Falls from height (FFH) represent a distinct form of blunt trauma in urban areas. This study aimed to identify independent predictors of in-hospital mortality after accidental or intentional falls in different age groups. We conducted a retrospective study of all patients consecutively admitted after a fall in eight years, recording mechanism, intentionality, height of fall, age, site, classification of injuries, and outcome. We built multivariate regression models to identify independent predictors of mortality. A total of 948 patients with 82 deaths were observed. Among the accidental falls, mortality was 5.2%, whereas intentional jumpers showed a mortality of 20.4%. The death rate was higher for increasing heights, age >65, suicidal attempts, and injuries with AIS ≥3 . Older patients reported a higher in-hospital mortality rate. Multivariate analysis identified height of fall, dynamic and severe head and chest injuries as independent predictors of mortality in the young adults’ group (18–65 years). For patients aged more than 65 years, the only risk factor independently related to death was severe head injuries. Our data demonstrate that in people older than 65, the height of fall may not represent a predictor of death. Falls from height (FFH) represent a distinct form of blunt trauma in which rapid vertical deceleration determines injuries to the victim’s body . Falls aVarious evidence available in the literature has already shown how increasing age and height of the fall correlate with worse outcomes ,6. The mThe present study is a retrospective analysis of prospectively collected data of all trauma patients consecutively admitted after falling from height at ASST  Niguarda Hospital, a level I Trauma Center in Milan, Italy, from October 2010 to December 2018. All details about trauma patients managed at Niguarda Hospital are collected in the Niguarda trauma registry, which is held by a Trauma Team consultant who is meant to keep it constantly updated, and is annually revised by the Head Department. The institution of trauma registry was approved by the Ethical Committee Milano Area 3 (record no. 534-102018). Given the retrospective nature of this study, specific board approval was not required.Demographic data, Injury Severity Score (ISS), the height of fall, intentionality of fall, and survival outcome as stated by the Atlanta Trauma Registry Workshop guidelines  were ret2 test or Fisher’s exact test when appropriate. The distribution of continuous variables was assessed with normality tests and, since no variables had a normal distribution, differences among groups were evaluated with the independent sample Mann–Whitney test.Data were recorded in a computerized spreadsheet  and analyzed with statistical software . Categorical variables were explored with the χ2 value. Multicollinearity was preventively assessed by examining the variance inflation factor (VIF). Models’ goodness of fit was explored with the Hosmer–Lemeshow test.In order to identify independent predictors of mortality in different age groups, three multivariate regression models were built, providing adjusted odds ratios and 95% CI . All variables not contributing to the model (overfitting) were removed one-by-one from the model at each step based on the Nagelkerk Rp-value < 0.05 was considered statistically significant for all tests.A two tailed p < 0.001) (p < 0.001), with an overall death rate of 8.6%.Data of 948 patients were retrieved from the Trauma Registry. The median age was 42 years (Interquartile Range IQR 22–59). Six hundred eighty-two were males (71.9%) and 266 females (28.1%). The intentionality of the fall was obtained in all cases and was accidental in 733 cases (77.3%) and a suicide attempt in 215 cases (22.7%). The height of the fall was obtained or calculated for all patients with a median of 3 m (IQR 2–6). The median height was 2 m (IQR 2–4) for accidental falls  and 7 m (IQR 5–9) for intentional jumps (“jumpers”) (< 0.001) . The hosAs shown in Detailed results of comparisons between survivors and non-survivors are reported in A significantly higher proportion of deaths was recorded in the over 65 years group. Moreover, among non-survivors, we detected a greater height of the fall, an increased proportion of ASA 3–4 patients, a higher number of intentional jumpers, a higher rate of AIS ≥ 3 head, AIS ≥ 3 chest, AIS ≥ 3 abdomen, and AIS ≥ 2 extremity injuries. Similarly, we detected a significantly greater proportion of patients with ISS > 15 among non-survivors.Variance inflation factor analysis pointed out significant multicollinearity (VIF > 2.5) between ISS and other variables meant to be entered in the multivariate models, therefore, it was excluded.Height of the fall, ASA score, intentionality of the fall, head, chest, abdomen, and extremities injuries AIS ≥ 3 were selected to be entered in the regression models. Age was a further variable selected for the general population model.p < 0.001; Odds Ratio—OR: 1.04; 95% CI: 1.03–1.06). Severe head injury was the only independent risk factor for mortality in the elderly group. Detailed results are reported in Multivariate analysis failed to identify any independent predictors of death in the pediatric population. Intentionality, height of the fall, severe head and chest injuries resulted in independent predictors of death in the general and young adults’ group models. Furthermore, in the general population, age was identified as an independent predictor of mortality, with a 4% increase in the risk per year of age  and the young adults’ group (93.0%).This study showed in a large population that death after a fall can be independently predicted in the general population by age, the height of fall, intentionality, and severe chest and head injuries. In the elderly, the height of the fall cannot be considered as an independent predictor of death.In Western countries, FFH represents one of the leading causes of admission to the Emergency Department , accountIn our study sample, we observed 82 deaths with an overall death rate of 8.6%. The study published by Goodacre et al. described a mortality rate of 1.4% , while op < 0.001). As already reported by other studies [p < 0.001) has been noticed, both in adult and elderly age groups. In contrast to the higher rate of suicidal falls among elder women reported in previous work by our group [p < 0.001). As shown in p < 0.001). Conversely, considering cephalic injuries, there were no differences between the two groups. Moreover, major trauma (ISS > 15) prevailed among the jumpers, confirming that greater heights are preferred by jumpers resulting in more severe injuries and worse survival outcomes.In the univariate analysis, we detected significant differences in proportions/distribution for most of the variables taken into account. The height of the fall has been identified as a risk factor of unfavorable prognosis, analogously to other authors ,10,15, A studies ,4,17, anur group , the preWe observed a linear growth of death rate by increasing height of fall due to higher energy dissipation at impact. The only exception was represented by elderly jumpers for whom our analysis failed to demonstrate this kind of proportional increase. Furthermore, looking at both young adults and elderly groups, we did not observe any lethal deceleration trauma among intentional jumpers for heights < 3 m (results not shown). As already reported by other authors , intentiOn the other hand, in case of accidental fall for the same height cluster, the orientation of the body during airtime cannot be controlled, leading to worse injuries. Indeed, as already reported by others ,4,6,14, As reported by Demetriades , mortaliTo identify independent predictors of adverse survival outcome, we built four multivariate regression models. The general population model pointed out a 4% and 16% increase in the risk of death per year of age and meter of height, respectively. Suicidal attempts accounted for a nearly 3-fold increased risk of mortality. Patients sustaining severe head and chest injuries had a 7.6-fold and 2.7-fold increased risk of death, respectively. For the pediatric population, logistic regression analysis failed to detect any risk factors related to mortality. In the young adults’ subgroup, all aforementioned variables (but age) included in the general population model were confirmed as independent predictors of death. Of note, severe head injuries were related to nearly 9-fold risk of death. Our results demonstrated that patients aged more than 65 years sustaining severe head injuries are at risk of worse survival outcomes regardless of height of the fall and intentionality. This interesting finding, in contrast with those reported by some authors [Nevertheless, to better interpret the apparently contradictory findings regarding the height of the fall in the general and >65 year-old models, one consideration should be done. For elderly patients, despite the relevant proportion of deaths, the average height of the fall was considerably lower compared to the adult population. This can explain why multiple regression failed to identify the height of the fall as an independent predictor of death in the elderly population.Liu C.C. et al. identified only severe head injury AIS ≥ 4 as an independent predictor of mortality, whereas chest injuries did not seem to play any role in survival outcomes . InteresTo our knowledge, our study represents one of the largest single-center representations of vertical deceleration injuries at a level 1 trauma center in Europe with the review of the data of 948 patients collected in a standardized registry during an 8-year time interval. Moreover, our results seem to be comparable to those reported by other studies in the literature, especially considering the height of the fall and elderly age as independent predictors of mortality. Finally, our results were supported by a strict statistical methodology that led to the realization of multivariate models with a remarkable predictive ability.This study has several limitations, first of all its retrospective nature. Furthermore, it did not take into account out-of-hospital mortality, which accounted for a significant proportion of deaths after FFH . FurtherThe present study demonstrated that age, height of the fall, suicidal attempt, and severe head and chest injuries represent independent predictors of mortality. Considering different age clusters, we noticed that for elderly patients (over 65 years), the height of the fall, even though correlated with a greater proportion of deaths may not represent a predictor of mortality.


