Treatment In Daily Clinical Practice Research Articles

Neurophysiology of hypokinetic movement’s disorders: New insights in daily clinical practice

Hypokinetic movement disorders encompass a group of clinically similar diseases that present challenges in discrimination during neurological examinations. Characterizing a specific hypokinetic disorder is necessary for the diagnosis and treatment in daily clinical practice. Neurophysiological tools, such as electromyography (EMG) combined with accelerometry, motor-evoked potentials (MEPs), electroencephalographic recording (EEG), Bereitschaftspotential (BP), auditory-evoked cognitive potential (P300), blink reflex (BR), and R2 blink reflex recovery cycle (R2BRRC), are useful in the differential diagnosis of movement disorders due to the common clinical features. However, neurophysiological assessments of movement disorders, especially hypokinetic diseases, are currently underutilized in clinical practice as compared to a few decades ago. This review aims to summarize practical insights gleaned from reported studies over the past 5 years (i.e., 2019 – 2023) regarding neurophysiological assessments of hypokinetic movement disorders, emphasizing the importance of their routine application. In particular, the methodology of the electrophysiologic evaluations pertaining to hypokinetic movement disorders is assessed. Moreover, a practical approach for the differential diagnosis of similar movement disorder syndromes based on specific neurophysiological features is proposed. Collectively, this review of the most recent neurophysiological implications in hypokinetic movement disorders highlights the practicality of these methods. Despite the advancement of other diagnostic techniques (e.g., neuroradiological methods), neurophysiological assessments may be a promising tool for clinical diagnoses, due to their high accuracy and ability to categorize and manage movement disorders (e.g., hypokinetic movement disorders) in daily clinical practice.

Effectiveness and safety of glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes: evidence from a retrospective real-world study.

Global phase III clinical trials have shown superior hypoglycemic efficacy to insulin and other oral hypoglycemic agents. However, there is a scarcity of real-world data comparing different glucagon-like peptide 1 receptor agonist (GLP-1RA) directly. This study aimed to assess the safety and effectiveness of various GLP-1RA in treating type 2 diabetes mellitus (T2DM) in a real-world clinical setting and identify predictive factors for favorable treatment outcomes. This was a retrospective, single-center, real-world study. The changes in HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the percentage of participants who achieved HbA1c of <7%, 7%-8%, and ≥ 8% after GLP-1RA treatment was analyzed. The clinical factors that affect the effectiveness of GLP-1RA were analyzed. At baseline, the 249 participants had a mean baseline HbA1c of 8.7 ± 1.1%. After at least three months of follow-up, the change in HbA1c was -0.89 ± 1.3% from baseline. Dulaglutide exerted a more significant hypoglycemic effect than immediate-release exenatide. The percentage of participants who achieved HbA1c<7% was substantial, from 6.0% at baseline to 28.9%. Average body weight decreased by 2.02 ± 3.8 kg compared to baseline. After GLP-1RA treatment, the reduction in SBP was 2.4 ± 7.1 mmHg from baseline. A shorter duration of diabetes and a higher baseline HbA1c level were more likely to achieve a good response in blood glucose reduction. This study provided real-world evidence showing that GLP-1RA significantly improved HbA1c, body weight, and SBP. The results can inform the decision-making about GLP-1RA treatment in daily clinical practice.

High inter-laboratory variability in the assessment of HER2-low breast cancer: a national registry study on 50,714 Danish patients

