CDK5-cyclin B1 regulates mitotic fidelity.

CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression1. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p392. Here, using independent chemical genetic approaches, we specifically abrogated CDK5 activity during mitosis, and observed mitotic defects, nuclear atypia and substantial alterations in the mitotic phosphoproteome. Notably, cyclin B1 is a mitotic co-factor of CDK5. Computational modelling, comparison with experimentally derived structures of CDK-cyclin complexes and validation with mutational analysis indicate that CDK5-cyclin B1 can form a functional complex. Disruption of the CDK5-cyclin B1 complex phenocopies CDK5 abrogation in mitosis. Together, our results demonstrate that cyclin B1 partners with both CDK5 and CDK1, and CDK5-cyclin B1 functions as a canonical CDK-cyclin complex to ensure mitotic fidelity.

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients.

PURPOSE: The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival. METHODS: This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2-9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP). RESULTS: After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1-5) and 2 (1-6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09). CONCLUSION: In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Assessment of cervical vascularization density in patients with locally advanced squamous cell cervical carcinoma evaluated in colour Doppler and power Doppler functions.

PURPOSE: The aim of the prospective study was to assess changes during treatment and prognostic significance of cervical vascularization density in patients with cervical squamous cell carcinoma (SCC) staged II B and III B and to find relationship of cervical vascularization density with tumour diameter, grading, staging and age of patients. METHODS: The study group included 50 patients who underwent transvaginal Doppler ultrasonography prior to chemoradiotherapy, after external beam radiation therapy (EBRT) and 6 weeks after HDR brachytherapy. The colour Doppler (CD) vascularity index (CDVI) and the power Doppler (PD) vascularity index (PDVI) in cervical tumour were examined. RESULTS: CDVI and PDVI values decreased significantly during radiotherapy (0.13 (95% CI 0.09-0.16); 0.09 (95% CI 0.07-0.11) and 0.05 (95% CI 0.03-0.06) for CDVI (p < 0.001) and 0.26 (95% CI 0.22-0.31); 0.18 (95% CI 0.14-0.22) and 0.08 (95% CI 0.06-0.11) for PDVI (p < 0.001)). No statistically significant associations of CDVI and PDVI with tumour diameter, grading, staging and age of patients were found. The higher (above median) CDVI values before EBRT were associated with better OS (p = 0.041). The higher (above median) PDVI values before EBRT were associated with superior DFS (p = 0.011) and OS (p < 0.001). DFS and OS did not differ significantly regarding CDVI and PDVI values after EBRT and after the treatment. CONCLUSIONS: In the study group, cervical vascularization density evaluated in CD and PD functions did not depend on tumour diameter, grading, staging and age of patients and decreased during radiotherapy. The prognosis for our patients with CDVI and PDVI before the treatment above the median value was better than compared to patients with these parameters below the median value.

Being a young radiation oncologist in Poland: results of a multi-institutional survey.

In 2018, Polish Society of Radiation Oncology formed a young section (yPTRO), dedicated to radiation oncologists under the age of 40. To evaluate their current situation, an anonymous, nationwide, online survey was carried out. Thirty-two-item-based questionnaire investigated young radiation oncologists' perception of employment, workload, education, malpractice lawsuits, scientific research, and board exam. A total of 44 physicians responded to the questionnaire, yielding a response rate of 25%. Results of the survey identified the main problematic areas. In general, young radiation oncologists in Poland are overloaded with bureaucracy. They complain on spending too much time at work and lack work-life balance. The risk of being sued for medical error is threatening two-thirds of responders in everyday work. Compensation is not satisfying for nearly half of the survey participants. Nearly all young radiation oncologists continue education and participate in national and international educational events. Forty-eight percent of responders do scientific research alongside clinical work. However, the perception of young radiation oncologists on the board exam is alarming and requires further discussion. Fifty-five percent of the survey participants think that current form of the exam is not appropriate. Hopefully, 75% of physicians feel fairly evaluated. The presented report is the first of its kind in Poland. Issues mentioned in our questionnaire will help newly formed yPTRO to develop strategic priorities for the upcoming years.

