An anti-tumor immune response is one of the most important factors that can determine treatment response and prognosis of cancer patients. Recent studies have demonstrated that radiotherapy can activate tumor-specific immune responses and that these responses contribute to the therapeutic efficacy. However, the exact mechanisms underlying the radiation-induced immune responses remain unclear. Better understanding of the mechanisms could facilitate the application of immune-activating radiotherapy and provide new treatment strategies. We previously demonstrated that tumor-specific T cell responses could be induced in esophageal cancer patients during and after chemoradiotherapy. Furthermore, in a mouse model, immune responses played an important role in determining the local and systemic therapeutic efficacy of radiotherapy that could be augmented by the immune checkpoint blockade. In this review, radiotherapy-induced immune responses, the mechanisms underlying the induction of those responses, and a practical application of the therapy are discussed.
Purpose: To validate the use of bone scintigraphy (BS) versus computed tomography (CT) for therapeutic monitoring in patients during treatment with zoledronic acid. Materials and Methods: Eleven patients with bone–only metastatic disease and being treated with zoledronic acid were included. The effects of therapies including chemotherapy and hormone therapy were evaluated in 25 separate examinations in total as follows: complete response (CR), when no bone metastasis was visible; partial response (PR), when a decrease in the lesion area was detected; stable disease (SD), when no or slight change was observed; and progressive disease (PD), when new or enlarged lesion areas were observed. Results: The accuracies of examination by Readers 1, 2, and 3 respectively were 76%, 80% and 76% for BS, 52%, 48%, and 40% for CT, and 64%, 52% and 60% for BS and CT combined with Readers 2 and 3 observing significant differences between CT and BS results. The rates of interobserver agreement between Readers 1 and 2, between Readers 1 and 3, and between Reader 2 and 3 respectively, were 84%, 80% and 88% (κ = 0.648, 0.561 and 0.766) for BS, 52%, 56%, and 60% (κ = 0.180, 0.278 and 0.282) for CT, and 52%, 60%, and 56% (κ = 0.215, 0.282 and 0.232) for CT and BS combined. Conclusion: BS is effective for assessing the response of bone metastasis to therapy in patients during zoledronic acid treatment.
The present study investigated the role of intensive care units (ICU) during disasters, including the responses of our ICU following the Great East Japan Earthquake on March 11, 2011. Our ICU comprises 8 beds for postoperative inpatients and those with rapidly deteriorating conditions; 20 beds in an emergency unit for critically ill patients; and 17 beds for neonates. It is important to secure empty beds when a major disaster occurs, as was the case after the Great Hanshin Earthquake, due to the resulting large numbers of trauma patients. Therefore, each ICU section cooperated to ensure sufficient space for admissions following the Great East Japan Earthquake. However, unlike the Great Hanshin Earthquake, securing beds was ultimately unnecessary due to the nature of the recent disaster, which also consisted of a subsequent tsunami and nuclear accident. Therefore, air quality monitoring was required on this occasion due to the risk of environmental radioactive pollution from the nuclear disaster causing problems with artificial respiration management involving atmospheric air. The variability in damage arising during different disasters thus requires a flexible response from ICUs that handle seriously ill patients.
We carried out a retrospective investigation on the effect of obesity on dexmedetomidine (DEX) requirements when administered with fentanyl (FEN) during mechanical ventilation after major surgeries. After Institutional Review Board approval, 14 obese patients with a body mass index (BMI) ≥ 30 kg/m2 and the same number of non-obese patients with similar backgrounds to the obese patients were selected from medical records. Doses of DEX in the first 48 h or until the end of sedation or extubation were calculated for comparison. In addition to comparison of dosing between the groups, associations between total body weight (TBW), BMI, and lean body mass (LBM) values and doses of DEX (mcg/h), between BMI and various indices (i.e., amount per TBW per hour and amount per LBM per hour) of DEX doses, and between above indices of DEX and FEN doses were also examined. There were no significant differences in DEX dose indices between the groups. However, DEX requirements (mcg/h) were significantly increased with TBW (kg) (r = 0.51, P = 0.003), BMI (r = 0.49, P = 0.006) and LBM (kg) (r = 0.42, P = 0.02), which might have enhanced the DEX metabolism with physiological changes with obesity. These findings will be beneficial for future clinical pharmacological analysis of DEX.
