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The normal functioning of the respiratory system is a leading factor, both for the survival of people caught in an aquatic environment in a marine casualty and for the effectiveness of the assistance activities. In view of this, in 2020 a team of researchers from Varna Medical University, the Naval Academy Varna and the Bulgarian Red Cross set out to study some physiological respiratory parameters and related anthropometric data of 51 individuals, 41 men and 10 women aged between 17 and 48 years of age. The subjects were divided into two groups: 1) trainees in the water rescue courses conducted at BRC-Varna and 2) 1st - year students of the Naval Academy. All participants in the study are non-smokers. The examination of the respiratory indicators is performed according to a standardized methodology with the same spirometer, which is able to measure and register over 30 indicators. Of these, three were analyzed in the present study: forced expiratory volume for 1 s (FEV1), forced vital capacity (FVC), and their FEV1/FVC percentage (Tiffeneau index). The results show that, according to anthropometric data, FVC and FEV1 are higher in water rescue trainees than in Naval Academy cadets. The Tiffeneau index is higher than the reference values ​​of the participants in both study groups, but the results are better in the group of naval cadets. As far as the functional capabilities of the respiratory system are essential for the activity of marine professionals, it can be assumed that the high results obtained from the spirometric examination of the participants from both groups are a prerequisite for higher efficiency of rescue operations and improvement of their personal safety. when working in a marine environment. The prospect is that after collecting a statistically significant amount of data combined with results obtained from other types of functional tests, to create better safety practices for people who are professionally engaged in maritime activities. As far as the functional capabilities of the respiratory system are essential for the activity of marine professionals, it can be assumed that the high results of the spirometric study in all study participants are a prerequisite for improving both their personal safety when working in the marine environment and for higher efficiency and success of rescue operations. The perspective is, after collecting a statistically significant volume of data and in combination with other functional studies, to create good practices to improve the safety systems of people in contact with the marine environment .

Simple Summary Reported clinical data on high dose rate mono brachytherapy of prostate cancer carried out using two different treatment regimens are analyzed in this study. The analysis is based on a mechanistic tumor control probability model, which accounts for a possible increase in the tumor radio-sensitivity during treatment. The aim of the study was to verify a hypothesis that the clinically observed better performance of the longer treatment regimen (28 days vs. 14 days) might be due to a state of initial hypoxia and its ensued overcoming by re-oxygenation and, hence, re-sensitization of the prostate cancer. The performed investigation confirmed the assumption of initially hypoxic stage of the tumor followed by its re-sensitization, thus providing a foundation for the use of prolonged schedules for low- to intermediate-risk prostate cancer treatment. Abstract Background: Mechanistic TCP (tumor control probability) models exist that account for possible re-sensitization of an initially hypoxic tumor during treatment. This phenomenon potentially explains the better outcome of a 28-day vs 14-day treatment schedule of HDR (high dose rate) brachytherapy of low- to intermediate-risk prostate cancer as recently reported. Methods: A TCP model accounting for tumor re-sensitization developed earlier is used to analyze the reported clinical data. In order to analyze clinical data using individual TCP model, TCP distributions are constructed assuming inter-individual spread in radio-sensitivity. Results: Population radio-sensitivity parameter values are found that result in TCP population values which are close to the reported ones. Using the estimated population parameters, two hypothetical regimens are investigated that are shorter than the ones used clinically. The impact of the re-sensitization rate on the calculated treatment outcome is also investigated as is the anti-hypothesis that there is no re-sensitization during treatment. Conclusions: The carried out investigation shows that the observed clinical data cannot be described without assuming an initially hypoxic state of the tumor followed by re-oxygenation and, hence, re-sensitization. This phenomenon explains the better outcome of the prolonged treatment schedule compared to shorter regimens based on the fact that prostate cancer is a slowly repopulating tumor.

Age-related macular degeneration is a leading cause of irreversible vision loss in individuals over 55 years of age worldwide. Conventionally, it is divided into two subtypes – dry (non-neovascular) and wet (neovascular) form. Neovascular age-related macular degeneration comprises only 10-15% of all patients but is responsible for more than 80% of blindness related to the disease. It requires early diagnosis and timely treatment. Fluorescein angiography is the current ‘gold standard’ for diagnosing neovascular forms. However, as an invasive procedure, it may be contraindicated in some circumstances and cause serious adverse effects. Optical coherence tomography-angiography is a relatively new, non-invasive and fast imaging modality gaining popularity in the diagnosis of age-related macular degeneration, especially for the neovascular form of the disease. It enables structural and functional information of blood vessels in the retina and choroid, without the need of an intravenous dye. In this study we present and discuss 3 cases of different subtypes of choroidal neovascularization secondary to neovascular age-related macular degeneration. All of them were examined by fluorescein angiography and optical coherence tomography-angiography. The results were qualitatively analyzed.

