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We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). Methods: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted ‘yes’ (yes/no). Results: The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients’ risk management. Conclusions: This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs, Desarrollar recomendaciones sobre el uso de metotrexato (MTX) en combinación con medicamentos modificadores de la enfermedad (DMARD) biológicos (b) o sintéticos específicos (ts) en la artritis reumatoide (AR). Se seleccionaron 11 expertos en AR. Dos coordinadores formularon 13 preguntas sobre la terapia combinada de MTX con bDMARD o tsDMARD. Se realizó una revisión sistemática para responder las preguntas. Se establecieron criterios de inclusión y exclusión, así como las estrategias de búsqueda (se realizaron búsquedas en Medline, Embase y la Biblioteca Cochrane hasta enero de 2019). Dos revisores seleccionaron los artículos y recopilaron datos. Simultáneamente, se evaluaron los resúmenes de las reuniones EULAR y ACR. Con base en esta evidencia, los coordinadores propusieron recomendaciones preliminares que los expertos discutieron y votaron en una reunión de grupo nominal. El nivel de evidencia y el grado de recomendación se establecieron utilizando el Centro de Oxford para Medicina Basada en Evidencia y el nivel de acuerdo con un Delphi. El acuerdo se estableció si al menos el 80% de los expertos votaron «sí» (sí/no). La revisión sistemática recuperó 513 citas, de las cuales finalmente se incluyeron 61. Se generaron, votaron y aceptaron un total de 10 recomendaciones. El nivel de acuerdo fue muy alto en todas ellas y se logró en la primera ronda de Delphi. Las recomendaciones finales cubren aspectos como la dosis óptima de MTX, la estrategia de reducción o la gestión del riesgo de los pacientes. Este documento está destinado a ayudar a los médicos a resolver preguntas clínicas habituales y facilitar la toma de decisiones al tratar a pacientes con AR con MTX, en combinación con bDMARD o tsDMARD

Video Video 1 Successfully combined therapy of Coca-Cola and endoscopic treatment for a giant diospyrobezoar in the duodenum using the electrosurgical endo-knife and ileus tube.

Rheumatoid arthritis (RA), as a chronic autoimmune disease, damages the bone and cartilage of patients, and even leads to disability. Therefore, the diagnosis and treatment of RA is particularly important. However, due to the complexity of RA, it is difficult to make effective early diagnosis of RA, which is detrimental to RA treatment. Besides, long-term intake of anti-RA drugs can also cause damage to patients’ organs. The emergence of nanotechnology provides the new train of thoughts for the diagnosis and treatment of RA. And the combination of diagnosis and therapy is an ideal method to solve the problem of disease management of RA patients. In this review, we summarize the mechanism and microenvironment of RA, discuss the commonly used diagnostic techniques and therapeutic drugs for RA, and review their advantages and disadvantages. New nanotherapy strategies such as drug-carrying nanoparticles, PTT, PDT are listed, and their applications in RA treatment are also summarized. In addition, multimodal imaging, combined therapy and responsive diagnosis and treatment are also summarized as important contents. At last, we also review typical nanocarriers that can be used in the integration of diagnosis and therapy, and discussed their potential applications in RA theranostics.

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.

Objective The purpose of the study is to evaluate whether the clinical effects of focused extracorporeal shockwave therapy (f-ESWT) and acupuncture anticipate the clinical response in patients with rotator cuff tendinopathy in the short term. Design An observational retrospective clinical study. Setting/Location Physical Medicine and Rehabilitation Unit, Sant'Andrea University Hospital in Rome, Italy. Subjects/Interventions We analyzed retrospectively thirty patients (22 females and 8 males) with rotator cuff tendinopathy. Fifteen patients underwent f-ESWT and acupuncture combined therapy (Group A) and fifteen patients underwent only f-ESWT therapy (Group B). Outcome measures The outcome measures were the Visual Analogic Scale (VAS), Assessment Shoulder and Elbow Scale (ASES) and Roles and Maudsley Score (RMS). The follow-ups were T0 (pre-treatment), T1 (3 weeks after the start of the treatment), and T2 (at 8 weeks). In order to compare groups, the ANOVA and Friedman tests were adopted. Group A patients had a more rapid and statistically significant improvement trend in VAS (P Conclusions The study showed that combined treatment decreases the recovery time of the shoulder involved in terms of pain and motor function in the short term. However, these results shall be confirmed by controlled randomized studies.

espanolObjetivo 1) Revisar sistematica y criticamente la evidencia sobre eficacia y seguridad de la terapia combinada con farmacos modificadores de la enfermedad (FAME) sinteticos en la artritis reumatoide (AR); 2) Emitir recomendaciones practicas sobre su uso. Metodos Se realizo una revision sistematica de la literatura con una estrategia de busqueda bibliografica sensible en Medline, Embase y Cochrane Library. Se seleccionaron ensayos clinicos aleatorizados que analizasen la eficacia y/o seguridad de 1) la terapia combinada con FAME sinteticos comparada con la terapia secuencial con FAME sintetico en la AR de inicio; y 2) la combinacion metotrexato + leflunomida o la triple terapia de FAME sinteticos en la AR establecida refractaria a FAME sinteticos. Dos revisores realizaron la primera seleccion por titulo y resumen y 11 la seleccion tras lectura en detalle y la recogida de datos. La calidad se evaluo con la escala de Jadad. En una reunion de grupo nominal en base sus resultados se consensuaron una serie de recomendaciones. Resultados Finalmente no se incluyo ningun articulo en la RSL. Del analisis de los articulos revisados se encontro la eficacia en las AR de inicio del tratamiento precoz con FAME sinteticos siguiendo una estrategia «treat to target» y en AR establecidas refractarias a FAME sinteticos la de la terapia combinada con FAME sinteticos. Con ello se generaron 5 recomendaciones sobre la terapia combinada con FAME sinteticos. Conclusiones Estas recomendaciones pretenden facilitar la toma de decisiones con el uso de la terapia combinada con FAME sinteticos en la AR. EnglishObjective 1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA); 2) To design practical recommendations on their use. Methods A systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of 1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA; and 2) combination of methotrexate + leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting. Results Ultimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a “treat to target” strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD. Conclusions These recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA.