Using the whole-cell voltage clamp technique, we investigated the effect of paclitaxel, an anticancer agent which promotes microtubule formation, on K+ current in H9c2 cells originated from rat embryonic cardiac myocytes. Paclitaxel inhibited Kv2.1 voltage-dependent K+ current (IKur) with ultra-rapidly activating and slowly inactivating kinetics in a concentration-dependent manner. The inhibitory effect of paclitaxel on IKur was time-dependent and more marked at 200 ms after the onset than at the beginning of the depolarizing pulse. The IC50 value of paclitaxel was 1.1 µM at 200 ms. The time-dependent inhibition suggests that paclitaxel might be an open channel blocker of Kv2.1. This inhibition of Kv2.1 may be involved in the adverse effects of paclitaxel on cardiac and neuronal cells.
Purpose: This study investigated the shape of bone grafts and associations with upper limb function over the long term after free vascularized fibular head graft (FVFHG) for reconstruction of the proximal humerus after wide resection for bone sarcoma. Methods: Patients comprised 3 women who had undergone FVFHG at least 5 years previously. Age at surgery was 12 years in 2 cases and 76 years in one. The mean follow-up periods were 10 years 4 months. Evaluated parameters comprised: 1) graft hypertrophy, and 2) shape of the fibular head as changes in shape of the bone graft; and 3) ISOLS score, and 4) DASH score as indicators of upper limb function. Results: Rates of graft hypertrophy of the fibular shaft were −14%, −17%, and −20%, respectively, with transverse diameter decreasing in all cases. In terms of changes in shape of the grafted fibular head, transverse diameter had diminished in 2 patients (−5 mm and −2 mm), and the head had been completely resorbed in the remaining patient. Both patients in whom the fibular head remained were young, and both had good ISOLS scores >80% and good DASH scores of 5.0 and 8.3. The patient in whom the fibular head had been resorbed was elderly, with ISOLS and DASH scores of 73.3% and 34.2, respectively; comparatively poor compared with the other two. A comparison of ISOLS and DASH scores before and after fibular head resorption, however, showed no deterioration in either score. Conclusions: Long-term follow-up of humerus reconstruction by FVFHG showed no deterioration in upper limb function despite the risk of fibular head resorption. FVFHG of the proximal humerus is a reconstruction technique that can provide good long-term upper limb function.
Background: The Fukushima Pregnancy and Birth Survey was launched to monitor pregnant mothers’ health after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant (NPP) accident. Several lines of investigations have indicated that a disaster impacts maternal mental health with childbirth. However, there is no research regarding mental health of mothers with fetal loss after a disaster. In this report, we focus on those women immediately after the Great East Japan Earthquake and Fukushima NPP accident and discuss their support needs. Materials and Methods: Data regarding 61 miscarriages, 5 abortions, and 22 stillbirths were analyzed among the women who were pregnant at the time of the accident in the present study. We used a two-item case-finding instrument for depression screening, and compared the childbirth group with the fetal loss groups. We also analyzed mothers’ opinions written as free-form text. Results: Among the three fetal loss groups, the proportion of positive depression screens was significantly higher in the miscarriage and stillbirth group than in the childbirth group. Mothers’ opinions were grouped into six categories, with pregnancy-related items being most common, especially in the miscarriage and stillbirth groups. Conclusion: A higher proportion of Fukushima mothers with fetal loss, especially those with miscarriage and stillbirth, had depressive symptoms compared to those who experienced childbirth. Health care providers need to pay close attention to this vulnerable group and respond to their concerns regarding the effects on their fertility.
