Risk factors predicting cervical spine fracture on CT in craniocervical trauma - retrospective study.

INTRODUCTION: The study identifies risk factors predicting cervical spine fracture on CT based on information in the referral form. METHODS: All patients aged over 18 years with a CT scan of the head and cervical spine completed at the University Hospital Brno in the year 2019 to exclude any fresh trauma were included in the retrospective study. The analyzed potential risk factors included gender, age over 65 years, unconsciousness or impaired consciousness, mechanism of injury, paresthesia or plegia suspected to be associated with trauma, cervical spine pain, other neurological symptomatology, presence of cervical collar, presence of intracranial hemorrhage on head CT, and presence of skull fracture on head CT. RESULTS: In total, a cervical or upper thoracic spine fracture was described in 51 of 1177 patients (4.3%). Statistically significant risk factors for cervical spine fracture on CT scan were identified as mechanism of injury similar to car accident or jumping into water (OR 2.52; p=0.004), pain of the cervical spine (OR 1.81; p.

Commissioning of the new water line of the Central wastewater treatment plant in Prague and its impact on the operation of the existing water line.

This paper describes the commissioning of the new water line (NWL) of the Central wastewater treatment plant in Prague and also the gradual reduction of the existing water line (EWL) loading. Concerning the NWL, the gradual start-up of the process without inoculation will be described. As to the EWL, the presentation describes the adaptation of the EWL operation to the relatively quick reduction of loading to approximately 35%.

[Comparison of Tension Banding and Modified Orthocord Sling in Acromioclavicular Dislocation Treatment - Non-Randomized Retrospective Study]. / Stabilizace akromioklavikulární luxace tahovou cerklází ve srovnání s jedním Kirschnerovým drátem doplneným klickou z cástecne vstrebatelného materiálu ­ nerandomizovaná retrospektivní studie.

PURPOSE OF THE STUDY Acromioclavicular joint dislocations (AC) represent one of the most frequent injury to the shoulder gridle. Low grade injuries type Rockwood I-II are treated non-operatively. Whereas high grade injuries type Rockwood III-VI are usually treated operatively. At present a wide spectrum of surgical techniques is used: Bosworth screw, hook plate, pinning and tension banding, PDS-sling. In our study the pinning and tension banding technique and the modified orthocord sling technique were compared. The goal of this study was to determine whether there are any clinical and radiological differences between these two techniques. MATERIAL AND METHODS This retrospective non-randomized level 3 evidence study included 58 patients. All of them have sustained a Tossy III AC dislocation. Of the 58 patients, 31 were treated with pinning and tension banding. Modified orthocord (absorbable knitted strand) sling technique (One 2.0-2.5 mm Kirchner wire, orthocord tension banding and coraco-clavicular ligament suture) was used in 27 patients. The same regime was used in postoperative follow up. For the clinical assessment the ASES and Constant score were used. The presence of calcification, degenerative changes, clavicular dislocation were assessed during the X-ray follow-ups. RESULTS The mean treatment time was 18.7 ± 4.9 weeks in the pinning and tension band group (Group A), whereas 15.8 ± 2.8 weeks in the modified orthocord sling technique (Group B). There was a significantly shorter period of healing in Group B. There were no statistically significant differences in the K wire removal time (Group A: 12.6 ± 3.7, Group B: 11.9 ± 3.2). No significant difference was observed between Group A and Group B on the ASES score (Group A: 95 ± 5.8, Group B: 98 ± 3.1) and on the Constant score (Group A: 97.7 ± 3.2, Group B: 97.9 ± 2.9). There were significant differences in both groups between the injured and non-injured shoulder on the Constant score. The mean secondary clavicular dislocation in Group A was 7.2 ± 1.8 mm in the operated shoulder and 4.8 ± 2.0 mm in the non-operated shoulder. The secondary dislocation in Group B was 7.5 ± 2.0 mm in the injured shoulder and 4.2 ± 1.2 mm in the non-injured shoulder. There was a significant difference between the injured and the non-injured shoulder in both groups. Calcification in coraco-clavicular ligament was observed in 15 (48.4%) Group A cases and in 13 (48.1%) Group B cases. Secondary AC joint arthrosis was observed in 8 (25.8%) Group A cases and in 1 (3.7%) Group B case. DISCUSSION No significant difference in clinical outcomes between both the surgical techniques was found. These results are comparable with other, recently published studies. On the other hand, we observed a significantly decreased treatment time with the modified orthocord sling technique. One, centrically inserted Kirschner wire, might better tolerate small rotation movements in the AC joint. Secondary clavicular dislocation, Kirschner wire dislocations and wound complications were similar in both groups and comparable to other, recently published studies. CONCLUSIONS Even though the tension banding and orthocord modified sling rank among the oldest and the cheapest techniques available for AC dislocation treatment, their results are comparable with modern and costly techniques. The orthocord modified sling technique has an advantage of fast and cheap material extraction in outpatient conditions. Key words: AC dislocation, acromioclavicular joint dislocation, orthocord sling, tension banding, AC disruption, acromioclavicular joint disruption.

