Sorafenib versus Lenvatinib Causes Stronger Oxidative Damage to Membrane Lipids in Noncancerous Tissues of the Thyroid, Liver, and Kidney: Effective Protection by Melatonin and Indole-3-Propionic Acid.

Sorafenib and lenvatinib are multi-targeted tyrosine kinase inhibitors which are currently approved to treat advanced hepatocellular carcinoma, renal cell carcinoma and radioiodine-refractory differentiated thyroid carcinoma. However this treatment is often limited due to common adverse events which may occur via oxidative stress. The study aims to compare sorafenib- and lenvatinib-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) in homogenates of porcine noncancerous tissues of the thyroid, the liver, and the kidney and to check if it can be prevented by antioxidants melatonin and indole-3-propionic acid (IPA). Homogenates of individual tissues were incubated in the presence of sorafenib or lenvatinib (1 mM, 100 µM, 10 µM, 1 µM, 100 nM, 10 nM, 1 nM, 100 pM) together with/without melatonin (5.0 mM) or IPA (5.0 mM). The concentration of malondialdehyde + 4-hydroxyalkenals, as the LPO index, was measured spectrophotometrically. The incubation of tissue homogenates with sorafenib resulted in a concentration-dependent increase in LPO (statistically significant for concentrations of 1mM and 100 µM in the thyroid and the liver, and of 1 mM, 100 µM, and 10 µM in the kidney). The incubation of thyroid homogenates with lenvatinib did not change LPO level. In case of the liver and the kidney, lenvatinib increased LPO but only in its highest concentration of 1 mM. Melatonin and IPA reduced completely (to the level of control) sorafenib- and lenvatinib-induced LPO in all examined tissues regardless of the drug concentration. In conclusion, sorafenib comparing to lenvatinib is a stronger damaging agent of membrane lipids in noncancerous tissues of the thyroid, the liver, and the kidney. The antioxidants melatonin and IPA can be considered to be used in co-treatment with sorafenib and lenvatinib to prevent their undesirable toxicity occurring via oxidative stress.

An attempt to explain the Vojta therapy mechanism of action using the surface polyelectromyography in healthy subjects: A pilot study.

BACKGROUND: Rehabilitation according to Vojta is a neurophysiological method used to obtain reflex responses in muscles following stimulation of particular activation zones. OBJECTIVES: This study aims to objectively evaluate the muscular responses following stimulation according to Vojta's method. The possible routes of spinal transmission responsible for the phenomenon of muscle activation in upper and lower extremities are considered. METHODS: Polyelectromyographic (pEMG) recordings in the upper and lower extremities in healthy volunteers (N = 25; aged 24 ± 1 year) were performed to find out the possible routes of spinal transmission, responsible for muscle activation. The left acromion and right femoral epicondyle were stimulated by a Vojta therapist; pEMG recordings were made including the bilateral deltoid and rectus femoris muscles. RESULTS AND DISCUSSION: Following acromion stimulation, muscle activation was mostly expressed in the contralateral rectus femoris, rather than the contralateral deltoid and the ipsilateral rectus femoris muscles. After stimulation of the lower femoral epicondyle, the following order was observed: contra lateral deltoid, ipsilateral deltoid and the contra lateral rectus femoris muscle. One of the candidates responsible for the main crossed neural transmission involved in the Vojta therapy mechanism would be the long propriospinal tract neurons.

Chemotherapy-Related Toxicity, Nutritional Status and Quality of Life in Precachectic Oncologic Patients with, or without, High Protein Nutritional Support. A Prospective, Randomized Study.

