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Purpose: Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment. Materials and methods: Patients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39–45 Gy/13–25 fractions. and 16.5–22 Gy/2–4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan–Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined. Results: Seventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively. Conclusion: HDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Given the strong association between high-risk HPV genotypes, such as HPV 16 and 18, and cervical cancer, this study aimed to compare the distribution of common HPV genotypes in the southwest Iranian population with those included in the available vaccines. Methods: Based on the sample quality, DNA was extracted from the biological samples of 8036 individuals included in the study using three different methods (automated instrument, column, and precipitation), and a total of 21 different HPV genotypes were detected using real-time PCR. Results: The majority of participants were women (> 99%), with a positive rate of HPV infection of 29.9%, in which high-risk genotypes were dominant in 84.9% cases. The highest rate of HPV infections was observed in the age ≤ 30 years (35.9%). HPV 6 and 16 were the most frequent low- and high-risk genotypes, respectively. Multi HPV infections were observed in 35% of positive samples and the highest cross infections were observed between HPV6 and 16. Co-infection with HPV 16 and 18 was observed in 21 positive samples (1%). Although vaccination is essential to reduce the outcome of HPV infections, such as cervical cancer, other frequently occurring high-risk genotypes are not included in the 9-valent vaccine. Conclusion: Since the association between cervical cancer and other high-risk HPV types rather than 16 and 18 has been less studied, investigating their pathogenicity in cervical cancer is recommended. Furthermore, the new generation of HPV vaccines should contain other frequently occurring high-risk genotypes beyond those currently covered in approved vaccines. [ABSTRACT FROM AUTHOR]

Background: For women at increased risk of breast cancer, the National Comprehensive Cancer Network (NCCN) guidelines recommend clinical encounters every 6–12 months. While screening mammography has corresponded with a relative risk reduction in breast cancer mortality of approximately 20%, evidence validating clinical breast examination (CBE) as an efficacious screening modality is deficient. Our study aimed to assess the conventional merit of regular CBE for breast cancer detection among individuals at increased risk of breast cancer development. Methods: Women > 18 years with documented high-risk encounters at Corewell Health West from 1 January 2018 to 31 December 22 were retrospectively reviewed. High-risk criteria included genetic predisposition, 5-year (> 1.7%) or lifetime (> 20%) Tyrer–Cuzick and/or Gail Model risk estimations, thoracic radiotherapy before age 30 years, lobular carcinoma in-situ, or atypical hyperplasia. Patients with a history of breast cancer or bilateral prophylactic mastectomy prior to 2018 were excluded. Results: Of the 9171 cumulative high-risk encounters among 2493 women, only one breast cancer was detected by CBE. CBE resulted in 1 (0.04%) cancer diagnosis compared with 30 (1.2%) detected on screening imaging and 10 (0.4%) self-reported. Of the 30 image-detected cancers, 28 (93.3%) had no detectable clinical findings at the time of preoperative consultation. Self-reported and CBE-detected cancers were more likely to be of higher clinical stage compared with imaging-detected malignancies. Conclusions: The role of routine CBE as a cancer detection modality in the high-risk patient population appears to be limited. Telemedicine can be offered to individuals who have completed screening imaging but are unable to commit and/or are inconvenienced by in-person high-risk breast cancer assessments. [ABSTRACT FROM AUTHOR]

Background: High-risk programs provide recommendations for surveillance/risk reduction for women at elevated risk for breast cancer development. This study evaluated the impact of high-risk surveillance program participation on clinicopathologic breast cancer features at the time of diagnosis. Methods: Women followed in the authors' high-risk program (high-risk cohort [HRC]) with a diagnosis of breast cancer from January 2015 to June 2021 were identified and compared with the general population of women undergoing breast cancer surgery at Memorial Sloan Kettering Cancer Center (MSK; general cohort [GC]) during the same period. Patient and tumor factors were collected. Clinicopathologic features were compared between the two cohorts and in a subset of women with a family history of known BRCA mutation. Results: The study compared 255 women in the HRC with 9342 women in the GC. The HRC patients were slightly older and more likely to be white and have family history than the GC patients. The HRC patients also were more likely to present with DCIS (41 % vs 23 %; p < 0.001), to have smaller invasive tumors (pT1: 100 % vs 77 %; p < 0.001), and to be pN0 (95 % vs 81 %; p < 0.001). The HRC patients had more invasive triple-negative tumors (p = 0.01) and underwent less axillary surgery (p < 0.001), systemic therapy (p < 0.001), and radiotherapy (p = 0.002). Among those with a known BRCA mutation, significantly more women in the HRC underwent screening mammography (75 % vs 40 %; p < 0.001) or magnetic resonance imaging (MRI: 82 % vs 9.9 %; p < 0.001) in the 12 months before diagnosis. Conclusions: Women followed in a high-risk screening program have disease diagnosed at an earlier stage and therefore require less-intensive breast cancer treatment than women presenting to a cancer center at the time of diagnosis. Identification of high-risk women and implementation of increased surveillance protocols are vital to improving outcomes. [ABSTRACT FROM AUTHOR]

The prognosis of thyroid cancer in patients varies significantly based on different pathological types or distinct clinical situations. Investigating the expression of immune checkpoint molecules PD-L1 and B7-H3 in high-risk thyroid cancer and their correlation with clinicopathological features and prognosis will contribute to the development of novel therapeutic strategies. A retrospective sample of 202 patients with thyroid cancer who underwent surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences was collected, including 33 cases of anaplastic thyroid cancer (ATC), 21 cases of differentiated thyroid cancer (DTC) with distant metastasis (DM), 7 cases of differentiated high-grade thyroid carcinoma (DHGTC), and 109 cases of aggressive subtypes of papillary thyroid carcinoma (PTC) (including 28 cases of tall cell PTC, 31 cases of diffuse sclerosing PTC, 20 cases of solid PTC, 15 cases of columnar cell PTC, and 15 cases of hobnail PTC). In the control group, there were 32 cases of classic PTC. The differences in protein expression between PD-L1 and B7-H3 in several high-risk thyroid cancers and normal tissues and controls were compared by immunohistochemical staining, and the clinicopathological features and prognostic relevance were statistically analyzed. The expression of PD-L1 in ATC (P < 0.001), tall cell PTC (P = 0.031), and DHGTC (P = 0.003) was significantly higher than that in classic PTC. The expression of B7-H3 in ATC (P < 0.001), DTC with DM (P = 0.001), diffuse sclerosing PTC (P = 0.013), columnar cell PTC (P = 0.007), solid PTC (P < 0.001), hobnail PTC (P < 0.001), and DHGTC (P < 0.001) was significantly higher than that in classic PTC. In ATC, PD-L1 expression correlated significantly with extrathyroidal extension (ETE) (P = 0.027) and B7-H3 expression correlated significantly with male patients (P = 0.031) and lymph node metastasis (LNM) (P = 0.026). The positive expression of B7-H3 (P = 0.041) was an independent risk factor for disease progression in ATC. B7-H3 positive expression (P = 0.049), PD-L1 positive expression (P = 0.015), and tumor diameter ≥ 2 cm (P = 0.038) were independent risk factors for disease progression in patients with DTC with DM. PD-L1 positive expression (P = 0.019) and tumor diameter ≥ 2 cm (P = 0.018) were independent risk factors for disease progression in patients with aggressive subtypes of PTC. B7-H3 and PD-L1 are expected to be effective prognostic indicators for patients with aggressive thyroid cancer, which can help in optimization of individualized treatment strategies. Immunotherapy targeting these two molecules may provide new and complementary ideas for the treatment of high-risk/refractory thyroid cancer. [ABSTRACT FROM AUTHOR]