Radiation Oncology Training in Poland: Multi-institutional Survey.

To evaluate the quality of radiation oncology training in Poland and to identify difficulties and needs of radiation oncology trainees (ROTs), an anonymous online survey using Google Forms was conducted in November 2018. All ROTs from Poland (n = 154) were invited to complete the survey. The survey consisted of 30 questions and regarded aspects such as satisfaction from training, cooperation with the supervisor, and education. During the study period, 105 ROTs from 22 Polish cities responded (the response rate was 68%). Almost 85% were satisfied with the choice of specialty, 43% with training and 81% with the teaching place. Clinical cooperation with the supervisor was described as difficult by 25%. With education, 38% of responders experienced obstacles and another 25% stated that educational cooperation with their supervisor was none. "Good practice" understood as treatment according to the latest guidelines or internal protocols were reported by 71%. Obligatory traineeships were shorter than recommended according to 67% of the responders, usually due to shortage of medical staff. Almost two-thirds of ROTs work only in clinics, while 34% perform both clinical and scientific work. The responders suggested that the introduction of organ-specified courses is an appropriate modification of the current program. Noteworthy, current diagnostic imaging and physics courses are not sufficient for the majority of participants (81% and 80%, respectively). Radiation oncology training is conducted relatively well in Poland. Some hospitals need to improve clinical and educational cooperation between trainees and their supervisors.

Assessment of cervical volume and spectral Doppler parameters in tumour dominant vessel of patients with locally advanced squamous cell cervical carcinoma.

We evaluated cervical volume and spectral Doppler parameters: peak systolic velocity (PSV), resistance index (RI) and pulsatility index (PI) in the tumour dominant vessel of 50 patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB and their changes during treatment. The patients underwent transvaginal Doppler ultrasonography prior to treatment, after external beam radiation therapy (EBRT) and 6 weeks after brachytherapy. Radiotherapy decreased cervical volume and PSV values of the tumour dominant vessel. The PSV values before EBRT in G1 + G2 tumours were higher than in G3 tumours. No correlations between cervical volume, PSV, RI and PI values with disease-free survival (DFS) and overall survival (OS) were found. We concluded, that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results. Spectral Doppler parameters PSV, RI and PI of tumour dominant vessel did not predict prognosis for these patients.Impact StatementWhat is already known on this subject? Transvaginal Doppler sonography is considered as a useful diagnostic method in patients with cervical carcinoma. However, despite numerous studies, the value of spectral Doppler parameters in tumour dominant vessel and cervical volume of patients with locally advanced cervical SCC is still not well defined.What the results of this study add? In our prospective study, we found that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results and spectral Doppler parameters of tumour dominant vessel did not predict prognosis for these patients.What the implications are of these findings for clinical practice and/or further research? Our study underlines the limited value of spectral Doppler technique in patients with cervical carcinoma. Further research should be focussed on identifying and validating novel prognostic and predictive factors.

The impact of G protein-coupled oestrogen receptor 1 on male breast cancer: a retrospective analysis.

INTRODUCTION: The G protein-coupled oestrogen receptor 1 (GPER-1) is a potential prognostic marker in breast cancer. However, its role in male breast cancer (MBC) is still unknown. This study evaluates the expression of GPER-1 in MBC samples and correlates these data with clinical and pathological parameters including patients' survival. MATERIAL AND METHODS: For this retrospective analysis of a prospectively maintained cohort of patients with MBC, we examined 161 specimens for GPER-1 expression using immunohistochemistry. An immunoreactive score (IRS) was calculated based on staining intensity and the percentage of positive tumour cells. Then, we correlated GPER-1 IRS with clinical and pathological parameters, and overall and relapse-free survival. RESULTS: About 40% of MBC samples were positive for GPER-1 expression (IRS ≥ 4). There was no significant correlation with clinicopathological parameters, such as hormone receptor status or grading. However, a statistical trend was observed for tumour size (≥ 2 cm, p = 0.093). Kaplan-Meier survival analysis revealed no significant correlation with relapse-free survival. However, there was a significant correlation with overall survival, but when we adjusted the log-rank p-value to compensate for the cut-off point optimization method, it rose above 0.1. Additionally, GPER-1-positive patients were older at diagnosis. When adjusted for age by multivariable Cox regression analysis, the significance of GPER-1 status for survival was further reduced. CONCLUSIONS: We found no significant prognostic value of GPER-1 in this MBC cohort as anticipated from studies on female BC. Future studies with higher sample size are needed to further verify a potential sex-specific role of GPER-1.

