Pseudoakathisia in a patient with clotiapine abuse: Report of a case

IntroductionObjective symptoms of akathisia in the absence of subjective symptoms is known as pseudoakathisia, more often diagnosed in older patients with long-term antipsychotic treatment.ObjectiveTo describe a case of pseudoakathisia in a patient with clotiapine abuse.AimsPseudoakathisia management.MethodsX is a 47-year-old male with chronic insomnia treated with clotiapine 40 mg/day for four years. He admits abusive neuroleptic consumption in the past eight months (160 mg/day), without any psychiatric control for years. In recent months he has experienced different organic complications, requiring multiple hospitalizations. During psychiatric examinations due to confusional states, repeated lower limbs movements were objectified. X reported he presented these movements for at least six months, without complaints of inner restlessness feeling. Neurological examination showed normal DAT-SCAN result. Clinical progression was evaluated using BARS scale (Barnes Akathisia Rating Scale).ResultsFollowing the results of tests and statements of drug history, X was diagnosed with clotiapine-induced pseudoakathisia. Neuroleptic treatment was suspended, and clonazepam 6 mg/day and propranolol in ascending doses up to 80 mg/day were initiated. In subsequent evaluations, progressive decrease in movement intensity was observed. However, complete remission after four months from clotiapine suspension was not achieved.ConclusionsPseudoakathisia is a concept not well defined at this moment and different hypotheses about its nature are considered. It has been suggested that it is a form of delayed dyskinesia, or a clinical progression from akathisia, with acquired subjective discomfort tolerance. The most widely used treatment includes benzodiazepines, beta-blockers and anticholinergics, although their effectiveness is limited.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Intramuscular maintenance treatment with ultra-high-dose long-acting injectable aripiprazole in an elderly patient suffering from chronic refractory schizophrenia: A case report

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.2120 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S573-S573 ◽

Cited By ~ 1

Author(s):

L. Bartova ◽

M. Dold ◽

N. Praschak-Rieder ◽

A. Naderi-Heiden ◽

S. Kasper

Keyword(s):

Side Effects ◽

Maintenance Treatment ◽

Rating Scale ◽

Antipsychotic Treatment ◽

High Dose ◽

Symptom Scale ◽

Meaningful Improvement ◽

Plasma Level Monitoring ◽

Competing Interest ◽

Long Acting

Long-acting injectable (LAI) aripiprazole is increasingly appreciated in the course of a maintenance treatment of schizophrenia due to efficacy in delaying – and decreasing relapse, and low rates of feared side effects. In line with the prescribing information, the maximal starting – as well as maintenance dose was restricted to 400 mg following a 26-day interval between the single doses.We present a 72-year-old female inpatient (66 kg) with an acute exacerbation of chronic refractory schizophrenia, exhibiting primarily positive symptoms including excessive persecutory delusions, self-care deficit, poor insight and insufficient adherence to continuous intake of oral medication. Since she developed a post-injection syndrome after an accidental intravascular administration of olanzapine LAI 405 mg, the antipsychotic treatment was switched to aripiprazole LAI 300 mg once monthly. Due to insufficient clinical response, aripiprazole LAI was gradually increased up to 1200 mg per month under continuous plasma level monitoring. Here, 2 single injections of aripiprazole LAI 300 mg were delivered into both gluteal muscles concurrently, every 14 days.Consequently, we observed a clinically meaningful improvement (a total-score reduction from 111 to 75 on the Positive and Negative Syndrome Scale), as well as no objectifiable side effects, assessed by “The Dosage Record Treatment Emergent Symptom Scale” and “The Barnes Akathisia Rating Scale”, despite multi-morbidity and rather advanced age of the patient.Our safe experience with applying the almost threefold higher monthly dose over 12 weeks may encourage researchers to further investigate the efficacy, tolerability as well as handling of highly dosed aripiprazole LAI in refractory schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Long-term metabolic effect of second-generation antipsychotics in first episode of psychosis

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.431 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S388-S388

Author(s):

J. Vázquez Bourgon ◽

R. Pérez-Iglesias ◽

V. Ortiz-García de la Foz ◽

B. Crespo-Facorro

Keyword(s):

