A pictorial view on false positive findings of 68Ga-PSMA-11 PET/CT and their prognostic value in patients with prostate carcinoma after radical prostatectomy and undetectable PSA values.

OBJECTIVE: Recently, gallium-68-prostate-specific membrane antigen-11 (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) has become a key imaging method in prostate carcinoma staging and biochemical progression, with varying sensitivities in different studies (from 40% to 80%). After four years of experience with 68Ga-PSMA-11 PET/CT, we found that it is possible to detect lesions with increased PSMA expression in patients with undetectable prostate specific antigen (PSA) levels after radical prostatectomy. The key questions we wanted to answer were as follows: if those lesions were malignant and could the early detection of those malignant lesions have a role in patient management? We aimed to identify and follow up PSMA-positive findings for a period of 4 years in patients with prostate cancer after radical prostatectomy and undetectable PSA values at the time of the examination. We also explored false-positive lesions in detail. SUBJECTS AND METHODS: The study included all patients who underwent radical prostatectomy and had undetectable PSA values <0.05ng/mL and who underwent 68Ga-PSMA-11 PET/CT between July 2019 and December 2019. We performed 220 studies and found 40 patients with these characteristics; these patients were included in this study. All of them were followed up until July 2023. Any finding with increased radiopharmaceutical accumulation above the background activity in the respective area was considered a false positive. Prostate-specific membrane antigen accumulation in established lesions was assessed semi-quantitatively by the maximum standardized uptake value (SUVmax) and qualitatively by the four-point visual scale proposed in the E-PSMA recommendations. RESULTS: We found 15/40 (37.5%) patients with PSMA-positive findings. These were predominantly bone changes without a corresponding CT abnormality or discrete cystic or osteoblastic lesions with above-background increased PSMA expression. The mean SUVmax of these non-specific lesions was 3.02 (SD 2.86). After 3.5-4 years of follow-up, biochemical progression was found in only two of the patients.The great sensitivity of the method nowadays is a powerful engine for the development of new therapeutic options. On the other side, the lower specificity due to false positive findings, if misinterpreted, might lead to switching to a higher stage, with the planned radical treatment replaced by palliative treatment. CONCLUSION: The presence of 68Ga-PSMA-11 PET/CT-positive findings in patients after radical prostatectomy and an undetectable PSA had a low predictive value for future progression. The interpretation of 68Ga-PSMA-11 PET/CT should always include a complex assessment of the clinical setting-the risk group, PSA value and degree of PSMA accumulation in the lesions. In these situations, further clarification of PSMA-positive findings is appropriate before deciding to change treatment.

KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer.

RAS somatic variants are predictors of resistance to anti-EGFR therapy for colorectal cancer (CRC) and affect the outcome of the disease. Our study aimed to evaluate the frequency of RAS, with a focus on KRAS variants, and their association with tumor location and some clinicopathological characteristics in Bulgarian CRC patients. We prospectively investigated 236 patients with advanced and metastatic CRC. Genomic DNA was extracted from FFPE tumor tissue samples, and commercially available kits were used to detect RAS gene somatic mutations via real-time PCR. A total of 115 (48.73%) patients tested positive for RAS mutations, with 106 (44.92%) testing positive for KRAS mutations. The most common mutation in exon 2 was c.35G>T p.Gly12Val (32.56%). We did not find a significant difference in KRAS mutation frequency according to tumor location. However, patients with a mutation in exon 4 of KRAS were 3.23 times more likely to have a tumor in the rectum than in other locations (95% CI: 1.19-8.72, p = 0.021). Studying the link between tumor location and KRAS mutations in exon 4 is crucial for better characterizing CRC patients. Further research with larger cohorts, especially in rectal cancer patients, could provide valuable insights for patient follow-up and treatment selection.

RIPK3 expression as a potential predictive and prognostic marker in metastatic colon cancer.