The prognostic value of red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in radiotherapy for oropharyngeal cancer.

BACKGROUND: Red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are known inflammatory indices. Elevated values are found in many cancers and may be associated with a poor prognosis. The article aimed to assess the impact of RDW, NLR, and PLR on overall survival (OS) of patients with oropharyngeal cancer treated with radiotherapy (RT). MATERIALS AND METHODS: This retrospective study includes 208 patients treated for oropharyngeal cancer with definitive RT or RT combined with neoadjuvant or concurrent systemic therapy, at one institution between 2004 and 2014. The receiver operating characteristic (ROC) method, log-rank testing, and Cox proportional hazards regression model were used for the analysis. RESULTS: The OS was significantly higher in RDW ≤ 13.8% (p = 0.001) and NLR ≤ 2.099 (p = 0.016) groups. The RDW index was characterized by the highest discriminatory ability [area under the curve (AUC) = 0.59, 95% confidence interval (CI): 0.51-0.67], closely followed by NLR (AUC = 0.58, 95% CI: 0.50-0.65). In the univariate Cox regression analysis, RDW [hazard ratio (HR): 1.28, 95% CI: 1.12-1.47, p < 0.001] and NLR (HR: 1.11, 95% CI: 1.06-1.18, p < 0.001) were associated with an increased risk of death. In the multivariate analysis, among the analyzed indices, only NLR was significantly associated with survival (HR: 1.16, 95% CI: 1.03-1.29, p = 0.012). CONCLUSIONS: In the study, only NLR proved to be an independent predictor of OS. However, its clinical value is limited due to the relatively low sensitivity and specificity.

GATA3 germline variant is associated with CRLF2 expression and predicts outcome in pediatric B-cell precursor acute lymphoblastic leukemia.

The germline variant at rs3824662 in GATA3 is a risk locus for Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), the biological subtype of B-cell precursor (BCP)-ALL defined by a distinct gene expression profile and the presence of specific somatic aberrations including rearrangements of CRLF2. In this study, we investigated whether rs3824662 in GATA3 associates with CRLF2 expression in leukemic cells and predicts prognosis in pediatric BCP-ALL patients treated according to the ALL Intercontinental Berlin-Frankfurt-Münster (IC BFM) 2009 (n = 645) and the ALL IC BFM 2002 (n = 216) protocols. High expression of CRLF2 was observed at both protein and mRNA levels (fourfold higher in AA than in CA + CC) among GATA3 AA variant carriers, independent of the presence of P2RY8-CRLF2 fusion. Additionally, the AA variant at rs3824662 was a significant factor affecting minimal residual disease level at the end of induction phase and overall survival regardless of the risk group and the protocol. The germline variant at rs3824662 in GATA3 is a prognostic factor which associates with CRLF2 expression in leukemic cells supporting the hypothesis that GATA3 may have a regulatory effect on the CRLF2 pathway in pediatric BCP-ALL.

Extracellular miRNAs as Biomarkers of Head and Neck Cancer Progression and Metastasis.

