[Incidence, Diagnosis and Risk Factors for Fracture-Related Infection (FRI): 3-Year Experience of Level I Trauma Centre]. / Incidence a diagnostika infektu pri zlomenine (FRI) a rizikové faktory jeho vzniku: tríleté zkusenosti traumacentra I. stupne.

PURPOSE OF THE STUDY The study aims to determine the incidence of fracture-related infection (hereinafter referred to as the FRI) at a Level I trauma centre over a three-year period. It also aimed to determine the risk factors, to observe confirmatory and suggestive criteria in line with the applicable recommendations, and to evaluate the bacterial spectrum in a diagnosed FRI. MATERIAL AND METHODS It is a retrospective-prospective study carried out through studying the documentation. The study included all patients diagnosed with FRI and treated between 2019 and 2021, except for the patients with hand fractures since minor phalangeal fractures of the fingers were largely treated by the outpatient department, no osteosynthesis was performed in the operating room, and these patients were not followed up at our department. RESULTS The FRI incidence was 2.33% of all osteosyntheses performed at the Level 1 trauma centre in the period 2019-2021. The FRI was most often caused by pyogenic cocci agents and the FRI developed most frequently within 6 months after osteosynthesis. The site at risk was the lower limb region. The FRI incidence was most often indicated by suggestive clinical criteria (redness, secretion, pain) and radiological criteria (delayed healing, non-union). Overall, 42.19% of treated nonunions were later diagnosed as FRI. At the time of FRI diagnosis, the CRP values were normal in 21.7% of patients. DISCUSSION The FRI incidence rate in 2019-2021 was 2.33%, which corresponds with the values reported in other papers focusing on the incidence of infectious complications after osteosynthesis. Fang and Depypere reported 1-2% of infectious complications. The most common risk factors are open fractures, which account for 20.16% in our cohort. Ktistakis and Depypere describe the incidence of osteomyelitis in 30% of treated open fractures. In our cohort, the incidence of FRI was significantly higher in lower limb fractures. Bezstarosti, Wang and Pesch published similar results, with some deviations. The time from osteosynthesis to final FRI diagnosis varied from a few weeks to several years. In more than half of the patients the FRI developed within 6 months after performed osteosynthesis. Metsemakers and Fang refer to the very same trend. The CRP levels in the study population varied a lot. Xing-qi Zhao describes CRP as a less sensitive (sensitivity 65.6%) but more specific marker (specificity 75.4%). According to the available literature, the most common agents causing infectious complications of osteosynthesis are gram-positive cocci, S. aureus in particular. In our study, G+ pyogenic cocci were clearly the most commonly detected, which is consistent with the results of studies by Fang and Depypere, focused on the incidence of infectious complications. The most common FRI clinical manifestations included wound secretion, redness, swelling and pain. Furthermore, suggestive radiological criteria, especially delayed healing and non-union also indicated the FRI occurrence. According to Fang, the most common clinical manifestations of infectious complications include pain, swelling, redness and wound dehiscence. Fang reports that the most common radiologic findings are the periosteal reaction, loosening of the implant and delayed healing or non-union, which is consistent with our cohort. In the cohort of non-unions surgically treated at our department, FRI was subsequently confirmed in 42.19% of cases. CONCLUSIONS The incidence of FRI at Level 1 trauma centre was 2.33% of operated fractures in 2019-2021, with pyogenic cocci being the most common infectious agents. The FRI usually developed within 6 months after osteosynthesis. The typical site for the FRI development was the lower limb region, the ongoing FRI was indicated by suggestive clinical criteria (redness, secretion, pain) and radiological criteria (delayed healing and a non-union). Overall, 42.19% of treated non-unions were later diagnosed as FRI. Key words: fracture-related infection, FRI, suggestive criteria, confirmatory criteria, FRI diagnosis, microbial, microbiology spectrum, osteosynthesis, complications, non-union.