BACKGROUND: Colorectal cancer is one of the primary causes of cancer-related deaths and 5-fluorouracil (5-FU) therapy remains the cornerstone of treatment in these patients. Resistance to 5-FU represents a major obstacle; therefore, finding new predictive and prognostic markers is crucial for improvement of patient outcomes. Recently a new type of programmed cell death was discovered-necroptosis, which depends on receptor interacting protein 3 (RIPK3). Preclinical data showed that necroptotic cell death is an important effector mechanism of 5-FU-mediated anticancer activity. PURPOSE: To investigate the predictive and prognostic performance of RIPK3 expression in primary tumors. METHODS: Colon cancer patients (n=74) with metastatic stage were included in this retrospective study and all were treated with first-line 5-FU based chemotherapy. Immunohistochemical staining was performed. RESULTS: The progression free survival for the low expression group of RIPK3 was 5.6 months (95% CI, 4.4-6.8) vs 8.4 months (95% CI, 6.4-10.3) of the group with high expression (p=0.02). Moreover, patients with high expression of RIPK3 were associated with lower risk of disease progression HR 0.61 (95% CI, 0.38-0.97; p=0.044). Patients with high expression levels of RIPK3 also had significantly longer mean overall survival (OS) of 29.3 months (95% CI, 20.8-37.8) as compared with those with low expression: 18.5 months (95% CI, 15.06-21.9) (p= 0.036). In addition, univariate analysis showed that high level of RIPK3 expression was associated with a longer OS HR 0.59 (95% CI, 0.35-0.98; p=0.044). CONCLUSIONS: This study suggests that expression of RIPK3 in primary tumors of metastatic colon cancer patients should be further investigated for its potential as a promising predictive and prognostic marker.

Changes in the sensorimotor system and semitendinosus muscle morphometry after arthroscopic anterior cruciate ligament reconstruction: a prospective cohort study with 1-year follow-up.

PURPOSE: To evaluate the time course of sensorimotor integration processes involved in balance capability during 1-year follow-up after arthroscopic anterior cruciate ligament (ACL) reconstruction. To evaluate whether an association exists between balance performance and semitendinosus muscle morphometry features. METHODS: Twenty-seven patients (mean age 29.6 ± 10.8 years) were prospectively followed with stabilometry and ultrasound at 3 months (T0), 6 months (T1), and 1 year (T2) after arthroscopic ACL reconstruction. Body sway and sensorimotor integration processes were evaluated by calculating the percentage difference of sway (PDS) on two surface conditions. RESULTS: A significant difference in PDS was observed over time (p < 0.001). The interaction "Time × Condition" showed significant differences (p = 0.02), with worse performance on the compliant than the firm surface. There was a significant difference in CSA (p < 0.001), MT (p < 0.001), and %HRD (p < 0.001) over time. The interaction "Time*side" was significant for CSA (p = 0.02) and %HRD (p = 0.01). A negative correlation between PDS on compliant surface and CSA was measured at 3- (r = - 0.71, n = 27, p < 0.001) and 6-month post-surgery (r = - 0.47, n = 27, p = 0.013). CONCLUSIONS: Balance was regained within the first 6 months after surgery, while morphometry of the semitendinosus muscle improved mostly between 6 and 12 months in patients who returned to sports activities. Balance capabilities paralleled semitendinosus muscle morphometry improvements. The instrumental assessment of sensorimotor integration processes is relevant in clinical practice as screening tests for primary and secondary prevention of ACL injury. LEVEL OF EVIDENCE: Prospective studies, Level II.

An Analysis of the Knowledge Among Midwifery Students at Medical University-Pleven Regarding Human Papillomavirus (HPV) and HPV-Associated Diseases.

Background and objective Comprehensive health literacy and prevention have been the key methods to reduce the spread of human papillomavirus (HPV) and HPV-associated disease development. Raising awareness among young individuals about the risk factors and the ways to prevent the infection is often the starting point of primary prevention. In light of this, we aimed to assess the awareness of midwifery students at Medical University-Pleven about (HPV) and HPV-associated diseases. Material and methods We conducted a survey-based study among first-year students at Medical University-Pleven in the period spanning January to March 2020, which involved a direct group survey. We initially reached out to 445 students and 284 (63.8%) of them responded; 12 of them were midwifery students. In the period from May through November 2022, the same type of survey was repeated among 75 midwifery students, and 47 (62.7%) responded. A set of classic statistical methods were used to present and analyze the collected quantitative and qualitative data. The responses in the questionnaires were reviewed and recoded according to the requirements of the statistical program. The significance of the results, the findings, and the conclusions was set at p<0.05. A comparative analysis was employed to statistically compare the results to present the differences between the groups of traits studied. Data processing was performed using MS Office Excel 2019 and SPSS Statistics v.28 (IBM Corp., Armonk, NY). Results Over half (70.6%) of the first-year midwifery students were aware of the infection caused by HPV. Among them, 10 students (29.4%) were familiar with the risk factors for HPV and HPV-associated diseases, and all of the fourth-year respondents knew about the studied issue. The majority of the respondents - 61.8% of the freshmen and 100% of the fourth-year students- were aware of HPV vaccine availability. Conclusions In the course of their training, the midwifery students at Medical University-Pleven acquired enough knowledge about the risk factors of HPV-associated diseases and the availability of vaccines to prevent them.