Basal Cell Carcinoma (BCC) is the most prevalent skin cancer and continues to witness a surge in incidence rates. The categorization of BCC subtypes into low or high risk, guided by recurrence and invasiveness metrics, underscores the need for precise differentiation. While the punch biopsy remains the gold standard for diagnosis, its invasiveness prompts a need for non-invasive alternatives. Ultrasound (US) has emerged as a noteworthy candidate, gaining momentum in its potential to offer a less intrusive diagnostic approach. We conducted a systematic review regarding features of the high-risk subtypes of BCC on US. A thorough literature search of PubMed Medline, Embase, and CINAHL databases was conducted according to PRISMA guidelines and a total of nine studies meeting our inclusion criteria were included in this review. Evidence is still nascent but US features such as lesional shape, depth, hyperechoic spots, and color doppler may be helpful in differentiating high-risk BCC subtypes. However, further prospective studies with standardized interventions and outcome measures are required. [ABSTRACT FROM AUTHOR]

Background and aims: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER. Methods: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS). Results: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43). Conclusion: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients. Methods: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes. Results: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.’s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision. Conclusion: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients. [ABSTRACT FROM AUTHOR]

Purpose: Treatment intensification of external beam radiotherapy (EBRT) plays a crucial role in the treatment of high-risk prostate cancer. Methods: We performed a critical narrative review of the relevant literature and present new developments in evidence-based treatment intensification strategies. Results: For men with high-risk prostate cancer, there is strong evidence to support prolonging androgen deprivation therapy (ADT) to 18–36 months and escalating the dose to the prostate using a brachytherapy boost. A potentially less toxic alternative to a brachytherapy boost is delivering a focal boost to dominant intraprostatic lesions using EBRT. In patients who meet STAMPEDE high-risk criteria, there is evidence to support adding a second-generation anti-androgen agent, such as abiraterone acetate, to long-term ADT. Elective pelvic lymph node irradiation may be beneficial in select patients, though more prospective data is needed to elucidate the group of patients who may benefit the most. Tumor genomic classifier (GC) testing and advanced molecular imaging will likely play a role in improving patient selection for treatment intensification as well as contribute to the evolution of treatment intensification strategies for future patients. Conclusion: Treatment intensification using a combination of EBRT, advanced hormonal therapies, and brachytherapy may improve patient outcomes and survival in men with high-risk prostate cancer. Shared decision-making between patients and multidisciplinary teams of radiation oncologists, urologists, and medical oncologists is essential for personalizing care in this setting and deciding which strategies make sense for individual patients. [ABSTRACT FROM AUTHOR]

Opinion statement: Localized high-risk (HR) prostate cancer (PCa) is a heterogenous disease state with a wide range of presentations and outcomes. Historically, non-surgical management with radiotherapy and androgen deprivation therapy was the treatment option of choice. However, surgical resection with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) is increasingly utilized as a primary treatment modality for patients with HRPCa. Recent studies have demonstrated that surgery is an equivalent treatment option in select patients with the potential to avoid the side effects from androgen deprivation therapy and radiotherapy combined. Advances in imaging techniques and biomarkers have also improved staging and patient selection for surgical resection. Advances in robotic surgical technology grant surgeons various techniques to perform RP, even in patients with HR disease, which can reduce the morbidity of the procedure without sacrificing oncologic outcomes. Clinical trials are not only being performed to assess the safety and oncologic outcomes of these surgical techniques, but to also evaluate the role of surgical resection as a part of a multimodal treatment plan. Further research is needed to determine the ideal role of surgery to potentially provide a more personalized and tailored treatment plan for patients with localized HR PCa. [ABSTRACT FROM AUTHOR]

Purpose: The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. Methods: HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1–3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). Results: A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003–10 (210), and GEICAM-2006–10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. Conclusions: This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted. Trial registration: ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127. [ABSTRACT FROM AUTHOR]

Purpose: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course. Methods: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested. Results: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC. Conclusion: Combined treatment improved RFS and PFS only in patients with Ta disease. [ABSTRACT FROM AUTHOR]

Background: To reach a consensus on recommendations for the management of high-risk and post-operative non-metastatic prostate cancer by a group of Radiation Oncologists in Catalonia dedicated to prostate cancer. Methods: A modified Delphi approach was employed to reach consensus on controversial topics in Radiation Oncology on high-risk non-metastatic (eight questions) and post-operative (eight questions) prostate cancer. An agreement of at least 75% was considered as consensus. The survey was electronically sent 6 weeks before an expert meeting where topics were reviewed and discussed. A second-round survey for the controversial questions only was sent and answered by participants after the meeting. Results: After the first round of the survey, 19 experienced Radiation Oncologists attended the meeting and 74% fulfilled the second-round online questionnaire. An agreement of 9 of the 16 questions was accounted for the first round. After the meeting, an additional agreement was reached in 3 questions leading to a final consensus on 12 of the 16 questions. There are still controversial topics like the use of PET for staging of high-risk and post-operative non-metastatic prostate cancer and the optimal dose to the prostate bed in the salvage setting. Conclusion: This consensus contributes to establish recommendations and a framework to help in prostate cancer radiation therapy and pharmacological management in daily clinical practice of high-risk and post-operative non-metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Recently, stratification of high-risk stage II colon cancer (CC) and the need for adjuvant chemotherapy have been the focus of attention. The aim of this retrospective study was to define high-risk factors for recurrent stage II CC using Prediction One auto-artificial intelligence (AI) software and develop a new predictive model for high-risk stage II CC. Methods: The study included 259 consecutive pathological stage II CC patients undergoing curative resection at our institution between January 2000 and December 2016. Prediction One software with five-fold cross-validation was used to create a predictive model and receiver operating characteristic (ROC) curve. Predictive accuracy of AI was evaluated using the area under the ROC curve (AUC). We also evaluated the importance of variables (IOV) using a method based on permutation feature importance (IOV > 0.01 defined high-risk factors) to evaluate disease-free survival (DFS). Results: The median observation period was 6.1 (range = 0.3–15.8) years. Thirty-seven patients had recurrence (14.3%); the AUC of the AI model was 0.775. Preoperative carcinoembryonic antigen > 5.0 ng/mL (IOV = 0.047), venous invasion (IOV = 0.014), and obstruction (IOV = 0.012) were high-risk factors contributing to cancer recurrence. Patients with 2–3 high-risk factors had lower 5-year DFS than those with 0–1 factor (87.4% vs 62.7%, p < 0.001). Conclusions: We developed a new predictive model that could predict recurrent high-risk stage II CC with high probability using auto-AI Prediction One software. Patients with ≥ 2 of the aforementioned factors are considered to have high risks for recurrent stage II CC and may benefit from adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence and types of inborn errors of metabolism (IEMs) in high-risk children using mass spectrometry techniques. Methods: Children considered high-risk for IEM were screened for metabolic diseases during a 3-y period. Dried blood spots and urine samples were analyzed by tandem mass spectrometry (LC–MS/MS) and gas chromatograph–mass spectrometry (GCMS). Samples with abnormal amino acids were confirmed by high-performance liquid chromatography (HPLC). Results: Eight hundred and twenty-two suspected cases were evaluated; of which, 87 possible cases of IEMs were identified. Homocystinuria (n = 51) was the most common IEM detected followed by biotinidase deficiency (n = 7), glutaric aciduria type 1 (n = 7), and carnitine uptake defect (n = 6). Overall, there were 45 (51.7%) cases of organic acidemia, 31 cases (35.6%) of amino acid defect, 9 (10.3%) cases of fatty-acid oxidation disorders, and 2 (2.3%) cases of probable mitochondrial disorder. Conclusion: IEMs are common in India, with a hospital-based incidence of 1 in approximately 6642 among high-risk children. Screening of high-risk children by mass spectrometry techniques is a valuable strategy for early diagnosis of IEMs where universal newborn screening is not yet available. [ABSTRACT FROM AUTHOR]

