Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia?

Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.     

Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Intra-seasonal variation of injury patterns among German Bundesliga soccer players

ObjectiveHigh fluctuations in injury-risk during the playing season in soccer have been reported. As seasons are structured in periods with homogenous loads and intensities, we investigated injury-risk over season periods, contrarily to previous studies adopting a month-based approach.DesignCohort study; Level of evidence, 2.MethodsIncidence-rate ratios (IRRs) for match and training injuries were compared across six consecutive seasons of German Bundesliga, divided into six periods each: Pre-season (PS), winter-break (WB), quarter 1–4: (Q1–Q4).ResultsSignificant variations in injury-risk were observed for match and training injuries. IRRs in matches was 1.30 (95% CI: 1.11–1.53) times higher in Q3 and 1.53 (95% CI: 1.31–1.78) higher in Q4 compared to Q1. For training injuries, IRR peaked in Q1 and Q3 followed by a marked decrease in each subsequent quarter. Compared to Q4, IRR was 1.62 (95% CI: 1.40–1.86) times higher during Q3 and 1.78 (95% CI: 1.53–2.07) times higher in Q1. IRR was significantly higher in the competitive season compared to pre-season across match (IRR: 2.00, 95% CI: 1.30–3.00) and training (IRR: 1.27, 95% CI: 1.11–1.43) injuries.ConclusionsThe increased match IRRs later during the season indicate that, in practice, coaches should consider putting even more emphasis on recovery in the last part of the season. Moreover, training injuries seem to indicate a carry-over effect. Further studies need to investigate how training during preparatory phases can be implemented in a way that prevents injuries during the competitive season.     

Voluntary ambulation using voluntary upper limb muscle activity and Hybrid Assistive Limb® (HAL®) in a patient with complete paraplegia due to chronic spinal cord injury: A case report

Context: We sought to describe our experience with the Hybrid Assistive Limb® (HAL®) for active knee extension and voluntary ambulation with remaining muscle activity in a patient with complete paraplegia after spinal cord injury.

Findings: A 30-year-old man with complete paraplegia used the HAL® for 1 month (10 sessions) using his remaining muscle activity, including hip flexor and upper limb activity. Electromyography was used to evaluate muscle activity of the gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in synchronization with the Vicon motion capture system. A HAL® session included a knee extension session with the hip flexor and voluntary gait with upper limb activity. After using the HAL® for one month, the patient’s manual muscle hip flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the left knee, and from 0/5 to 1/5 for the extension of both knees.

Conclusion/clinical relevance: Knee extension sessions with HAL®, and hip flexor and upper-limb-triggered HAL® ambulation seem a safe and feasible option in a patient with complete paraplegia due to spinal cord injury.     

Outcome of isolated posterior cruciate ligament reconstruction at mean 6.3-year follow up: a consecutive case series

Objectives: There is a paucity of reporting on surgical outcomes of isolated posterior cruciate ligament reconstruction (PCLR). We hypothesize that isolated PCL injuries failing nonoperative treatment achieve good outcomes and are able to return to sport following PCLR.

Methods: A retrospective analysis was performed to identify patients with isolated PCL injuries that underwent reconstruction between 2001 and 2014. Patients with multi-ligamentous injury or another concomitant knee pathology were excluded. Medical records were reviewed for demographic, clinical and operative data. Patients were contacted for administration of a telephone-based questionnaire which included the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form, Lysholm-Tegner scales, Marx activity scale (MAS), return to sport status, and patient satisfaction instruments.

Results: A total of 15 isolated PCL reconstructions in 14 patients with a mean age of 27.5 years (range 17–43) met the study inclusion criteria; mean follow up was 6.3 years (range 1.4–15.2). Pre-operatively, the primary complaint was knee instability in all patients; on physical examination, lack of a firm end point during posterior drawer testing was found in 93% (14/15) of the knees. In total, 12 of 15 knees underwent transtibial, single-bundle PCLR and three of 15 underwent tibial inlay, double bundle PCLR. Graft types included: quadriceps autograft (7/15), Achilles allograft (6/15), and hamstring autograft (2/15). There were no graft failures in our patient cohort. At most recent follow up the mean scores respectively on the IKDC form, Lysholm-Tegner scales and MAS were (standard deviation): 77.3 (16.5), 83.1 (17.9), 6.13 (2.6), and 7.1 (6.0). All fourteen patients were athletes prior to their injury and 79% (11/14) returned to sport and overall patient satisfaction was 9.2/10.

Conclusions: Isolated PCLR provides good outcomes at mean medium-term follow up with restoration of function, high rate of return to sport and overall patient satisfaction.     