Impact of Cognitive Disturbances and Clinical Symptoms on Disability in Patients with Paranoid Schizophrenia: A Study of a Bulgarian Clinical Sample.

The study aimed to assess the impact of clinical symptoms and cognitive impairment on disability in patients with paranoid schizophrenia (PS). METHODS: 108 patients with schizophrenia were included (66 male and 42 female). Their average age was 38.86 ± 10.02 years and the disease duration was 12.80 ± 8.20 years, with mean disease onset of 24 years. Clinical symptoms were assessed with the PANSS, and cognitive performance was measured using a seven-item neurocognitive battery. The disability level of the subjects was assessed using the World Health Organization-Disability Assessment Schedule 2.0 (WHO-DAS 2.0). The relation between the variables studied was assessed using Spearman's rank correlation coefficient (rs) at a probability level of p < 0.05. RESULTS: An increase in symptom severity resulted in worsening of the "participation in society" (r = 0.56, p < 0.01), "life activities-household" (r = 0.55, p < 0.01), and "getting along with people" (r = 0.59, p < 0.01) WHO-DAS 2.0 domains. Positive symptoms (13.89 ± 3.48) correlated strongly with "getting along with people" (r = 0.55, p < 0.01), "life activities-household" (r = 0.58, p < 0.01), and "participation in society" (r = 0.62, p < 0.01), and negative symptoms (14.25 ± 4.16) with "participation in society" (r = 0.53, p < 0.01) and "life activities-household" (r = 0.48, p < 0.01). Symptoms of disorganization (15.67 ± 4.16) had the highest impact on "life activities-household" (r = 0.81, p < 0.01), "getting along with people" (r = 0.56, p < 0.05), and "participation in society" (r = 0.65, p < 0.01). Episodic memory (r = -0.28, p < 0.01) was remotely related to comprehension and communication. The information processing speed (rs = 0.38, p < 0.01), visual memory (rs = -0.30, p < 0.01), and focused executive functions showed moderate correlations with all domains on the WHO-DAS 2.0 scale (rs = 0.38, p < 0.01). Attention (rs = -0.33, p < 0.01) was moderately related to community activities. Semantic (rs = -0.29, p < 0.01) and literal (rs = -0.27, p < 0.01) verbal fluency demonstrated weak correlations with "cognition-understanding", "getting along with people", and "participation in society". CONCLUSION: Symptoms of disorganization and disturbed executive functions contribute most to disability in patients with schizophrenia through impairment of real-world functioning, especially in social interactions and communication. Severe clinical symptoms (negative and disorganization-related ones) as well as deficits in executive function, verbal memory, and verbal fluency cause the biggest problems in the functional domains of interaction with other people and participation in society.

Toxoplasma gondii seropositivity and cognitive function in adults with schizophrenia.

Introduction and methods: Based on the limited research focusing on the severity of cognitive deterioration in schizophrenia with preceding toxoplasmosis, we sampled 89 demographically matched paranoid schizophrenia patients (mean age 38.97 years) with (n = 42) and without (n = 47) seroprevalence of IgG type anti T. gondii antibodies as marker of past infection. They underwent examination of verbal memory (10 words Luria test), logical memory and visual memory (BVRT), processing speed (TMT-A/DSST) and executive functions (TMT-B/verbal fluency). We compared the results of both groups, taking into account the normative values for the Bulgarian population where available. We also compared the two groups in terms of clinical severity as evidenced by positive, negative and disorganization sub-scores of the PANSS. Results: While both groups were expectedly under the population norms for verbal and logical memory, seropositive patients showed significantly bigger impairment in verbal memory (Luria Smax = 72.85 vs 78.51; p = 0.029), psychomotor speed (TMT-A 50.98 s vs 44.64 s; p = 0.017), semantic verbal fluency (27.12 vs 30.02; p = 0.011) and literal verbal fluency (17.17 vs 18.78; p = 0.014) compared to the seronegative ones. In addition to that, they gave less correct answers on the BVRT (2.98 vs 4.09; p = 0.006) while making markedly more errors (13.95 vs 10.21; p = 0.002). Despite not reaching statistical significance, past toxoplasmosis was associated with higher score on the PANSS disorganization sub-scale (16.50 points vs 14.72 points) and with lower educational attainment. Conclusion: Our results suggest a more profound neuropathological insult(s) resulting in greater cognitive impairment in schizophrenia cases that are exposed to T. gondii infection.

