Amifostine enhances recovery and expansion of peripheral FAS/CD95+ T- and NK-cell subpopulations during radiotherapy of patients with head-neck cancer

Purpose:?Experimental studies suggest that the FAS/APO-1/CD95 (cytokine receptor protein TNF-receptor superfamily, member 6) cell surface molecule is involved in the apoptotic effect of radiotherapy. In this study we investigated the role of amifostine in protecting the CD95+ (CD: cluster of differentiation) lymphocytic subpopulation in patients with head and neck cancer undergoing radiotherapy.

Materials and methods:?Using flow-cytometry we examined the expression of FAS/CD95 antigen on CD4+ (helper/inducer T cells), CD8+ (suppressor/cytotoxic T cells) and CD56+ (NK, natural killer) T-lymphocytes of 28 patients with head and neck cancer undergoing radiotherapy (with and without amifostine).

Results:?The numbers of peripheral blood lymphocytes were significantly reduced after treatment from (mean value ± STD error) 1477 ± 129 to 1015 ± 77 for T lymphocytes, 700 ± 70 to 454 ± 38 for CD4, 449 ± 46 to 296 ± 34 for CD8 and, 140 ± 18 to 118 ± 13 for NK, before and after treatment, respectively. CD95 expressing lymphocytes showed a faster recovery rate in patients receiving amifostine. CD95 expressing CD56 lymphocytes increased during radiotherapy in patients receiving daily cytoprotection with amifostine to values higher than the pre-treatment levels (p = 0.004).

Conclusion:?It is suggested that amifostine enhances recovery of T- and NK-lymphocyte subpopulations expressing the CD95 antigen in head-neck cancer patients undergoing RT and may enhance the efficacy of the later by interfering FAS-related immunological pathways.     

Secular trends in adiposity and musculoskeletal dimensions of elite heavyweight boxers between 1889 and 2019

Purpose

With improving nutrition and health, athletes have grown taller and heavier over the past century. Since there is no weight restriction in the heavyweight class, secular changes in anthropometric measurements of heavyweight boxers may mirror those of contemporary general populations.

Objectives

We aimed to (1) examine secular trends in adiposity and musculoskeletal measurements in heavyweight boxers, (2) determine anthropometric differences between champions and unsuccessful challengers.

Methods

Detailed demographics taken at time of contest (first official World Championship to current contest: 1889–2019) were collected from media archives.

Results

All 237 boxers (83 champions, 154 challengers) contesting a recognised heavyweight World Championships were identified. They had mean (±?SD) age?=?28.9?±?4.1 years, height?=?187.3?±?6.5 cm, reach?=?195.2?±?9.4 cm, weight?=?97.5?±?11.5 kg, BMI?=?27.8?±?2.4 kg/m² and waist?=?87.9?±?6.2 cm. Contest years explained 25.9% (p?<?0.001) of the variance in BMI for champions and 30.9% (p?<?0.001) for challengers, 9.1% (p?<?0.071) in WC for champions and 19.9% (p?<?0.001) for challengers. Contest years correlated with height (r?=?0.531, p?<?0.001), reach (r?=?0.341, p?<?0.001), weight (r?=?0.603, p?<?0.001) and BMI (r?=?0.370, p?=?0.001) among all documented boxers, and with waist only in challengers (r?=?0.349, p?<?0.001) but not in champions (r?=?0.078, p?=?0.509). Compared with challengers, champions had greater stature by +?3.4 cm (p?<?0.001), reach +?3.6 cm (p?=?0.005) and weight +?3.7 kg (p?=?0.017), with similar BMI and waist. Champions had larger biceps and forearms but did not differ from challengers in other musculoskeletal dimensions.

Conclusions

Over 130 years elite heavyweight boxers have increased in size (BMI) and reach but waists in champions have remained static. Being heavier, taller with longer and bigger arms, but with similar in BMI and waist, appear to be differentiating factors between champions and challengers.

     

Changes in peripheral blood lymphocyte subsets in patients undergoing radiotherapy.

