Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: A cohort study from the European paediatric Soft tissue sarcoma Study Group

Background

Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.

Methods

This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.

Results

The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.

Conclusions

The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.

Plain Language Summary

• Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors.
• Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases.
• This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.

     

Defining minimum volume thresholds to increase quality of care: a new patient-oriented approach using mixed integer programming

A positive relationship between treatment volume and outcome quality has been demonstrated in the literature and is thus evident for a variety of procedures. Consequently, policy makers have tried to translate this so-called volume–outcome relationship into minimum volume regulation (MVR) to increase the quality of care—yet with limited success. Until today, the effect of strict MVR application remains unclear as outcome quality gains cannot be estimated adequately and restrictions to application such as patient travel time and utilization of remaining hospital capacity are not considered sufficiently. Accordingly, when defining MVR, its effectiveness cannot be assessed. Thus, we developed a mixed integer programming model to define minimum volume thresholds balancing utility in terms of outcome quality gain and feasibility in terms of restricted patient travel time and utilization of hospital capacity. We applied our model to the German hospital sector and to four surgical procedures. Results showed that effective MVR needs a minimum volume threshold of 125 treatments for cholecystectomy, of 45 and 25 treatments for colon and rectum resection, respectively, of 32 treatments for radical prostatectomy and of 60 treatments for total knee arthroplasty. Depending on procedure type and incidence as well as the procedure’s complication rate, outcome quality gain ranged between 287 (radical prostatectomy) and 977 (colon resection) avoidable complications (11.7% and 11.9% of all complications). Ultimately, policy makers can use our model to leverage MVR’s intended benefit: concentrating treatment delivery to improve the quality of care.

     

Oxygen uptake plateau occurrence depends on oxygen kinetics and oxygen deficit accumulation

We tested the hypothesis that participants with an oxygen uptake () plateau during incremental exercise exhibit a lower VO₂‐deficit (VO_2DEF)‐accumulation in the submaximal intensity domain due to faster ramp and square wave O₂‐kinetics. Twenty‐six male participants performed a standard ramp test (increment: 30 W·min^?1), a ramp test with an individualized ramp slope and a two‐step (moderate and severe) square wave exercise followed by a ‐verification bout. VO_2DEF was calculated by the difference between individualized ramp test O₂ and O₂‐demand estimated from steady‐state O₂‐kinetics. Twenty‐four participants verified their O_2max in the verification test. Ten of them showed a plateau in the individualized ramp test. VO_2DEF at the end of this ramp test (4.34 ± 0.60 vs 4.54 ± 0.43 L) was not different between the plateau and the non‐plateau group (P > 0.05). The plateau group had a significantly (P < 0.05) lower VO_2DEF 2 minutes before termination of the individualized ramp test (2.24 ± 0.40 vs 2.78 ± 0.33 L). This coincided with a shorter mean response time (43 ± 9 vs 53 ± 7 seconds), a higher increase in O₂ per W (10.1 ± 0.2 vs 9.2 ± 0.5 mL·min^?1·W^?1) at the individualized ramp test as well as shorter time constants of moderate (36 ± 6 vs 48 ± 7 seconds) and severe (62 ± 9 vs 86 ± 10 seconds) square wave kinetics (all P < 0.05). We conclude that the O₂‐plateau occurrence requires a fast O₂‐kinetics and a low VO_2DEF‐accumulation at intensities below O_2max.     

Impact of Food Intake on Liver Stiffness Determined by 2-D Shear Wave Elastography: Prospective Interventional Study in 100 Healthy Patients

The aim was to evaluate the influence of food intake on liver stiffness measurement (LSM), performed with 2-D shear wave elastography (Logiq E9, GE Medical Systems, Wauwatosa, WI, USA). One hundred healthy volunteers were prospectively enrolled. Mean age was 25.8 (19–55) y, and mean body mass index was 22.43 (17.3–30.8) kg/m². Patients fasted for at least 3 h and subsequently ingested a liquid meal of 800 kcal. Liver stiffness and portal vein velocity were measured before and after food intake. Food intake resulted in significantly higher LSM values compared with baseline LSM (5.74 ± 0.94 kPa vs. 4.80 ± 0.94 kPa, p < 0.001). On multiple linear regression analysis, body mass index was significantly positively correlated with the LSM increase after food intake (p?=?0.01). No correlation between the increase in LSM and the increase in post-prandial portal vein velocity was observed (r?=?0.09). In summary, food intake has a significant influence on LSM. There is an 11% risk of misclassifying non-fasting, healthy patients as having significant fibrosis.     

Multicenter Evaluation of 434 Hospital Deaths From COVID-19: How Can We Improve End-of-Life Care During a Pandemic?