We investigated the impact of human demineralized bone matrix (hDBM) plus adipose-derived stem cells (hADS) plus photobiomodulation (PBM) on a critical-sized femoral defect (CSFD) in ovariectomy induced osteoporosis in rats. There were 6 groups as follows. In group 1 (control, C), only CSFDs were created. Groups 2–6 were implanted with DBM into the CSFD (DBM-CSFD). In group 2 (S), only DBM was transplanted into the CSFD. In group 3 (S + PBM), the DBM-CSFDs were treated with PBM. In group 4, the DBM-CSFDs were treated with alendronate (S + ALN). In group 5, ADSs were seeded into DBM-CSFD (S + ADS). In group 6, ADSs were seeded into DBM-CSFD and the CSFDs were treated with PBM (S + PBM + ADS). At week eight (catabolic phase of bone repair), the S + ALN, S + PBM + ADS, S + PBM, and S + ADS groups all had significantly increased bone strength than the S group (ANOVA, p = 0.000). The S + PBM, S + PBM + ADS, and S + ADS groups had significantly increased Hounsfield unit than the S group (ANOVA, p = 0.000). ALN, ADS, and PBM significantly increased healed bone strength in an experimental model of DBM-treated CSFD in the catabolic phase of bone healing in osteoporotic rats. However, ALN alone and PBM plus ADS were superior to the other protocols.

Objective: To observe the impacts of the combined treatment of Tongdu Tiaoshen moxibustion (moxibustion for promoting the circulation of the governor vessel and regulating the spirit) and rehabilitation training on the motor function recovery in the patients with apoplectic hemiplegia. Methods: A total of 50 patients with apoplectic hemiplegia and qualified in the trial recruitment criteria were divided into two groups according to random number table, 25 cases in each group. In the control group, the simple rehabilitation training was provided. In the observation group, on the base of the treatment as the control group, Tongdu Tiaoshen moxibustion was given. Main acupoints: Baihui (百会GV20), Fēngfŭ (风府GV16) and Dazhuī (大椎GV14). The treatment was given once a day, 6 treatments a week, 4 weeks as one course and two courses of treatment were required. Before and after treatment, the scores of Fugle-Meyer assessment (FMA), the modified Barthel index (MBI) and action research arm test (ARAT) were detected before and after treatment in the two groups separately. Results: After 4 and 8 weeks of treatment, the scores of FMA, MBI and ARAT were all improved obviously as compared with those before treatment respectively in patients of the two groups(all P Conclusion: The combined treatment of Tongdu Tiaoshen moxibustion and rehabilitation training promotes the recovery of the upper limb motor function and improves the self-ability of living activities in the patients with apoplectic hemiplegia. The long-term effect of this combined therapy is superior to that of simple rehabilitation training.

BACKGROUND: Myofacial pain dysfunction syndrome (MPDS) is of the commonest form of orofacial pain encountered in the clinics. Though, many therapies have been suggested in the recent past, still the management of this condition remains a therapeutic problem. The search for newer, relatively safe and effective long term approach lead to the use of magnetic stimulation in pain modulation. Bio Electro Magnetic Energy Regulation is one such modality that has been studied in the musculoskeletal disorders. However, no studies in this regard have been explored in orofacial region. OBJECTIVES: The objective of the present study was to evaluate the efficacy of BEMER therapy as an adjuvant to relieve pain in myofascial pain dysfunction syndrome. MATERIALS AND METHODS: The present randomized comparative study was on 40 patients who were diagnosed with Myofacial pain dysfunction syndrome(MPDS). They were grouped into two groups of 20 each. Group 1 patients were administered analgesic + muscle relaxants & Group 2 was receiving both analgesic + muscle relaxants with BEMER therapy. All the patients were evaluated for pain relief on visual analog scale (VAS) and the mouth opening (MO)was measured using digital vernier callipers. RESULTS: The group 2 showed a significant improvement in the symptoms even after 2 months follow up. In group 2 the mean mouth opening was 45.60 ± 3.648(P

Background Scleroderma renal crisis is a condition that affects approximately 4–6% of patients with systemic sclerosis, especially with diffuse compromise. Clinical manifestations are variable, representing a diagnostic challenge. Objective The study aims to describe and analyze the different pharmacological treatments available for the management of scleroderma renal crisis. Materials and methods A systematic literature review was done based on observational studies and clinical trials about the treatment of scleroderma renal crisis, using monotherapy or combined therapy. The studies were identified using electronic scientific databases, including MEDLINE PUBMED and EMBASE, in English, published between January 1990 and August 2019. Results Eleven studies were included (ten observational studies and one open clinical trial). Of them, seven were cohorts, one case series, and two case–control studies. Overall, 1113 patients were included in the analyzed studies. All studies used angiotensin-converting enzyme inhibitors as exposition, case definition, and/or comparison in the clinical trial. Regarding the need for dialysis, approximately 53.9% of patients required it temporarily or permanently. Approximately 6–27% of patients required temporal dialysis, and 19–78% required permanent dialysis. One-year survival range was between 64 and 84%; two-year survival was between 53 and 74%; five-year survival between 40 and 90%, and finally ten–year survival between 35 and 47%. Conclusions Angiotensin-converting enzyme inhibitors continue to be the first line of treatment for scleroderma renal crisis by contributing to a decrease in short-term mortality. However, alternative therapeutic options are required as a high percentage of patients still require dialysis. Future clinical trials are necessary to assess the effectiveness and safety of different therapeutic options.