Objectives: Frailty is a geriatric syndrome associated with increased vulnerability of older adults. Knee osteoarthritis (OA) is the most prevalent joint disease and one of the leading causes of disability and poor physical activity (PA) of elderly individuals worldwide. Total knee arthroplasty TKA has been recognized as an effective surgical treatment in end-stage of knee OA. There is a lack of consensus regarding the universally accepted rehabilitation protocol for frail elderly subjects after TKA. Aim: to evaluate the potential benefits in functional ambulation (FA) and PA among frail elderly Bulgarian subjects underwent TKA, a novel group-based rehabilitation protocol was performed from the subjects. Materials and methods: A total of 130 frail elderly Bulgarian TKA recipients (67 women and 63 men aged 72, 69 ± 0.44,) were included. FA was assessed by the six-minute walking distance (6MWD). PA was evaluated by the PASE questionnaire. Participants were evaluated one week before TKA, as well as 3 and 6 months after the group-based rehabilitation. Results: Significant increase in FA was observed at the third and sixth month after the group-based intervention (p< 0.001). PASE score, was increased at the third and sixth month after the group-based intervention (p

PURPOSE Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5 T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose. MATERIAL AND METHODS For twenty PC patients treated by 35 Gy (Dp) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (Drec). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D95% ≥ 95%Dp to PTV, and D1cc ≤ Dp to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from Drec. A cumulative dose (Dsum) was calculated from the five daily Drec deformed onto the simulation MRi. RESULTS For each patient, CTV coverage resulted in D95% > 95%Dp when estimated as ifa by Drec. No significant difference for D95% and D99% metrics to CTV resulted between groups I and II. D1cc was

Vertebrobasilar junction aneurysms occur rarely, but have a higher rupture rate than supratentoral aneurysms, and higher morbidity and mortality. Their location ventral to the neuroaxis makes them a challenging surgical lesion. In this paper, we share our experience with the surgical technique for the management of these complex aneurysms. An in-depth understanding of the anatomy of these aneurysms, careful preoperative planning, and a meticulous surgical technique, including knowledge of every detail of the procedure—positioning, an advanced skull base technique, and careful aneurysm dissection and clipping—is essential for a successful outcome of the surgery.

Eye injuries caused by air-gun pellets are some of the most severe ocular injuries and can lead to loss of vision. We present the case of a 16-year-old boy with a retained intraocular air-gun pellet who underwent hybrid 20/23-gauge phacovitrectomy with foreign body removal and silicone oil tamponade. The patient’s visual acuity before surgery was perception of light. Computer tomography scans detected the intraocular localization of a metal foreign body. Once removed, the air-gun pellet was revealed to be 7 mm long. Traumatic cataract, vitreous hemorrhage, and retinal detachment were present. During the 3‑month follow-up period there were no signs of inflammation. Best-corrected visual acuity reached 20/200.

Physical capacity and mental resilience are the basis on which the skills of navy professionals are built. The high results in these complex characteristics are important in extreme sea conditions, especially in risky situations when the protection of human life depends on them. This report presents an ongoing study of lifeguard trainees. Its aim is to study their personality traits and the changes which come after the end of the training. To achieve this, there was a research at the beginning and end of the course. Psychological questionnaires were used to determine the level of resistance to stress and personal traits such as anxiety, frustration, aggression and regression. The results were compared with an analogous group of navy professionals (cadets). The initial results show a correlation between their maintenance of sports activity and their level of stress. The existing correlation between the level of stress and rigidity is interesting. The created model of research should continue until the optimum number of studied individuals is reached and the scope of the study should be extended to studies of non-professionals in maritime activities compared the current group and a group of trained lifeguards.

The impact of a rectal spacer and an increased near maximum target dose in VMAT prostate SBRT is studied. For a group of 11 patients (35Gy-in-five-fractions VMAT prostate SBRT) a set of 4 plans were generated, namely two VMAT plans, with D2%⩽37.5Gy (Hom) and with D2%⩽40.2Gy (Het), were created for each of two CT scans taken before (NoSpc) and after (Spc) transperineal spacer insertion. Consequently the methodology for parameter invariant TCP (tumor control probability) plan ranking was applied for comparison of the plans in terms of tumor control. NTCPs (normal tissue complication probabilities) were calculated for rectum and bladder using Lyman's model. For all 11 patients the TCP plan ranking has shown that the Het plans would perform considerably better in TCP terms than the Hom ones. The plans without rectal spacer were ranked worse compared to those with rectal spacer except for one set of Hom plans. The calculated NTCPs for rectum produced by the Het plans were quite similar to the NTCPs of the Hom ones. The rectal NTCPs of the Hom Spc plans were always lower than the NTCPs of the Hom NoSpc plans. The NTCP values for bladder were extremely low in all cases. The use of rectal spacer leads in general to lower risk of rectal complications, as expected, and even to better tumor control. Plans with increased near maximum target dose (D2%⩽40.2Gy) are expected to perform much better in terms of tumor control than those with D2%⩽37.5Gy.