Side Effects ◽

Second Generation ◽

Resistance Index ◽

Metabolic Parameters ◽

First Episode ◽

Antipsychotic Treatment ◽

Metabolic Side Effects ◽

Long Term Follow Up ◽

Competing Interest

IntroductionThere is growing evidence indicating that the use of second-generation antipsychotic (SGA) treatments in psychosis is related to potential metabolic side effects. Previous studies have shown clear metabolic side effects at short-term (12 weeks). However, to detect clinically-relevant impairment in metabolic parameters a long-term follow-up is preferred.ObjectivesThe aim of this study was to investigate the effect of aripiprazole, ziprasidone and quetiapine on metabolic measures in medication-naïve first episode psychosis patients after 1 year of treatment.MethodsOne hundred and sixty-eight, drug-naïve patients, suffering from a non-affective first episode of psychosis, were included in the present study. Patients were randomly assigned to quetiapine, ziprasidone or aripiprazole treatment lines. Weight and glucemic/lipid parameters were recorded at baseline and after 1 year of treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.ResultsWeight (t = −10.85; P < 0.001), BMI (t = −11.38; P < 0.001), total cholesterol (t = −5.37; P < 0.001), LDL-cholesterol (t = −5.21; P < 0.001), triglycerides (t = −5.18; P < 0.001) and the triglyceride/HDL insulin resistance index (t = −4.09; P < 0.001), showed statistically significant increments after 1 year of treatment.Moreover, on comparing the percentage of patients with pathological levels before and 1 year after the antipsychotic treatment, we detected higher percentages of patients with obesity (5.1% vs. 15.3%; P < 0.001), hypercholesterolemia (23.2% vs. 39.6%; P < 0.001) and hypertriglyceridemia (5.8% vs. 14.2%; P = 0.021) after 1 year of treatment.ConclusionsThe primary exposure to SGAs during the first year of psychosis was associated with significant increments in weight and metabolic parameters leading to a significant increment in the proportion of obesity, hypertriglyceridemia and hypercholesterolemia in our sample.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Effect of Disrupted-in-Schizophrenia 1 gene on treatment response in patients with a first episode of psychosis

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.401 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S183-S183

Author(s):

J. Vázquez Bourgon ◽

R. Ayesa Arriola ◽

P. Suarez Pinilla ◽

R. Roiz Santiañez ◽

D. Tordesillas Gutierrez ◽

...

Keyword(s):

Treatment Response ◽

Negative Symptoms ◽

Rating Scale ◽

Genetic Alterations ◽

Individual Variability ◽

First Episode ◽

Antipsychotic Treatment ◽

Positive Symptoms ◽

Drug Naïve ◽

Competing Interest

IntroductionThere is substantial evidence suggesting that individual variability in antipsychotic treatment response could be genetically determined. Disrupted-in-Schizophrenia 1 (DISC1) gene has been previously associated to the illness and to treatment response in a sample of patients suffering from psychosis. However, there is a lack of studies on the effect of DISC1 on treatment response in samples of first episode psychosis.ObjectivesThe aim of this study was to explore the relation between variations in DISC1 gene and treatment response to antipsychotics in a sample of drug-naïve patients with a first episode of psychosis.MethodsTwo hundred and twenty Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys), rs6675281 (Leu607Phe) and rs1000731. Early (6 weeks) response to antipsychotic treatment was assessed with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.ResultsWe found a significant association between rs1000731 and treatment response. Thus, those patients homozygous for the G allele of rs1000731 were more frequently non-responders, measured with SANS, after 6 weeks of treatment, than those carrying the A allele (X2 = 4.019; P = 0.032). Moreover, when analysing the clinical improvement longitudinally, we observed that those patients carrying the A allele for the rs1000731 presented a greater improvement in positive symptoms dimension (F = 8.905; P = 0.003).ConclusionsOur results suggest a minor contribution to antipsychotic drug response of genetic alterations in the DISC1 gene.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Antipsychotic-induced tardive dyskinesia: The role of glutamatergic system

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.069 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S97-S97

Author(s):

A. Boiko ◽

S. Ivanova ◽

A. Semke

Keyword(s):