Isoniazid and rifampicin are well-known anti-mycobacterial agents and are widely used to treat pulmonary tuberculosis (TB) as part of the combined therapy approach, recommended by the World Health Organization. The ingestion of these first-line TB drugs are, however, not free of side effects, and are toxic to the liver, kidney, and central nervous system. These side effects are associated with poor treatment compliance, resulting in TB treatment failure, relapse and drug resistant TB. This occurrence has subsequently led to the recent application of novel research technologies, towards a better understanding of the underlying toxicity mechanisms of TB drugs in humans, mostly focussing on the 2 most important TB drugs: isoniazid and rifampicin. In this review, we discuss the contribution that one such an approach, termed metabolomics has made toward this field, and also highlight the impact that this might have towards the development of improved TB treatment regimens.

This document on COPD from the Latin American Chest Association (ALAT-2019) uses PICO methodology to analyze new evidence on inhaled medication and answer clinical questions. The following key points emerged from this analysis: 1) evidence is lacking on the comparison of short-acting vs. long-acting bronchodilators in patients with mild COPD; patients with moderate-to-severe COPD obtain greater benefit from long-acting bronchodilators; 2) the benefits of monotherapy with long-acting antimuscarinic agents (LAMA) and combined therapy with long-acting β2-agonists and inhaled corticosteroids (LABA/ICS) are similar, although the latter is associated with a greater risk of pneumonia; 3) LABA/LAMA offer greater benefits in terms of lung function and risk of exacerbation than LABA/ICS (the latter involve an increased risk of pneumonia), 4) LAMA/LABA/ICS have greater therapeutic benefits than LABA/LAMA on the risk of moderate-severe exacerbations. With regard to the role of eosinophils in guiding the use of ICS, ICS withdrawal must be considered when the initial indication was wrong or no response is elicited, in patients with side effects such as pneumonia, and in patients with a low risk of exacerbation and an eosinophil blood count of

Purpose To investigate the prognostic factors for the combined therapy of ranibizumab and prompt verteporfin photodynamic therapy (vPDT) for eyes with polypoidal choroidal vasculopathy (PCV). Methods Sixty-two PCV eyes of 62 patients that received the initial treatment of intravitreal ranibizumab followed by vPDT within 1 week plus a 2nd intravitreal ranibizumab 1 month later in one single medical center were retrospectively enrolled. Best-corrected visual acuity (BCVA) and parameters obtained from optical coherence tomography at baseline, 3 months, 6 months and 1 year were measured and compared. Factors associated with polyp regression, recurrent hemorrhage and visual improvement were analyzed. Results After the loading treatment, complete and partial polyp regression was achieved in 53.6% and 39.3% of cases, respectively at Month 3. The mean logarithm of the minimum angle of resolution of BCVA improved from 0.64 ± 0.38 to 0.55 ± 0.46 (P = 0.008) at Month 12. Recurrent hemorrhage (P = 0.001) and previous anti-vascular endothelial growth factor (VEGF) treatment (P = 0.017) were associated with poorer visual improvement at Month 12. Incomplete polyp regression (P = 0.038) and previous anti-VEGF treatment (P = 0.005) were associated with a higher risk of recurrent hemorrhage. Conclusions Recurrent hemorrhage was associated with poor visual improvement after combined ranibizumab and vPDT for PCV. Complete polyp eradication was associated with a lower risk of recurrent hemorrhage. Patients who had previously received anti-VEGF were associated with recurrent hemorrhage and poor visual improvement; more frequent follow-ups and more aggressive subsequent treatments may be needed for these cases.

Iron chelators are extensively used to reduce iron overload. Our purpose was to compare effects of deferasirox versus deferasirox and deferoxamine in patients with thalassemia major.This randomized and double blind trial was performed on 62 patients. Patients were assigned 1:1 to oral 30 mg/kg deferasirox daily or oral 30 mg/kg deferasirox daily plus SC 50 mg/kg deferoxamine for 5 days a week. Treatment continued for 12 months in both groups.Fifty-five patients completed the 1 year of treatment. Mean age was 24.5 years with an excess of females. Combined therapy caused a significant increase in myocardial T2* from 23.1 ± 7.5 ms at baseline to 27.1 ± 7.0 ms at 12 months (P 0.05). This difference was statistically significant between 2 groups at 12 months (P = 0.01). Combined therapy and monotherapy had no significant effect on liver T2*. At 12 months, serum ferritin levels were reduced in two groups; however, the difference was significant (737 ± 459 μg/ml vs 1085 ± 919 μg/ml, P 0.01).Our study indicates that combined treatment with deferasirox and deferoxmaine is more effective than deferasirox for reduction of iron over load in patients with thalassemia major.

Little is known about long-term outcomes for pediatric brain arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS). This study investigated annual hemorrhage rates and nidus obliteration rates, and the factors affecting them, in pediatric AVMs treated with GKRS.We examined 189 pediatric AVM patients (age ≤15 years) who underwent GKRS and had at least 12 months of follow-up. The Spetzler-Martin (S-M) grade was I in 29 patients (15%), II in 57 (30%), III in 82 (43%), IV in 16 (9%), and V in 5 (3%). The median treatment volume was 2.2 cmThe mean follow-up period was 136 months. During a cumulative latency period to nidus obliteration of 813 years, 23 hemorrhages occurred, resulting in an annual post-GKRS hemorrhage rate of 2.8%. The cumulative hemorrhage rates after GKRS were 3.3%, 8.5%, and 11.9% at 3, 5, and 10 years, respectively. Higher S-M grade was significantly associated with intracranial hemorrhages during the latency period (P0.001). The actuarial nidus obliteration rates with repeated GKRS were 64% and 81% at 5 and 10 years, respectively. Absence of pre-GKRS embolization (P = 0.023) and higher marginal dose (P = 0.029) were significant factors predicting nidus obliteration.GKRS is a reasonable treatment option in pediatric AVMs to prevent future hemorrhages. Because higher S-M grade AVMs are more likely to hemorrhage during the latency period, a combined therapy with endovascular embolization should be considered to prevent AVM rupture.

