Objective:
This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without ...resection).
Background:
Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking.
Methods:
Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015–December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS.
Results:
Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months,
P
< 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS Hazard Ratio (HR) 0.344, 95% confidence interval (0.222–0.534),
P
< 0.01, with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%,
P
< 0.01).
Conclusions:
Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.
Background and Objectives
Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially ...unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC.
Methods
From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first‐line FOLFIRINOX (April 2015–December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated.
Results
A total of 252 patients were included, with a median OS of 14 months. Thirty‐two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index ≤1, and CA 19.9 < 274 were independent factors predicting a better OS (c‐index: 0.61). WHO ps >1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein ≥ 270° were independent factors decreasing the probability of resection (c‐index: 0.79).
Conclusions
Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision‐making process and counseling of these patients.
Aim
This study evaluated the recognition and management practices with regard to congenital cytomegalovirus (cCMV) infections by a select group of experts and through a national surveillance study.
...Method
A questionnaire was sent to international experts involved in mother and infant care in 2014–2015. Monthly surveillance was conducted among Dutch paediatricians for cases of cCMV infections from 2013 until 2015.
Results
The questionnaire was completed by 63/103 (62%) respondents, who indicated that recognition and management practices varied. Maternal screening was performed by 17/63 (27%) and infant screening by 3/61 (5%) of the respondents. Infant CMV diagnostics were most frequently initiated due to hepatosplenomegaly and/or an increase in liver transaminases. Management practices included cranial ultrasound (57/63, 91%) and audiological follow‐up in symptomatic (61/63, 97%) and asymptomatic (52/63, 83%) infants. In terms of antiviral treatment, 46/63 (73%) treated symptomatic infants only and 6/63 (9%) treated all infected infants. In total, 48 cases were registered through the Dutch surveillance study and 43/48 (90%) infants were symptomatic.
Conclusion
This study indicates that infants with cCMV infection were insufficiently recognised and highlights the need for consensus on management practices. Screening of infants and the development of an international management guideline are recommended.
Motor development is one of the first signals to identify whether an infant is developing well. For very preterm (VPT) infants without severe perinatal complications, little is known about their ...motor developmental curves.
Explore gross motor developmental curves from 3 until 18 months corrected age (CA) of VPT infants, and related factors. Explore whether separate profiles can be distinguished and compare these to profiles of Dutch term-born infants.
Prospective cohort study with parents repeatedly recording their infant, using the Alberta Infant Motor Scale (AIMS) home-video method, from 3 to 18 months CA.
Forty-two Dutch infants born ≤32.0 weeks gestational age and/or with a birthweight (BW) of <1500 g without severe perinatal complications.
Gross motor development measured with the AIMS.
In total 208 assessments were analyzed, with 27 infants ≥five assessments, 12 with <four, and three with one assessment. Sigmoid-shaped gross motor curves show unidirectional growth and variability. No infant or parental factors significantly influenced motor development, although a trend was seen for the model where lower BW, five-minute Apgar score <7, and Dutch native-speaking parents were associated with slower motor development. Three motor developmental profiles of VPT infants were identified, early developers, gradual developers, and late bloomers, which until 12 months CA are comparable in shape and speed to profiles of Dutch term-born infants.
VPT infants show great intra- and interindividual variability in gross motor development, with three motor profiles being distinguished. From 12 months CA onwards, VPT infants appear to develop at a slower pace. With some caution, classifying infants into motor developmental profiles may assist clinical decision-making.
The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase ...response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are further aggravated by islet encapsulation, inflammation, and undesirable cell-biomaterial interactions. To identify biomaterials that would not further increase damaging oxidative stress levels and that are also suitable for manufacturing a beta cell encapsulation device, we studied five clinically approved polymers for their effect on oxidative stress and islet (alpha and beta cell) function. We found that 300 poly(ethylene oxide terephthalate) 55/poly(butylene terephthalate) 45 (PEOT/PBT300) was more resistant to breakage and more elastic than other biomaterials, which is important for its immunoprotective function. In addition, it did not induce oxidative stress or reduce viability in the MIN6 beta cell line, and even promoted protective endogenous antioxidant expression over 7 days. Importantly, PEOT/PBT300 is one of the biomaterials we studied that did not interfere with insulin secretion in human islets.
•PEOT/PBT300 does not induce oxidative stress in pancreatic alpha and beta cells.•PET and PVDF induce oxidative stress in alpha cells, but not in beta cells.•Beta cells can protect themselves against oxidative stress induced by certain biomaterials.
IMPORTANCE: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based ...guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. OBJECTIVE: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. EVIDENCE REVIEW: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. FINDINGS: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). CONCLUSIONS AND RELEVANCE: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.
Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that ...Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis.
Aim: In this study, we determined whether outcome of preterm neonates has improved over a period of 16 years.
Study design: Inborn neonates with a gestational age of 25.0–29.9 weeks were included. ...Patients with severe congenital malformations were excluded. Mortality and morbidity (chronic lung disease; CLD, intraventricular haemorrhage: IVH grade III or IV, cystic periventricular leukomalacia: cPVL, perforated necrotizing enterocolitis: NEC, severe retinopathy of prematurity needing surgery: ROP and cerebral palsy: CP) were compared in three periods (period 1: 1991–1996 n = 434; period 2: 1997–2001 n = 356; period 3: 2002–2006 n = 422).
Results: Infant mortality decreased from 15.2% to 10.9%. CLD did not differ significantly between periods (14.1–14.8%). Perforated NEC decreased from 2.8% to 1.6%. IVH grade III and IV both remained at 5.7% in period 3, whereas cPVL decreased significantly from 4.5% to 1.6%. Cerebral palsy decreased from 5.8% to 3.5% in period 3. Two neonates in each period were in need of surgery for ROP.
Conclusion: Inborn preterm patients showed an improved survival and a significant reduction in cPVL and CP. Perforated NEC showed a trend to decrease. CLD and IVH grade III and IV remain a matter of concern.
To systematically examine gross motor development in the first 18 months of life of preterm infants.
A total of 800 preterm infants (356 boys), ages between 1 and 18 months and corrected for degree ...of prematurity, were assessed with the use of the Alberta Infant Motor Scale.
Comparison of the mean Alberta Infant Motor Scale scores of the preterm infants with the norm-referenced values derived from term infants revealed that as a group, the preterm infants scored significantly lower at all age levels, even with full correction for degree of prematurity.
In general, preterm infants exhibit different gross motor developmental trajectories compared with term infants in the first 18 months of life. The gross motor developmental profile of preterm infants may reflect a variant of typical gross motor development, which seems most likely to be specific for this population. As a consequence, adjusted norms should be used for proper evaluation and clinical decision-making in relation to preterm infants.
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