Development and Validation of a Dermoscopic Severity Score for Female Pattern Hair Loss

<b><i>Introduction:</i></b> Despite the high prevalence and impact on quality of life, there are no objective methods to estimate the severity of female pattern hair loss (FPHL). Here, we aimed to develop a dermoscopic severity score for FPHL. <b><i>Methods:</i></b> Cross-sectional study involving 76 women with FPHL and 12 controls. Standardized dermoscopic photos of the scalp were taken to evaluate the main findings of FPHL. The variable selection and their scores in the final model were defined by multivariate methods. Twenty participants were retested to assess the reliability, and 10 participants were tested before and after treatment for estimating its sensibility to change after 6 months. <b><i>Results:</i></b> Eight patients (11%) presented the Sinclair clinical scale grade I, 40 (53%) presented at grade II, 19 (25%) presented at grade III, and 9 (12%) presented at grades IV and V. In the multivariate exploration, the following variables were considered significant: total terminal hairs, total miniaturized hairs, brown peripilar sign, scalp honeycomb pigmentation, white peripilar sign, and yellow dots. The final model resulted in a high correlation (rho = 0.89) with the ranked clinical assessment. <b><i>Conclusion:</i></b> An objective and reliable severity score of FPHL was developed and validated, allowing its use as an additional outcome in therapeutic trials.

Cardiac involvement in sarcoidosis: Evolving concepts in diagnosis and treatment

Clinically evident cardiac involvement has been noted in at least 2 to 7% of patients with sarcoidosis, but occult involvement is much higher (> 20%). Cardiac Sarcoidosis (CS) is often not recognized as an antemortem, as sudden death may be the presenting feature. Cardiac involvement may occur at any point during the course of sarcoidosis and may occur in the absence of pulmonary or systemic involvement. Sarcoidosis can involve any part of the heart. The prognosis of CS is related to the extent and site(s) of involvement. Most deaths due to CS are due to arrhythmias or conduction defects, but granulomatous infiltration of the myocardium may cause progressive and ultimately lethal cardiomyopathy. The definitive diagnosis of isolated CS is difficult and the yield of Endomyocardial Biopsies (EMB) is low. Treatment of CS is often warranted even in the absence of histologic proof. Radionuclide scans are integral to the diagnosis. Gadolinium-enhanced cardiac magnetic imaging scans and 18Fluorodeoxyglucose (18FDG)-Positron Emission Tomography (PET) are the key imaging modalities to diagnose CS. The prognosis of CS is variable, but mortality rates of untreated CS are high. Randomized therapeutic trials have not been done, but corticosteroids (alone or combined with additional immunosuppressive agents) are the mainstay of therapy. Additionally, anti-arrhythmic agents and therapy for heart failure are often required. Because of the potential for sudden cardiac death, an Implantable Cardioverter-Defibrillator (ICD) should be placed in any patient with CS and serious ventricular arrhythmias or heart block and should be considered for cardiomyopathy. Cardiac transplantation is a viable option for patients with end-stage CS refractory to medical therapy.

Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment

Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians.

Targeted Therapies for the Neurofibromatoses

Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their spontaneous counterparts. Focus has shifted to therapy aimed at minimizing symptoms given the risks of persistent, multiple tumors and new tumor growth. In this review, we will highlight the translation of preclinical data to therapeutic trials for patients with neurofibromatosis, particularly neurofibromatosis type 1 and neurofibromatosis type 2. Successful inhibition of MEK for patients with neurofibromatosis type 1 and progressive optic pathway gliomas or plexiform neurofibromas has been a significant advancement in patient care. Similar success for the malignant NF1 tumors, such as high-grade gliomas and malignant peripheral nerve sheath tumors, has not yet been achieved; nor has significant progress been made for patients with either neurofibromatosis type 2 or schwannomatosis, although efforts are ongoing.

Clinical and biological markers for predicting ARDS and outcome in septic patients

Sepsis is a common cause of acute respiratory distress syndrome (ARDS) associated with a high mortality. A panel of biomarkers (BMs) to identify septic patients at risk for developing ARDS, or at high risk of death, would be of interest for selecting patients for therapeutic trials, which could improve ARDS diagnosis and treatment, and survival chances in sepsis and ARDS. We measured nine protein BMs by ELISA in serum from 232 adult septic patients at diagnosis (152 required invasive mechanical ventilation and 72 had ARDS). A panel including the BMs RAGE, CXCL16 and Ang-2, plus PaO2/FiO2, was good in predicting ARDS (area under the curve = 0.88 in total septic patients). Best performing panels for ICU death are related to the presence of ARDS, need for invasive mechanical ventilation, and pulmonary/extrapulmonary origin of sepsis. In all cases, the use of BMs improved the prediction by clinical markers. Our study confirms the relevance of RAGE, Ang-2, IL-1RA and SP-D, and is novel supporting the inclusion of CXCL16, in BMs panels for predicting ARDS diagnosis and ARDS and sepsis outcome.