Tardive Dyskinesia ◽

Glutamate Transporter ◽

Antipsychotic Treatment ◽

Nucleotide Polymorphisms ◽

Antipsychotic Therapy ◽

Drug Induced ◽

Schizophrenic Patients ◽

Competing Interest

Tardive dyskinesia (TD) occurs in 20–25% of patients with long-term antipsychotic therapy. Abnormalities in glutamatergic transmission are considered one of the key components of the pathogenesis of drug-induced side effects. Glutamate acts as excitotoxin under certain conditions and in excessive concentrations.Aim is to study the concentration of glutamate and analysis of single nucleotide polymorphisms (SNP) in genes coding the glutamate transporter and NMDA-receptors in schizophrenic patients with TD and without it.The study group included 156 patients with schizophrenia receiving long-term antipsychotic treatment. Patients were divided into two groups: 63 patients with TD and 93 patients without it. Glutamate was determined in serum by spectrophotometric method. Determination of allelic variants of gene SLC1A2 (rs4354668) and GRIN2A (rs2650427, rs1969060) was performed by polymerase chain reaction in real-time.We found a significant (P < 0.05) increase of the concentration of glutamate in patients with TD. Significant (P < 0.05) reduction in frequency of genotype GG of GRIN2A (rs1969060) and TT of SLC1A2 (rs4354668) were found in patients with TD in comparison to group without TD. In the study of glutamate concentration depending on the genotype GRIN2A (rs1969060) and genotype SLC1A2 (rs4354668) we observed a statistically significant change: elevated levels of glutamic acid identified with the heterozygous genotype in patients.It is possible to suggest that reduction in frequency of these genotypes increases the risk of movement disorders due to the protective effect of these genotypes.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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FRI0412 DOES SEVERE ACUTE POSTOPERATIVE PAIN RESULT IN MORE LONG-TERM PAIN AFTER TOTAL HIP OR KNEE ARTHROPLASTY (THA OR TKA) FOR OSTEOARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.493 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 805.2-805

Author(s):

D. A. J. M. Latijnhouwers ◽

C. H. Martini ◽

R. G. H. H. Nelissen ◽

H. M. J. Van der Linden ◽

T. P. M. Vliet Vlieland ◽

...

Keyword(s):

Postoperative Pain ◽

Acute Pain ◽

Missing Values ◽

Rating Scale ◽

Acute Postoperative Pain ◽

Preoperative Pain ◽

Mixed Effect ◽

Total Hip ◽

Chronic Postsurgical Pain

Background:Chronic pain is a frequently reported unfavourable outcome of total hip and knee arthroplasties (THA/TKA) (7-23% and 10-34%, respectively) in osteoarthritis (OA) patients (1), which is difficult to treat as underlying mechanisms are not fully understood. Acute postoperative pain has been identified as risk factor for development of long-term pain in other surgical procedures, such as mastectomy and thoracotomy (2). However, the effect of acute postoperative pain on development of long-term pain in THA and TKA patients is unknown.Objectives:To investigate if acute pain following THA/TKA in OA patients is associated with long-term pain and if acute pain affects the course of pain up to 1-year postoperatively.Methods:From a longitudinal multicenter study, OA patients scheduled for primary THA or TKA were included. Acute pain scores, using Numeric Rating Scale (NRS), were routinely collected as part of standard care (≤72 hours after surgery). In case of ≥2 NRS scores the two highest scores were averaged (n=160), else the single score was taken. Pain was dichotomized into severe (NRS≥5) and mild (NRS<5). Pain was assessed preoperatively, at 3 (only THA), 6 and 12 months postoperatively using HOOS/KOOS subscale pain. Separate mixed-effect models for THA and TKA patients were used, with dichotomized acute pain as fixed-effect and long-term pain as outcome, while adjusting for confounders (age, sex, BMI, preoperative pain, mental component scale of the SF12 (MCS-12), and duration of the surgery and hospitalization). We included an interaction between time of measurement and acute postoperative pain to analyse whether effect modification was present. Missing values in preoperative pain and MCS-12 were imputed using multiple imputation methods.Results:81 THA and 87 TKA patients were included, of whom 32.1% and 56.3% reported severe acute pain. The results did not show an associated between severe acute pain and long term pain (THA: β=2.0, 95%-CI:-10.9-7.0; TKA: β=3.8, 95%-CI:-10.6-2.9). Furthermore, It seems that there is no effect present of difference in severity of acute pain and the course of pain over time (THA 6-months: β=6.4, 95%-CI:1.9-10.9 and 12-months: β=0.2, 95%-CI:-4.4-4.8; TKA 12-months: β=3.2, 95%-CI:-0.5-6.8).Conclusion:We did not find an association between acute pain and the development of long-term pain nor that severity of acute pain affects the course of postoperative pain in THA and TKA patients. The fact that THA and TKA patients often experience chronic preoperative pain might be a possible explanation for this finding. Nonetheless, future studies including additional measures of acute pain and pain sensitization in patients with chronic preoperative pain are necessary to draw stronger conclusions.References:[1]Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of prospective studies in unselected patients. BMJ open. 2012;2(1):e000435.[2]Katz J, Seltzer Ze. Transition from acute to chronic postsurgical pain: risk factors and protective factors. Expert review of neurotherapeutics. 2009;9(5):723-44.Acknowledgments:We would like to thank the study group that consists of: B.L. Kaptein, Leiden University Medical Center, Leiden; S.B.W Vehmeijer, Reinier de Graaf Hospital, Delft; R. Onstenk, Groene Hart Hospital, Gouda; S.H.M. Verdegaal, Alrijne Hospital, Leiderdorp; H.H. Kaptijn, LangeLand Hospital, Zoetermeer; W.C.M. Marijnissen, Albert Schweitzer Hospital, Dordrecht; P.J. Damen, Waterland Hospital, Hoorn; the NetherlandsDisclosure of Interests:None declared