Highlights • Significance of resection in patients with pancreatic metastasis from lung cancer. • A long-term survivor of pancreatic metastasis from lung cancer after pancreatectomy. • Consider resection if the disease is localized and the patient’s condition is good., Introduction Pancreatic metastasis from lung cancer is not an indication for surgical resection because patients with such a condition present with multiple-organ metastases. Therefore, the significance of resection in patients with pancreatic metastasis from lung cancer remains unclear. Here we report a case of a long-term survivor of pancreatic metastasis from lung cancer after pancreatectomy. Case presentation A 67-year-old woman presented with a pancreatic mass. She had undergone left lower lobectomy for stage IIIA lung adenocarcinoma 6 years prior to presentation. Following surgery, she received adjuvant treatment with gefitinib for 7 months. However, this treatment was discontinued due to its side effects. The patient received radiation therapy for mediastinal lymph node metastasis 2 years after resection and she became cancer-free. Six years after the initial pulmonary resection, the patient’s tumor marker level increased, and abdominal computed tomography (CT) revealed a 20-mm tumor in the pancreatic tail. Positron emission tomography–CT revealed an abnormal uptake in the pancreatic tail. However, no other abnormal lesions were observed. The diagnosis was primary pancreatic cancer or metastasis from lung cancer. Distal pancreatectomy with lymph node dissection was performed, and the pathological diagnosis was metastasis from lung cancer. The patient survived for more than 5 years without recurrence but she died of acute renal failure after acquiring pneumonia. Conclusion Surgical treatment should be considered for pancreatic metastasis from lung cancer if the disease is localized and the patient’s condition is good. Additionally, combined therapy, including surgical resection, may be effective for repeated recurrence.

Demand for noninvasive aesthetic medicine options is increasing because of the popularity of nonsurgical procedures and industry's focus on direct-to-consumer marketing. Such techniques as nonablative and ablative lasers, intense pulsed light, radiofrequency, high-intensity focused ultrasound, and skin care with peeling agents may also be used in conjunction with surgery to optimize overall aesthetic results. To maximize benefits, the provider must have a detailed understanding of the science behind each device. Combined therapy is safe and well tolerated by many patients in an office-based setting. Although surgery remains the gold standard, nonsurgical therapy should be a portion of surgical practices.

Severe forms of periodontitis can often result in pathological tooth migration. In such cases, orthodontic realignment is an indispensable complement to periodontal management. However, in some cases involving very advanced periodontal destruction, the question arises as to the limits of conservative treatment. Are the results of orthodontic periodontic treatment stable over time? All orthodontic treatment must be preceded by reduction of the inflammation. This paper uses clinical cases to illustrate each step to be followed in the periodontal therapeutic process in order to achieve successful orthodontic-periodontal treatment from etiologic therapy to surgical decontamination and long-term periodontal follow-up.

Hepatic injury is the major limitation of long-term albendazole administration in patients with cystic echinococcosis (CE), which could give rise to cessation of treatment. The objective of the present study was to evaluate the protective effects of Zataria multiflora aromatic water (AW) against the hepatic injury induced by long-term albendazole treatment in mice with CE. Fifty healthy BALB/c female mice were infected intraperitoneally by injection of 1500 protoscoleces per animal. Five months after infection, the infected animals were divided into five treatment groups including Z. multiflora (40ml/l in drinking water for 90days), albendazole (200mg/kg/day for 90days), Z. multiflora+albendazole 200 (40ml/l Z. multiflora and 200mg/kg/day albendazole for 90days), Z. multiflora+albendazole100 (40ml/l Z. multiflora and 100mg/kg/day albendazole for 90days), and untreated (control) group. At the end of the treatment period, anesthesia was performed and blood samples were collected directly from the heart prior to euthanasia. Liver variables and oxidative stress markers were measured in the blood serum samples. A decrease in serum liver enzyme activity in the both Z. multiflora+albendazole groups was observed when compared to control, Z. multiflora and albendazole groups; however, the results for Z. multiflora+albendazole 100 were significant (p

Objective To observe the clinical effect on thoracic facet joint disorder syndrome treated with the sitting-pushing manipulation, acupuncture at Yanglingquan (阳陵泉 GB34) and bloodletting at Wĕizhōng (委中 BL40). Methods A total of 40 patients of thoracic facet joint disorder syndrome were treated with the combined therapy of the sitting-pushing manipulation, acupuncture at GB34 and bloodletting at BL40, once every two days. The therapeutic effect was evaluated 6 days later. Results After treatment, of 40 cases of thoracic facet joint disorder syndrome, 31 cases were cured, 5 cases improved, 2 cases effective and 2 cases failed. The curative rate was 77.5% and the total effective rate was 95%. Visual analog scale (VAS) was (4.1 ± 1.4) points before treatment and was (2.2 ± 0.6) points after treatment, indicating the statistical difference in comparison before and after treatment (P Conclusion The sitting-pushing manipulation combined with acupuncture at GB34 and bloodletting at BL 40 achieves a very satisfactory therapeutic effect on thoracic facet joint disorder syndrome. Such combined therapy is a kind of favorable method for thoracic facet joint disorder syndrome.

