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Frontiers in Oncology 2020The prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to...
Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis.
BACKGROUND
The prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to limited evidence. This study aimed to conduct an updated meta-analysis to re-investigate the predictive significance of PD-L1 expression.
METHODS
PubMed, EMBASE and Cochrane Library databases were searched. The associations between PD-L1 expression status and prognosis [overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), cancer-specific survival (CSS) or disease-free survival (DFS)], clinical parameters [FIGO stage, lymph node metastasis (LNM), tumor size, infiltration depth, lymphovascular space invasion (LVSI) or grade] and response to anti-PD-1/PD-L1 treatment [objective response rate (ORR)] were analyzed by hazard ratios (HR) or relative risks (RR).
RESULTS
Fifty-five studies were enrolled. Overall, high PD-L1 expression was not significantly associated with OS, PFS, RFS, CSS and DFS of gynecological cancers. However, subgroup analysis of studies with reported HR (HR = 1.27) and a cut-off value of 5% (HR = 2.10) suggested that high PD-L1 expression was correlated with a shorter OS of gynecological cancer patients. Further sub-subgroup analysis revealed that high PD-L1 expressed on tumor-infiltrating immune cells (TICs) predicted a favorable OS for ovarian (HR = 0.72), but a poor OS for cervical cancer (HR = 3.44). PD-L1 overexpression was also correlated with a lower OS rate in non-Asian endometrial cancer (HR = 1.60). High level of PD-L1 was only clinically correlated with a shorter PFS in Asian endometrial cancer (HR = 1.59). Furthermore, PD-L1-positivity was correlated with LNM (for overall, ovarian and endometrial cancer expressed on tumor cells), advanced FIGO stage (for overall, ovarian cancer expressed on tumor cells, endometrial cancer expressed on tumor cells and TICs), LVSI (for overall and endometrial cancer expressed on tumor cells and TICs), and increasing infiltration depth/high grade (only for endometrial cancer expressed on TICs). Patients with PD-L1-positivity may obtain more benefit from anti-PD-1/PD-L1 treatment than the negative group, showing a higher ORR (RR = 1.98), longer OS (HR = 0.34) and PFS (HR = 0.61).
CONCLUSION
Our findings suggest high PD-L1 expression may be a suitable biomarker for predicting the clinical outcomes in patients with gynecological cancers.
PubMed: 33634012
DOI: 10.3389/fonc.2020.572203 -
Neurological Sciences : Official... May 2021The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may... (Review)
Review
BACKGROUND AND PURPOSE
The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive theĀ appropriate treatment (e.g. thrombolysis).
METHODS
We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords "insular stroke" and "insular infarction", to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed.
RESULTS
We identified 25 reports including a total of 49 patients (59.7 Ā± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache.
CONCLUSIONS
The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations.
Topics: Aphasia; Cerebral Cortex; Dysarthria; Female; Humans; Male; Speech; Stroke
PubMed: 33575921
DOI: 10.1007/s10072-021-05109-1 -
Neurological Sciences : Official... Apr 2021Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in... (Review)
Review
BACKGROUND
Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies.
OBJECTIVE
This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis.
METHODS
We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-D-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed.
DISCUSSION
The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.
Topics: Basal Ganglia; Encephalitis; Humans; Tic Disorders; Tics; Tourette Syndrome
PubMed: 33486621
DOI: 10.1007/s10072-021-05065-w -
Journal of Neurology, Neurosurgery, and... Dec 2020Functional movement disorders (FMD) are proposed to reflect a specific problem with voluntary control of movement, despite normal intent to move and an intact neural...
Functional movement disorders (FMD) are proposed to reflect a specific problem with voluntary control of movement, despite normal intent to move and an intact neural capacity for movement. In many cases, a positive diagnosis of FMD can be established on clinical grounds. However, the diagnosis remains challenging in certain scenarios, and there is a need for predictors of treatment response and long-term prognosis.In this context, we performed a systematic review of biomarkers in FMD. Eighty-six studies met our predefined criteria and were included.We found fairly reliable electroencephalography and electromyography-based diagnostic biomarkers for functional myoclonus and tremor. Promising biomarkers have also been described for functional paresis, gait and balance disorders. In contrast, there is still a lack of diagnostic biomarkers of functional dystonia and tics, where clinical diagnosis is often also more challenging. Importantly, many promising findings focus on pathophysiology and reflect group-level comparisons, but cannot differentiate on an individual basis. Some biomarkers also require access to time-consuming and resource-consuming techniques such as functional MRI.In conclusion, there are important gaps in diagnostic biomarkers in FMD in the areas of most clinical uncertainty. There is also is a lack of treatment response and prognostic biomarkers to aid in the selection of patients who would benefit from rehabilitation and other forms of treatment.