BackgroundConsidering the recent advancements in the treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2), we aimed to examine inter-laboratory variability in the assessment of HER2-low breast cancer across all Danish pathology departments.MethodsFrom the Danish Breast Cancer Group, we obtained data on all women diagnosed with primary invasive breast cancer in 2007–2019 who were subsequently assigned for curatively intended treatment.ResultsOf 50,714 patients, HER2 score and status were recorded for 48,382, among whom 59.2% belonged to the HER2-low group (score 1+ or 2+ without gene amplification), 26.8% had a HER2 score of 0, and 14.0% were HER2 positive. The proportion of HER2-low cases ranged from 46.3 to 71.8% among pathology departments (P < 0.0001) and from 49.3 to 65.6% over the years (P < 0.0001). In comparison, HER2 positivity rates ranged from 11.8 to 17.2% among departments (P < 0.0001) and from 12.6 to 15.7% over the years (P = 0.005). In the eight departments with the highest number of patients, variability in HER2-low cases increased from 2011 to 2019, although the same immunohistochemical assay was used. By multivariable logistic regression, the examining department was significantly related to both HER2 score 0 and HER2 positivity (P < 0.0001) but showed greater dispersion in odds ratios in the former case (range 0.25–1.41 vs. 0.84–1.27).ConclusionsOur data showed high inter-laboratory variability in the assessment of HER2-low breast cancer. The findings cast doubt on whether the current test method for HER2 is robust and reliable enough to select HER2-low patients for HER2-targeted treatment in daily clinical practice.

Retrospective Data Analysis of the Use of an Autologous Multilayered Leukocyte, Platelet, and Fibrin Patch for Diabetic Foot Ulcers Treatment in Daily Clinical Practice.

To describe the healing outcome of chronic, hard-to-heal diabetic foot ulcers (DFUs) treated with an autologous multilayered leukocyte, platelet, and fibrin (MLPF) patch in addition to the best standard of care, in a real-world clinical setting of two US amputation preventive centers. In this retrospective study of patients treated between September 2021 and October 2022, the authors analyzed DFU healing outcomes based on Wound, Ischemia, and foot Infection-derived amputation risk. All 36 patients had a diagnosis of type 2 diabetes and 29 (81%) were male. Their average age was 61.4 years, body mass index was 29.2 kg/m2, and glycated hemoglobin was 7.9. Twenty-seven patients (78%) were diagnosed with peripheral vascular disease, 20 (56%) underwent a peripheral vascular procedure, 15 (42%) had a prior amputation, and 6 (17%) were on hemodialysis. Average wound size was 4.9 cm2, and wound age was 9.5 months. Twelve patients (32%) were classified as low risk, 15 (39%) as moderate risk, and 11 (29%) as high risk for amputation. Within 12 weeks of the first MLPF patch application, nine wounds (24%) healed. After 20 weeks, 23 wounds (61%) were closed, and by follow-up, 30 wounds (79%) healed. No amputations were noted. Compared with published data, 40% fewer patients underwent readmission within 30 days, with 72% shorter admission duration. Real-world clinical experiences using the MLPF patch to treat hard-to-heal DFUs resulted in the majority of wounds healing. Few patients experienced a readmission within 30 days, and the average admission duration was short.

Dynamic Quantitative Imaging of the Masseter Muscles in Bruxism Patients with Myofascial Pain: Could It Be an Objective Biomarker?

We aimed to investigate whether the collaboration of shear wave elastosonography (SWE) and B-mode ultrasonography (US) could be offered as diagnostic tools to assess the presence, severity, and progress of bruxism, as well as a biomarker for the effectiveness of treatment in daily clinical practice. The study was designed as a quantitative evaluation of the masseter muscles (MMs) of the clinically diagnosed bruxism patients suffering from myofascial pain and MMs of the healthy individuals. Clinical examinations were made according to the diagnostic criteria for temporomandibular disorders (DC/TMD), and pain was assessed using a visual analog scale (VAS). Painful MMs with VAS scores ≥ 4 were assigned to Group A, and healthy MMs were assigned to Group B. Also, the MMs of the painful bruxers were analyzed based on wearing occlusal splints. Group A was divided into two subgroups as splint users (Group AI) and non-users (Group AII). All the participants were scanned with dynamic US and SWE to quantify the size and stiffness of the MMs. Measurements of each muscle pair while the jaw is in a resting position (relaxation) and clenching position (contraction) were recorded. The significant differences in stiffness and thickness became visible in the relaxation state. Bruxism patients with myofascial pain had significantly harder and thinner MMs than healthy individuals. During the relaxation, the mean thickness and elasticity values were 9.17 ± 0.40 mm and 39.13 ± 4.52 kPa for Group A and 10.38 ± 0.27 and 27.73 ± 1.92 for Group B, respectively. Also, stiffer MMs were measured in Group AII (38.16 ± 3.61 kPa) than in Group AI (26.91 ± 2.13 kPa). In conclusion, the combination of SWE and US using a dynamic examination technique has the potential to be a valuable tool for the management of bruxism patients suffering from myofascial pain.