Combined therapy can improve the curative effect and reduce side effect, so it has a broad application prospect in the treatment of bacterial infections especially bacterial biofilm infections. Herein, we propose a photothermal-activated multifunctional nano-antibacterial platform that is constructed by Introducing indocyanine green (ICG) photosensitizers and silver nanoparticles (AgNPs) onto Molybdenum disulfide (MoS2) nanosheets surface. The constructed nanoplatform (MoS2/ICG/Ag) has the combined chemo/photothermal/photodynamic triple-mode antibacterial capability under a single 808 nm laser irradiation. Briefly, the photonic hyperthermia generated by MoS2 nanosheets can not only directly kill bacteria, but also accelerate the release of ICG and silver ions, and the latter is a commonly used chemical antibacterial reagent. The released ICG can catalyze the conversion of oxygen into singlet oxygen with the help of 808 nm light, achieving the photodynamic sterilization. Encouragingly, the loaded ICG and AgNPs can in turn enhance the heat, which is a mutually reinforcing effect that can produce a combined or even synergistic therapeutic effect. In vitro experiments demonstrate that the MoS2/ICG/Ag with triple bactericidal modalities has good broad-spectrum antibacterial performance. Importantly, it can remarkably inhibit the S. aureus biofilms formation and effectively eradicate the bacteria deep in the biofilms. In addition, the MoS2/ICG/Ag is successfully used for treating S. aureus biofilms-infected wound in vivo with minimal toxicity. Taken together, the developed MoS2/ICG/Ag nanoplatform may serve as a potential nano-antibacterial agent for photothermally activated multimodal combined antibacterial and antibiofilm therapy.

Aims: Besides suppressing anti-tumoral immune responses, tumor-intrinsic inhibitory immune checkpoints have been implicated in tumor development. Herein, we aimed to investigate the significance of tumor-intrinsic CD73, as an inhibitory immune checkpoint, in non-small cell lung cancer (NSCLC) development and propose a novel therapeutic approach. Main methods: We investigated the cell viability, chemosensitivity, apoptosis, migration, and the cell cycle of A-549 and NCI-H1299 following treatment with cisplatin and CD73-small interfering RNA (siRNA) transfection. The 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to study the viability of studied groups and chemosensitivity of tumoral cells. Flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining were used to investigate the apoptosis of NSCLC cells. Flow cytometry and the wound-healing assay were used to investigate the cell cycle and migration of NSCLC cells, respectively. The mRNA expression levels of c-Myc, caspase 3, ROCK, and MMP-9 were investigated to study the underlying molecular mechanism. Key findings: CD73-siRNA transfection has significantly decreased the cell viability and enhanced the chemosensitivity of A-549 and NCI-H1299 cells to cisplatin. CD73-siRNA has considerably stimulated apoptosis, arrested the cell cycle, inhibited tumor migration, downregulated the mRNA expression of c-Myc, MMP-9, and ROCK, and upregulated caspase 3 expression in NSCLC cells. Besides, combined cisplatin therapy with CD73-siRNA transfection has potentiated the aforementioned anti-tumoral effects of cisplatin on NSCLC cells. Significance: Besides suppressing anti-tumoral immune responses, tumor-intrinsic CD73 can facilitate NSCLC development, and the combined cisplatin therapy with CD73-siRNA transfection can substantially enhance the chemosensitivity of NSCLC to cisplatin and potentiates cisplatin-induced anti-tumoral effects on NSCLC.

Nucleic acid (NA) therapeutics are a rapidly growing class of biomedicines with the ability to manipulate gene expression in potent and specific manner, and with the enormous potential in the treatment of life-threatening diseases. Sensibility towards physiological barriers that compromises their therapeutic applicability led to design of highly functional polymeric micelles (PMs). PMs constitute colloidal polymer-based core-shell structures composed of amphiphilic building blocks, serving as efficient NA delivery platforms based on their ability to accommodate NAs mainly through electrostatic-driven complexation processes. Facile manipulation of polymeric building blocks offers the possibility to tune crucial parameters indispensable for NA protection and efficacious delivery to targeted sites. Ordered core-shell structure enables incorporation of other therapeutic/diagnostic agents, presenting possibility for combined therapy and theranostics. In this review we highlight design, characterization, major developments and latest applications of PMs, and provide a critical overview of current challenges and future prospects of PMs as potential NA-based delivery systems aimed at improved NA therapies.

Highlights • Primary breast lymphoma (PBL) is a rare disease accounting for 0.04–0.5% of all breast malignancies. • The clinical and imaging findings in breast lymphoma can mimic those of breast carcinoma. • Sometimes, PBL presentation is suggestive of Inflammatory breast cancer. • Diagnosis depends on adequate tissue sampling for histology examination and immunophenotyping. • The therapeutic management of PBL is controversial and is not clearly established, but many studies support that it is not a surgical disease and can be treated successfully with combined chemotherapy and radiotherapy. • Imaging is a useful method to monitor a patient’s response to therapy., Introduction Primary breast lymphoma (PBL) is a rare disease accounting for 0.04–0.5% of all breast malignancies. Presentation of case This article reports a clinical case of a 81-year-old woman with a history of right breast erythema and edema associated to breast pain, with over two weeks duration. Physical examination demonstrated mammary asymmetry and inflammatory signs with orange peel skin. She had the right upper limb swollen and palpable axillar and supraclavicular lymph nodes. The principal suspicion was an inflammatory breast cancer. Imaging was unspecific. Core needle biopsy of an axillary lymph node and of the breast mass identified morphological and immunophenotypic features consistent with diagnosis of primary non-Hodgkin DLBCL. Patient was guided by Hematology. Discussion The clinical and imaging findings in breast lymphoma can mimic those of breast carcinoma. Sometimes, PBL presentation is suggestive of Inflammatory breast cancer. Diagnosis depends on adequate tissue sampling for histology examination and immunophenotyping. The therapeutic management of PBL is controversial and is not clearly established, but many studies support that it is not a surgical disease and can be treated successfully with combined chemotherapy and radiotherapy. Conclusion Breast lymphoma must be considered in the differential diagnosis of a breast lump, even in the presence of cutaneous inflammatory changes. PBL can be treated successfully with combined therapy.