The aim of the work is to investigate the impact of radiation-independent (natural or spontaneous) tumor cell death on tumor control probability (TCP) during and following fractionated external-beam radiotherapy employing both analytical and numerical methods. The analytical method solves a TCP model accounting for tumor repopulation and non-radiation tumor cell death during fractionated external-beam radiotherapy. The numerical method is based on a Monte Carlo simulation of the processes of radiation-induced cell kill, as well as cell division and natural cell death randomly taking place in the time interval between fractions. Distributions of the number of surviving cells are constructed using the Monte Carlo method for cases with and without natural cell death. The analytically and numerically calculated values of TCP were found to be in excellent agreement (as shown in the Method and materials section), thereby validating both methods. The TCP model is then fitted to two different experimental data sets with the aim of determining the model parameter values, primarily the natural death rate. Two versions of the linear-quadratic model of cell damage-with and without assumed re-sensitization of the tumor cells during treatment-are used. In two of the fits a strong correlation between the repopulation and spontaneous cell death rates is observed. It was possible to determine separately the values of the two rates only in the fit of the model with resensitization to the most diversified data set consisting of seven different fractionation regimes. The observed correlation together with a theoretical consideration leads to the conclusion that in most cases it is the net effect of the two processes of birth and death rather than the processes separately that determines treatment outcome. However, depending on the values of the rates of the two processes and the duration of the treatment, the treatment outcome may be more accurately determined by the absolute values of the two rates rather than just by their difference.

Макулната дегенерация, свързана с възрастта е водеща причина за необратима загуба на зрителната функция при хора над 65 години в развитите страни. Заболеваемостта ѝ се очаква да се увеличи с около 50% до 2020 г. предвид удължената продължителност на живот и увеличение на застаряващото население в световен мащаб. Загубата на централното зрение при късните форми на болестта - географска атрофия и хориоидална неоваскуларизация, представлява сериозен социален и икономически проблем. Това изисква редовен скрининг, ранно диагностициране и своевременно лечение на заболяването. Ангио-оптичната кохерентна томография e сравнително нов диагностичен метод. Базирайки се на своята неинвазивност, методът е все по-разпространен при макулната дегенерация, свързана с възрастта.

In small NSCLC, 88% local control at three years from SBRT was reported both for schedule (20-22 Gy ×3) (Fakiris et al 2009 Int. J. Radiat. Oncol. Biol. Phys. 75 677-82), actually close to (18-20 Gy ×3) if density correction is properly applied, and for schedules (18 Gy ×3) and (11 Gy ×5) (Palma et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 82 1149-56). Here, we compare our computed iso-TCP = 88% dose per fraction (d88) for three and five fractions (n) with such clinically adopted ones. Our TCP model accounts for tumour repopulation, at rate λ (d(-1)), reoxygenation of chronic hypoxia (ch-), at rate a (d(-1)) and fluctuating oxygenation of acute hypoxia (ah-), with hypoxic fraction (C) of the acutely hypoxic fractional volume (AHF). Out of the eight free parameters whose values we had fitted to in vivo animal data (Ruggieri et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 83 1603-8), we here maintained (a(d(-1)), C, OERch, OERah/OERch, AHF, CHF) = (0.026, 0.17, 1.9, 2.2, 0.033, 0.145) while rescaling the initial total number of clonogens (N(o)) according to the ratio of NSCLC on animal median tumour volumes. From the clinical literature, the usually assumed (αo/βo(Gy), λ(d(-1))) = (10, 0.217) for the well-oxygenated (o-)cells were taken. By normal (lognormal) random sampling of all parameter values over their 95% C.I., the uncertainty on present d88(n) computations was estimated. Finally, SBRT intra-tumour dose heterogeneity was simulated by a 1.3 dose boost ratio on 50% of tumour volume. Computed d88(±1σ) were 19.0 (16.3; 21.7) Gy, for n = 3; 10.4 (8.7; 12.1) Gy, for n = 5; 5.8 (5.2; 6.4) Gy, for n = 8; 4.0 (3.6; 4.3) Gy, for n = 12. Furthermore, the iso-TCP = 88% total dose, D88(n) = d88(n)*n, exhibited a relative minimum around n = 8. Computed d88(n = 3, 5) are strictly consistent with the clinically adopted ones, which confirms the validity of LQ-model-based TCP predictions at the doses used in SBRT if a highly radioresistant cell subpopulation is properly modelled. The computed minimum D88(n) around n = 8 suggests the adoption of 6 ≤ n ≤ 10 instead of n = 3 in SBRT of small NSCLC tumours.

The efficacy of Stereotactic Body Radiation Therapy (SBRT) in early-stage non-small cell lung cancer for severely hypofractionated schedules is clinically proven. Tumour control probability (TCP) modelling might further optimize prescription dose and number of treatment fractions (n). To this end, we will discuss the following controversial questions. Which is the most plausible cell-survival model at doses per fraction (d) as high as 20Gy? Do clinical data support a dose-response relationship with saturation over some threshold-dose? Given the reduced re-oxygenation for severe hypofractionation, is the inclusion of tumour hypoxia in TCP modelling relevant? Can iso-effective schedules be derived by assuming a homogeneous tumour-cell population with α/β≈10Gy, or should distinct cell subpopulations, with different α/β values, be taken into account? Is there scope for patient-specific individualization of n? Despite the difficulty of providing definite answers to the above questions, reasonable suggestions for lung SBRT can be derived from the literature. The LQ model appears to be the best-fitting model of cell-survival even at such large d, and is therefore the preferred choice for TCP modelling. TCP increases with dose, reaching saturation above 90% local control, but there is still uncertainty on the threshold-dose. In silico simulations accounting for variations in tumour oxygenation are consistent with an improved therapeutic ratio at 5-8 fractions instead of the current 3-fraction reference schedules. Tumour hypoxia modelling might also explain how α/β changes with n, identifying the clonogen subpopulation which determines tumour response. Finally, an optimal patient-specific n can be derived from the planned lung dose distribution.