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COVID-19 era in long-term cardiac rehabilitation programs: how was muscle strenght and lean mass affected in cardiovascular patients?

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.362 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

M Borges ◽

M Lemos Pires ◽

R Pinto ◽

G De Sa ◽

I Ricardo ◽

...

Keyword(s):

Muscle Strength ◽

Cardiac Rehabilitation ◽

Lean Mass ◽

Lower Limb ◽

Lower Limbs ◽

Phase Iii ◽

Face To Face ◽

Home Based ◽

Lower Limb Strength

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Exercise prescription is one of the main components of phase III Cardiac Rehabilitation (CR) programs due to its documented prognostic benefits. It has been well established that, when added to aerobic training, resistance training (RT) leads to greater improvements in peripheral muscle strength and muscle mass in patients with cardiovascular disease (CVD). With COVID-19, most centre-based CR programs had to be suspended and CR patients had to readjust their RT program to a home-based model where weight training was more difficult to perform. How COVID-19 Era impacted lean mass and muscle strength in trained CVD patients who were attending long-term CR programs has yet to be discussed. Purpose To assess upper and lower limb muscle strength and lean mass in CVD patients who had their centre-based CR program suspended due to COVID-19 and compare it with previous assessments. Methods 87 CVD patients (mean age 62.9 ± 9.1, 82.8% male), before COVID-19, were attending a phase III centre-based CR program 3x/week and were evaluated annually. After 7 months of suspension, 57.5% (n = 50) patients returned to the face-to-face CR program. Despite all constraints caused by COVID-19, body composition and muscle strength of 35 participants (mean age 64.7 ± 7.9, 88.6% male) were assessed. We compared this assessment with previous years and established three assessment time points: M1) one year before COVID-19 (2018); M2) last assessment before COVID-19 (2019); M3) the assessment 7 months after CR program suspension (last trimester of 2020). Upper limbs strength was measured using a JAMAR dynamometer, 30 second chair stand test (number of repetitions – reps) was used to measure lower limbs strength and dual energy x-ray absorptiometry was used to measure upper and lower limbs lean mass. Repeated measures ANOVA were used. Results Intention to treat analysis showed that upper and lower limbs lean mass did not change from M1 to M2 but decreased significantly from M2 to M3 (arms lean mass in M2: 5.68 ± 1.00kg vs M3: 5.52 ± 1.06kg, p = 0.004; legs lean mass in M2: 17.40 ± 2.46kg vs M3: 16.77 ± 2.61kg, p = 0.040). Lower limb strength also decreased significantly from M2 to M3 (M2: 23.31 ± 5.76 reps vs M3: 21.11 ± 5.31 reps, p = 0.014) after remaining stable in the year prior to COVID-19. Upper limb strength improved significantly from M1 to M2 (M1: 39.00 ± 8.64kg vs M2: 40.53 ± 8.77kg, p = 0.034) but did not change significantly from M2 to M3 (M2 vs M3: 41.29 ± 9.13kg, p = 0.517). Conclusion After CR centre-based suspension due to COVID-19, we observed a decrease in upper and lower limbs lean mass and lower limb strength in previously trained CVD patients. These results should emphasize the need to promote all efforts to maintain physical activity and RT through alternative effective home-based CR programs when face-to-face models are not available or possible to be implemented.

