediction error for various combinations of anthropometric measures ranged between 13.9 and 14.9 days. Longitudinal FH alone predicted GA within 14.9 days with relatively stable prediction errors across individual race/ethnicities [whites (13.9 days), blacks (15.1 days), Hispanics (15.5 days) and Asians (13.1 days)], and correctly identified 75% of preterm births. The model was robust to additional scenarios. CONCLUSIONS: In low-risk, non-obese women, longitudinal FH measures alone can provide a reasonably accurate assessment of GA when ultrasound measures are not available. TWEETABLE ABSTRACT: Longitudinal fundal height alone predicts gestational age at birth when ultrasound measures are unavailable.

Quantitative assessment of myocardial scar heterogeneity using cardiovascular magnetic resonance texture analysis to risk stratify patients post-myocardial infarction.

AIM: To determine whether heterogeneity of cardiac scar, as assessed by cardiovascular magnetic resonance (CMR) texture analysis, may provide insight into better risk stratification for patients with previous myocardial infarction (MI). MATERIALS AND METHODS: Patients with previous MI (n=76) were followed for a median of 371.5 days after late gadolinium enhancement (LGE) CMR. The primary endpoint was a composite of ventricular tachycardia, ventricular fibrillation, or unexplained syncope. Areas of LGE were identified and manually segmented on a short-axis projection. The characteristics of the scar heterogeneity were evaluated via CMR texture analysis. This is a filtration-histogram technique, where images are filtered using the Laplacian of a Gaussian filter to extract features different sizes (2-6 mm in radius) corresponding to fine, medium, and coarse texture scales followed by a quantification step using histogram analysis (skewness and kurtosis). RESULTS: Patients suffering arrhythmic events during the follow-up period demonstrated significantly higher kurtosis (coarse-scale, p=0.005) and lower skewness (fine-scale, p=0.046) compared to those suffering no arrhythmic events. Furthermore, Kaplan-Meier analysis showed significantly higher coarse kurtosis (p=0.004), and lower fine skewness (p=0.035) were able to predict increased incidence of ventricular arrhythmic events. CONCLUSIONS: In this pilot study, indices of texture analysis reflecting textural heterogeneity were significantly associated with a greater incidence of arrhythmic events. Further work is required to delineate the role of texture analysis techniques in risk stratification post-MI.

Oral leukoplakia remains a challenging condition.

Crispian Scully had many interests in the realm of oral diseases. But oral leukoplakia was one that piqued his curiosity when he was still an academic neophyte and remained a topic which he studied throughout his enormously productive career. It is easy to understand why. While the clinical manifestations of oral leukoplakia are common, we still do not fully understand why one version of the condition is benign, while another, similar in appearance, progresses to a malignancy. The diagnosis of oral leukoplakia is based on expert clinical and histopathological examamination. Management and treatment of leukoplakia remain challenging especially for large lesions and the proliferative subtype. This review aims to provide a general overview on leukoplakia, explore current challenges in its diagnosis and management and discuss the opportunities to better understand the condition.

Oral stomatitis and mTOR inhibitors: A review of current evidence in 20,915 patients.

BACKGROUND: Traditional treatment of malignancies with chemotherapeutic agents is often affected by the damage inflicted on non-cancerous cells. Toxicities of the oral cavity, such as mucositis and stomatitis, are some of the most significant and unavoidable toxicities associated with anti-cancer therapies. For such reason, in the last decades, newer targeted agents have been developed aiming to decrease the rates of side effects on healthy cells. Unfortunately, targeted anti-cancer therapies also showed significant rate of toxicity on healthy tissues. mTOR inhibitors showed some adverse events, such as hyperglycemia, hyperlipidemia, hypophosphatemia, hematologic toxicities, and mucocutaneous eruption, but the most important are still stomatitis and skin rash, often reported as dose-limiting side effects. PATIENTS AND METHODS: A search of the literature was performed by authors on the PubMed online database using the following key words: "sirolimus" OR "everolimus" OR "temsirolimus" OR "deforolimus" OR "ridaforolimus" combined with the Boolean operator AND with the terms: "stomatitis" OR "mucositis" OR "oral pain." Titles and abstracts of 382 potentially relevant studies were screened; of these, 114 studies were excluded because they did not report the inclusion criteria. In the second round, 268 studies were read full-text, but only 135 reported the inclusion criteria and were included for data extraction. Of the included studies, 95 referred to everolimus use, 16 to ridaforolimus, and 26 to temsirolimus (two studies referred to both everolimus and temsirolimus). RESULTS: The incidence rate of stomatitis according to the agent used was 25.07% (3,959/15,787) for everolimus, 27.02% (724/2,679) for temsirolimus, and 54.76% (598/1,092) for ridaforolimus. All the three agents analyzed showed high rates of low-grade stomatitis (G1-G2), while the onset of severe stomatitis (G3-G4) was rare. CONCLUSIONS: Analysis of the reports with patients treated with everolimus, temsirolimus, and ridaforolimus showed a clear prevalence of stomatitis grade 1 or 2. These data differ from that of patients treated with conventional chemotherapy in which mucositis is predominantly of grade 3 or 4.