Several studies have shown that an adequate therapy for glycemic control in patients with type 2 diabetes mellitus (T2DM) can delay or prevent complications derived from this condition. To achieve the control objectives an adequate therapy should be performed by using insulin alone or in combination with an oral hypoglycemic agent. However, the key point of glycemic control is to determine the amount of insulin to be delivered. In order to achieve the above different strategies have been proposed, one of them is the design of feedback control algorithms. In this article a robust feedback control algorithm of glycemia in T2DM was designed. The algorithm determines the continuous insulin infusion to be delivered to maintain normoglycemia considering a combined therapy with a dose of metformin. The problem approach was to find a controller that minimized in the sense of the H∞ norm: i) the difference between the glycemia of a T2DM patient and a healthy subject (tracking problem) and ii) the effect of disturbances due to glucose intake and noise from a glucose sensor.

As one of the main elements in the living organisms, phosphorus makes an important impact on the life activity. Phosphorus contained compounds have been widely applied in the biomedical field. As nanotechnology develops, a variety of phosphorus-based nanomaterials have also been developed for the biomedical application. The recently discovered superior biological property of two-dimensional black phosphorus (2D BP), i.e. phosphorene, including low toxicity and biodegradability, makes it especially outstanding, such as biosensors for the disease diagnosis. Upon light or ultrasound irradiation on the phosphorene, reactive oxygen species (ROS) or heat can be generated for the disease therapy. Moreover, phosphorene can smartly and efficiently deliver drugs. Thus, it is suitable in many single or combined therapy modalities. This short article reviews the progress from phosphorus to phosphorene to be used as biomedical materials, especially the phosphorene as the biosensor and sensitizer for the disease diagnosis and therapy, including the tumor, the neurodegenerative disease, the bone disease and other diseases. The challenges and prospective of the phosphorene for the biomedical applications are also discussed.

We previously reported the anticancer activity of 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N′-methylpropylamino]-3,4-dihydroquinazoline (OZ-001), a T-type calcium channel (TTCC) blocker, against non-small cell lung cancer (NSCLC) in vitro and in vivo. Here, we evaluated the synergistic effect of OZ-001 and cisplatin on A549 human lung cancer cells and A549 xenograft mice. Our study demonstrated that treatment with OZ-001 and cisplatin sensitized A549 cells to cisplatin and significantly inhibited cell growth, increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and induced poly (ADP-ribose) polymerase (PARP) cleavage in A549 cells and an A549 xenograft tumor mouse model. Moreover, our findings showed that mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and signal transducer and activator of transcription (STAT3) inactivation was required for apoptosis induced by the combination of OZ-001 and cisplatin in in vitro and in vivo experiments. Our results suggest that combined treatment with OZ-001 and cisplatin could potentiate antiproliferative effects via suppression of the mTOR/p70S6K and STAT3 pathways and may be considered a potential therapeutic agent for NSCLC.

Tissue engineering strategies, notably biomaterials, can be modularly designed and tuned to match specific patient needs. Although many challenges within tissue engineering remain, the incorporation of diagnostic strategies to create theranostic (combined therapy and diagnostic) biomaterials presents a unique platform to provide dual monitoring and treatment capabilities and advance the field toward personalized technologies. In this review, we summarize recent developments in this young field of regenerative theranostics and discuss the clinical potential and outlook of these systems from a tissue engineering perspective. As the need for precision and personalized medicines continues to increase to address diseases in all tissues in a patient-specific manner, we envision that such theranostic platforms can serve these needs.

Early detection and efficient treatment of cancer disease remains a drastic challenge in 21st century. Throughout the bulk of funds, studies, and current therapeutics, cancer seems to aggressively advance with drug resistance strains and recurrence rates. Nevertheless, nanotechnologies have indeed given hope to be the next generation for oncology applications. According to US National cancer institute, it is anticipated to revolutionize the perspectives of cancer diagnosis and therapy. With such success, nano-hybrid strategy creates a marvelous preference. Herein, graphene-gold based composites are being increasingly studied in the field of oncology, for their outstanding performance as robust vehicle of therapeutic agents, built-in optical diagnostic features, and functionality as theranostic system. Additional modes of treatments are also applicable including photothermal, photodynamic, as well as combined therapy. This review aims to demonstrate the various cancer-related applications of graphene-gold based hybrids in terms of detection and therapy, highlighting the major attributes that led to designate such system as a promising ally in the war against cancer.

The complex heterogeneous structure of biofilms confers to bacteria an important survival strategy. Biofilms are frequently involved in many chronic infections in consequence of their low susceptibility to antibiotics as well as resistance to host defences. The increasing need of novel and effective treatments to target these complex structures has led to a growing interest on bacteriophages (phages) as a strategy for biofilm control and prevention. Phages can be used alone, as a cocktail to broaden the spectra of activity, or in combination with other antimicrobials to improve their efficacy. Here, we summarize the studies involving the use of phages for the treatment or prevention of bacterial biofilms, highlighting the biofilm features that can be tackled with phages or combined therapy approaches., This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the project PTDC/BBB-BSS/6471/2014, the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). This work was also supported by BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte., info:eu-repo/semantics/publishedVersion

Summary Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

Myeloproliferative neoplasms are driven by activated JAK2 signaling due to somatic mutations in JAK2, the thrombopoietin receptor MPL or the chaperone calreticulin in hematopoietic stem/progenitor cells. JAK2 inhibitors have been developed, but despite clinical benefits, they do not signficantly reduce the mutant clone. Loss of response to JAK2 inhibitors occurs and several mechanisms of resistance, genetic and functional, have been identified. Resistance mutations have not been reported in MPN patients suggesting incomplete target inhibition. Alternative targeting of JAK2 by HSP90 inhibitors or type II JAK2 inhibition overcomes resistance to current JAK2 inhibitors. Additional combined therapy approaches are currently being evaluated.