Young adults, particularly college students, report a higher prevalence of risky sexual behavior than the general population, increasing their likelihood for unplanned pregnancy, sexually transmitted infections (STIs), and negative psychological outcomes. Although sexual risk behavior and its consequences are a major public health concern, current prevention literature is insufficient and relies on sexual risk measures with limited psychometric support. The present study, therefore, examined the psychometric properties of a sexual risk survey (SRS; Turchik, Garske, in Arch Sex Behav 38:936–948, 2009), using data from the first year of a longitudinal study following the outcomes of college students with and without attention-deficit/hyperactivity disorder (ADHD; N = 410). Principal components analyses were conducted to assess the factorial structure of the SRS comparing results from a general college population and a college population considered to be high-risk (ADHD). Results revealed four components across both samples. Internal consistency estimates for component scores and total scores ranged from.627 to 918. Implications of the findings are discussed and suggestions for future studies are advanced. [ABSTRACT FROM AUTHOR]

To date, no specific studies have evaluated early death (ED) in patients with acute promyelocytic leukaemia (APL) homogeneously treated with arsenic trioxide induction therapy and investigated according to the white blood cell (WBC) count at onset. Such patients were retrospectively analysed in this study, including 314 patients with a WBC count ≤ 10 × 109/L (standard-risk (SR) group) and 144 with a WBC count > 10 × 109/L (high-risk (HR) group). The baseline clinical characteristics and risk factors for ED were compared between the two groups. The incidence of fibrinogen < 1.0 g/L and elevated serum uric acid, aspartate aminotransferase and creatinine levels were higher in the HR group than in the SR group (P = 0.001; P < 0.001; P < 0.001; P = 0.044, respectively). The ED rate was significantly higher in the HR group than in the SR group (29.17% vs. 10.83%, P < 0.001). The main cause of ED was bleeding, followed by infection and differentiation syndrome (DS) in the HR group, while it was bleeding, followed by DS and infection in the SR group. Male sex, age > 50 years old, and fibrinogen < 1.0 g/L were independent risk factors for ED in the SR group. Increased serum creatinine levels, decreased albumin levels, and fibrinogen < 1.0 g/L were independent risk factors for ED in the HR group. Overall, the incidence of ED was higher in the HR group, and the baseline clinical characteristics, causes, times, and predictors of ED in the HR group differed from those in the SR group. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the use of the combined model based on clinical and enhanced CT texture features for predicting the liver metastasis of high-risk gastrointestinal stromal tumors (GISTs). Methods: This retrospective study was conducted including 204 patients with pathologically confirmed high-risk GISTs from the Zhejiang Cancer Hospital from January 2015 to June 2021, and 76 cases of them were diagnosed with simultaneous liver metastasis. We randomly divided the cohort into a training cohort (n = 142) and a validation cohort (n = 62) with a ratio of 7:3. All volumes of interest (VOIs) of the high-risk GISTs were manually segmented on the portal venous phase CT images using the ITK-SNAP software. The least absolute shrinkage and selection operator (Lasso) algorithm was performed to determine the most valuable features from a total of 110 texture features extracted by the A-K software to reflect the texture information of the given VOIs. Texture-based predictive model was built from the selected texture features. Independent clinical risk factors were identified through univariate logistic analysis. Then, the texture-based model incorporated the clinical predictors to develop a combined model by multivariate logistic regression. Receiver operating characteristic curve, calibration curve, and decision curve analysis were utilized to analyze the discrimination capacity and clinical application value of the predictive models. Results: The nine optimal texture features were remained after the reduction of dimension using Lasso method. Another four clinical parameters (BMI, location, gastrointestinal bleeding, and CA125 level) were included in the clinical-based predictive model. Finally, with the combination of remaining texture and clinical features, a multivariate logistic regression classifier was built to predict the liver metastasis potential of high-risk GISTs. The remarkable classification performance of the combined model for the prediction of liver metastasis in the subjects with high-risk GISTs was obtained with area under curve (AUC) = 0.919, sensitivity = 83.9%, specificity = 89.7%, and accuracy = 84.9% in our validation group. Conclusion: The texture-based radiomic signature derived from the portal venous phase CT images could predict liver metastasis of high-risk GISTs in a non-invasive way. Integrating additional clinical variables into the model further leads to an improvement of liver metastasis risk prediction. [ABSTRACT FROM AUTHOR]

Purpose: MRI-based screening in women with a ≥ 25% lifetime risk of breast cancer , but no identifiable genetic mutations may be associated with false positives. This study examined the psychological impact of abnormal screens and biopsies in non-mutation carriers participating in high-risk screening with no personal history of breast cancer. Methods: Non-mutation carriers participating in the High-Risk Ontario Breast Screening Program at two sites were mailed demographic surveys, psychological scales, and chart review consent. Scales included the Consequences of Screening in Breast Cancer questionnaire, Lerman Breast Cancer Worry Scale, and Worry Interference Scale. Missing data were managed with multiple imputation. Multivariable regression was used to assess whether abnormal screens or biopsies were associated with adverse psychological effects. Results: After contacting 465 participants, 169 non-mutation carriers were included. Median age was 46 years (range 30–65). Over a median 3 years of screening, 63.9% of women experienced at least one abnormal screen, and 24.9% underwent biopsies. Statements relating to cancer worry/anxiety scored highest, with 19.5% indicating they worried "a lot". Higher scores among anxiety-related statements were strongly associated with higher dejection scores. Overall, coping and daily functioning were preserved. Women indicated some positive reactions to screening, including improved existential values and reassurance they do not have breast cancer. Abnormal screens and biopsies were not significantly associated with any psychological scale, even after adjustment for patient characteristics. Conclusion: Non-mutation carriers undergoing MRI-based screening had considerable baseline anxiety and cancer worry, although daily functioning was not impaired. Abnormal screens and biopsies did not appear to have adverse psychological effects. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the associations between temperamental reactivity and regulation and the emergence of anxiety traits in a longitudinal sample of infants enriched for later ASD. Parents of 143 infants who were at high- and low-risk for ASD rated their child's temperament traits when they were 9, 15 and 24 months old; they rated anxiety and ASD traits when they were 36 months old. The findings suggest that behavioural inhibition may be an early predictor of later anxiety in children with and without ASD and that lower levels of effortful control in children who later develop ASD may contribute to the higher expression of anxiety within this population. [ABSTRACT FROM AUTHOR]

This paper applies Collaborative Language Systems (CLS) theory to programs working with high-risk adolescent fathers. Research shows that many barriers prevent these fathers from meaningfully engaging in intervention programs due to a variety of tangible (e.g., lack of transportation, variable employment schedules) and intangible (e.g., poor family-of-origin relationships, discord with child's mother, history of trauma, perceived stigma) factors. In order to engage and retain fathers, intervention programs need to address these barriers by understanding the needs and cultural values of fathers, creating open and nonjudgmental spaces, and building relationships rather than solely administering curricula. The purpose of this paper is to illustrate how CLS principles provide a particularly relevant framework to reduce engagement barriers for this population. Using examples from interviews with n = 27 high-risk adolescent fathers (19–27 years of age, 93% racial or ethnic minority) who participated in fathering programming, this paper shows how CLS provides a theoretical foundation for addressing barriers and working alongside fathers. Several aspects of CLS emerged through thematic coding, which suggest that creating a sense of belonging through non-judgmental spaces and fostering open group dynamics characterized by equality motivated fathers' engagement in fathering programming. This paper adds to the meager research on theoretically grounded and effective methods for engaging fathers in parenting programs. [ABSTRACT FROM AUTHOR]

