A multicenter, randomized phase 2 study to establish combinations of CBP501, cisplatin and nivolumab for ≥3rd-line treatment of patients with advanced pancreatic adenocarcinoma.

BACKGROUND: There is no standard of care for ≥ 3rd-line treatment of metastatic pancreatic adenocarcinoma (PDAC). CBP501 is a novel calmodulin-binding peptide that has been shown to enhance the influx of platinum agents into tumor cells and tumor immunogenicity. This study aimed to (1) confirm efficacy of CBP501/cisplatin/nivolumab for metastatic PDAC observed in a previous phase 1 study, (2) identify combinations that yield 35% 3-month progression-free survival rate (3MPFS) and (3) define the contribution of CBP501 to the effects of combination therapy. METHODS: CBP501 16 or 25 mg/m2 (CBP(16) or CBP(25)) was combined with 60 mg/m2 cisplatin (CDDP) and 240 mg nivolumab (nivo), administered at 3-week intervals. Patients were randomized 1:1:1:1 to (1) CBP(25)/CDDP/nivo, (2) CBP(16)/CDDP/nivo, (3) CBP(25)/CDDP and (4) CDDP/nivo, with randomization stratified by ECOG PS and liver metastases. A Fleming two-stage design was used, yielding a one-sided type I error rate of 2.5% and 80% power when the true 3MPFS is 35%. RESULTS: Among 36 patients, 3MPFS was 44.4% in arms 1 and 2, 11.1% in arm 3% and 33.3% in arm 4. Two patients achieved a partial response in arm 1 (ORR 22.2%; none in other arms). Median PFS and OS were 2.4, 2.1, 1.5 and 1.5 months and 6.3, 5.3, 3.7 and 4.9 months, respectively. Overall, all treatment combinations were well tolerated. Most treatment-related adverse events were grade 1-2. CONCLUSIONS: The combination CBP(25)/(16)/CDDP/nivo demonstrated promising signs of efficacy and a manageable safety profile for the treatment of advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT04953962.

Patient-reported outcomes before treatment for localized prostate cancer: are there differences among countries? Data from the True North Global Registry.

INTRODUCTION: Similar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison. METHODS: We analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance. RESULTS: The sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians' differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions. CONCLUSIONS: Patients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries. The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments' effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.

Optical coherence tomography angiography findings in retinal cavernous hemangioma: New cases and review of the literature.

INTRODUCTION: Retinal cavernous hemangioma (RCH) is a rare retinal vascular disease characterized by grape-like clusters of saccular aneurysms, usually unilateral, asymptomatic and non-progressive. The diagnosis is made by multimodal imaging including conventional fluorescein angiography (FA). The recent introduction of swept source optical coherence tomography angiography (SS-OCTA) has allowed new insight into vascular diseases, allowing non-invasive, more precise visualization of retinal and choroidal blood flow, and represents a possible alternative to FA. METHODS: We herein describe two cases of RCH with multimodal imaging, including SS-OCTA, and compare our findings with those previously described. RESULTS: On OCTA, the presence of a draining vessel, a reduction in flow signal in the SCP and DCP, and a fluid level can be observed. CONCLUSION: These OCTA signs are in accordance with those described on conventional fluorescein angiography, allowing this invasive exam to be avoided in typical cases.

Pesticides as a potential independent childhood leukemia risk factor and as a potential confounder for electromagnetic fields exposure.