Topics: Biomarkers; Brain; Conversion Disorder; Dystonia; Electroencephalography; Electromyography; Functional Neuroimaging; Gait Disorders, Neurologic; Humans; Magnetic Resonance Imaging; Movement Disorders; Myoclonus; Neuronal Plasticity; Paresis; Positron-Emission Tomography; Reaction Time; Tics; Tremor
PubMed: 33087421
DOI: 10.1136/jnnp-2020-323141 -
Neuroscience and Biobehavioral Reviews Dec 2020Tourette syndrome (TS) and chronic motor/vocal tic disorder (CTD) are neurodevelopmental conditions defined by the occurrence of multiple tics. Besides the well-known... (Review)
Review
Tourette syndrome (TS) and chronic motor/vocal tic disorder (CTD) are neurodevelopmental conditions defined by the occurrence of multiple tics. Besides the well-known association with attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), rage attacks (RA) represent common and detrimental symptoms for patients. Inorder to explore prevalence of RA in tic disorders, relation to tic severity/comorbidities and available treatments, we performed a systematic literature review based on PRISMA Guidelines. 32 studies published between January 2008 - December 2019 were deemed suitable for the analysis and provided a prevalence of 20-67 %. Most findings showed a direct correlation with tic severity and a significant impact on psychosocial functioning. Although apparently related to comorbid ADHD, RA also frequently occur as independent manifestations. Association with other comorbidities, such as OCD, impulse control and mood disorders has also been reported, not yet fully established. Behavioral interventions appear to be effective, whereas there is limited evidence concerning the efficacy of medication. In TS/CTD, RA may be regarded as a major comorbidity that requires clinical investigation in order to develop personalized treatments.
Topics: Attention Deficit Disorder with Hyperactivity; Comorbidity; Humans; Obsessive-Compulsive Disorder; Tic Disorders; Tics; Tourette Syndrome
PubMed: 32980398
DOI: 10.1016/j.neubiorev.2020.09.019 -
Current Alzheimer Research 2020Telephone-based cognitive assessments may be preferable to in-person testing in terms of test burden, economic and opportunity cost. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Telephone-based cognitive assessments may be preferable to in-person testing in terms of test burden, economic and opportunity cost.
OBJECTIVE
We sought to determine the accuracy of telephone-based screening for the identification of dementia or Mild Cognitive Impairment (MCI).
METHODS
Five multidisciplinary databases were searched. Two researchers independently screened articles and extracted data. Eligible studies compared any multi-domain telephone-based assessment of cognition to the face-to-face diagnostic evaluation. Where data allowed, we pooled test accuracy metrics using the bivariate approach.
RESULTS
From 11,732 titles, 34 papers were included, describing 15 different tests. There was variation in test scoring and quality of included studies. Pooled analyses of accuracy for dementia: Telephone Interview for Cognitive Status (TICS) (<31/41) sensitivity: 0.92, specificity: 0.66 (6 studies); TICSmodified (<28/50) sensitivity: 0.91, specificity: 0.91 (3 studies). For MCI: TICS-modified (<33/50) sensitivity: 0.82, specificity: 0.87 (3 studies); Telephone-Montreal Cognitive Assessment (<18/22) sensitivity: 0.98, specificity: 0.69 (2 studies).
CONCLUSION
There is limited diagnostic accuracy evidence for the many telephonic cognitive screens that exist. The TICS and TICS-m have the greatest supporting evidence; their test accuracy profiles make them suitable as initial cognitive screens where face to face assessment is not possible.
Topics: Cognitive Dysfunction; Humans; Interviews as Topic; Mental Status and Dementia Tests; Neuropsychological Tests; Reproducibility of Results
PubMed: 32589557
DOI: 10.2174/1567205017999200626201121 -
Journal of the Canadian Academy of... May 2020Agitation and aggression are commonly cited reasons for psychiatry consultation for individuals diagnosed with autism spectrum disorder (ASD). While risperidone and...
BACKGROUND
Agitation and aggression are commonly cited reasons for psychiatry consultation for individuals diagnosed with autism spectrum disorder (ASD). While risperidone and aripiprazole do not carry Health Canada approval for management of ASD-associated irritability, both are used for this indication but are not universally effective and carry substantial risk of adverse effects. This necessitates use of off-label medications to assist in management of behavioral dysregulation. Clonidine, an alpha-2 receptor agonist, is approved in Canada for treatment of hypertension. The evidence base also supports its use for attention deficit/hyperactivity disorder (ADHD) and for tics in Tourette's disorder. This review focuses on examining the literature regarding clonidine as a treatment of challenging behaviours in the ASD population.
METHOD
Systematic search of MEDLINE, EMBASE, and PsycINFO databases resulted in 540 unique records. Ten publications were relevant to this review.
RESULTS
Two cross-over studies, one open-label case series, and seven case reports were identified. One of two controlled studies suggested benefit from clonidine versus placebo. Caregivers typically noted improvement in behaviour with clonidine versus baseline. Clonidine was generally well-tolerated. Sedation was the most consistently reported adverse effect. Despite being an anti-hypertensive medication, few discontinued clonidine due to hypotension or bradycardia.