Restless legs syndrome (RLS) is highly prevalent among pregnant women. In the present study, a neurological–obstetrical sample of 561 postpartum women was retrospectively screened for RLS symptoms during pregnancy and in the first 12 weeks postpartum. The first screening took place within 1 to 6 days of delivery (T0) and the second 12 weeks after childbirth (T1). The pregnancy-related RLS prevalence rate was found to be 21% (n = 119), with the women suffering from RLS being more often affected by psychiatric history and having been more exposed to stressful life events. They were also found to have experienced baby blues more frequently shortly after childbirth. However, RLS in pregnancy did not appear to have any effect on the development of postpartum depression. Additionally, a positive trend was observed toward an association between pregnancy-related RLS and gestational diabetes and hypertension. Of the 119 women, 23 (19.3%) remained affected by RLS 12 weeks postpartum. Body mass index (BMI), weight gain, parity, childbearing history, or chronic stress exposure in pregnancy as measured by hair cortisol were not found to be linked to RLS. In summary, a comprehensive understanding of the interaction of clinical, environmental, and anamnestic factors can help shed valuable light on this pregnancy-related condition. Restless legs syndrome (RLS) is a common sensorimotor disorder with a 5–10% prevalence in the adult population . The preFrequently, RLS either appears for the first time during pregnancy or worsens during this period ,9,10; itPregnancy-related RLS has been reported to be most prevalent in the third trimester 23%), gradually increasing from about 10% in the first trimester ,9,10. Al%, graduaWhile women with pregnancy-related RLS have been found to suffer from poorer health compared to their non-RLS counterparts, the evidence for specific disease associations is mixed. The findings of previous studies, however, raise the question whether pregnancy-related RLS symptoms may be early indicators of metabolic and cardiovascular problems later in life.The aim of the present study was to estimate the prevalence, natural course, and specific risk factors of RLS in pregnancy and during the early postpartum period in this relatively large sample. As pregnancy is frequently associated with new manifestations or exacerbation of a CVD, the secondary purpose of the study was to investigate the link between gestational diabetes and gestational hypertension and pregnancy-related RLS. Conditions such as anemia, weight gain or hypothyroidism, which are frequently manifested during pregnancy, were also systematically looked at, as was the relationship between pregnancy-related RLS and postpartum mood, psychiatric history and history of stressful life events. Finally, the participants who were found to remain affected by RLS 12 weeks postpartum were identified in order to highlight the specific characteristics of the group and the risk factors that can potentially contribute to the condition persisting beyond childbirth. This study is part of an ongoing prospective longitudinal project aiming at early recognition of postpartum depression (PPD). The women were recruited in the Department of Gynecology and Obstetrics at the University Hospital Aachen within 1 to 6 days of childbirth (T0) between January 2016 and March 2020. The inclusion criteria were being aged between 18 and 45, being in the early postpartum period, and being healthy at the time of recruitment. The exclusion criteria of the study included alcoholic or psychotropic substance dependency or use during pregnancy, medication during pregnancy, neurological conditions, history of psychosis or manic episodes, depressive episodes in the current pregnancy, and inadequate proficiency in German or English. To control for the exclusion criteria, a brief non-standardized clinical interview was conducted according to the Diagnostic and Statistical Manual of Mental Disorders V (DSM V) criteria by an experienced psychiatrist (NC). A detailed sociodemographic description of the study population is provided in Following receipt of the participants’ informed consent, all participants were screened for RLS symptoms in pregnancy by means of the International Restless Legs Syndrome Rating Scale (IRLSS)  based onAt T0, in addition to the IRLSS, the Stressful Life Events Screening Questionnaire (SLESQ)  was usedThe second screening for postpartum RLS symptoms was carried out 12 weeks after delivery (T1). At T1 (12 weeks postpartum), the IRLSS and EPDS were applied for the second time. Further, in a subset of participants, the data on baby blues severity were assessed using the Maternity Blues Questionnaire (MBQ) . These pThe study was conducted in compliance with the Helsinki Declaration and was approved by the local ethics committee of the Medical Faculty, RWTH Aachen University, Germany.Hair cortisol concentration (HCC) is widely regarded as a biomarker of chronic stress . The parp 0.05 was considered significant.Independent sample T-tests (for parametric data) and Mann–Whitney-U tests (for non-parametric continuous variables), as well as chi-square tests , were used to assess differences between the RLS group and control group. Within-group differences were analyzed by means of paired samples t-tests, and repeated-measures ANOVA was used to assess the course of RLS symptoms over time. Pearson correlations and Spearman correlations are reported for the parametric and non-parametric data, respectively. IBM Statistics 25  was used for the analysis. For all statistics, a In the present study, a neurological–obstetrical sample of 561 women in their early postpartum period were retrospectively screened for RLS symptoms during pregnancy. In the longitudinal study, the second screening was done 12 weeks postpartum. In total, 119 (21.2%) of the 561 women reported to have experienced RLS symptoms during pregnancy. While for 41 (34.5%) women this was the first pregnancy, for 73 (61.3%) women it was a=their second or third pregnancy. Of these 73 women, 34 (46.6%) had already experienced RLS symptoms during a previous pregnancy. Here, 85 women (77.3%) reported the RLS symptoms to have been most severe during the third trimester. The mean IRLSS score at T0 was M = 17.54, SD = 6.98 for all women experiencing RLS (n = 119).2 = 4.59, p = 0.032. In addition, a significantly larger number of women in the RLS group  experienced stressful life events (SLE) compared to the control group , χ2  = 10.46, p = 0.001. RLS in pregnancy, however, did not appear to have any effect on the development of a postpartum depression (PPD). The participants with RLS symptoms during pregnancy more often reported a psychiatric history  compared to women without RLS , χ2  = 3.98, p = 0.046. The severity of baby blues was also found to be significantly linked to the severity of RLS symptoms  (p = 0.006) appeared to be affected by the severity of premenstrual syndrome (PMS)  compared to women without RLS , χ= 0.021) . Additiome (PMS) .2  = 3.71, p = 0.054. The differentiation between insulin-dependent gestational diabetes and dietary gestational diabetes showed women with RLS to be more often diagnosed with insulin-dependent diabetes (11.8%) compared to those without RLS (5.7%), ᵪ2  = 6.30, p = 0.098. Additionally, women in the RLS group were found to have experienced hypertension more often (7.6%) during pregnancy compared to their non-RLS counterparts (3.6%), ᵪ2  = 3.42, p = 0.064. A number of factors such as body mass index (BMI) (before and after pregnancy), weight gain