PURPOSE: To investigate the changes in peripheral blood lymphocyte subpopulations in patients undergoing radiotherapy. MATERIALS AND METHODS: In 8 patients undergoing external beam radiotherapy to the pelvis, the different lymphocyte subpopulations were followed during treatment. The lymphocyte populations were determined using two-colour flow cytometry. The study comprises the T-helper, T-suppressor/cytotoxic cells, the B-lymphocytes and natural killer (NK) cells. RESULTS: The B-cells were characterized by a steep decrease at the beginning of the radiotherapy. They reached their lowest level at an equivalent total body dose of approximately 1.5 Gy and remained constant during the rest of the therapy (10% of the initial level). In T-cells (both T-helper and T-suppressor subsets) the steep decrease was less pronounced. T-lymphocytes reached a base level at 2.5 Gy equivalent total body dose (20% of the initial level). No significant differences between the T-helper and the T-suppressor/cytotoxic cells were observed. NK cells were characterized by a weak decline during the first weeks of therapy, being less pronounced than in the other populations. Near the end of therapy, the NK cells reached the level of the T-lymphocytes. CONCLUSION: In vivo, NK cells were the most radioresistant and B-cells the most radiosensitive lymphocytes. No significant differences between T-helper and T-suppressor/cytotoxic cells were observed. These data are in agreement with the differences in apoptosis induction in peripheral blood lymphocyte subpopulations after in vitro gamma-irradiation of whole blood lymphocytes.     

COVID-19 pandemic impacts physical activity levels and sedentary time but not sleep quality in young badminton athletes

Purpose

Regular physical activity is a good strategy to maintain the health of athletes, and prevent pain and decreased joint flexibility during the pandemic. On the other hand, higher sedentary time during the pandemic period can have deleterious effects. The objective of this study was to compare physical activity levels, sedentary time, and sleep parameters during the pre-COVID period and the COVID-19 pandemic period in young badminton athletes.

Methods

Fifteen young badminton athletes were evaluated during a pre-COVID period (July 2019) and during the COVID-19 period (July 2020). Sleep parameters, physical activity level, and sedentary time were measured using a tri-axial accelerometer. Participants wore the accelerometer on their dominant wrist for 7 days consecutively. In addition, the average of each sleep parameter [time in bed and total sleep time in hours per day, sleep efficiency (%), wake after sleep onset (WASO, total per day), and sleep latency (minutes per day)] was reported over the 7-day period.

Results

Athletes presented increased sedentary time (pre-COVID?=?7.0?±?1.1 vs.COVID-19?=?8.9?±?1.9 h/day, p?=?0.004, d?=?1.30) and significant decreases in the total PA observed in counts per day (pre-COVID?=?2,967,064.4?±?671,544.1 vs. COVID-19?=?1,868,210.2?±?449,768.4 counts/day, p?=?0.001, d?=?1.99), time in vigorous PA (pre-COVID?=?7.7?±?0.9 vs. COVID-19?=?6.1?±?1.2 h/day, p?=?0.001, d?=?1.56), and time in moderate-to-vigorous PA (pre-COVID?=?8.1?±?0.9 vs. COVID-19?=?6.5?±?1.3 h/day, p?=?0.001, d?=?1.48). There were no significant differences for time in light and moderate PA or in sleep parameters (p?>?0.05).

Conclusion

Young badminton athletes presented increased sedentary time, and decreased total physical activity, time in MVPA, and time in vigorous activities during the COVID-19 pandemic compared to the pre-COVID period, however, there were no significant differences in sleep parameters.

     

Lymphocyte subsets and their H2AX phosphorylation in response to in vivo irradiation in rats

Abstract

Purpose: The objective of the study was to investigate differences in the radiosensitivity of rat peripheral blood lymphocyte subsets identified by expression of surface clusters of differentiation markers (CD3, CD4, CD8, CD45RA, CD161) after whole-body in vivo gamma-ray irradiation and to assess their individual histone H2AX phosphorylation as an early cell response to irradiation.