Head and neck squamous cell carcinomas (HNSCCs) contribute to over 300,000 deaths every year worldwide. Although the survival rates have improved in some groups of patients, mostly due to new treatment options and the increasing percentage of human papillomavirus (HPV)-related cancers, local recurrences and second primary tumors remain a great challenge for the clinicians. Presently, there is no biomarker for patient surveillance that could help identify patients with HNSCC that are more likely to experience a relapse or early progression, potentially requiring closer follow-up or salvage treatment. MicoRNAs (miRNAs) are non-coding RNA molecules that posttranscriptionally modulate gene expression. They are highly stable and their level can be measured in biofluids including serum, plasma, and saliva, enabling quick results and allowing for repeated analysis during and after the completion of therapy. This has cemented the role of miRNAs as biomarkers with a huge potential in oncology. Since altered miRNA expression was described in HNSCC and many miRNAs play a role in radio- and chemotherapy resistance, cancer progression, and metastasis, they can be utilized as biomarkers of these phenomena. This review outlines recent discoveries in the field of extracellular miRNA-based biomarkers of HNSCC progression and metastasis, with a special focus on HPV-related cancers and radioresistance.

Ossifying fasciitis at an extraordinary site - a case report and analysis of diagnostic pitfalls.

Ossifying fasciitis is a very rare disease of reactive character; however, it can mimic malignant lesions, especially osteosarcoma. We report a case of a 30-year-old woman, who experienced a rapidly growing painful lesion of the left knee joint, preceded by a trauma. The tumor was resected, and the histopathological image suggested a malignant lesion with features of an osteosarcoma. A detailed correlation with a clinicopathological and radiological analysis led to the final diagnosis of ossifying fasciitis at an extraordinary site of patellar retinaculum. Our case shows that the close similarity between ossifying fasciitis and osteosarcoma may be challenging.

Being overweight has limited effect on SCARF osteotomy outcome for hallux valgus correction.

PURPOSE: The purpose of this study was to investigate the association between body mass index (BMI) and the results of SCARF osteotomy of the first metatarsal for hallux valgus (HV) correction, as the literature on this is scant. METHODS: This prospective study was carried out between 2011 and 2015. One hundred and thirty-three patients diagnosed with moderate to severe HV underwent a SCARF corrective osteotomy. We divided the patients into two groups according to their BMI: normal and overweight. Postoperative follow-up was two years. All patients were examined twice by two medical doctors simultaneously: pre-operatively and post-operatively at two years' follow-up. Data collected included biometrical records, X-rays [HV angle (HVA), intermetatarsal angle (IMA), American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal Index (AOFAS-HMI) and visual analogue scale (VAS) for pain and satisfaction]. RESULTS: There was a significant difference between patient age (p = 0.001), age at onset (p < 0.001) and AOFAS-HMI (p = 0.035) at follow-up. Other parameters were similar in both groups. CONCLUSION: Regardless of BMI, the radiological outcome was comparable. Despite a significant difference in AOFAS-HMI results, pain and satisfaction level were similar. The authors agreed that high BMI has protective role in the prevalence of HV.

The antero-lateral approach with corpectomy in the management of the ventral meningioma of the spinal canal.

The authors present the anterior approach to cervical spine, which enabled complete resection of tumor located in the anterior part of the spinal canal. Considering there are not many reports in the literature, the authors present a case of a meningioma at the level C5-C6 resected with good result through anterolateral approach.

Neurofibromatosis type 2 (NF 2) or schwannomatosis?--Case report study and diagnostic criteria.

INTRODUCTION: Neurofibromatosis type 2 (NF2) and schwannomatosis are entities that may, due to the similarity of clinical symptoms, cause diagnostic difficulties. Incidence rate of both diseases is similar and estimated between 1:25,000 and 1:40,000. The genes associated with the development of the aforementioned disorders are located on chromosome 22 and lay in proxmity. Schwannomatosis is characterized by an incomplete penetrance and the risk of its transmission to the offspring is significantly lower than in the case of NF 2. Schwannomatosis clinical characteristic is similar to the NF2, however vestibular schwannomas are not present. Therefore the imaging studies evaluated by an experienced radiologist play a key role in the diagnostic process. CASE REPORT: Forty two-year-old female hospitalized three times because of the tumors of the spinal canal was admitted to the Department of Neurosurgery and Peripheral Nerve Surgery in 2008 because of the cervical pain syndrome with concomitant headache. She was diagnosed with a schwannomatosis, recently distinguished, the third form of neurofibromatosis. MRI imaging revealed craniocervical junction tumor. Suboccipital craniectomy with concomitant C1-C2 laminectomy was done in order to remove the lesion. After the surgery the patient did not present any deficits in neurological examination and was discharged from hospital in good general condition. CONCLUSIONS: The patient was diagnosed with schwannomatosis, recently established neurofibromatosis entity which may resemble NF2 clinically. In patients after the age of 30, in whom we observe multiple schwannomas without the concomitant hearing impairment, the diagnosis of schwannomatosis is very likely.