during pregnancy, diagnosis of postpartum anemia and hemoglobin (Hb) value shortly after childbirth, diagnosis of hypothyroidism, TSH value, and hair cortisol concentration (HCC) at T0 and T1 were also considered, although none appeared to have any influence on RLS. The same applied to parity, birth mode, and birthweight of children . All of the others  reported not to have experienced any RLS symptom following childbirth (pregnancy-associated RLS). Women with persistent RLS reported their RLS symptoms to be more severe  at T0 compared to those with pregnancy-related RLS , t (117) = −1.19, p = 0.030  = 9.74, p = 0.021). Apart from that, women with persistent RLS did not differ from their counterparts with pregnancy-related RLS with respect to any other variable  continued to experience RLS 12 weeks after childbirth (persistent RLS), although the severity of the symptoms was lower at this stage  = 8.17, .030 see .. The grable see ..In a neurological–obstetrical sample of 561 postpartum women, we looked at various factors associated with pregnancy and the postpartum period of 12 weeks in the context of RLS. In our sample, the prevalence rate of the condition was found to be 21%. While in about 20% of those cases the symptoms were still reported 12 weeks postpartum , in 80% of the cases the women experienced a complete recovery shortly after delivery. The majority of our participants (about 77%) experienced the RLS symptoms as most severe and most frequent in the last trimester of pregnancy. Women with persistent RLS, on the other hand, reported the symptoms to be equally severe in all trimesters of the pregnancy. Among those who had experienced RLS in a previous pregnancy, the symptoms in the current pregnancy showed a high tendency toward being repetitions of the ones experienced before (46.6%). These observations are in line with the results of previous studies on the prevalence and time course of pregnancy-related RLS . In a comparison between the participants with and without RLS symptoms, those with pregnancy-related RLS were found to experience SLE more often than the ones without RLS. They were also more likely to have had a psychiatric history compared to their non-RLS counterparts (depression in 21.2% of the cases and anxiety in 3.4%). SLE is known to influence human behavior in multiple ways, often increasing the risk of suicide and depression ,35,36. IA positive association has previously been found between idiopathic RLS and CVD ,50. Our While some studies have reported an association between lower Hb and pregnancy-related RLS ,53, the As for the limitations of the study, there are three notable ones. First, the diagnosis of RLS was based solely on a self-report questionnaire (IRLSS), although it is a widely used measure in RLS diagnosis that possesses a good level of content validity . Second,In conclusion, it can be stated that RLS in pregnancy is a heterogeneous syndrome with differences in onset timing. Our results indicate that this condition may also be linked to cardiovascular and metabolic diseases. Some of the clinical syndromes a woman experiences during pregnancy reappear later in life with the debilitating effects of ageing . Thus, i


Eccrine porocarcinoma is a rare aggressive cutaneous malignancy. Complete surgical excision is the standard of care, although there are high rates of local and distant recurrence. We present a unique case of locally recurrent and metastatic subungal porocarcinoma successfully treated with intralesional interleukin-2. Eccrine porocarcinoma is a rare cutaneous malignancy derived from the dermal sweat gland and acrosyringium . It is mGiven the rarity of porocarcinoma, no current guidelines exist regarding the optimal treatment of this aggressive malignancy; however, complete surgical excision with wide margins is the standard of care . RecentlAlthough porocarcinoma is perceived as a chemo-resistant disease, there have been reports of successful treatment of metastatic disease with specific regimens including carboplatin and epirubicin , and pacA 56-year-old male presented initially to the plastic surgery clinic with a right thumb lesion that had been present for approximately 2 years, and underwent a wide excision with flap closure. Final pathology revealed invasive porocarcinoma, measuring 1.3 cm, with positive margins and dermal lymphatic involvement, and consisted of nests and cord of atypical, mitotically active epithelial cells involving ulcerated epidermis, dermis, and subcutis without bone involvement. The cells exhibited marked nuclear pleomorphism and focal comedonecrosis. Some epithelial nests contained luminal structures, a distinguishing feature between porocarcinoma and squamous cell carcinoma . LymphovWithin weeks of his original surgery, the patient developed a new nodular recurrence at the suture line and subsequently underwent a partial amputation at the distal interphalangeal joint demonstrating persistent porocarcinoma with lymphatic involvement. At that time, a palpable right axillary node was detected and fine-needle aspiration was positive for malignant cells.A complete metastatic workup revealed no evidence of distant disease, and he underwent a radical axillary lymph node dissection including nodal levels 1–3; 2/28 nodes were positive with the largest node measuring 3.7 cm. Given the burden of nodal disease, he went on to receive 4800 cGy in 20 fractions of adjuvant axillary external beam radiation.Surveillance CT scans at 6 months post lymph node dissection did not reveal any evidence of new metastatic disease; however; within 7 months of surgery, he developed multiple cutaneous lesions with a papular, cystic appearance, located on the right hand and chest .A biopsy confirmed metastatic porocarcinoma. A re-staging CT did not demonstrate any visceral metastasis. Given the new diagnosis of cutaneous metastasis, he was then treated with palliative intent carboplatin and paclitaxel. After 4 cycles, there was an excellent clinical and radiographic response with almost complete resolution of all lesions and a negative PET CT. However, he developed significant chemotoxicities including neutropenia and peripheral neuropathy, and no further chemotherapy was administered.Within one month of his last chemotherapy, there was growth of all cutaneous metastasis and development of new lesions. Given that all other treatment modalities had been attempted and failed, the multidisciplinary team decided to proceed with the novel use of intralesional IL-2 in the treatment of this patient’s porocarcinoma. Quoted risks of IL-2 injection include pain, flu-like symptoms, fever, and hypotension. Consent was obtained and each cutaneous met was injected with varying volumes of 500,000 IU/0.1 mL of IL-2, with a total injected volume of 2.4 mL . Two weeks later, another 5 vials (4 mL) were injected.Two weeks following the second injection, a dramatic clinical response was appreciated, with decrease in size of all lesions. We continued for a total of 7 injections to all visible lesions every 2–4 weeks. The injected IL-2 volume ranged from 2–4 mL per session. The patient reported minimal side effects, aside from becoming hypotensive after his second treatment, with a systolic blood pressure in the 90s after treatment with 4 mL of IL-2.Since completing treatment with IL-2, he has undergone a surveillance PET CT scan 6 months after the last dose of IL-2, which revealed no definitive active disease, and biopsies of two separate persistent lesions demonstrated fibrosis without evidence of porocarcinoma. At this point, the patient has