Memorial Ankara Hospital

Next-Generation Gene Therapy Few disciplines in contemporary clinical research have experienced the high expectations directed at the gene therapy field. However, gene therapy has been challenging to translate to the clinic, often because the therapeutic gene is expressed at insufficient levels in the patient or because the gene delivery vector integrates near protooncogenes, which can cause leukemia (see the Perspective by Verma ). Biffi et al. ( 1233158 , published online 11 July) and Aiuti et al. ( 1233151 ; published online 11 July) report progress on both fronts in gene therapy trials of three patients with metachromatic leukodystrophy (MLD), a neurodegenerative disorder, and three patients with Wiskott-Aldrich syndrome (WAS), an immunodeficiency disorder. Optimized lentiviral vectors were used to introduce functional MLD or WAS genes into the patients' hematopoietic stem cells (HSCs) ex vivo, and the transduced cells were then infused back into the patients, who were then monitored for up to 2 years. In both trials, the patients showed stable engraftment of the transduced HSC and high expression levels of functional MLD or WAS genes. Encouragingly, there was no evidence of lentiviral vector integration near proto-oncogenes, and the gene therapy treatment halted disease progression in most patients. A longer follow-up period will be needed to further validate efficacy and safety.

OBJECTIVE: The aim of this study was to measure the elasticity of various tissues and report it in kilopascals. SUBJECTS AND METHODS: The thyroid, submandibular, and parotid glands, masseter and gastrocnemius muscles, supraspinatus and Achilles tendons, renal cortex and pelvis, pancreas, and spleen of 127 healthy volunteers (89 women, 38 men; mean age, 37.72 ± 9.11 years; range, 17-63 years) were evaluated with shear-wave ultrasound elastography. RESULTS: The mean elasticity values were determined to be 10.97 ± 3.1 kPa for the thyroid, 10.92 ± 3.1 kPa for the submandibular glands, 10.38 ± 3.5 kPa for the parotid glands, 10.4 ± 3.7 kPa for the masseter muscle, 11.1 ± 4.1 kPa for the gastrocnemius muscle, 31.2 ± 13 kPa for the supraspinatus muscle, 51.5 ± 25.1 kPa for the Achilles tendons, 5.0 ± 2.9 kPa for the renal cortex, 23.6 ± 5.4 kPa for the renal pelvis, 4.8 ± 3 kPa for the pancreas, and 2.9 ± 1.8 kPa for the spleen. CONCLUSION: Elasticity values were determined for different tissues with shear-wave ultrasound elastography. Further studies comparing the elasticity values of normal and pathologic tissues are necessary to determine the diagnostic role of this technique.

Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.

INTRODUCTION: The Woven EndoBridge Intrasaccular Therapy (WEB-IT) Study is a pivotal, prospective, single-arm, investigational device exemption study designed to evaluate the safety and effectiveness of the WEB device for the treatment of wide-neck bifurcation aneurysms. METHODS: One-hundred and fifty patients with wide-neck bifurcation aneurysms were enrolled at 21 US and six international centers. Angiograms from the index procedure, and 6-month and 1-year follow-up visits were all reviewed by a core laboratory. All adverse events were reviewed and adjudicated by a clinical events adjudicator. A data monitoring committee provided oversight during the trial to ensure subject safety. RESULTS: One-hundred and forty-eight patients received the WEB implant. One (0.7%) primary safety event occurred during the study-a delayed ipsilateral parenchymal hemorrhage-on postoperative day 22. No primary safety events occurred after 30 days through 1 year. At the 12-month angiographic follow-up, 77/143 patients (53.8%) had complete aneurysm occlusion. Adequate occlusion was achieved in 121/143 (84.6%) subjects. CONCLUSIONS: The prespecified safety and effectiveness endpoints for the aneurysms studied in the WEB-IT trial were met. The results of this trial suggest that the WEB device provides an option for patients with wide-neck bifurcation aneurysms that is as effective as currently available therapies and markedly safer. TRIAL REGISTRATION NUMBER: NCT02191618.

