Gait dysfunction in Alzheimer disease.

Alzheimer's disease (AD) is the most common cause of age-associated dementia and will exponentially rise in prevalence in the coming decades, supporting the parallel development of the early stage detection and disease-modifying strategies. While primarily considered as a cognitive disorder, AD also features motor symptoms, primarily gait dysfunction. Such gait abnormalities can be phenotyped across classic clinical syndromes as well as by quantitative kinematic assessments to address subtle dysfunction at preclinical and prodromal stages. As such, certain measures of gait can predict the future cognitive and functional decline. Moreover, cross-sectional and longitudinal studies have associated gait abnormalities with imaging, biofluid, and genetic markers of AD across all stages. This suggests that gait assessment is an important tool in the clinical assessment of patients across the AD spectrum, especially to help identify at-risk individuals.

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP / Programas de optimización del uso de antimicrobianos en hospitales: guía de recomendaciones de expertos para actividades en poblaciones específicas, síndromes y otros aspectos (PROA-2) de la SEIMC, SEFH, SEMPSPGS y SEIP

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.(AU)

En 2012, las Sociedades Españolas de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), Farmacia Hospitalaria (SEFH) y Medicina Preventiva, Salud Pública y Gestión Sanitaria (SEMPSPGS) lideraron un documento de consenso que incluía recomendaciones para la implementación de Programas de optimización del uso de antimicrobianos (PROA) en hospitales de agudos en España. Si bien estas recomendaciones fueron críticas para el desarrollo de estos programas en muchos centros, actualmente es necesario establecer unas guías para la implementación de las actividades de los PROA en determinadas poblaciones de pacientes, síndromes clínicos y otros aspectos específicos que no se incluyeron en el documento previo o que desde entonces se han desarrollado significativamente. El objetivo de esta guía de recomendaciones de expertos es revisar la información disponible acerca de esas actividades en estas poblaciones o circunstancias de pacientes y proporcionar unas recomendaciones que sirvan de guía sobre ellas. Con este objetivo, la SEIMC, la SEFH y la SEMPSPGS, así como la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y la Sociedad Española de Infectología Pediátrica (SEIP), seleccionaron un panel de expertos que eligieron los diferentes aspectos a incluir en el documento. Debido a la ausencia de evidencia de alto nivel en la implementación de las diferentes actividades, el panel optó por realizar una revisión narrativa de la literatura de los diferentes aspectos, en los que las recomendaciones se acordaron por consenso. El documento se abrió para consulta pública a los miembros de estas sociedades para sus comentarios y sugerencias, que fueron revisadas y consideradas por el panel.(AU)

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP.

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.

Clinical Correlates of Common Acute Heart Failure Syndrome.

BACKGROUND: Acute heart failure (AHF) is a medical emergency with different clinical syndromes / presentations. The clinical syndrome guides management decisions, and stratifies prognosis. The most common clinical syndrome of AHF and its associates are not established in our practice. AIM: To determine the most common clinical syndrome of AHF and its correlates. MATERIALS AND METHODS: This was a prospective cross-sectional study of hospitalized AHF patients. It was conducted in the medical wards and emergency department of a tertiary hospital. Data on socio-demographic and clinical variables were obtained. Relevant data from electrocardiography and echocardiography were also documented. The data were managed as appropriate and p values less than 0.05 were considered statistically significant. RESULTS: AHF constituted 159 (15.8%) of 1,006 medical hospitalizations. The mean age was 63.21years, and males constituted 84 (52.8%). The mean left ventricular ejection fraction and systolic blood pressure were 36.83% and 119.81mmHg, respectively. The frequency of acute decompensated chronic heart failure (ADCHF) and acute de novo HF (ADNVHF) were 120 (75.5%) and 39 (24.5%), respectively. Precipitating factors and comorbidities were detected in 111 (69.8%) and 84 (52.6%), respectively. The association of AHF with comorbidities, precipitants, and blood pressure gave p values of 0.000, 0.012, and 0.000, respectively. CONCLUSION: AHF constitutes 15.8% of medical hospitalizations in our center. Acute decompensated chronic heart failure (ADCHF) is the most common AHF syndrome. It is associated with comorbidities, precipitating factors, and lower blood pressure. It should therefore be the first consideration in any patient presenting with AHF in the emergency.