N-乙酰-5-羟色胺对视网膜缺血-再灌注损伤大鼠视网膜 Fas、FasL 蛋白表达的影响

目的　探讨N-乙酰-5-羟色胺（N-acetylserotonin，NAS）对视网膜缺血-再灌注损伤（retina ischemia-reperfusion injury，RIRI）大鼠视网膜Fas、FasL蛋白表达的影响。方法　取健康成年Sprague Dawley大鼠54只，将大鼠随机分为正常组（6只）、RIRI组（24只）与NAS组（24只）；采用高眼压法建立大鼠RIRI模型，依据造模后不同时间点将RIRI组与NAS组大鼠又分为6 h、12 h、24 h及72 h四个亚组。NAS组于造模前30 min腹腔注射NAS（5 mg·kg^-1），RIRI组腹腔注射等剂量的生理盐水。通过HE染色在光学显微镜下观察各组大鼠视网膜形态学变化，并记录各组大鼠视网膜厚度及视网膜神经节细胞数，采用免疫组织化学染色法检测NAS对RIRI大鼠视网膜Fas、FasL蛋白表达的影响。结果　HE染色显示，正常组大鼠视网膜各层细胞分界清晰，形态正常，神经细胞排列整齐；RIRI组大鼠再灌注后6 h视网膜各层出现水肿，以神经节细胞层及内核层较显著，神经节细胞数较正常组减少；随后视网膜水肿进一步加重，神经节细胞继续减少；NAS组大鼠在再灌注后6 h、12 h、24 h 视网膜水肿程度较 RIRI组轻，NAS组在再灌注后72 h视网膜厚度较 RIRI组厚，NAS组各时间点神经节细胞数均较 RIRI组多，差异均有统计学意义（均为P＜0.05）。免疫组织化学染色显示，正常组几乎未见 Fas⁺细胞。再灌注后6 h，RIRI组视网膜神经节细胞及内核层开始出现少量 Fas⁺细胞；再灌注后12 h，RIRI组视网膜 Fas⁺细胞表达逐渐增多；再灌注后24 h视网膜Fas⁺细胞数达到高峰，棕色阳性染色细胞分布在视网膜神经节细胞层、内丛状层、内核层及神经纤维层；再灌注后 72 h 视网膜 Fas⁺细胞较再灌注后 24 h 减少。NAS组在再灌注后6 h、12 h、24 h、72 h 视网膜 Fas⁺细胞数均较 RIRI组各时间点减少，再灌注后24 h，Fas⁺细胞数达较高水平，随后下降，差异均有统计学意义（均为P＜0.05）。正常组视网膜可见 FasL 全层低表达。RIRI组再灌注后 6 h，视网膜神经节细胞层和神经纤维层存在少量 FasL⁺细胞；再灌注后12 h FasL蛋白表达逐渐增多；再灌注后24 h FasL⁺细胞数达高峰，可见深棕色的细胞膜及细胞质染色细胞分布在视网膜神经节细胞层、内丛状层、内核层及神经纤维层；再灌注后72 h FasL蛋白的阳性表达逐渐减少。NAS组再灌注后6 h、12 h、24 h、72 h 视网膜FasL⁺细胞数均少于 RIRI组各时间点阳性细胞数，差异均有统计学意义（均为P＜0.05）。结论　NAS可通过抑制RIRI大鼠视网膜细胞Fas、FasL蛋白的表达，减轻缺血再灌注对大鼠视网膜细胞造成的损伤。     

A conceptual model and detailed framework for stress-related,strain-related,and overuse athletic injury

A multitude of athletic injuries occur when the various tissues that make up the human body experience stresses and strains that exceed their material strength. The precise amount of stress and strain that any given tissue can withstand is determined by the mechanical properties and resultant strength of that particular tissue. These mechanical properties are directly determined by an individual’s physiology and acute regulation of these properties. A number of theoretical frameworks for athletic injury occurrence have been proposed, however, a detailed conceptual framework for injury aetiology that considers the interplay between the physiological and mechanical factors and outlines the causal pathways to tissue damage and injury is needed. This will guide injury research towards a more thorough investigation of causal mechanisms and understanding of risk factors. Further, it is important to take into account the considerable differences in loading patterns which can result in varying injury outcomes such as acute stress-related, strain-related, or overuse injury. Within this article a simplified conceptual model of athletic injury is proposed along with a detailed, evidence-informed, conceptual framework for athletic injury aetiology that focuses on stress-related, strain-related, and overuse injury.     

Contextualizing the lived experience of quality of life for persons with spinal cord injury: A mixed-methods application of the response shift model

Objective: The objective of this study was to gain greater insight into individuals’ quality of life (QOL) definitions, appraisals, and adaptations following spinal cord injury (SCI).