Materials and methods: The relative representations of CD45RA B-lymphocytes, CD161 natural killer cells (NK cells), CD3CD4 T-lymphocyte subset and CD3CD8 T-lymphocyte subset in the rat peripheral blood were studied 24–72 hours after irradiation in a dose range of 0–5 Gy. Their intracellular H2AX phosphorylation (γ-H2AX) after 4 Gy and 9 Gy whole-body in vivo irradiation was assessed by multicolour flow cytometry.

Results: We determined the linear dose response of radioresistant CD161 NK cells (24 h), both radiosensitive T-lymphocyte subsets (24 h) and CD45RA B-lymphocytes (72 h) after in vivo irradiation. CD45RA B-lymphocytes showed the highest radiosensitivity and we observed pronounced H2AX phosphorylation which remained expressed in these cells for over 4 h after irradiation.

Conclusion: The combination of the surface immunophenotyping together with intracellular detection of γ-H2AX offers the possibility to assess the absorbed dose of ionizing irradiation with high sensitivity post irradiation and could be successfully applied to biodosimetry.     

Prognostic value of 18F-FDG PET/CT in patients with soft tissue sarcoma: comparisons between metabolic parameters

Objectives

To investigate the relationship between volume-based PET parameters and prognosis in patients with soft tissue sarcoma (STS).

Methods

We retrospectively reviewed 55 patients with pathologically proven STS who underwent pretreatment with ¹⁸?F-Fluorodeoxyglucose (¹⁸F-FDG) PET/CT. The maximum standardized uptake value (SUV_max), average SUV (SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors were measured using a threshold SUV as liver activity for determining the boundary of tumors. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables.

Results

Cancer-related death occurred in 19 of 55 patients (35 %) during the follow-up period (29?±?23 months). On univariate analysis, AJCC stage (stage IV vs. I-III, hazard ratio (HR)?=?2.837, p?=?0.028), necrosis (G2 vs. G0-G1, HR?=?3.890, p?=?0.004), SUV_max (1 unit - increase, HR?=?1.146, p?=?0.008), SUV_avg (1 unit - increase, HR?=?1.469, p?=?0.032) and treatment modality (non-surgical therapy vs. surgery, HR?=?4.467, p?=?0.002) were significant predictors for overall survival. On multivariate analyses, SUV_max (HR?=?1.274, p?=?0.015), treatment modality (HR?=?3.353, p?=?0.019) and necrosis (HR?=?5.985, p?=?0.006) were identified as significant independent prognostic factors associated with decreased overall survival.

Conclusions

The SUV_max of the primary tumor is a significant independent metabolic prognostic factor for overall survival in patients with STS. Volume-based PET parameters may not add prognostic information outside of the SUV_max.     

Water-based resistance training program with isolated concentric action improves physical functional capacity and muscular strength in older women

Background

Resistance training has proven to be an excellent method for counteracting aging physical dysfunctions. However, its application in the liquid environment is not yet fully elucidated.

Aim

To investigate the effects of water-based resistance training (WBRT) with the concentric phase performed as fast as possible, compared to conventional resistance training (CRT), on physical functional capacity, muscle strength, and body composition in older women.

Methods

Thirteen healthy older women participated in the WBRT and 11 in the CRT. Estimation statistics focused on the effect size of the experiment/intervention were used. We also analyzed the intervention effect based on the percentage delta between WBRT and CRT.

Results

The WBRT group showed a negative large effect (d?=?? 0.922; p?=?0.0274) for the timed up and go, and a large effect for chair rise in 30″ and the elbow flex test (d?=?1.58; p?=?0.0012; d?=?2.8; p?=?0.01) respectively. Intervention comparisons based on the delta percentage between WBRT and CRT presented an intermediate effect (d?=?0.606; p?=?0.157) for the stair climb, a large effect (d?=?0.988; p?=?0.0282) for the timed up and go, and a large negative effect [d?=?? 1.32 (90.0% CI ? 1.92, ? 0.646); p?=?0.0038] for the elbow flex test. Concentric extensor-flexor peak torque (60°/s) showed an intermediate effect (d?=?0.749; p?=?0.0876; d?=?0.65; p?=?0.122 respectively). Body fat (%) demonstrated an intermediate effect (d?=?0.523; p?=?0.234).