CONTEXTE: L'insuffisance cardiaque aiguë (ICA) est une urgence médicale avec différents syndromes/présentations cliniques. Le syndrome clinique guide les décisions de gestion et stratifie le pronostic. Le syndrome clinique le plus courant de l'AHF et ses associés ne sont pas établis dans notre pratique. OBJECTIF: Déterminer le syndrome clinique le plus fréquent de l'AHF et ses corrélats. MATÉRIEL ET MÉTHODES: Il s'agissait d'une étude prospective transversale de patients hospitalisés pour une FHA. Elle a été menée dans les services de médecine et d'urgence d'un hôpital tertiaire. Des données sur les variables socio-démographiques et cliniques ont été obtenues. Les données pertinentes de l'électrocardiographie et de l'échocardiographie ont également été documentées. Les données ont été gérées de manière appropriée et les valeurs p inférieures à 0,05 ont été considérées comme statistiquement significatives. RÉSULTATS: L'AHF a constitué 159 (15,8%) des 1.006 hospitalisations médicales. L'âge moyen était de 63,21 ans, et les hommes constituaient 84 (52,8%). La fraction d'éjection ventriculaire gauche et la pression artérielle systolique moyennes étaient respectivement de 36,83 % et de 119,81 mmHg. La fréquence de l'insuffisance cardiaque chronique décompensée aiguë (ICCA) et de l'insuffisance cardiaque de novo aiguë (ICNA) était de 120 (75,5 %) et 39 (24,5 %), respectivement. Les facteurs précipitants et les comorbidités ont été détectés chez 111 (69,8%) et 84 (52,6%), respectivement. L'association de l'AHF avec les comorbidités, les facteurs précipitants et la pression artérielle a donné des valeurs p de 0,000, 0,012 et 0,000, respectivement. CONCLUSION: L'AHF constitue 15,8% des hospitalisations médicales dans notre centre. L'insuffisance cardiaque chronique décompensée aiguë (ICCA) est le syndrome d'AHF le plus fréquent. Il est associé à des comorbidités, des facteurs précipitants et une pression artérielle basse. Il devrait donc être la première considération chez tout patient se présentant aux urgences avec une IAH. Mots clés: Insuffisance Cardiaque aiguë, Syndromes cliniques.

A multicenter prospective study validated a nomogram to predict individual risk of dependence in ambulation after rehabilitation.

OBJECTIVES: To develop the Functional Risk Index for Dependence in Ambulation (FRIDA) score, a nomogram to predict individual risk of dependence in ambulation at discharge from postacute rehabilitation and validate its performance temporally and spatially. STUDY DESIGN AND SETTING: We analyzed the database of a multicenter prospective observational quality cohort study conducted from January 2012 to March 2016, including data from 8,796 consecutive inpatients who underwent rehabilitation after stroke, hip fracture, lower limb joint replacement, debility, and other neurologic, orthopedic, or miscellaneous conditions. RESULTS: A total of 3,026 patients (34.4%) were discharged dependent in ambulation. In the training set of 5,162 patients (58.7%), Lasso-regression selected advanced age, premorbid disability, and eight indicators of medical and functional adverse syndromes at baseline to establish the FRIDA score. At the temporal validation obtained on an external set of 3,234 patients (41.3%), meta-analyses showed that the FRIDA score had good and homogeneous discrimination (summary area under the curve 0.841, 95% confidence interval = 0.826-0.855, I2 = 0.00%) combined with accurate calibration (summary Log O/E ratio 0.017, 95% confidence interval -0.155 to 0.190). These performances remained stable at spatial validation obtained on 3,626 patients, with substantial heterogeneity of estimates across nine facilities. Decision curve analyses showed that a FRIDA score-supported strategy far outperformed the usual "treat all" approach in each impairment categories. CONCLUSION: The FRIDA score is a new clinically useful tool to predict an individual risk for dependence in ambulation at rehabilitation discharge in many different disabilities, and may also reflect well the case-mix composition of the rehabilitation facilities.