The iBerry Study, a Dutch population-based high-risk cohort (n = 1022) examines the transition from subclinical symptoms to psychiatric disorders in adolescents. Here, we present the first follow-up measurement, approximately 3 years after baseline assessment and 5 years after the screening based on self-reported emotional and behavioral problems (SDQ-Y). We give an update on the data collection, details on the (non)response, and the results on psychopathology outcomes. The first follow-up (2019–2022) had a response rate of 79% (n = 807). Our results at baseline (mean age 15.0 years) have shown the effectiveness of using the SDQ-Y to select a cohort oversampled for the risk of psychopathology. At first follow-up (mean age 18.1 years), the previously administered SDQ-Y remains predictive for selecting adolescents at risk. At follow-up, 47% of the high-risk adolescents showed significant mental health problems based on self- and parent reports and 46% of the high-risk adolescents met the criteria for multiple DSM-5 diagnoses. Compared to low-risk adolescents, high-risk adolescents had a sevenfold higher odds of significant emotional and behavioral problems at follow-up. Comprehensive assessment on psychopathology, substance abuse, psychotic symptoms, suicidality, nonsuicidal self-injury, addiction to social media and/or video gaming, and delinquency, as well as social development, and the utilization of healthcare and social services were conducted. This wave, as well as the ones to follow, track these adolescents into their young adulthood to identify risk factors, elucidate causal mechanisms, and discern pathways leading to both common and severe mental disorders. Results from the iBerry Study will provide leads for preventive interventions. [ABSTRACT FROM AUTHOR]

The iBerry study is a population-based cohort study designed to investigate the transition from subclinical symptoms to a psychiatric disorder. Adolescents were selected based on their self-reported emotional and/or behavioral problems assessed by completing the strengths and difficulties questionnaire-youth (SDQ-Y) in their first year of high school. A total of 16,736 SDQ-Y questionnaires completed in the academic years 2014–2015 and 2015–2016 by students in the greater Rotterdam area in the Netherlands were screened. A high-risk group of adolescents was then selected based on the 15% highest-scoring adolescents, and a low-risk group was randomly selected from the 85% lowest-scoring adolescents, with a 2.5:1 ratio between the number of high-risk and low-risk adolescents. These adolescents were invited to come with one parent for a baseline visit consisting of interviews, questionnaires, neuropsychological tests, and biological measurements to assess determinants of psychopathology. A total of 1022 high-risk and low-risk adolescents (mean age at the first visit: 15.0 years) enrolled in the study. The goal of the iBerry study is to follow these adolescents for a 10-year period in order to monitor any changes in their symptoms. Here, we present the study design, response rate, inclusion criteria, and the characteristics of the cohort; in addition, we discuss possible selection effects. We report that the oversampling procedure was successful at selecting a cohort of adolescents with a high rate of psychiatric problems based on comprehensive multi-informant measurements. The future results obtained from the iBerry Study will provide new insights into the way in which the mental health of high-risk adolescents changes as they transition to adulthood. These findings will therefore facilitate the development of strategies designed to optimize mental healthcare and prevent psychopathology. [ABSTRACT FROM AUTHOR]

Purpose: Prostate-specific membrane antigen (PSMA) PET/CT shows better diagnostic performance for detection of lymph node and bone metastases as compared to conventional imaging. Studies of PSMA PET/CT in primary staging comprise highly selected patient cohorts. This study evaluates 18F-DCFPyL PET/CT as first-line imaging modality for primary staging of high-risk prostate cancer. Material: From February 2018 until April 2019, all patients with high-risk prostate cancer received 18F-DCFPyL PET/CT for staging of prostate cancer. Baseline characteristics, findings at 18F-DCFPyL PET/CT, number and type of required additional diagnostic procedures, findings at additional diagnostic procedures, and effects of therapy on PSA levels for all patients treated with curative intent were collected and evaluated. Results: One hundred-sixty patients were included in the study of which 90 (56%) had evidence of metastasized disease (N1, M1a, M1b and, M1c in 49%, 28%, 31%, and 3% respectively). Additional diagnostic imaging was needed in 2/160 patients (1%) because of equivocal findings on 18F-DCFPyL PET/CT. Eighty-one patients had evidence of PSMA-positive lymph node metastases, of whom 39 (48%) had no enlarged lymph nodes on CT; 18F-DCFPyL PET detected additional metastatic lymph nodes in 41/42 patients that had evidence of lymph node metastases on CT. 18F-DCFPyL PET altered patients' management in 17% of patients. Conclusion: 18F-DCFPyL PET/CT can be used as first-line imaging modality for therapy selection in patients with primary high-risk prostate cancer, without need for further diagnostic imaging procedures in the majority of patients. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis is a principal prognostic factor for the treatment of endometrial cancer. Added value of para-aortic lymphadenectomy to only pelvic lymphadenectomy for intermediate/high-risk endometrial cancer patients remains controversial.Objective: A systematic review and meta-analysis was performed to assess the impact of combined pelvic and para-aortic lymph node dissection (PPALND) compared to only pelvic lymph node dissection (PLND) on survival outcomes of intermediate and/or high-risk patients.Study Design: The systematic review and meta-analysis adhered to the PRISMA guidelines for meta-analyses of interventional studies. Pubmed, Scopus, EMBASE and Cochrane were searched up to April 20, 2018. Included studies were those comparing high-risk endometrial cancer patients that had performed pelvic and para-aortic lymph node dissection (PPALND) vs. only pelvic lymph node dissection (PLND) apart from standard procedure (total hysterectomy with bilateral salpingo-oophorectomy, TAHBSO). Primary outcomes of the study were overall survival and disease-free survival rates. Methodological quality of the included studies was assessed using the ROBINS-I tool. Overall quality of the evidence for the primary and secondary outcomes was evaluated as per GRADE guideline using the GRADE pro GD tool.Results: There were 13 studies identified with 7349 patients included. All studies were retrospective observational as no RCTs or prospective studies adhering to inclusion criteria were retrieved. Combined pelvic and para-aortic lymphadenectomy was associated with 46% decreased risk for death (HR 0.54, 95% CI 0.35-0.83, I2 = 62.1%) and 49% decreased risk for recurrence (HR 0.51, 95% CI 0.28-0.93). It was also associated with increased 5-year OS rate (RR 1.13, 95% CI 1.04-0.24, I2 = 57.3%) and increased 5-year DFS rate (RR 1.23, 95% CI 1.14-1.31, I2 = 85.5) compared with only pelvic lymphadenectomy.Conclusion: Combined pelvic and para-aortic lymphadenectomy is associated with improved survival outcomes compared with only pelvic lymphadenectomy in women with intermediate/high-risk endometrial cancers. Further prospective studies should be performed. [ABSTRACT FROM AUTHOR]