BACKGROUND: Neuroinflammation has an important role in the pathophysiology of migraine, which is a complex neuro-glio-vascular disorder. The main aim of this review is to highlight findings of cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma from the inflammasome perspective. In addition, we discuss the limited data of the contribution of inflammasomes to other aspects of migraine pathophysiology, foremost the activation of the trigeminovascular system and thereby the generation of migraine pain. MAIN BODY: Inflammasomes are signaling multiprotein complexes and key components of the innate immune system. Their activation causes the production of inflammatory cytokines that can stimulate trigeminal neurons and are thus relevant to the generation of migraine pain. The contribution of inflammasome activation to pain signaling has attracted considerable attention in recent years. Nucleotide-binding domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is the best characterized inflammasome and there is emerging evidence of its role in a variety of inflammatory pain conditions, including migraine. In this review, we discuss, from an inflammasome point of view, cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma, the connection with genetic factors that make the brain vulnerable to CSD, and the relation of the inflammasome with diseases that are co-morbid with migraine, including stroke, epilepsy, and the possible links with COVID-19 infection. CONCLUSION: Neuroinflammatory pathways, specifically those involving inflammasome proteins, seem promising candidates as treatment targets, and perhaps even biomarkers, in migraine.

Abstract Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic 1,2 . Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches 1 , while maintaining proven prevention measures using a vaccines-plus approach 2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities 3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

OBJECTIVE: To detect the effectiveness of incremental speed-dependent treadmill training on postural instability, dynamic balance and fear of falling in patients with idiopathic Parkinson's disease. DESIGN: Randomized controlled trial. SETTING: Ankara Education and Research Hospital, 2nd PM&R Clinic, Cardiopulmonary Rehabilitation Unit. SUBJECTS: Fifty-four patients with idiopathic Parkinson's disease in stage 2 or 3 of the Hoehn Yahr staging entered, and 31 patients (21 training, 10 control) had outcome data. INTERVENTIONS: Postural instability of patients with Parkinson's disease was assessed using the motor component of the Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale. Twenty-one patients with Parkinson's disease participated in an eight-week exercise programme using incremental speed-dependent treadmill training. Before and after the training programme, balance, gait, fear of falling and walking distance and speed on treadmill were assessed in both Parkinson's disease groups. MAIN MEASURES: Walking distance and speed on treadmill, UPDRS, Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale. RESULTS: Initial total walking distance of the training group on treadmill was 266.45 +/- 82.14 m and this was progressively increased to 726.36 +/- 93.1 m after 16 training session (P < 0.001). Tolerated maximum speed of the training group on treadmill at baseline was 1.9 +/- 0.75 km/h and improved to 2.61 +/- 0.77 km/h (P < 0.001). Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale scores of the training group were improved significantly after the training programme (P < 0.01). There was no significant improvement in any of the outcome measurements in the control group (P > 0.05). CONCLUSIONS: Specific exercise programmes using incremental speed-dependent treadmill training may improve mobility, reduce postural instability and fear of falling in patients with Parkinson's disease.

Coronavirus disease (COVID-19) was firstly reported at the end of 2019. The disease rapidly spread all around the world in a few months and was declared a worldwide pandemic by WHO in March 2020. By April 9, there were 1,436,198 confirmed COVID-19 cases in the world, nearly with 6% mortality rate. This novel infectious disease causes respiratory tract illness that may generally occur as mild upper respiratory tract disease or pneumonia. In older patients and/or patients with underlying conditions, it may result in acute respiratory distress syndrome, multi organ failure and even death. According to the current literature, children account approximately for 1%-5% of diagnosed COVID-19 cases. Generally, COVID-19 seems to be a less severe disease for children than adults. Approximately 90% of pediatric patients are diagnosed as asymptomatic, mild, or moderate disease. However, up to 6.7% of cases may be severe. Severe illness is generally seen in patients smaller than 1 year of age and patients who have underlying disesases. The epidemiological and clinical patterns of COVID-19 and treatment approaches in pediatric patients still remain unclear although many pediatric reports are published. This review aims to summarize the current epidemics, clinical presentations, diagnosis, and treatment of COVID-19 in pediatric patients.