Belumosudil Combination Therapy in Refractory Chronic Graft-Versus-Host Disease

Background: There are now 3 FDA approved oral drugs for chronic graft-versus-host disease (cGVHD) after 1-2 or more prior lines of therapy- ibrutinib, ruxolitinib and belumosudil. Encouraging overall response rates have been reported for all 3 agents; however, complete responses are rare and there are still a large number of patients who do not respond or lose the response over time. One of the approaches to overcome potential resistance to single agent use is to combine the new agents with each other or with other therapies (such as extracorporeal photopheresis (ECP), sirolimus, MMF) as there can be synergy across agents with different mechanisms of action. The 3 new drugs are all kinase inhibitors that block lymphocyte activation pathways and the production of proinflammatory cytokines. Preclinical studies showed their potential effects in cGVHD. Since the FDA approvals, it has been possible to use these drugs in various combinations for cGVHD treatment in daily clinical practice. In this retrospective review, we summarize our institution's real-world practice of using the ROCK2-inhibitor belumosudil in combination therapies since its FDA approval in July 2021. Methods: We conducted a retrospective chart review of patients treated with belumosudil in combination with other therapeutic agents at the Stanford Cancer Institute from July 2021 to July 2022. We collected descriptive statistics of standard outcomes of response as defined by the 2014 NIH Consensus Project on Criteria for Clinical Trials in cGVHD. Refractory cGVHD was defined as steroid-refractory or steroid-dependent cGVHD. Results: A cohort of 26 patients were evaluated (Table 1). The most common organ affected was skin (n = 20), followed by mouth (n = 19), eyes (n = 15) and joints/fascia (n=15). Patients were treated with a median number of 3 lines of prior therapies before initiating belumosudil. Combination therapies with belumosudil included several 3-4 drug combinations with concurrent use of ruxolitinib, ECP, prednisone, sirolimus or CNI. In instances in which belumosudil was combined with ruxolitinib, belumosudil was the add-on drug. The median follow-up period following initiation of belumosudil was 213.5 days. The overall response rate (ORR) following the addition of belumosudil was 77% (20/26). Responses to belumosudil used in combination were based on organ symptom scoring and global rating by clinician assessment according to the 2014 NIH Consensus Criteria and were seen in 85% (17/20) patients with skin involvement; 53% (8/15) patients with joint/fascial involvement, 33% (5/15) patients with eye involvement, 30% (3/10) patients with lung involvement, 11% (2/19) patients with mouth involvement, and 13% (1/8) patients with liver involvement (Table 2). No responses were seen in patients with GI (lower tract) involvement. No clinically evident adverse drug reactions occurred in the belumosudil combinations although variable dosing of the combined agents was used with the approved belumosudil dose of 200 mg po daily. Infectious adverse events occurred in 42% (11/26) of patients, consistent with the immunosuppressive effects of cGVHD therapies. Of these, 36% (5/14) was due to SARS-CoV2 infection, 29% (4/14) cytomegalovirus reactivation, 21% (3/14) bacterial infection, 7% (1/14) rhinovirus infection, and 7% (1/14) respiratory syncytial virus. The number of infection events with the new agent combination of belumosudil plus ruxolitinib was reviewed separately and was not increased over the other belumosudil combinations. No deaths have occurred in this cohort of 26 patients to date. Conclusion: In our institutional practice, administration of belumosudil in combination therapy appears safe, tolerable, and effective in patients with established, refractory cGVHD. The results of our retrospective study highlight the feasibility of the next phase of belumosudil research for combination therapy in this difficult-to-treat population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prospective Cohort Study of Palbociclib Treatment in Postmenopausal Patients With Unresectable and Metastatic Hormone Receptor-Positive Breast Cancer: Study Protocol for a CSPOR-BC Palbociclib Cohort Trial.