Conclusion

WBRT with the concentric phase performed as fast as possible was able to improve physical functional capacity and maximal knee extension strength of older women.

     

Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

Purpose

Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients.

Materials and methods

All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F?=?42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months.

Results

Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3–32.5) and SUVmean 6.4 (range: 1.5–13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p?=?0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84–14.01 %), CD8-TILs of 2.9 % (range: 0.11–11.92 %), PD-1 of 0.65 % (range: 0.02–5.87 %), and PD-L1 of 0.7 % (range: 0.03–10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho?=?0.31; p?=?0.027) and PD-1 (rho?=?0.33; p?=?0.017 and rho?=?0.36; p?=?0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho?=?0.45; p?=?0.001), CD8 TILs and PD-L1 (rho?=?0.41; p?=?0.003), CD68-TAMs and PD-L1 (rho?=?0.30; p?=?0.027), PD-1 and PD-L1 (rho?=?0.26; p?=?0.059). With respect to patients’ outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p?=?0.002, 0.004, and <0.001, respectively).

Conclusions

The present study shows a direct association between metabolic parameters on FDG-PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors.

     

Role of the bradykinin B2 receptor in a rat model of local heart irradiation

Abstract

Purpose: Radiation-induced heart disease (RIHD) is a delayed effect of radiotherapy for cancers of the chest, such as breast, esophageal, and lung. Kinins are small peptides with cardioprotective properties. We previously used a rat model that lacks the precursor kininogen to demonstrate that kinins are involved in RIHD. Here, we examined the role of the kinin B2 receptor (B2R) in early radiation-induced signaling in the heart.

Materials and methods: Male Brown Norway rats received the B2R-selective antagonist HOE-140 (icatibant) via osmotic minipump from 5 days before until 4 weeks after 21 Gy local heart irradiation. At 4 weeks, signaling events were measured in left ventricular homogenates and nuclear extracts using western blotting and real-time polymerase chain reaction. Numbers of CD68-positive (monocytes/macrophages), CD2-positive (T-lymphocytes), and mast cells were measured using immunohistochemistry.

Results: Radiation-induced c-Jun phosphorylation and nuclear translocation were enhanced by HOE-140. HOE-140 did not modify endothelial nitric oxide synthase (eNOS) phosphorylation or alter numbers of CD2-positive or mast cells, but enhanced CD68-positive cell counts in irradiated hearts.

Conclusions: B2R signaling may regulate monocyte/macrophage infiltration and c-Jun signals in the irradiated heart. Although eNOS is a main target for kinins, the B2R may not regulate eNOS phosphorylation in response to radiation.     

Post-irradiation viability and cytotoxicity of natural killer cells isolated from human peripheral blood using different methods

Purpose We compared the pre- and post-irradiation viability and cytotoxicity of human peripheral natural killer cell (NK) populations obtained using different isolation methods.

Material and methods Three methods were used to enrich total NK cells from buffy coats: (I) a Ficoll-Paque gradient, plastic adherence and a nylon wool column; (II) a discontinuous Percoll gradient; or (III) the Dynal NK cell isolation kit. Subsequently, CD16⁺ and CD56⁺ NK cell subsets were collected using (IV) flow cytometry or (V) magnetic-activated cell sorting (MACS) NK cell isolation kits. The yield, viability, purity and cytotoxicity of the NK cell populations were measured using trypan blue exclusion, flow cytometry using propidium iodide and ⁵¹Cr release assays after enrichments as well as viability and cytotoxicity after a single radiation dose.