To verify whether a tumor control probability (TCP) model which mechanistically incorporates acute and chronic hypoxia is able to describe animal in vivo dose-response data, exhibiting tumor reoxygenation.The investigated TCP model accounts for tumor repopulation, reoxygenation of chronic hypoxia, and fluctuating oxygenation of acute hypoxia. Using the maximum likelihood method, the model is fitted to Fischer-Moulder data on Wag/Rij rats, inoculated with rat rhabdomyosarcoma BA1112, and irradiated in vivo using different fractionation schemes. This data set is chosen because two of the experimental dose-response curves exhibit an inverse dose behavior, which is interpreted as due to reoxygenation. The tested TCP model is complex, and therefore, in vivo cell survival data on the same BA1112 cell line from Reinhold were added to Fischer-Moulder data and fitted simultaneously with a corresponding cell survival function.The obtained fit to the combined Fischer-Moulder-Reinhold data was statistically acceptable. The best-fit values of the model parameters for which information exists were in the range of published values. The cell survival curves of well-oxygenated and hypoxic cells, computed using the best-fit values of the radiosensitivities and the initial number of clonogens, were in good agreement with the corresponding in vitro and in situ experiments of Reinhold. The best-fit values of most of the hypoxia-related parameters were used to recompute the TCP for non-small cell lung cancer patients as a function of the number of fractions, TCP(n).The investigated TCP model adequately describes animal in vivo data exhibiting tumor reoxygenation. The TCP(n) curve computed for non-small cell lung cancer patients with the best-fit values of most of the hypoxia-related parameters confirms previously obtained abrupt reduction in TCP for n10, thus warning against the adoption of severely hypofractionated schedules.

Key Clinical Message A 15‐year‐old female patient presented with neck pain accompanied by cervical scoliosis, on the existence of torticollis. Although rare, hemivertebra of the cervical spine is a congenital deformation associated with these three clinical features.

To analytically investigate the possibility of a parameter invariant ranking of radiotherapy (RT) plans based on comparing the tumor control probabilities (TCPs) produced by the competing plans for different values of the radiobiological model parameters determining the radiation response.Individual TCP models based on the Single hit model of cell kill and on the linear-quadratic (LQ) model of cell damage, with and without repopulation, are considered. The tumor dose distributions in case of heterogeneous dose irradiation are described by a Gaussian distribution function on the basis of which a TCP expression is derived depending only on the mean dose to the tumor and its standard deviation and the TCP model parameters.It is shown that in case of homogeneous dose to the tumor the plan ranking in terms of TCP is parameter invariant. In case of heterogeneous dose to the tumor there are cases when the plan ranking is parameter invariant and cases when the parameter invariance is violated. An interesting dependence of the extent of the parameter invariance violation on the model of cell kill as well as on the size and repopulation rate of the tumor is noted.We conclude that in many cases RT plan ranking in terms of TCP is parameter invariant. However, since there exist cases where the parameter invariance is lost an investigation of the specific plans to be ranked should be performed applying the proposed approach.

To investigate the capacity of two phenomenological expressions to describe the population tumor response in case of a heterogeneous irradiation of the tumor. The generalization of the individual tumor control probability (TCP) models to include the case of a heterogeneous irradiation is a trivial problem. However, an analytical solution that results in a closed form population TCP formula for the heterogeneous case is, unfortunately, a very complex mathematical problem. Therefore we applied a numerical approach to the problem.Pseudo-experimental data sets are constructed through the generation of dose distributions and population TCP data obtained by a numerical solution of a multi-dimensional integral over an individual TCP model. The capacity of the following two phenomenological - Poisson and equivalent uniform dose (EUD) based - TCP expressions: [Figure: see text] to describe the population tumor response in case of heterogeneous irradiation is investigated through their fitting to the psuedo-experimental data sets. RESULTS AND CONCLUSIONS. While both expressions produce statistically acceptable fits to the pseudo-experimental data within 2% TCP error band, the use of the second expression is preferable since it produces considerably better fits to the data sets.

Two patients with thalassemia minor and end-stage renal failure on hemodialysis were treated with epoetin zeta (Silapo®, Retacrit®; STADA, Germany), a medicinal product that was developed and registered as biosimilar to epoetin alfa. Dosing was titrated individually for two patients to achieve a stable hemoglobin (Hb) concentration of 10.5–12.0 g/dL. One patient was treated intravenously with epoetin zeta; the other patient was treated subcutaneously. After 12 weeks of therapy both patients achieved Hb levels within the target range, confirming the effi cacy of epoetin zeta in patients with thalassemia minor.