completed his intralesional IL-2 treatment, and has no clinical, pathologic, or radiographic evidence of porocarcinoma ten months after his last treatment of IL-2 .In this case report, we have described the successful clearance of metastatic porocarcinoma, in a patient who had previously been treated with surgical resection, chemotherapy and radiation. The use of intralesional IL-2 for porocarcinoma has, to our knowledge, only been described once before in the literature. In 1992, Dummer et al. described a case of a 74-year-old male with eccrine porocarcinoma of the fifth finger who developed cutaneous metastasis status post-amputation of the fourth and fifth finger and axillary lymphadnopathy . After tOther local therapies have been described in the treatment of porocarcinoma. Imiquimod and maxacalcitol, as well as intralesional photodynamic therapy have been used successfully in the treatment of primary porocarcinoma not amenable to surgery ,10. SimiIL-2 is a cytokine that plays an important role in inflammation and cellular immunity. It promotes the proliferation and survival of CD4+ and CD8+ T-cells . Given iIn addition to demonstrating the successful treatment of a rare, aggressive malignancy, this case also highlights an uncommon presentation of porocarcinoma and illustrates the difficulty around diagnosis. The most common location for porocarcinoma is the head and neck, and the lower extremity ,4. In a In summary, we present a case of a 56-year-old male with locally recurrent subungual porocarcinoma of the right thumb with axillary and cutaneous metastatic disease. He was successfully treated with thumb amputation, radical axillary lymphadenectomy, and axillary external beam radiation for local control and intralesional IL-2 for the control of metastatic cutaneous lesions. Ten months after his last IL-2 therapy, he has no clinical, pathologic, or radiographic evidence of disease, and his injections were well tolerated. We propose that the use of intralesional IL-2 in the treatment of metastatic porocarcinoma warrants further investigation and represents a potential disease altering treatment for a rare and aggressive malignancy.


Some Okinawan vegetables have been reported to have anti-diabetic activity; however, no prospective cohort study has clarified whether consumption of Okinawan vegetables is associated with a risk of type 2 diabetes. This study aimed to determine the association between consumption of Okinawan vegetables and risk of type 2 diabetes through a large-scale, population-based, prospective study in Japan.We examined 10,732 participants  aged 45–74 years who resided in Okinawa. Participants were asked to answer a 147-item food frequency questionnaire. We calculated the overall amount of Okinawan vegetables consumed and the amount of seven specific kinds of Okinawan vegetables consumed. The odds ratios (ORs) for self-reported type 2 diabetes during 5 years of follow-up were estimated via multivariate logistic regression analysis.P-trend = 0.53) or in women . The consumption of seven specific kinds of Okinawan vegetables was also not associated with the risk of type 2 diabetes.During the 5-year period, 216 new cases (123 men and 93 women) of type 2 diabetes were reported. Comparing the highest tertile to the lowest tertile of intake, the overall amount of Okinawan vegetables consumed was not associated with risk of type 2 diabetes in men (OR 1.22; 95% confidence interval [CI], 0.74–2.01, The consumption of total Okinawan vegetables was not associated with the risk of type 2 diabetes. These complications not only markedly lower the patient’s quality of life, but also incur high healthcare costs.2 Therefore, preventing type 2 diabetes is clearly an important public health priority.Diabetes mellitus is a serious health condition that is becoming an increasingly important public health concern worldwide. In the Japanese population, approximately 20 million people were estimated as the sum of those strongly suspected and those with possibilities of having diabetes in 2016.3 In particular, vegetables contain high amounts of anti-oxidants, such as polyphenols, carotenoids, and ascorbic acid, and vegetable consumptions has been associated with a decreased risk of type 2 diabetes.4 While meta-analyses of prospective studies showed no association between vegetable and fruit intake and the risk of type 2 diabetes,5–7 green leafy vegetables reduced the risk of type 2 diabetes.6,7 Therefore, vegetables in general may not be associated with the risk of type 2 diabetes, but specific groups of vegetables may reduce its risk.Food ingredients, such as dietary fiber and magnesium, play an important role in the prevention and development of type 2 diabetes.8 but it is now shorter than the national average. In this study, we analyze the data from a period when longevity was high in Okinawan and assess whether the Okinawan diet may reduce the risk of type 2 diabetes. This research may contribute to improving Okinawans’ present health by assessing the benefits of the historical diet. Vegetables such as pak choi (Chingentsuai), leaf mustard, bitter gourd, Swiss chard, loofah, mugwort, and papaya are consumed more frequently in Okinawa than in other areas of Japan.9 These Okinawan vegetables contain high amounts of anti-oxidants, such as polyphenols, carotenoids, and ascorbic acid,10 and some Okinawan vegetables have been reported to exhibit anti-diabetic activity.11,12 These studies suggest that the consumption of Okinawan vegetables may reduce the risk of type 2 diabetes. However, to our knowledge, no prospective study has investigated the association of Okinawan vegetable intake with the risk of type 2 diabetes among the Japanese. Here, we aimed to determine the association between Okinawan vegetable intake and the risk of type 2 diabetes in the Okinawa population through a large-scale, population-based prospective cohort study. Moreover, although Kurotani et al reported that vegetable and fruit consumption was not associated with risk of type 2 diabetes in research using the Japan Public Health Center-Based Prospective Study (JPHC Study) cohort,13 no study has examined this topic specifically in the Okinawan population. Therefore, for comparison with consumption of Okinawan vegetables, we also examined the risk of type 2 diabetes with respect to overall vegetable and fruit consumption.Historically, the average life expectancy of Okinawan was longer than the national average in Japan,14 The JPHC Study protocol has been described previously.15 The study protocol and data analysis plan were approved by the institutional review board of the National Cancer Center, Tokyo, Japan, and Azabu University, respectively.The JPHC Study contained two cohorts based on the public health center (PHC) area. Cohort I started in 1990 and consisted of participants 40–59 years of age from five PHC areas. Cohort II started in 1993 and consisted of participants 40–69 years of age from six PHC areas.To identify the associations between Okinawan vegetable consumption and the risk of type 2 diabetes, we limited the research area to Okinawa Prefecture because the level of Okinawan vegetable intake was low in other areas. The median value of Okinawan vegetable intake was 43.7 g/day  in the Okinawa Prefecture, and 2.4 g/day  in other PHC areas. Participants consisted of 28,315 residents  , and those who were lost to follow-up before the starting point , leaving 21,001 participants. Then, we excluded those who did not respond to the 5-year follow-up survey , leaving 15,448 participants (73.6%). We