Purpose: We aim to study certain histopathological characteristics of the retinoblastoma (RB) tumors in globes with clinically advanced RB, which can be correlated with the high-risk features including: tumor differentiation, growth pattern and focality. We also aim to reclassify the tumor pathologically in the analyzed cases according to the American Joint Committee on Cancer (AJCC) 8th edition in an attempt to compare the validity of this newest classification. Methods: Retrospective study of patients diagnosed with clinical RB of groups D and E during the period: January 2013 to December 2017 at King Khaled Eye Specialist Hospital (KKESH) and King Abdulaziz University Hospital (KAUH). Charts were reviewed for demographic and basic clinical data. Histopathological features (tumor differentiation, growth pattern, focality, seeding, and presence of choroidal invasion (focal versus massive), level of optic nerve (ON) invasion, anterior chamber invasion, scleral and extra-scleral extension, and finally the documented pathological tumors (pT) classification based on the AJCC 7th edition were collected. Results: We included 146 eyes with advanced retinoblastoma (groups D and E) from 104 patients. Gender distribution was almost equal with 54 males. Median age was 12 months (range 1–96 months), and a mean age was 17.1 ± 15.1 months. No family history was found in the majority (94.2%). Clinically, the most common presenting symptoms: leukocoria (73.3%), squint (33.6%) and least commonly proptosis (2.7%). A total of 106 enucleation specimens were reviewed. Degree of RB differentiation was: well differentiated (18%), moderate (30%), poor (35%), and undifferentiated (17%). The most common high-risk features were ON invasion (68%) with the majority being prelaminar in nature, choroidal invasion (45%) with more than half being massive, iris/trabecular meshwork (TM)/Schlemm's canal invasion (8.5%), and then intra-scleral/extra-scleral extension (5%). Less tumor differentiation doubles the relative risk of massive choroidal invasion (with 95% CI) with a statistically significant P value (P = 0.030). Endophytic RB was associated with vitreous seeding, while exophytic tumors were associated with subretinal seeding (P = 0.001) each. Ten cases with combined ON invasion (pre-laminar) and focal choroidal invasion were reclassified pT2a in the AJCC 8th edition instead of pT2b in the older 7th edition. Conclusions: Our demographic and basic clinical data for advanced RB are comparable to other similar reports. The tumor growth pattern correlates well with the type of seeding observed in enucleated globes with RB. Less tumor differentiation is a relative risk of massive choroidal invasion. It is advocated to implement the AJCC 8th edition by ocular pathologists worldwide aiming to histopathologically classify the RB tumor in cases for selective adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: The standard treatment of high-risk localized extremity and trunk soft-tissue sarcoma is wide local excision and radiation therapy, which can be delivered pre- or postoperatively. Improved care for sarcoma patients at expert centres with multidisciplinary tumour boards, specialized pathologists, surgeons, radio-oncologists, and medical oncologists, according to national or international guidelines, has improved outcomes. Yet, a substantial number of patients will experience disease recurrence with metastatic spread and ultimately die from their disease. In many solid tumours neo/adjuvant chemotherapy has become an accepted standard treatment, whereas in soft-tissue sarcoma discussions on the use of cytotoxic therapy in localized and resectable disease are ongoing. Some centres demonstrated the feasibility and now treat with concomitant neoadjuvant chemoradiotherapy as standard. Others argue that treatments should be given in the order of the accompanying evidence (surgery → radiotherapy → chemotherapy), which does not take biology of the disease into account and probably attempts to simplify complex decision making processes. It is important to enhance our ability to identify patients at highest risk of recurrence, and to generate data and develop tools to predict which patients will benefit from neo/adjuvant systemic therapy most. [ABSTRACT FROM AUTHOR]

Objective: Assess achievement of low-density lipoprotein cholesterol (LDL-C) targets in European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines.Design: Systematic literature review.Data Sources: Medline, EMBASE, Cumulated Index to Nursing and Allied Health Literature.Eligibility Criteria: Observational studies reporting LDL-C levels/target attainment, measured between 1 August 2006 to 31 August 2017, in European adults with established cardiovascular disease (CVD), diabetes with target organ damage, familial hypercholesterolaemia (FH) or 10-year risk of fatal CVD ≥ 5% (assessed by Systematic Coronary Risk Evaluation [SCORE]).Data Extraction and Synthesis: Two reviewers independently extracted relevant studies and assessed study quality using the Risk of Bias for Non-Randomised Studies-Interventions (ROBINS-I) tool. Primary outcome was the proportion of patients achieving LDL-C targets in the 2011/2016 ESC/EAS guidelines. Where available, patient characteristics were presented as means weighted by sample size. The proportions of patients achieving LDL-C targets in the 5 years before and after publication of the 2011 guidelines were compared using a chi-square test.Results: Across 81 eligible studies (303,534 patients), achievement of LDL-C < 1.8 mmol/L was poor among patients with established CVD (16%; range 9-56%) and at very high risk of CVD (SCORE ≥ 10% [18%; 14-25%]). In individuals with FH, SCORE 5-10%, or diabetes and target organ damage, LDL-C < 2.5 mmol/L was achieved by 15% (9-22%), 46% (21-55%) and 13% (6-34%), respectively. Comparing the 5 years before/after publication of the 2011 guidelines, target achievement increased significantly over time but remained suboptimal (LDL-C < 1.8, 22% versus 15%; LDL-C < 2.5, 68% versus 61%; both p < 0.001; established CVD group only).Conclusions: These data show suboptimal LDL-C control among European patients at high risk of CVD. Those at greatest overall risk (clinically established CVD or at least a 10% 10-year risk of fatal CVD) had the lowest achievement of 2011/2016 EAS/ESC LDL-C targets. With lower LDL-C targets advocated in 2019 ESC/EAS guidelines, this unmet need will increase.Protocol Registration: PROSPERO registration number; CRD77844. [ABSTRACT FROM AUTHOR]

Background: Evidence from epidemiological, clinical and high-risk studies has established that the peak period of risk for onset of bipolar disorder spans late adolescence and early adulthood. However, the proposal of the existence of a pre-pubertal form of bipolar disorder manifesting in early childhood created substantial debate. In this narrative review, the literature and contributing factors pertaining to the controversy surrounding the proposed pre-pubertal bipolar disorder subtype are discussed. The resolution of the debate and lessons learned are highlighted. Main body: In the mid 1990s US researchers proposed that chronic irritability and explosive temper in pre-pubertal children with pre-existing ADHD and/or other learning and developmental disorders might represent a variant of mania. A number of factors contributed to this proposal including severely ill children with no diagnostic home given changes in the ADHD DSM diagnostic criteria and over-reliance on symptoms and structured interviews rather than on a clinical assessment incorporating developmental history, social context and clinical course. Prospective studies of children at high familial risk did not support the proposed pre-pubertal bipolar phenotype; but rather provided convergent evidence that bipolar disorder onset in adolescence and early adulthood not uncommonly preceded by sleep and internalizing symptoms and most often debuting as depression in adolescence (after puberty). Epidemiological studies of population and hospital discharge data provided evidence that the pre-pubertal bipolar phenotype was largely a US driven phenomenon. Conclusions: Psychiatric diagnosis is particularly challenging given the current lack of objective biomarkers. However, validity and utility of clinical diagnoses can be strengthened if all available predictive information is used to formulate a diagnosis. As in other areas of medicine, critical information required to make a valid diagnosis includes developmental history, clinical course, family history and treatment response—weighed against the known trajectories of classical disorders. Moreover, given that psychiatric disorders are in evolution over childhood and adolescence and symptoms, in of themselves, are often non-specific, a thorough clinical assessment incorporating collateral history and psychosocial context is paramount. Such an approach might have avoided or at least brought a more timely resolution to the debate on pre-pubertal mania. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa.Methods: Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both.Results: Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p < 0.001). Completely resected disease had a five-year OS of 30.5%, incomplete resections 31.4% versus no surgery 6.0% (p < 0.001). Radiated patients had a five-year OS of 21.3% versus 14.2% without radiotherapy (p < 0.001). Patients who received radiotherapy without surgical interventions, had a marginally better five-year OS of 12.5% as opposed to 5.4% (p < 0.001). Patients who underwent surgery had a longer mean overall survival of 60.9 months, while patients, who were irradiated, had a longer mean overall survival of 7.9 months (p < 0.001). On multivariate analysis, complete metastatic remission (p < 0.001), surgical status (p = 0.027), and radiotherapy status (p = 0.040) were significant predictive factors in abdominal primaries.Conclusion: Surgery and radiotherapy significantly improve outcomes regardless of the primary tumor site, emphasizing the importance of local control in neuroblastoma. [ABSTRACT FROM AUTHOR]

The quality of caregiving is often compromised when mothers have co-occurring difficulties such as substance misuse and problems associated with extreme emotional dysregulation. These, in turn, are associated with poor child outcomes. The aim of the current study was twofold. First, to investigate the potential differences in risk factors associated with poor child outcome by comparing three groups: substance misusing mothers (Substance Misusing Mothers; SMM); mothers matched on demographic characteristics (Matched Comparison Mothers; MCM) and mothers recruited from the community (Matched Control Comparison; MCC). Second, to investigate the underlying mechanisms which are associated with poor child outcome by testing a mediated moderation model to ascertain (i) whether environmental risk and borderline psychopathology was a mediator between maternal childhood trauma and quality of caregiving and (ii) maternal substance misuse status moderated outcome. There were no significant differences found between the SMM and MCM groups on the key variables, but significant differences on all variables for both SMM and MCM compared to CCM. The moderated mediation analysis found that while there was significant mediation of environmental risk and borderline pathology between maternal childhood trauma and child outcome, this was not moderated by maternal substance abuse status. The importance of environmental-risk as a mechanism leading to reduced caregiving quality suggest treatment programs need to consider targeting these factors in high risk families. [ABSTRACT FROM AUTHOR]