Proliferative leukoplakia: Proposed new clinical diagnostic criteria.

OBJECTIVE: We aimed to characterize proliferative verrucous leukoplakia (PVL) from a clinical and histopathological standpoint and suggest an updated classification. SUBJECTS AND METHODS: Records of patients seen at three oral medicine centers with a clinical diagnosis of PVL were reviewed for clinical and histopathological features and malignant transformation (MT). RESULTS: There were 42 patients (median age: 69 years [range: 36-88]; 35 females). 12.2% were current smokers. Family history of cancer was present in 43.7% of patients. Partial demarcation of lesion margins was present in 31.3% of lesions, followed by verrucous (27.5%), smooth (22.7%) erythematous (22.3%), and fissured (18.3%) appearance. Large and contiguous and multisite and non-contiguous lesions comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had prominent erythema (erythroleukoplakia). The most common histopathological diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT occurred in 71.4% patients after a median of 37 months [range: 1-210] from initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION: The generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL because 18.3% were fissured and 22.7% erythematous. We also propose the term proliferative erythroleukoplakia to more accurately describe the subset of PL with prominent erythema, which had the highest MT rate.

[Medicaments and oral healthcare. Systematic review of the -literature assessing the effect of drugs on the salivary glands]. / Serie: Medicamenten en mondzorg.Systematisch literatuuronderzoek naar effect van medicatie op de speekselklieren.

Evidence-based reviews of drugs causing medication-induced salivary gland dysfunction, such as xerostomia (sensation of oral dryness) and subjective sialorrhea are lacking. To compile a list of medicaments that influence salivary gland function, electronic databases were searched for relevant articles published up to June 2013. A total of 269 papers out of 3,867 records located satisfied the inclusion criteria (relevance, quality of methodology, strength of evidence). A total of 56 active substances with a higher level of evidence and 50 active substances with a moderate level of evidence of causing salivary gland dysfunction are described in this article. While xerostomia was a commonly reported outcome, the objective effect on salivary secretion was rarely measured. Xerostomia was, moreover, mostly reported as a negative side effect instead of the intended effect of that drug. A comprehensive list of medications having documented effects on salivary gland function or symptoms was compiled, which may assist practitioners in assessing patients who complain of dry mouth while taking medications.

Homozygous deletion of RAG1, RAG2 and 5' region TRAF6 causes severe immune suppression and atypical osteopetrosis.

Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. A biallelic microdeletion encompassing the 5' region of TRAF6, RAG1 and RAG2 genes was identified. TRAF6, a tumor necrosis factor receptor-associated family member, plays an important role in T cell signaling and in RANKL-dependent osteoclast differentiation and activation but its role in human OP has not been previously reported. The RAG proteins are essential for recombination of B and T cell receptors, and for the survival and differentiation of these cells. This is the first study to report a homozygous deletion of TRAF6 as a cause of human disease.

Tumor-induced osteomalacia: experience from a South American academic center.