Results The purity of the preparations, as measured by the CD16⁺ and CD56⁺ cell content, was equally good between methods I–III (p?=?0.323), but the content of CD16⁺ and CD56⁺ cells using these methods was significantly lower than that using methods IV and V (p?=?0.005). The viability of the cell population enriched via flow cytometry (85.5%) was significantly lower than that enriched via other methods (99.4–98.0%, p?=?0.003). The cytotoxicity of NK cells enriched using methods I–III was significantly higher than that of NK cells enriched using methods IV and V (p?=?0.000). In vitro the NK cells did not recover cytotoxic activity following irradiation. In addition, we detected considerable inter-individual variation in yield, cytotoxicity and radiation sensitivity between the NK cells collected from different human donors.

Conclusions The selection of the appropriate NK cell enrichment method is very important for NK cell irradiation studies. According to our results, the Dynal and MACS NK isolation kits best retained the killing capacity and the viability of irradiated NK cells.     

Biochemical and pathological changes in the male rat kidney and bladder following exposure to continuous 900-MHz electromagnetic field on postnatal days 22–59*

Purpose: To investigate the effect on male rat kidney and bladder tissues of exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal days 22–59, inclusive.

Materials and methods: Twenty-four male Sprague Dawley rats, aged 21 days, were used. These were divided equally into one of three groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any procedure. SG rats were kept inside a cage, without being exposed to the effect of EMF, for 1?h a day on postnatal days 22–59, inclusive. EMFG rats were exposed to continuous 900-MHz EMF for 1?h a day under the same conditions as those for the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and Masson trichrome for histomorphological evaluation. The TUNEL method was used to assess apoptosis. Transmission electron microscopy (TEM) was also used for the kidney tissue. Oxidant/antioxidant parameters were studied in terms of biochemical values.

Results: The findings showed that tissue malondialdehyde increased in EMFG compared to CG and SG in both kidney (p?=?0.004 and p?=?0.004, respectively) and bladder tissue (p?=?0.004, p?=?0.006, respectively), while catalase and glutathione levels decreased compared to CG (p?=?0.004; p?= 0.004, respectively) and SG (p?=?0.004; p?=?0.004, respectively). In the EMF group, pathologies such as dilatation and vacuolization in the distal and proximal tubules, degeneration in glomeruli and an increase in cells tending to apoptosis were observed in kidney tissue. In bladder tissue, degeneration in the transitional epithelium and stromal irregularity and an increase in cells tending to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited glomerular capillary degeneration with capillary basement membranes under TEM.

Conclusions: We conclude that continuous exposure to the effect of 900-MHz EMF for 1?h a day on postnatal days 22–59, inclusive, causes an increase in oxidative stress and various pathological changes in male rat kidney and bladder tissues.     

Low dose radiation induced immunomodulation: Effect on macrophages and CD8+ T cells

Purpose: The aim of the present investigation was to study the effect of fractionated whole body low dose ionizing radiation (LDR) on the functional responses of T lymphocytes, their subpopulations and macrophages.

Materials and methods: C57BL/6 mice were exposed to 4 cGy from a ⁶⁰Co source, at 0.31 cGy/min, at 24 h intervals for 5 days (total dose 20 cGy). Phagocytic activity was measured by flow cytometry using Bioparticles® and nitric oxide generation was estimated by spectrophotometry. Proliferation of lymphocytes in response to concanavalin A (con A) and alloantigens was measured by ³H thymidine incorporation. Expression of cell surface markers was assessed by flow cytometric analysis of antibody labeled cells. Target cell killing by cytotoxic T cells (CTL) generated against allogenic cells was assessed by flow cytometry using PKH26 labeled target cells. Cytokines were estimated by enzyme linked immunosorbent assay.

Results: Exposure to LDR enhanced nitric oxide secretion and phagocytosis. The expression of early activation antigen, CD69, was enhanced in CD8⁺ T lymphocytes concomitant with enhanced proliferation in response to con A. In addition, mixed lymphocyte reaction (MLR) and CTL response were augmented and secretion of interferon gamma (IFN-γ) was suppressed following LDR exposure.

Conclusions: LDR exposure enhanced the function of macrophages and responses of CD8⁺ T cells in C57BL/6 mice.     