BACKGROUND: Both pesticides and high magnetic fields are suspected to be childhood leukemia risk factors. Pesticides are utilized at commercial plant nurseries, which sometimes occupy the areas underneath high-voltage powerlines. OBJECTIVES: To evaluate whether potential pesticide exposures (intended use, chemical class, active ingredient) utilized at plant nurseries act as an independent childhood leukemia risk factor or as a confounder for proximity to, or magnetic fields exposure from, high-voltage powerlines. METHODS: We conducted a state-wide records-based case-control study for California with 5788 childhood leukemia cases and 5788 controls that examined specific pesticide use, magnetic field exposures and distances to both powerlines and plant nurseries. Exposure assessment incorporated geographic information systems, aerial satellite images, and other historical information. RESULTS: Childhood leukemia risk was potentially elevated for several active pesticide ingredients: permethrin (odds ratio (OR) 1.49, 95% confidence interval (CI) (0.83-2.67), chlorpyrifos (OR 1.29, 95% CI 0.89-1.87), dimethoate (OR 1.79, 95% CI 0.85-3.76), mancozeb (OR 1.41, 95% CI 0.85-2.33), oxyfluorfen (OR 1.41, 95% CI 0.75-2.66), oryzalin (OR 1.60, 95% CI 0.97-2.63), and pendimethalin (OR 1.82, 95% CI 0.81-2.25). Rodenticide (OR 1.42, 95% CI 0.78-2.56) and molluscicide (OR 1.22, 95% CI 0.82-1.81) exposure also presented potentially elevated childhood leukemia risks. Childhood leukemia associations with calculated fields or powerline proximity did not materially change after adjusting for pesticide exposure. Childhood leukemia risks with powerline proximity remained similar when pesticide exposures were excluded. DISCUSSION: Pesticide exposure may be an independent childhood leukemia risk factor. Childhood leukemia risks for powerline proximity and magnetic fields exposure were not explained by pesticide exposure.

Soft Tissue Sarcomas in Octogenarian Patients: Are Treatment Options and Oncological Outcomes Different? A SEER Retrospective Study.

AIMS: As the US population continues to age, oncological strategies and outcomes for soft tissue sarcomas (STSs) should continue to be examined for varying age groups. The aim of this study was analyse and compare treatment strategies and oncological outcomes for octogenarian patients with STSs. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology and End Results (SEER) national database were used. Varying treatment modalities were studied when utilised for specific tumour staging with respect to the eighth edition of the American Joint Committee on Cancer. RESULTS: In total, 24 666 patients were included for analysis, where 3341 (14%) were 80 years old or older. The octogenarian group was diagnosed with more advanced disease (stages II-IV), relative to their younger counterparts (85% versus 75%, P < 0.001). However, a smaller proportion of the older patients underwent surgical resection (74% versus 86%, P < 0.001). Likewise, the octogenarians received less chemotherapy (4% versus 21%, P < 0.001) and radiotherapy (29% versus 42%, P = 0.010). Surgical resection and chemotherapy significantly improved overall survival for those older patients with stage II STS, whereas surgical resection and radiotherapy improved mortality in this cohort with both stage III and IV STS. Overall survival at 1 and 5 years of follow-up was lower within the octogenarian group compared with the younger group (1 year: 68% versus 88%, P < 0.001 and 5 years: 7% versus 58%, P < 0.001). CONCLUSIONS: Octogenarian patients, in most cases, are diagnosed with stage III or metastatic disease. Surgical resection of the primary tumour was beneficial in both age cohorts, with radiotherapy correlating to better overall survival when used in those patients with higher stage STS. Chemotherapy was associated with better mortality in the younger cohort with respect to tumour stage. The octogenarian overall survival at 1 and 5 years was lower than for younger patients.

Mathematical models to describe the growth curves of Vietnamese Ri chicken / Modelos matemáticos para descrever as curvas de crescimento do frango Ri vietnamita

Ri chicken is the most popular backyard chicken breed in Vietnam, but little is known about the growth curve of this breed. This study compared the performances of models with three parameters (Gompertz, Brody, and Logistic) and models containing four parameters (Richards, Bridges, and Janoschek) for describing the growth of Ri chicken. The bodyweight of Ri chicken was recorded weekly from week 1 to week 19. Growth models were fitted using minpack.lm package in R software and Akaike’s information criterion (AIC), Bayesian information criterion (BIC), and root mean square error (RMSE) were used for model comparison. Based on these criteria, the models having four parameters showed better performance than the ones with three parameters, and the Richards model was the best one for males and females. The lowest and highest value of asymmetric weights (α) were obtained by Bridges and Brody models for each of sexes, respectively. Age and weight estimated by the Richard model were 8.46 and 7.51 weeks and 696.88 and 487.58 g for males and for females, respectively. Differences in the growth curves were observed between males and female chicken. Overall, the results suggested using the Richards model for describing the growth curve of Ri chickens. Further studies on the genetics and genomics of the obtained growth parameters are required before using them for the genetic improvement of Ri chickens.