Quantitative Digitography Solves the Remote Measurement Problem in Parkinson's disease

Background: Assessment of motor signs in Parkinson's disease (PD) has required an in-person examination. However, 50% of people with PD do not have access to a neurologist. Wearable sensors can provide remote measures of some motor signs but require continuous data acquisition for several days. A major unmet need is reliable metrics of all cardinal motor signs, including rigidity, from a simple short active task that can be performed remotely or in the clinic. Objective: Investigate whether thirty seconds of repetitive alternating finger tapping (RAFT) on a portable quantitative digitography (QDG) device, which measures amplitude and timing, produces reliable metrics of all cardinal motor signs in PD Methods: Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and clinical motor assessment. Eighteen individuals were followed longitudinally with repeated assessments for an average of three years and up to six years. Results: QDG-RAFT metrics differentiated individuals with PD from controls and provided validated metrics for total motor disability (MDS-UPDRS III) and for rigidity, bradykinesia, tremor, gait impairment and freezing of gait (FOG). Additionally, QDG-RAFT tracked disease progression over several years off therapy, and differentiated akinetic rigid from tremor dominant phenotypes, as well as people with from those without FOG. Conclusions: QDG is a reliable technology, which will improve access to care, allows complex remote disease management, and accurate monitoring of disease progression over time in PD. QDG-RAFT also provides the comprehensive PD motor metrics needed for therapeutic trials.

Lung function trajectory in progressive fibrosing interstitial lung disease

Proposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criterion remains unknown. Because survival is rarely employed as the primary endpoint in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design. A retrospective, multi-center longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centers (test cohort) and one UK center (validation cohort). One-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modeling. Subgroup analyses were performed to determine whether results varied across key subgroups. One thousand two hundred twenty-seven patients were included, with CTD-ILD predominating. Six of nine PF-ILD criteria were associated with differential one-year change in FVC, with radiologic progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiologic pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype. These findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria.

Presentation of Chemotherapy Options in Cachexia in the Literature: A Scientometric Evaluation

Background: Cachexia is a multifactorial syndrome characterized by weight loss, muscle wasting, and symptoms such as fatigue and anorexia. The primary aim of this study was to quantitatively and qualitatively examine the research trends and hotspots on chemotherapy options in cachexia.Methods: A scientometric analysis was carried out according to the Science Citation Index-Expended database in the Web of Science. By utilizing bibliometric software, the performance of the total articles was covered from records, authors and affiliations, journals and research categories, to burst references, citation relationship network, and the keywords co-occurrence overlay visualization.Results: A total of 1,111 articles were retrieved. The United States occupied the top position both on the total outputs and the cooperation with other countries. Journal of Cachexia, Sarcopenia and Muscle had the highest impact factor and the most publications. Eight main groups were clustered by the similarity of the research topic. Ongoing weight loss has been the main bottleneck either in mechanistic research or therapeutic trials. In addition to nutritional supplements, the major options for pharmacological therapy were progestational agents, such as megestrol acetate and corticosteroids. ‘Computed tomography’ and strategies dealing with ‘skeletal muscle mass’, ‘muscle mass’, ‘sarcopenia’ and ‘muscle atrophy’ might be the breakthrough for the future diagnosis and treatment of cachexia.Conclusions: We considered the publication information by summarizing the literature on the pharmacological treatment of cachexia. In summary, this study provides novel and useful data for related scientific research and will help researchers explore cachexia chemotherapy options more intuitively and effectively.

Migraine: beyond pain

Most people who see, treat or experience migraine will be aware that its clinical manifestations exceed the symptom of head pain. However, available acute treatments so far have targeted migraine symptoms only in the context of the pain phase of an attack. The associated disability clearly involves more than just these symptoms, and the phenotype can include additional painless features, including alterations in mood,cognition and homeostasis and sensory sensitivities. Recognising these symptoms, understanding their neurobiological basis and systematically recording them prospectively in clinical therapeutic trials are likely to offer valuable pathophysiological and therapeutic insights into this complex brain disorder, ultimately helping to improve the quality of lives of sufferers. We aim to explore the multifaceted disorder that is migraine, with a particular focus on the non-painful non-aura symptoms.