Tag: nevin manimala

N Engl J Med. 2022 Apr 4. doi: 10.1056/NEJMoa2109191. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear.

METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohorts (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression.

RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events.

CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

PMID:35373933 | DOI:10.1056/NEJMoa2109191

Diabetes Obes Metab. 2022 Apr 4. doi: 10.1111/dom.14709. Online ahead of print.

ABSTRACT

AIM: To assess whether low-carbohydrate (LC) diets are associated with differences in weight loss and well-being in people with obesity, and to assess their cardiovascular and renal safety.

METHODS: Meta-analysis of Randomized Controlled Trials longer than 3 months, retrieved through an extensive search on MedLine and Embase online databases, comparing weight loss with LC diets and control diets in people with BMI >30 kg/m² .

RESULTS: We retrieved 25 trials. LC diets were associated with significant reduction of body weight at 3-4 (MD -2.59 [-3.93, -1.25] kg), and at 6-8 months (MD -2.64 [-4.32, -0.95]), no diffeence at 10-14 and 18-30 months, vs controls. Compared with controls, LC diets were associated with significantly greater BMI reduction at 3-4 months (-1.66 [-2.70, -0.61] kg/m²⁾ , but not at other timepoints. Since only four trials reported data on renal function and psychological parameters, renal safety and impact on well-being could not be assessed. Differences in fasting plasma glucose at any time point were not statistically significant. No significant difference in total or LDL Cholesterol or blood pressure were found in the long-term, whereas a long-term reduction of triglycerides (23.26 [-45.53, -0.98] mg/dl, at 18-30 months), and increase of HDL cholesterol, MD 4.94 [0.30, 9.57] mg/dl at 18-30 months), was observed.

CONCLUSION: LC diets are associated with greater short-term weight loss than non-carbohydrate-restricted diets and a longer-term favorable effect on cardiovascular risk factors. Further evidence on long-term efficacy and renal safety is needed before LC diets can be recommended as the preferred diets in obese persons. This article is protected by copyright. All rights reserved.

PMID:35373905 | DOI:10.1111/dom.14709

Pediatr Blood Cancer. 2022 Apr 4:e29697. doi: 10.1002/pbc.29697. Online ahead of print.

ABSTRACT

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT).

METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children’s Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40).

RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs.

CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.

PMID:35373903 | DOI:10.1002/pbc.29697

Diabetes Obes Metab. 2022 Apr 4. doi: 10.1111/dom.14706. Online ahead of print.

ABSTRACT

BACKGROUND: In Europe regulatory approval of the Medtronic Minimed^TM 670G is limited to those above 7 years. Thus, additional information on the incremental differences between using a sensor-augmented pump (SAP) without automated insulin delivery (AID), using it with predictive low-glucose suspension (PLGM) or as hybrid closed loop (HCL) in preschool and school children is needed.

METHODS: We conducted a monocentric, randomized, controlled, two-phase cross-over study in 38 children 2-6 and 7-14 years of age. Primary endpoint was percentage of time in range (TIR) of 70-180 mg/dl. Other CGM metrics, HbA1c, patient related outcomes (DISABKIDS questionnaire, Fear of Hypoglycemia Survey) and safety events were also assessed. Results from 2 weeks SAP, 8 weeks PLGM and 8 weeks HCL were compared using a paired t-test or Wilcoxon signed-rank test.

RESULTS: Overall we found a high rate of TIR target (>70%) achievement with HCL in preschool (88%) and school children (50%), with average times in Auto Mode of 93% and 87% respectively. Preschool children achieved a mean TIR of 73±6% (+8% vs. SAP, +6% vs. PLGM) and school children 69±8% ( +15% vs. SAP and +14% vs. PLGM). Overall HbA1c improved from 7.4±0.9% to 6.9±0.5%. (p=0.0002). Diabetes burden and worries and fear of hypoglycemia remained on low levels without significant changes vs. PLGM. No events of severe hypoglycemia or diabetic ketoacidosis occurred.

CONCLUSIONS: Preschool children profit from AID at least as much as those age 7 and above. To ensure safe use and prescribing modalities, regulatory approval is required also for young children. This article is protected by copyright. All rights reserved.

PMID:35373894 | DOI:10.1111/dom.14706

Pediatr Blood Cancer. 2022 Apr 4:e29575. doi: 10.1002/pbc.29575. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns between tumor molecular background, imaging features, and patient outcome, a retrospective study was performed in a group of non-neurofibromatosis type 1 (non-NF1) grade 1 PLGGs.