O frango Ri é a raça de frango de quintal mais popular do Vietnã, mas pouco se sabe sobre a curva de crescimento dessa raça. Este estudo comparou o desempenho de modelos com três parâmetros (Gompertz, Brody e Logistic) e modelos contendo quatro parâmetros (Richards, Bridges e Janoschek) para descrever o crescimento do frango Ri. O peso corporal do frango Ri foi registrado semanalmente da semana 1 à semana 19. Os modelos de crescimento foram ajustados usando o pacote minpack.lm no software R e o critério de informação de Akaike (AIC); critério de informação bayesiano (BIC) e erro quadrático médio (RMSE) foram usados para comparação de modelos. Com base nesses critérios, os modelos com quatro parâmetros apresentaram melhor desempenho do que os com três parâmetros, sendo o modelo de Richards o melhor para homens e mulheres. O menor e o maior valor dos pesos assimétricos (α) foram obtidos pelos modelos Bridges e Brody para cada um dos sexos, respectivamente. A idade e o peso estimados pelo modelo de Richard foram de 8,46 e 7,51 semanas e 696,88 e 487,58 g para homens e mulheres, respectivamente. Diferenças nas curvas de crescimento foram observadas entre frangos machos e fêmeas. No geral, os resultados sugeriram o uso do modelo de Richards para descrever a curva de crescimento de frangos Ri. Mais estudos sobre a genética e genômica dos parâmetros de crescimento obtidos são necessários antes de usá-los para o melhoramento genético de frangos Ri.

Mathematical models to describe the growth curves of Vietnamese Ri chicken

Abstract Ri chicken is the most popular backyard chicken breed in Vietnam, but little is known about the growth curve of this breed. This study compared the performances of models with three parameters (Gompertz, Brody, and Logistic) and models containing four parameters (Richards, Bridges, and Janoschek) for describing the growth of Ri chicken. The bodyweight of Ri chicken was recorded weekly from week 1 to week 19. Growth models were fitted using minpack.lm package in R software and Akaikes information criterion (AIC), Bayesian information criterion (BIC), and root mean square error (RMSE) were used for model comparison. Based on these criteria, the models having four parameters showed better performance than the ones with three parameters, and the Richards model was the best one for males and females. The lowest and highest value of asymmetric weights () were obtained by Bridges and Brody models for each of sexes, respectively. Age and weight estimated by the Richard model were 8.46 and 7.51 weeks and 696.88 and 487.58 g for males and for females, respectively. Differences in the growth curves were observed between males and female chicken. Overall, the results suggested using the Richards model for describing the growth curve of Ri chickens. Further studies on the genetics and genomics of the obtained growth parameters are required before using them for the genetic improvement of Ri chickens.

Resumo O frango Ri é a raça de frango de quintal mais popular do Vietnã, mas pouco se sabe sobre a curva de crescimento dessa raça. Este estudo comparou o desempenho de modelos com três parâmetros (Gompertz, Brody e Logistic) e modelos contendo quatro parâmetros (Richards, Bridges e Janoschek) para descrever o crescimento do frango Ri. O peso corporal do frango Ri foi registrado semanalmente da semana 1 à semana 19. Os modelos de crescimento foram ajustados usando o pacote minpack.lm no software R e o critério de informação de Akaike (AIC); critério de informação bayesiano (BIC) e erro quadrático médio (RMSE) foram usados para comparação de modelos. Com base nesses critérios, os modelos com quatro parâmetros apresentaram melhor desempenho do que os com três parâmetros, sendo o modelo de Richards o melhor para homens e mulheres. O menor e o maior valor dos pesos assimétricos () foram obtidos pelos modelos Bridges e Brody para cada um dos sexos, respectivamente. A idade e o peso estimados pelo modelo de Richard foram de 8,46 e 7,51 semanas e 696,88 e 487,58 g para homens e mulheres, respectivamente. Diferenças nas curvas de crescimento foram observadas entre frangos machos e fêmeas. No geral, os resultados sugeriram o uso do modelo de Richards para descrever a curva de crescimento de frangos Ri. Mais estudos sobre a genética e genômica dos parâmetros de crescimento obtidos são necessários antes de usá-los para o melhoramento genético de frangos Ri.