Efficacy of salvage stereotactic radiotherapy (SRT) for locally recurrent brain metastases after initial SRT and characteristics of target population

Objectives Due to a steadily growing use of stereotactic radiotherapy (SRT) for treatment of brain metastases (BMs), the in-field failure after an initial stereotaxy is an increasingly frequent problem. Repeat stereotactic radiotherapy (re-SRT) shows encouraging results in terms of local control. However, the evidence on prognostic factors limiting the overall survival (OS) of re-treated patients is scarce. Here, we sought to analyze the patients’ and treatment characteristics influencing the survival outcomes after re-SRT. Methods Data of all patients with local failure of initial SRT treated from 2012 to 2019 were retrospectively reviewed and cases treated with salvage SRT were analyzed. We analyzed the impact of patients’ and treatment characteristics on overall survival after re-SRT by Kaplan–Meier method and Cox regression models. Local and distant brain control, cause of death, and radionecrosis rate were also assessed. Results Forty-seven patients with 55 BMs treated with re-SRT were evaluated. Median OS after re-SRT was 9.2 months and the overall local control was 83.6%. Nine BMs (16.4%) presented local relapse (LR), 12 (21.8%) radionecrosis, while 21 patients (44.7%) developed new BMs. Only absence of extracranial metastases at BMs diagnosis (HR 0.42, CI 95%; 0.18–0.97), extracranial disease progression (HR 2.39, CI 95%; 1.06–5.38) and distant brain failure (HR 3.94, CI 95%; 1.68–9.24) after re-SRT were significantly associated with patients’ survival. Extracranial progression following re-SRT was an independent prognosticator of worse OS. Conclusion Re-SRT after LR presented excellent local control with acceptable RN rate and improved patients’ survival, limited mainly by extracranial and distant brain progression (AU)

Efficacy of salvage stereotactic radiotherapy (SRT) for locally recurrent brain metastases after initial SRT and characteristics of target population.

OBJECTIVES: Due to a steadily growing use of stereotactic radiotherapy (SRT) for treatment of brain metastases (BMs), the in-field failure after an initial stereotaxy is an increasingly frequent problem. Repeat stereotactic radiotherapy (re-SRT) shows encouraging results in terms of local control. However, the evidence on prognostic factors limiting the overall survival (OS) of re-treated patients is scarce. Here, we sought to analyze the patients' and treatment characteristics influencing the survival outcomes after re-SRT. METHODS: Data of all patients with local failure of initial SRT treated from 2012 to 2019 were retrospectively reviewed and cases treated with salvage SRT were analyzed. We analyzed the impact of patients' and treatment characteristics on overall survival after re-SRT by Kaplan-Meier method and Cox regression models. Local and distant brain control, cause of death, and radionecrosis rate were also assessed. RESULTS: Forty-seven patients with 55 BMs treated with re-SRT were evaluated. Median OS after re-SRT was 9.2 months and the overall local control was 83.6%. Nine BMs (16.4%) presented local relapse (LR), 12 (21.8%) radionecrosis, while 21 patients (44.7%) developed new BMs. Only absence of extracranial metastases at BMs diagnosis (HR 0.42, CI 95%; 0.18-0.97), extracranial disease progression (HR 2.39, CI 95%; 1.06-5.38) and distant brain failure (HR 3.94, CI 95%; 1.68-9.24) after re-SRT were significantly associated with patients' survival. Extracranial progression following re-SRT was an independent prognosticator of worse OS. CONCLUSION: Re-SRT after LR presented excellent local control with acceptable RN rate and improved patients' survival, limited mainly by extracranial and distant brain progression.

Radiation-induced lymphopenia: the main aspects to consider in immunotherapy trials for endometrial and cervical cancer patients.

BACKGROUND: Although the chemotherapy-induced depletion of circulating white blood cells (WBC) is well recognized, the impact of exclusive radiotherapy (RT) on the different subpopulations of WBC remains unexplored. This may be important for immunotherapy administrated in combination with radiation, especially in malignant tumors usually treated with RT or chemoradiotherapy (CRT), and characterized by a high mutational burden, such as endometrial (EC) or cervical cancer (CC). We aimed to evaluate the impact of RT and CRT on circulating WBC in uterine cancers and its correlation with survival. MATERIAL AND METHODS: A total of 202 consecutive patients with uterine cancers treated with RT or CRT between 2009 and 2016 in a large European center and with available basal and post-treatment blood tests were retrospectively evaluated. EC and CC patients were analyzed separately. The differences between pre- and post- treatment WBC mean values were evaluated independently in patients treated with CRT and exclusive RT. Two-sided T test for paired samples and Kaplan-Meier curves were applied for analysis (p value < 0.05, SPSS v.23). RESULTS: Among EC patients, 29 received CRT and 34 exclusive postoperative RT, while in CC cohort, 105 were treated with CRT and 34 with RT. In both cohorts, CRT affected significantly all WBC subtypes, whereas exclusive RT decreased only lymphocytes population (p = 0.000). Radiation-induced lymphopenia (RIL) had no impact on survival outcomes. CONCLUSIONS: The selective depletion of lymphocytes after RT was significant in both EC and CC. Our results are of interest for further research on RIL and for design of immunotherapy-based clinical trials.