Corrigendum: Socio-Demographic and Clinical Characteristics of Psychiatric Patients Who Have Committed Suicide: Analysis of Bulgarian Regional Suicidal Registry for 10 Years.

[This corrects the article DOI: 10.3389/fpsyt.2021.665154.].

Socio-Demographic and Clinical Characteristics of Psychiatric Patients Who Have Committed Suicide: Analysis of Bulgarian Regional Suicidal Registry for 10 Years.

Introduction: Suicide is a major public health problem but factors determining suicide risk are still unclear. Studies in this field in Bulgaria are limited, especially on a regional level. Methods: By a cross-sectional design, we accessed the medical records of all psychiatric patients committed suicide over a 10-year period (2009-2018) in one major administrative region of Bulgaria. A statistical analysis was performed of the association between age of suicide as an indirect yet measurable expression of the underlying suicidal diathesis and a number of socio-demographic and clinical characteristics. Results: Seventy-seven of 281 suicides (28%) had psychiatric records. Most common diagnoses were mood disorders (44%), followed by schizophrenia (27%), anxiety disorders (10%), substance use disorders (9%) and organic conditions (8%). Male gender, single/divorced marital status, early illness onset, co-occurring substance misuse and lower educational attainment (for patients aged below 70) were significantly associated with earlier age of suicide whereas past suicide attempts and psychiatric hospitalizations, comorbid somatic conditions and unemployment showed insignificant association. Substantial proportion of patients (60%) had contacted psychiatric service in the year preceding suicide, with nearly half of these encounters being within 30 days of the accident. Conclusion: Severe mental disorders are major suicide risk factor with additional contribution of certain socio-demographic and illness-related characteristics. Monitoring for suicidality must be constant in chronic psychiatric patients. Registration of suicide cases in Bulgaria needs improvement in terms of information concerning mental health. More studies with larger samples and longitudinal design are needed to further elucidate distal and proximal suicide risk factors.

State of the art and challenges for the classification of studies on electromechanical and robotic devices in neurorehabilitation: a scoping review.

INTRODUCTION: The rapid development of electromechanical and robotic devices has profoundly influenced neurorehabilitation. Growth in the scientific and technological aspects thereof is crucial for increasing the number of newly developed devices, and clinicians have welcomed such growth with enthusiasm. Nevertheless, improving the standard for the reporting clinical, technical, and normative aspects of such electromechanical and robotic devices remains an unmet need in neurorehabilitation. Accordingly, this study aimed to analyze the existing literature on electromechanical and robotic devices used in neurorehabilitation, considering the current clinical, technical, and regulatory classification systems. EVIDENCE ACQUISITION: Within the CICERONE Consensus Conference framework, studies on electromechanical and robotic devices used for upper- and lower-limb rehabilitation in persons with neurological disabilities in adulthood and childhood were reviewed. We have conducted a literature search using the following databases: MEDLINE, Cochrane Library, PeDro, Institute of Electrical and Electronics Engineers, Science Direct, and Google Scholar. Clinical, technical, and regulatory classification systems were applied to collect information on the electromechanical and robotic devices. The study designs and populations were investigated. EVIDENCE SYNTHESIS: Overall, 316 studies were included in the analysis. More than half (52%) of the studies were randomised controlled trials (RCTs). The population investigated the most suffered from strokes, followed by spinal cord injuries, multiple sclerosis, cerebral palsy, and traumatic brain injuries. In total, 100 devices were described; of these, 19% were certified with the CE mark. Overall, the main type of device was an exoskeleton. However, end-effector devices were primarily used for the upper limbs, whereas exoskeletons were used for the lower limbs (for both children and adults). CONCLUSIONS: The current literature on robotic neurorehabilitation lacks detailed information regarding the technical characteristics of the devices used. This affects the understanding of the possible mechanisms underlying recovery. Unfortunately, many electromechanical and robotic devices are not provided with CE marks, strongly hindering the research on the clinical outcomes of rehabilitation treatments based on these devices. A more significant effort is needed to improve the description of the robotic devices used in neurorehabilitation in terms of the technical and functional details, along with high-quality RCT studies.

Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer.