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Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington’s Disease: Results From the ARC-HD Open-label Study

CNS Spectrums ◽

10.1017/s1092852920002655 ◽

2021 ◽

Vol 26 (2) ◽

pp. 164-165

Author(s):

Samuel Frank ◽

Claudia M. Testa ◽

David Stamler ◽

Elise Kayson ◽

David Oakes ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Rating Scale ◽

Study Drug ◽

Motor Dysfunction ◽

Open Label ◽

Entire Treatment Period ◽

End Of Treatment ◽

Pharmaceutical Industries

AbstractBackgroundChorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.MethodsPatients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.ResultsOf 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.ConclusionsThe type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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Long-term improvements following a residential combined physical and psychological programme for chronic low back pain

BMJ Open Quality ◽

10.1136/bmjoq-2020-001068 ◽

2021 ◽

Vol 10 (2) ◽

pp. e001068

Author(s):

Shaun Wellburn ◽

Cormac G Ryan ◽

Andrew Coxon ◽

Alastair J Dickson ◽

D John Dickson ◽

...

Keyword(s):

Low Back Pain ◽

Back Pain ◽

Outcome Measures ◽

Chronic Low Back Pain ◽

Rating Scale ◽

Secondary Outcome ◽

Low Back ◽

Residential Setting ◽

Wide Range

ObjectivesEvaluate the outcomes and explore experiences of patients undergoing a residential combined physical and psychological programme (CPPP) for chronic low back pain.DesignA longitudinal observational cohort design, with a parallel qualitative design using semistructured interviews.SettingResidential, multimodal rehabilitation.Participants136 adults (62 male/74 female) referred to the CPPP, 100 (44 male/56 female) of whom completed the programme, during the term of the study. Ten (2 male/8 female) participated in the qualitative evaluation.InterventionA 3-week residential CPPP.Outcome measuresPrimary outcome measures were the STarT Back screening tool score; pain intensity—11-point Numerical Rating Scale; function—Oswestry Disability Index (ODI); health status/quality of life—EQ-5D-5L EuroQol five-Dimension-five level; anxiety—Generalised Anxiety Disorder-7; depression—Patient Health Questionnaire-9. Secondary outcome measures were the Global Subjective Outcome Scale; National Health Service Friends and Family Test;.ResultsAt discharge, 6 and 12 months follow ups, there were improvements from baseline that were greater than minimum clinically important differences in each of the outcomes (with the sole exception of ODI at discharge). At 12 months, the majority of people considered themselves a lot better (57%) and were extremely likely (86%) to recommend the programme to a friend. The qualitative data showed praise for the residential nature of the intervention and the opportunities for interaction with peers and peer support. There were testimonies of improvements in understanding of pain and how to manage it better. Some participants said they had reduced, or stopped, medication they had been taking to manage their pain.ConclusionsParticipants improved, and maintained long term, beyond minimum clinically important differences on a wide range of outcomes. Participants reported an enhanced ability to self-manage their back pain and support for the residential setting.

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Clinical Outcomes, Structure, and Function Improve With Both Heavy and Moderate Loads in the Treatment of Patellar Tendinopathy: A Randomized Clinical Trial

The American Journal of Sports Medicine ◽

10.1177/0363546520988741 ◽

2021 ◽

Vol 49 (4) ◽

pp. 982-993

Author(s):

Anne-Sofie Agergaard ◽

Rene B. Svensson ◽

Nikolaj M. Malmgaard-Clausen ◽

Christian Couppé ◽

Mikkel H. Hjortshoej ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Outcome ◽

