Long-term results of postoperative and definitive (chemo)radiotherapy in sinonasal carcinoma. Adult Comorbidity Evaluation 27 score as a predictor of survival.

Background: The objective was to evaluate the efficacy and toxicity of curative radiotherapy in patients with sinonasal carcinoma and to identify prognostic factors influencing treatment outcomes. Materials and methods: The authors conducted a retrospective study of 61 consecutive patients treated with postoperative or definitive radiotherapy from 2002 to 2018 (median age 59 years, current/former smokers 71%, maxillary sinus 67%, nasal cavity 26%). The majority of patients were diagnosed with locally advanced disease (85% clinical stage ≥ III). Regional cervical metastases were initially diagnosed in 23% of patients. The most common histology was squamous cell carcinoma (61%). Radiation therapy was preceded by radical surgery in 64% of patients. 29 patients received chemotherapy (48%). Results: The median follow-up was 53 months. The median total dose of radiotherapy achieved was 70 Gy. The 5- and 10-year locoregional control, distant control, overall survival, and disease-free survival were 74% and 64%, 90% and 90%, 51% and 35%, and 38% and 25%, respectively. Severe acute toxicity occurred in 36%, severe late toxicity in 23% of patients. Severe unilateral visual impairment occurred in 6 patients, temporal lobe necrosis in 1 patient, and osteoradionecrosis requiring surgery in 2 patients. Conclusion: The results of the study demonstrated the high effectiveness of curative treatment in patients with sinonasal carcinoma with long-term locoregional and distant control. The multivariate analysis indicated that N-staging, age, comorbidity score [as assessed by Adult Comorbidity Evaluation 27 (ACE-27)] and initial response to treatment were the strongest prognostic factors.

Negative Prognostic Impact of Smoking on Long-term Survival in Patients With Nasopharyngeal Carcinoma Treated With Curative (Chemo)radiotherapy.

BACKGROUND/AIM: To evaluate the effectiveness of curative (chemo)radiotherapy in patients with nasopharyngeal carcinoma and to identify prognostic factors influencing treatment outcomes. PATIENTS AND METHODS: We conducted a retrospective study of 73 consecutive patients, treated with definitive (chemo)radiotherapy from 2002 to 2019 (median stage III/IV 78%). The median total dose of radiotherapy achieved was 70 Gy. Concomitant chemotherapy was given to 82% of patients. RESULTS: The five- and ten-year locoregional controls were 73% and 72%, respectively; the five- and ten-year distant controls were 93% and 93%, respectively. The five- and ten-year overall survival rates were 46% and 34%, respectively. A multivariate analysis identified age, smoking, and the initial response to treatment as the strongest prognostic factors in predicting survival. CONCLUSION: Smoking ≤5 years before starting curative (chemo)radiotherapy for nasopharyngeal carcinoma was shown to be an independent negative prognostic factor for overall survival with a four-fold higher risk of death compared to non-smokers.

Long-term results of radio(chemo)therapy in metastatic carcinoma to cervical lymph nodes from an unknown primary. Adult Comorbidity Evaluation 27 score as a predictor of survival.