The aim of this multicentric retrospective study is to evaluate the predictive and prognostic performance of neutrophil to lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and their dynamics in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab as a second line. Patients with metastatic NSCLC (n = 119), whose tumors expressed programmed death-ligand 1 (PD-L1) ≥ 1%, were retrospectively analyzed between Apr 2017 and Apr 2019. All patients received platinum-containing chemotherapy as a first line treatment. Pre-treatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood before the first pembrolizumab infusion. Progression free survival (PFS) and overall survival (OS) was compared by Kaplan-Meier method and Cox Proportional Hazard model. Patients with NLR > 5 before immunotherapy showed significantly shorter mean PFS of 6.86 months (95% CI: 5.81-7.90) as compared to those with NLR ≤ 5 of 18.82 months (95% CI: 15.87-21.78) (long rank test p < 0.001). Furthermore in the multivariate analysis, only NLR > 5 was an independent predictive factor for shorter PFS (HR: 4.47, 95% CI: 2.20-9.07, p < 0.001). In multivariate analysis, presence of bone metastases (HR: 2.08, 95% CI: 1.10-4.94, p = 0.030), NLR > 5 before chemotherapy (HR: 8.09, 95% CI: 2.35-27.81, p = 0.001) and high PLR before chemotherapy (HR: 2.81, 95% CI: 1.13-6.97, p = 0.025) were found to be independent negative prognostic factors for poor OS. Our data suggests that NLR ≤ 5 is a potential predictive marker, which may identify patients appropriate for immunotherapy as a second line treatment.

Four-week trunk-specific exercise program decreases forward trunk flexion in Parkinson's disease: A single-blinded, randomized controlled trial.

INTRODUCTION: Pathological forward trunk flexion is a disabling and drug-refractory motor complication of Parkinson's disease (PD) leading to imbalance, pain, and fall-related injuries. Since it might be reversible, early and multidisciplinary management is emphasised. The primary aim was to compare the effects of a four-week trunk-specific rehabilitation program on the severity of the forward trunk flexion. The secondary aim was to compare the training effects on the motor impairments, dynamic and static balance, pain, falls, and quality of life. METHODS: 37 patients with PD (H&Y ≤ 4) and forward trunk flexion were randomized in the experimental (n = 19) or control group (n = 18). The former consisted of active self-correction exercises with visual and proprioceptive feedback, passive and active trunk stabilization exercises and functional tasks. The latter consisted of joint mobilization, muscle strengthening and stretching, gait and balance exercises. Protocols lasted 4 weeks (60 min/day, 5 days/week). Before, after, and at 1-month follow-up, a blinded examiner evaluated patients using primary and secondary outcomes. The primary outcome was the forward trunk flexion severity (degree). Secondary outcomes were the UPDRS III, dynamic and static balance, pain falls, and quality of life assessment. RESULTS: The experimental group reported a significantly greater reduction in forward trunk flexion than the control group from T0 to both T1 (p = 0.003) and T2 (p = 0.004). The improvements in dynamic and static balance were significantly greater for the experimental group than the control group from T0 to T2 (p = 0.017 and 0.004, respectively). Comparable effects were reported on the other outcomes. Pre-treatment forward trunk flexion values were highly correlated to post-treatment trunk deviation changes. CONCLUSION: The four-week trunk-specific rehabilitation training decreased the forward trunk flexion severity and increased postural control in patients with PD. NCT03741959.

Effectiveness of Robot-Assisted Upper Limb Training on Spasticity, Function and Muscle Activity in Chronic Stroke Patients Treated With Botulinum Toxin: A Randomized Single-Blinded Controlled Trial.

Background: The combined use of Robot-assisted UL training and Botulinum toxin (BoNT) appear to be a promising therapeutic synergism to improve UL function in chronic stroke patients. Objective: To evaluate the effects of Robot-assisted UL training on UL spasticity, function, muscle strength and the electromyographic UL muscles activity in chronic stroke patients treated with Botulinum toxin. Methods: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with UL spastic hemiparesis. The experimental group (n = 16) received robot-assisted UL training and BoNT treatment. The control group (n = 16) received conventional treatment combined with BoNT treatment. Training protocols lasted for 5 weeks (45 min/session, two sessions/week). Before and after rehabilitation, a blinded rater evaluated patients. The primary outcome was the Modified Ashworth Scale (MAS). Secondary outcomes were the Fugl-Meyer Assessment Scale (FMA) and the Medical Research Council Scale (MRC). The electromyographic activity of 5 UL muscles during the "hand-to-mouth" task was explored only in the experimental group and 14 healthy age-matched controls using a surface Electromyography (EMGs). Results: No significant between-group differences on the MAS and FMA were measured. The experimental group reported significantly greater improvements on UL muscle strength (p = 0.004; Cohen's d = 0.49), shoulder abduction (p = 0.039; Cohen's d = 0.42), external rotation (p = 0.019; Cohen's d = 0.72), and elbow flexion (p = 0.043; Cohen's d = 1.15) than the control group. Preliminary observation of muscular activity showed a different enhancement of the biceps brachii activation after the robot-assisted training. Conclusions: Robot-assisted training is as effective as conventional training on muscle tone reduction when combined with Botulinum toxin in chronic stroke patients with UL spasticity. However, only the robot-assisted UL training contributed to improving muscle strength. The single-group analysis and the qualitative inspection of sEMG data performed in the experimental group showed improvement in the agonist muscles activity during the hand-to-mouth task. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03590314.