Objective To develop a model describing the relationship between the parotid gland radiation dose and salivary flow reduction. Salivary function was described by the "relative flow reduction" (RFR)—a continuous variable in contrast to the traditional binary response used in normal tissue complication probability estimations. Methods and materials Twenty-three patients with squamous cell carcinoma of the head and neck who were treated with intensity-modulated radiotherapy (RT) were the subject of this study. Of these patients, 19 had sufficiently long follow-up to be eligible for analysis. All were treated with curative intent, most (14 of 19) in the postoperative setting. The planning objectives were to deliver a mean dose of 50, 60, or 70 Gy, respectively, to low-risk microscopic, high-risk microscopic, and gross disease areas, while maintaining a mean dose of ≤20 Gy to the spared portion of one or both parotid glands. The mean dose to all parotid glands (right and left) was 30.2 Gy. All submandibular glands received >50 Gy when not surgically removed. Whole-mouth saliva collections, including both stimulated and unstimulated saliva flow, were obtained before treatment and at regular intervals after RT. These measurements were converted to the RFR by comparing the posttreatment and pretreatment flow rates. Any follow-up flow rates greater than baseline were scored as 0 relative reduction. We used Lyman's model to relate the equivalent uniform dose to RFR at various points for each patient. The equivalent uniform dose was calculated using the linear quadratic model, with an assumed α/β ratio of 3 Gy for the parotid gland. Measurements were modeled 1–3 months after RT (early) and >6 months after RT (late), and using the best and worst measurements, regardless of when measured. Results Fitting the Lyman model to RFR data of unstimulated flow revealed a statistically significant dose–complication relationship. We observed a stepwise reduction in flow, with the threshold dose D 50 at 2 Gy per fraction (D 50 ) increasing from 12.4 Gy (early) to 43.9 Gy (late). For the worst and best flow measurements, the corresponding D 50 (2 Gy/fr) was 13.0 Gy and 40.1 Gy, respectively. For most stimulated flow measurements, a weak relationship was found between the RFR and equivalent uniform dose. In those cases, the model did not yield a statistically significant description of the data. However, in the case of late measurements, the relationship was statistically significant and similar to that seen in the unstimulated cases, with a D 50 (2 Gy/fr) of 47.5 Gy. Conclusion We observed a strong relationship between the generalized mean parotid gland dose and RFR. The threshold dose increased markedly between the early and late measurements, indicating a statistically significant recovery effect in this tissue. Compared with unstimulated flow, the RFR for stimulated flow was not described as well by the model, because the effect of the stimulant was not included in the model.

In this work we study the descriptive power of the main tumor control probability (TCP) models based on the linear quadratic (LQ) mechanism of cell damage with cell recovery. The Poisson, binomial, and a dynamic TCP model, developed recently by Zaider and Minerbo are considered. The Zaider-Minerbo model takes cell repopulation into account. It is shown that the Poisson approximation incorporating cell repopulation is conceptually incorrect. Based on the Zaider-Minerbo model, an expression for the TCP for fractionated treatments with varying intervals between two consecutive fractions and with cell survival probability that changes from fraction to fraction is derived. The models are fitted to an experimental data set consisting of dose response curves that correspond to different fractionation regimes. The binomial TCP model based on the LQ mechanism of cell damage solely was unable to fit the fractionated response data. It was found that the Zaider-Minerbo model, which takes tumor cell repopulation into account, best fits the data.

The AIM of this study was to analyse the results of the surgery and compare the outcomes of unicondylar knee arthroplasty and high tibial osteotomy performed in isolated gonarthrosis. PATIENTS AND METHODS: Between 2007 and 2011, 65 patients were implanted a partial knee endo-prosthesis in the Clinic of Orthopedics and Traumatology. Men were 23 (35.4%) and women were 42 (64.6%). High tibial osteotomy was performed to manage the unicompartmental gonarthrosis in 92 patients (47 men and 45 women) for 13 years between 1975 and 1987. These two modalities were used only in cases in which one of the knee joint compartments was affected. Clinical, para-clinical, functional tests and radiographic examination were conducted of the affected knee joint. RESULTS: The results of the study were assessed by the rating system proposed by the Knee Society and modified by John Insall. At four-year follow-up study the outcomes of the partial prosthesis were assessed as excellent in 85.13%, good - in 13.11% and satisfactory in 1.77% of patients. After high tibial osteotomy the results were considered very good in 54.18% of patients, good - in 32.29%, satisfactory - in 6.25%, and poor - in 7.8%. CONCLUSIONS: Partial knee arthroplasty is a resurfacing procedure, while high tibial osteotomy is used only to slow the overall degenerative process with gradual progressive exacerbation of osteoarthritis with age. The results after prosthetic treatment had a better dynamics than that in high tibial osteotomy

A method for determining the optimum dose distribution in the planning target volume is proposed when target volumes are deliberately enlarged to account for tumour mobility in external beam radiotherapy. The optimum dose distribution is a dose distribution that will result in an acceptable level of tumour control probability (TCP) in most of the arising cases of tumour dislocation. An assumption is made that the possible shifts of the tumour are subject to a Gaussian distribution with mean zero and known variance. The idea of a reduced (mean in ensemble) tumour cell density is introduced. On this basis, the target volume and dose distribution in it are determined. The tumour control probability as a function of the shift of the tumour has been calculated. The Monte Carlo method has been used to simulate TCP distributions corresponding to tumour mobility characterized by different variances. The obtained TCP distributions are independent of the variance of the mobility because the dose distribution in the planning target volume is prescribed so that the mobility variance is taken into account. For simplicity a one-dimensional model is used but three-dimensional generalization can be done.