BACKGROUND: The present study examined the relationship between psychological variables, including anxiety, depression, and patient-controlled analgesia (PCA) use in patients who underwent radical mastectomy. METHODS: Ninety-nine ASA I-II women with breast cancer between 18 and 60 years scheduled for modified radical mastectomy completed the state scale of the state-trait anxiety inventory and the Beck depression inventory before the day of surgery. Standard general anesthesia, surgery, and IV-PCA therapy was conducted. Postoperative ratings of pain intensity, opioid consumption and satisfaction with PCA were recorded for the first 24 h on the ward. The degree of pain intensity was evaluated by a visual analog scale (VAS, 1-10). Satisfaction with pain control was reported using an five-point scale from 1 (very dissatisfied) to 5 (very satisfied). RESULTS: The pain intensity, total analgesic consumption and dose/demand ratio were significantly related to preoperative anxiety and depression (P<0.05). Degree of dissatisfaction with PCA was significantly correlated with preoperative anxiety and depression (P<0.01). CONCLUSION: Patients with higher anxiety and depression levels had higher postoperative pain and analgesic requirements in this study.

OBJECTIVE: The frequency of vaccine refusal, which is associated with many factors, is increasing worldwide. The aim of this study was to predict the frequency of vaccine refusal against domestic and foreign COVID-19 vaccines and identify the factors underlying refusal. METHODS: A survey consisting of 16 questions about COVID-19 vaccination was conducted either face-to-face or online with 428 parents who agreed to participate in the study. The parents had children who were inpatients or outpatients in the Children's Hospital of Ankara City Hospital. In the survey, parents were asked about family sociodemographic characteristics, opinions on domestic and foreign COVID-19 vaccines, and reasons for vaccine refusal. RESULTS: While 66.1% of parents were reluctant to receive foreign COVID-19 vaccines, only 37.4% were reluctant to receive domestic COVID-19 vaccines. The participants' preference for the domestic vaccine was significantly higher for themselves and their children (P < 0.05). Women were less likely to be willing to receive foreign vaccines than men (P < 0.05). As the education level increased, fewer parents preferred the domestic vaccine for themselves (P = 0.046) and their children (P = 0.005). Both domestic and foreign vaccine acceptability for parents and their children was higher among parents with high anxiety levels regarding COVID-19 infection (P < 0.05). The most common reasons for refusal were anxiety about vaccine side effects, lack of knowledge about the effectiveness of vaccines, and distrust of vaccines originating from abroad. CONCLUSION: Most of the participants were hesitant about COVID-19 vaccines. This study demonstrates that vaccine uptake can be increased by considering the higher preference for domestic vaccines.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the available evidence to publish a joint consensus document on hypertension and cardiac arrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and the patient in light of all of the circumstances presented by that patient.

BACKGROUND: Tarlatamab, a bispecific delta-like ligand 3-directed T-cell engager immunotherapy, received accelerated approval for the treatment of patients with previously treated small-cell lung cancer. Whether tarlatamab is more effective than chemotherapy in the treatment of patients whose small-cell lung cancer has progressed during or after initial platinum-based chemotherapy is not known. METHODS: We conducted a multinational, phase 3, open-label trial to compare tarlatamab with chemotherapy as second-line treatment in patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. Patients were randomly assigned to receive tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin). The primary end point was overall survival. Key secondary end points were investigator-assessed progression-free survival and patient-reported outcomes. Results of the prespecified interim analysis (data-cutoff date, January 29, 2025) are reported. RESULTS: A total of 509 patients were randomly assigned to receive tarlatamab (254 patients) or chemotherapy (255 patients). Treatment with tarlatamab resulted in significantly longer overall survival than chemotherapy (median, 13.6 months [95% confidence interval {CI}, 11.1 to not reached] vs. 8.3 months [95% CI, 7.0 to 10.2]; stratified hazard ratio for death, 0.60; 95% CI, 0.47 to 0.77; P<0.001). Tarlatamab treatment also had a significant benefit with respect to progression-free survival and cancer-related dyspnea and cough as compared with chemotherapy. The incidence of adverse events of grade 3 or higher was lower with tarlatamab than with chemotherapy (54% vs. 80%), as was the incidence of adverse events resulting in treatment discontinuation (5% vs. 12%). CONCLUSIONS: Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. (Funded by Amgen; DeLLphi-304 ClinicalTrials.gov number, NCT05740566.).

