Search

• Phase II study on safety and feasibility of hypofractionated proton and carbon ion beam therapy for sacrococcygeal chordomas. • The trial enrolled 82 patients, achieving 96% 2-year and 81% 4-year overall survival rates. • Local progression-free survival rates were 84% at 2 years and 70% at 4 years. • The treatment with carbon ions or protons was delivered in 16 fractions of 4 Gy RBE over 5-6 fractions per week. • No significant differences were observed between the proton and carbon ion therapy groups with this distinct fractionation scheme. Sacrococcygeal chordomas have high recurrence rates and are challenging to treat. In this phase II prospective, randomized, stratified trial, the safety and feasibility of hypofractionated ion radiation therapy were investigated. The primary focus was monitored through the incidence of Grade 3–5 NCI-CTC-AE toxicity. Secondary endpoints included local progression-free (LPFS) and overall survival (OS). The study enrolled 82 patients with primary (87 %) and recurrent (13 %) inoperable or incompletely resected sacral chordomas from January 2013 to July 2022, divided equally into proton therapy (Arm A) and carbon ion beam therapy (Arm B) groups, each receiving a total dose of 64 Gy (RBE) in 16 fractions, 5–6 fractions per week. Overall 74 % of patients received no previous surgery and 66 % of tumors were confirmed by a brachyury staining. The mean and median Gross Tumor Volume at the time of treatment (GTV) was 407 ml and 185 ml, respectively. The median follow-up of the surviving patients was 44.7 months, and the 2-year and 4-year OS rates were 96 % and 81 %, respectively. Factors such as smaller GTV and younger age trended towards better OS. The LPFS after 2-year and 4-year was 84 % and 70 %, respectively. Male gender emerged as a significant predictor of LPFS. There was no significant difference between the treatment groups. We observed five grade 4 wound healing disorders (6 %). The initial response rates were promising; however local control was not sustained. More comparative research on fractionation schemes is essential to refine treatment approaches for inoperable sacral chordoma. [ABSTRACT FROM AUTHOR]

ABSTRACT. The results of recent surveys in the United States have suggested a rising tide of fatalities due to child abuse or neglect (CAN). Because these surveys lack consistency in case definition and are incomplete in coverage, the use of death certificate data to estimate the number of CAN deaths was explored. To estimate these deaths among children 0 through 17 years old for 1979 through 1988, three models were formulated, each comprising six coding categories: (1) deaths coded explicitly as due to CAN, (2) homicides, (3) injury deaths of undetermined intentionality, (4) accidental injury deaths, (5) sudden infant death syndrome fatalities, and (6) natural-cause deaths. Research studies and crime data were relied on to estimate the proportions of deaths in categories 2 through 6 that were actually due to CAN, and other assumptions were varied to create a range of estimates. For the 10-year period, the estimated mean annual CAN fatalities ranged from 861 to 1814 for ages 0 through 4, and from 949 to 2022 for ages 0 through 17. Child abuse and neglect death rates did not increase over the period; in fact, they were relatively stable for ages 0 through 17 and showed a modest decline for 0 through 4. Ninety percent of fatal CAN occurs among children younger than 5 years old, and 41% occurs among infants. About 85% of CAN deaths are recorded as due to other causes. It is concluded that the magnitude of fatal CAN can be estimated from death certificates. It is recommended that the death coding system be modified to make CAN identification easier and that this study's methodology be refined to provide the basis for ongoing surveillance. [ABSTRACT FROM AUTHOR]

Summary The liver stage of the Plasmodium parasite remains one of the most promising targets for intervention against malaria as it is clinically silent, precedes the symptomatic blood stage and represents a bottleneck in the parasite life cycle. However, many aspects of the development of the parasite during this stage are far from understood. During the liver stage, the parasite undergoes extensive replication, forming tens of thousands of infectious merozoites from each invading sporozoite. This implies a very efficient and accurate process of cytokinesis and thus also of organelle development and segregation. We have generated for the first time Plasmodium berghei double-fluorescent parasite lines, allowing visualization of the apicoplast, mitochondria and nuclei in live liver stage parasites. Using these we have seen that in parallel with nuclear division, the apicoplast and mitochondrion become two extensively branched and intertwining structures. The organelles then undergo impressive morphological and positional changes prior to cell division. To form merozoites, the parasite undergoes cytokinesis and the complex process of organelle development and segregation into the forming daughter merozoites could be analysed in detail using the newly generated transgenic parasites. [ABSTRACT FROM AUTHOR]

The protozoan parasite Plasmodium is transmitted by female Anopheles mosquitoes and undergoes obligatory development within a parasitophorous vacuole in hepatocytes before it is released into the bloodstream. The transition to the blood stage was previously shown to involve the packaging of exoerythrocytic merozoites into membrane-surrounded vesicles, called merosomes, which are delivered directly into liver sinusoids. However, it was unclear whether the membrane of these merosomes was derived from the parasite membrane, the parasitophorous vacuole membrane or the host cell membrane. This knowledge is required to determine how phagocytes will be directed against merosomes. Here, we fluorescently label the candidate membranes and use live cell imaging to show that the merosome membrane derives from the host cell membrane. We also demonstrate that proteins in the host cell membrane are lost during merozoite liberation from the parasitophorous vacuole. Immediately after the breakdown of the parasitophorous vacuole membrane, the host cell mitochondria begin to degenerate and protein biosynthesis arrests. The intact host cell plasma membrane surrounding merosomes allows Plasmodium to mask itself from the host immune system and bypass the numerous Kupffer cells on its way into the bloodstream. This represents an effective strategy for evading host defenses before establishing a blood stage infection. [ABSTRACT FROM AUTHOR]