Near infrared (NIR) light allows deep tissue penetration and high spatial resolution due to the reduced scattering of long-wavelength photons. NIR light-activatable polymer nanoparticles are widely exploited for enhanced cancer imaging (diagnosis) and therapy owing to their superior photostability, photothermal conversion efficiency (or high emission rate), and minimal toxicity to cells and tissues. This review surveys the most recent advances in the synthesis of different NIR-absorbing and emissive polymer nanoformulations, and their applications for cancer imaging, photothermal therapy, theranostics and combination therapy by delivering multiple small molecule chemotherapeutics. Photo-responsive drug delivery systems for NIR light-triggered drug release are also discussed with particular emphasis on their molecular designs and formulations as well as photo-reaction mechanisms. Finally, outlook and challenges are presented regarding potential clinical applications of NIR light-activatable nanoformulations.

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease.The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations.This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs. Resumen: La incorporación de nuevos medicamentos para modificar el curso de la esclerosis múltiple y la complejidad de su uso plantea la conveniencia de utilizar consensos terapéuticos. El consenso actual ha sido elaborado por el grupo de enfermedades desmielinizantes de la Sociedad Española de Neurología y actualiza consensos previamente publicados.Se enumeran los medicamentos aprobados para la esclerosis múltiple con sus indicaciones oficiales. Se analizan aspectos relacionados con el tratamiento, como la presencia de actividad, la precocidad, el mantenimiento terapéutico, el seguimiento, el fallo terapéutico, los cambios de medicación y el tratamiento en situaciones especiales.Se elaboran indicaciones de tratamiento desde el síndrome desmielinizante aislado a las distintas formas de esclerosis múltiple detallando recomendaciones de tratamiento inicial, cambios de medicación, con consideraciones sobre terapia combinada e inducción y aspectos prácticos del uso de medicamentos. Keywords: Multiple sclerosis, Consensus statement, Disease-modifying drugs, Lines of therapy, Changes in medication, Algorithm, Palabras clave: Esclerosis múltiple, Consenso, Medicamentos para el curso de la enfermedad, Líneas terapéuticas, Cambios de medicación, Algoritmo

Embolization has been proposed to reduce the size of the arteriovenous malformation (AVM) nidus in advance of radiosurgical treatment. Embolization followed by radiosurgery for brain AVMs, however, is controversial.We assessed the impact of embolization on nidal size before radiosurgical treatment and evaluated cure rates and complications by using embolization followed by radiosurgery.A retrospective review of our institutional AVM database identified 91 patients treated from 1995 to 2009 with embolization followed by radiosurgery. Pre- and postembolization AVM volumes were measured with angiography, and the modified radiation-based AVM scores (RBAS) also were calculated pre- and postembolization. RBAS determined from pre-embolization volumes were correlated with postradiosurgical obliteration.Median AVM volume declined from 18.8 mL (interquartile range, 10.2-32.2 mL) to 9.9 mL (3.1-19.2 mL) after embolization, P0.00003. Median RBAS scores decreased from 2.6 mL (1.8-3.9 mL) to 1.8 mL (1.0-2.8 mL), P0.00003. Two of 91 (2.2%) had new fixed deficits after embolization; however, no patient had new disabling deficits (modified Rankin Scale score2). A total of 71 of 91 (79%) have had3 years' follow-up, and 40 (56%) had complete obliteration, with 38 (53%) having excellent outcomes (complete obliteration without neurologic decline). Excellent outcome was seen in 90% of patients with modified RBAS score1, 66% of patients with score 1-1.5, 50% patients with score 1.5-2, and 43% of patients with score2.These data suggest that embolization of brain AVMs can safely and effectively reduce the treatment volume before radiosurgery. Combined therapy with embolization and radiosurgery does not appear to adversely affect rates of excellent outcome.

Objective To observe the clinical therapeutic effects on acne treated with the combined therapy of acupuncture, cupping and circling moxibustion. Methods At the ratio of 4:3, a total of 70 patients were randomized into an acupuncture-cupping group (40 cases) and a western medication group (30 cases). In the acupuncture-cupping group, acupuncture was used in combination with cupping and circling moxibustion. The therapy was given once every other day for totally 30 days. In the western medication group, the routine medication of minocyline capsules was prescribed, 2 times per day and 30 days were in total. Results After the treatment, the total effective rates were 95.00% and 76.67% in the acupuncture-cupping group and the western medicine group respectively, indicating the significant difference in statistic (P Conclusion Acupuncture combined with cupping and circling moxibustion achieves the superior clinical therapeutic effects as compared with minocyline. This therapy deserves to be promoted in clinical practice.

Purpose To evaluate the efficacy of topical ivermectin-metronidazole combined therapy in the management of Demodex-associatedblepharitis. Methods Sixty patients with a diagnosis of Demodex-associatedblepharitis were recruited in a randomized clinical trial. Thirty receiving topical ivermectin (0.1%)-metronidazole (1%) gel treatment on days 0, 15 and 30. Thirty additional patients were used as a control group receiving vehicle on days 0, 15 and 30. The primary efficacy measure was the number of Demodex spp. mitesin the eyelashes of patients. The secondary outcomes included clinical improvement of signs and adverse events. Results Complete eradication of Demodex spp. was found in 96.6% of patients in the treatment group. Furthermore, a significant reduction of inflammation signs were found in all treated patients versus controls. None of the patients experienced any adverse effects associated with the treatment. Conclusion Demodex infection was controlled satisfactorily with the ivermectin (0.1%)-metronidazole (1%) gel, and no adverse effects were observed. Application of this gel for the treatment of different parasitic infections of the eyelids could be feasible, and this requires further exploration.