Robot-Assisted Stair Climbing Training on Postural Control and Sensory Integration Processes in Chronic Post-stroke Patients: A Randomized Controlled Clinical Trial.

BACKGROUND: Postural control disturbances are one of the important causes of disability in stroke patients affecting balance and mobility. The impairment of sensory input integration from visual, somatosensory and vestibular systems contributes to postural control disorders in post-stroke patients. Robot-assisted gait training may be considered a valuable tool in improving gait and postural control abnormalities. OBJECTIVE: The primary aim of the study was to compare the effects of robot-assisted stair climbing training against sensory integration balance training on static and dynamic balance in chronic stroke patients. The secondary aims were to compare the training effects on sensory integration processes and mobility. METHODS: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with postural instability. The experimental group (EG, n = 16) received robot-assisted stair climbing training. The control group (n = 16) received sensory integration balance training. Training protocols lasted for 5 weeks (50 min/session, two sessions/week). Before, after, and at 1-month follow-up, a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Berg Balance Scale (BBS). Secondary outcomes:10-meter walking test, 6-min walking test, Dynamic gait index (DGI), stair climbing test (SCT) up and down, the Time Up and Go, and length of sway and sway area of the Center of Pressure (CoP) assessed using the stabilometric assessment. RESULTS: There was a non-significant main effect of group on primary and secondary outcomes. A significant Time × Group interaction was measured on 6-min walking test (p = 0.013) and on posturographic outcomes (p = 0.005). Post hoc within-group analysis showed only in the EG a significant reduction of sway area and the CoP length on compliant surface in the eyes-closed and dome conditions. CONCLUSION: Postural control disorders in patients with chronic stroke may be ameliorated by robot-assisted stair climbing training and sensory integration balance training. The robot-assisted stair climbing training contributed to improving sensorimotor integration processes on compliant surfaces. Clinical trial registration (NCT03566901).

Characterization of Upper Limb Impairments at Body Function, Activity, and Participation in Persons With Multiple Sclerosis by Behavioral and EMG Assessment: A Cross-Sectional Study.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and disabling disease which primarily affects individuals in their early life between 20 and 40 years of age. MS is a complex condition, which may lead to a variety of upper limb (UL) dysfunctions and functional deficits. Objective: To explore upper limb impairments at body function, activity, and participation in persons with MS (PwMS) and severe hand dexterity impairment by behavioral and surface electromyography (sEMG) assessments. Methods: This observational cross-sectional study involved 41 PwMS with severe hand dexterity impairment stratified according to the Expanded Disability Status Scale (EDSS) into mild-moderate (n = 17; EDSS, 1-5.5), severe ambulant (n = 15; EDSS, 6-6.5), and severe nonambulant (n = 9; EDSS, 7-9.5). Behavioral outcome measures exploring body function, activity, and participation were administered. The sEMG activity of six upper limb muscles of the most affected side was measured during a reaching task. Results: The most severe group was significantly older and more affected by secondary progressive MS than the other two groups. Positive significant associations between UL deterioration and impairments at different International Classification of Functioning, Disability, and Health domains were noted in the most severe group. The progressive decline in manual dexterity was moderately to strongly associated with the deterioration of the overall UL activity (ρ = 0.72; p < 0.001) and disuse (amount of use ρ = 0.71; p < 0.001; quality of movement ρ = 0.77; p < 0.001). There was a low correlation between manual dexterity and UL function (ρ = 0.33; p = 0.03). The muscle activation pattern investigated by sEMG was characterized by a decrease in modularity and timing delay in the wrist extensor muscles activation in the severe ambulant patients (EDSS, 6-6.5). Similar impairments were observed in the proximal muscles (anterior deltoid) in the more advanced stages (EDSS ≥ 7). Conclusion: Behavioral assessment, together with measures of muscle activation patterns, allows investigating the pathophysiology of UL impairments in PwMS across progressive neurological disability severity to implement task-specific rehabilitation interventions.