Background: Carbon monoxide (CO) was previously only considered as a highly toxic pollutant since it binds to hemoglobin with high affinity. Recently, however, it has been recognized as a signaling molecule with regulatory roles in many physiological and pathophysiological processes within the cardiovascular system. The aim of this study was to clarify the behavior of CO in patients with acute coronary syndrome (ACS). Methods: We assessed 235 patients with suspected ACS, 98 smokers (88 male, 62 ± 14 years) and 137 nonsmokers (77 male, 72 ± 13 years), who had undergone emergent cardiac catheterization and blood sampling for calculation of carboxyhemoglobin (COHb). Patients were categorized into 4 groups: smoking patients with ACS (n=77), smoking patients without ACS (n=21), non-smoking patients with ACS (n=97), and non-smoker patients without ACS (n=40). We investigated whether biomarkers were related to COHb levels. Results: LogCOHb was significantly higher in the smoking patients compared to non-smoking patients (0.30 ± 0.12 vs. 0.45 ± 0.18, P < 0.01). Interestingly, among the non-smoking patients, COHb was increased in the ACS patients compared to the non ACS patients (0.31 ± 0.12 vs. 0.25 ± 0.12 P < 0.01). In contrast, among the smoking patients, there was no difference in COHb between the ACS and non-ACS patients (0.45 ± 0.18 vs. 0.44 ± 0.18, n.s.). There were no correlations between COHb and any of the biomarkers. Conclusions: These results suggest that endogenous CO may be useful to assess the risk of cardiovascular stress.
An appropriate treatment strategy for left main trunk (LMT) lesions is still controversial in the drug-eluting stent (DES) era. Consecutive LMT stenting cases (n = 155) between January 2008 and January 2013 in 4 hospitals in Fukushima city were retrospectively analyzed. We excluded the patients suffering from cardiogenic shock before the stenting procedure. Among those cases, 60 patients had acute coronary syndrome, and remaining 95 had stable angina pectoris. Out of 155 cases, 45 patients were treated with bare metal stents (BMSs) and 110 patients were treated with DESs. All cases were succeeded in the initial procedure. Mean stent size of BMS was 3.85 ± 0.34 mm while that of DES was 3.46 ± 0.17 mm (P<0.001). At the follow up coronary angiography (255-day on average), % stenosis of BMS group was 26.6 ± 15.0% and that of DES group was 20.4 ± 12.6% (P = 0.006). The mean observation period for clinical events was 738.8 ± 480.3 days. Major adverse cardiac events-free rates for each group were compared and no significant differences were evident between the 2 groups (11.1% vs. 19.1%, ns). The present study demonstrated that use of BMSs would be a viable option in the treatment of LMT lesions when it is possible to use a large-sized stent (>3.5 mm).
Stressful life situation can trigger the onset and flare-ups of Behçet’s disease (BD). In addition, the association of systemic sclerosis (SSc) and BD is rare. In this study, we report a patient who had Sjögren’s syndrome as a primary disease and subsequently developed SSc and BD after an earthquake disaster and the death of her father.
Several studies have shown that brain hypothermia therapy (BHT) after neonatal hypoxic-ischemic encephalopathy (HIE) can improve neurodevelopmental outcomes. However, there have been no reports of the neurodevelopmental outcomes for the infant with a serum creatine kinase (CK) level above 20,000 IU/L in association with neonatal HIE. We report a female infant with a very high serum CK level (26,428 IU/L) associated with neonatal asphyxia. We diagnosed this infant with moderate HIE, and BHT was achieved by head cooling within 6 hours after birth to an esophageal temperature of 34.5°C. There were no significant adverse events during BHT, and the CK level spontaneously decreased. Although we report only the short-term outcomes for this case, she presents neurodevelopmental delays at the age of 18 months. It may be correlated between high serum CK level and long-term neurodevelopmental delays. Abbreviations: CK, creatine kinase; HIE, hypoxic-ischemic encephalopathy; BHT, brain hypothermia therapy; NRFS, non-reassuring fetal status; CK-MB, creatine kinase-myocardial band; MRI, magnetic resonance imaging; CK-BB, creatine kinase-brain band.