Unveiling the mechanisms of immune evasion in pancreatic cancer: may it be a systemic inflammation responsible for dismal survival?

PURPOSE: Pancreatic cancer (PC) is one of the most aggressive malignancies with no effective treatment if diagnosed in advanced stage. Systemic inflammation is a recognized characteristic of cancer progression, and we believe that the understanding of the influence of inflammatory parameters may contribute to therapeutic improvement in PC. Here, we validated the Eosinophil/Lymphocyte Ratio (ELR) together with the Neutrophil/Lymphocyte Ratio (NLR) and their components, as prognostic factors in PC patients treated with chemoradiation. METHODS: A total of 66 consecutive patients (p) diagnosed with PC stage I-III and treated with External Beam Radiotherapy + chemotherapy ± surgery (28p) in our institution from 2007 to 2018 were retrospectively evaluated. The impact of pre-treatment ELR ≥ 0.04, NLR ≥ 1.9, neutrophilia (≥ 7.0 × 10(9)/l), eosinophilia (≥ 0.5 × 10(9)/l) and lymphopenia (< 1.0 × 10(9)/l) on Overall Survival (OS) and Time-to-Progression (TTP) was evaluated both in the entire cohort and separately according to surgical status. RESULTS: Higher ELR was associated with longer OS and TTP, both in surgically treated and not operable patients. On univariate analysis, elevated ELR was associated with better OS (HR = 0.3, 95% IC 0.13-0.65, p = 0.003), contrarily to neutrophilia (HR = 2.7, 95% IC 1.2-6.5, p = 0.026) and age > 50 years (HR = 2.6, 95% IC 1.03-6.6, p = 0.044), while NLR, lymphopenia and Ca-19.9 were not significant. On multivariate regression, independent prognosticators for OS were: ELR, age and neutrophilia; while for TTP: ELR, neutrophilia, eosinophilia and lymphopenia. CONCLUSIONS: The host's immune response influences survival outcomes of PC patients and may be of interest for future research.

[Comparison of Plaster Fixation and Kirschner Wire Transfixation as Temporary Fixation of Displaced Ankle Fractures - Randomised Prospective Study]. / Porovnání sádrové fixace a transfixace Kirschnerovými dráty pri docasné fixaci dislokovaných zlomenin hlezna ­ randomizovaná prospektivní studie.