FVIIIra, CD15, and tryptase performance in the diagnosis of skin stab wound vitality in forensic pathology

The timing of skin wounds is one of the most challenging problems in forensic pathology. In the first minutes or hours after infliction, histological examination fails to determine whether a wound was sustained before or after death. The aim of this study was to evaluate the use of three immunohistochemical markers (FVIIIra, CD15, and tryptase) for the interpretation of the timing of cutaneous stab wounds. We evaluated these markers in intravital wounds from autopsy cases (n?=?12) and surgical specimens (n?=?58). As controls, we used normal skin samples from autopsies (n?=?8) and an original ex vivo surgical human model of recent postmortem wounds (n?=?24). We found overexpression of FVIIIra in 100 % of vital wounds, but also in 53 % of the controls. The number of CD15-positive cells was higher in wound margins than in internal controls (p?<?0.0001) and was significantly correlated with the time interval between incision and devascularization (p?=?0.0005; minimal time for positivity, 9 min). Using the anti-tryptase antibody, we found that the mast cell degranulation rate was higher in wound margins (p?<?0.0001) and correlated with the time interval (minimal time, 1 min). The sensitivity and specificity for the diagnosis of vitality were respectively 100 and 47 % for FVIIIra, 47 and 100 % for CD15, and 60 and 100 % for tryptase. The inter-observer agreement coefficients were 0.68 for FVIIIra, 0.90 for CD15, and 0.46 for tryptase. Finally, we demonstrated that these markers were not reliable in putrefied or desiccated specimens. In conclusion, CD15 and tryptase, but not FVIIIra, may be useful markers for differentiating recent antemortem from postmortem injuries.     

In vitro cellular radiosensitivity in relationship to late normal tissue reactions in breast cancer patients: a multi-endpoint case-control study

Purpose: A minority of patients exhibits severe late normal tissue toxicity after radiotherapy (RT), possibly related to their inherent individual radiation sensitivity. This study aimed to evaluate four different candidate in vitro cellular radiosensitivity assays for prediction of late normal tissue reactions, in a retrospective matched case-control set-up of breast cancer patients.

Methods: The study population consists of breast cancer patients expressing severe radiation toxicity (12 cases) and no or minimal reactions (12 controls), with a follow-up for at least 3 years. Late adverse reactions were evaluated by comparing standardized photographs pre- and post-RT resulting in an overall cosmetic score and by clinical examination using the LENT-SOMA scale. Four cellular assays on peripheral blood lymphocytes reported to be associated with normal tissue reactions were performed after in vitro irradiation of patient blood samples to compare case and control radiation responses: radiation-induced CD8+ late apoptosis, residual DNA double-strand breaks, G0 and G2 micronucleus assay.

Results: A significant difference was observed for all cellular endpoints when matched cases and controls were compared both pairwise and grouped. However, it is important to point out that most case-control pairs showed a substantial overlap in standard deviations, which questions the predictive value of the individual assays. The apoptosis assay performed best, with less apoptosis seen in CD8+ lymphocytes of the cases (average: 14.45%) than in their matched controls (average: 30.64%) for 11 out of 12 patient pairs (p?p?p?Conclusion: This matched case-control study in breast cancer patients, using different endpoints for in vitro cellular radiosensitivity related to DNA repair and apoptosis, suggests that patients’ intrinsic radiosensitivity is involved in the development of late normal tissue reactions after RT. Larger prospective studies are warranted to validate the retrospective findings and to use in vitro cellular assays in the future to predict late normal tissue radiosensitivity and discriminate individuals with marked RT responses.     

Memory CD4 T-cell subsets discriminated by CD43 expression level in A-bomb survivors

Purpose:?Our previous study showed that radiation exposure reduced the diversity of repertoires of memory thymus-derived cells (T cells) with cluster of differentiation (CD)- 4 among atomic-bomb (A-bomb) survivors. To evaluate the maintenance of T-cell memory within A-bomb survivors 60 years after radiation exposure, we examined functionally distinct memory CD4 T-cell subsets in the peripheral blood lymphocytes of the survivors.