Cytokine Release Syndrome and Sepsis: Analogous Clinical Syndromes with Distinct Causes and Challenges in Management.

Both cytokine release syndrome (CRS) and sepsis are clinical syndromes rather than distinct diseases and share considerable overlap. It can often be challenging to distinguish between the two, but it is important given the availability of targeted treatment options. In addition, several other clinical syndromes overlap with CRS and sepsis, further making it difficult to differentiate them. This has particularly been highlighted in the recent coronavirus disease-2019 pandemic. As we start to understand the differences in the inflammatory markers and presentations in these syndromes, hopefully we will be able to enhance treatment and improve outcomes.

Characteristics of hospital admissions for pulmonary alveolar proteinosis: analysis of the nationwide inpatient sample (2012-2014).

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome involving the accumulation of lipid-rich proteinaceous material in the alveoli. There is a paucity of published studies on this condition. To better characterize the demographics, complication rates, mortality, and healthcare costs of patients hospitalized for PAP in the United States, a secondary analysis on the Hospital Cost and Utilization Project's Nationwide Inpatient Sample (NIS) was performed on patients admitted from 2012 to 2014 with a diagnosis of pulmonary alveolar proteinosis. METHODS: Using the NIS database, a secondary analysis was performed on 500 admissions with the diagnosis "pulmonary alveolar proteinosis." The clinical variables and outcome measures extracted were: patient demographics, hospital costs, length of stay, frequency of admissions, and inpatient mortality rate. RESULTS: Among a weighted estimate of 500 hospital admissions from 2012 to 2014, the number of PAP admissions averaged 4.7 per million. The population was predominantly male (55%) with a mean age of 41.45 (CI 38.3-44.5) from all socioeconomic levels. Inpatient mortality was calculated to be 5%, which may result from the fact that the majority of admitted patients had few or no comorbid conditions (CCI 0.72). The most common procedure performed during admission was a bronchoalveolar lavage. Mean length of stay was 6.2 days (CI 3.9-8.5) and average cost of admission was $29,932.20 (CI 13,739-46,124). Of note, 50% of these admissions were considered "elective." CONCLUSIONS: Demographics of patients with PAP who have been hospitalized in the United States are similar to previously reported demographics from prior patient cohorts, specifically a male predominance and a mean age in the 40 s. The inpatient mortality rate of 5% we found is consistent with prior studies demonstrating good disease-specific survival rates. Notably, the cost per admission and overall annual cost associated with PAP hospitalization was calculated to be $29932.20 and $5 million respectively. This reflects the high economic cost associated with hospitalization of PAP patients, and provokes thought about ways to make treatment more cost-effective.

Acute Clinical Syndromes and Suspicion of SARS-CoV-2 Infection: The Experience of a Single Romanian Center in the Early Pandemic Period.