BackgroundCombining palbociclib with letrozole or fulvestrant improved progression-free survival in hormone receptor (HR)-positive and human epidermal growth factor receptor-negative metastatic breast cancer. However, combining palbociclib to endocrine treatment increases toxicity and cost compared with the endocrine treatment alone. Moreover, palbociclib treatment may affect the outcome of the subsequent treatment because its benefit in terms of overall survival has not been observed yet. Therefore, it is crucial to examine whether palbociclib can improve clinical outcomes and quality of life (QoL) of patients in the real world.MethodsA prospective observational study with palbociclib is planned in 3 cohorts (A, B, and C) as per the line of endocrine treatment (i.e., first-line, second-line, or third-line or later-line treatment) for postmenopausal metastatic or unresectable breast cancer. The primary endpoint is progression-free survival in each treatment line, the most commonly used endpoint for global phase 3 studies. As per the results of these studies, the planned sample size is 700 cases: cohort A, 340 cases; cohort B, 200 cases; and cohort C, 130 cases. The secondary endpoints are overall survival, clinical benefit rate, time to chemotherapy, adverse events (AEs), patient-reported outcomes (PROs), and health-related QoL (HRQoL). These endpoints are evaluated again during the subsequent treatment. This study will examine whether the efficacy, safety, and QoL effects of palbociclib treatment in daily clinical practice are not inferior compared to those in clinical trials and whether palbociclib treatment affects the efficacy and safety of the subsequent treatment. Moreover, this study would provide information on the most effective time of adding palbociclib to endocrine treatment.DiscussionThe reproducibility of randomized clinical trials (RCTs) using real-world data must be confirmed to evaluate whether real-world treatment benefits are similar to those observed in RCTs. Although the efficacy of palbociclib has been confirmed in RCTs, Aes of this drug, including its toxicities and cost, are not comparable to those of mono-hormone therapies. Thus, PROs/HRQoL is an important element of this study because several patients with HR-positive metastatic breast cancer have diseases for which sequential hormone therapy is preferential.

To Drill or not to Drill: A Turnabout in Endodontic Practices during Corona Virus Disease -2019- A South India Based Study.

Introduction:The emergence of coronavirus disease-2019 (COVID-19) pandemic poses an immense global health challenge. It also had a profound impact on dentistry with all elective treatment grinding to half initially and a slow phased return to normal services. The aim of the article is to provide an insight into the effect of COVID-19 on endodontic treatment.Materials and Methods:A cross-sectional study among endodontists of various southern states of India was conducted from January 1, 2021 to March 31, 2021, using an online questionnaire. A total of 300 dentists who perform endodontic treatment in daily clinical practice were chosen for the survey. The information was coded, entered, and analyzed utilizing SPSS 20.0 version.Results:A total of 263 questionnaires were answered by the selected group. About 92.01% of endodontists have made changes in infection control including modification in their personal protective equipment and duration of the interval between their appointments. A whopping 74.14% of endodontists faced the economic loss of varying degrees due to the pandemic. In general tremendous changes have been occurred in their daily practice following the pandemic.Conclusion:The pandemic's current and enduring consequences on every part of our lives have been a cause of pain and frustration, but it has also highlighted the human spirit's resilience. Ideally, endodontists must be able to select the best arrangements for safely performing their procedures.

Evaluation of Neuroprotective Effects of Sugammadex Following a Head Trauma in an Experimental Study.

To compare the efficacy of mannitol, the first choice of treatment in daily clinical practice for head trauma, and sugammadex, a frequently used neuroanesthesia in recent years. A total of 35 male rats were randomly selected and were divided into 5 groups, each comprising 7 rats. The groups were divided into Group I, sham (n = 7); Group II, control (head trauma, n = 7); Group III, treated with mannitol (head trauma, mannitol 20% 1 g/kg, n = 7); Group IV, treated with sugammadex (head trauma, sugammadex 100 mg/ kg, n = 7); and Group V, treated with mannitol and sugammadex (head trauma, mannitol 20% 1 g/kg and sugammadex 100 mg/kg, n = 7). After the sacrification, histological examination and immu-nohistochemical staining were performed in the brain of all subjects. Mann-Whitney U test was used to evaluate the significance between neuronal density, neuronal nuclei, and activated caspase-3 immunohistochemistry results measured from the prefrontal cortex. Neuronal density showing neuronal viability was observed to significantly increase in Group III compared to Group IV. However, neuronal nuclei immunohistochemistry showing apoptotic neurons also significantly increased. The present study has shown that sugammadex, an agent reversing the effects of neuromuscular blocking agents, has neuroprotective effects and is as effective as mannitol.