ContextThe pandemic has substantially increased the workload of hospital palliative care providers, requiring them to be responsive and innovative despite limited information on the specific end of life care needs of patients with COVID-19. Multi-site data detailing clinical characteristics of patient deaths from large populations, managed by specialist and generalist palliative care providers are lacking.ObjectivesTo conduct a large multicenter study examining characteristics of COVID-19 hospital deaths and implications for care.MethodsA multi-center retrospective evaluation examined 434 COVID-19 deaths in 5 hospital trusts over the period March 23, 2020 to May 10, 2020.ResultsEighty three percent of patients were over 70.32% were admitted from care homes. Diagnostic timing indicated over 90% of those who died contracted the virus in the community. Dying was recognized in over 90% of patients, with the possibility of dying being identified less than 48 hours from admission for a third. In over a quarter, death occurred less than 24 hours later. Patients who were recognized to be dying more than 72 hours prior to death were most likely to have access to medication for symptom control.ConclusionThis large multicenter study comprehensively describes COVID-19 deaths throughout the hospital setting. Clinicians are alert to and diagnose dying appropriately in most patients. Outcomes could be improved by advance care planning to establish preferences, including whether hospital admission is desirable, and alongside this, support the prompt use of anticipatory subcutaneous medications and syringe drivers if needed. Finally, rapid discharges and direct hospice admissions could better utilize hospice beds and improve care.     

Autophagy as a therapeutic target in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterised by early metastasis and resistance to anti-cancer therapy, leading to an overall poor prognosis. Despite continued research efforts, no targeted therapy has yet shown meaningful efficacy in PDAC; mutations in the oncogene KRAS and the tumour suppressor TP53, which are the most common genomic alterations in PDAC, have so far shown poor clinical actionability. Autophagy, a conserved process allowing cells to recycle altered or unused organelles and cellular components, has been shown to be upregulated in PDAC and is implicated in resistance to both cytotoxic chemotherapy and targeted therapy. Autophagy is thus regarded as a potential therapeutic target in PDAC and other cancers. Although the molecular mechanisms of autophagy activation in PDAC are only beginning to emerge, several groups have reported interesting results when combining inhibitors of the extracellular-signal-regulated kinase/mitogen-activated protein kinase pathway and inhibitors of autophagy in models of PDAC and other KRAS-driven cancers. In this article, we review the existing preclinical data regarding the role of autophagy in PDAC, as well as results of relevant clinical trials with agents that modulate autophagy in this cancer.Subject terms: Pancreatic cancer, Pancreatic cancer     

Epilepsie,Schlaf und plötzlicher unerwarteter Tod

Clinical Epileptology - Der plötzliche unerwartete Tod stellt eine seltene, aber schwerwiegende Komplikation für Epilepsiepatienten dar. Das Risiko hierfür ist u. a. nachts und...     

Intratympanic application of triamcinolone in sudden hearing loss—radiologic anatomy in cone beam CT and its’ correlation to clinical outcome

European Archives of Oto-Rhino-Laryngology - To evaluate temporal bone cone-beam CT in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) being treated with primary and secondary...     

Gaming-Gambling Convergence: Trends,Emerging Risks,and Legislative Responses

A convergence of gaming and gambling products, services, and platforms is presently drawing considerable policy debate. This convergence may be giving rise to a critical area of consumer vulnerability given the addictive potential of gaming and gambling. While some convergence aspects are gaining research attention, the broader contexts of the phenomenon have not been adequately examined. In light of this, the present study aimed to inform four key enquiry areas pertaining to gaming-gambling convergence—contexts and drivers, definitions and framings, risk and harm, and legislative response. Using a narrative review method, 108 articles from the academic and grey literature were examined and thematically summarised to provide an overview of the convergence phenomenon. Findings indicate convergence in multiple overlapping contexts (gaming elements in gambling, games incorporating gambling elements, gambling on games, free simulated online gambling, and social media games and gambling) driven by technological advances and commercial interests. Findings related to definitions and framing include the industry’s strategic use of the term gaming to reduce negative connotations associated with gambling, and community perceptions of gaming as legitimate and harmless entertainment. Potential risks include transitions from games (without money) to real-money gambling, and problem co-existence. Legislative responses are beginning to emerge with the greatest focus being on loot boxes in games. However, the limited evidence of risk and harm has led to hesitancies in legislative actions to regulate gaming-gambling hybrids in some jurisdictions. Considering that convergence is supported by rapid advances in technology and is taking place largely on the Internet (accessible 24 h), harms for consumers could manifest quickly and spread broadly across societies before their existence and severity are established. Based on the Precautionary Principle, the present evidence base call for harm prevention policies and regulations in addition to changes in the definition of money (including digital currency and microtransaction) in gaming and gambling laws.