Design: A mixed-methods design, applying the Schwartz and Sprangers response shift (RS) model. RS is a cognitive process wherein, in response to a change in health status, individuals change internal standards, values, or conceptualization of QOL

Setting: Community-dwelling participants who receive medical treatment at a major Midwestern medical system and nearby Veterans’ Affairs hospital.

Participants: A purposive sample of participants with SCI (N?=?40) completed semi-structured interviews and accompanying quantitative measures.

Interventions: Not applicable.

Outcome Measures: Qualitative data were analyzed using content analysis to identify themes. Analysis of variance were performed to detect differences based on themes and QOL, well-being, and demographic and injury characteristics.

Results: Four RS themes were identified, capturing the range of participant perceptions of QOL. The themes ranged from complete RS, indicating active engagement in maintaining QOL, to awareness and comparisons redefining QOL, to a relative lack of RS. Average QOL ratings differed as a function of response shift themes. PROMIS Global Health, Anxiety, and Depression also differed as a function of RS themes.

Conclusion: The RS model contextualizes differences in QOL definitions, appraisals, and adaptations in a way standardized QOL measures alone do not.     

The marks of gunshot wounds to the face

IntroductionThis article deals with the occurrence of health problems due to gunshot wounds to the face among military police officers, in the metropolitan region of Rio de Janeiro, who were submitted to surgery at the Oral and Maxillofacial Surgery and Traumatology Clinic of Hospital Central da Polícia Militar.ObjectiveTo identify the profile of patients submitted to surgery as a result of gunshot wounds, the anatomical distribution of maxillofacial fractures, the identified sequelae and complications, the health specialties involved in the rehabilitation of these patients, and to discuss the social, emotional and work performance-related effects of work among these subjects.MethodsA retrospective epidemiological study was carried out based on secondary data from military police officers who were submitted to surgery at Hospital Central da Polícia Militar due to gunshot wounds from June 2003 to December 2017.ResultsDuring the study period, 778 surgeries were performed in the operating room by the Oral and Maxillofacial Surgery and Traumatology service at Hospital Central da Polícia Militar, 186 of which were due to gunshot wounds (23.9%). All patients were males and the mean age 34.7 years. Bone segment loss was the most common sequela. Facial esthetic impairment and reports of insomnia were the most often identified late consequences of impact on health and social life. Regarding the occupational impacts of the sustained injury, the mean time away from work due to medical leave for the treatment of maxillofacial injuries was 11.7 months.ConclusionThe treatment of gunshot wounds patients with facial injuries requires multiple surgical interventions and their rehabilitation requires the involvement of different health specialties. Further studies are needed to qualitatively analyze the impact of this type of facial trauma on the patients' lives and their social consequences.     

Relationship between 3D lower limb bone morphology and 3D gait variables in children with uni and bilateral Cerebral Palsy

BackgroundMedical and surgical interventions to prevent or reduce bone deformities and improve gait in children with cerebral palsy (CP) are based on empirical evidence that there is a relationship between bone deformities and gait deviations.Research questionWhat is the relationship between tibial-femoral bone morphology and kinematic gait variables in ambulant children with CP?MethodsA retrospective analysis was conducted on data from 121 children with uni- (n = 64, mean age 9.9 (SD 3.4) years) and bi- lateral (n = 57, mean age 10.4 (SD 3.6) years) CP who had undergone 3D gait analysis and biplanar X-rays (EOS® system). The limbs were split as DIP (the more impaired limb of children with bilateral CP), HEMI (the impaired limb of unilateral CP) and REF (the unimpaired limb of unilateral CP). Multi-variable Linear Regressions were performed between 23 kinematic variables, the Gait Deviation Index (GDI) and a model composed of nine 3D bone variables for each limb type.ResultsWhen the whole sample was pooled, 72% of R² values were poor, 16% were fair, and 12% were moderate. Lower limb bone morphology models explained less than 1% of GDI variability. Correlations between tibial-femoral rotational parameters and hip rotation were mostly poor. Mean foot progression angle was the only kinematic parameter that was fairly to moderately correlated with bone variables in the 3 limb types. A tibial-femoral bone model explained 48% of the variability of mean foot progression angle in the REF limbs, 31% in the HEMI limbs and 25% in the DIP limbs.SignificanceTibial-femoral bone morphology was only weakly related to kinematic gait variables, in contrast with common clinical assumptions. These results suggest that factors other than bone morphology influence gait quality and thus a thorough clinical examination and gait analysis is required prior to making treatment decisions.