Background and Objectives: During the coronavirus disease 2019 (COVID-19) pandemic, patients with chronic diseases suffering exacerbations have required acute medical care. The purpose of our study was to determine useful criteria for the differentiation of patients with acute clinical syndromes and suspicion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Materials and Methods: This was an observational retrospective study, conducted in an internal medicine clinic from April to May 2020. We collected clinical, biological, and computed tomography (CT) data on patients with exacerbations of chronic diseases and clinical suspicion of SARS-CoV-2 infection. Patients with an already-positive real-time reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 on presentation at the emergency department were excluded from our study. Results: Of 253 suspected cases, 20 were laboratory-confirmed as having SARS-CoV-2 infection by RT-PCR, whereas COVID-19 diagnosis was ruled out in the remaining 233. Venous thromboembolism (VTE) correlated significantly with COVID-19 diagnosis in suspected patients, while laboratory markers were not significantly different between the two groups. Of the suspected patients, significantly higher percentages of dry cough, fever, myalgias, sore throat, loss of smell and appetite, and ground-glass opacities (GGOs) on CT were found in SARS-CoV-2-positive individuals. Conclusions: The study demonstrated that, until receiving the result of an RT-PCR test for SARS-CoV-2 (usually 12-24 h), association with VTE as a comorbidity, fever, dry cough, and myalgia as clinical features, and GGO on CT are the main markers for the identification of COVID-19 patients among those suspected with acute clinical syndromes. Our results also provide evidence for doctors not to rely solely on biological markers in the case of suspected SARS-CoV-2 infection in patients with exacerbations of chronic diseases. These data are useful for faster decision-making with regard to suspected COVID-19 patients before receiving RT-PCR test results, thus avoiding keeping patients in crowded emergency departments.

Posterior cord syndrome: Demographics and rehabilitation outcomes.

Context/Objectives: To describe demographics, clinical characteristics, and functional outcomes of patients with incomplete spinal cord injuries and posterior cord syndrome (PCS).Design: Five-year retrospective case series.Setting: Spinal cord injury (SCI) rehabilitation unit at a Level 1 tertiary university medical center.Participants: 9 patients with incomplete cord injuries diagnosed with PCS admitted to rehabilitation within the past 5 years.Outcome measures: Functional Independence Measure (FIM) motor scores, length of stay (LOS), discharge disposition.Results: Incidence of PCS was 2% with an average age of 62.0 years. The most common etiology for PCS was spinal cord compression from localized tumors (78%). Seven (78%) patients had paraparesis. All patients had an American Spinal Injury Association impairment scale (AIS) classification of AIS D. SCI-related complications most commonly included: neuropathic pain (78%), spasticity (44%), and neurogenic bladder (78%). Average LOS on the rehabilitation unit was 28 days. Average admission and discharge FIM motor scores were significantly improved (P = 0.001) from 41 to 65, respectively. Two-thirds (67%) of patients were able to walk at least 150 feet with a rolling walker prior to discharge. Most (78%) patients were discharged to home. Continence improved from admission to discharge from 22% vs 56% (bladder) and 67% vs 78% (bowel).Conclusions: We can conclude that PCS most often results in paraparesis due to tumor compression. Typical SCI-related medical complications are encountered. These patients often experience significant functional improvements during SCI rehabilitation with the majority also having bladder and bowel continence allowing them to return home at discharge.

Data Mining-Based Macroscopic Exploration of Clinical Medication of Chinese Medicine for Liver Cancer / 中国实验方剂学杂志

Objective:To explore the macroscopic medication rule of Chinese medicine for the treatment of primary liver cancer and provide references for clinical medication. Method:The databases of CNKI，VIP， and Wanfang Data were searched for research articles published from September 1959 to June 2019 with the terms of "Chinese medicine" and "liver cancer". A database was established based on the collected Chinese medicinal prescriptions for the treatment of primary liver cancer. The frequency，clustering， and association rules were analyzed by Excel， etc. Result:In this study，106 effective articles were included，and after the modified prescriptions were removed， 92 effective prescriptions were screened out，involving 281 Chinese herbal medicines used for 1 181 times in total. The top 5 high-frequency drugs were Poria （deficiency-tonifying），Astragali Radix （heat-clearing），Bupleuri Radix （blood-activating and stasis-resolving），Paeoniae Radix Alba （urination-promoting and dampness-draining）， and Codonopsis Radix （Qi-regulating）. The analysis of drug flavor with a frequency higher than 10 showed that most of the drugs were sweet，bitter， and pungent in flavor，cold，warm， and plain in nature，and acted on spleen and liver meridians. Four combinations and 10 herbal pairs were obtained by the cluster analysis of high-frequency drugs and association analysis， respectively. The high-frequency drugs and potential herbal pairs were classified targeting the specific clinical syndromes in different stages of liver cancer. Conclusion:Replenishing Qi， invigorating spleen，clearing heat， removing toxin，activating blood， and resolving stasis were the basic principles for the treatment of primary liver cancer. The combination of those drugs was the main therapeutic strategy. In addition，the resulting 10 potential herbal pairs from high-frequency drugs and cluster analysis could inspire the clinical treatment of primary liver cancer in different clinical stages with various clinical syndromes， which was of reference value for the clinical medication.