CONCLUSION
Clonidine has a limited evidence base for use in the management of behavioural problems in patients with ASD. Most evidence originates from case reports. Given the paucity of pharmacological options for addressing challenging behaviours in ASD patients, a clonidine trial may be an appropriate and cost-effective pharmaceutical option for this population.
PubMed: 32405312
DOI: No ID Found -
Neuroscience and Biobehavioral Reviews Jun 2020Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple tics. In addition to common behavioral co-morbidities such as...
Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple tics. In addition to common behavioral co-morbidities such as obsessive-compulsive disorder and attention-deficit and hyperactivity disorder, patients with TS can present with self-injurious behavior (SIB): deliberate, non-accidental, repetitive infliction of self-harm without suicidal intent. In order to determine the prevalence and clinical correlates of SIB in TS, we conducted a systematic literature review in accordance to the methodology described in the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies in Epidemiology. The literature search yielded 20 cohort studies that were suitable for quantitative synthesis. Combined results showed that SIB is present in 35 % of patients with TS. Obsessive-compulsive behaviors appear to be associated with SIB in patients with TS, and their presence should alert clinicians to the possible co-occurrence of SIB, particularly if the patient has multiple behavioral co-morbidities. Since the reviewed studies were methodologically heterogeneous and were conducted in specialist clinics, our findings cannot be generalized to patients with TS in the wider community.
Topics: Attention Deficit Disorder with Hyperactivity; Comorbidity; Humans; Obsessive-Compulsive Disorder; Prevalence; Self-Injurious Behavior; Tics; Tourette Syndrome
PubMed: 32205150
DOI: 10.1016/j.neubiorev.2020.03.022 -
Tijdschrift Voor Psychiatrie 2019Attention-deficit/hyperactivity disorder (ADHD) is a frequently occurring problem in child and adolescent psychiatry. Most prevalent comorbid disorders are oppositional...
Attention-deficit/hyperactivity disorder (ADHD) is a frequently occurring problem in child and adolescent psychiatry. Most prevalent comorbid disorders are oppositional defiant behavior, tics, autism spectrum disorder, anxiety and depression. Stimulants are the first pharmacological choice. Recently, long-acting guanfacin became available in Belgium and the Netherlands.
AIM: To investigate the efficacy of guanfacin on comorbid symptoms in ADHD.
METHOD: A systematic search in Medline and Cochrane databases for randomized controlled trials in which the effect of guanfacin on comorbid symptoms is evaluated.
RESULTS: Guanfacin had an effect on autism symptoms, oppositional defiant symptoms and possibly on tics in children and adolescents with adhd. On anxiety symptoms, no effect was reported. The effect on depression needs to be further investigated. The side effects of guanfacin are similar in comorbid disorders and pure ADHD.
CONCLUSION: Guanfacin is a treatment option for ADHD in children and adolescents with comorbid autism or behavioural symptoms and possibly also tics, as it has a demonstrated effect on these comorbid features. Further research is necessary in order to decide on the preference for a particular medication in ADHD with these various comorbid disorders.Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Comorbidity; Female; Guanfacine; Humans; Male; Tic Disorders; Treatment Outcome
PubMed: 31907899
DOI: No ID Found -
Neurological Sciences : Official... May 2020Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple motor and phonic tics, often associated with co-morbid behavioural...
BACKGROUND
Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple motor and phonic tics, often associated with co-morbid behavioural problems. Tics can be modulated by environmental factors and are characteristically exacerbated by psychological stress, among other factors. This observation has led to the development of specific behavioural treatment strategies, including relaxation therapy.
OBJECTIVE
This review aimed to assess the efficacy of relaxation therapy to control or reduce tic symptoms in patients with TS.
METHODS
We conducted a systematic literature review of original studies on the major scientific databases, including Medline, EMBASE, and PsycInfo, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes measures included both tic severity and tic frequency.
RESULTS
Our literature search identified three controlled trials, with a total number of 40 participants (range: 6-18 participants). In all three studies, relaxation therapy decreased the severity and/or the frequency of tic symptoms. However, the only trial comparing relaxation therapy to two other behavioural techniques found relaxation therapy to be the least effective intervention, as it reduced the number of tics by 32% compared to 44% with self-monitoring and 55% with habit reversal.
DISCUSSION
The results of this systematic literature review provide initial evidence for the use of relaxation therapy as a behavioural treatment intervention for tics in patients with TS. Caution is needed in the interpretation of these findings, because the reviewed trials had small sample sizes and there was high heterogeneity across the study protocols.
Topics: Humans; Relaxation Therapy; Tics; Tourette Syndrome; Treatment Outcome
PubMed: 31872351
DOI: 10.1007/s10072-019-04207-5