[Arthroscopic Resection and Spongioplasty of Scapholunate Joint in Treating Chronic Dynamic Scapholunate Instability]. / Artroskopická resekce a spongioplastika skafolunátního kloubu v lécbe chronické dynamické skafolunátní nestability.

PURPOSE OF THE STUDY The study evaluated the method of arthroscopic stabilisation of dynamic scapholunate (SL) instability by scapholunate joint resection using bone graft to create synarthrosis between the scaphoid and lunate. MATERIAL AND METHODS Twenty-six patients with chronic dynamic SL instability of Geisler-Messina - EWAS grade IIIB, C and IV were treated by artificial synarthrosis of SL joint using an arthroscopic technique. The mean follow-up period of the patients was 32.2 months (28-39 months, when the range of motion and grip strength were assessed. The functional results were evaluated through the Mayo wrist score. RESULTS Post-operatively, a statistically significant improvement in grip strength was reported, with the mean improvement of 9 kg. On the other hand, significant worsening of flexion with a mean change of -6°, a mean change in extension of -5° and ulnar deviation -2° were identified. According to the visual analogue scale, there was a significant reduction in pain associated with everyday activity (mean change -4) as well as with heavy manual work (mean change -4). According to the Mayo wrist score, the overall results in 3 patients were excellent, in 16 patients good, in 6 patients satisfactory, and in one patient poor. DISCUSSION A limited range of motion significantly influencing the overall results of the functional assessment on the Mayo wrist score does not have a substantial subjective impact on patients and their routine activities. All the studies evaluating the operative techniques restoring stability of proximal row of the carpal bones report limited range of motion in the wrist. These interventions aim at a strong, pain-free grip with preserved wrist function. CONCLUSIONS This study illustrates that the arthroscopic stabilisation of scapholunate joint by synarthrosis is a reliable, minimally invasive surgical method to treat the higher grade of dynamic SL instability. This method makes it possible to achieve good stability of the damaged joint and leads to satisfactory functional results. Key words:wrist, instability, scapholunate joint, arthroscopy, bone graft.

[Symptomatic Intraosseous Ganglion of the Trapezium. Case Report and Literature Review]. / Symptomatické intraoseální ganglion os trapezium ­ kazuistika a prehled literatury.

An intraosseous ganglion cyst has been reported in nearly all of the carpal bones; it is a rare cause of chronic wrist pain. The case presented here is a rare finding of symptomatic intraosseous ganglion of the trapezium bone. The relevant literature is reviewed. Key words: ganglion cyst, trapezium bone, wrist.

Post-transplantation diabetes mellitus: evaluation of treatment strategies.

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) is a serious complication after kidney transplantation, but evidence regarding long-term outcomes of treatment regimens remains scarce. AIM AND METHODS: The aim of this retrospective cohort analysis was to assess the long-term efficiency and safety of antidiabetic treatments in kidney transplant recipients (KTRs), who were diagnosed with PTDM by an oral glucose tolerance test (OGTT). RESULTS: Of 561 KTRs that were screened for PTDM at our outpatient clinic, 71 (13%) had a diabetic OGTT and were included in this study. Mean follow-up was 34.2 ± 16.1 months. Thirty-six PTDM patients (51%) received antidiabetic treatment after diagnosis with either a dipeptidyl peptidase-4 (DPP-4) inhibitor, a sulfonylurea, pioglitazone, or insulin. These patients had significantly higher fasting glucose and two-h plasma glucose (2HPG) values at baseline than those who remained without therapy. In contrast to lifestyle modification alone or sulfonylureas, DPP-4 inhibitors improved glycemic control significantly. Adverse events were generally mild and occurred at similar rates in all groups. CONCLUSION: While sulfonylureas failed to improve glycemic control, DPP-4 inhibitors appeared effective and safe for the therapy of PTDM after kidney transplantation.