Analysis of Animal Models of Constipation Based on Characteristics of Clinical Symptoms of Traditional Chinese and Western Medicine / 中国实验方剂学杂志

Constipation is a common functional gastrointestinal disease with obstructive constipation， prolonged defecation time， or difficulty in defecation as the main symptoms， its prevalence is increasing year by year. Copying the animal model that is highly consistent with the clinical characteristics of traditional Chinese medicine （TCM） and western medicine is the basis for the related research on constipation. Based on the clinical characteristics， etiology and pathogenesis， clinical diagnostic criteria and TCM syndrome differentiation of constipation， a comparative analysis of the anastomosis between common animal models and clinical symptoms was carried out. Existing animal models of constipation were mostly drug induction and non-pharmaceutical intervention methods， and the modeling method was relatively simple， which was different from the multi-factors of constipation in clinical practice， and the evaluation indicators were mainly charcoal-powder propelling rate， defecation function， colon tissue and serum biochemical indicators. TCM syndrome differentiation lacked perfect evaluation system， such as laborious defecation， palpitation， shortness of breath， forgetfulness， cold pain in the abdomen， and other indicators that had not been embodied in the animal models， and the observation indicators were inconsistent with the diagnostic criteria of TCM. The same pathogenic factor could cause different syndromes， such as shortness of breath and fatigue， hot flashes and night sweats in the diagnostic criteria of TCM. Therefore， it is necessary to further explore the animal model of constipation that is highly consistent with the clinical characteristics of TCM and western medicine， in order to promote clinical treatment of constipation.

Personality Profiles and Psychological Adjustment in Breast Cancer Patients.

Dispositional personality characteristics may play a role in psychosocial adjustment to any disease, including cancer. PURPOSE: The purpose of this study is to identify personality profiles in breast cancer patients and to determine whether these profiles are associated with psychological adjustment or psychopathology. METHODS: Participants were 109 women (mean age, 52.01) diagnosed with breast cancer. They completed the Millon Clinical Multiaxial Inventory-III (MCMI-III), the Life Orientation Test-Revised (LOT-R), the Satisfaction with Life Scale, and the Positive and Negative Affect Scales. RESULTS: The analysis revealed two different personality profiles: (a) one group, comprising 38.23% of the sample, was characterized by paranoid, negativistic, and dependent personality traits and was considered as a "vulnerable group"; and (b) another group (61.77%) was characterized by compulsive, histrionic, and narcissistic personality traits and was considered as a "psychologically adjusted group". The vulnerable group scored higher than the psychologically adjusted group on all clinical syndromes, with scores above 60 on the anxiety, somatoform, dysthymic, and bipolar scales (score on anxiety being above 75); in contrast, the psychologically adjusted group did not reach a base rate score of 60 on any of the clinical syndromes, showing no manifestations of psychopathology. Additionally, the vulnerable group scored lower than the psychologically adjusted group on optimism, life satisfaction, and positive affect, but higher on negative affect. CONCLUSIONS: The results suggest that personality traits could affect the psychological adjustment of breast cancer survivors. We discuss the implications of belonging to each group and highlight the importance of early identification of vulnerable women in order to facilitate clinical and psychological support.