Altered platelets' morphological parameters in children with type 1 diabetes ­ a case-control study.

BACKGROUND: Platelet hyperreactivity is a factor which contributes towards increased risk of cardiovascular events in adults with type 2 diabetes (T2DM). However, little is known about platelets' disturbances among children with type 1 diabetes (T1DM). The aim of the study was to investigate whether platelets' morphology or function are altered in children with type 1 diabetes, potentially predisposing them to cardiovascular events in the future. METHODS: The study group consisted of 389 children with T1DM during the 2008-2010 period. Patients with acute diabetes complications and ongoing infections were excluded from the study. An equinumerous (N = 389), age and sex-matched control group was assembled from children undergoing routine, minor surgical procedures in the same hospital. Platelet: count (PLT), mean volume (MPV), distribution width (PDW) and platelet large cell ratio (P-LCR) as well as HbA1c levels were measured. For statistical analysis we used Chi-square tests, the student's t-test, one-way analysis of variance (ANOVA), the Pearson's correlation coefficient and linear regression models in order to adjust for covariates. RESULTS: MPV, PDW and P-LCR were significantly higher among children with diabetes in comparison with the control group (MPV 10.47+/-0.85 fL vs 10.23+/-0.94 fL, p = 0.0007; PDW 12.09+/-1.80% vs 11.66+/-1.90%, p = 0.0032; P-LCR 28.21+/-6.15% vs 26.29+/-6.38%, p < 0.0001). PLT however, were shown to be similar (263.55+/-60.04 vs 268.77+/-65.78 10(3)/µl; p = 0.5637). In both cases and controls age was inversely correlated with platelet count (for study group: r = -0.30, p < 0.0001; for control group: r = -0.34, p < 0.0001), positively correlated with MPVs (r = 0.20, p < 0.0001; r = 0.26, p < 0.0001), PDW (r = 0.25, p < 0.0001 and r = 0.24, p < 0.0001) and P-LCR (r = 0.26, p < 0.0001; r = 0.26, p < 0.0001). After adjustment for confounding factors, higher platelet counts were associated with poorer metabolic control (beta = 0.20; 0.0001). CONCLUSIONS: Platelets of paediatric patients with T1DM show morphological evidence of hyperreactivity (higher MPV, PDW and P-LCR), while poorer metabolic control increases their number potentially predisposing the patients to future cardiovascular events.

Is Spirometry a Sufficient Test for Assessing Respiratory Function after Lung Resection?

BACKGROUND: The prediction of postoperative functional status in non-small cell lung cancer patients based on preoperative assessment of physical and respiratory capacity is inadequate based on recent RCTs. MATERIAL AND METHODS: Prospectively collected spirometry data and the six-minute walk test results of 57 patients treated with lobectomy for non-small cell lung cancer were analyzed. The tests were performed before surgery, and 30 and 90 days after lobectomy. All patients underwent a respiratory functional and physical capacity assessment. RESULTS: All 57 patients underwent lobectomy. Before surgery, mean FEV1 was 2.4 ± 0.7 L, corresponding to %FEV1 of 88.3 ± 17.3%. The mean absolute and expected 6MWT distance was 548 ± 74.6 m and 108.9 ± 14.5%, respectively. At the first postoperative evaluation 30 days after surgery, FEV1 and %FEV1 decreased significantly by an average of 0.5 ± 0.3 L and 15.1 ± 10.7%, while 6MWT and expected 6MWT decreased minimally by an average of 1.0 m and 0.8%, respectively. Three months after lobectomy, FEV1 and %FEV1, compared with the initial assessment, decreased by an average of 0.3 ± 0.3 l and 7.8 ± 10.0%, while 6MWT and its expected score increased to 564.6 ± 84.6 m and 112.8 ± 15.8%, respectively. CONCLUSIONS: After lobectomy, FEV1 decreased slightly and less than expected, while 6MWT increased proportionally compared to the preoperative evaluation.