This paper offers a general mathematical approach to dose distribution optimization which allows tumours with different degrees of complexity to be considered. Two different biological criteria - A) keeping the control probability of the different parts of the tumour (local tumour control probability) uniform throughout the tumour and B) minimizing the mean dose delivered to the tumour are studied. For both criteria we impose the requirement that the whole tumour control probability be kept on a certain desired level. It is proved that the adoption of the first criterion requires a dose distribution logarithmic with the cell density and proportional to the inverse of the cell radiosensitivity while the adoption of the second criterion necessitates a homogeneous dose distribution when the cell radiosensitivity is constant. The corresponding formula for the dose distribution in case of heterogeneous cell radiosensitivity is also given. The two criteria are compared in terms of local tumour control probability and mean dose delivered to the tumour. It is concluded that maintaining constant local tumour control probability (criterion A) may be of greater clinical importance then minimizing the mean dose (criterion B).

An analytic solution to the problem of finding the value of the dose DR delivered to the edge of the tumour in the case of the tumour model studied by Webb and Nahum is suggested.

Osteoporosis is a disease in which the mineral density of bone is reduced, its microarchitecture disrupted, and the expression profile of non- collagenous proteins altered. Normal fracture treatment is a complicated, multistage process, involving different cellular events and regulated by local and systematic factors. The objective of this study was to develop bio- active nanostructured materials, in both acellular and autologous cell-seeded forms to enhance bone fracture fixation and healing thought creating highly porous structures which will promote osteogenesis. The approach to develop highly effective hydrogels for counteracting the effects of osteoporosis followed different ways: (a) synthetic and biological polymer chemistry, by using a thermally gelling polymer and nanodiamonds (ultradisperse diamond UDD) (b) experiments with cell models (endothelial progenitor cells EPC). Our investigations demonstrated that in vitro EPC transformation to osteo- blasts was enhanced in the presence of a osteoprogenitor medium and UDD. These results provided initial evidence that synthetic nanomaterials may exhibit certain properties that are comparable to natural one, and nano- material architecture may serve as a superior scaffolding for promoting EPC transformation and biomineralization.

The dose heterogeneity in the tumor is often described as being normally distributed. Besides the normal distribution we propose the Fermi function describing Fermi statistics as a possible dose heterogeneity descriptor. In order to demonstrate the adequacy of the proposed functions as dose distribution descriptors 30 clinical gross tumor volume (GTV) dose-volume histograms (DVHs) are gathered and fit with the examined functions.

The aim of this study is to develop a magnetic resonance imaging (MRI)-based treatment planning procedure for intracranial lesions. The method relies on (a) distortion correction of raw magnetic resonance (MR) images by using an adaptive thresholding and iterative technique, (b) autosegmentation of head structures relevant to dosimetric calculations (scalp, bone and brain) using an atlas-based software and (c) conversion of MR images into computed tomography (CT)-like images by assigning bulk CT values to organ contours and dose calculations performed in Eclipse (Philips Medical Systems). Standard CT + MRI-based and MRI-only plans were compared by means of isodose distributions, dose volume histograms and several dosimetric parameters. The plans were also ranked by using a tumor control probability (TCP)-based technique for heterogeneous irradiation, which is independent of radiobiological parameters. For our 3 T Intera MRI scanner (Philips Medical Systems), we determined that the total maximum image distortion corresponding to a typical brain study was about 4 mm. The CT + MRI and MRI-only plans were found to be in good agreement for all patients investigated. Following our clinical criteria, the TCP-based ranking tool shows no significant difference between the two types of plans. This indicates that the proposed MRI-based treatment planning procedure is suitable for the radiotherapy of intracranial lesions.