further excluded participants who reported a history of diabetes, use of anti-diabetic medication , or severe disease  at the 5-year follow-up survey. We also excluded participants who reported extreme total energy intake  and those who did not respond to the questionnaire items on Okinawan vegetables (368 subjects) at the 5-year follow-up survey. Finally, we excluded participants who did not respond to the subsequent 10-year follow-up questionnaire . A total of 10,732 participants  were included in our study.16 The FFQ used in the 5-year follow-up survey of the JPHC study has been detailed previously.17 Briefly, the FFQ assessed the daily intake of seven Okinawan vegetables , 15 fruits, and 24 other vegetables commonly consumed in the past year.17 In Okinawa Prefecture, green papaya is eaten raw as salad, simmered, or stir-fried.18 Therefore, we included papaya as an Okinawan vegetable in our research. The daily consumption of Okinawan vegetables was calculated by multiplying the daily intake frequency by the typical portion size.The FFQ contains 138 food items, including seven Okinawan vegetables, which contributed greatly to nutrient intake by the Okinawa participants.The validity and reproducibility of the FFQ were investigated in a subsample of participants in the Chubu PHC area from Cohort I and Miyako PHC area from Cohort II . The participants completed both a dietary record for a total of 28-days (Miyako PHC area) or 14-days (Chubu PHC area) and a FFQ at a 1-year interval. For Okinawan vegetables, the energy-adjusted deattenuated correlation coefficients for the validity of the FFQ in men and women were 0.17 and 0.19 and the energy-adjusted correlation coefficients for the reproducibility of the FFQ in men and women were 0.43 and 0.52, respectively. For seven specific Okinawan vegetables, the energy-adjusted deattenuated correlation coefficients for the validity of the FFQ in men and women were 0.02 and 0.60 for pak choi, −0.11 and 0.20 for leaf mustard, 0.18 and 0.20 for bitter gourd, 0.61 and 0.40 for swiss chard, 0.39 and 0.34 for loofah, 0.51 and 0.20 for mugwort, and 0.26 and 0.45 for papaya, respectively. For the reproducibility of the FFQ, energy-adjusted correlation coefficients in men and women were 0.36 and 0.54 for pak choi, 0.66 and 0.69 for leaf mustard, 0.36 and 0.46 for bitter gourd, 0.45 and 0.46 for swiss chard, 0.52 and 0.47 for loofah, 0.52 and 0.39 for mugwort, and 0.43 and 0.39 for papaya, respectively.19Type 2 diabetes was confirmed via self-administered questionnaire. Only subjects who were newly diagnosed at the 10-year follow-up survey were considered as incident cases. Because the 5-year follow-up survey was used as the baseline survey in this study, only those who were subsequently diagnosed were regarded as incident cases during the follow-up. Kato et al reported about the validity of self-reported diabetes, 94% of cases of self-reported diabetes were confirmed in the medical records.2); smoking status ; alcohol consumption ; metabolic equivalent task-hours per day (tertiles); family history of diabetes mellitus (yes or no); history of hypertension (yes or no); total energy intake ; coffee consumption ; and energy-adjusted dietary consumption of foods  such as meat, rice, vegetables (except for Okinawan vegetables), and fruits (except for papaya). Trend associations were assessed by assigning the ordinal numbers 0–2 to the three categories of total Okinawan vegetable and specific Okinawan vegetables consumption. An indicator variable for missing data was created for each covariate. Trend associations between confounding factors, and Okinawan vegetable intake were assessed using the Mantel-Haenszel χ2 test for categorical variables and linear regression analysis for continuous variables. Each food group consumption was adjusted according to the total energy intake using the residual method. In addition, to eliminate the influence of known predictors for the risk of diabetes, such as age,20 obesity,21 smoking,22 alcohol consumption,23 and menopause status,24 we further performed stratified analyses according to age (<65 or ≥65 years), BMI (<25 or ≥25 kg/m2), cigarette smoking status (smoker or non-smoker), alcohol intake (<150 or ≥150 g ethanol/week), fat intake (<median or ≥median), pork intake (<median or ≥median), red meat intake (<median or ≥median), processed meat intake (<median or ≥median), and menopause status (premenopause or postmenopause). We chose not to adjust for multiple comparisons because such adjustments could lead to possibly important findings being missed.25 Two-sided P-values <0.05 or 95% confidence intervals that did not include unity were considered statistically significant. All analyses were performed using SAS software .Analyses were performed by gender. Participants in each group were divided into tertiles of food intake (T1–T3) according to each consumer, with the lowest category as the reference. Because there were more than 50% of participants whose Swiss chard intake level was 0 g, participants were divided into two groups (0 g or >0 g) according to the amount of Swiss chard intake. To evaluate the association between diabetes risk and intake of Okinawan vegetables, specific Okinawan vegetable, multivariate logistic regression was used to estimate odds ratios (ORs), and 95% confidence intervals (CIs) were estimated using the Wald method. The first model was adjusted for age (years) and study area (two areas). In a second model assessing diabetes risk and consumption of either total Okinawan vegetables or seven specific Okinawan vegetables, we adjusted for body mass index , fruits (except for papaya), rice, fish, coffee, and each Okinawan vegetable. They also had higher intake of protein, calcium, magnesium, dietary fiber, vitamin D, and polyunsaturated fatty acids. Only men with higher intakes of Okinawan vegetables were less likely to be an alcohol drinker. The women with higher intakes of Okinawan vegetables were more likely to be physically active and less likely to consume meat Table . The medP-trend = 0.53) or in women . The seven specific Okinawan vegetables were not associated with the risk of type 2 diabetes in both men and women  of type 2 diabetes were self-reported. There was no statistically significant association with the risk of type 2 diabetes and intakes of Okinawan vegetables. Comparing the highest tertile to the lowest tertile of intake, the overall amount of Okinawan vegetables consumed was not associated with risk of type 2 diabetes in men . Further stratified analyses according to age, BMI, cigarette smoking status, and alcohol intake also showed no meaningful associations (data not shown). Our previous research using all area of JPHC study have reported that green leafy vegetable intake reduced the risk of type 2 diabetes in Japanese population.13 Therefore, we also analyzed associations between Okinawan green leafy vegetable  intake and the risk of type 2 diabetes; no association was observed (data not shown). In the present study, the range of Okinawan vegetable and seven specific Okinawan vegetable intakes were narrow; therefore, the variation was small. This may have attenuated the association between intake of Okinawan vegetables overall or of the seven specific Okinawan vegetables and the risk of type 2 diabetes.Okinawan vegetables are commonly eaten by stir-frying and are often eaten with processed meat or red meat, such as pork. Several cohort studies have shown no association between total fat intake and risk of type 2 diabetes.19 Nevertheless, the misclassification of