Hemodynamically unstable pulmonary embolism (PE) represents a complex and life-threatening event with a highly variable course and poor prognosis in the short-term period. Despite an immediate reperfusion treatment is recommended in these patients, previous investigations have reported a lower use of systemic thrombolysis (ST). The aim of the present review is to assess and describe the real use of ST in hemodynamically unstable patients with acute PE enrolled in prospective—multicenter registries between the 1990 and 2018. Over that period, 1216 articles were identified in Pubmed. After excluding the duplicates obtained using the different searching MeSH (n = 703), 513 articles were screened and then excluded for not meeting inclusion criteria due the article type, design of the study or no English language. As result, 13 articles were assessed for eligibility and carefully reviewed. Finally, five studies met the inclusion criteria and were included in the analysis. The identified study registries enrolled prospectively 41364 consecutive patients with acute PE between the 1993 and the 2016. Among these, 2168 (5.2%) were hemodynamically unstable at presentation. ST was administered in 29.7% (n = 645) of patients while catheter-direct treatment (CDT) was used only in 1.4% (n = 32) of cases. Conversely, surgical pulmonary embolectomy (SPE) was adopted as reperfusion treatment in 39 patients (1.7%). Intriguingly, the 68% of patients not received a reperfusion treatment despite they were hemodynamically unstable at admission. Despite the internationals guidelines recommendations, a prompt reperfusion is performed only in one on three hemodynamically unstable patients with acute PE. [ABSTRACT FROM AUTHOR]

Changes in the surface morphology of the orbitofrontal cortex (OFC), such as a fewer orbital sulci and altered sulcogyral pattern of the 'H-shaped' orbital sulcus, have been reported in schizophrenia, possibly reflecting abnormal neurodevelopment during gestation. However, whether high-risk subjects for developing psychosis also exhibit these gross morphologic anomalies is not well documented. This multicenter MRI study from four scanning sites in Japan investigated the distribution of the number of intermediate and posterior orbital sulci, as well as the OFC sulcogyral pattern, in 125 individuals with an at-risk mental state (ARMS) [of whom 22 later developed psychosis (ARMS-P) and 89 did not (ARMS-NP)] and 110 healthy controls. The ARMS group as a whole had a significantly lower number of intermediate and posterior orbital sulci compared with the controls, which was associated with prodromal symptomatology. However, there was no group difference in OFC pattern distribution. The ARMS-P and -NP groups did not differ in OFC surface morphology. These results suggest that gross morphology of the OFC in high-risk subjects may at least partly reflect neurodevelopmental pathology related to vulnerability to psychosis. [ABSTRACT FROM AUTHOR]

To investigate temperament as an early risk marker for autism spectrum disorder (ASD), we examined parent-reported temperament for high-risk (HR, n = 170) and low-risk (LR, n = 77) siblings at 8, 14, and 24 months. Diagnostic assessment was performed at 36 months. Group-based analyses showed linear risk gradients, with more atypical temperament for HR-ASD, followed by HR-Atypical, HR-Typical, and LR siblings. Temperament differed significantly between outcome groups (0.03 ≤ ηp2 ≤ 0.34). Machine learning analyses showed that, at an individual level, HR-ASD siblings could not be identified accurately, whereas HR infants without ASD could. Our results emphasize the discrepancy between group-based and individual-based predictions and suggest that while temperament does not facilitate early identification of ASD individually, it may help identify HR infants who do not develop ASD. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer survivors face numerous challenges after diagnosis and treatment. Several models have been developed to attempt to improve quality of care. Here, we describe characteristics and outcomes of patients who participated in survivorship visits (SV) at Johns Hopkins (JH).Methods: We retrospectively reviewed charts of breast cancer patients who participated in an optional SV 1-3 months after completing locoregional therapy and initial systemic therapy. We report patient demographics, comorbidities, tumor characteristics, treatments, and responses to symptom questionnaires. We compared the characteristics of SV participants to stage I-III analytical cases in the 2010-2015 JH Cancer Registry (JHCR).Results: We identified 87 women with stage I-III breast cancer who participated in SVs from 2010 to 2016. Compared to patients in the JHCR (n = 2942), SV participants were younger, more likely to be African American and more likely to have a higher TNM stage, hormone receptor-negative disease, and HER2-positive disease. They were more likely to have received chemotherapy and radiation therapy. They also have similar recurrence rates despite the SV cohort's shorter median follow-up time. Among SV participants, the prevalence of comorbidities including peripheral neuropathy, anemia, lymphedema, anxiety, deep vein thrombosis, and depression increased significantly from time of diagnosis to most recent follow-up.Conclusions: Compared to the JHCR cohort, SV participants had higher risk cancers and a high frequency of comorbidities potentially associated with breast cancer and therapy. These high-risk patients may benefit most from specific interventions targeting survivorship care, and their experiences may help improve care delivery models. [ABSTRACT FROM AUTHOR]

Shared vulnerability in offspring of individuals with schizophrenia (SzO) and bipolar disorder (BpO) might manifest early during development through common temperament traits. Temperament dimensions in child and adolescent BpO (N = 80), SzO (N = 34) and the offspring of community controls (CcO) (N = 101) were assessed using the Revised Dimensions of Temperament Survey. The association between temperament dimensions and lifetime psychopathology (including threshold and subthreshold DSM-IV-TR diagnoses) and current socio-academic adjustment was assessed using logistic regression. Fully adjusted models showed that both BpO and SzO scored significantly lower in the positive mood dimension and in the adaptability factor than CcO, with small-medium effect sizes (Cohen’s d ~ 0.3-0.5). BpO also scored lower in the activity factor and the activity dimensions than CcO (Cohen’s d ~ 0.3). Lower scores in the positive mood dimension were associated with increased risk of impaired adjustment both in BpO [OR 2.30, 95% CI (1.18-4.46)] and in SzO [OR 2.87, 95% CI (1.07-7.66)]. In BpO, lower scores in positive mood were also associated with increased likelihood of internalizing [OR 1.84, 95% CI (1.28-2.64)] and externalizing disorders [OR 1.48, 95% CI (1.01-2.18)]; in SzO, higher scores in activity and flexibility were associated with increased likelihood of internalizing [OR 2.31, 95% CI (1.22-4.38)] and externalizing disorders [OR 3.28, 95% CI (1.2-9)], respectively. Early difficulties in emotion regulation might represent a shared vulnerability phenotype in BpO and SzO. The identification of extreme temperament traits could help to characterize subgroups at greater risk of psychopathology and impaired adjustment, in which targeted interventions are warranted. [ABSTRACT FROM AUTHOR]

To analyze the efficacy of Green Light photoselective vaporization of the prostate (PVP) in elderly high-risk benign prostatic hyperplasia (BPH) patients with glands over 80 ml. From December 2013 to February 2016, we allocated 84 elderly (age 71-97) high-risk patients who underwent preoperative transrectal ultrasound (TRUS) examination with glands over 80 ml and divided them into two groups to receive 120 W (n = 40) and 180 W (n = 44) PVP. All the patients have been observed at least one intraoperative comorbidity: hypertension, diabetes mellitus, NYHA II, or combined. They were followed up for 12 months. All the conventional parameters were compared in this study. All the patients received successful operations without severe complications, and no patient needed blood transfusion. The operation time and catheterization time of the 180 W patients were significantly shorter than that of the 120 W patients (p < 0.05). The International Prostate Symptom Scores (IPSS), quality of life (QoL) scores, maximum flow rate (Qmax), and residual urine volume (RUV) in both groups have been significantly improved. PVP is safe and effective for high-risk aging patients with gland over 80 ml. In addition, 180 W XPS system has a short operation time and catheterization time and less inflammatory response. [ABSTRACT FROM AUTHOR]