Mathematical models to describe the growth curves of Vietnamese Ri chicken / Modelos matemáticos para descrever as curvas de crescimento do frango Ri vietnamita

Abstract Ri chicken is the most popular backyard chicken breed in Vietnam, but little is known about the growth curve of this breed. This study compared the performances of models with three parameters (Gompertz, Brody, and Logistic) and models containing four parameters (Richards, Bridges, and Janoschek) for describing the growth of Ri chicken. The bodyweight of Ri chicken was recorded weekly from week 1 to week 19. Growth models were fitted using minpack.lm package in R software and Akaike's information criterion (AIC), Bayesian information criterion (BIC), and root mean square error (RMSE) were used for model comparison. Based on these criteria, the models having four parameters showed better performance than the ones with three parameters, and the Richards model was the best one for males and females. The lowest and highest value of asymmetric weights (α) were obtained by Bridges and Brody models for each of sexes, respectively. Age and weight estimated by the Richard model were 8.46 and 7.51 weeks and 696.88 and 487.58 g for males and for females, respectively. Differences in the growth curves were observed between males and female chicken. Overall, the results suggested using the Richards model for describing the growth curve of Ri chickens. Further studies on the genetics and genomics of the obtained growth parameters are required before using them for the genetic improvement of Ri chickens.

Resumo O frango Ri é a raça de frango de quintal mais popular do Vietnã, mas pouco se sabe sobre a curva de crescimento dessa raça. Este estudo comparou o desempenho de modelos com três parâmetros (Gompertz, Brody e Logistic) e modelos contendo quatro parâmetros (Richards, Bridges e Janoschek) para descrever o crescimento do frango Ri. O peso corporal do frango Ri foi registrado semanalmente da semana 1 à semana 19. Os modelos de crescimento foram ajustados usando o pacote minpack.lm no software R e o critério de informação de Akaike (AIC); critério de informação bayesiano (BIC) e erro quadrático médio (RMSE) foram usados ​​para comparação de modelos. Com base nesses critérios, os modelos com quatro parâmetros apresentaram melhor desempenho do que os com três parâmetros, sendo o modelo de Richards o melhor para homens e mulheres. O menor e o maior valor dos pesos assimétricos (α) foram obtidos pelos modelos Bridges e Brody para cada um dos sexos, respectivamente. A idade e o peso estimados pelo modelo de Richard foram de 8,46 e 7,51 semanas e 696,88 e 487,58 g para homens e mulheres, respectivamente. Diferenças nas curvas de crescimento foram observadas entre frangos machos e fêmeas. No geral, os resultados sugeriram o uso do modelo de Richards para descrever a curva de crescimento de frangos Ri. Mais estudos sobre a genética e genômica dos parâmetros de crescimento obtidos são necessários antes de usá-los para o melhoramento genético de frangos Ri.

[Radiation-induced retinopathy: actual knowledge and new concepts]. / La rétinopathie radique : données actuelles et perspectives.