Post recovery manifestations have become another concern in patients who have recovered from coronavirus disease 2019 (COVID-19). Numerous reports have shown that COVID-19 has a variety of long-term effects on almost all systems including respiratory, cardiovascular, gastrointestinal, neurological, psychiatric, and dermatological systems. We aimed to investigate the prevalence and characteristics of the post-COVID syndrome among COVID-19 survivors and to determine the factors associated with persistent symptoms. This prospective study enrolled in patients with COVID-19 followed in hospital or outpatient clinics in Ankara City Hospital. We performed a special questionnaire to inquire about the presence of persistent symptoms beyond 12 weeks from the first diagnosis. Demographic data, comorbid diseases, characteristics of acute COVID-19, presence of persistent symptoms by systems, and knowledge about outpatient clinic visits after recovery were assessed. Of a total of 1007 participants, 39.0% had at least one comorbidity, and 47.5% had persistent symptoms. Fatigue/easy fatigability, myalgia, and loss of weight were the most frequent persistent symptoms (overall 29.3%) followed by respiratory symptoms (25.4%). A total of 235 participants had visited outpatient clinics due to several reasons during the post-COVID-19 period, and 17 of them were hospitalized. Severe acute COVID-19, hospitalization, and presence of comorbidity were independent factors for the development of persistent symptoms. Fully understanding the spectrum of the post-COVID syndrome is essential for appropriate management of all its long-term effects. Our study once again underlined the fact that the prevalence of post-COVID syndrome is higher than expected and concerns many systems, and a multidisciplinary follow-up should be provided to COVID-19 survivors in the post recovery period.

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.

There is a current debate on whether triple negative breast carcinomas (estrogen receptor--ER-negative, progesterone receptor--PR-negative and HER2-negative) have a poor prognosis. Our aim in this retrospective study was to determine whether triple negative feature is a prognostic factor for disease-free survival (DFS) in 322 breast carcinoma patients, of whom 80 (24.8%) had triple negative tumor histology. In the multivariate analysis, tumor subgroup (triple vs non-triple, p<0.0001; hazard ratio [HR], 4.2; 95% confidence interval [95%CI], 2.2-8.2) was a significant factor related to relapse, in addition to number of metastatic nodes (>4 vs <or=4, p=0.04; HR, 1.6; 95%CI, 1.2-2.4), lymphatic vascular invasion (yes vs no, p=0.002; HR, 2.0; 95%CI, 1.3-3.1) and HER2 (positive vs negative, p<0.0001; HR, 5.9; 95%CI, 3.0-10.0). This result indicated that patients with triple negative histology had a poor disease-free survival and this histology was an independent significant prognostic factor for DFS.

OBJECTIVE: Evaluation of the parental perspective regarding cochlear implants and the child's progress after a minimum of 1 year after cochlear implantation. STUDY DESIGN: A closed-set questionnaire was used to assess the parental point of view. The questionnaire that was mailed to families included the following sections: decision to implant, process of implantation, positive effect of the implant, communication, supporting the child, self-reliance, well-being and happiness, social relationships, education, and pre- and postoperative services provided by the implant center. SETTING: The study was conducted at SSK Ankara Hospital, which is a tertiary care center. PATIENTS: Parents of 28 children with congenital deafness or who became deaf before the age of 3 years and received cochlear implantation were included in the study. To obtain reliable information, selected patients had a minimum of 1 year experience after implantation. The subjects were the parents of a group of children including 19 boys and 9 girls with ages ranging from 2 to 13 years (mean, 5.07 years; standard deviation, 2.33 years). The period of cochlear implant usage ranged from 12 to 30 months (mean, 19.5 months; standard deviation, 15.95 months). MAIN OUTCOME MEASURE: Assessment of parental view about cochlear implantation. RESULTS: Of 28 questionnaires sent, 27 were returned. Making decision for cochlear implantation was one of the most stressful steps for the parents. Although speech and language development was the major concern, parents reported outstanding improvement in communication skills, social relationships, and self-confidence for their child. All the families were anxious about a possible device failure, and maintenance of the cochlear implant equipment was another major concern. CONCLUSIONS: During pre- and postimplantation processes, parents provide an important link between the child and professional staff and have a vital role in the child's life and rehabilitation. The parental perspective presented in this study can be useful to the implant centers to revise their practice accordingly and improve the information given to candidate families.