Clinical syndrome of childhood asthma based on key indicators detection.

This study was conducted to investigate the clinical syndromes of asthma in children based on the detection of key indicators. A total of 50 children with asthma were selected based on the asthma diagnostic methods categorised according to cough, wheezing, sputum and wheezing sound. The levels of D-dimer (DD) and fibrinogen (Fg) in plasma and blood gas analysis were also measured. The diagnostic symptoms were divided into TCM diagnostic statistics and western medicine diagnostic scores. The analysis showed male children to be affected much more than female children, and the age of 2-5 years was more common. Blood tests showed that the plasma levels of DD and Fg in children with acute asthma increased significantly. The onset of asthma in children was closely related to history of allergy and family inheritance. More than half of the children had a history of allergy. Respiratory tract infection caused by cold air was the most important cause of asthma in children. Most children with asthma were febrile with cough (moderate to severe) and sputum. The syndromes in this study included wind-heat syndrome, lung-qi deficiency syndrome and wind-cold syndrome, which could lay a foundation for the prevention, diagnosis and treatment of asthma in children.

Genotype-phenotype correlates of infantile-onset developmental & epileptic encephalopathy syndromes in South India: A single centre experience.

INTRODUCTION: A paucity of literature exists on genotype- phenotype correlates of 'unknown-etiology' infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE METHODS: An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016-2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification. Yield was considered based on demonstration of pathogenic/likely pathogenic variants only and variants of unknown significance (VUS) were documented. RESULTS: Pathogenic/likely pathogenic variants were identified in 26 (31.7 %) out of 82 children with DEE. These included those variants responsible for primarily DEE- 21(76.7 %); neuro-metabolic disorders- 3(18.6 %) and chromosomal deletions- 2(4.7 %). Of these patients, early-infantile epilepsy onset ≤ 6 months age was noted in 22(84.6 %). The DEE studied included Ohtahara syndrome associated with STXBP1 and SCN8A variants with yield of 50 % (2/4 tested); early myoclonic encephalopathy (no yield in 2); West syndrome with CDKL5, yield of 13.3 % (2/15 tested); epilepsy of infancy with migrating partial seizures due to CACNA1A and KCNT1 variants, yield of 67 % (2/3 tested); DEE-unclassified with KCNQ2, AP3B2, ZEB2, metabolic variants (SUOX, ALDH7A1, GLDC) and chromosome deletions (chr 1p36, chr2q24.3); yield of 32 % (8/25 tested). Patients with Dravet syndrome/Dravet-like phenotypes (N = 33) had variants in SCN1A (N = 10), SCN1B, CHD2; yield of 36.4 % (12/33 tested; 57.1 % from NGS). Eighteen patients with potential variants (SCN1A, SCN2A, SCN8A, KCNQ2, ALDH7A1 which also included VUS) could be offered targeted therapy. CONCLUSIONS: Our study confirms a good yield of genetic testing in neonatal and infantile-onset DEE provided robust phenotyping of infants is attempted with prognostic and therapeutic implications, particularly relevant to centres with resource constraints.

Outcomes of Spinal Cord Injury: WFNS Spine Committee Recommendations.