PATIENTS AND METHODS: Seventy-eight children, followed from 2004 to 2017, were retrospectively reported. In this population, we analyzed radiological and molecular parameters. Their therapeutic management comprised surgery or surgery plus chemotherapies.

RESULTS: Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with postoperative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas four deaths occurred only in the highly treated patients. As expected, in the global cohort, PLGG with BRAF p.V600E and/or CDKN2A loss exhibited poor outcomes and we evidenced significant associations between those molecular characteristics and their imaging presentation. In the chemo-treated patients, when associating initial and 6-month magnetic resonance imaging (MRI) parameters to the molecular features, the good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis and the appearance during treatment of a higher cystic proportion that we called cystic conversion.

CONCLUSION: So, additionally to the presence of BRAF p.V600E or CDKN2A deletion in grade 1 PLGGs, the absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy were significantly linked to a worst prognosis and response to treatment. These imaging features should be considered as prognostic markers in future PLGG studies.

PMID:35373885 | DOI:10.1002/pbc.29575

BJOG. 2022 Apr 4. doi: 10.1111/1471-0528.17174. Online ahead of print.

ABSTRACT

OBJECTIVE: To establish pregnancy-specific reference ranges for fasting and postprandial total serum bile acids (TSBA) concentrations.

DESIGN: Cross-sectional study.

SETTING: Tertiary care university hospital.

POPULATION: Healthy pregnant women at term admitted to the Obstetrics Department over one year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any co-existing condition of increased risk for ICP.

METHODS AND MAIN OUTCOME MEASURES: Both fasting (8-14 hours of fasting) and postprandial (2 hours after meal) TSBA concentrations were measured in 612 women (528 fasting and 377 postprandial samples) by automated enzymatic-spectrophotometric assay.

RESULTS: Reference intervals of 4.4-14.1 μmol/L for fasting TSBA, and 4.7-20.2 μmol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting measurements, with a median increase of 1.0 μmol/L (p< 0.0001). A correlation between fasting TSBA concentrations and postprandial concentrations was found, as well as with fetal gender, parity, and assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values in the winter season (p < 0.01 and 0.02, respectively).

CONCLUSIONS: Normal pregnancy is associated with mild hypercholanaemia, therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limit observed in our healthy pregnant population (14 μmol/L for fasting and 20 μmol/L for postprandial TSBA). As the fasting measurement is more specific for the diagnosis, and the postprandial is essential for severity assessment, it is recommended to measure both values, rather than use random samplings.

PMID:35373886 | DOI:10.1111/1471-0528.17174

Head Neck. 2022 Apr 4. doi: 10.1002/hed.27033. Online ahead of print.

ABSTRACT

BACKGROUND: To assess the prognostic value of the systemic inflammation response index (SIRI) combined with plasma load of Epstein-Barr virus (EBV) DNA in children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC).

METHODS: A total of 205 consecutive patients with CALANPC were enrolled. We used recursive partitioning analysis (RPA) to classify patients into various risk groups, with a primary endpoint of overall survival (OS).

RESULTS: Elevated SIRI (≥1.53) and EBV DNA (≥4000 copy/ml) were significantly associated with inferior OS in CALANPC. RPA categorized patients into low- and high-risk groups based on prognostic factors. Survival curves showed excellent discrimination in OS (95.3% vs 77.6%; p < 0.001) between the low- and high-risk groups. A significant improvement was confirmed using the prognostic methods for conventional TNM staging systems (p < 0.05).

CONCLUSIONS: The combination of SIRI with EBV DNA provided a more detailed understanding of patient risks, and enhanced risk discrimination in CALANPC.

PMID:35373866 | DOI:10.1002/hed.27033

Lasers Surg Med. 2022 Apr 4. doi: 10.1002/lsm.23542. Online ahead of print.

ABSTRACT

PURPOSE: High-powered lasers are commonly used for tissue resection in surgeries, including liver resection, medically known as hepatectomy; however, such lasers inevitably induce thermal damage that causes postoperative complications. This study aims to explore the effects of water cooling and different laser output modes on laser-induced thermal damage during hepatectomy.