Background. A property of the integral dose-volume histogram (DVH) space is analytically investigated in this work. A curve called an alpha-iso-NTCP (normal tissue complication probability) envelope is constructed by connectingpoints belonging to step-like integral DVHs, each corresponding to homogeneous partial organ irradiation of a relative volume vk to dose Dk such that the resulting NTCP has, in all cases, a particular value alpha. The two subspaces into which the envelope divides the DVH space are analytically explored in terms of the equivalent uniform doses (EUDs) corresponding to the different DVHs. It is theoretically proven that any DVH, other than the step-like DVH, passing through a point (Dk1 vk) from the alpha-iso-NTCP envelope, will result in an NTCP > alpha. Conclusions. Thus, it is proven thatany DVH that at least partially lies above the envelope results in an NTCP> alpha. For some of the DVHs lying under the envelope, e.g. those that are tangential to the envelope, it is also true that the resulting NTCP > alpha. However, it was numerically demonstrated elsewhere that there east DVHslying entirely in the lower subspace that result in an NTCP < alpha. Therefore, one can conclude that since there is a chance that a DVH lying under the alpha-iso-NTCP envelope will result in NTCP < alpha, it would be preferable in the treatment optimization process to seek solutions for DVHs lying entirely under an iso-NTCP envelope and avoid solutions that have DVHs above an iso-NTCP envelope. Izhodišča. V članku smo raziskali lastnost prostora integralnega dozno-volumskega histograma (DVH). Krivuljo enake verjetnosti poškodbe zdravega tkiva (alfa-izo-NTCP (normal tissue complication probability)) smo oblikovali s povezovanjem točk, ki pripadajo intervalom vk stopničastega integralnega DVH s pripadajočo dozo Dk in posledičnim NTCP z vrednostjo alfa. Podprostora, na katera krivulja razdeli DVH prostor, smo raziskali v smislu ekvivalentnih uniformnih doz (EUD), ki pripadajo različnim DVH-jem. Zaključki.Teoretično je dokazano, da ima vsak DVH, ki je različen od stopničastega DVH in ki gre skozi točko (Dk1 vk) alfa-izo-NTCP ovojnice, NTCP > alfa. Iz česar sledi, da vsakemu DVH, ki vsaj delno leži nad ovojnico, pripada NTCP > alfa. Nekaterim DVH, ki ležijo pod ovojnico, npr. se je dotikajo, prav tako pripada NTCP > alfa. Vendar je bilo numerično dokazano, daima DVH, ki v celoti leži v spodnjem podprostoru, NTCP < alfa. Glede na slednje bi bilo v postopku optimizacije zdravljenja zaželeno iskati rešitve z DVH povsem pod izo-NTCP ovojnico in se izogibati tistim, ki ležijo nad njo.

In this work, the functional form similarity between the individual and fundamental population TCP models is investigated. Using the fact that both models can be expressed in terms of the geometric parameters gamma50 and D50, we show that they have almost identical functional form for values of gamma50 >= 1. The conceptual inadequacy of applying an individual model to clinical data is also discussed. A general individual response TCP expression is given,parameterized by Df and gammaf - the dose corresponding to a control level of f, and the normalized slope at that point. It is shown that the dose-response may be interpreted as an individual response only if gamma50 is sufficiently high. Based on the functional form equivalency between the individual and the population TCP models, we discuss the possibility of applying the individual TCP model for the case of heterogeneous irradiations. Due to the fact that the fundamental population TCP model is derived for homogeneous irradiations only, we propose the use of the EUD, given by the generalized mean dose, when the fundamental population TCP model is used to fit clinical data. Raziskali smo podobnost TCP modelov za posameznika in populacijo. Z ozirom na to, da lahko oba modela opišemo z geometrijskima parametroma gama50 in D50, smo pokazali, da dobita skoraj enako obliko pri vrednostih gama50 >= 1. Obravnavali smo neprimernost uporabe modela za posameznika na kliničnih podatkih. Podali smo splošen izraz za TCP in ga parametrizirali z Df in gamaf - z dozo, kjer TCP zavzame vrednost f in z normaliziranim naklonom v tej točki. Izkazalo se je, da lahko krivuljo interpretiramo kot odziv posameznika le ob dovolj velikem gama50. Na osnovi podobnosti TCP modelov za posameznika in populacijo smo obravnavali možnost uporabe slednjega v primeru neenakomernega obsevanja. Ker osnovni TCP model za populacijo predpostavlja enakomerno obsevanje, smo predlagali, da se pri uporabi na kliničnih podatkih vrednost parametra EUD izenači s povprečno dozo.

In volumetric-modulated arc therapy (VMAT) prostate stereotactic body radiotherapy (SBRT), dose coverage of the planning target volume (PTV) becomes challenging when the sparing of rectum, bladder and urethra is strictly pursued. Our current 35-Gy-in-five-fraction plans only assure 33.2 Gy to ≥95% PTV ([Formula: see text] ≥ 95%). Looking for an improved [Formula: see text], increased near-maximum target dose (D2%) and prostate-rectum spacer insertion were tested.For 11 patients, two VMAT plans, with D2% ≤ 37.5 Gy (Hom) or D2% ≤ 40.2 Gy (Het), on each of two CT studies, before or after spacer insertion, were computed. All plans assured [Formula: see text] ≥95%, and1 cm(3) of rectum, bladder and urethra receiving ≥35 Gy. By hypothesis testing, several dose-volume metrics for target coverage and rectal sparing were compared across the four groups of plans. The impact of spacer insertion on the fractions of rectum receiving more than 18, 28 and 32 Gy ([Formula: see text]) was further tested by linear correlation analysis.By hypothesis testing, the increased D2% was associated with improvements in target coverage, whereas spacer insertion was associated with improvements in both target coverage and rectal [Formula: see text]. By linear correlation analysis, spacer insertion was related to the reductions in rectal [Formula: see text] for X ≥ 28 Gy.A slightly increased D2% or the use of spacer insertion was each able to improve [Formula: see text]. Their combined use assured [Formula: see text] ≥ 98% to all our patients. Spacer insertion was further causative for improvements in rectal sparing.For VMAT plans in prostate SBRT, the distinct dosimetric usefulness of increased D2% and of the use of spacer insertion were validated in terms of target coverage and rectal sparing.