Hintergrund: Die präoperative Konditionierung vor komplexen viszeralonkologischen Operationen nimmt eine immer wichtigere Rolle ein.Ziel der Arbeit: Ziel dieser Arbeit ist die Darstellung von Spezialsituationen der Präkonditionierung bei viszeralonkologischen Patienten. Als Spezialsituation mit konsekutiv erhöhtem Risikoprofil wurden folgende Bedingungen definiert: Kardiopulmonale Begleiterkrankungen, der geriatrische Patient, neoadjuvante Therapie und simultane Fatigue.Material und Methoden: Es erfolgte eine selektive Literaturübersicht, basierend auf einer Recherche in den elektronischen Datenbanken MEDLINE, PubMed, Cochrane Library und ISRCTN (International Standard Randomization Controlled Trial Number).Ergebnisse: Die Identifikation von Hochrisikopatienten ist essenzieller Bestandteil der anästhesiologischen Evaluation vor einem chirurgischen Eingriff. Dabei wird neben dem kardiovaskulären auch das pulmonale Risikoprofil mittels Prädiktionsindizes und der Erfassung patienten- und eingriffsspezifischer Risikofaktoren erhoben. Der vermehrte Einsatz neuer oraler Antikoagulanzien und einer dualen Thrombozytenaggregationshemmung erfordert individuelle Behandlungsstrategien. Zahlreiche Studien belegen klinisch relevante Effekte bewegungstherapeutischer Interventionen über alle Phasen der onkologischen Behandlung. Neben positiven Einflüssen auf therapieassoziierte Nebenwirkungen kann Sport auch bei Krebspatienten Auswirkungen von Bewegungsmangel entgegenwirken und die gesundheitsspezifische Lebensqualität verbessern. Die Wirksamkeit von Sport- und Bewegungstherapien sowie psychologischen Interventionen bei onkologischen Patienten mit Fatigue (CRF) ist breit, wobei wichtige Bausteine die Motivation und Compliance sind.Diskussion: Bei Risikopatienten ist ein interdisziplinäres Vorgehen der Planung und Durchführung der Prähabilitation essenziell, um perioperative Risikofaktoren und potenzielle Komplikationen frühzeitig zu erkennen und zu optimieren mit dem Ziel einer schnelleren Rekonvaleszenz, reduzierten Morbidität und Mortalität sowie auch der Möglichkeit eines verbesserten Langzeitüberlebens und einer gesteigerten Lebensqualität. [ABSTRACT FROM AUTHOR]

Haplo-identical transplants (Haplo-Tx) are an important alternative for patients with hematological malignancies who lack a HLA-identical donor. Seventy-one T-replete Haplo-Tx were performed in 70 high-risk patients at our center; 22/70 (31%) patients with refractory/relapsed leukemia received sequential salvage therapy (SeqTh) with high-dose chemotherapy followed by Haplo-Tx during the chemotherapy-induced neutropenia. Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (days + 3 and + 4) with tacrolimus and mycophenolic acid. After a median follow-up of 29.2 months, 3-year overall survival (OS) and event-free survival (EFS) were 43.8 and 40.2%, while 3-year cumulative incidences (CIs) of non-relapse mortality (NRM) and relapse (RI) were 27 and 33%. Day 100 and day 400 CI of grade III-IV acute and moderate-severe chronic GVHD were 11 and 15%. Three-year RI was significantly lower in patients in complete remission (CR) versus those not in CR at the time of transplant (21.5 vs. 48%, p = 0.009) and in patients who received PBSC as compared to BM (22 vs. 45%, p = 0.009). In patients treated with SeqTh, 3-year OS was 19%, while 3-year RI and NRM were 52 and 28% at a median follow-up of 50 months. Overall, Haplo-Tx was feasible in heavily pretreated high-risk patients without a suitable HLA-identical donor. [ABSTRACT FROM AUTHOR]

Background: The Japanese Children’s Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies.Methods: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy.Results: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification.Conclusions: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort. [ABSTRACT FROM AUTHOR]

Odor identification deficits are well documented in patients with schizophrenia, but it remains unclear whether individuals at clinical high-risk for psychosis exhibit similar changes and whether their olfactory function is related to social/cognitive functions and symptomatology. In this study, we investigated odor detection sensitivity and identification ability in 32 individuals with at-risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls using a T&T olfactometer. The ARMS and schizophrenia subjects were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) to assess their cognitive and social functions, and the Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS and schizophrenia subjects had lower odor identification ability when compared with healthy controls, while no significant difference was found in the odor detection sensitivity. The lower odor identification ability in the ARMS group correlated with the severity of negative symptoms and weakly correlated with lower performance on the BACS verbal fluency test. The olfactory measures of schizophrenia patients did not correlate with illness duration, medication, symptom severity, and social and cognitive functions. For the ARMS and schizophrenia groups, the olfactory measures did not correlate with the SOFAS and SCoRS scores. These findings suggest that high-risk subjects for psychosis already show odor identification deficits similar to those observed in schizophrenia patients, which probably reflect a biological trait related to vulnerability to psychosis. [ABSTRACT FROM AUTHOR]

We integrated multiple behavioural and developmental measures from multiple time-points using machine learning to improve early prediction of individual Autism Spectrum Disorder (ASD) outcome. We examined Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales, and early ASD symptoms between 8 and 36 months in high-risk siblings (HR; n = 161) and low-risk controls (LR; n = 71). Longitudinally, LR and HR-Typical showed higher developmental level and functioning, and fewer ASD symptoms than HR-Atypical and HR-ASD. At 8 months, machine learning classified HR-ASD at chance level, and broader atypical development with 69.2% Area Under the Curve (AUC). At 14 months, ASD and broader atypical development were classified with approximately 71% AUC. Thus, prediction of ASD was only possible with moderate accuracy at 14 months. [ABSTRACT FROM AUTHOR]

Background: Data from randomized trials evaluating the efficacy of on- versus off-pump coronary artery bypass grafting remain inconclusive, particularly in high-risk populations.Aims: The aim of this study is to compare the outcomes associated with on- versus off-pump coronary artery bypass grafting among high-risk patients.Methods: We performed a meta-analysis of randomized control trials comparing on- versus off-pump coronary artery bypass grafting, focusing on high-risk populations. Studies focusing on “high-risk” features: European System of Cardiac Operative Risk Evaluation (EuroSCORE) ≥ 5, age > 70 years, preexisting renal insufficiency, history of stroke(s), and the presence of left ventricular dysfunction were included. MEDLINE, Scopus, and Embase were searched for all publications between January 1, 2000 and August 1, 2016, using the following terms: on-pump, off-pump, coronary artery bypass, high-risk, left ventricular dysfunction, elderly, aged, and renal insufficiency. Endpoints included cardiovascular and all-cause mortality, non-fatal myocardial infarction, stroke, need for revascularization, renal failure, and length of hospital stay.Results: Nine studies incorporating 11,374 patients with a mean age of 70 years were selected. There was no statistical difference in cardiovascular mortality, all-cause mortality, non-fatal myocardial infarction, and renal failure between the two groups. There was a decrease in further revascularization at 1 year with on-pump (OR 0.67 (0.50-0.89)). However, there was an increase in length of hospital stay by 2.24 days (p = 0.03) among the on-pump group with no difference in stroke (OR 1.34 (1.00-1.80)).Conclusions: On-pump is associated with a decreased risk of additional revascularization by 1 year. However, this appears to be a cost of longer hospitalization. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have reported that peri-procedural administration of rectal indomethacin reduces the risk of pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Based on these studies, gastrointestinal (GI) societies recommend prophylactic rectal indomethacin for all patients undergoing ERCP. However, recent studies have reported contradictory results. The aim of this study was to perform a systematic review and meta-analysis to estimate the pooled relative risk (RR) of post-ERCP pancreatitis (PEP) in unselected patients who received rectal indomethacin before the ERCP (pre-ERCP) compared to patients who received pre-ERCP rectal placebo.Methods: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through September 1, 2017) to identify randomized control trials (RCTs) investigating the role of pre-ERCP rectal indomethacin in reducing the risk of PEP in unselected patients undergoing ERCP. The databases included Ovid, Medline, In-Process, and Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science. We calculated a pooled estimate of the RR of PEP in patients who received pre-ERCP rectal indomethacin compared to patients who received pre-ERCP rectal placebo. The meta-analysis was performed using the random effects model.Results: Six RCTs with a total of 2229 patients were included in the final meta-analysis. There were 1143 patients in the rectal indomethacin group and 1086 patients in the rectal placebo group. There were 71 events of PEP in the rectal indomethacin group and 114 events of PEP in the rectal placebo group. Pre-ERCP administration of rectal indomethacin significantly reduced the risk of PEP compared to pre-ERCP rectal placebo (RR 0.60, 95% CI, 0.45-0.80; p<0.0001). There was no heterogeneity between the studies (I2 = 0).Conclusion: The results of this meta-analysis support the routine pre-ERCP administration of rectal indomethacin in unselected patients to prevent PEP. [ABSTRACT FROM AUTHOR]