Efficacy and safety of vildagliptin in new-onset diabetes after kidney transplantation--a randomized, double-blind, placebo-controlled trial.

New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation, but therapeutic strategies remain underexplored. Dipeptidyl peptidase-4 (DPP-4) inhibitors selectively foster insulin secretion without inducing hypoglycemia, which might be advantageous in kidney transplant recipients (KTRs) with NODAT. We conducted a randomized, double-blind, placebo-controlled, phase II trial to assess safety and efficacy of the DPP-4 inhibitor vildagliptin. Intraindividual differences in oral glucose tolerance test (OGTT)-derived 2-h plasma glucose (2HPG) from baseline to 3 months after treatment served as primary endpoint. Among secondary outcomes, we evaluated HbA1c, metabolic and safety parameters, as well as OGTTs at 1 month after drug discontinuation. Of 509 stable KTRs who were screened in our outpatient clinic, 63 (12.4%) had 2HPG ≥ 200 mg/dL, 33 of them were randomized and 32 completed the study. In the vildagliptin group 2HPG and HbA1c were profoundly reduced in comparison to placebo (vildagliptin: 2HPG = 182.7 mg/dL, HbA1c = 6.1%; placebo: 2HPG = 231.2 mg/dL, HbA1c = 6.5%; both p ≤ 0.05), and statistical significance was achieved for the primary endpoint (vildagliptin: 2HPG-difference -73.7 ± 51.3 mg/dL; placebo: -5.7 ± 41.4 mg/dL; p < 0.01). Adverse events were generally mild and occurred at similar rates in both groups. In conclusion, DPP-4 inhibition in KTRs with overt NODAT was safe and efficient, providing a novel treatment alternative for this specific form of diabetes.

Role of Adjuvant Radiotherapy in Acinic Cell Carcinoma of the Salivary Glands: A Systematic Review.

A systematic review was carried out to evaluate if adjuvant radiotherapy for acinic cell carcinomas (ACCs) of salivary glands improves survival. Twelve retrospective studies published between 2000 and 2020 that analysed the effect of radiotherapy on salivary gland neoplasms and ACCs of salivary glands and met the inclusion criteria were included in the review. The overall quality of the studies was moderate to low. There was no high-quality evidence for improved survival with radiotherapy for ACCs of the salivary gland. Some evidence suggests that there may be an advantage for patients with high-grade tumours, but these data should be interpreted with caution due to the small number of patients and low-quality evidence. Good quality of evidence is lacking. Recommendation for adjuvant radiotherapy for tumours with poor prognostic factors will require discussion and shared decision-making with the patients.

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer.

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

Osteoradionecrosis after treatment of head and neck cancer: a comprehensive analysis of risk factors with a particular focus on role of dental extractions.

In head and neck cancer (HNC), osteoradionecrosis (ORN) is one of the most significant complications of radiotherapy (RT). With an absence of effective non-surgical treatment, prevention of the development of ORN is the best approach. The purpose of this study was to identify the risk factors for the development of ORN in HNC. Records of 1,118 patients with HNC treated with radical RT (≥55Gy) from January 2010 to December 2019 were reviewed. After applying the exclusion criteria, 935 patients were included in the final analysis. In patients with confirmed ORN, exact RT doses were mapped. In total, 91 patients were found (9.7%) with a median (range) time of eight (3-89) months to the development of ORN. Smoking, having a primary site in the oropharynx, bone surgery before adjuvant RT, the addition of concurrent chemotherapy, the presence of xerostomia, dental extraction pre-RT, the time ≤20 days between dental extraction and start of RT, and receiving >55Gy RT dose were significant factors for its development. This comprehensive analysis including the precise RT dose mapping has shown the risk factors for the development of ORN. In practice, every effort should be made to avoid these risk factors without compromising the oncology treatment. The findings of this analysis may provide a basis for future prospective research on this topic.