This comprehensive review article aims to provide some definitive statements on the factors like clinical syndromes, radiological findings, and decompressive surgery, that may influence the outcomes in cervical spinal cord injury management. Literature search on these factors published in the last decade were analyzed and definite statements prepared and voted for consensus opinion by the WFNS Spine Committee members and experts in this field at a meeting in Moscow in June 2019 using Delphi method. This was re-evaluated in a meeting in Pakistan in November 2019. Finally, the consensus statements were brought out as recommendations by the committee to the world literature. Traumatic Spinal Cord Syndromes have good prognosis except in elderly and when the presenting neurological deficit was very poor. Though conservative management provides satisfactory results, results can be improved with surgery when instability and progressive compression was present. Locked facet with spinal cord injury denotes poor prognosis. Magnetic resonance imaging T2 imaging is the essential prognostic indicator that apart from sagittal grade, length of injury, maximum canal compromise, maximum spinal cord compression, axial grading (BASIC) score. Diffusion tensor imaging is the next promising predictor in the pipeline. Decompressive surgery when done earlier especially within 24 hours of injury provides better result and there is no clear evidence to show medical management is better or equivalent to delayed surgical management. Clinical syndromes, radiological syndromes, and surgical decompression have strong impact on the out comes in the management of cervical spinal cord injury. Our comprehensive review and final recommendations on this subject will be of great importance in understanding the complex treatment methods in use.

Which Psychopathological Syndromes Could Be Associated with the Risk of Suicide among Substance Users?

Background: Research has shown that suicide is a highly present phenomenon among the drug dependent population. Moreover, individuals with substance use disorder (SUD) present high psychopathological comorbidity. This study aimed to describe which clinical syndromes are linked to the presence of risk of suicide. Methods: The study was based on a consecutive non-probabilistic convenience sample of 196 patients who attended the Public Addiction Center in Girona (Spain). Sociodemographic data, as well as suicide risk and drug related characteristics, were recorded. The risk of suicide was assessed with the Spanish version of "risk of suicide". Complicated grief was assessed with the Spanish version of the Inventory of Complicated Grief. Clinical syndromes were measured with the Spanish version of MCMI-III. Results: The syndromes most frequently associated with the presence of risk of suicide were complicated grief, major depression and thought disorder. Conclusions: Different psychopathological syndromes were identified in relation to risk of suicide among patients with SUD. The present results highlight the importance of accurately diagnosing those individuals.

First-line Chemotherapy Responsiveness and Patterns of Metastatic Spread Identify Clinical Syndromes Present Within Advanced KRAS Mutant Non-Small-cell Lung Cancer With Different Prognostic Significance.

BACKGROUND: Unsuccessful KRAS-specific treatment approaches in non-small-cell lung cancer (NSCLC) might reflect underlying disease heterogeneity. We sought to define clinical "syndromes" within advanced KRAS mutant NSCLC to improve future clinical trials and create a clinical framework for future molecular development. PATIENTS AND METHODS: To test a series of a priori hypotheses regarding KRAS-mutant NSCLC clinical syndromes, we conducted a multi-institutional retrospective medical record review. Survival probabilities were estimated using the Kaplan-Meier model. Between-group differences were assessed using the log-rank test. Multivariate Cox regression analyses and Wilcoxon rank sum testing were used to assess progression-free survival and overall survival (OS) differences. RESULTS: Among 218 patients with advanced KRAS-mutant NSCLC, OS and progression-free survival with first-line chemotherapy did not differ by intrathoracic versus extrathoracic spread, smoking intensity, or the specific KRAS mutation. Metastatic disease at diagnosis resulted in significantly worse OS than recurrent, unresectable disease (median OS, 14.6 vs. 40.9 months; P = .001). Among the patients with metastatic disease at diagnosis, nonscalp, soft tissue metastases (syndrome X; 6% of cases; 95% confidence interval [CI], 2.5%-10.1%) signified a poor prognosis (median OS, 7.5 vs. 15.9 months for the controls; P = .021). The response to first-line chemotherapy (syndrome Y; 41% of cases; 95% CI, 32.3%-50.6%) signified a good prognosis (median OS, 26.7 vs. 11.9 months; P = .002). The overlap between these 2 syndromes was minimal (2 of 111). Multivariate analysis confirmed these observations. The hazard ratio for death for syndromes X and Y was 2.64 (95% CI, 1.13-6.14) and 0.45 (95% CI, 0.28-0.76), respectively. CONCLUSION: Chemotherapy-responsive disease and nonscalp, soft tissue spread might represent distinct clinical syndromes within KRAS-mutant NSCLC. The molecular biology underlying this heterogeneity warrants future studies.