BACKGROUND: Cancer disease is usually associated with impaired nutritional status, which is one of the factors contributing to deterioration of the results of surgery, chemotherapy or radiotherapy. OBJECTIVES: The aim of the study was to determine whether nutritional support with high protein (ONS) in adult oncologic patients in the first step of cancer cachexia-asymptomatic precachexia, has an influence on the toxicity of systemic therapy. However, secondary endpoints were established: to determine whether high protein ONS influences the nutritional status, the quality of life, and the performance status. MATERIALS AND METHODS: A total of 114 persons aged 40-84 years old with colorectal cancer were examined. Based on the randomization, 47 patients were qualified to the interventional group (ONS group) and 48 to Control group. To evaluate the nutritional status NRS-2002 (Nutritional Risk Screening), SGA (Subjective Global Assessment), SCRINIO (SCReenIng the Nutritional status In Oncology) Working Group classification, VAS (Visual Analog Scale) for appetite was used. FAACT (Functional Assessment of Anorexia/Cachexia Therapy) questionnaire was used for assessment of the quality of life. The health status of patients was evaluated based on the Karnofsky Performance Scale. Anthropometric measurements were done. RESULTS: Severe complications of chemotherapy, which caused the end of treatment, a slight complication of the gastrointestinal tract such as diarrhea grade 2 according to ECOG (Eastern Cooperative Oncology Group) score regardless of the studied group, were observed. There were no statistical differences in the number and severity of the observed complications, i.e., neutropenia, leucopenia, thrombocytopenia, anemia, abdominal pain, nausea and vomiting, and diarrhea. During the follow-up the significant changes of SGA, VAS, albumin and prealbumin were observed between groups. In the ONS group an improvement in nutritional status was noticed (increased appetite VAS, p = 0.05; increased points in SGA, p = 0.015, and increased levels of albumin and prealbumin, p = 0.05). In Control group nutritional status was stable during observation. The performance status and quality of life were stable in both groups. No statistical differences between groups (ONS vs. Control) in the numbers for disqualification, resignation, delay in treatment, or dose reduction were observed. CONCLUSIONS: Results of the study did not indicate that nutritional support in precachectic oncologic patients influenced the toxicity of systemic therapy. High protein nutritional support improved nutritional status assessed by SGA, VAS for appetite, albumin, and prealbumin. The performance status and quality of life were stable throughout the observation and were not changed under the supplementation.

Nutritional status assessment in colorectal cancer patients qualified to systemic treatment.

AIM OF THE STUDY: Cancer is usually associated with impaired nutritional status, which is one of the factors contributing to the deterioration of the results of surgery, chemotherapy, or radiotherapy. The aim of this study was the assessment of the nutritional status of patients with CRC qualified to chemotherapy. MATERIAL AND METHODS: Seventy-five persons aged 40-86 years with colorectal cancer were examined. To evaluate the nutritional status NRS 2002, SGA, SCRINIO Working Group classification, VAS scale for appetite, and FAACT questionnaire were used. The health status of patients was evaluated based on the Karnofsky Performance Scale. Anthropometric measurements were made. RESULTS: The results indicate that 75% of patients present pre-cachexia status based on SCRINIO Working Group classification. According to both NRS-2002 and SGA, 73.3% of patients were moderately malnourished and 2.7% were severely malnourished. 37.0% of patients had moderate appetite and 6.0% (n = 5) had poor appetite. The Karnofsky score indicates the state of normal activity, and minor signs and symptoms of the disease among most of the patients. A statistically significant positive correlation was found between the VAS and the Karnofsky score (R = 0,4; p < 0.05). The FACCT average score (78.5) indicates a reduction in the quality of life of the patients in all aspects of functioning. CONCLUSIONS: Evaluation of the baseline nutritional status of patients with CRC should be a part of routine clinical practice. Because of the high incidence of confirmed pre-cachexia, this group of patients also requires early adequate nutrition intervention.

Efficacy and safety of biosimilar filgrastim in primary and secondary prevention of febrile neutropenia.

Neutropenia and febrile neutropenia (FN) are among the most common side effects/complications of chemotherapy. The aim of the present study was to evaluate the practice of the use of biosimilar filgrastim in the primary and secondary prevention of FN, and assess its efficacy and safety. A multi-center, non-interventional epidemiological study of 170 cancer patients aged 23-82 years was conducted. Data were collected via a questionnaire completed based on medical documentation and patient examination over five chemotherapy visits. The risk of FN related to the chemotherapy protocol used was in the range of 10-20% in >50% of the patients (53.5%) and a majority (74.7%) had additional FN risk factors. 60% of the patients received filgrastim as primary prevention of FN, and 40% received it as secondary prevention. In 40.6% of cases, six cycles of chemotherapy were used. More than 90% of patients continued chemotherapy according to the initial recommended dose. In majority of patients, no FN was observed following the final cycle of chemotherapy. Median neutrophil count at visit 1 was 2.2×103/µl and did not fall below that level. Majority of patients (>70%) performed self-injections of filgrastim, and 86.3% of patients were continuing therapy with this drug at the last visit. No treatment-related side effects were recorded. The use of biosimilar filgrastim in the primary and secondary prevention of FN allows to maintain initial chemotherapy dosage. Furthermore, the use of biosimilar filgrastim is safe and tolerable, and has a high acceptance by patients.