PURPOSE: To evaluate the effectiveness and toxicity of curative (chemo)radiotherapy in patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. METHODS: Retrospective study of 90 consecutive patients, treated with curative radiotherapy from 2003 to 2018 (median age 59 years; current/former smokers 76%) was conducted. The distribution of nodal staging was as follows: N1: 12%, N2a: 21%, N2b: 43%, N2c: 10%, N3: 13%. In 62% of patients, neck dissection was performed before radiotherapy. Concomitant chemotherapy was given to 64% of patients. RESULTS: The median follow-up of surviving patients was 86 months. The median total radiotherapy dose achieved was 70 Gy. The 5­ and 10-year locoregional control were 84% in both cases, while 5­ and 10-year distant control were 90% and 89%, respectively. A primary tumor in the head and neck area was detected in only 2 patients. No patient had an initial failure in the pharyngeal axis or contralateral cervical nodes. The 5­ and 10-year overall survival were 55% and 42%, respectively. Severe early toxicity occurred in 71%; severe late toxicity in 33% of patients. Multivariate analysis demonstrated N­status (hazard ratio [HR] 2.424; 95% confidence interval [CI] 1.121-5.241; p = 0.024) and comorbidity scores assessed by ACE-27 (Adult Comorbidity Evaluation; HR 3.058; 95% CI 1.489-6.281; p = 0.002) as two independent prognostic factors for overall survival. CONCLUSION: The results of our work study demonstrate the high effectiveness of curative (chemo)radiotherapy on the pharyngeal axis and bilateral cervical nodes with long-term locoregional and distant control in 3/4 of the treated patients. N­status and comorbidity scores were shown as strong prognostic factors influencing overall survival.

Identification of salicylic acid-independent responses in an Arabidopsis phosphatidylinositol 4-kinase beta double mutant.

BACKGROUND AND AIMS: We have recently shown that an Arabidopsis thaliana double mutant of type III phosphatidylinositol-4-kinases (PI4Ks), pi4kß1ß2, constitutively accumulated a high level of salicylic acid (SA). By crossing this pi4kß1ß2 double mutant with mutants impaired in SA synthesis (such as sid2 impaired in isochorismate synthase) or transduction, we demonstrated that the high SA level was responsible for the dwarfism phenotype of the double mutant. Here we aimed to distinguish between the SA-dependent and SA-independent effects triggered by the deficiency in PI4Kß1 and PI4Kß2. METHODS: To achieve this we used the sid2pi4kß1ß2 triple mutant. High-throughput analyses of phytohormones were performed on this mutant together with pi4kß1ß2 and sid2 mutants and wild-type plants. Responses to pathogens, namely Hyaloperonospora arabidopsidis, Pseudomonas syringae and Botrytis cinerea, and also to the non-host fungus Blumeria graminis, were also determined. Callose accumulation was monitored in response to flagellin. KEY RESULTS: We show here the prominent role of high SA levels in influencing the concentration of many other tested phytohormones, including abscisic acid and its derivatives, the aspartate-conjugated form of indole-3-acetic acid and some cytokinins such as cis-zeatin. We show that the increased resistance of pi4kß1ß2 plants to the host pathogens H. arabidopsidis, P. syringae pv. tomato DC3000 and Bothrytis cinerea is dependent on accumulation of high SA levels. In contrast, accumulation of callose in pi4kß1ß2 after flagellin treatment was independent of SA. Concerning the response to Blumeria graminis, both callose accumulation and fungal penetration were enhanced in the pi4kß1ß2 double mutant compared to wild-type plants. Both of these processes occurred in an SA-independent manner. CONCLUSIONS: Our data extensively illustrate the influence of SA on other phytohormone levels. The sid2pi4kß1ß2 triple mutant revealed the role of PI4Kß1/ß2 per se, thus showing the importance of these enzymes in plant defence responses.

Anti-phospholipid antibodies against phosphatidylinositol, and phosphatidylserine are more significant in reproductive failure than antibodies against cardiolipin only.

PROBLEM: The humoral immune response to phospholipids was investigated in women with reproductive failure [1073 women after one in vitro fertilization (IVF), 853 women after two and more IVF, 627 women after three and more repeated spontaneous miscarriages or missed abortions, 412 women after diagnostic laparoscopy] and compared with that of 391 healthy fertile women. METHOD OF STUDY: Sera from all women in the study were tested by enzyme-linked immunosorbent assay (ELISA) for the detection of IgG, IgA, and IgM isotypes of antibodies against seven phospholipids (aPLs), i.e. cardiolipin, L-phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylacid as well as against beta2-glycoprotein I. RESULTS: Patients after two and more IVF (48 and 50%, respectively), patients with three and more repeated spontaneous miscarriages (50 and 46.5%, respectively) are associated with significantly higher serum levels of aPLs against inositol, and L-serine (P < 0.01). A quarter of them were positive for three and more aPLs. CONCLUSION: It seems that determination of aPLs only against cardiolipin in reproductive failure is not sufficient for obstetric-gynecology diagnosis as the primary anti-phospholipid syndrome. Our long-ranging study (from 1998 to 2003) shows the necessity to test for a complete aPLs profile. Sera from patients after two and more IVF procedures, and sera from women after three and more repeated abortions are immunologically more active than sera from women after one unsuccessful IVF and sera from women after diagnostic laparoscopy. This important result is very significant for future treatment.