Radiotherapy treatment planning is becoming ever more complex, driven largely by the growing use of intensity modulated radiotherapy (IMRT). There is a corresponding need to improve the computer-based programs being designed to optimize the process of planning the spatial and temporal distributions of dose for such treatments. This article reviews the general objectives of treatment planning, and also the various physical and biological/statistical criteria that have been explored to serve as the bases for optimization objective functions. Keywords: radiotherapy treatment planning; optimization of treatment planning; radiotherapy optimization; radiotherapy treatment planning dose distribution; radiotherapy dose-response model biological dose-response modeling

The effects of radiation damage, tumour repopulation and cell sublethal damage repair and the possibility of extracting information about the model parameters describing them are investigated in this work. Previously published data on two different cultured cell lines were analysed with the help of a tumour control probability (TCP) model that describes tumour cell dynamics properly. Different versions of a TCP model representing the cases of full or partial cell recovery between fractions of radiation, accompanied by repopulation or no repopulation were used to fit the data and were ranked according to statistical criteria. The data analysis shows the importance of the linear–quadratic mechanism of cell damage for the description of the in vitro cell dynamics. In a previous work where in vivo data were analysed, the employment of the single hit model of cell kill and cell repopulation produced the best fit, while ignoring the quadratic term of cell damage in the current analysis leads to poor fits. It is also concluded that more experiments using different fractionation regimes producing diverse data are needed to help model analysis and better ranking of the models.

The critical volume (CV) normal tissue complication probability (NTCP) model was used to fit experimental data on radiation pneumonitis in mice to test the model and determine the values of the model parameters characterizing the lung structure: relative critical volume and cell radiosensitivity. The entire lungs of mice from ten different strains were irradiated acutely and homogeneously to different doses. The experimental animals from the different strains expressed different radiation sensitivities, forming ten well-defined dose-response curves. The most widely accepted biological NTCP model (the individual CV NTCP) readily applicable to cases of acute uniform irradiation was used to fit all the individual dose-response curves simultaneously. To account for the apparent difference in the response of the different strains, it was assumed that the strains differed in their (cell) radiosensitivity. The maximum likelihood method of fitting was used. The obtained fit was statistically highly acceptable. The best-fit value of the relative critical volume, mu, was 78%, which is extremely close to the histologically observed value of around 72%. The values of radiosensitivity, alpha, ranged between 0.26 and 0.37 Gy(-1) for the different strains. The best-fit numbers of functional subunits (FSU) constituting the lung, N, and the number of cells in an FSU, N(o), were implausibly low: N = 9 and N(o) = 23, respectively. The best-fit value of N(o)N was a very small number that was unlikely to correspond to the total number of cells comprising the lung, suggesting that a different interpretation of N and N(o) was required. The individual CV model provided a simultaneous description of the individual responses of different mouse strains through assumed interindividual variability in alpha only. A new interpretation is given to the entities corresponding to N(o) and N. N(o)N is interpreted as the number of certain elementary structures. These structures are considered to be equivalent to the classical functional subunit, which is much larger than a cell and plays a fundamental role in determining the radiation response of the organ. N is identified as the number of the few large subdivisions of the lungs, M = microN is the number that have to be damaged for the lung to fail. N(o) is interpreted as the mean number of elementary structures (FSU) per large subdivision. This imposes a picture of damage to large, contiguous subdivisions containing many FSU, which is consistent with the histological appearance of the lungs of mice in respiratory distress. This picture is in marked contrast to the random distribution of small areas of damage expected for the small size of an FSU. This random distribution is characteristic of earlier stages of the development of radiation pneumonitis, suggesting that some additional process spreads injury from damaged FSU to adjacent, undamaged FSU during the terminal phase.

Purpose: To compare the partially wide tangent (PWT) technique of breast and internal mammary chain irradiation with photon/electron (P/E) and standard tangent (ST) techniques in terms of dose homogeneity within breast and the dose to critical structures such as the heart and lung. Methods and Materials: Sixteen left breast cancer patients underwent CT simulation. The breasts, lungs, heart, and internal mammary chain were contoured and treatment plans generated on a three-dimensional planning system (Helax-TMS). Results: The mean dose to the left breast volume with the ST, P/E, and PWT techniques was 94.7%, 98.4%, and 96.5%, respectively (p 0.029). The left lung received the lowest mean dose with the ST technique (13.9%) compared with PWT (22.8%) and P/E (24.3%). The internal mammary chain volume was most consistently treated with the PWT (mean dose 99%) vs. P/E (86%) and ST (38.4%) techniques. The heart received the least dose with ST (mean dose 6.7%) vs. PWT (10.3%) and P/E (19%). The PWT treated the greatest amount of contralateral breast (mean dose 5.8%) vs. ST (3.2%) vs. P/E (2.8%). Conclusion: The PWT technique treats the internal mammary chain with acceptable toxicity to major organs, especially the heart, and with reasonable dose homogeneity in patients with mastectomy or intact breasts. © 2003 Elsevier Science Inc.