PURPOSE OF THE STUDY The purpose of the study was to assess two therapeutic procedures of temporary fixation of displaced ankle fractures, namely the plaster fixation or Kirschner wire (KW) transfixation via the sole of the foot. MATERIAL AND METHODS Group of patients The randomised prospective study conducted in the period 02/2016-02/2017 compared two methods of temporary fixation of displaced ankle fractures. In total, 38 patients were included in the study (18 patients treated with plaster fixation, 20 patients treated with KW). Methods During the randomisation (by envelopes, drawing of lots by the patient), in one group of patients, temporary stabilisation by plaster fixation was performed, whereas the other group was treated by percutaneously inserted KWs. The attention was focused on the quality of achieved reduction, its retention until the final treatment, and soft tissue status. After one year, the final examination was performed, in which we focused on the assessment of the clinical condition of the ankle joint with the use of the Olerud-Molander Ankle Score (OMAS), the AOFAS (American Orthopedic Foot and Ankle Society) score, and the Visual Analogue Scale (VAS) measuring the overall satisfaction. Moreover, in both the methods potential incidence of arthritic changes was monitored on radiographs. RESULTS Both the methods achieved 100% successful reduction rate. The group with plaster fixation reported a loss of reduction in six patients (33.3%) as against the KW group where no loss of reduction occurred. This difference was significant (p = 0.007). In plaster fixation method, after its removal local complications occurred on skin in 56%, of which skin necrosis in 16.7%, and it always occurred in association with the loss of reduction, which was statistically significant (p = 0.245). In KW method, local complications on skin were present in 25% only. In the group of patients with KW, there was not a single case of surface or deep infection reported. No KW migration was observed. DISCUSSION Potential complications of conservative treatment of displaced fractures with plaster fixation include the migration of fragments and widening of the ankle fork during the further course which may threaten the vitality of soft tissues. A total of six patients (33.3%) treated with plaster fixation showed a failure of reduction, which is by approximately 10% more than described in literature. In seven cases after the plaster fixation removal bullae were observed (38.9%) and in three cases skin necrosis was present (16.7%), which occurred in re-displaced fractures only. The bullae were present whether the reduction was successfully maintained or not. In literature, local complications after plaster fixation removal are reported in roughly 14%. Temporary percutaneous ankle KW transfixation is applied to maintain the reduced fracture in a favourable position and to facilitate monitoring and treating the soft tissues. Prior to the final surgical solution, bullae were observedin four cases (20%), of which skin necrosis in one case (5%). Bullae formation and necrosis are most likely related to the initial damage to soft tissues due to the injury and were not caused by the KW insertion. The literature describes local complications in 7% with respect to the KW technique, however, the type of complications is not specified. In our group, at a one-year follow-up arthritic changes grade I and II according to Kellgren and Lawrence scale were reported in 70% of cases with KW technique. Whether the osteoarthritis was caused by fixation or the fracture itself and what would be the percentage of individual types of osteoarthritis after several years of follow-up is a question. CONCLUSIONS Plaster fixation or Kirschner wires for temporal fixation of displaced ankle fractures shall be applied on a case by case basis. Based on our findings, the application of plaster fixation to displaced ankle fractures does not provide adequate stability of the reduced fracture and in case of re-displacement the status of soft tissues deteriorates. The impossibility to control the status of soft tissues in plaster fixation and the lower complication rate in fixation with K wires constitute additional reasons why this fixation technique via the sole of the foot appears to reap more benefits. Key words:displaced ankle fractures, temporal fixation, plaster fixation, Kirschner wire transfixation, complications.

Impact of systemic inflammation biomarkers on the survival outcomes of cervical cancer patients.

BACKGROUND: Inflammatory biomarkers have recently attracted attention as valuable prognosticators and predictors of survival outcomes in many cancers. We describe a new pre-treatment biomarker, expressed as the eosinophil-lymphocytes ratio (ELR) and validate other biomarkers such as the level of circulating eosinophils, neutrophil-lymphocytes ratio (NLR), platelet-lymphocytes ratio (PLR) and systemic immune-inflammatory index (SII) as prognostic factors in cervical cancer (CC) patients. METHODS: A retrospective cohort of 151 consecutive patients diagnosed with CC and treated according to the European guidelines with radiotherapy and/or chemotherapy and/or surgery in our institution from 2009 to 2016 were evaluated. Patients were categorized into two different groups based on the optimal cut-off for each biomarker, according to the receiver operating characteristic (ROC) curves. Impact of blood biomarkers on overall survival (OS), cancer-specific survival (CCS) and progression-free survival (PFS) were examined. RESULTS: Higher values of ELR, eosinophils and age ≥ 50 years were associated with better OS in univariate Cox analysis, while high NLR, PLR, SII, neutrophils ≥ 7.0, Bulky tumor and FIGO stage III-IV at diagnosis were prognosticators of worse survival outcomes. In multivariate analysis, the only factors independently impacting OS were ELR ≥ 0.07 (HR = 0.49, p = 0.048) and FIGO stage III-IV (HR = 2.5, p = 0.018). High PLR and SII were associated with shorter PFR. CONCLUSIONS: Increased values of ELR and eosinophils portend better OS in CC. To our best knowledge, this is the first report describing eosinophils-related biomarker as an independent prognostic factor in CC.