The majority of tumor-induced osteomalacia cases have been reported in the Northern Hemisphere and Asia. In this first series of South American patients, we show that the clinical presentation and sensitivity of plasmatic fibroblast growth factor 23 and somatostatin analog-based imaging are similar to those described in other populations. INTRODUCTION: Describe the experience of clinical presentation, diagnostic study, and treatment of patients with tumor-induced osteomalacia (TIO) in a South American academic center in comparison to literature. METHODS: Analysis of the records of patients diagnosed with TIO. The clinical presentation, diagnostic studies, and treatment were analyzed. Fibroblast growth factor 23 (FGF23) was measured by ELISA. RESULTS: Six patients were diagnosed with TIO during the studied period. The patients' median age was 53 years (range 22-64). All patients presented with weakness and pain in the extremities. Four experienced fractures during their evolution. The median time to diagnosis was 4.5 years (1-20). Biochemical studies showed hypophosphatemia, median of 1.4 mg/dL (1.2-1.6), with low maximum rates of tubular reabsorption of phosphate adjusted for glomerular filtration rate. FGF23 was elevated in 4/6 patients and inappropriately normal in the other two. In three patients, the location of the tumor was clinically evident and confirmed with anatomical imaging. In the remaining patients, two tumors were located with 68Ga DOTATATE-PET/CT and one with OctreoScan. The causal tumors were located in the lower extremities in five patients and invading the frontal sinus in one patient. In all patients, tumors were successfully removed. Within 14 days, there was normalization of phosphate and FGF23 levels and resolution of clinical symptoms in all patients. In all cases, the histopathology was compatible with a phosphaturic mesenchymal tumor. CONCLUSIONS: The clinical presentation, delay time to diagnosis, FGF23 diagnostic sensitivity and histopathology in this first series of South American patients is similar to those described in other populations. The success of localization by somatostatin analog-based imaging, suggests this may the optimal imaging modality.

Oral mucous membrane pemphigoid and pemphigus vulgaris-a retrospective two-center cohort study.

OBJECTIVES: Few studies have compared oral mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Descriptive analysis of oral features, extent of extra-oral involvement, and management outcomes were performed. SUBJECTS AND METHODS: Patients with PV and MMP, the latter with exclusive oral involvement at first presentation, were included. RESULTS: There were 26 MMP (46%) and 31 PV (54%) patients. Desquamative gingivitis was evident in 84% of MMP cases compared to 28% of PV cases (P < 0.05). Non-gingival lesions were noted in 6% of MMP cases compared to 55% of PV cases (P < 0.01). Management of MMP consisted of only topical corticosteroids in 88% of cases while 12% of cases required concomitant systemic therapy. All PV cases (100%) required systemic therapy. No patients with MMP developed scarring or ocular lesions, and one patient (4%) developed cutaneous lesions. Five PV cases (16%) had oral cavity involvement only with three (60%) developing pharyngeal involvement and two (40%) developing cutaneous lesions on follow-up. CONCLUSION: Oral MMP presents primarily as desquamative gingivitis, infrequently involving extragingival sites, and is highly amenable to topical therapy, while PV is a systemic mucocutaneous disease with extensive non-gingival oral lesions that almost always requires systemic therapy.

Consistency of heterogeneous synchronization patterns in complex weighted networks.

Synchronization within the dynamical nodes of a complex network is usually considered homogeneous through all the nodes. Here we show, in contrast, that subsets of interacting oscillators may synchronize in different ways within a single network. This diversity of synchronization patterns is promoted by increasing the heterogeneous distribution of coupling weights and/or asymmetries in small networks. We also analyze consistency, defined as the persistence of coexistent synchronization patterns regardless of the initial conditions. Our results show that complex weighted networks display richer consistency than regular networks, suggesting why certain functional network topologies are often constructed when experimental data are analyzed.

Toxicodynetics in nordiazepam and oxazepam overdoses.

OBJECTIVES: Toxicodynetics aims at defining the time-course of major clinical events in drug overdose. We report the toxicodynetics in mono-intoxications with oxazepam and nordiazepam. METHODS: Cases of oxazepam or nordiazepam overdoses collected at the Paris poison control centre from 1999 to 2014 on the basis of self-report. A particular attention was paid to eliminate the concomitant alcohol or psychotropic co-ingestions. The toxicodynetic parameters were assessed as previously described. Results are expressed using 10-90 percentiles. In adults, the dose was normalized (TI, toxic Index) by dividing the supposed ingested dose by the maximal recommended dose. RESULTS: Two hundred and fifty-one and 74 cases of oxazepam and nordiazepam poisonings were included, respectively. The Emax for oxazepam and nordiazepam were sleepiness or obtundation in 106 and 36 cases, respectively. Coma was used to qualify only one oxazepam overdose. The median delay in onset of the Emax was 1.5h (0.33-15) in nordiazepam and 4h (0.5-15) in oxazepam overdose. In both overdoses, the onset of Emax occurred on an "on-off" mode. In adults, the greatest TIs in nordiazepam and oxazepam overdoses were 45 and 26.7, respectively. The TI in the oxazepam-induced coma was 26.7, the largest dose. CONCLUSION: Data collected in PCC allow determining a number of toxicodynetic parameters. Toxicodynetics showed that nordiazepam is not a cause of coma even in large overdose while oxazepam causes coma only at a very high dose. Deep coma in nordiazepam overdose whatever the dose and deep coma in overdose with oxazepam involving TI less than 20 result from unrecognized drug-drug interaction.