Statins and age: is there a limit beyond which primary prevention is futile?

Hypercholesterolaemic patients at an advanced age (>75 years) with and without known cardiovascular disease are at higher cardiovascular risk than younger subjects, and the frequency of vascular events in this group of the patient increases with increasing age. However, in clinical practice, these subjects are undertreated for various reasons: conservative cultural attitude, fear of side effects, doubts about efficacy, lack of specific trials. Two recent meta-analyses have shown that the use of lipid-lowering drugs is as safe and effective in this age group as in younger subjects. Subjects aged >75 years in primary prevention are poorly represented in trials but should be considered for treatment in daily clinical practice, because, in the risk assessment (SCORE algorithm), they are very often classified as intermediate or high risk but can also be reclassified at increased risk if an additional assessment step with clinical markers (diabetes and reduced glomerular filtrate) or cardiovascular imaging is used for the detection of subclinical atherosclerosis. Greater attention to treatment methods and monitoring of possible side effects is recommended, but the only limit to the treatment is its ‘futility’ in the fragile patient.

Fractures of the penis.

A penile fracture is a traumatic rupture of the tunica albuginea of the corpora cavernosa in an erect penis, usually as a result of blunt trauma during sexual activity. The aetiology varies with geographical region, with the USA and Europe having a higher incidence of sexual trauma and the Middle East having a higher rate of self-manipulation. Diagnosis is usually clinical, but numerous imaging modalities have been used to confirm the fracture site and to help plan appropriate surgical management. Clinical examination will find a detumescent penis with a diffuse penile swelling and ecchymosis: the classic eggplant sign. The penis will often deviate away from the side of the injury. A history of the patient's inability to pass urine after the injury or of blood at the urethral meatus suggests an associated urethral injury. Immediate surgical management is the mainstay of treatment, with many surgeons favouring a degloving approach. Penile fractures also carry a risk of urethral tears and urethral repair may be necessary. This article describes the aetiology, presentation and management of penile fractures to enable identification and treatment in daily clinical practice.

Endodontic treatment during COVID-19 pandemic

Aim: This study evaluated, by the application of questionnaires, the impact of the COVID-19 pandemic on the clinical routine and inspection by the competent authorities, on the flow of patients in the office, as well as on possible changes in Endodontic treatment costs and the amounts charged to patients. Methods: This cross-sectional study was conducted from May 2nd, 2020 to May 6th, 2020, using an online questionnaire with a convenience sample. The inclusion criterion was professionals who perform endodontic treatments in daily clinical practice and who professional setting is private practice. The questionnaire brought questions about the impact on costs and the amount charged to the patient. Results: A total of 1042 questionnaires were answered from all the different states of Brazil, by professional who usually perform Endodontic treatment, and who is working in private practice. A total of 1010 (96.9%) respondents affirm it was necessary to modify the protective equipment in endodontic treatment due to pandemic and longer intervals between appointments was cited by 922 (88.5%), economically affecting the dental practice. There was no association between routine changes and economic impacts with gender, professional experience, area of residence or education level. Conclusion: In conclusion, most dental professionals recognized changes in the routine of endodontic treatment during the COVID-19 pandemic. They have a perception of increase in endodontic costs, and reduction in the volume of patients.