Silicone Arthroplasty as an Alternative to Arthrodesis in the Metatarsophalangeal Degenerative Disease of Hallux Valgus-A 5-Year Observational Study.

Background: Arthroplasty is gaining more and more popularity in the treatment of osteoarthritis (OA) of the metatarsophalangeal I joint (MTP1). The aim of our study was to evaluate the early and long-term objective clinical and radiographic results, as well as the subjective results, of MTP1 arthroplasty in comparison to MTP1 arthrodesis among patients with OA and a valgus deformity of their MTP 1 joint. Methods: Patients with OA MTP1 were examined before surgery and in the 5-year period after surgery. The inclusion criteria for the study were OA of the MTP1 joint and a non-axial position of the toe in valgus between 20 and 40 degrees. Prostheses were created for the patients with higher demands for mobility of their MTP 1 joint and arthrodesis was carried out for those with lower expectations. The treatment outcomes were assessed by clinical examination, radiography, the AOFAS scale, the SEFAS scale, and using patient-related outcome measures (PROM). Results: A total of 39 people, 37 women and 2 men, aged 55 to 67 years old (average, 61 years old) participated in the study. During the follow-up period, there were no complications in the form of infection or a loosening of the implant after both arthroplasty and arthrodesis. The follow-up examination 60 months after the surgery showed an improvement in scores (>20 points) on both the AOFAS and SEFAS scales. All patients, after surgery, reported reduced pain. Conclusions: The use of a silicone prosthesis in the surgical treatment of degenerative changes in the MTPI joint, with appropriate indications and excluding cases with large hallux valgus, gives better results than arthrodesis.

Heterogeneity in precision oncology.

Precision oncology is a rapidly evolving concept that holds great promise in cancer treatment. However, a cancer complexity attributed to genomic and acquired tumour heterogeneity limits treatment effectiveness and increases toxicity. These limitations refer to both systemic therapies and radiotherapy, which are two mainstays of non-invasive cancer treatment. By understanding cancer heterogeneity and utilising advanced tools to personalise treatment strategies, precision oncology has the potential to revolutionise cancer care. In this article, we review the current status of precision oncology in solid tumours, specifically focusing on the impact of tumour heterogeneity and genomic patient features on systemic therapies and radiation. We also discuss the implementation of novel tools, such as next-generation sequencing and liquid biopsies, to overcome this problem.

Extreme acute radiation-induced toxicity in a patient with polymorphous low-grade adenocarcinoma of the nasopharynx and rare variants in DNA repair genes.

BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) is an extremely rare finding in the nasopharynx. There are no guidelines for the treatment of PLGA in this localization. Radiotherapy may be administered to treat this malignancy; however, in radiosensitive individuals, it is associated with a risk of severe radiotherapy-induced toxicity. METHODS: We present a case of a 73-year-old woman with locally advanced polymorphous low-grade adenocarcinoma of the nasopharynx who developed a severe adverse acute reaction to radiotherapy leading to treatment discontinuation. Despite intensive treatment, the patient died 40 days after RT initiation. Whole genome sequencing was performed using DNA from peripheral blood mononuclear cells in the search for variants that could explain such extreme toxicity. RESULTS: We identified a combination of pathogenic variants that may have contributed to the patient's reaction to radiation therapy, including predisposing variants in XRCC1, XRCC3, and LIG4. We also identified candidate variants, not previously described in this context, which could be associated with radiation toxicity based on plausible mechanisms. We discuss previous reports of this rare tumor from the literature and known contributors to radiation-induced toxicity. CONCLUSIONS: Genetic causes should be considered in cases of extreme radiosensitivity, especially when is not explained by clinical factors.