World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction.

The aim of this paper was to perform a systematic review of the pathogenesis of medication-induced salivary gland dysfunction (MISGD). Review of the identified papers was based on the standards regarding the methodology for systematic reviews set forth by the World Workshop on Oral Medicine IV and the PRISMA statement. Eligible papers were assessed for both the degree and strength of relevance to the pathogenesis of MISGD as well as on the appropriateness of the study design and sample size. A total of 99 papers were retained for the final analysis. MISGD in human studies was generally reported as xerostomia (the sensation of oral dryness) without measurements of salivary secretion rate. Medications may act on the central nervous system (CNS) and/or at the neuroglandular junction on muscarinic, α-and ß-adrenergic receptors and certain peptidergic receptors. The types of medications that were most commonly implicated for inducing salivary gland dysfunction were those acting on the nervous, cardiovascular, genitourinary, musculoskeletal, respiratory, and alimentary systems. Although many medications may affect the salivary flow rate and composition, most of the studies considered only xerostomia. Thus, further human studies are necessary to improve our understanding of the association between MISGD and the underlying pathophysiology.

Reflectance confocal microscopy for the diagnosis of vulvar naevi: six cases.

BACKGROUND AND OBJECTIVES: The differential diagnosis between vulvar naevi and melanoma is challenging. In vivo reflectance-mode confocal microscopy (RCM) is an emerging technique that allows non-invasive high-resolution imaging of the skin and mucosa. It has recently been used for the study of vulvar melanosis and melanoma, but it has not been so far employed for the diagnosis of genital naevi. The objective of this study is to evaluate RCM features of vulvar naevi and to compare them with dermoscopical and histopathological aspects. METHODS: Clinical, dermoscopical, in vivo RCM and histological features of six vulvar naevi were evaluated. RESULTS: The clinical and/or dermoscopical aspects were suspicious in all six cases. RCM showed a blue naevus, an atypical genital naevus, a junctional naevus and three compound naevi that were later confirmed by histological examination. In one compound naevus, RCM showed focal cytological atypia and architectural irregularity without clear features of malignancy, confirmed by histological examination. CONCLUSIONS: Reflectance-mode confocal microscopy can play a role in non-invasive diagnosis of vulvar naevi, but further broader studies are required to validate our observations.

Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease.

INTRODUCTION: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare, treatable, beta-oxidation disorder responsible for neuromuscular symptoms in adults. This case series describes the clinical and biochemical features of 13 French patients with late-onset MADD. METHODS AND RESULTS: Thirteen ambulant patients (eight women, five men), with a median age at onset of 27 years, initially experienced exercise intolerance (n=9), isolated muscle weakness (n=1) and a multisystemic pattern with either central nervous system or hepatic dysfunction (n=3). During the worsening period, moderate rhabdomyolysis (n=5), a pseudomyasthenic pattern (n=5) and acute respiratory failure (n=1) have been observed. Weakness typically affected the proximal limbs and axial muscles, and there was sometimes facial asymmetry (n=3). Moderate respiratory insufficiency was noted in one case. Median baseline creatine kinase was 190IU/L. Lactacidemia was sometimes moderately increased at rest (3/10) and after exercise (1/3). The acylcarnitine profile was characteristic, with increases in all chain-length acylcarnitine species. Electromyography revealed a myogenic pattern, while muscle biopsy showed lipidosis, sometimes with COX-negative fibers (n=2). The mitochondrial respiratory chain was impaired in five cases, with coenzyme Q10 decreased in two cases. All patients harbored mutations in the ETFDH gene (four homozygous, seven compound heterozygous, two single heterozygous), with nine previously unidentified mutations. All patients were good responders to medical treatment, but exercise intolerance and/or muscular weakness persisted in 11 of them. CONCLUSION: Late-onset forms of MADD may present as atypical beta-oxidation disorders. Acylcarnitine profiling and muscle biopsy remain the most decisive investigations for assessing the diagnosis. These tests should thus probably be performed more widely, particularly in unexplained cases of neuromuscular and multisystemic disorders.