Association Between Serum CK-18 Levels and the Degree of Liver Damage in Fructose-Induced Metabolic Syndrome.

BACKGROUND: The pathogenesis of nonalcoholic fatty liver disease as a component of metabolic syndrome (MetS) involves the activation of apoptosis in steatotic hepatocytes. Caspase-generated fragments such as cytokeratin-18 (CK-18) in patients with various hepatic impairments are investigated as markers for diagnosis and assessment of disease severity. The goal of the study was to capture early biomarkers of apoptosis and elucidate their role in assessing the presence and extent of hepatic damage in a MetS model. MATERIALS AND METHODS: We used male Wistar rats, divided into two groups (n = 7): control and high-fructose drinking (HFD) (35% fructose corn syrup for 16 weeks). Metabolic disorders and liver damage were studied by histochemistry (hematoxylin and eosin), immunohistochemical, immunological, and biochemical testing. RESULTS: Our results showed significant increase in liver and serum levels of CK-18 and pro/antiapoptotic Bax/Bcl2 ratio, and decreased levels of HMGB1 (marker of necrosis) in the HFD group when compared with the control. All HFD rats developed obesity, hyperglycemia, hepatomegaly, microvesicular steatosis, an imbalance in hepatic antioxidative defense by measuring malondialdehyde and sulfhydryl groups (SH) with no inflammation and fibrosis, elevated serum levels of triglycerides, tumor necrosis factor alpha (TNF-α), and C-reactive protein without changes in serum aminotransferase levels relative to the control group. As a result of the applied regression analysis, we have determined that the variables TNF-α (0.92) and SH (0.659) have a strong complex effect on hepatic CK-18 levels with predicted value of the model R = 0.9. CONCLUSION: The elevated CK-18 serum levels in the HFD group and their association with the histological changes in the liver and biochemical indicators demonstrate the key role of apoptosis in the pathogenesis of HFD-induced liver damage and the reliability of CK-18 as a biomarker for noninvasive assessment of liver damages in MetS.

Does myofascial and trigger point treatment reduce pain and analgesic intake in patients undergoing onabotulinumtoxinA injection due to chronic intractable migraine?

BACKGROUND: Chronic migraine is a disabling disorder associated with myofascial and trigger point disorders in the neck. Pharmacological management is the first line of treatment; however, rehabilitation procedures aimed at lessening symptoms of myofascial and trigger point disorders may add value in the management of headache symptoms. AIM: The aim of this study was to evaluate the feasibility of myofascial and trigger point treatment in chronic migraine patients receiving prophylactic treatment with onabotulinumtoxinA. To evaluate the treatment effects on headache frequency and intensity, analgesic consumption, cervical range of motion, trigger point pressure pain threshold, quality of life, and disability. DESIGN: Pilot, single-blind randomized controlled trial with two parallel groups. SETTING: Neurorehabilitation Unit. POPULATION: Twenty-two outpatients with chronic migraine. METHODS: Patients were randomly assigned to receive either cervicothoracic manipulative treatment (N.=12) or transcutaneous electrical nerve stimulation (TENS) in the upper trapezius (N.=10). Treatment consisted of 4 sessions (30 min/session, 1 session/week for 4 weeks). A rater blinded to treatment allocation evaluated outcomes before treatment, during treatment, and 1 month after the end of treatment. Consistent with the pilot nature of the study, feasibility was considered the primary outcome and efficacy the secondary outcome. RESULTS: All patients completed the study. No adverse events were reported. No significant between-group differences in pain intensity were observed during the study period. At post-treatment evaluation, the total consumption of analgesics (P=0.02) and non-steroidal anti-inflammatory (P=0.02) drugs was significantly lower in the manipulative treatment group than in the TENS group. These effects paralleled significant improvements in trigger point sensitivity and cervical active range of motion. CONCLUSIONS: Manipulative techniques aimed at reducing peripheral nociceptive triggers might add value in the management of chronic migraine symptoms and lower acute medication use. CLINICAL REHABILITATION IMPACT: An interdisciplinary approach comprising pharmacological and non-pharmacological strategies can reduce analgesic consumption and myofascial dysfunction symptoms in chronic migraine patients.

Effects of High-intensity Robot-assisted Hand Training on Upper Limb Recovery and Muscle Activity in Individuals With Multiple Sclerosis: A Randomized, Controlled, Single-Blinded Trial.