Exposure to the COVID-19 pandemic environment and generosity.

We report data from an online experiment which allows us to study how generosity changed over a 6-day period during the initial explosive growth of the COVID-19 pandemic in Andalusia, Spain, while the country was under a strict lockdown. Participants (n = 969) could donate a fraction of a €100 prize to an unknown charity. Our data are particularly rich in the age distribution and we complement them with daily public information about COVID-19-related deaths, infections and hospital admissions. We find correlational evidence that donations decreased in the period under study, particularly among older individuals. Our analysis of the mechanisms behind the detected decrease in generosity suggests that expectations about others' behaviour, perceived mortality risk and (alarming) information play a key-but independent-role for behavioural adaptation. These results indicate that social behaviour is quickly adjusted in response to the pandemic environment, possibly reflecting some form of selective prosociality.

Pharmacokinetics, pharmacodynamics, safety, and tolerability of single-dose fingolimod (FTY720) in adolescents with stable renal transplants.

Oral fingolimod signals the sphingosine 1-phosphate receptor and this in turn mediates immunomodulatory activity. No data of fingolimod in any pediatric population existed before this study. We put our study results in perspective against data from adult renal transplant patients. We investigated pharmacokinetics and pharmacodynamics of single-dose fingolimod (0.07 mg/kg) and its effects on lymphocytes and heart rate in seven adolescents (14.1 ± 1.6 yr) with stable renal transplants. Blood samples for pharmacokinetics and lymphocytes were collected at screening, baseline, and up to 28 days post-dosing. Cardiac monitoring included 12-lead ECG, 24-h Holter monitoring, and echocardiography. A fingolimod dose of 0.07 mg/kg resulted in mean AUC of 731 ± 240 ng·h/mL and C(max) of 3.6 ± 0.6 ng/mL. Drug exposure was nearly identical to adults receiving the same dose. Absolute lymphocyte count decreased 85% from baseline; average nadir occurred by six h post-dose. Heart rate decreased from 74 bpm (predose mean) to 53 bpm (nadir) three h post-dose. Mean heart rates recovered by Day 14 (75 bpm). Weight-adjusted doses of fingolimod in adolescents resulted in drug exposure similar to adults. Adolescents and adults shared comparable negative chronotropic effects and decreased lymphocyte count. Recovery trajectories of these parameters back to baseline were similar between age groups.

Sotrastaurin and everolimus pharmacokinetics after single-dose coadministration.

INTRODUCTION: Sotrastaurin is an immunosuppressant that blocks T-lymphocyte activation via protein kinase C inhibition. The authors determined whether a pharmacokinetic interaction occurs between sotrastaurin and everolimus, both of which are substrates and inhibitors of CYP3A4. METHODS: This was a randomized, three-period, crossover study in 18 healthy subjects. They received single oral doses of (1) 100 mg sotrastaurin, (2) 2 mg everolimus, and (3) the drug combination. Clinical and pharmacokinetic data were collected to Day 5 after each treatment. RESULTS: Coadministration of everolimus decreased sotrastaurin C(max) from 638 +/- 295 to 539 +/- 211 ng/ml yielding a combination/ monotherapy ratio (90% confidence interval) of 0.87 (0.76 - 1.00). Sotrastaurin total AUC was not altered by everolimus with values of 3660 +/- 1853 versus 3630 +/- 2006 ng*h/ml and a ratio of 1.00 (0.88 - 1.13). Sotrastaurin increased everolimus C(max) from 15 +/- 6 to 16 +/- 6 ng/ml yielding a ratio of 1.15 (0.99 - 1.33) and increased everolimus total AUC from 114 +/- 50 to 137 +/- 56 ng*h/ml yielding a ratio of 1.20 (1.05 - 1.37). The possibility that a higher dose of sotrastaurin than used in this study might further increase everolimus blood levels cannot be excluded. CONCLUSIONS: Coadministration of a single 100 mg dose sotrastaurin with a single 2 mg dose everolimus did not alter sotrastaurin pharmacokinetics to a clinically relevant extent. Everolimus AUC was increased 20% by sotrastaurin.