Radiation retinopathy is an occlusive vascular pathology following radiotherapy, generally targeted on the eye or peri-ocular structures. Despite increasingly precise techniques (stereotactic radiosurgery, proton therapy, etc.), the inclusion of the retina in the radiation field is sometimes unavoidable. This can lead to a severe pathology, which can ultimately cause blindness or even the anatomical loss of the eye when neovascular glaucoma occurs, due to the abnormal proliferation of neovessels. Radiation retinopathy have been described for more than a century, but it has recently seen great advances in both diagnosis and treatment. The advances of efficient and less invasive examinations in our clinical practice, such as OCT-angiography, allows for easier screening and diagnosis at earlier stages. Thus a new approach to the pathology is necessary, first of all through new definitions and classifications including previously undetected minimal forms. Furthermore, the recent appearance of intravitreal therapies by injection of anti-VEGF or dexamethasone implants has drastically changed the visual prognosis of these patients, who were previously treated only by retinal photocoagulation of the ischaemic areas. Recent studies have even shown the effectiveness of these new molecules in preventing the development of radiation retinopathy. This review of the literature provides an update on this disease and details how these recent diagnostic and therapeutic developments may play a role in the management of this complication.

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study.

BACKGROUND: Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. METHODS: We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. RESULTS: We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). CONCLUSION: Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

To mask or not to mask mosaicism? The impact of reporting embryo mosaicism on reproductive potential.

PURPOSE: To evaluate euploidy rates and probability of having at least one euploid embryo for transfer per cycle when mosaicism is reported compared to when it is masked. METHODS: Women age 18-46 years who underwent PGT-A with next generation sequencing of blastocyst biopsies were analyzed. When reported, mosaic embryos were classified as low-level, 20-40% mosaic, or high-level, 41-80% mosaic. When masked, low-level mosaics were categorized as euploid and high-level mosaics were considered aneuploid. Comparative analyses were performed with χ2 tests and t-tests. RESULTS: A total of 22,504 PGT-A biopsy cycles from 18,401 patients were included. These cycles were from 293 different clinics with a mean of 1.22 cycles per patient. The majority of cycles (94.8%) reported mosaicism, and only 5.2% cycles were masked. The euploidy rate was significantly lower when mosaicism was reported versus masked (38.7% v 47.4%, p < 0.0001), which remained significant for age 40 years old and younger. The mosaic reporting cohort was less likely to have at least one euploid embryo for transfer (68.8%) compared to the masked cohort (75.7%) (p < 0.0001); however, this was no longer significant after stratification by age. CONCLUSION: Mosaicism reporting shows an overall expected reduction in euploidy rate. In turn, the probability of having a euploid embryo to transfer depends on clinic transfer practices and patient preference. If mosaic embryos are not transferred, we observe a reduction in probability of having an embryo for transfer. Although the magnitude of these differences is small, our data show that mosaic reporting may contribute to embryo attrition rate.

Commercial outdoor plant nurseries as a confounder for electromagnetic fields and childhood leukemia risk.

BACKGROUND: Close residential proximity to powerlines and high magnetic fields exposure may be associated with elevated childhood leukemia risks as reported by prior studies and pooled analyses. Magnetic fields exposure from high-voltage powerlines is associated with proximity to these powerlines and consequently with any factor varying with distance. Areas underneath powerlines in California may be sites for commercial plant nurseries that can use pesticides, a potential childhood leukemia risk factor. OBJECTIVES: Assess if potential pesticide exposure from commercial plant nurseries is a confounder or interacts with proximity or magnetic fields exposure from high-voltage powerlines to increase childhood leukemia risk. METHODS: A comprehensive childhood leukemia record-based case-control study with 5788 cases and 5788 controls (born and diagnosed in California, 1986-2008) was conducted. Pesticide, powerline, and magnetic field exposure assessment utilized models that incorporated geographical information systems, aerial satellite images, site visits and other historical information. RESULTS: The relationship for calculated fields with childhood leukemia (odds ratio (OR) 1.51, 95% confidence interval (CI) 0.70-3.23) slightly attenuated when controlling for nursery proximity (OR 1.43, 95% CI 0.65-3.16) or restricting analysis to subjects living far (>300 m) from nurseries (OR 1.43, 95% CI 0.79-2.60). A similar association pattern was observed between distance to high-voltage powerlines and childhood leukemia. The association between nursery proximity and childhood leukemia was unchanged or only slightly attenuated when controlling for calculated fields or powerline distance; ORs remained above 2 when excluding subjects with high calculated fields or close powerline proximity (OR 2.16, 95% CI 0.82-5.67 and OR 2.15, 95% CI 0.82-5.64, respectively). The observed relationships were robust to different time periods, reference categories, and cut points. DISCUSSION: Close residential proximity to nurseries is suggested as an independent childhood leukemia risk factor. Our results do not support plant nurseries as an explanation for observed childhood leukemia risks for powerline proximity and magnetic fields exposure, although small numbers of subjects concurrently exposed to high magnetic fields, close powerline proximity and plant nurseries limited our ability to fully assess potential confounding.

Secretion and uptake of copper via a small copper carrier in blood fluid.

Studies with Wilson disease model mice that accumulate excessive copper, due to a dysfunctional ATP7B "copper pump" resulting in decreased biliary excretion, showed that the compensatory increase in urinary copper loss was due to a small copper carrier (∼1 kDa) (SCC). We show here that SCC is also present in the blood plasma of normal and Wilson disease model mice and dogs, as determined by ultrafiltration and size exclusion chromatography (SEC). It is secreted by cultured hepatic and enterocytic cells, as determined by pretreatment with 67Cu nitrilotriacetate (NTA) or nonradioactive 5-10 µM Cu-NTA, and collecting and examining 3 kDa ultrafiltrates of the conditioned media, where a single major copper peak is detected by SEC. Four different cultured cell types exposed to the radiolabeled SCC all took up the 67Cu at various rates. Rates differed somewhat when uptake was from Cu-NTA. Uptake of SCC-67Cu was inhibited by excess nonradioactive Cu(I) or Ag(I) ions, suggesting competition for uptake by copper transporter 1 (CTR1). Knockout of CTR1 in fibroblasts reduced uptake rates by 60%, confirming its participation, but also involvement of other transporters. Inhibitors of endocytosis, or an excess of metal ions taken up by divalent metal transporter 1, did not decrease SCC-67Cu uptake. The results imply that SCC may play a significant role in copper transport and homeostasis, transferring copper particularly from the liver (but also intestinal cells) to other cells within the mammalian organism, as well as spilling excess into the urine in copper overload-as an alternative means of copper excretion.

Xanthogranulomatous cholecystitis: Diagnosis and management.

Xanthogranulomatous cholecystitis (XGC) is a rare form of cholecystitis, characterized by the presence of xanthogranuloma, prominent yellow structures within the gallbladder wall that is very often lithiasic. When XGC presents in its pseudo-tumoral form with occasional adjacent organ involvement, it can mimic gallbladder carcinoma (GBC). The etiopathogenesis of XGC is inflammatory destruction of Rokitansky-Aschoff sinuses containing biliary and cholesterol pigments within the gallbladder wall; this leads to a florid granulomatous histiocytic inflammatory reaction. The prevalence ranges from 1.3% to 8.8% of all cholecystectomies and varies from country to country; XGC occurs predominantly in patients over 50 years of age, and is equally distributed between males and females. Its association with GBC remains a topic of debate in the literature (between 0 and 20%). Symptoms are non-specific and generally similar to those of acute or chronic cholecystitis. XGC, when associated with altered health status, leads to the suspicion of GBC. XGC can also come to light due to an acute complication of cholecystolithiasis, in particular, gallstone migration. Imaging by sonography and CT scan is suggestive, but magnetic resonance imaging is more specific. In difficult cases, biopsy may be necessary to eliminate the diagnosis of tumor. In case of pre- or intra-operative diagnostic doubt, the opinion of a hepatobiliary specialty center can be of help. When diagnosis of GBC has been eliminated, laparoscopic cholecystectomy is recommended, although with a high risk of conversion to laparotomy and complications.

A systematic review and network meta-analysis of second-line therapy in hepatocellular carcinoma.

Background: In patients with advanced hepatocellular carcinoma (hcc) following sorafenib failure, it is unclear which treatment is most efficacious, as treatments in the second-line setting have not been directly compared and no standard therapy exists. This systematic review and network meta-analysis (nma) aimed to compare the clinical benefits and toxicities of these treatments. Methods: A systematic review of randomized controlled trials (rcts) was conducted to identify phase iii rcts in advanced hcc following sorafenib failure. Baseline characteristics and outcomes of placebo were examined for heterogeneity. Primary outcomes of interest were extracted for results, including overall survival (os), progression-free survival (pfs), objective response rate (orr), grade 3/4 toxicities, and subgroups. An nma was conducted to compare both drugs through the intermediate placebo. Comparisons were expressed as hazard ratios (hrs) for os and pfs, and as risk difference (rd) for orr and toxicities. Subgroup analyses for os and pfs were also performed. Results: Two rcts were identified (1280 patients) and compared through an indirect network; celestial (cabozantinib vs. placebo) and resorce (regorafenib vs. placebo). Baseline characteristics of patients in both trials were similar. Both trials also had similar placebo outcomes. Cabozantinib, compared with regorafenib, showed similar os [hazard ratio (hr): 1.21; 95% confidence interval (ci): 0.90 to 1.62], pfs (hr: 1.02; 95% ci: 0.78 to 1.34) and orr (-3.0%; 95% ci: -7.6% to 1.7%). Both treatments showed similar toxicities, but there were marginally higher risks of grade 3/4 hand-foot syndrome (5%; 95% ci: 0.1% to 9.8%), diarrhea (4.8%; 95% ci: 1.1% to 8.5%), and anorexia (4.4%; 95% ci: 0.8% to 8.0%) for cabozantinib. Subgroup results for os and pfs were consistent with overall results. Conclusions: Overall, this nma determined that cabozantinib and regorafenib have similar clinical benefits and toxicities for second-line hcc.

Robot-assisted ultrasound navigation platform for 3D HIFU treatment planning: Initial evaluation for conformal interstitial ablation.

Interstitial Ultrasound-guided High Intensity Focused Ultrasound (USgHIFU) therapy has the potential to deliver ablative treatments which conform to the target tumor. In this study, a robot-assisted US-navigation platform has been developed for 3D US guidance and planning of conformal HIFU ablations. The platform was used to evaluate a conformal therapeutic strategy associated with an interstitial dual-mode USgHIFU catheter prototype (64 elements linear-array, measured central frequency f = 6.5 MHz), developed for the treatment of HepatoCellular Carcinoma (HCC). The platform included a 3D navigation environment communicating in real-time with an open research dual-mode US scanner/HIFU generator and a robotic arm, on which the USgHIFU catheter was mounted. 3D US-navigation was evaluated in vitro for guiding and planning conformal HIFU ablations using a tumor-mimic model in porcine liver. Tumor-mimic volumes were then used as targets for evaluating conformal HIFU treatment planning in simulation. Height tumor-mimics (ovoid- or disc-shaped, sizes: 3-29 cm3) were created and visualized in liver using interstitial 2D US imaging. Robot-assisted spatial manipulation of these images and real-time 3D navigation allowed reconstructions of 3D B-mode US images for accurate tumor-mimic volume estimation (relative error: 4 ± 5%). Sectorial and full-revolution HIFU scanning (angular sectors: 88-360°) could both result in conformal ablations of the tumor volumes, as soon as their radii remained ≤ 24 mm. The presented US navigation-guided HIFU procedure demonstrated advantages for developing conformal interstitial therapies in standard operative rooms. Moreover, the modularity of the developed platform makes it potentially useful for developing other HIFU approaches.

Standardization in Quantitative Imaging: A Multicenter Comparison of Radiomic Features from Different Software Packages on Digital Reference Objects and Patient Data Sets.

Radiomic features are being increasingly studied for clinical applications. We aimed to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included standardized feature definitions and common image data sets. Ten sites (9 from the NCI's Quantitative Imaging Network] positron emission tomography-computed tomography working group plus one site from outside that group) participated in this project. Nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture. The common image data sets were: three 3D digital reference objects (DROs) and 10 patient image scans from the Lung Image Database Consortium data set using a specific lesion in each scan. Each object (DRO or lesion) was accompanied by an already-defined volume of interest, from which the features were calculated. Feature values for each object (DRO or lesion) were reported. The coefficient of variation (CV), expressed as a percentage, was calculated across software packages for each feature on each object. Thirteen sets of results were obtained for the DROs and patient data sets. Five of the 9 features showed excellent agreement with CV < 1%; 1 feature had moderate agreement (CV < 10%), and 3 features had larger variations (CV ≥ 10%) even after attempts at harmonization of feature calculations. This work highlights the value of feature definition standardization as well as the need to further clarify definitions for some features.

The role of dwelling type when estimating the effect of magnetic fields on childhood leukemia in the California Power Line Study (CAPS).

PURPOSE: The type of dwelling where a child lives is an important factor when considering residential exposure to environmental agents. In this paper, we explore its role when estimating the potential effects of magnetic fields (MF) on leukemia using data from the California Power Line Study (CAPS). In this context, dwelling type could be a risk factor, a proxy for other risk factors, a cause of MF exposure, a confounder, an effect-measure modifier, or some combination. METHODS: We obtained information on type of dwelling at birth on over 2,000 subjects. Using multivariable-adjusted logistic regression, we assessed whether dwelling type was a risk factor for childhood leukemia, which covariates and MF exposures were associated with dwelling type, and whether dwelling type was a potential confounder or an effect-measure modifier in the MF-leukemia relationship under the assumption of no-uncontrolled confounding. RESULTS: A majority of children lived in single-family homes or duplexes (70%). Dwelling type was associated with race/ethnicity and socioeconomic status but not with childhood leukemia risk, after other adjustments, and did not alter the MF-leukemia relationship upon adjustment as a potential confounder. Stratification revealed potential effect-measure modification by dwelling type on the multiplicative scale. CONCLUSION: Dwelling type does not appear to play a significant role in the MF-leukemia relationship in the CAPS dataset as a leukemia risk factor or confounder. Future research should explore the role of dwelling as an effect-measure modifier of the MF-leukemia association.

Molecular Cytogenetic Characterization of a Karyotype of a Female Patient with Secondary Amenorrhea with a Cell Line Showing 46,X,+mar.

OBJECTIVES: Disorders of sex development (DSD) include a group of conditions in which genotypes do not correlate with the typical male and female phenotypes. Numerical and structural abnormalities involving both autosomes and sex chromosomes have been observed in DSD. Specifically, deletions, duplications, and translocations involving specific genes as well as point mutations and less common aberrations have been implicated in the pathogenesis of these conditions. Finally, recent advances in analytical tools, namely chromosomal microarrays and sequencing methods, have greatly enhanced the precision with which DSD are genetically characterized and phenotypically correlated. Herein we report a case of a 24-year-old female patient who presented with secondary amenorrhea. Cytogenetic studies of her peripheral blood showed an abnormal clone with 45,X in three cells and the other was initially observed by chromosome analysis as 46,X,+mar in 27 cells. Molecular cytogenetics were performed to characterize the marker chromosome that showed two copies of the SRY, two copies of the heterochromatin Yq12, and two copies of the Y centromere Yp11.1-q11.1 on the marker chromosome, resulting in the identification of an isodicentric Y chromosome. Females with a 46,XY karyotype have gonadal dysgenesis and typically present as mosaic, along with a 45,X cell line. Some show small deletions of the short arm of the Y chromosome. Further studies based on the clinical picture, as well as possible prophylactic gonadectomy due to an increased risk of gonadal malignancy, gonadoblastoma or dysgerminoma, are suggested. Genetic counseling was recommended.