Methods:?Three functionally different subsets of memory CD4 T cells were identified by differential CD43 expression levels and measured using flow cytometry. These subsets consist of functionally mature memory cells, cells weakly responsive to antigenic stimulation, and those cells functionally anergic and prone to spontaneous apoptosis.

Results:?The percentages of these subsets within the peripheral blood CD4 T-cell pool all significantly increased with age. Percentages of functionally weak and anergic subsets were also found to increase with radiation dose, fitting to a log linear model. Within the memory CD4 T-cell pool, however, there was an inverse association between radiation dose and the percentage of functionally mature memory cells.

Conclusion:?These results suggest that the steady state of T cell memory, which is regulated by cell activation and/or cell survival processes in subsets, may have been perturbed by prior radiation exposure among A-bomb survivors.     

DNA double-strand breaks induced by mammographic screening procedures in human mammary epithelial cells

Abstract

Purpose: To assess in vitro mammographic radiation-induced DNA damage in mammary epithelial cells from 30 patients with low (LR) or high (HR) family risk of breast cancer.

Materials and methods: Spontaneous and radiation-induced DNA double-strand breaks (DSB) were quantified by using immunofluorescence of the phosphorylated H2AX histone (γH2AX) in different conditions of mammography irradiation (2, 4, 2 + 2 mGy).

Results: HR patients showed significantly more spontaneous γH2AX foci than LR patients (p = 0.014). A significant dose-effect was observed, with an exacerbation in HR patients (p = 0.01). The dose repetition (2 + 2 mGy) provided more induced and more unrepaired DSB than 2 mGy and 4 mGy, and was exacerbated in HR (p = 0.006).

Conclusions: This study highlights the existence of DSB induced by mammography and revealed by γH2AX assay with two major radiobiological effects occurring: A low-dose effect, and a LOw and Repeated Dose (LORD) effect. All these effects were exacerbated in HR patients. These findings may lead us to re-evaluate the number of views performed in screening using a single view (oblique) in women whose mammographic benefit has not properly been proved such as HR patients.     

Prognostic value of myocardial perfusion imaging performed pre-renal transplantation: post-transplantation follow-up and outcomes

Purpose

Noninvasive stress testing is commonly performed as part of pre-renal transplantation (RT) evaluation. We evaluated the prognostic value of myocardial perfusion imaging (MPI)—myocardial perfusion, left ventricular ejection fraction (LVEF) and heart rate response (HRR)—post-RT.

Methods

Consecutive RT recipients were identified at our institution. MPI was considered abnormal when there was a perfusion defect or reduced ejection fraction. HRR to vasodilator stress was calculated as percentage change from baseline. The primary outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI) and coronary revascularization (CR) post-RT; all-cause mortality was the secondary endpoint.

Results

Among 1189 RT recipients, 819 (69%) underwent MPI. Of those, 182 (22%) had abnormal MPI, and 31 (4%) underwent CR pre-RT. During a median follow-up of 56 months post-RT, the annual CV event and mortality rates for patients who had no MPI, normal MPI and abnormal MPI were 1.5%, 3.1% and 4.3% (p?<?0.001), and 1.8%, 2.6% and 3.6% (p?=?0.016), respectively. After multivariate adjustment, compared to patients without MPI, the hazard ratios (HRs) for CV events for normal and abnormal MPI were 1.47 ([0.93–2.33], p?=?0.1) and 1.78 ([1.03–3.06], p?=?0.04). Blunted HRR was an independent predictor of CV events (HR?=?1.73 [1.04–2.86], p?=?0.034) and all-cause death (HR?=?2.26 [1.28–3.98], p?=?0.005) after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR pre-RT had annual mortality rates similar to those with no or normal MPI (1.9% vs. 1.7–2.6%, p?=?0.2), while those who did not undergo CR had higher annual mortality (4% vs. 1.7–2.6%, p?=?0.003).