Reduced inducibility of SOCS3 by interferon gamma associates with higher resistance of human breast cancer lines as compared to normal mammary epithelial cells.

The resistance to interferons (IFNs) limits their anticancer therapeutic efficacy. Here we studied the antiproliferative effect of interferon gamma in relation to SOCS3 expression in a panel of breast cancer cell lines and normal mammary epithelial cells. Compared to normal cells most breast cancer lines (7/8) were highly resistant to IFN-gamma. Using Northern blot and real time RT-PCR we investigated transcription of SOCS3 genes. All normal epithelial cells (4/4) showed SOCS3 induction (2-14 fold) while most breast cancer lines did not or weakly activated SOCS3 after the interferon gamma treatment. Among the cancer lines, the MDA-MB-468 cells showed increased sensitivity to IFN-gamma and relatively high level of SOCS3 induction (2-3 fold). Together, there was a good correlation

Intensity-modulated radiotherapy (55 Gy in 20 fractions) for high-grade laryngeal dysplasia: report of acute toxicity and functional outcome.

OBJECTIVE: Radiotherapy is an option to treat high-grade laryngeal dysplasia. This study aimed to evaluate the use of intensity-modulated radiotherapy, 55 Gy in 20 daily fractions, in treating this disease. METHODS: Acute toxicity was evaluated in all 14 patients treated. In 10 patients, functional voice outcome was measured using the Voice Handicap Index, and the Grade, Roughness, Breath, Asthenia, Strain ('GRBAS') scale. These measurements were performed pre-treatment and three months after intensity-modulated radiotherapy. RESULTS: All but one patient managed to complete radiotherapy. Acute toxicity was significant (one patient developed grade 4 and three patients developed grade 3 dysphagia). Four patients required hospital admission. In 9 out of 10 patients, radiotherapy improved voice quality. CONCLUSION: This radiotherapy regimen using intensity-modulated radiotherapy for laryngeal dysplasia is feasible and provided excellent functional outcome, but acute toxicity was significant. Dose de-escalation can be considered in the framework of clinical trials.

Cetuximab in the management of nasopharyngeal carcinoma - a narrative review.

BACKGROUND: Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease. METHOD: A literature search was performed using the keywords 'nasopharyngeal neoplasm', 'cetuximab' and 'Erbitux'. RESULTS: Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting. CONCLUSION: There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.

Hypofractionated Concomitant Chemoradiation in Inoperable Locally Advanced Non-small Cell Lung Cancer: A Report on 100 Patients and a Systematic Review.

AIMS: Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation. MATERIALS AND METHODS: One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan-Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included. RESULTS: In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time. CONCLUSION: Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.

The chemokine receptor Cxcr3 is not essential for acute cardiac allograft rejection in mice and rats.

Chemokine receptors have gained attention as potential targets for novel therapeutic strategies. We investigated the mechanisms of allograft rejection in chemokine receptor Cxcr3-deficient mice using a model of acute heart allograft rejection in the strain combination BALB/c to C57BL/6. Allograft survival was minimally prolonged in Cxcr3-deficient mice compared to wild-type (wt) animals (8 vs. 7 days) and treatment with a subtherapeutic dose of cyclosporine A (CsA) led to similar survival in Cxcr3-deficient and wt recipients (13 vs. 12 days). At rejection grafts were histologically indistinguishable. Microarray analysis revealed that besides Cxcr3 only few genes were differentially expressed in grafts or in spleens from transplanted or untransplanted animals. Transcript analysis by quantitative RT-PCR of selected cytokines, chemokines, or chemokine receptors or serum levels of selected cytokines and chemokines showed similar levels between the two groups. Furthermore, in a rat heart allograft transplantation model treatment with a small molecule CXCR3 antagonist did not prolong survival despite full blockade of Cxcr3 in vivo. In summary, Cxcr3 deficiency or pharmacologic blockade does not diminish graft infiltration, tempo and severity of rejection. Thus, Cxcr3 does not appear to play a pivotal role in the allograft rejection models described here.