Lack of efficacy of two consecutive treatments of radioimmunotherapy with 131I-cG250 in patients with metastasized clear cell renal cell carcinoma.

PURPOSE: A previous activity dose-escalation study using 131I-labeled chimeric monoclonal antibody cG250 in patients with progressive metastatic renal cell carcinoma (RCC) resulted in occasional therapeutic responses. The present study was designed to determine the safety and therapeutic efficacy of two sequential high-dose treatments with 131I-cG250. PATIENTS AND METHODS: Patients (n = 29) with progressive metastatic RCC received a low dose of (131)I-cG250 for assessment of preferential targeting of metastatic lesions, followed by the first radioimmunotherapy (RIT) with 2220 MBq/m2 131I-cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low-dose 131I-cG250 (n = 20) was given 3 months later. When blood clearance was not accelerated, a second RIT of 131I-cG250 was administered at an activity-dose of 1110 MBq/m2 (n = 3) or 1665 MBq/m2 (n = 16). Patients were monitored weekly for toxicity, and tumor size was evaluated by computed tomography once every 3 months intervals. RESULTS: The maximum-tolerated dose (MTD) of the second RIT was 1,665 MBq/m2 because of dose-limiting hematological toxicity. Based on an intention-to-treat analysis, after two RIT treatments, the disease stabilized in five of 29 patients, whereas it remained progressive in 14 of 29 patients. Two patients received no RIT, and eight of 29 received only one 131I-cG250 RIT because of grade 4 hematologic toxicity, formation of human antichimeric antibodies, or disease progression. CONCLUSION: In patients with progressive end-stage RCC, the MTD of the second treatment was 75% of the MTD of the first RIT. In the majority of patients, two cycles of 131I-cG250 could be safely administered without severe toxicity. No objective responses were observed, but occasionally two RIT doses resulted in stabilization of previously progressive disease.     

Human papillomavirus vaccination: Where are we now?

The development of efficacious prophylactic human papillomavirus vaccines provided an opportunity for the primary prevention of related infections and diseases. Certain oncogenic human papillomaviruses that preferentially infect the genital epithelium cause cervical cancer and a substantial proportion of anal, penile, vaginal, vulvar and oropharyngeal cancers. Following extensive clinical trials demonstrating their efficacy and safety, two vaccines have been in global use for over 6 years. This review summarises the accumulated evidence regarding their high level of efficacy, safety in population usage, reductions in genital warts, infections and cervical disease following their adoption, and facilitators and barriers to achieving high vaccination coverage. The review also discusses practical issues and frequently asked questions regarding duration of effect, vaccination of women treated for cervical disease and alternate vaccination schedules, as well as the need to review cervical screening strategies in the post‐ vaccination environment.     

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

Degree of exposure and peritraumatic dissociation as determinants of PTSD symptoms in the aftermath of the Ghislenghien gas explosion

Background

This paper investigates risk factors for the development of posttraumatic stress symptoms in the different survivor groups involved in a technological disaster in Ghislenghien (Belgium). A gas explosion instantly killed five firefighters, one police officer and 18 other people. Moreover, 132 people were wounded among which many suffered severe burn injuries.

Methods

In the framework of a large health survey of people potentially involved in the disaster, data were collected from 3,448 households, of which 7,148 persons aged 15 years and older, at 5 months (T1) and at 14 months (T2) after the explosion. Hierarchical regression was used to determine the significant predictors and to assess their proportion in variance accounted for.

Results

The degree of exposure to the disaster was a predictor of the severity of posttraumatic stress symptoms. Peritraumatic dissociation appeared to be the most important predictor of the development of posttraumatic stress symptoms at T1. But at T2, posttraumatic stress symptoms at T1 had become the most important predictor. Dissatisfaction with social support was positively linked to development of posttraumatic stress symptoms at T1 and to the maintenance of these symptoms at T2. Survivors who received psychological help reported significant benefits.

Conclusions

In harmony with the findings from studies on technological disasters, at T1 6,0% of the respondents showed sufficient symptoms to meet all criteria for a full PTSD. At T2, 6,6% still suffered from posttraumatic stress symptoms. The symptoms of the different victim categories clearly indicated the influence of the degree of exposure on the development of posttraumatic stress symptoms. Problems inherent to retrospective scientific research after a disaster are discussed.     

Artificial intelligence in gastroenterology: A state-of-the-art review

The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (e.g., identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus, pancreatic malignancies), detection of lesions (e.g., polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [e.g., determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.     

Bioengineering Approaches for Placental Research

Research into the human placenta’s complex functioning is complicated by a lack of suitable physiological in vivo models. Two complementary approaches have emerged recently to address these gaps in understanding, computational in silico techniques, including multi-scale modeling of placental blood flow and oxygen transport, and cellular in vitro approaches, including organoids, tissue engineering, and organ-on-a-chip models. Following a brief introduction to the placenta’s structure and function and its influence on the substantial clinical problem of preterm birth, these different bioengineering approaches are reviewed. The cellular techniques allow for investigation of early first-trimester implantation and placental development, including critical biological processes such as trophoblast invasion and trophoblast fusion, that are otherwise very difficult to study. Similarly, computational models of the placenta and the pregnant pelvis at later-term gestation allow for investigations relevant to complications that occur when the placenta has fully developed. To fully understand clinical conditions associated with the placenta, including those with roots in early processes but that only manifest clinically at full-term, a holistic approach to the study of this fascinating, temporary but critical organ is required.