Purpose This study aimed to evaluate pain levels before and after Su Jok therapy. Methods This research was a retrospective study from data collected in September–December 2019 in Indonesia. A total of 33 females and 13 males complaining of physical pain when visiting community services’ activities and treated by a certified Su Jok therapist were included in this study. Physical pain scale was analyzed before and after therapy. Wilcoxon signed-rank tests were used for statistical analysis. Results As many as 57 physical complaints were recorded from 46 respondents. The most common area of pain was the extremities (32%). The types of therapy were energy therapy, correspondence therapy and combined therapy (energy and correspondence therapy). Combination therapy had 100% success in reducing the pain scale. There were significant differences in pain level before and after Su Jok therapy (p Conclusion Su Jok therapy provides an effective treatment in reducing pain.

We have evaluated the effect of POLI-CHI hydrogel based on policaju (POLI) from cashew tree (Anacardium occidentale L.) gum and chitosan (CHI), associated or not with Low level laser therapy (LLLT), in wound healing. Sixty male Wistar rats were assigned into four groups: POLI-CHI hydrogel (H); LLLT (L); POLI-CHI with LLLT (HL) and saline control (C). Macroscopic evaluations were carried out using clinical observations and area measurements, as well as microscopic analysis by histological criteria. H and HL presented more esthetical scar tissue and larger wound contraction compared to C. Histopathological analyzes showed: stronger presence of fibrin-leukocyte crust in L and HL at day 3; stronger collagen presence in H, L and HL; weak presence of focal necrosis at 7 and 14days in H; weak neutrophilic exudate in H, L and HL; regression of the vascular neoformation at 7days in H, and modulation of the same in L and HL. These results demonstrated that POLI-CHI contributed to more efficient healing process and modulation of the inflammation; furthermore, the combined use with LLLT subtle potentiated this process.

Few investigations evaluated the long-term effects of psychotherapies in borderline personality disorder (BPD). In a previous study, we compared efficacy of combination of fluoxetine and interpersonal psychotherapy adapted to BPD (IPT-BPD) versus single fluoxetine administered for 32 weeks. This study is aimed to investigate whether the results obtained with the addition of IPT-BPD persist during a follow-up period. Forty-four patients who completed the 32 weeks trial underwent 24 months of follow-up receiving fluoxetine 20-40 mg/day. Clinical Global Impression Severity (CGI-S), Hamilton Rating Scales for Depression and Anxiety (HDRS, HARS), Social and Occupational Functioning Assessment Scale (SOFAS), Satisfaction Profile (SAT-P), and Borderline Personality Disorder Severity Index (BPDSI) were repeated at 6, 12, and 24 months. Statistical analysis was performed with the general linear model. Results showed that most of the differences between combined therapy and single pharmacotherapy at the end of the 32 weeks trial were maintained after 24 months follow-up. The addition of IPT-BPD to medication produced greater effects on BPD symptoms (impulsivity and interpersonal relationships) and quality of life (perception of psychological and social functioning) that endured after termination of psychotherapy. On the contrary, different effects on anxiety symptoms and affective instability were lost after 6 months.

A double-blind, randomized controlled trial was conducted in an endemic focus for Schistosoma mansoni in Kafr El-Sheikh Governorate, Northern Nile Delta, Egypt, to evaluate the prophylactic effect of artemether (ART) given in conjunction with praziquantel (PZQ). The study encompassed 913 primary school children randomly assigned to two treatment groups PZQ/ART and PZQ/ART-placebo. At baseline, both groups received 40 mg/kg body weight of PZQ twice four weeks apart, after which one group received 6 mg/kg body weight of ART every 3 weeks in 5 cycles during the transmission season and the other group received ART-placebo. At the end of the study, prevalence of infection among the PZQ/ART was approximately half that of the PZQ/ART-placebo group, i.e. 6.7% versus 11.6%, and incidence of new infections for the PZQ/ART was 2.7% versus 6.5% for the PZQ/ART-placebo. In conclusion, PZQ/ART combined therapy might be considered as an adjunct measure against human schistosomiasis, by specifically reducing transmission and therefore contribute to disease elimination.

A variety of conservative treatments for burn scars are available, but there is no clear consensus on the evidence. The purpose of this study was to summarize the available literature on the effects of conservative treatments of burn scars in adults. RCTs and CCTs were sought in three databases, reference lists of retrieved articles and relevant reviews. The Scottish Intercollegiate Guidelines Network scoring system was used to assess the quality of the selected studies. Information on the study characteristics, results and interventions was extracted. Twenty-two articles were included into the review and categorized in six topics: 5 on massage therapy, 4 on pressure therapy, 6 on silicone gel application, 3 on combined therapy of pressure and silicone, 3 on hydration and 1 on ultrasound. Pressure and silicone therapy are evidence-based conservative treatments of hypertrophic scar formation after a burn producing clinically relevant improvement of scar thickness, redness and pliability. Massage therapy could have a positive result on scar pliability, pain and pruritus, but with less supporting evidence. The use of moisturizers and lotions could have an effect on itching, but the findings are contradictory. Of all other non-invasive treatments such as splinting, casting, physical activity, exercise and mobilizations no RCTs or CCTs were found. publisher: Elsevier articletitle: The effects of conservative treatments on burn scars: A systematic review journaltitle: Burns articlelink: http://dx.doi.org/10.1016/j.burns.2015.12.006 content_type: article copyright: © 2015 Elsevier Ltd and ISBI. All rights reserved. ispartof: Burns vol:42 issue:3 pages:508-518 ispartof: location:Netherlands status: published

The 21st century has seen rapid, positive changes in the management of chronic lymphocytic leukaemia from the patient's perspective. New prognostic and predictive markers have ushered in the start of more precise and individualized therapy. For the first time, combined therapy [fludarabine, cyclophosphamide and rituximab] has been shown to prolong life significantly. Clinical trials have become more adaptive, faster and more patient friendly. Perhaps the greatest change of all is the development of novel oral agents (ibrutinib and idelalisib) and powerful monoclonal antibodies that offer robust and durable disease control. Finally, access to and understanding of these changes through an empowered and educated patient population has grown through live education forums and the Internet.