Randomized Clinical Trial ◽

Clinical Outcomes ◽

Rating Scale ◽

Power Doppler ◽

Patellar Tendinopathy ◽

Short Term ◽

Level Of Evidence

Background: Loading interventions have become a predominant treatment strategy for tendinopathy, and positive clinical outcomes and tendon tissue responses may depend on the exercise dose and load magnitude. Purpose/Hypothesis: The purpose was to investigate if the load magnitude influenced the effect of a 12-week loading intervention for patellar tendinopathy in the short term (12 weeks) and long term (52 weeks). We hypothesized that a greater load magnitude of 90% of 1 repetition maximum (RM) would yield a more positive clinical outcome, tendon structure, and tendon function compared with a lower load magnitude of 55% of 1 RM when the total exercise volume was kept equal in both groups. Study Design: Randomized clinical trial; Level of evidence, 1. Methods: A total of 44 adult participants with chronic patellar tendinopathy were included and randomized to undergo moderate slow resistance (MSR group; 55% of 1 RM) or heavy slow resistance (HSR group; 90% of 1 RM). Function and symptoms (Victorian Institute of Sport Assessment–Patella questionnaire [VISA-P]), tendon pain during activity (numeric rating scale [NRS]), and ultrasound findings (tendon vascularization and swelling) were assessed before the intervention, at 6 and 12 weeks during the intervention, and at 52 weeks from baseline. Tendon function (functional tests) and tendon structure (ultrasound and magnetic resonance imaging) were investigated before and after the intervention period. Results: The HSR and MSR interventions both yielded significant clinical improvements in the VISA-P score (mean ± SEM) (HSR: 0 weeks, 58.8 ± 4.3; 12 weeks, 70.5 ± 4.4; 52 weeks, 79.7 ± 4.6) (MSR: 0 weeks, 59.9 ± 2.5; 12 weeks, 72.5 ± 2.9; 52 weeks, 82.6 ± 2.5), NRS score for running, NRS score for squats, NRS score for preferred sport, single-leg decline squat, and patient satisfaction after 12 weeks, and these were maintained after 52 weeks. HSR loading was not superior to MSR loading for any of the measured clinical outcomes. Similarly, there were no differences in functional (strength and jumping ability) or structural (tendon thickness, power Doppler area, and cross-sectional area) improvements between the groups undergoing HSR and MSR loading. Conclusion: There was no superior effect of exercising with a high load magnitude (HSR) compared with a moderate load magnitude (MSR) for the clinical outcome, tendon structure, or tendon function in the treatment of patellar tendinopathy in the short term. Both HSR and MSR showed equally good, continued improvements in outcomes in the long term but did not reach normal values for healthy tendons. Registration: NCT03096067 (ClinicalTrials.gov identifier)

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Immunological and genetic kinetics from diagnosis to clinical progression in chronic lymphocytic leukemia

Biomarker Research ◽

10.1186/s40364-021-00290-z ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Isabel Jiménez ◽

Bárbara Tazón-Vega ◽

Pau Abrisqueta ◽

Juan C. Nieto ◽

Sabela Bobillo ◽

...

Keyword(s):

T Cells ◽

Chronic Lymphocytic Leukemia ◽

Ex Vivo ◽

Clonal Evolution ◽

Lymphocytic Leukemia ◽

Clinical Progression ◽

Molecular Changes ◽

Main Driver ◽

Altered Gene

Abstract Background Mechanisms driving the progression of chronic lymphocytic leukemia (CLL) from its early stages are not fully understood. The acquisition of molecular changes at the time of progression has been observed in a small fraction of patients, suggesting that CLL progression is not mainly driven by dynamic clonal evolution. In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological scenarios. Methods We performed genetic and immunological longitudinal analysis using paired primary samples from untreated CLL patients that underwent clinical progression (sampling at diagnosis and progression) and from patients with stable disease (sampling at diagnosis and at long-term asymptomatic follow-up). Results Molecular analysis showed limited and non-recurrent molecular changes at progression, indicating that clonal evolution is not the main driver of clinical progression. Our analysis of the immune kinetics found an increasingly dysfunctional CD8+ T cell compartment in progressing patients that was not observed in those patients that remained asymptomatic. Specifically, terminally exhausted effector CD8+ T cells (T-betdim/−EomeshiPD1hi) accumulated, while the the co-expression of inhibitory receptors (PD1, CD244 and CD160) increased, along with an altered gene expression profile in T cells only in those patients that progressed. In addition, malignant cells from patients at clinical progression showed enhanced capacity to induce exhaustion-related markers in CD8+ T cells ex vivo mainly through a mechanism dependent on soluble factors including IL-10. Conclusions Altogether, we demonstrate that the interaction with the immune microenvironment plays a key role in clinical progression in CLL, thereby providing a rationale for the use of early immunotherapeutic intervention.

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