Haemoglobin monitoring in endometrial cancer patients undergoing radiotherapy

Purpose. To evaluate the level of anaemia monitoring and to determine the prevalence of anaemia in patients with endometrial carcinoma (EC) undergoing postoperative pelvic radiotherapy (RT). Methods. We evaluated 233 consecutive patients diagnosed with EC receiving RT in our institution between January 2011 and December 2015. One hundred and fifty-two patients (65.2%) received a combination of external beam radiotherapy (EBRT) and high dose rate brachytherapy (HDR-BT) (mean dose 53.4 Gy, range 21-75), and 71 patients (30.5%) were exclusively treated with HDR-BT (mean dose 10.2 Gy, range 7-20). Blood test results with haemoglobin (Hb) levels were collected at three specific time points were: pre-RT (Hb1), during RT (Hb2) and post-RT (Hb3). Anaemia was defined as Hb <12 g/dL. Results. Anaemia was detected in 54% of patients (67 patients) in the pre-RT analysis. Only 53.7% (n = 36) of the patients with anaemia detected pre-RT underwent subsequent Hb controls (during or post-RT). Blood tests were performed in 124 patients (53.20%) pre-RT, in 51 (17.59%) during RT and in 90 patients (38.62%) post-RT. Significant differences were observed between the mean Hb levels at Hb1-Hb3 (p = 0.001) and Hb2-Hb3 (p = 0.004). Patients with a pre-RT Hb level <12 g/dL presented a worse overall survival (OS) (p = 0.021, χ2 5.3) with a mean OS of 53.39 months (range 45.5-61.3) vs. 61.4 (range 58.4-64.4) in patients with Hb ≥12 g/dL. Conclusion. Although the presence of anaemia is frequent in patients with EC (53.2% of patients affected at cancer diagnosis) and influences the OS, Hb monitoring in patients receiving RT remains suboptimal (no controls during RT in 46.3%). There is a strong need to pay attention to blood test prescription for all the patients during and after RT (AU)

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Haemoglobin monitoring in endometrial cancer patients undergoing radiotherapy.

PURPOSE: To evaluate the level of anaemia monitoring and to determine the prevalence of anaemia in patients with endometrial carcinoma (EC) undergoing postoperative pelvic radiotherapy (RT). METHODS: We evaluated 233 consecutive patients diagnosed with EC receiving RT in our institution between January 2011 and December 2015. One hundred and fifty-two patients (65.2%) received a combination of external beam radiotherapy (EBRT) and high dose rate brachytherapy (HDR-BT) (mean dose 53.4 Gy, range 21-75), and 71 patients (30.5%) were exclusively treated with HDR-BT (mean dose 10.2 Gy, range 7-20). Blood test results with haemoglobin (Hb) levels were collected at three specific time points were: pre-RT (Hb1), during RT (Hb2) and post-RT (Hb3). Anaemia was defined as Hb <12 g/dL. RESULTS: Anaemia was detected in 54% of patients (67 patients) in the pre-RT analysis. Only 53.7% (n = 36) of the patients with anaemia detected pre-RT underwent subsequent Hb controls (during or post-RT). Blood tests were performed in 124 patients (53.20%) pre-RT, in 51 (17.59%) during RT and in 90 patients (38.62%) post-RT. Significant differences were observed between the mean Hb levels at Hb1-Hb3 (p = 0.001) and Hb2-Hb3 (p = 0.004). Patients with a pre-RT Hb level <12 g/dL presented a worse overall survival (OS) (p = 0.021, χ 2 5.3) with a mean OS of 53.39 months (range 45.5-61.3) vs. 61.4 (range 58.4-64.4) in patients with Hb ≥12 g/dL. CONCLUSION: Although the presence of anaemia is frequent in patients with EC (53.2% of patients affected at cancer diagnosis) and influences the OS, Hb monitoring in patients receiving RT remains suboptimal (no controls during RT in 46.3%). There is a strong need to pay attention to blood test prescription for all the patients during and after RT.

Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients

PURPOSE: To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily. Materials and methods: 154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I-IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. Results: With a median follow-up of 46.7 months (36.6-61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1-G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1-G2 but 1 G3) and in 27.7 % in vagina (all G1-G2 but one G4). In Group 2, 6.7 % developed acute G1-G2 bladder and 6.6 % acute vaginal (G1-G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1-G2 presented late problems in vagina. Conclusions: The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity

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Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients.

PURPOSE: To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily. MATERIALS AND METHODS: 154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I-IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. RESULTS: With a median follow-up of 46.7 months (36.6-61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1-G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1-G2 but 1 G3) and in 27.7 % in vagina (all G1-G2 but one G4). In Group 2, 6.7 % developed acute G1-G2 bladder and 6.6 % acute vaginal (G1-G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1-G2 presented late problems in vagina. CONCLUSIONS: The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity.

[Long-term results of nailing of extra-articular proximal humerus fractures]. / Dlouhodobé výsledky hrebování extraartikulárních zlomenin proximálního humeru.

PURPOSE OF THE STUDY To evaluate the long-term results of intramedullary nailing of extra-articular proximal humerus fractures. MATERIAL AND METHODS Thirty-six patients with 36 extra-articular fractures, types 11-A2 and 11-A3, treated by intramedullary nailing were reassessed after an average follow-up of 54 (30-86) months. The group included five type 11-A2 and 31 type 11-A3 fractures according to the AO/OTA classification. Radiographic and clinical outcomes - the absolute Constant score (CSabs) and the relative Constant score (compared to the contralateral side, CSrel) were evaluated. The rate of complications was assessed. RESULTS All fractures healed. The mean long-term CSabs was 73 pts, the mean CSrel was 89% of the unaffected side. Thirty (83%) patients achieved excellent or good results (CSrel higher than 80%), four (11%) had satisfactory and two patients (5.5%) had poor results (CSrel less than 60%). No significant difference was observed in functional results between different age groups. No non-union, loss of reduction or deep infection was encountered. Two cases of prolonged healing were observed, one implant-related complication happened due to locking screw breakage. Conclusion Nailing can be recommended for the safe treatment of extra-articular fractures of the proximal humerus. If the procedure is performed properly, the possibility of excellent functional results is high and the rate of complications is minimal. Age does not influence the final functional result. Key words: proximal humerus, extra-articular fractures, intramedullary nail, long-term results.

[AO type 13-C distal humerus fractures. Results of surgical treatment]. / Zlomeniny distálního humeru AO 13 C - výsledky operacní lécby.

PURPOSE OF THE STUDY: The aim of this retrospective study was to evaluate the results of surgical treatment in 41 fractures of the distal humerus classified as type C according to the AO system using conventional versus angle-stable locking plates. MATERIAL: Fifty-one patients were treated by the open reduction and internal fixation method at our department between 2005 and 2008. The group included 28 women and 23 men with an average age of 52.5 years. Forty-one patients came to the final treatment evaluation. The average follow-up was 19 months. Of the 41 injuries, 34% were open fractures. METHODS: All patients were operated on from the standard dorsal approach. Olecranon osteotomy was performed in 83% and the Bryan-Morrey procedure was used in 17% of the patients. Stable osteosynthesis with two reconstruction plates was used in 14 patients (34%), two locking distal humeral plates (DHP) in 21 patients (51%) and a reconstruction plate combined with a DHP was employed in six patients (15%).Controlled early passive rehabilitation was started as soon as acute pain after surgery had resolved. Follow-up at 4, 8 and 12 weeks and at 6 and 12 months included clinical and radiographic examination. The functional outcome was assessed using the Mayo Elbow Performance Score (MEPS) system. RESULTS: The average MEPS was 83.6 points. Excellent results were recorded in 19 (46%), good in 14 (34%), satisfactory in five (12%) and poor in three (8%) patients. Healing was achieved within 3 months of surgery in 82% and within 4 months in 12% of the patients. Non-union due to failure of osteosynthesis was recorded in 5 % of the patients. No differences were found in the duration of healing in relation to the implant used. The average flexion/extension range of motion (ROM) at the elbow was 108 degrees (range, 40 to 145 degrees). The complications included failure of osteosynthesis in three patients, deep wound infection in two, superficial infection in one and heterotopic ossification in five patients. Of 16 patients (39%) with ulnar nerve irritation, 15 had impairment in sensory function and one in motor function. The average operative time was 163 min. DISCUSSION: The results of our study correspond to relevant data reported in the present-day literature. There is an agreement in excellent and good functional outcomes, as assessed using the MEPS, in ROM values and operative time as well as in complications such as non-union, infection or heterotopic ossification. Compared with other studies, the proportion of ulnar nerve irritation in our group was higher. As reported, excellent results are achieved with the use of locking compression plates, particularly in comminuted fractures of the distal humerus in osteoporotic bone. CONCLUSIONS: The method of open reduction and internal fixation with two plates performed by an experienced surgeon brings about good results in the treatment of AO type C fractures of the distal humerus.