Correlation between esthetic expectations for orthognathic treatment and psychological characteristics among Chinese adult patients

This study aimed to evaluate the association of esthetic expectations with self-reported personal characteristics, anxiety, depression, self-esteem, oral health-related quality of life, and the Orthognathic Quality of Life Questionnaire (OQLQ) in Chinese adult patients before orthognathic treatment. This study involved 213 patients with clinically significant skeletal deformity requiring orthognathic surgery for comprehensive treatment. Each patient completed a series of Chinese version scales, including the self-rating anxiety scale, self-rating depression scale, self-esteem scale, the Oral Health Impact Profile-14 questionnaire, and the OQLQ. The patients' self-reported personal characteristics were also recorded, including facial appearance ratings before and after orthognathic treatment, highest education level, mean monthly income, and enthusiasm toward orthodontic or orthognathic treatment. The Least Absolute Shrinkage and Selection Operator multivariate linear regression model was conducted for the selection of the above factors. The final multivariate linear regression model was built with variables identified under the optimal tuning parameter. A total of 213 patients (87 men and 126 women) were included in this study. The patients' esthetic expectation scores were significantly associated with their total scores, which encompassed the education level, mean monthly income, enthusiasm toward orthodontic or orthognathic treatment, self-esteem scale, the Chinese version of the 14-item Oral Health Impact Profile questionnaire, OQLQ, etc. In the multivariate linear regression model, the OQLQ, enthusiasm toward orthognathic treatment, depression, and expected facial appearance score after the treatment were the most important factors to predict esthetic expectation. High esthetic expectations for orthognathic treatment were mostly associated with higher expected facial appearance scores after the treatment, greater enthusiasm toward orthognathic treatment, worse depression (confusion), and 2 domains (social aspects of deformity and oral function) of OQLQ. Therefore, OQLQ, enthusiasm toward orthognathic treatment, and expected facial appearance score after treatment may be used to predict patients' esthetic expectations before commencing orthognathic treatment in daily clinical practice.

Influence of prognosis factors on the prescription of targeted treatments in rheumatoid arthritis: A Delphi survey.

To explore current evidence on the management of poor prognostic factors in rheumatoid arthritis (RA) and to investigate whether this evidence is taken into account by clinicians when deciding on treatment in daily clinical practice. We performed a systematic literature review (SLR) to analyse the effects of currently available biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) on the classically accepted poor prognostic factors of RA. All randomized controlled trials reporting subgroup analyses about effects on prognostic factors were identified and synthesized. In a second phase, a two-round Delphi survey was carried out to contrast the SLR results with the grade of agreement of a large group of rheumatologists about the effectiveness of each drug class on each prognostic factor. According to the Delphi results, the only prognostic factor that significantly influenced the selection of treatment was the presence of interstitial lung disease (ILD), being the preferred treatment in this scenario abatacept or rituximab. The rest of the poor prognostic factors (including high disease activity at baseline, disability as measured by the Health Assessment Questionnaire index, seropositivity, elevated acute-phase reactants, and evidence of erosions based on plain radiography or ultrasonography) did not seem to significantly influence rheumatologists when choosing a treatment. The results of the SLR results did not show solid evidence regarding the use of any specific therapy in the management of patients with specific poor factors, except in the case of RA-ILD, although the data in the literature in this regard are not free of bias. The only prognostic factor that seems to significantly influence the selection of treatment is the presence of RA-ILD.

Feasibility of using Treatment based Classification System to Plan Management of Patients with Low Back Pain

Background: Low back pain (LBP) is an extremely common symptom and most troublesome of complaints in the general population. Pain can vary from a dull constant ache to a sudden sharp feeling. At any point in time 80% of general population will experience some type of low back pain1. Treatment efficacy for the increasing prevalence of this back pain is a great challenge for both health care providers and individuals coping with this problem3. In order to select an effective and efficient treatment in daily clinical practice, low back pain patients should be classified by symptoms during testing and physical examination. One of the main classification systems which focus individual clinical presentation is treatment based classification system. Treatment based classification system will also have impact on clinical decision-making in the management of low back pain3. Objectives: To educate all therapist working with patients with back pain to categorize each patients using treatment based classification system. To establish the consistency and accuracy of therapists in using treatment based classification system for patients with LBP. To analyze therapists opinion of the feasibility of treatment based classification system to plan the management of LBP. Study design: Observational study Method: A total of 46 patients were recruited in this observational study. Each patients was assessed and allocated to treatment based classification system. Visual analogue scale and Patient-Specific Functional Scale for first and last day of the treatment was taken and number of session also documented by the trained therapist. Results: Results were analysed by the questions obtained from the five therapists. All five agreed for the accuracy in categorization and time, 60% agreed for the consistency in usage and goal setting and only 40% agreement for the usefulness. The total feasibility level was 75%. Conclusion: The study concludes that using TBC system to plan management for low back pain is feasible in terms of categorization, accuracy and time but not cost effectiveness.