METHODS: To avoid the influence of superposition, a 980-nm diode laser was used for a single-point hepatectomy. Eighteen Sprague-Dawley rats were used to explore the effects of water cooling and different laser output modes. A constant energy 10-J laser was used to cut the liver tissue with a power of 10 W and time of 1 second. The rats were randomly divided into six groups. The first three groups were assigned as test subjects for different laser output modes. Group 1 was operated with a continuous laser output for a duration of 1 second. Groups 2 and 3 were operated with a pulsed laser output for a duration of 1 second and a pulse width of 0.5 and 0.25 seconds, respectively. Groups 4, 5, and 6 were assigned for the water cooling test. Water cooling was performed based on the parameters of the first three groups. Medical saline (0.9% NaCl) was used for water cooling. The main observation indicators were resection efficiency and thermal damage, including the area of the thermal damage zone. Resection efficiency is calculated by dividing the resection area by the total thermal damage area.

RESULTS: In the three water cooling groups, the area of the resection, carbonized, sub-boiling coagulated, and total thermal damage zones were 0.0677, 0.00, 1.7293, and 2.2982 mm² in Group 4; 0.0465, 0.00, 1.3205, and 1.8414 mm² in Group 5; and 0.0565, 0.00, 1.4301, and 1.9650 mm² in Group 6, respectively. Compared with the first three groups, the water cooling groups exhibited significantly reduced thermal damage areas of in the carbonized, sub-boiling coagulated, and total thermal damage zones (p < 0.001 for all). In addition, there was no statistical difference in the resection area, vacuolated area, and resection efficiency. Furthermore, there was no statistical difference in the area of each thermal damage zone between the continuous and pulsed output groups. The resection efficiencies were 4.82%, 3.34%, 3.73%, 3.93%, 3.36%, and 3.01% in Groups 1 to 6, respectively. Moreover, there was no statistical difference (p > 0.05) in the resection efficiencies.

CONCLUSION: Water cooling can reduce the total laser-induced thermal damage area and prevent tissue carbonization. Therefore, this cooling method can be used as a simple and safe strategy for controlling thermal damage during hepatectomy.

PMID:35373842 | DOI:10.1002/lsm.23542

Cochrane Database Syst Rev. 2022 Apr 4;4:CD011136. doi: 10.1002/14651858.CD011136.pub3.

ABSTRACT

BACKGROUND: Tracheal intubation is a common procedure performed to secure the airway in adults undergoing surgery or those who are critically ill. Intubation is sometimes associated with difficulties and complications that may result in patient harm. While it is traditionally achieved by performing direct laryngoscopy, the past three decades have seen the advent of rigid indirect videolaryngoscopes (VLs). A mounting body of evidence comparing the two approaches to tracheal intubation has been acquired over this period of time. This is an update of a Cochrane Review first published in 2016.

OBJECTIVES: To assess whether use of different designs of VLs in adults requiring tracheal intubation reduces the failure rate compared with direct laryngoscopy, and assess the benefits and risks of these devices in selected population groups, users and settings.

SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and Web of Science on 27 February 2021. We also searched clinical trials databases, conference proceedings and conducted forward and backward citation searches.

SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs with adults undergoing laryngoscopy performed with either a VL or a Macintosh direct laryngoscope (DL) in any clinical setting. We included parallel and cross-over study designs.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for the following outcomes: failed intubation, hypoxaemia, successful first attempt at tracheal intubation, oesophageal intubation, dental trauma, Cormack-Lehane grade, and time for tracheal intubation.

MAIN RESULTS: We included 222 studies (219 RCTs, three quasi-RCTs) with 26,149 participants undergoing tracheal intubation. Most studies recruited adults undergoing elective surgery requiring tracheal intubation. Twenty-one studies recruited participants with a known or predicted difficult airway, and an additional 25 studies simulated a difficult airway. Twenty-one studies were conducted outside the operating theatre environment; of these, six were in the prehospital setting, seven in the emergency department and eight in the intensive care unit. We report here the findings of the three main comparisons according to videolaryngoscopy device type. We downgraded the certainty of the outcomes for imprecision, study limitations (e.g. high or unclear risks of bias), inconsistency when we noted substantial levels of statistical heterogeneity and publication bias. Macintosh-style videolaryngoscopy versus direct laryngoscopy (61 studies, 9883 participants) We found moderate-certainty evidence that a Macintosh-style VL probably reduces rates of failed intubation (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.26 to 0.65; 41 studies, 4615 participants) and hypoxaemia (RR 0.72, 95% CI 0.52 to 0.99; 16 studies, 2127 participants). These devices may also increase rates of success on the first intubation attempt (RR 1.05, 95% CI 1.02 to 1.09; 42 studies, 7311 participants; low-certainty evidence) and probably improve glottic view when assessed as Cormack-Lehane grade 3 and 4 (RR 0.38, 95% CI 0.29 to 0.48; 38 studies, 4368 participants; moderate-certainty evidence). We found little or no clear difference in rates of oesophageal intubation (RR 0.51, 95% CI 0.22 to 1.21; 14 studies, 2404 participants) but this finding was supported by low-certainty evidence. We were unsure of the findings for dental trauma because the certainty of this evidence was very low (RR 0.68, 95% CI 0.16 to 2.89; 18 studies, 2297 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I² = 96%). Hyperangulated videolaryngoscopy versus direct laryngoscopy (96 studies, 11,438 participants) We found moderate-certainty evidence that hyperangulated VLs probably reduce rates of failed intubation (RR 0.51, 95% CI 0.34 to 0.76; 63 studies, 7146 participants) and oesophageal intubation (RR 0.39, 95% CI 0.18 to 0.81; 14 studies, 1968 participants). In subgroup analysis, we noted that hyperangulated VLs were more likely to reduce failed intubation when used on known or predicted difficult airways (RR 0.29, 95% CI 0.17 to 0.48; P = 0.03 for subgroup differences; 15 studies, 1520 participants). We also found that these devices may increase rates of success on the first intubation attempt (RR 1.03, 95% CI 1.00 to 1.05; 66 studies, 8086 participants; low-certainty evidence) and the glottic view is probably also improved (RR 0.15, 95% CI 0.10 to 0.24; 54 studies, 6058 participants; data for Cormack-Lehane grade 3/4 views; moderate-certainty evidence). However, we found low-certainty evidence of little or no clear difference in rates of hypoxaemia (RR 0.49, 95% CI 0.22 to 1.11; 15 studies, 1691 participants), and the findings for dental trauma were unclear because the certainty of this evidence was very low (RR 0.51, 95% CI 0.16 to 1.59; 30 studies, 3497 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I² = 99%). Channelled videolaryngoscopy versus direct laryngoscopy (73 studies, 7165 participants) We found moderate-certainty evidence that channelled VLs probably reduce rates of failed intubation (RR 0.43, 95% CI 0.30 to 0.61; 53 studies, 5367 participants) and hypoxaemia (RR 0.25, 95% CI 0.12 to 0.50; 15 studies, 1966 participants). They may also increase rates of success on the first intubation attempt (RR 1.10, 95% CI 1.05 to 1.15; 47 studies, 5210 participants; very low-certainty evidence) and probably improve glottic view (RR 0.14, 95% CI 0.09 to 0.21; 40 studies, 3955 participants; data for Cormack-Lehane grade 3/4 views; moderate-certainty evidence). We found little or no clear difference in rates of oesophageal intubation (RR 0.54, 95% CI 0.17 to 1.75; 16 studies, 1756 participants) but this was supported by low-certainty evidence. We were unsure of the findings for dental trauma because the certainty of the evidence was very low (RR 0.52, 95% CI 0.13 to 2.12; 29 studies, 2375 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I² = 98%).

AUTHORS’ CONCLUSIONS: VLs of all designs likely reduce rates of failed intubation and result in higher rates of successful intubation on the first attempt with improved glottic views. Macintosh-style and channelled VLs likely reduce rates of hypoxaemic events, while hyperangulated VLs probably reduce rates of oesophageal intubation. We conclude that videolaryngoscopy likely provides a safer risk profile compared to direct laryngoscopy for all adults undergoing tracheal intubation.

PMID:35373840 | DOI:10.1002/14651858.CD011136.pub3

Soft Matter. 2022 Apr 4. doi: 10.1039/d2sm00200k. Online ahead of print.

ABSTRACT

Understanding the process-property relations of helical polymers using molecular simulations has been an attractive research field over the years. Specifically, isotactic polypropylene still remains a challenge for current computational experimentation, as it exhibits phenomena such as crystallization that emerge on large spatial and temporal scales. Coarse-graining is an efficient technique for approaching such phenomena, although previous coarse-grained models lack in preserving important atomistic and structural details. In this paper we develop a new coarse-grained model, based on the popular MARTINI force field, that is able to reproduce the helical behavior of isotactic polypropylene. To test the model, the predicted statistical and structural properties (characteristic ratio, density, entanglement molecular weight, solubility parameter in the melt) are compared with previous simulation results and available experimental data. For the development of the new coarse-grained force field, a single unperturbed chain Monte Carlo algorithm has been implemented: an efficient algorithm which samples conformations representative of a melt by simulating just a single chain.

PMID:35373807 | DOI:10.1039/d2sm00200k