Surface electromyography studies in standing position confirm that ankle strategy remains disturbed even following successful treatment of patients with a history of sciatica.

[Purpose] It is hypothesized that ankle strategy can be changed in patients with a history of sciatica. The aim of this study was to detect residual disturbances following successful treatment. [Subjects and Methods] In patients with a history of sciatica (N=11) and pseudo-sciatica (N=9), differences in muscle activity were recorded with bilateral surface polyelectromyography and stability measurements (center of foot pressure sway and center of spectrum) in normal standing and tandem positions. Results were compared with recordings in healthy people (N=9) to identify abnormalities in electromyographic and postural studies. [Results] Increased amplitude of electromyographic recordings from the gastrocnemius and extensor digiti muscles on the affected side was detected more in patients with a history of sciatica than pseudo-sciatica syndromes in tandem position. Fewer amplitude fluctuations were observed in both positions preferably in patients following sciatica. Changes in center of foot pressure sway and center of spectrum during balance platform studies were detected in normal standing position in this group of patients. No similar abnormalities in electromyographic and postural studies were detected in healthy people. [Conclusion] Sciatica and pseudo-sciatica evoke persistent disturbances in activity of muscles responsible for ankle strategy. Electromyography differentiates the two groups of patients better than postural studies.

Hip strategy alterations in patients with history of low disc herniation and non-specific low back pain measured by surface electromyography and balance platform.

PURPOSE: The appearance of pathology in the lumbar spine, such as a previous episode of low disc herniation or non-specific low back pain contributes to improper activation of the hip muscles. The aim of the study was to detect alterations in hip strategy manifested by differences in balance parameters and rectus femoris and gluteus maximus activity in people with previous episode of pain radiation to one lower limb caused by low disc herniation or non-specific low back pain. METHODS: We studied 11 patients with history of low-disc herniation, 9 patients with history of non-specific low back pain and 10 healthy subjects. Hip strategy alterations were detected by measuring rectus femoris and gluteus maximus activity in bilateral surface polyelectromyographic recordings and by stability measurements on a balance platform. RESULTS: In the surface polyelectromyography study, in both patients' group the value of the average amplitude was higher and the amount of the fluctuations was lower than in healthy subjects. There were no significant differences in stability parameters. CONCLUSIONS: A changed pattern of hip muscles activity was detected in the patients without changes in stability parameters. Greater disorder occurs in people in with previous episode of pain radiation to one lower limb caused by low disc herniation than in people with non-specific low back pain.

Application of osteopathic manipulative technique in the treatment of back pain during pregnancy.

Changes in body posture, musculoskeletal disorders and somatic dysfunctions are frequently observed during pregnancy especially ligament, joint and myofascial impairment. The aim of the paper is to present the use of osteopathic manipulative treatment (OMT) for back and pelvic pain in pregnancy on the basis of a review of the available literature. MEDLINE and Cochrane Library were searched in January 2014 for relevant reports, randomized controlled trials, clinical and case studies of OMT use in pregnant women. Each eligible source was verified and analyzed by two independent reviewers. OMT procedures appear to be effective and safe for pelvic and spinal pain management in the lumbosacral area in pregnant women.

Evaluation of palpation, pressure algometry, and electromyography for monitoring trigger points in young participants.