Clinical syndromes associated with Coenzyme Q10 deficiency.

Primary Coenzyme Q deficiencies represent a group of rare conditions caused by mutations in one of the genes required in its biosynthetic pathway at the enzymatic or regulatory level. The associated clinical manifestations are highly heterogeneous and mainly affect central and peripheral nervous system, kidney, skeletal muscle and heart. Genotype-phenotype correlations are difficult to establish, mainly because of the reduced number of patients and the large variety of symptoms. In addition, mutations in the same COQ gene can cause different clinical pictures. Here, we present an updated and comprehensive review of the clinical manifestations associated with each of the pathogenic variants causing primary CoQ deficiencies.

Predictors of early dropout in treatment for gambling disorder: The role of personality disorders and clinical syndromes.

Several treatment options for gambling disorder (GD) have been tested in recent years; however dropout levels still remain high. This study aims to evaluate whether the presence of psychiatric comorbidities predicts treatment outcome according to Millon's evolutionary theory, following a six-month therapy for GD. The role of severity, duration of the disorder, typology of gambling (mainly online or offline) and pharmacological treatment were also analysed. The recruitment included 194 pathological gamblers (PGs) to be compared with 78 healthy controls (HCs). Psychological assessment included the South Oaks Gambling Screen and the Millon Clinical Multiaxial Inventory-III. The "treatment failure" group (n = 70) comprised PGs who prematurely dropped out of the treatment whereas the "abstinent group" (n = 124) included PGs who completed the treatment regardless of whether the outcome was successful or not. As expected, the presence of psychiatric comorbidities was highlighted as a significant predictor in dropping out of the therapy. Specifically negativistic personality disorder, antisocial personality disorder, drug dependence and PTSD were associated with early dropout. These variables were predictive of treatment outcome independently from the typology of gambling, severity, duration of the disorder and pharmacological treatment. Implications for psychological and psychiatric care are discussed.

Personality disorders in cluster headache: a study using the Millon Clinical Multiaxial Inventory-III.

A great deal of studies suggests that cluster headache (CH) patients are usually comorbid to anxiety-mood spectrum disorders and psychopathological symptoms; however, the personality profiles reported in the literature strictly depend on type of assessment used. Psychiatric comorbidities have been extensively studied in migraine and they are recognized to represent a major risk factor associated with poorer outcome, playing a role in the headache chronification process at once as cause and consequence of it. By contrast the incidence and role of psychopathological aspects in CH is still not clarified, insufficiently explored as the striking severity of such a physical pain apparently leaves no room to psychological explanations. The aim of the present study is to describe psychopathological aspects of CH patients by means of the Millon Clinical Multiaxial Inventory-III (MCMI-III), a psychological assessment tool compatible to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) that correlates personality disorders (PDs) and clinical syndromes. We included all consecutive inward patients with CH between January 2014 and December 2016. Patients were evaluated using the MCMI-III a validated inventory assessing 14 PDs Scales (coordinate with DSM-IV Axis II disorders) and ten Clinical Syndrome Scales (coordinate with DSM-IV Axis I disorders). Twenty-six CH patients (24 chronic CH) were tested. Personality disorders were present in 92% of the patients. The most frequent PDs were: obsessive-compulsive (30.8%), histrionic (26.9%), narcissistic (11.5%), paranoid (11.5%) and avoidant (11.5%). According to the MCMI-III, patients with CH showed a high prevalence of personality disorders (Axis II-DSM-IV). PDs in CH patients can play an important role in determining CH course toward chronification. These preliminary results suggest that behavioral treatments can find room to support more conventional drug and neurostimulation therapies in these patients. In addition, the very high prevalence of PDs in our patients suggests that CH could in some cases be considered among the spectrum of somatoform and pain syndromes in patients with PDs.