diagnosis of type 2 diabetes may have distorted the results to some extent. Third, dietary assessments were only performed once. Therefore, the changes of dietary pattern not be reflected, and there is a possibility that underestimation via misclassification may have occurred on dietary intake. Fourth, the follow-up period was relatively short (5 years). To evaluate the preventive effect of Okinawan vegetables through improvement of insulin resistance, longer follow-up period may be required. Finally, we could not rule out the possibility of unmeasured and residual confounding.The strengths of this study include the population-based prospective design based on a large number of participants both men and women, and adjustment or stratification with potentially important confounding variables. However, there are some limitations to note. First, the FFQ had low validity for estimating the intake of Okinawan vegetables overall and of the even specific Okinawan vegetables due to the small variation from the narrow range of intake. Thus, the association between Okinawan vegetable intake and the risk of type 2 diabetes may have been attenuated. However, at present, Okinawan vegetables are widely distributed not only in Okinawa Prefecture but throughout Japan, and thus the number of people consuming Okinawan vegetables throughout Japan constitute a larger sample and larger variation than in this research. Therefore, further investigation is required to verify the association between Okinawan vegetable intake and the risk of type 2 diabetes. Second, the diagnosis of type 2 diabetes was ascertained via self-reports, the incidence of diabetes in our study may be lower than that defined using laboratory data. A validation study conducted in three of JPHC cohort areas including Okinawa area, 94% of self-reported diabetes cases were confirmed to have diabetes after a medical chart review.In conclusion, this prospective study shows that the consumption of total Okinawan vegetables was not associated with the risk of type 2 diabetes among the residents of Okinawan Prefecture. Further studies on the relationship between specific Okinawan vegetables and the risk of type 2 diabetes are required.


Individuals of an older age, who were male, with comorbidities, and had a critical illness had the highest death probability, with 21%, 36%, 46%, and 54% within 1–4 weeks after the symptom onset. Risk factors, including demographic characteristics, clinical symptoms, and laboratory factors were confirmed to be important determinants of fatality of COVID-19. Our predictive model can provide scientific evidence for a more rational, evidence-driven allocation of scarce medical resources to reduce the fatality of COVID-19.An increasing number of patients are being killed by coronavirus disease 2019 (COVID-19), however, risk factors for the fatality of COVID-19 remain unclear. A total of 21,392 COVID-19 cases were recruited in the Hubei Province of China between December 2019 and February 2020, and followed up until March 18, 2020. We adopted Cox regression models to investigate the risk factors for case fatality and predicted the death probability under specific combinations of key predictors. Among the 21,392 patients, 1,020 (4.77%) died of COVID-19. Multivariable analyses showed that factors, including age , sex , severity of the disease , comorbidity , highest body temperature , white blood cell counts (>10 × 10  •21,392 COVID-19 patients constituted one of the largest cohort studies to date•Elderly male patients with critical illness and comorbidities had higher death rate•The death probability increased with time, which was evident for critically ill patients•The highest death probability within 1 month can reach 54% by the predictive model•The predictive model could guide the allocation of medical resources We further constructed a predictive model based on the estimated parameters from Cox analyses, which could be used in clinical decision-making.As of February 27, 2020, 70,233 COVID-19 cases were reported in Hubei Province, including confirmed, clinical, suspected, and asymptomatic cases, some of which were excluded from diagnosis during follow-up. Among them, 21,392 cases were selected for our interview and included in this study. 9/L , lymphocytes lower than 0.8 × 109/L , lymphocyte percentage below 20% , and neutrophil percentage above 70%  were also associated with a higher fatality risk from COVID-19.Our sensitivity analysis based on confirmed cases produced similar results . For exaThe established nomogram demonstrated the contributions of each stratum within a specific variable to the probability of death . For exaWith data from 21,392 COVID-19 patient, we confirmed several important risk factors of fatality of COVID-19, including demographic factors, comorbidity, clinical symptoms, and laboratory findings. We further established a predictive model for the probability of death for COVID-19 patients using age, sex, severity of this disease, and comorbidity as the independent predictors. Findings from this study will provide important implications for the appropriate treatment of the COVID-19 cases in a more rational way worldwide.,,Consistent with previous studies, our study found that age and sex were important independent predictors of fatality risk of COVID-19 patients.,,We found that the severe and critical status of illness were significantly associated with increased fatality risks. This finding was consistent with the study by Chen et al.,Existing comorbidity was found to be associated with increased fatality risk of COVID-19 in our study, which was consistent with a few previous studies. For example, Huang et al.The observed protective effect of muscular soreness was beyond our expectation, but the underlying reason for this finding was not clear. We speculate that it might be because the clinical identification of muscular soreness was subjective. It is possible that different clinical doctors might have different criteria for the diagnosis of this symptom, so this finding should be interpreted cautiously.,,,Laboratory tests suggested that higher WBC counts, lower lymphocyte counts, and higher neutrophil counts may be risk factors of the risk of fatality. Several laboratory studies on immune cells supported this finding.Admission after February 8 was a protective factor for death compared with admission before February 8. It may be due to a scarcity of knowledge and understanding of the infection at the early stage as well as a lack of medical resources, which were largely improved by subsequent measures, including the establishment of more hospitals and the dispatch of medical experts and medical supplies from the national and provincial level.It was beyond our expectation that a shorter time interval from symptom onset to diagnosis, being admitted to higher levels of hospital, and patients in Wuhan were associated with a higher fatality risk in this study. It was possible that patients with a longer interval between symptom onset and diagnosis were more likely to be the mild cases, and the patients admitted to the higher levels of hospitals had a severe illness.The severity of the disease was found to play a critical role in disease progression, followed by age. The individuals prone to be affected were found to be elderly men over 60 years with a critical stage of the illness and previous comorbidities. These observations were in agreement with previous studies. For example, Zhou et al.In the context of the ongoing global pandemic of COVID-19 and the limited medical resources to