Conclusions

One in five RT recipients who underwent screening MPI had an abnormal study, an independent predictor of CV events. A blunted HRR to vasodilator stress was associated with increased risk of CV events and death, even after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR were at low risk of mortality following RT. MPI is a useful tool to aid in risk stratification pre-RT.

     

Role of radiotherapy in the chemotherapy-containing multidisciplinary management of patients with resected pancreatic adenocarcinoma

Background

To analyze prognostic factors associated with long-term outcomes in patients with resected pancreatic cancer treated with chemotherapy (CT) and surgery with or without external beam radiotherapy (EBRT).

Patients and methods

From January 1995 to December 2012, 95 patients with adenocarcinoma of the pancreas and locoregional disease [clinical stage IB-IIA (n?=?45; 47?%), IIB-IIIC (n?=?50; 53?%)] were treated with curative resection [R0 (n?=?52; 55?%), R1 (n?=?43, 45?%)] and CT with (n?=?60; 63?%) or without (n?=?35; 37?%) EBRT (45–50.4 Gy). Additionally, 29 patients (48?%) also received a pre-anastomosis IOERT boost (applicator diameter size, 7–10 cm; dose, 10–15 Gy; beam energy, 9–18 MeV).

Results

With a median follow-up of 17.2 months (range, 1–182), 2-year overall survival (OS), disease-free survival (DFS), and locoregional control were 28, 20, and 53?%, respectively. Univariate analyses showed that IIB-IIIC stage (HR, 2.23; p?=?0.04), R1 margin resection status (HR, 2.09; p?=?0.04), no vascular resection (HR, 0.42; p?=?0.02), and not receiving external beam radiotherapy (HR, 2.70; p?=?0.004) were associated with locoregional recurrence. In the multivariate analysis, only R1 margin resection status (HR, 2.63; p?=?0.009) and not receiving EBRT (HR, 2.91; p?=?0.002) retained significance with regard to locoregional recurrence. We observed no difference in toxicity between patients treated with or without EBRT (p?=?0.44). Overall treatment mortality was 3?%. No long-term treatment–related death occurred.

Conclusions

Although adjuvant CT is still the standard of care for resected pancreatic tumors, OS remains modest owing to the high risk of distant metastases. Locoregional treatment needs to be tested in the context of more efficient systemic therapy.

     

Inferior vena cava diameter on CT angiography predicts mesenteric angiography positive for extravasation in colonic diverticular bleeding

Purpose

Transcatheter arterial embolization (TAE) for colonic diverticular bleeding (CDB), an established procedure for hemostasis, is sometimes complicated by spontaneous hemostasis and unclear bleeding site on angiography despite active arterial bleeding on preoperative computed tomography angiography (CTA). Therefore, to investigate and increase the feasibility of TAE, this retrospective study evaluates the clinical and radiological features related to positive extravasation on angiography.

Material and methods

Sixty CDB patients with extravasation on CTA underwent TAE between January 2011 and February 2021 and were divided into extravasation-positive (P-group; n?=?25) and -negative groups (N-group; n?=?35) based on the superior or inferior mesenteric angiography. Patient characteristics, laboratory findings, the diameter of the inferior vena cava (IVCD), the diameter of superior and inferior mesenteric veins, and technical outcomes were evaluated.

Results

TAE was successful in 24 patients in the P-group (96%) and 14 in the N-group (40%) (p?<?0.001). Univariate analysis revealed “usage of anticoagulant” (p?<?0.05) and “larger IVCD (p?<?0.05) on preoperative CTA” to be significant predictors of positive extravasation. In the multivariate analysis, IVCD remained significant with an adjusted odds ratio of 1.17. The IVCD cutoff value was 13.6 mm (area under the curve?=?0.72, sensitivity?=?84.0%, specificity?=?54.3%). There were no significant differences in other parameters.

Conclusion

Measurement of IVCD in CDB with the cutoff value of 13.6 mm can be a simple and useful indicator to predict the detectability of extravasation following TAE procedures.