Children who live in the context of maternal incarceration (MI) are exposed to both general environmental risk and incarceration-specific risk increasing the probability of their developing externalizing and internalizing behaviors problems. Little research has examined the socio-emotional mechanisms that account for the psychological effects of MI. This research examined children's anger and sadness regulation as mediators between environmental and incarceration-specific risk and psychological functioning. Participants were 117 children (60% Black; 52% boys; M age = 9.85 years, SD = 1.65 years), their incarcerated mother, and current caregiver. All informants completed questionnaires assessing children's anger and sadness regulation as well as externalizing and internalizing behaviors. Mothers and caregivers provided information concerning children's exposure to environmental risk and all three reporters provided information on incarceration-specific risk experiences (ISRE). Structural equation modeling was used to test indirect effects of risk variables (ISRE, environmental) on psychological functioning (externalizing, internalizing behaviors) via emotion regulation (anger, sadness). Gender, age, and race were covariates. The analyses revealed significant indirect effects of incarceration-specific risk on both externalizing and internalizing behavior problems via anger regulation but not via sadness regulation. The findings highlight the centrality of emotion regulation as a mechanism that helps explain the negative psychological outcomes experienced by children exposed to ISRE with implications for preventive interventions. [ABSTRACT FROM AUTHOR]

We assessed trends in HIV testing outcomes during a period of clinic-based initiatives introduced to increase HIV testing among gay and bisexual men (GBM) attending sexual health clinics (SHCs) in New South Wales (NSW). A cohort of 25,487 HIV-negative GBM attending 32 SHCs in NSW (2009–2015) was classified into six sub-groups each year based on client-type (new/existing), risk-status (low/high-risk), and any recent HIV testing. Poisson regression methods were used to assess HIV testing outcomes in sub-groups of GBM. HIV testing outcomes and the sub-groups with greatest statistically significant annual increases were: individuals attending (26% in high-risk existing clients with recent testing); testing uptake (4% in low-risk existing clients with no recent testing); testing frequency (6% in low-risk existing clients with no recent testing and 5% in high-risk existing clients with recent testing); and total tests (31% in high-risk existing clients with recent testing). High-risk existing clients with recent testing had a 13% annual increase in the proportional contribution to total tests. Our findings show improved targeting of testing to high-risk GBM at NSW SHCs. The clinic-based initiatives should be considered for translation to other similar settings. [ABSTRACT FROM AUTHOR]

Background: Relatively little is known about the onset of bipolar disorder, yet the early illness course is already associated with significant morbidity and mortality. Therefore, characterizing the bipolar illness trajectory is key to risk prediction and early intervention advancement. Main body: In this narrative review, we discuss key findings from prospective longitudinal studies of the high-risk offspring of bipolar parents and related meta-analyses that inform us about the clinical trajectory of emerging bipolar disorder. Challenges such as phenotypic and etiologic heterogeneity and the non-specificity of early symptoms and syndromes are highlighted. Implications of the findings for both research and clinical practice are discussed. Conclusion: Bipolar disorder in young people at familial risk does not typically onset with a hypomanic or manic episode. Rather the first activated episode is often preceded by years of impairing psychopathological states that vary over development and across emerging bipolar subtype. Taking heterogeneity into account and adopting a more comprehensive approach to diagnosis seems necessary to advance earlier identification and our understanding of the onset of bipolar disorder. [ABSTRACT FROM AUTHOR]

Purpose: The benefits of robotic-assisted radical cystectomy (RARC) are unclear, especially in patients with high-risk disease (pT3/T4). We evaluated pathological and postoperative outcomes of RARC versus open radical cystectomy (ORC) in these patients. Methods: We identified bladder cancer patients treated with RARC or ORC from January 2010-August 2014. Clinicodemographic factors were examined for potential confounding. Our primary outcome of interest was positive soft-tissue surgical margins (STSMs). Secondary outcomes included post-operative complications and length of stay (LOS). We used logistic regression to define the association between clinical factors with outcomes of interest, focusing on patients with locally advanced disease. Results: We identified 472 patients treated with ORC (407, 86.2 %) or RARC (65, 13.8 %) of which 215 (45.6 %) were high-risk cases based on advanced pathologic stage (pT3/4). RARC patients were more commonly men (96.9 vs. 73.2 %, p < 0.01), had better performance status (ECOG 0, 78.5 vs. 59.7 %, p = 0.031), and received less neoadjuvant chemotherapy (21.5 vs. 39.3 %, p = 0.006). Total (52.3 vs. 59.7 %, p = 0.26) and high-grade complication rates (13.8 vs. 19.7 %, p = 0.27) were similar, but median LOS was shorter after RARC (6 vs. 7 days, p < 0.01). On multivariate analysis, prior pelvic radiation (OR: 4.78, 95 % CI: 2.16-10.57), and advanced tumor stage (OR: 3.06, 95 % CI: 1.56-6.03) were independently associated with positive STSMs in high-risk patients but robotic surgical approach was not (OR: 0.81, 95 % CI: 0.29-2.30; p = 0.69). Conclusion: RARC had similar short-term postoperative outcomes compared to ORC and did not compromise oncological control in patients with extravesical disease. [ABSTRACT FROM AUTHOR]

Introduction: The REGAL (RSV evidence-a geographical archive of the literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This third publication covers the risk and burden of RSV infection in infants with chronic lung disease (CLD), formerly called bronchopulmonary dysplasia (BPD). Methods: A systematic review was undertaken of publications between January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov. Studies reporting data for hospital visits/admissions for RSV infection among infants with CLD/BPD who were not prophylaxed, as well as studies reporting RSV-associated morbidity, mortality, and healthcare costs, were included. Burdens of disease data were compared with preterm infants without CLD/BPD, other high-risk groups and term infants. Study quality and strength of evidence (SOE) were graded using recognized criteria. Results: A total of 1837 studies were identified and 39 were included. CLD/BPD is a significant independent risk factor for RSV hospitalization [RSVH (odds ratio 2.2-7.2); high SOE]. Infants and young children with CLD/BPD had high RSVH rates which were generally similar in Europe, the United States, and Canada, mostly varying between 12 and 21%. Infants with CLD also had a longer length of hospital stay than other high-risk groups and term infants (high SOE). On average, infants spent 4-11 days in hospital (moderate SOE). Once hospitalized for RSV, affected children were at risk for a more severe course of disease than children with no RSVH (moderate SOE). Conclusion: Severe RSV infection in infants and young children with CLD/BPD poses a significant health burden in Western countries. Further studies focussing on the burden of RSV infection in this well-recognized population at high risk for severe disease are needed to help improve outcomes and plan allocation of healthcare resources. Funding: AbbVie. [ABSTRACT FROM AUTHOR]

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