Seven antiphospholipid antibodies in HIV-positive patients: correlation with clinical course and laboratory findings.

OBJECTIVE: To compare the clinical course of HIV-1-infected patients, their CD4+, CD8+ T lymphocytes, and viral loads (VL) with the levels of seven antiphospholipid antibodies (aPLs) before, during, and after the highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: aPLs were examined in patients (20 men, 10 women, aged 12-64 years, median 33 years) from the AIDS center of Western Bohemia before the initiation of HAART, and two (23 patients), and five (20 patients) years later. Flow-cytometry was used for CD4+ and CD8+ T lymphocytes analysis, commercial kits were used for VL-measurements, and commercial enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of anti-beta2-glycoprotein I (GPI) of immunoglobulin G (IgG) and IgA isotypes, and anticardiolipin levels (ACA) of IgG and IgM isotypes. APLs screening also included L-alpha-phosphatidic (ph) acid, L-alpha-phosphatidylethanolamine, L-alpha-phosphatidyl-DL-glycerol, L-alpha-phosphatidylinositol, and L-alpha-phosphatidylserine of IgG and IgM autoantibodies. Statistical analysis was performed using cut-off levels for immunoglobulin-isotypes of aPLs using 3 S.D. or 95th percentile calculated using Statgraphics-software. RESULTS: In 14 of 21 patients treated by HAART an increased number of CD4+ T lymphocytes was detected, and in 14 of 21 patients VL decreased below detection threshold during the 5 years of observation. We did not observe correlations of aPLs with age, the initial low CD4+ and high number of CD8+ T lymphocytes, and the viremic levels over the entire observation period. We did not find the elevation of aPLs in 2 of 5 patients in stage C (AIDS). Ten of 11 HIV-positive homosexuals had positive aPLs, and the same result was seen in 7 of 10 patients infected through heterosexual intercourse. aPLs levels were significantly increased in 18 of 30 patients at the beginning of HAART. ACA IgG was elevated in 14 of 30 cases, IgG antibodies against L-alpha-ph-acid in 5 of 30, ph-ethanolamine in 10 of 30, ph-inositol in 9 of 30, and L-serine in 14 of 30, combined positivity of six aPLs together was detected in 10 HIV positive patients. Significantly decreased levels of aPLs because of HAART were found in eight patients. APLs were still present in only four patients after 5 years of the treatment. Abnormalities in blood clotting were not present in any of our patients. CONCLUSION: Results of screening for seven aPLs in HIV-positive patients suggest that HAART also positively influences the autoimmune response represented by aPLs levels, but individual differences in aPLs levels were observed.

Progesterone inhibits embryotoxic effect of the complement system.

The complement system of normal human serum (NHS) manifests a strong, dose dependent embryotoxic potential when administered to chick embryos inducing, among others, also malformations of the brain. We have demonstrated, however, that the degree of complement-induced embryotoxicity varied remarkably in the course of the menstrual cycle of fertile healthy women, although the complement serum activity (CH100) exhibited no significant fluctuation. On the other hand, the variation of embryotoxicity appeared negatively associated with progesterone levels. Following our results high progesterone levels occurring physiologically in luteal phase of the menstrual cycle suppress the embryotoxic action of the complement system.