Targeted Therapies for Driver Gene Mutation-positive Lung Cancer Patients with Brain Metastasis

脑是晚期肺癌转移最常见的部位，驱动基因阳性者脑转移发病率更高，肺癌脑转移患者预后较差，且不同治疗方式的选择影响肺癌脑转移患者的病程转归及预后。近年来，随着精准医学的发展，针对肺癌脑转移，尤其是具有特殊靶点的驱动基因阳性患者治疗方式的选择越来越成为人们的研究热点，并逐步取得进展。本文主要阐述了肺癌脑转移治疗存在的挑战，系统综述了驱动基因阳性肺癌脑转移的靶向治疗进展，以期在精准医学时代下，指导此类患者临床实践中个体化精准治疗方案的抉择。

Observational study to describe the impact of treatment combinations with Daratumumab versus other alternative regimens in patients with relapsed / refractory multiple myeloma. Spain real world evidence (RWE) data. GeminiS study.

The current national treatment scenario for relapsed / refractory multiple myeloma (RRMM) and the effectiveness of the different treatment alternatives in daily clinical practice outside clinical trials (CT) is unknown. In recent years, several treatment regimens have been approved representing effective treatment alternatives and a hope for a better-quality of life for patients, according to the results obtained in CT. It is necessary to evaluate the results of these treatments in daily clinical practice in order to elucidate the real impact of the incorporation of new treatments to the therapeutic arsenal already available and to know as objectively as possible the benefit they bring to the patients.

KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer - practical implications for the clinician.

BackgroundColorectal cancer is a successful model of genetic biomarker development in oncology. Currently, several predictive or prognostic genetic alterations have been identified and are used in clinical practice. The RAS gene family, which includes KRAS and NRAS act as predictors for anti-epithelial growth factor receptor treatment (anti-EGFR), and it has been suggested that NRAS mutations also play a role in prognosis: patients harboring NRAS alterations have a significantly shorter survival compared to those with wild type tumours. BRAF V600E mutations are rare and occur mostly in tumors located in the ascending colon in elderly female patients. BRAF is instrumental in establishing prognosis: survival is shorter by 10–16 months in BRAF-mutant patients, and BRAF may be a negative prognostic factor for patients who undergo hepatic or pulmonary metastasectomy. Moreover, this mutation is used as a negative predictive factor for anti-EGFR therapies. Two new biomarkers have recently been added to the metastatic colorectal cancer panel: HER2 and microsatellite instability. While HER2 is still being investigated in different prospective studies in order to validate its prognostic role, microsatellite instability already guides clinical decisions in substituted with advanced colorectal cancer.ConclusionsThere are current evidences that support using above mentioned genetic biomarkers to better identify the right medicine that is supposed to be used in the right patient. This approach contributes to a more individualized patient-oriented treatment in daily clinical practice.

A practical algorithm for using rTMS to treat patients with chronic pain

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has a good level of evidence of efficacy as a method for providing analgesic effects in patients with chronic pain. However, there is still no consensus regarding the parameters of stimulation to use and the detailed protocol to apply for therapeutic practice. In this article, we review the main technical points to address, and we propose a practical algorithm of how to use rTMS for chronic pain treatment in daily clinical practice.

Concomitant methotrexate has little effect on clinical outcomes of abatacept in rheumatoid arthritis: a propensity score matching analysis.

To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(-)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period. Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(-)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (- 1.35/- 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52weeks. In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX. • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in 'real-world' settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians.