| 1. |
|
|
| 2. |
- Hellström, Ann, 1959, et al.
(författare)
-
Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity A Randomized Clinical Trial
- 2021
-
Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 175:4, s. 359-367
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). OBJECTIVE To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100mg/kg/d) and DHA (50mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcomewas severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P =.02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P <.001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P =.03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
|
|
| 3. |
- Almotairi, Fawaz, et al.
(författare)
-
Chiari I malformation—neuropsychological functions and quality of life
- 2020
-
Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 162:7, s. 1575-1582
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the neuropsychological (NP) functioning and quality of life (QOL) before and 3months after surgery on adults with Chiari I malformation (CMI). Patients and methods: All adult patients who had been diagnosed with CMI were invited to participate. Those who participated were assessed using a Hospital Anxiety and Depression scale (HAD) and NP examinations. Their QOL was assessed using the self-reported life satisfaction checklist, LiSat-11 and the five-dimensional EuroQol measurement of health outcome, EQ-5D-5L. All assessments were carried out both before and 3months after surgery was performed. Demographic data and comorbidities were also registered. Results: Of the 11 patients who underwent NP assessment, the majority demonstrated cognitive functioning within the normal range. However, postoperatively, their performance in verbal learning, psychomotor speed, colour naming speed and the ability to manage interference through response selection and inhibition (aspects of executive functioning) was significantly improved. Thirteen patients completed QOL assessments. When LiSat-11 item domains were compared with those of healthy subjects, patients reported a lower level of satisfaction with their life quality both before and after surgery. However, the EQ-5D-5L measurements, i.e., the descriptive system and the visual analogue, indicated that their QOL of life was significantly improved after surgery. Conclusion: There is scarcely any literature documenting effects of surgery on the QOL of CMI patients. The study we present here breaks new ground by comparing pre- and postoperative NP functions in CMI. We also examine the value of surgery for improving both NP functions and QOL in CMI. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.
|
|
| 4. |
- Challis, Pontus, et al.
(författare)
-
Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)
- 2024
-
Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109, s. 87-93
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.
|
|
| 5. |
- Challis, Pontus, et al.
(författare)
-
Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)
- 2024
-
Ingår i: Archives of Disease in Childhood. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109:1, s. 87-93
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.
|
|
| 6. |
|
|
| 7. |
- Dolinska, Monika, et al.
(författare)
-
Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
- 2023
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
-
Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
|
|
| 8. |
- Ekström, Claes, et al.
(författare)
-
Evaluation of recombinant human IGF-1/IGFBP-3 on intraventricular hemorrhage prevention and survival in the preterm rabbit pup model
- 2023
-
Ingår i: Scientific Reports. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral blood flow. In this work, using different experimental setups, we aimed to (i) establish an optimal time-point for glycerol-induction of IVH in relation to time-point of recombinant human (rh) IGF-1/rhIGFBP-3 administration, and (ii) to evaluate the effects of a physiologic replacement dose of rhIGF-1/rhIGFBP-3 on prevention of IVH and survival in the preterm rabbit pup. The presence of IVH was evaluated using high-frequency ultrasound and post-mortem examinations. In the first part of the study, the highest incidence of IVH (> 60%), occurred when glycerol was administered at the earliest timepoint, e.g., 6h after birth. At later time-points (18 and 24h) the incidence decreased substantially. In the second part of the study, the incidence of IVH and mortality rate following rhIGF-1/rhIGFBP-3 administration was not statistically different compared to vehicle treated animals. To evaluate the importance of maintaining intrauterine serum levels of IGF-1 following preterm birth, as reported in human interventional studies, additional studies are needed to further characterize and establish the potential of rhIGF-1/rhIGFBP-3 in reducing the prevalence of IVH and improving survival in the preterm rabbit pup.
|
|
| 9. |
- Elias, Khalid, et al.
(författare)
-
Gastrointestinal Physiology Before and After Duodenal Switch with Comparisons to Unoperated Lean Controls : Novel Use of the SmartPill Wireless Motility Capsule
- 2021
-
Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 31:8, s. 3483-3489
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Bariatric surgery alters gastrointestinal anatomy. In this exploratory study, the SmartPill® wireless motility capsule (WMC) was used to study changes in gastrointestinal physiology following biliopancreatic diversion with duodenal switch (BPD/DS).MATERIAL AND METHODS: Twenty-eight BPD/DS patients (35 ± 11 years, 50% females, body mass index [BMI] 56 ± 5) were to be examined preoperatively and postoperatively. In addition to transit time, appetite control and gastrointestinal symptoms were studied by patient-scored questionnaires (visual analogue scale and Gastrointestinal Symptom Rating Scale (GSRS)). Data was compared to 41 lean unoperated controls.RESULTS: About 1.8 years postoperatively, 18 patients (BMI 35.8 ± 8.3) returned for a second WMC test. As expected, small bowel transit time was reduced, from 3.9 ± 1.6 h to 2.8 ± 2.0, p = 0.02, and at both these time points, it was shorter than in lean controls (5.4 ± 1.9 h, p = 0.001). Postoperatively, a trend towards reduced colon and whole gut transit times was seen in BPD/DS-patients, thus approaching those of lean controls. Surprisingly, BPD/DS patients scored higher satiety than controls preoperatively as well as increased hunger and desire to eat postoperatively. Compared to lean, BPD/DS patients reported a higher total GSRS score at both time points (1.2 ± 0.2 vs 1.7 ± 0.6 and 2.3 ± 0.5, p < 0.001). Postoperatively, the scores for diarrhea and indigestion increased.CONCLUSIONS: The novel use of the SmartPill system in BPD/DS patients gave the expected readouts. Although small bowel transit time was further shortened after BPD/DS, whole gut transit time did not differ from controls. Typical gastrointestinal symptoms were reported postoperatively.
|
|
| 10. |
- Elias, Khalid, 1975-, et al.
(författare)
-
Impact of biliopancreatic diversion with duodenal switch on glucose homeostasis and gut hormones and their correlations with appetite
- 2022
-
Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier. - 1550-7289 .- 1878-7533. ; 18:12, s. 1392-1398
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundBiliopancreatic diversion with duodenal switch (BPD/DS) results in lifelong changes in gastrointestinal physiology with unclear associations with appetite perception.ObjectiveTo explore mixed meal–induced changes in glucose homeostasis and gut hormones and their correlations with appetite perception.SettingUniversity hospital.MethodsOf 28 patients studied preoperatively (age: 38.4 ± 11.3 years; body mass index [BMI]: 56.5 ± 5.1 kg/m2; 14 women), 19 (68%) returned for postoperative follow-up. Plasma was sampled for 180 minutes during a 260-kcal standardized mixed meal. Concentrations of leptin, glucose, insulin, triglycerides, active acyl-ghrelin, motilin, total glucose-dependent insulinotropic polypeptide (GIP), active glucagon-like peptide 1 (GLP-1), and total peptide YY (PYY) were measured. Subjective appetite sensations were scored.ResultsBPD/DS resulted in 66.1% ± 23.3% excess BMI loss. Leptin was halved. Glucose and insulin levels were reduced, blunting a preoperative peak at 30 minutes, giving a lower homeostasis model assessment for insulin resistance (HOMA-IR; 13.9 versus 4.8). In contrast, reduced ghrelin and motilin concentrations were accompanied by pronounced peaks 20–30 minutes prior to meal responses. GIP was reduced, whereas GLP-1 and PYY responses were markedly increased, with an early postprandial peak (P < .05, for all). HOMA-IR correlated with insulin (r = .72) and GIP (r = .57). Postoperatively, satiety correlated with GLP-1 (r = .56), whereas the gastric motility index correlated with the desire to eat (r = .60), percentage excess BMI loss (r = –.55), and percentage total weight loss (r = –.49). Delta insulin, GLP-1, and leptin correlated positively with percentage total weight loss (r = .51, r = .48, and r = .58, respectively).ConclusionsBPD/DS reduces leptin, HOMA-IR, and GIP while markedly increasing GLP-1 and PYY. This study marks the magnitude change in GLP-1 with additional effects of PYY as important factors for weight loss.
|
|