deal with the outbreak,Our study possessed a few advantages. We recruited 21,392 COVID-19 cases from Hubei, China, as our study subjects. The large sample size ensured that this study has a greater power to detect any differences that truly exist in the population. The study began in December 2019 and the follow-up was completed on March 18, 2020, which essentially covers the complete course of the COVID-19 outbreak in Hubei, China.,Several limitations should be noted. Selection bias was possible as we only recruited 21,392 participants out of the 70,233 cases in the study area, and our analysis observed a relatively higher CFR among excluded patients. There were 8,533 included patients who lacked complete laboratory testing results, which may lead to some degree of inaccuracy in our analysis. We only recruited the COVID-19 cases in Hubei Province, which might also result in selection bias. However, the bias would not be serious because approximately 75% of the cases in China occurred in Hubei. Data on clinical treatment and medical resources were not available for our analyses, which may potentially confound the estimate to some extent. Due to the inaccessibility of the data, we can only obtain laboratory test indicators of WBCs, lymphocytes, and neutrophils, and about 40% of participants had missing values for these laboratory testing. We suggest that more indicators that can reflect the physiological injury, such as C-reactive protein, D-dimer, and interleukin-6, should be included in future studies. In addition, because the detailed information of some variables cannot be obtained, there may be variable collinearity problems  in the process of model analysis. Only age, sex, severity of this disease, and comorbidity were included in the predictive model, as robust evidence suggested that the four indicators were closely related to the progression of COVID-19.Our study confirms a wide range of risk factors to be determinants for COVID-19 fatality. These factors include demographic , clinical , and laboratory factors (decreased number of lymphocytes). The combination effects of age, sex, severity of the disease, and pre-existing diseases estimated from the predictive model could help identify the vulnerable populations and guide the allocation of medical resources.We constructed a retrospective cohort based on the National Notifiable Infectious Disease Reporting System and medical records of patients in Hubei Province, China. A total of 21,392 COVID-19 patients were selected to conduct a face-to-face interview. The inclusion criteria included that the patients were diagnosed with COVID-19 in Hubei Province and that their illness onset occurred between December 10, 2019, and February 27, 2020. Participants were excluded if they had missing information on important clinical variables  and laboratory testing results . To examine the representativeness of the included participants, we compared the demographic characteristics of these patients with remaining, excluded patients. The participants were recruited from December 10, 2019, to February 27, 2020, and their survival status was followed up until March 18, 2020.This study was approved by the Ethics Review Committee of School of Public Health, Sun Yat-sen University (No.: 2020016). As the data collection was part of the infectious disease outbreak investigation, informed consent was waived.The baseline demographic information was extracted from the National Notifiable Infectious Disease Reporting System. We collected additional information through face-to-face interviews, such as the comorbidity, occupation, and residence. The illness-related information was collected from hospital records, including the clinical symptoms, the date of symptom onset, the levels of the hospital of admittance, and laboratory testing results. Data for the analysis included age , sex , days between symptom onset and diagnosis , occupation , residence , hospitals level ,2/FiO2 ratio ≤300 mm Hg. Critical severe cases were defined according to at least one of the following criteria: shock, respiratory failure requiring mechanical ventilation, combination with other organ failures, and admission to the intensive care unit. In this study, due to the lack of detailed information about the patient's clinical process, disease severity was defined according to whether the patient experienced a severe or critical severe condition. For example, if a patient was admitted to hospital with mild symptoms but had severe conditions during the study period, they were defined as a severe patient.The classification of the severity was based on a comprehensive analysis according to the guidelines for diagnosis and treatment of COVID-19 issued by Chinese National Health Commission.Considering that a shortage of medical resources during the early stages of the pandemic may have been associated with a higher fatality rate of COVID-19, we included an indicator to reflect this temporal trend, with February 8 as the cutoff point according to the date of hospitalization of the patients; patients admitted to the hospital before February 8 were defined as 1 and those after February 8 as 0. The date of February 8 was selected for two reasons, first, two specifically designated hospitals  and several Fangcang hospitals started to treat COVID-19 patients at around February 8; second, a number of medical workers and resources from other provinces arrived in Hubei around that time.9/L), reference (4–10 × 109/L), and high levels (>10 × 109/L); lymphocytes were divided to low (<0.8 × 109/L), reference (0.8–4 × 109/L), and high levels (>4 × 109/L); lymphocyte percentage was divided to low (<20%), reference (20%–40%), and high levels (>40%); neutrophil percentage was grouped to low (<50%), reference (50%–70%), and high levels (>70%).Laboratory testing data  were classified into three groups according to the normal ranges.According to national guidelines, the COVID-19 cases were diagnosed using four different definitions in Hubei Province. A confirmed case was defined as a positive result of high-throughput sequencing or real-time reverse transcription polymerase chain reaction (RT-PCR) in throat swab specimens.We summarized the distribution of continuous variables by median and interquartile range values. The differences of continuous variables across deceased and living groups were examined by Student’s t tests, and categorical variables were compared with chi-square test and Fisher's exact test.,Univariate and multivariate Cox proportional hazards models were fitted to quantify the associations of potential risk factors with the fatality of COVID-19.Sensitivity analyses were conducted to test the robustness of the findings. We performed one analysis by restricting the participants to the confirmed COVID-19 cases. We also compared some demographic factors among the included  and excluded participants  and assessed the associations of these factors with CFR in the two groups.,,A predictive model was then constructed based on the nomogram approach. A nomogram is a reliable tool to quantify survival likelihood of one individual by incorporating the important factors affecting the prognosis of the disease and has been widely used to evaluate prognostic factors in cancer patients.The concordance index (C-index) represents the performance of model prediction. It varies from 0.5 to 1.0, with 0.5 showing random chance and 1.0 indicating a good ability to discriminate the outcome.All statistical analyses were performed using R 3.4.3, with p < 0.05 (two-sided) as statistically significant.


Previous work has demonstrated that metastases are not uniformly distributed across the brain. This study aims to determine there are low-risk brain metastasis (BM) areas that may be avoided during whole-brain radiotherapy (WBRT) to reduce neurocognitive toxicity.Clinical and magnetic resonance imaging (MRI) data of 991 metastases in 192 patients with advanced cancer were analyzed retrospectively. Eleven anatomically defined regions of interest (ROIs) were contoured, and the locations of the BMs were recorded. Using the same definition, ROIs were contoured in 20 healthy volunteers.The proportions of patients with BMs in different ROIs, proportion of BMs, and proportion of different ROI volumes relative to the total volume were calculated.The proportion of observed BMs was lower than expected in the brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary gland. The proportion of BMs was significantly higher than expected in the parietal lobe, occipital lobe, and cerebellum. For those patients with single BM, there was very low rate of low-risk ROIs involvement (0%), with 2–4 BMs, 6–13% of the patients had low-risk ROIs involvement, with ≥5 BMs, significant (> 30%) of the patients had low-risk ROIs involvement.The brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary gland demonstrate low risk for metastatic involvement. Involvement of low risk areas occurs in patients with more than 1 BM. The incidence of brain metastasis (BM) is approximately 20–40% , and theThe application of new therapeutic methods, such as targeted therapy and immunotherapy, in the clinic setting has increased the survival time of patients with BM, bringing attention to issues regarding neurocognitive toxicity related to WBRT . RadiatiIntracranial progression after radiotherapy is another common challenge. Bender et al.  reportedRecently, Yanagihara et al.  conducteA single-center retrospective study was conducted. The study was approved by the institutional ethics committee (No: P2019022). Consecutive patients with first time diagnosis of BM between January 2015 and February 2019 were included. Sex, age, location of the primary tumor, pathological type, and number of BMs were recorded. The inclusion criteria were (1) primary pathology proven extracranial lesions; (2) age ≥ 18 years; (3) BMs diagnosed on MRI. The exclusion criteria were (1) no post-contrast images on MRI; (2) history of traumatic injury, neurosurgery, brain radiotherapy, cerebral hemorrhage, infarction, or infective diseases of the brain; and (3) history of primary brain neoplasms.Contrast-enhanced T1-weighted MRI (Siemens 3.0 T MAGNETOM Skyra MR/ Signa HDxt 1.5 T GEHCGEHC) scans of all patients were introduced into the Oncentra MasterPlan® treatment planning system . A double dose of gadopentetate dimeglumine  was administered intravenously 10 min before acquiring a 3-dimensional, coronal, inversion-recovery, spoiled-gradient, recalled acquisition sequence with 1.5 mm × 1.2 mm × 1.1 mm voxels . Eleven anatomically-defined ROIs, including the frontal lobe, parietal lobe, occipital lobe, temporal lobe, insula, internal structures , diencephalon, brainstem, cerebellar hemispheres, vermis, corpus callosum, and pituitary gland were contoured on the OTP [The BMs were contoured on the OTP, and the locations of the BMs were recorded. If a BM involved two or more ROIs, the ROI where the largest BM volume was located was considered a positive anatomical area. The contours of the ROIs were independently drawn by two experienced radiation oncologists. When the ROI contours differed, a third radiation oncologist made the final decision.A is:We assumed that the proportion of BMs per unit volume is the same, and the proportion of expected BMs in ROIA is volume of ROIA and Vtotal is total volume of all 11 ROIs).where VAs BMs have a space occupying effect which affects the brain ROI volume, we selected 20 patients with normal MRI results, contoured 11 ROIs according to the above method, and recorded the volume of ROIs to calculate the proportion of expected BMs. The ROIs of 20 normal brain MRI scans were also independently determined by two experienced radiation oncologists. The volume of different ROIs in the same patient was calculated as the average value of the two results.P-value of 0.05 or less was considered to indicate statistical significance.SPSS 22.0 software  was used for statistical analysis. The observed and expected rate of BMs for each ROI were compared using the proportional two-tailed hypothesis test . There wA total of 243 patients with BMs were included, of which 37 patients had only a head enhanced computed tomography examination and two patients had only a plain scan head MRI due to a contrast agent allergy and could not display the number and location of BMs accurately. In total, 204 patients with enhanced head MRI were imported into OTP, and 12 patients had indistinct MRI results due to motion artifact. Finally, 991 metastases in 192 patients with advanced cancer were analyzed in the study. The clinical characteristics of the patients are shown in Table P < 0.001), occipital lobe , and cerebellum  was significantly higher than the proportion of expected BMs. The incidence of BMs in the brainstem, insula, diencephalon and internal structures, and corpus callosum was low, and there were 9 (4.7%), 7 (3.6%), 8 (4.2%) and 4 (2.1%) patients with metastasis, respectively. The proportion of observed BMs in the brainstem , insula , diencephalon and internal structures , and corpus callosum  was significantly lower than the proportion of expected BMs, and the incidence of BMs located in pituitary was zero. The meninges were not an area of focus in this study; however, meningeal metastasis occurred in two patients.The parietal lobe, occipital lobe, frontal lobe, cerebellum, and temporal lobe were common BM sites, and there were 115 (59.9%), 81 (42.2%), 80 (41.7%), 71 (37.0%), 51 (26.6%) patients with corresponding ROI metastasis, respectively. The proportion of observed BMs in the parietal lobe , Table The low-risk ROIs  were analyzed as a single area Fig. . The proThe main purpose of this study was to determine the low-risk and high-risk BM areas through the analysis of metastasis sites of newly-diagnosed patients with BM to provide the basis to prevent low-risk areas and increase the irradiation dose of the high-risk areas during WBRT. Some studies , 20 haveThrough the integrated analysis of the brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary, we found that both the proportion of patients with BMs in this region and the expected proportion of BMs in this region increased, which may be caused by the increase of volume when all low-risk areas are analyzed as a whole. However, we found that the proportion of observed BMs in the brainstem, insula, diencephalon and internal structures, and corpus callosum was significantly lower than the proportion of expected BMs, and the proportion of observed BMs in the parietal lobe, cerebellum, and occipital lobe was significantly higher than the proportion of expected BMs. Therefore, our previous assumption that “the opportunity of BMS per unit volume is the same” is wrong. Volume may be only one of the reasons that affect the distribution of brain metastasis, and there may be other reasons, such as differences in pathological types and primary tumors –23. In YWe found that the proportion of observed BMs in low-risk ROIs was only 3.0%, significantly lower than the proportion of expected BMs. Yanagihara et al.  also fouWhen the number of BMs < 5, the possibility of BMs in low-risk areas may be low, especially for those patients with single BM, We didn’t find metastasis in the low-risk areas, which makes it possible to protect these areas when performing WBRT. However, a “low-risk” area of the brain might only be low risk for metastasis failure, but not necessarily low risk clinically. Even though the incidence of brain metastasis of these important structures may be very low, once there is a metastasis, it is often fatal. Therefore, whether these areas can be avoided during WBRT requires more rigorous prospective randomized controlled clinical trials. We found that the incidence of BMs in the parietal lobe, cerebellum, and occipital lobe was higher than the corresponding ROI volumes relative to the total volume of all 11 ROIs. The parietal lobe, cerebellum, and occipital lobe were high-risk for having BMs, which was also confirmed in other studies. Bender et al.  found thP = 0.762). (2)The hippocampus area has been confirmed to be an area with a low-risk of developing BM [The limitations of this study are as follows: (1) regarding patient selection, we noticed that NRG-CC001 did not include small cell lung cancer (SCLC) patients because of the possibility of diffuse intracranial metastasis of SCLC. Our study is a retrospective study aiming to describe the probability of brain metastases in different regions of the brain regardless of primary tumor histology, so we included patients with SCLC. We divided the pathological types into three categories: small cell lung cancer, non-small cell lung cancer, and others; 13, 15.3, and 10.4%, respectively, of the patients had low-risk areas metastasis, and there was no significant difference between the three groups (oping BM . TherefoWe found that the brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary are low risk areas for BMs, which may be avoided when treating with WBRT, but WBRT may not necessarily avoid low-risk ROIs in patients with BMs ≥5. Future studies are needed to confirm whether the avoidance of those ROIs on WBRT can reduce the incidence of neurocognitive and endocrine toxicity under the condition of similar intracranial tumor control rates.