OBJECTIVE: The aims of this study were to assess trigger points (TrPs), their pain threshold, and the activity of motor units in the neck and shoulder girdle muscles of young volunteers and to assess palpation, algometry, and surface electromyography (EMG) for their detection. METHODS: Seventy participants aged from 19 to 26 years (20.6 ± 1.4 years [mean ± SD]) were examined to identify TrPs through palpation, an algometer test for pressure pain threshold (PPT), a test for the activity of muscle motor units at rest (rEMG) and at maximal contraction (mcEMG) with surface EMG recordings. RESULTS: Palpation studies revealed numerous symmetrical nonreferring latent TrPs (379/560 performed tests), referring latent TrPs (91/560), and few active TrPs (4/560). Algometry confirmed the lowest PPT in active TrPs and the highest PPT in participants with no TrPs (86/560). Pressure pain thresholds were lower in nonpregnant women than in men, especially in the trapezius and sternocleidomastoid muscles with nonreferring and referring latent TrPs. Trigger points evoked a moderate increase of rEMG amplitude but with no evident changes in mcEMG. CONCLUSIONS: This study showed that the preliminary algometry and rEMG recordings monitored a decrease in PPT and an increase in muscle tension in all cases of TrPs in each of the 3 types detected in people younger than 30 years.

Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging.

Treatment of patients sustaining a complete spinal cord injury remains an unsolved clinical problem because of the lack of spontaneous regeneration of injured central axons. A 38-year-old man sustained traumatic transection of the thoracic spinal cord at upper vertebral level Th9. At 21 months after injury, the patient presented symptoms of a clinically complete spinal cord injury (American Spinal Injury Association class A-ASIA A). One of the patient's olfactory bulbs was removed and used to derive a culture containing olfactory ensheathing cells and olfactory nerve fibroblasts. Following resection of the glial scar, the cultured cells were transplanted into the spinal cord stumps above and below the injury and the 8-mm gap bridged by four strips of autologous sural nerve. The patient underwent an intense pre- and postoperative neurorehabilitation program. No adverse effects were seen at 19 months postoperatively, and unexpectedly, the removal of the olfactory bulb did not lead to persistent unilateral anosmia. The patient improved from ASIA A to ASIA C. There was improved trunk stability, partial recovery of the voluntary movements of the lower extremities, and an increase of the muscle mass in the left thigh, as well as partial recovery of superficial and deep sensation. There was also some indication of improved visceral sensation and improved vascular autoregulation in the left lower limb. The pattern of recovery suggests functional regeneration of both efferent and afferent long-distance fibers. Imaging confirmed that the grafts had bridged the left side of the spinal cord, where the majority of the nerve grafts were implanted, and neurophysiological examinations confirmed the restitution of the integrity of the corticospinal tracts and the voluntary character of recorded muscle contractions. To our knowledge, this is the first clinical indication of the beneficial effects of transplanted autologous bulbar cells.

A new concept for evaluating muscle function in the lower extremities in cases of low back pain syndrome in anamnesis.

INTRODUCTION: There are difficulties in objective evaluation of activity of the muscles in the lower extremities of patients after successful treatment of sciatica and pseudosciatica, when no clear clinical symptoms are detected. However, the existence of some muscle dysfunction can be hypothesised and its detection was the aim of the study. OBJECTIVE: Recordings from chosen lower extremity muscles during standing were performed as supplementary differential diagnosis in evaluation of these patients. EMG in standing positions constitutes a new methodological approach not described in detail. METHODS: Twenty patients (11 after sciatica and 9 after sciatica-like episodes) were enrolled into the study. On the day of examination, clinical and electroneurographical (ENG; M and F waves tests) studies showed no pathology. The percentage of maximal voluntary contraction (MVC) defined muscle activity during standing. Mean amplitude and number of changes in muscle activity (fluctuations) were measured in surface electromyography recordings (sEMG) during normal standing and tandem positions. RESULTS AND CONCLUSIONS: Activity of proximal lower extremity muscles expressed as percentage of MVC was bilaterally increased in patients after sciatica in normal standing position, compared with results from the group of healthy volunteers (N=9). Patients after sciatica were also characterized with a significant increase of mean sEMG amplitude, recorded especially in distal muscles on the affected side during tandem position. This pathological change was related to decrease in 'fluctuations' frequency in patients after sciatica (P<0.001) more than after pseudosciatica (P<0.01) groups in both standing positions, compared to parameters of healthy volunteers. Sciatica and pseudosciatica in anamnesis cause different abnormal patterns of lower extremity muscle activity during standing positions when recorded with surface EMG.