The recent reports on the treatment of azoospermia patients, in which spermatozoa could not be traced in their testes, are focused more on the potential use of adult stem cells, like mesenchymal stem cells (MSCs). The aim of this study was to demonstrate the potential use of MSCs derived from adipose tissue in the treatment of azoospermia using rat disease models. After busulfan application, the rats (n = 20) were injected with the GFP(+) MSCs into left rete testes. After 12 weeks, the testes with cell injection (right testes) were compared to control (left testes) after dimensional and immunohistochemical analyses. Testes treated with MSCs appeared morphologically normal, but they were atrophic in rats without stem cell treatment, in which the seminiferous tubules were empty. Spermatogenesis was detected, not in every but in some tubules of cell-treated testes. GFP(+)/VASA(+) and GFP(+)/SCP1(+) cells in testes indicated the transdifferentiation of MSCs into spermatogenetic cells in the appropriate microenvironment. Rats with cell treatment were mated to show the full recovery of spermatogenesis, and continuous generations were obtained. The expression of GFP was detected in the mesenchymal stem cells derived from adipose tissue and bone marrow and also in the sperms of offspring. In conclusion, MSCs might be studied for the same purpose in humans in future.

Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts' immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing, starting with unfit elderly patients and also for palliative treatment. The literature reviewed in this article mainly demonstrates that metronomic chemotherapy is advantageous for selected patients and for certain types of malignancies, which make it a promising therapeutic approach for filling in the gaps. More clinical studies are needed to establish a solidified role for metronomic chemotherapy with other treatment models in modern cancer management.

OBJECTIVE: Shoulder pain is a common complication after stroke that can limit the patients' ability to reach their maximum functional potential and impede rehabilitation. The aim of our study was to examine the occurrence of hemiplegic shoulder pain in a group of Turkish patients and clarify contributing factors such as glenohumeral subluxation, reflex sympathetic dystrophy, tonus changes, motor functional level, limitation in shoulder range of motion, thalamic pain, neglect, and time since onset of hemiplegia. The effect of shoulder pain on the duration of rehabilitation stay was also identified. DESIGN: A total of 85 consecutive patients with hemiplegia admitted to a national rehabilitation center were evaluated for the presence of shoulder pain. A brief history of pain was taken for each patient, and each patient was evaluated by radiographic and ultrasonographic examination. The subjects with shoulder pain were compared with those without pain in regard to certain of the above variables. RESULTS: Of the 85 patients with stroke, 54 patients (54/85, 63.5%) were found to have shoulder pain. Shoulder pain was significantly more frequent in subjects with reflex sympathetic dystrophy, lower motor functional level of shoulder and hand (P < 0001), subluxation, and limitation of external rotation and flexion of shoulder (P < 0,05). Age was also a significant factor in the development of shoulder pain. We were unable to demonstrate a significant relationship between shoulder pain and sex, time since onset of disease, hemiplegic side, pathogenesis, spasticity, neglect, and thalamic pain. There was no prolongation of rehabilitation stay in patients with shoulder pain. CONCLUSION: These results indicate that shoulder pain is a frequent complication after stroke and that it may develop from a variety of factors. To prevent and alleviate shoulder pain, efforts should be directed toward proper positioning of the shoulder, range of motion activities, and the avoidance of immobilization.