Background : Integration of robotics and upper limb rehabilitation in people with multiple sclerosis (PwMS) has rarely been investigated. Objective: To compare the effects of robot-assisted hand training against non-robotic hand training on upper limb activity in PwMS. To compare the training effects on hand dexterity, muscle activity, and upper limb dysfunction as measured with the International Classification of Functioning. Methods: This single-blind, randomized, controlled trial involved 44 PwMS (Expanded Disability Status Scale:1.5-8) and hand dexterity deficits. The experimental group (n = 23) received robot-assisted hand training; the control group (n = 21) received non-robotic hand training. Training protocols lasted for 5 weeks (50 min/session, 2 sessions/week). Before (T0), after (T1), and at 1 month follow-up (T2), a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Action Research Arm Test. Secondary outcomes: Nine Holes Peg Test; Fugl-Meyer Assessment Scale-upper extremity section; Motricity Index; Motor Activity Log; Multiple Sclerosis (MS) Quality of Life-54; Life Habits assessment-general short form and surface electromyography. Results: There were no significant between-group differences in primary and secondary outcomes. Electromyography showed relevant changes providing evidence increased activity in the extensor carpi at T1 and T2. Conclusion: The training effects on upper limb activity and function were comparable between the two groups. However, robot-assisted training demonstrated remarkable effects on upper limb use and muscle activity. https://clinicaltrials.gov NCT03561155.

Feasibility and safety of early lower limb robot-assisted training in sub-acute stroke patients: a pilot study.

BACKGROUND: So far, the development of robotic devices for the early lower limb mobilization in the sub-acute phase after stroke has received limited attention. AIM: To explore the feasibility of a newly robotic-stationary gait training in sub-acute stroke patients. To report the training effects on lower limb function and muscle activation. DESIGN: A pilot study. SETTING: Rehabilitation ward. POPULATION: Two sub-acute stroke inpatients and ten age-matched healthy controls were enrolled. Healthy controls served as normative data. METHODS: Patients underwent 10 robot-assisted training sessions (20 minutes, 5 days/week) in alternating stepping movements (500 repetitions/session) on a hospital bed in addition to conventional rehabilitation. Feasibility outcome measures were compliance, physiotherapist time, and responses to self-report questionnaires. Efficacy outcomes were bilateral lower limb muscle activation pattern as measured by surface electromyography (sEMG), Motricity Index (MI), Medical Research Council (MRC) grade, and Ashworth Scale (AS) scores before and after training. RESULTS: No adverse events occurred. No significant differences in sEMG activity between patients and healthy controls were observed. Post-training improvement in MI and MRC scores, but no significant changes in AS scores, were recorded. Post-treatment sEMG analysis of muscle activation patterns showed a significant delay in rectus femoris offset (P=0.02) and prolonged duration of biceps femoris (P=0.04) compared to pretreatment. CONCLUSIONS: The robot-assisted training with our device was feasible and safe. It induced physiological muscle activations pattern in both stroke patients and healthy controls. Full-scale studies are needed to explore its potential role in post-stroke recovery. CLINICAL REHABILITATION IMPACT: This robotic device may enrich early rehabilitation in subacute stroke patients by inducing physiological muscle activation patterns. Future studies are warranted to evaluate its effects on promoting restorative mechanisms involved in lower limb recovery after stroke.

Role of the pretreatment 18F-fluorodeoxyglucose positron emission tomography maximal standardized uptake value in predicting outcomes of colon liver metastases and that value's association with Beclin-1 expression.

The current study sought to evaluate the predictive and prognostic performance of the maximum standardized uptake value (SUVmax) prior to treatment in 43 patients with colon cancer and unresectable liver metastases. Patients with colon cancer who underwent 18F-FDG-PET/computed tomography (CT) scans for staging before the start of first-line 5-fluorouracil-based chemotherapy were retrospectively analyzed. Expression of Beclin-1 in cancer cells was evaluated in primary tumors using immunohistochemical staining. The pretreatment SUVmax for liver metastases was not able to predict progression-free survival but was significantly associated with poorer overall survival, with a hazard ratio of 2.05 (95 % CI, 1.016-4.155). Moreover, a negative correlation was noted between SUVmax and expression of a marker of autophagy - Beclin-1 (rho = -0.42, p = 0.006). This suggests that the pretreatment SUVmax in 18F-FDG PET/CT is a useful tool to help predict survival outcome in patients with colon cancer and unresectable liver metastases and may significantly distinguish between patients with low and high levels of Beclin-1 expression (AUC = 0.809, 95% CI: 0.670-0.948, p = 0.001).