Three-dimensional structure analysis of mu-agatoxins: further evidence for common motifs among neurotoxins with diverse ion channel specificities.

We report the solution structure of mu-agatoxin-I (mu-Aga-I) and model structures of the closely related mu-agatoxin-IV (mu-Aga-IV) which were isolated from venom of the American funnel web spider, Agelenopsis aperta. These toxins, which modify the kinetics of neuronal voltage-activated sodium channels in insects, are C-terminally amidated peptides composed to 36 amino acids, including four internal disulfide bonds. The structure of mu-Aga-I was determined by NMR and distance geometry/molecular dynamics calculations. Structural calculations were carried out using 256 interresidue NOE-derived distance restraints and 25 angle restraints obtained from vicinal coupling constants. The peptide contains eight cysteines involved in disulfide bonds, the pairings of which were uncertain and had to be determined from preliminary structure calculations. The toxin has an average rmsd of 0.89 A for the backbone atoms among 38 converged conformers. The structure consists of a well-defined triple-stranded beta-sheet involving residues 7-9, 20-24, and 30-34 and four tight turns. A homologous peptide, mu-Aga-IV, exhibited two distinct and equally populated conformations in solution, which complicated spectral analysis. Analysis of sequential NOE's confirmed that the conformers arose from cis and trans peptide bonds involving a proline at position 15. Models were developed for both conformers based on the mu-Aga-I structure. Our structural data show that the mu-agatoxins, although specific modifiers of sodium channels, share common secondary and tertiary structural motifs with phylogenetically diverse peptide toxins targeting a variety of channel types. The mu-agatoxins add voltage-sensitive sodium channel activity to a growing list of neurotoxic effects elicited by peptide toxins which share the same global fold yet differ in their animal origin and ion channel selectivity.

Design and structure-activity relationships of C-terminal cyclic neurotensin fragment analogues.

Neurotensin (NT) is a linear tridecapeptide with a broad range of central and peripheral pharmacological effects. The C-terminal hexapeptide of NT (NT8-13) has been shown to possess similar properties to NT itself, and in fact, an analogue of NT8-13 (N alpha MeArg8-Lys-Pro-Trp-Tle-Leu13, Tle = tert-leucine) has been reported to possess central activity after peripheral administration. Cyclic derivatives of this hexapeptide were synthesized by a combination of solution and solid-phase peptide synthetic methodologies, and several analogues had low nanomolar binding affinity for the NT receptor. In particular, cyclo[Arg-Lys-Pro-Trp-Glu]-Leu (cyclized between the alpha amine of Arg and the gamma carboxylate of Glu) possessed 16 nM NT receptor affinity and was determined to be an agonist in vitro. 1H-NMR and 13C-edited 1H-NMR spectroscopy were performed on this and related cyclic analogues to help identify structural properties which may be important for receptor recognition. These cyclic peptides represent novel molecular probes to further investigate NT receptor pharmacology, as well as to advance our understanding of the structure-conformation relationships of NT and to help establish a working basis for additional pharmacophore mapping studies.

[The problem of gallstone dissolution (author's transl)]. / Das Problem der Gallensteinauflösung.

Stones in the gallbladder and the bile ducts can be dissolved by oral medication. The stones present in the bile ducts can also be dislodged and caused to disappear by local irrigation. For cholesterol stones the most effective treatment at present is application of Chenodeoxycholic Acid. However, surgery must be considered in the first instance. In case of bile duct stones it is suggested that prophylactic and conservative treatment should be attempted.